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Sample records for cisplatin-induced acute kidney

  1. Suramin protects from cisplatin-induced acute kidney injury.

    Science.gov (United States)

    Dupre, Tess V; Doll, Mark A; Shah, Parag P; Sharp, Cierra N; Kiefer, Alex; Scherzer, Michael T; Saurabh, Kumar; Saforo, Doug; Siow, Deanna; Casson, Lavona; Arteel, Gavin E; Jenson, Alfred Bennett; Megyesi, Judit; Schnellmann, Rick G; Beverly, Levi J; Siskind, Leah J

    2016-02-01

    Cisplatin, a commonly used cancer chemotherapeutic, has a dose-limiting side effect of nephrotoxicity. Approximately 30% of patients administered cisplatin suffer from kidney injury, and there are limited treatment options for the treatment of cisplatin-induced kidney injury. Suramin, which is Federal Drug Administration-approved for the treatment of trypanosomiasis, improves kidney function after various forms of kidney injury in rodent models. We hypothesized that suramin would attenuate cisplatin-induced kidney injury. Suramin treatment before cisplatin administration reduced cisplatin-induced decreases in kidney function and injury. Furthermore, suramin attenuated cisplatin-induced expression of inflammatory cytokines and chemokines, endoplasmic reticulum stress, and apoptosis in the kidney cortex. Treatment of mice with suramin 24 h after cisplatin also improved kidney function, suggesting that the mechanism of protection is not by inhibition of tubular cisplatin uptake or its metabolism to nephrotoxic species. If suramin is to be used in the context of cancer, then it cannot prevent cisplatin-induced cytotoxicity of cancer cells. Suramin did not alter the dose-response curve of cisplatin in lung adenocarcinoma cells in vitro. In addition, suramin pretreatment of mice harboring lung adenocarcinomas did not alter the initial cytotoxic effects of cisplatin (DNA damage and apoptosis) on tumor cells. These results provide evidence that suramin has potential as a renoprotective agent for the treatment/prevention of cisplatin-induced acute kidney injury and justify future long-term preclinical studies using cotreatment of suramin and cisplatin in mouse models of cancer.

  2. Blockade of KCa3.1 potassium channels protects against cisplatin-induced acute kidney injury.

    Science.gov (United States)

    Chen, Cheng-Lung; Liao, Jiunn-Wang; Hu, Oliver Yoa-Pu; Pao, Li-Heng

    2016-09-01

    Tubular cell apoptosis significantly contributes to cisplatin-induced acute kidney injury (AKI) pathogenesis. Although KCa3.1, a calcium-activated potassium channel, participates in apoptosis, its involvement in cisplatin-induced AKI is unknown. Here, we found that cisplatin treatment triggered an early induction of KCa3.1 expression associated with HK-2 cell apoptosis, the development of renal tubular damage, and apoptosis in mice. Treatment with the highly selective KCa3.1 blocker TRAM-34 suppressed cisplatin-induced HK-2 cell apoptosis. We further assessed whether KCa3.1 mediated cisplatin-induced AKI in genetic knockout and pharmacological blockade mouse models. KCa3.1 deficiency reduced renal function loss, renal tubular damage, and the induction of the apoptotic marker caspase-3 in the kidneys of cisplatin-treated KCa3.1 (-/-) mice. Pharmacological blockade of KCa3.1 by TRAM-34 similarly attenuated cisplatin-induced AKI in mice. Furthermore, we dissected the mechanisms underlying cisplatin-induced apoptosis reduction via KCa3.1 blockade. We found that KCa3.1 blockade attenuated cytochrome c release and the increase in the intrinsic apoptotic mediators Bax, Bak, and caspase-9 after cisplatin treatment. KCa3.1 blocking inhibited the cisplatin-induced activation of the endoplasmic reticulum (ER) stress mediator caspase-12, which is independent of calcium-dependent protease m-calpain activation. Taken together, KCa3.1 blockade protects against cisplatin-induced AKI through the attenuation of apoptosis by interference with intrinsic apoptotic and ER stress-related mediators, providing a potential target for the prevention of cisplatin-induced AKI. PMID:26438401

  3. Baicalein, a Bioflavonoid, Prevents Cisplatin-Induced Acute Kidney Injury by Up-Regulating Antioxidant Defenses and Down-Regulating the MAPKs and NF-κB Pathways.

    Directory of Open Access Journals (Sweden)

    Bidya Dhar Sahu

    Full Text Available Acute renal failure is a serious complication of the anticancer drug cisplatin. The potential role of baicalein, a naturally occurring bioflavonoid on cisplatin-induced renal injury is unknown. Here, we assessed the effect of baicalein against a murine model of cisplatin-induced acute renal failure and investigated the underlying possible mechanisms. Renal function, kidney histology, inflammation, oxidative stress, renal mitochondrial function, proteins involved in apoptosis, nuclear translocation of Nrf2 and effects on intracellular signaling pathways such as MAPKs, and NF-κB were assessed. Pretreatment with baicalein ameliorated the cisplatin-induced renal oxidative stress, apoptosis and inflammation and improved kidney injury and function. Baicalein inhibited the cisplatin-induced expression of iNOS, TNF-α, IL-6 and mononuclear cell infiltration and concealed redox-sensitive transcription factor NF-κB activation via reduced DNA-binding activity, IκBα phosphorylation and p65 nuclear translocation in kidneys. Further studies demonstrated baicalein markedly attenuated cisplatin-induced p38 MAPK, ERK1/2 and JNK phosphorylation in kidneys. Baicalein also restored the renal antioxidants and increased the amount of total and nuclear accumulation of Nrf2 and downstream target protein, HO-1 in kidneys. Moreover, baicalein preserved mitochondrial respiratory enzyme activities and inhibited cisplatin-induced apoptosis by suppressing p53 expression, Bax/Bcl-2 imbalance, cytochrome c release and activation of caspase-9, caspase-3 and PARP. Our findings suggest that baicalein ameliorates cisplatin-induced renal damage through up-regulation of antioxidant defense mechanisms and down regulation of the MAPKs and NF-κB signaling pathways.

  4. Baicalein, a Bioflavonoid, Prevents Cisplatin-Induced Acute Kidney Injury by Up-Regulating Antioxidant Defenses and Down-Regulating the MAPKs and NF-κB Pathways.

    Science.gov (United States)

    Sahu, Bidya Dhar; Mahesh Kumar, Jerald; Sistla, Ramakrishna

    2015-01-01

    Acute renal failure is a serious complication of the anticancer drug cisplatin. The potential role of baicalein, a naturally occurring bioflavonoid on cisplatin-induced renal injury is unknown. Here, we assessed the effect of baicalein against a murine model of cisplatin-induced acute renal failure and investigated the underlying possible mechanisms. Renal function, kidney histology, inflammation, oxidative stress, renal mitochondrial function, proteins involved in apoptosis, nuclear translocation of Nrf2 and effects on intracellular signaling pathways such as MAPKs, and NF-κB were assessed. Pretreatment with baicalein ameliorated the cisplatin-induced renal oxidative stress, apoptosis and inflammation and improved kidney injury and function. Baicalein inhibited the cisplatin-induced expression of iNOS, TNF-α, IL-6 and mononuclear cell infiltration and concealed redox-sensitive transcription factor NF-κB activation via reduced DNA-binding activity, IκBα phosphorylation and p65 nuclear translocation in kidneys. Further studies demonstrated baicalein markedly attenuated cisplatin-induced p38 MAPK, ERK1/2 and JNK phosphorylation in kidneys. Baicalein also restored the renal antioxidants and increased the amount of total and nuclear accumulation of Nrf2 and downstream target protein, HO-1 in kidneys. Moreover, baicalein preserved mitochondrial respiratory enzyme activities and inhibited cisplatin-induced apoptosis by suppressing p53 expression, Bax/Bcl-2 imbalance, cytochrome c release and activation of caspase-9, caspase-3 and PARP. Our findings suggest that baicalein ameliorates cisplatin-induced renal damage through up-regulation of antioxidant defense mechanisms and down regulation of the MAPKs and NF-κB signaling pathways.

  5. Antioxidant and anti-inflammatory potential of pomegranate rind extract to ameliorate cisplatin-induced acute kidney injury.

    Science.gov (United States)

    Karwasra, Ritu; Kalra, Prerna; Gupta, Yogendra Kumar; Saini, Deepika; Kumar, Ajay; Singh, Surender

    2016-07-13

    Cisplatin is a chemotherapeutic agent, but the therapeutic utility is limited due to its dose dependent nephrotoxicity. The aim of the present study was to evaluate the nephroprotective effect of pomegranate in cisplatin-induced acute kidney injury. Wistar rats were allocated into six groups as follows: the normal control, cisplatin-induced, pomegranate rind extract treatment (50, 100 and 200 mg kg(-1)) and pomegranate rind extract per se group. All the experimental test drugs/vehicle were administered orally for a period of ten days. Intraperitoneal injection of cisplatin (8 mg kg(-1)) was administered on day 7 to all the groups except the normal control and pomegranate per se group. On day 10, cisplatin resulted in significant nephrotoxicity in Wistar rats with a drastic elevation of serum creatinine and BUN, a decline in the concentrations of GSH, MDA and superoxide dismutase (SOD), and an elevation in the TNF-α level in renal tissues. Pathological changes in renal tissues were examined by histopathology and dysfunction in mitochondria and proximal tubule cells was detected by transmission electron microscopy. The rate of apoptosis and the expression of caspase-3, Il-1β and IL-6 in rat renal tissues were detected by immunohistochemistry. The administration of pomegranate at a dose of 200 mg per kg body weight significantly (p stress and inflammation. PMID:27273121

  6. Long Term Study of Protective Mechanisms of Human Adipose Derived Mesenchymal Stem Cells on Cisplatin Induced Kidney injury in Sprague-Dawley Rats

    OpenAIRE

    Elhusseini, Fatma M; Saad, Mohamed-Ahdy A.A; Anber, Nahla; Elghannam, Doaa; Sobh, Mohamed-Ahmed; ALSAYED, AZIZA; El-dusoky, Sara; SHEASHAA, HUSSEIN; Abdel-Ghaffar, Hassan; Sobh, Mohamed

    2016-01-01

    Background/Aims: Long-term evaluation of cisplatin induced nephrotoxicity and the probable renal protective activities of stem cells are lacking up until now. We evaluated the early and long-term role of human adipose derived mesenchymal stem cells (ADMSCs) in prevention or amelioration of cisplatin induced acute kidney injury (AKI) in Sprague-Dawley rats. For this, we determined the kidney tissue level of oxidative stress markers in conjugation with a renal histopathological scoring system o...

  7. Attenuation of cisplatin-induced acute renal failure is associated with less apoptotic cell death.

    Science.gov (United States)

    Zhou, H; Miyaji, T; Kato, A; Fujigaki, Y; Sano, K; Hishida, A

    1999-12-01

    To clarify the pathophysiologic role of apoptosis in acute renal failure (ARF), we examined whether the attenuation of cisplatin-induced ARF is associated with the change in the degree of apoptotic cell death. The administration of cisplatin (CDDP) (6 mg/kg body weight) in rats induced ARF at day 5, as manifested by a significant increase in serum creatinine (Scr) and tubular damage. CDDP-induced apoptotic cell death was confirmed by electron microscopic examination, agarose gel electrophoresis, and increased cells positive for TaT-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) in the outer medulla of the kidney. Treatment with dimethylthiourea (DMTU)--a scavenger of hydroxyl radicals--or glycine abrogated CDDP-induced increases in Scr, the tubular damage score, and the number of TUNEL-positive cells. Pretreatment with uranyl acetate (UA) induced a significant expression of Bcl-2 in the kidney and ameliorated CDDP-induced increases in Scr, the tubular damage score, and TUNEL-positive cells in the outer stripe of the outer medulla. Our findings indicate (1) that the attenuation of CDDP-induced ARF was associated with less apoptotic cell death and (2) that the induction of the anti-apoptotic protein Bcl-2 attenuated apoptosis and tubular damage. Our results suggest that apoptotic cell death may play an important role in the development of cisplatin-induced ARF. PMID:10595794

  8. Bardoxolone methyl modulates efflux transporter and detoxifying enzyme expression in cisplatin-induced kidney cell injury.

    Science.gov (United States)

    Atilano-Roque, Amandla; Aleksunes, Lauren M; Joy, Melanie S

    2016-09-30

    Cisplatin is prescribed for the treatment of solid tumors and elicits toxicity to kidney tubules, which limits its clinical use. Nuclear factor erythroid 2-related factor 2 (Nrf2, NFE2L2) is a critical transcription factor that has been shown to protect against kidney injury through activation of antioxidant mechanisms. We aimed to evaluate the ability of short-term treatment with the Nrf2 activator bardoxolone methyl (CDDO-Me) to protect against cisplatin-induced kidney cell toxicity. Cell viability was assessed in human kidney proximal tubule epithelial cells (hPTCs) exposed to low, intermediate, and high cisplatin concentrations in the presence and absence of CDDO-Me, administered either prior to or after cisplatin. Treatment with cisplatin alone resulted in reductions in hPTC viability, while CDDO-Me administered prior to or after cisplatin exposure yielded significantly higher cell viability (17%-71%). Gene regulation (mRNA expression) studies revealed the ability of CDDO-Me to modify protective pathways including Nrf2 induced detoxifying genes [GCLC (increased 1.9-fold), NQO1 (increased 9.3-fold)], and an efflux transporter [SLC47A1 (increased 4.5-fold)] at 12h. Protein assessments were in agreement with gene expression. Immunofluorescence revealed localization of GCLC and NQO1 to the nucleus and cytosol, respectively, with CDDO-Me administered prior to or after cisplatin exposure. The findings of enhanced cell viability and increased expression of detoxifying enzymes (GCLC and NQO1) and the multidrug and toxin extrusion protein 1 (MATE1) efflux transporter (SLC47A1) in hPTCs exposed to CDDO-Me, suggest that intermittent treatment with CDDO-Me prior to or after cisplatin exposure may be a promising approach to mitigate acute kidney injury. PMID:27480280

  9. Neuropeptide Y protects kidney against cisplatin-induced nephrotoxicity by regulating p53-dependent apoptosis pathway

    Science.gov (United States)

    Kim, Namoh; Min, Woo-Kie; Park, Min Hee; Lee, Jong Kil; Jin, Hee Kyung; Bae, Jae-sung

    2016-01-01

    Cisplatin is a platinum-based chemotherapeutic drug for treating various types of cancers. However, the use of cisplatin is limited by its negative effect on normal tissues, particularly nephrotoxicity. Various mechanisms such as DNA adduct formation, mitochondrial dysfunction, oxidative stress, and apoptosis are involved in the adverse effect induced by cisplatin treatment. Several studies have suggested that neuropeptide Y (NPY) is involved in neuroprotection as well as restoration of bone marrow dysfunction from chemotherapy induced nerve injury. However, the role of NPY in chemotherapy-induced nephrotoxicity has not been studied. Here, we show that NPY rescues renal dysfunction by reducing the expression of pro-apoptotic proteins in cisplatin induced nephrotoxicity through Y1 receptor, suggesting that NPY can protect kidney against cisplatin nephrotoxicity as a possible useful agent to prevent and treat cisplatin-induced nephrotoxicity. [BMB Reports 2016; 49(5): 288-292] PMID:26728272

  10. Sappanone A protects mice against cisplatin-induced kidney injury.

    Science.gov (United States)

    Kang, Lin; Zhao, Huanfen; Chen, Chen; Zhang, Xiuzhi; Xu, Mingtang; Duan, Huijun

    2016-09-01

    Cisplatin (CP) is an anti-cancer drug that often causes nephrotoxicity due to enhanced inflammatory response and oxidative stress. Sappanone A (SA), a homoisoflavanone isolated from the heartwood of Caesalpinia sappan, has been known to have antioxidant and anti-inflammatory effects. In this study, we aimed to investigate the protective effects and mechanism of SA on CP-induced kidney injury in mice. The results showed that treatment of SA improved CP-induced histopathalogical injury and renal dysfunction. SA also inhibited CP-induced MPO, MDA, TNF-α and IL-1β production and up-regulated the activities of SOD and GSH-PX decreased by CP. SA significantly inhibited the apoptosis rate of kidney tissues induced by CP. Furthermore, SA was found to inhibit CP-induced NF-κB activation. Treatment of SA up-regulated the expression of Nrf2 and HO-1 in a dose-dependent manner. In vitro, SA dose-dependently inhibited CP-induced TNF-α and IL-1β production and NF-κB activation in HK-2 cells. In conclusion, these results suggested that SA inhibited CP-induced kidney injury through activating Nrf2 and inhibiting NF-κB activation. SA was a potential therapeutic drug for treating CP-induced kidney injury. PMID:27318179

  11. Fetal kidney stem cells ameliorate cisplatin induced acuterenal failure and promote renal angiogenesis

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    AIM To investigate whether fetal kidney stem cells(fKSC) ameliorate cisplatin induced acute renal failure(ARF) in rats and promote renal angiogenesis.METHODS: The fKSC were isolated from rat fetusesof gestation day 16 and expanded in vitro up to 3rdpassage. They were characterized for the expressionof mesenchymal and renal progenitor markers by flowcytometry and immunocytochemistry, respectively.The in vitro differentiation of fKSC towards epitheliallineage was evaluated by the treatment with specificinduction medium and their angiogenic potential bymatrigel induced tube formation assay. To study theeffect of fKSC in ARF, fKSC labeled with PKH26 wereinfused in rats with cisplatin induced ARF and, the bloodand renal tissues of the rats were collected at differenttime points. Blood biochemical parameters werestudied to evaluate renal function. Renal tissues wereevaluated for renal architecture, renal cell proliferationand angiogenesis by immunohistochemistry, renal cellapoptosis by terminal deoxynucleotidyl transferase nickendlabeling assay and early expression of angiogenicmolecules viz . vascular endothelial growth factor (VEGF),hypoxia-inducible factor (HIF)-1α and endothelial nitricoxide synthase (eNOS) by western blot.RESULTS: The fKSC expressed mesenchymal markersviz . CD29, CD44, CD73, CD90 and CD105 as well as renal progenitor markers viz . Wt1, Pax2 and Six2. Theyexhibited a potential to form CD31 and Von Willebrandfactor expressing capillary-like structures and could bedifferentiated into cytokeratin (CK)18 and CK19 positiveepithelial cells. Administration of fKSC in rats with ARF ascompared to administration of saline alone, resulted in asignificant improvement in renal function and histology onday 3 (2.33 ± 0.33 vs 3.50 ± 0.34, P 〈 0.05) and on day7 (0.83 ± 0.16 vs 2.00 ± 0.25, P 〈 0.05). The infusedPKH26 labeled fKSC were observed to engraft in damagedrenal tubules and showed increased proliferation andreduced

  12. Protective effect of metalloporphyrins against cisplatin-induced kidney injury in mice.

    Directory of Open Access Journals (Sweden)

    Hao Pan

    Full Text Available Oxidative and nitrative stress is a well-known phenomenon in cisplatin-induced nephrotoxicity. The purpose of this work is to study the role of two metalloporphyrins (FeTMPyP and MnTBAP, water soluble complexes, in cisplatin-induced renal damage and their ability to scavenge peroxynitrite. In cisplatin-induced nephropathy study in mice, renal nitrative stress was evident by the increase in protein nitration. Cisplatin-induced nephrotoxicity was also evident by the histological damage from the loss of the proximal tubular brush border, blebbing of apical membranes, tubular epithelial cell detachment from the basement membrane, or intra-luminal aggregation of cells and proteins and by the increase in blood urea nitrogen and serum creatinine. Cisplatin-induced apoptosis and cell death as shown by Caspase 3 assessments, TUNEL staining and DNA fragmentation Cisplatin-induced nitrative stress, apoptosis and nephrotoxicity were attenuated by both metalloporphyrins. Heme oxygenase (HO-1 also plays a critical role in metalloporphyrin-mediated protection of cisplatin-induced nephrotoxicity. It is evident that nitrative stress plays a critical role in cisplatin-induced nephrotoxicity in mice. Our data suggest that peroxynitrite is involved, at least in part, in cisplatin-induced nephrotoxicity and protein nitration and cisplatin-induced nephrotoxicity can be prevented with the use of metalloporphyrins.

  13. Renoprotective mechanisms of chlorogenic acid in cisplatin-induced kidney injury

    International Nuclear Information System (INIS)

    Highlights: • Chlorogenic acid attenuated cisplatin-induced renal oxidative stress by reducing the expression of 4-HNE, HO-1 and CYP2E1. • The inhibition of inflammatory response was achieved through the reduction of TNF-α and COX-2 expression. • The expression of p53, Bax, active caspase-3 and LC3B was suppressed, suggesting the inhibition of apoptosis and autophagy. • Attenuation of Mrp1 and Mrp2 expression and the increase in Oct2 expression indicated reduced burden of tubular cells. • The recovery of kidneys form cisplatin injury was accompanied by the suppression of cyclin D1 and augmented PCNA expression. - Abstract: The aim of this study was to investigate the renoprotective activity of chlorogenic acid (CA) in a murine model of cisplatin (CP)-induced kidney injury. Male BALB/cN mice were gavaged daily with CA at 3, 10 and 30 mg/kg for two successive days, 48 h after intraperitoneal injection of CP (13 mg/kg). On the fifth day, serum creatinine and blood urea nitrogen (BUN) levels were significantly increased in CP-intoxicated mice, which was recovered by CA. Renal oxidative stress, evidenced by increased 4-hydroxynonenal (4-HNE) expression, was significantly reduced with CA. Simultaneously, the overexpression of heme oxygenase 1 (HO-1) and cytochrome P450 E1 (CYP2E1) was attenuated. The inhibition of inflammatory response by CA was achieved through the reduction of tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) expression. Additionally, CA significantly suppressed p53, Bax active caspase-3, cyclin D1 and microtubule-associated protein 1 light chain 3 isoform B (LC3B) expression, suggesting the inhibition of both apoptosis and autophagy. The expression of multidrug resistance-associated proteins (Mrp1 and Mrp2) increased and organic cation transporter 2 (Oct2) decreased by CP, protecting the kidneys from nephrotoxicity by reducing the burden of tubular cells. CA dose-dependently restored Mrp1, Mrp2 and Oct2 expression. The recovery

  14. Hydroxyl radical scavenger ameliorates cisplatin-induced nephrotoxicity by preventing oxidative stress, redox state unbalance, impairment of energetic metabolism and apoptosis in rat kidney mitochondria.

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    Santos, N A G; Bezerra, C S Catão; Martins, N M; Curti, C; Bianchi, M L P; Santos, A C

    2008-01-01

    Nephrotoxicity is the major dose-limiting factor of cisplatin chemotherapy. Reactive oxygen species generated in mitochondria are thought to be the main cause of cellular damage in such injury. The present study examined, in vivo, the protective potential of the hydroxyl radical scavenger dimethylthiourea (DMTU) against cisplatin-induced effects on renal mitochondrial bioenergetics, redox state and oxidative stress. Adult male Wistar rats (200 to 220 g) were divided into four groups of eight animals each. The control group was treated only with an intraperitoneal (i.p.) injection of saline solution (1 ml/100 g body weight). The second group was given only DMTU (500 mg/kg body weight, i.p, followed by 125 mg/Kg, i.p., twice a day until they were killed). The third group was given a single injection of cisplatin (10 mg/kg body weight, i.p.). The fourth group was given DMTU (500 mg/kg body weight, i.p.), just before the cisplatin injection (10 mg/kg body weight, i.p.), followed by injections of DMTU (125 mg/kg body weight, i.p.) twice a day until they were killed. Animals were killed 72 h after the treatment. Besides not presenting any direct effect on mitochondria, DMTU substantially inhibited cisplatin-induced mitochondrial injury and cellular death by apoptosis, suppressing the occurrence of acute renal failure. All the following cisplatin-induced effects were prevented by DMTU: (1) increased plasmatic levels of creatinine and blood urea nitrogen (BUN); (2) decreased ATP content, calcium uptake and electrochemical potential; (3) oxidation of lipids, including cardiolipin; and oxidation of proteins, including sulfhydryl, and aconitase enzyme, as well as accumulation of carbonyl proteins; (4) depletion of the antioxidant defense (NADPH and GSH) and (5) increased activity of the apoptosis executioner caspase-3. Our findings show the important role played by mitochondria and hydroxyl radicals in cisplatin-induced nephrotoxicity, as well as the effectiveness of DMTU in

  15. Assessment of cisplatin-induced kidney injury using an integrated rodent platform

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yafei [Global Safety Assessment, AstraZeneca R and D Waltham, MA 02451 (United States); Brott, David [Patient Safety, AstraZeneca R and D Wilmington, DE 19850 (United States); Luo, Wenli [Discovery Statistics, AstraZeneca R and D Waltham, MA 02451 (United States); Gangl, Eric [DMPK, AstraZeneca R and D Waltham, MA 02451 (United States); Kamendi, Harriet; Barthlow, Herbert; Lengel, David; Fikes, James; Kinter, Lewis [Global Safety Assessment, AstraZeneca R and D Waltham, MA 02451 (United States); Valentin, Jean-Pierre [Global Safety Assessment, AstraZeneca R and D Alderley Park, Macclesfield, SK10 4TG (United Kingdom); Bialecki, Russell, E-mail: russell.bialecki@astrazeneca.com [Global Safety Assessment, AstraZeneca R and D Waltham, MA 02451 (United States)

    2013-05-01

    Current diagnosis of drug-induced kidney injury (DIKI) primarily relies on detection of elevated plasma creatinine (Cr) or blood urea nitrogen (BUN) levels; however, both are indices of overall kidney function and changes are delayed with respect to onset of nephron injury. Our aim was to investigate whether early changes in new urinary DIKI biomarkers predict plasma Cr, BUN, renal hemodynamic and kidney morphological changes associated with kidney injury following a single dose of cisplatin (CDDP) using an integrated platform in rodent. Conscious surgically prepared male Han Wistar rats were given a single intraperitoneal dose of CDDP (15 mg/kg). Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), urinalysis, DIKI biomarkers, CDDP pharmacokinetics, blood pressures, heart rate, body temperature and electroencephalogram (EEG) were measured in the same vehicle- or CDDP-treated animals over 72 h. Plasma chemistry (including Cr and BUN) and renal tissues were examined at study termination. Cisplatin caused progressive reductions of GFR, ERPF, heart rate and body temperature from day 1 (0–24 h). DIKI biomarkers including alpha-glutathione S-transferase (α-GST) significantly increased as early as 6 h post-dose, which preceded significant declines of GFR and ERPF (24 h), increased plasma Cr and BUN (72 h), and associated with renal acute tubular necrosis at 72 h post-dose. The present study adds to the current understanding of CDDP action by demonstrating that early increases in urinary excretion of α-GST predict DIKI risk following acute exposure to CDDP in rats, before changes in traditional DIKI markers are evident. - Highlights: ► CDDP causes direct damage to kidneys without affecting EEG or CVS function. ► α-GST and albumin detect DIKI earlier when compared with traditional indices. ► Integrated “cardiovascular-EEG-renal” model to better understand DIKI mechanisms ► Promotes 3R's principles in drug discovery and development.

  16. Assessment of cisplatin-induced kidney injury using an integrated rodent platform

    International Nuclear Information System (INIS)

    Current diagnosis of drug-induced kidney injury (DIKI) primarily relies on detection of elevated plasma creatinine (Cr) or blood urea nitrogen (BUN) levels; however, both are indices of overall kidney function and changes are delayed with respect to onset of nephron injury. Our aim was to investigate whether early changes in new urinary DIKI biomarkers predict plasma Cr, BUN, renal hemodynamic and kidney morphological changes associated with kidney injury following a single dose of cisplatin (CDDP) using an integrated platform in rodent. Conscious surgically prepared male Han Wistar rats were given a single intraperitoneal dose of CDDP (15 mg/kg). Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), urinalysis, DIKI biomarkers, CDDP pharmacokinetics, blood pressures, heart rate, body temperature and electroencephalogram (EEG) were measured in the same vehicle- or CDDP-treated animals over 72 h. Plasma chemistry (including Cr and BUN) and renal tissues were examined at study termination. Cisplatin caused progressive reductions of GFR, ERPF, heart rate and body temperature from day 1 (0–24 h). DIKI biomarkers including alpha-glutathione S-transferase (α-GST) significantly increased as early as 6 h post-dose, which preceded significant declines of GFR and ERPF (24 h), increased plasma Cr and BUN (72 h), and associated with renal acute tubular necrosis at 72 h post-dose. The present study adds to the current understanding of CDDP action by demonstrating that early increases in urinary excretion of α-GST predict DIKI risk following acute exposure to CDDP in rats, before changes in traditional DIKI markers are evident. - Highlights: ► CDDP causes direct damage to kidneys without affecting EEG or CVS function. ► α-GST and albumin detect DIKI earlier when compared with traditional indices. ► Integrated “cardiovascular-EEG-renal” model to better understand DIKI mechanisms ► Promotes 3R's principles in drug discovery and development

  17. Does dexamethasone enhance control of acute cisplatin induced emesis by ondansetron?

    OpenAIRE

    Smyth, J. F.; Coleman, R E; Nicolson, M.; Gallmeier, W M; Leonard, R C; Cornbleet, M. A.; Allan, S G; Upadhyaya, B K; Bruntsch, U

    1991-01-01

    OBJECTIVE--To determine the contribution of dexamethasone to the efficacy of the 5-hydroxytryptamine antagonist ondansetron in control of cisplatin induced nausea and vomiting. DESIGN--Randomised double blind crossover study. SETTING--Two cancer centres in teaching hospitals, one in the United Kingdom and the other in Germany. SUBJECTS--100 patients (53 men and 47 women) new to cisplatin chemotherapy, 84 of whom completed two consecutive courses of chemotherapy. INTERVENTIONS--Patients were g...

  18. Pre-stimulation of the kallikrein system in cisplatin-induced acute renal injury: An approach to renoprotection

    Energy Technology Data Exchange (ETDEWEB)

    Aburto, Andrés [Program of M.Sc., Faculty of Medicine, Universidad Austral de Chile, Valdivia (Chile); Barría, Agustín [School of Biochemistry, Faculty of Sciences, Universidad Austral de Chile, Valdivia (Chile); Cárdenas, Areli [Ph.D. Program, Faculty of Sciences, Universidad Austral de Chile, Valdivia (Chile); Carpio, Daniel; Figueroa, Carlos D. [Department of Anatomy, Histology and Pathology, Universidad Austral de Chile, Valdivia (Chile); Burgos, Maria E. [Department of Nephrology, Faculty of Medicine, Universidad Austral de Chile, Valdivia (Chile); Ardiles, Leopoldo, E-mail: leopoldoardiles@gmail.com [Department of Nephrology, Faculty of Medicine, Universidad Austral de Chile, Valdivia (Chile)

    2014-10-15

    Antineoplastic treatment with cisplatin is frequently complicated by nephrotoxicity. Although oxidative stress may be involved, the pathogenic mechanisms responsible for renal damage have not been completely clarified. In order to investigate the role of the renal kinin system in this condition, a group of rats was submitted to high potassium diet to stimulate the synthesis and excretion of tissue kallikrein 1 (rKLK1) previous to an intraperitoneal injection of 7 mg/kg cisplatin. A significant reduction in lipoperoxidation, evidenced by urinary excretion of malondialdehyde and renal immunostaining of hidroxy-nonenal, was accompanied by a decline in apoptosis. Coincident with these findings we observed a reduction in the expression of renal KIM-1 suggesting that renoprotection may be occurring. Stimulation or indemnity of the renal kinin system deserves to be evaluated as a complementary pharmacological measure to diminish cisplatin nephrotoxicity. - Highlights: • Mechanisms of cisplatin-induced-renal damage have not been completely clarified. • Cisplatin induces oxidative stress and apoptosis. • The renal kallikrein-kinin system is protective in experimental acute renal damage. • Kallikrein stimulation reduces oxidative stress and apoptosis induced by cisplatin. • Protection of the kallikrein-kinin system may reduce cisplatin toxicity.

  19. Pre-stimulation of the kallikrein system in cisplatin-induced acute renal injury: An approach to renoprotection

    International Nuclear Information System (INIS)

    Antineoplastic treatment with cisplatin is frequently complicated by nephrotoxicity. Although oxidative stress may be involved, the pathogenic mechanisms responsible for renal damage have not been completely clarified. In order to investigate the role of the renal kinin system in this condition, a group of rats was submitted to high potassium diet to stimulate the synthesis and excretion of tissue kallikrein 1 (rKLK1) previous to an intraperitoneal injection of 7 mg/kg cisplatin. A significant reduction in lipoperoxidation, evidenced by urinary excretion of malondialdehyde and renal immunostaining of hidroxy-nonenal, was accompanied by a decline in apoptosis. Coincident with these findings we observed a reduction in the expression of renal KIM-1 suggesting that renoprotection may be occurring. Stimulation or indemnity of the renal kinin system deserves to be evaluated as a complementary pharmacological measure to diminish cisplatin nephrotoxicity. - Highlights: • Mechanisms of cisplatin-induced-renal damage have not been completely clarified. • Cisplatin induces oxidative stress and apoptosis. • The renal kallikrein-kinin system is protective in experimental acute renal damage. • Kallikrein stimulation reduces oxidative stress and apoptosis induced by cisplatin. • Protection of the kallikrein-kinin system may reduce cisplatin toxicity

  20. Acute kidney failure

    Science.gov (United States)

    Kidney failure; Renal failure; Renal failure - acute; ARF; Kidney injury - acute ... To prevent acute kidney failure: Health problems such as high blood pressure or diabetes should be well controlled. Avoid drugs and medicines that can cause kidney injury.

  1. Changes in expression of renal Oat1, Oat3 and Mrp2 in cisplatin-induced acute renal failure after treatment of JBP485 in rats

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Tao, E-mail: liutaomedical@qq.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China); Meng, Qiang, E-mail: mengq531@yahoo.cn [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University (China); Wang, Changyuan, E-mail: wangcyuan@163.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University (China); Liu, Qi, E-mail: llaqii@yahoo.com.cn [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University (China); Guo, Xinjin, E-mail: guo.xinjin@163.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China); Sun, Huijun, E-mail: sunhuijun@hotmail.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University (China); Peng, Jinyong, E-mail: jinyongpeng2005@163.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University (China); and others

    2012-11-01

    The purpose of this study is to investigate whether the effect of cyclo-trans-4-L-hydroxyprolyl-L-serine (JBP485) on acute renal failure (ARF) induced by cisplatin is related to change in expression of renal Oat1, Oat3 and Mrp2 in rats. JBP485 reduced creatinine, blood urea nitrogen (BUN) and indoxyl sulfate (IS) in plasma and malondialdehyde (MDA) in kidney, and recovered the glomerular filtration rate (GFR) and the activity of superoxide dismutase (SOD) in cisplatin-treated rats. The plasma concentration of PAH (para-aminohippurate) determined by LC–MS/MS was increased markedly after intravenous administration of cisplatin, whereas cumulative urinary excretion of PAH and the uptake of PAH in kidney slices were significantly decreased. qRT-PCR and Western-blot showed a decrease in mRNA and protein of Oat1 and Oat3, an increase in mRNA and protein of Mrp2 in cisplatin-treated rats, and an increase in IS (a uremic toxin) after co-treatment with JBP485. It indicated that JBP485 promoted urinary excretion of toxins by upregulating renal Mrp2. This therefore gives in part the explanation about the mechanism by which JBP485 improves ARF induced by cisplatin in rats. -- Highlights: ► Cisplatin induces acute renal failure (ARF). ► The expression of Oat1, Oat3 and Mrp2 were changed during ARF. ► The regulated expression of Oat1, Oat3 and Mrp2 is an adaptive protected response. ► JBP485 could facilitate the adaptive protective action.

  2. Amniotic Fluid-Derived Mesenchymal Stem Cells Cut Short the Acuteness of Cisplatin-Induced Nephrotoxicity in Sprague-Dawley Rats

    Science.gov (United States)

    Al-Husseiny, Fatma; Sobh, Mohamed Ahmed; Ashour, Rehab H.; Foud, Samah; Medhat, Tarek; El-Gilany, Abdel-Hady; Elghannam, Doaa; Abdel-Ghaffar, Hassan; Saad, Mohamed-Ahdy; Sobh, Mohamed

    2016-01-01

    Background and objectives Cisplatin is a nephrotoxic chemotherapeutic agent. So, preventive measures worth to be evaluated. Human amniotic fluid stem cells (hAFSCs) in prevention or amelioration of cisplatin-induced acute kidney injury (AKI) in Sprague-Dawley rates have been tested. Methods 80 Sprague-Dawley rats (250~300 g) were used and divided into 4 major groups, 20 rats each. Group I: Saline-injected group. Group II: Cisplatin-injected group (5 mg/kg I.P). Group III: Cisplatin-injected and hAFSCs-treated group (5×106 hAFSCs I.V. one day after cisplatin administration). Group IV: Cisplatin-injected and culture media-treated group. Each major group was further divided into 4 equal subgroups according to the timing of sacrifice; 4, 7, 11 and 30 days post-cisplatin injection. Renal function tests were done. Kidney tissue homogenate oxidative stress parameters malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) were determined. Histopathological scoring systems for active injury, regenerative and chronic changes were analyzed separately. Results hAFSCs characterization and differentiation was proved. Cisplatin injection resulted in a significant increase in serum creatinine and MDA and decrease in SOD, GSH and creatinine clearance. These changes were attenuated early by day 4 with the use of hAFSCs. Cisplatin injection induced tubular necrosis, atrophy, inflammatory cells infiltration and fibrosis. The use of hAFSCs was associated with significantly lowered injury score at day 4, 7, 11 and 30 with marked regenerative changes starting from day 4. Conclusion hAFSCs have both a protective and regenerative activities largely through an antioxidant activity. This activity cut short the acuteness of cisplatin nephrotoxicity. PMID:27426088

  3. [Acute kidney injury

    NARCIS (Netherlands)

    Hageman, D.; Kooman, J.P.; Lance, M.D.; Heurn, L.W. van; Snoeijs, M.G.

    2012-01-01

    - 'Acute kidney injury' is modern terminology for a sudden decline in kidney function, and is defined by the RIFLE classification (RIFLE is an acronym for Risk, Injury, Failure, Loss and End-stage kidney disease).- Acute kidney injury occurs as a result of the combination of reduced perfusion in the

  4. Co-culture of bone marrow-derived mesenchymal stem cells overexpressing lipocalin 2 with HK-2 and HEK293 cells protects the kidney cells against cisplatin-induced injury.

    Science.gov (United States)

    Halabian, Raheleh; Roudkenar, Mehryar Habibi; Jahanian-Najafabadi, Ali; Hosseini, Kamran Mousavi; Tehrani, Hossein Abdul

    2015-02-01

    Conditioned medium of mesenchymal stem cells (MSCs) is now being used for its cytoprotective effects, especially when the cells are equipped with cytoprotective factors to strengthen them against unfavorable microenvironments. Overexpression of Lcn2 in MSCs mimics in vivo kidney injury. Hence, unraveling how Lcn2-engineered MSCs affect kidney cells has been investigated. Cisplatin treated HK-2 or HEK293 kidney cells were co-cultivated with Lcn2 overexpressing MSCs in upper and lower chambers of transwell plates. Proliferation, apoptosis, and expression of growth factors and cytokines were assessed in the kidney cells. Co-cultivation with the MSCs-Lcn2 not only inhibited cisplatin-induced cytotoxicity in the HK-2 and HEK293 cells, but increased proliferation rate, prevented cisplatin-induced apoptosis, and increased expression of growth factors and the amount of antioxidants in the kidney cells. Thus Lcn2-engineered MSCs can ameliorate and repair injured kidney cells in vitro, which strongly suggests there are beneficial effects of the MSCs-Lcn2 in cell therapy of kidney injury.

  5. Cisplatin Induced Nephrotoxicity

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    Seyed Seifollah Beladi Mousavi

    2014-02-01

    The standard approach to prevent cisplatin-induced nephrotoxicity is the administration of lower doses of cisplatin in combination with the administration of full intravenous isotonic saline before and after cisplatin administration. Although a number of pharmacologic agents including sodium thiosulfate, N-acetylcysteine, theophylline and glycine have been evaluated for prevention of nephrotoxicity, none have proved to have an established role, thus, additional clinical studies will be required to confirm their probable effects.

  6. Proximal tubule-targeted heme oxygenase-1 in cisplatin-induced acute kidney injury.

    Science.gov (United States)

    Bolisetty, Subhashini; Traylor, Amie; Joseph, Reny; Zarjou, Abolfazl; Agarwal, Anupam

    2016-03-01

    Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that catalyzes the breakdown of heme to biliverdin, carbon monoxide, and iron. The beneficial effects of HO-1 expression are not merely due to degradation of the pro-oxidant heme but are also credited to the by-products that have potent, protective effects, including antioxidant, anti-inflammatory, and prosurvival properties. This is well reflected in the preclinical animal models of injury in both renal and nonrenal settings. However, excessive accumulation of the by-products can be deleterious and lead to mitochondrial toxicity and oxidative stress. Therefore, use of the HO system in alleviating injury merits a targeted approach. Based on the higher susceptibility of the proximal tubule segment of the nephron to injury, we generated transgenic mice using cre-lox technology to enable manipulation of HO-1 (deletion or overexpression) in a cell-specific manner. We demonstrate the validity and feasibility of these mice by breeding them with proximal tubule-specific Cre transgenic mice. Similar to previous reports using chemical modulators and global transgenic mice, we demonstrate that whereas deletion of HO-1, specifically in the proximal tubules, aggravates structural and functional damage during cisplatin nephrotoxicity, selective overexpression of HO-1 in proximal tubules is protective. At the cellular level, cleaved caspase-3 expression, a marker of apoptosis, and p38 signaling were modulated by HO-1. Use of these transgenic mice will aid in the evaluation of the effects of cell-specific HO-1 expression in response to injury and assist in the generation of targeted approaches that will enhance recovery with reduced, unwarranted adverse effects. PMID:26672618

  7. An interaction of ondansetron and dexamethasone antagonizing cisplatin-induced acute and delayed emesis in the ferret.

    OpenAIRE

    Rudd, J. A.; Naylor, R. J.

    1996-01-01

    1. Cisplatin, 5 mg kg-1, i.p., administered as a single treatment, induced an acute (day 1) and delayed (days 2 and 3) emetic response in the ferret that was used to investigate the potential anti-emetic activity of ondansetron and dexamethasone and their interaction over a three day period. 2. Ondansetron, 1 mg kg-1, i.p., administered three times per day in two experiments, antagonized significantly the retching and vomiting that occurred on days 1 and 2 by 60-76 and 73-84%. On the third da...

  8. Cisplatin-Induced Eosinophilic Pneumonia

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    Hideharu Ideguchi

    2014-01-01

    Full Text Available A 67-year-old man suffering from esophageal cancer was admitted to our hospital complaining of dyspnea and hypoxemia. He had been treated with cisplatin, docetaxel, and fluorouracil combined with radiotherapy. Chest computed tomography revealed bilateral ground-glass opacity, and bronchoalveolar lavage fluid showed increased eosinophils. Two episodes of transient eosinophilia in peripheral blood were observed after serial administration of anticancer drugs before the admission, and drug-induced lymphocyte stimulation test to cisplatin was positive. Thus cisplatin-induced eosinophilic pneumonia was suspected, and corticosteroid was effectively administered. To our knowledge, this is the first reported case of cisplatin-induced eosinophilic pneumonia.

  9. Long-Term Aerobic Exercise Protects against Cisplatin-Induced Nephrotoxicity by Modulating the Expression of IL-6 and HO-1

    OpenAIRE

    Miyagi, Mariana Yasue Saito; Seelaender, Marilia; Castoldi, Angela; de Almeida, Danilo Candido; Bacurau, Aline Villa Nova; Andrade-Oliveira, Vinicius; Enjiu, Lucas Maceratesi; Pisciottano, Marcus; Hayashida, Caroline Yuri; Hiyane, Meire Ioshie; Brum, Patricia Chakur; Camara, Niels Olsen Saraiva; Amano, Mariane Tami

    2014-01-01

    Nephrotoxicity is substantial side effect for 30% of patients undergoing cancer therapy with cisplatin and may force them to change or even abandon the treatment. Studies regarding aerobic exercise have shown its efficacy for the treatment of many types of diseases and its capacity to reduce tumors. However, little is known about the impact of physical exercise on cisplatin-induced acute kidney injury (AKI). In the present study, our aim was to investigate the role of physical exercise in AKI...

  10. Riboflavin ameliorates cisplatin induced toxicities under photoillumination.

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    Iftekhar Hassan

    Full Text Available BACKGROUND: Cisplatin is an effective anticancer drug that elicits many side effects mainly due to induction of oxidative and nitrosative stresses during prolonged chemotherapy. The severity of these side effects consequently restricts its clinical use under long term treatment. Riboflavin is an essential vitamin used in various metabolic redox reactions in the form of flavin adenine dinucleotide and flavin mononucleotide. Besides, it has excellent photosensitizing property that can be used to ameliorate these toxicities in mice under photodynamic therapy. METHODS AND FINDINGS: Riboflavin, cisplatin and their combinations were given to the separate groups of mice under photoilluminated condition under specific treatment regime. Their kidney and liver were excised for comet assay and histopathological studies. Furthermore, Fourier Transform Infrared Spectroscopy of riboflavin-cisplatin combination in vitro was also conducted to investigate any possible interaction between the two compounds. Their comet assay and histopathological examination revealed that riboflavin in combination with cisplatin was able to protect the tissues from cisplatin induced toxicities and damages. Moreover, Fourier Transform Infrared Spectroscopy analysis of the combination indicated a strong molecular interaction among their constituent groups that may be assigned for the protective effect of the combination in the treated animals. CONCLUSION: Inclusion of riboflavin diminishes cisplatin induced toxicities which may possibly make the cisplatin-riboflavin combination, an effective treatment strategy under chemoradiotherapy in pronouncing its antineoplastic activity and sensitivity towards the cancer cells as compared to cisplatin alone.

  11. Perioperative acute kidney injury

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    Calvert Stacey

    2012-07-01

    Full Text Available Abstract Acute kidney injury (AKI is a serious complication in the perioperative period, and is consistently associated with increased rates of mortality and morbidity. Two major consensus definitions have been developed in the last decade that allow for easier comparison of trial evidence. Risk factors have been identified in both cardiac and general surgery and there is an evolving role for novel biomarkers. Despite this, there has been no real change in outcomes and the mainstay of treatment remains preventive with no clear evidence supporting any therapeutic intervention as yet. This review focuses on definition, risk factors, the emerging role of biomarkers and subsequent management of AKI in the perioperative period, taking into account new and emerging strategies.

  12. [Ascites and acute kidney injury].

    Science.gov (United States)

    Piano, Salvatore; Tonon, Marta; Angeli, Paolo

    2016-07-01

    Ascites is the most common complication of cirrhosis. Ascites develops as a consequence of an abnormal splanchnic vasodilation with reduction of effecting circulating volume and activation of endogenous vasoconstrictors system causing salt and water retention. Patients with ascites have a high risk to develop further complications of cirrhosis such as hyponatremia, spontaneous bacterial peritonitis and acute kidney injury resulting in a poor survival. In recent years, new studies helped a better understanding of the pathophysiology of ascites and acute kidney injury in cirrhosis. Furthermore, new diagnostic criteria have been proposed for acute kidney injury and hepatorenal syndrome and a new algorithm for their management has been recommended with the aim of an early diagnosis and treatment. Herein we will review the current knowledge on the pathophysiology, diagnosis and treatment of ascites and acute kidney injury in patients with cirrhosis and we will identify the unmet needs that should be clarified in the next years.

  13. [Ascites and acute kidney injury].

    Science.gov (United States)

    Piano, Salvatore; Tonon, Marta; Angeli, Paolo

    2016-07-01

    Ascites is the most common complication of cirrhosis. Ascites develops as a consequence of an abnormal splanchnic vasodilation with reduction of effecting circulating volume and activation of endogenous vasoconstrictors system causing salt and water retention. Patients with ascites have a high risk to develop further complications of cirrhosis such as hyponatremia, spontaneous bacterial peritonitis and acute kidney injury resulting in a poor survival. In recent years, new studies helped a better understanding of the pathophysiology of ascites and acute kidney injury in cirrhosis. Furthermore, new diagnostic criteria have been proposed for acute kidney injury and hepatorenal syndrome and a new algorithm for their management has been recommended with the aim of an early diagnosis and treatment. Herein we will review the current knowledge on the pathophysiology, diagnosis and treatment of ascites and acute kidney injury in patients with cirrhosis and we will identify the unmet needs that should be clarified in the next years. PMID:27571467

  14. Perioperative acute kidney injury.

    Science.gov (United States)

    Goren, O; Matot, I

    2015-12-01

    Perioperative acute kidney injury (AKI) is not uncommon and is associated with considerable morbidity and mortality. Recently, several definition systems for AKI were proposed, incorporating both small changes of serum creatinine and urinary output reduction as diagnostic criteria. Novel biomarkers are under investigation as fast and accurate predictors of AKI. Several special considerations regarding the risk of AKI are of note in the surgical patient. Co-morbidities are important risk factors for AKI. The surgery in itself, especially emergency and major surgery in the critically ill, is associated with a high incidence of AKI. Certain types of surgeries, such as cardiac and transplantation surgeries, require special attention because they carry higher risk of AKI. Nephrotoxic drugs, contrast dye, and diuretics are commonly used in the perioperative period and are responsible for a significant amount of in-hospital AKI. Before surgery, the anaesthetist is required to identify patients at risk of AKI, optimize anaemia, and treat hypovolaemia. During surgery, normovolaemia is of utmost importance. Additionally, the surgical and anaesthesia team is advised to use measures to reduce blood loss and avoid unnecessary blood transfusion. Hypotension should be avoided because even short periods of mean arterial pressure patients. Urine output can be reduced significantly during surgery and is unrelated to perioperative renal function. Thus, fluids should not be given in excess for the sole purpose of avoiding or treating oliguria. Use of hydroxyethyl starch needs to be reconsidered. Recent evidence indicates a beneficial effect of administering low-chloride solutions. PMID:26658199

  15. Acute kidney injury in children.

    Science.gov (United States)

    Merouani, A; Flechelles, O; Jouvet, P

    2012-04-01

    Acute kidney injury (AKI) affects 5% of critically ill hospitalized children and is a risk factor for increased morbidity and mortality. The current review focuses on new definitions of acute kidney injury, standardized to reflect the entire spectrum of the disease, as well as on ongoing research to identify early biomarkers of kidney injury. Its also provides an overview of current practice and available therapies, with emphasis on new strategies for the prevention and pharmacological treatment of diarrhea-associated hemolytic uremic syndrome. Furthermore, a decision-making algorithm is presented for the use of renal replacement therapies in critically ill children with AKI. PMID:22495187

  16. Ultrasound in Acute Kidney Disease.

    Science.gov (United States)

    Meola, Mario; Nalesso, Federico; Petrucci, Ilaria; Samoni, Sara; Ronco, Claudio

    2016-01-01

    Kidneys' imaging provides useful information in acute kidney injury (AKI) diagnosis and management. Today, several imaging techniques give information on kidneys anatomy, urinary obstruction, differential diagnosis between AKI and chronic kidney disease (CKD), renal blood flow and glomerular filtration rate. Ultrasound is a safe, non-invasive and repeatable imaging technique so it is widely used in the first level work-up of AKI. The utility of contrast-enhanced computed tomography and magnetic resonance imaging in AKI or in AKI during CKD is limited because of renal toxicity associated with contrast agents used. PMID:27169556

  17. Assessment standards: comparing histopathology, digital image analysis, and stereology for early detection of experimental cisplatin-induced kidney injury in rats.

    Science.gov (United States)

    Shea, Katherine; Stewart, Sharron; Rouse, Rodney

    2014-08-01

    Histopathology generally represents the reference standard for performance evaluation of nonclinical biomarkers used to inform regulatory decision making. This study uses drug-induced nephrotoxicity in rats to evaluate histopathology methods utilized in biomarker performance assessments. Male Sprague-Dawley rats received a single dose of cisplatin (0.5-5.0 mg/kg, intraperitoneally) to produce mild renal injury. Animals were euthanized 72 hr postdose and perfusion fixed. Kidneys were processed for histology and stereology procedures. Kidney injury molecule-1 (Kim-1) was measured in urine and in kidney tissue. Digital slide images were generated and analyzed by pathologists after collaborating on a training set of glass slides and digital images. Image analysis identified immunohistochemistry (IHC)-defined tubular injury. Stereology methods yielded estimations of proximal tubular cell number and volume. Statistical relationships among data sets were determined using correlation coefficients. Receiver operator characteristic (ROC) analyses determined the effect of method on biomarker assessment. Urinary Kim-1 was strongly correlated with digital image analysis and secondarily to histopathology evaluations. Stereology demonstrated weak or no correlation to pathology and urinary Kim-1. In ROC analyses, semiquantitative evaluations determined higher values for urinary Kim-1 performance than did IHC-based qualitative digital analyses. Semiquantitative evaluation as used in this study was most predictive of urinary Kim-1 values.

  18. Acute kidney injury after pediatric cardiac surgery

    OpenAIRE

    Sarvesh Pal Singh

    2016-01-01

    Acute kidney injury is a common complication after pediatric cardiac surgery. The definition, staging, risk factors, biomarkers and management of acute kidney injury in children is detailed in the following review article.

  19. Acute Kidney Injury in the Elderly

    OpenAIRE

    Abdel-Kader, Khaled; Palevsky, Paul

    2009-01-01

    The aging kidney undergoes a number of important anatomic and physiologic changes that increase the risk of acute kidney injury (formerly acute renal failure) in the elderly. This article reviews these changes and discusses the diagnoses frequently encountered in the elderly patient with acute kidney injury. The incidence, staging, evaluation, management, and prognosis of acute kidney injury are also examined with special focus given to older adults.

  20. Novel Imaging Techniques in Acute Kidney Injury

    OpenAIRE

    Kalantarinia, Kambiz

    2009-01-01

    Imaging of the kidneys can provide valuable information in the work up and management of acute kidney injury. Several different imaging modalities are used to gather information on anatomy of the kidney, to rule out obstruction, differentiate acute kidney injury (AKI) and chronic kidney disease and to obtain information on renal blood flow and GFR. Ultrasound is the most widely used imaging modality used in the initial work up of AKI. The utility of contrast enhanced computerized tomography a...

  1. Targeted fibrillar nanocarbon RNAi treatment of acute kidney injury

    Science.gov (United States)

    Alidori, Simone; Akhavein, Nima; Thorek, Daniel L. J.; Behling, Katja; Romin, Yevgeniy; Queen, Dawn; Beattie, Bradley J.; Manova-Todorova, Katia; Bergkvist, Magnus; Scheinberg, David A.; McDevitt, Michael R.

    2016-01-01

    RNA interference has tremendous yet unrealized potential to treat a wide range of illnesses. Innovative solutions are needed to protect and selectively deliver small interfering RNA (siRNA) cargo to and within a target cell to fully exploit siRNA as a therapeutic tool in vivo. Herein, we describe ammonium-functionalized carbon nanotube (fCNT)–mediated transport of siRNA selectively and with high efficiency to renal proximal tubule cells in animal models of acute kidney injury (AKI). fCNT enhanced siRNA delivery to tubule cells compared to siRNA alone and effectively knocked down the expression of several target genes, including Trp53, Mep1b, Ctr1, and EGFP. A clinically relevant cisplatin-induced murine model of AKI was used to evaluate the therapeutic potential of fCNT-targeted siRNA to effectively halt the pathogenesis of renal injury. Prophylactic treatment with a combination of fCNT/siMep1b and fCNT/siTrp53 significantly improved progression-free survival compared to controls via a mechanism that required concurrent reduction of meprin-1β and p53 expression. The fCNT/siRNA was well tolerated, and no toxicological consequences were observed in murine models. Toward clinical application of this platform, fCNTs were evaluated for the first time in nonhuman primates. The rapid and kidney-specific pharmacokinetic profile of fCNT in primates was comparable to what was observed in mice and suggests that this approach is amenable for use in humans. The nanocarbon-mediated delivery of siRNA provides a therapeutic means for the prevention of AKI to safely overcome the persistent barrier of nephrotoxicity during medical intervention. PMID:27009268

  2. The cell cycle and acute kidney injury

    OpenAIRE

    Price, Peter M.; Safirstein, Robert L.; Megyesi, Judit

    2009-01-01

    Acute kidney injury (AKI) activates pathways of cell death and cell proliferation. Although seemingly discrete and unrelated mechanisms, these pathways can now be shown to be connected and even to be controlled by similar pathways. The dependence of the severity of renal-cell injury on cell cycle pathways can be used to control and perhaps to prevent acute kidney injury. This review is written to address the correlation between cellular life and death in kidney tubules, especially in acute ki...

  3. Pre-treatment with cardamonin protects against cisplatin-induced nephrotoxicity in rats: Impact on NOX-1, inflammation and apoptosis

    International Nuclear Information System (INIS)

    Cisplatin is an effective anti-cancer drug; however, its clinical use is usually associated with nephrotoxicity as a dose-limiting side effect. Several molecular mechanisms have been found to be involved in this nephrotoxicity such as oxidative stress, inflammation and apoptosis. The aim of this study was to explore the potential nephroprotective effect of cardamonin, a flavone found in Alpinia plant, in a rat model of cisplatin-induced nephrotoxicity. The possible mechanisms underlying this nephroprotective effect were investigated. Cardamonin was given at two different doses; 10 and 30 mg/kg orally for two weeks, starting one week before giving a single nephrotoxic dose of cisplatin (7 mg/kg). Acute nephrtoxicity was evident by significantly increased blood urea nitrogen and serum creatinine levels. Also, cisplatin increased lipid peroxidation and depleted reduced glutathione level and superoxide dismutase. Additionally, cisplatin showed a marked pro-inflammatory response as evidenced by significant increase in tissue levels of IL-1β, TNF-α, NF-kB, iNOS, ICAM-1 and MCP-1. Pre-treatment with cardamonin significantly attenuated the nephrotoxic effects, oxidative stress and inflammation induced by cisplatin, in a dose-dependent manner. Also, cardamonin decreased caspase-3 expression and Bax/Bcl-2 ratio as compared to cisplatin group. Besides, cradamonin reversed cisplatin-induced decrease in EGF. Furthermore, up-regulation of NOX-1 was found to be involved in cisplatin-induced nephrotoxicity and its expression was significantly reduced by cardamonin. Histopathological examination further confirmed the nephroprotective effect of cardamonin. Moreover, pre-treatment with subtoxic concentration of cardamonin has significantly enhanced cisplatin cytotoxic activity in four different human cancer cell lines; hela, hepG2, PC3 and HCT116 cancer cell lines. In conclusion, these findings suggest that cardamonin improves therapeutic index of cisplatin and that NOX-1 is

  4. Pre-treatment with cardamonin protects against cisplatin-induced nephrotoxicity in rats: Impact on NOX-1, inflammation and apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    El-Naga, Reem N., E-mail: reemelnaga@hotmail.com

    2014-01-01

    Cisplatin is an effective anti-cancer drug; however, its clinical use is usually associated with nephrotoxicity as a dose-limiting side effect. Several molecular mechanisms have been found to be involved in this nephrotoxicity such as oxidative stress, inflammation and apoptosis. The aim of this study was to explore the potential nephroprotective effect of cardamonin, a flavone found in Alpinia plant, in a rat model of cisplatin-induced nephrotoxicity. The possible mechanisms underlying this nephroprotective effect were investigated. Cardamonin was given at two different doses; 10 and 30 mg/kg orally for two weeks, starting one week before giving a single nephrotoxic dose of cisplatin (7 mg/kg). Acute nephrtoxicity was evident by significantly increased blood urea nitrogen and serum creatinine levels. Also, cisplatin increased lipid peroxidation and depleted reduced glutathione level and superoxide dismutase. Additionally, cisplatin showed a marked pro-inflammatory response as evidenced by significant increase in tissue levels of IL-1β, TNF-α, NF-kB, iNOS, ICAM-1 and MCP-1. Pre-treatment with cardamonin significantly attenuated the nephrotoxic effects, oxidative stress and inflammation induced by cisplatin, in a dose-dependent manner. Also, cardamonin decreased caspase-3 expression and Bax/Bcl-2 ratio as compared to cisplatin group. Besides, cradamonin reversed cisplatin-induced decrease in EGF. Furthermore, up-regulation of NOX-1 was found to be involved in cisplatin-induced nephrotoxicity and its expression was significantly reduced by cardamonin. Histopathological examination further confirmed the nephroprotective effect of cardamonin. Moreover, pre-treatment with subtoxic concentration of cardamonin has significantly enhanced cisplatin cytotoxic activity in four different human cancer cell lines; hela, hepG2, PC3 and HCT116 cancer cell lines. In conclusion, these findings suggest that cardamonin improves therapeutic index of cisplatin and that NOX-1 is

  5. Adenovirus-Mediated Over-Expression of Nrf2 Within Mesenchymal Stem Cells (MSCs Protected Rats Against Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    Mohammad Mohammadzadeh-Vardin

    2015-06-01

    Full Text Available Purpose: Recent developments in the field of cell therapy have led to a renewed interest in treatment of acute kidney injury (AKI. However, the early death of transplanted mesenchymal stem cells (MSCs in stressful microenvironment of a recipient tissue is a major problem with this kind of treatment. The objective of this study was to determine whether overexpression of a cytoprotective factor, nuclear factor erythroid-2 related factor 2 (Nrf2, in MSCs could protect rats against AKI. Methods: The Nrf2 was overexpressed in MSCs by recombinant adenoviruses, and the MSCs were implanted to rats suffering from cisplatin-induced AKI. Results: The obtained results showed that transplantation with the engineered MSCs ameliorates cisplatin-induced AKI. Morphologic features of the investigated kidneys showed that transplantation with the MSCs in which Nrf2 had been overexpressed significantly improved the complications of AKI. Conclusion: These findings suggested that the engineered MSCs might be a good candidate to be further evaluated in clinical trials. However, detailed studies must be performed to investigate the possible carcinogenic effect of Nrf2 overexpression.

  6. Acute kidney injury in children

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    Peco-Antić Amira

    2014-01-01

    Full Text Available Acute kidney injury (AKI is a clinical condition considered to be the consequence of a sudden decrease (>25% or discontinuation of renal function. The term AKI is used instead of the previous term acute renal failure, because it has been demonstrated that even minor renal lesions may cause far-reaching consequences on human health. Contemporary classifications of AKI (RIFLE and AKIN are based on the change of serum creatinine and urinary output. In the developed countries, AKI is most often caused by renal ischemia, nephrotoxins and sepsis, rather than a (primary diffuse renal disease, such as glomerulonephritis, interstitial nephritis, renovascular disorder and thrombotic microangiopathy. The main risk factors for hospital AKI are mechanical ventilation, use of vasoactive drugs, stem cell transplantation and diuretic-resistant hypervolemia. Prerenal and parenchymal AKI (previously known as acute tubular necrosis jointly account for 2/3 of all AKI causes. Diuresis and serum creatinine concentration are not early diagnostic markers of AKI. Potential early biomarkers of AKI are neutrophil gelatinase-associated lipocalin (NGAL, cystatin C, kidney injury molecule-1 (KIM-1, interleukins 6, 8 and 18, and liver-type fatty acid-binding protein (L-FABP. Early detection of kidney impairment, before the increase of serum creatinine, is important for timely initiated therapy and recovery. The goal of AKI treatment is to normalize the fluid and electrolyte status, as well as the correction of acidosis and blood pressure. Since a severe fluid overload resistant to diuretics and inotropic agents is associated with a poor outcome, the initiation of dialysis should not be delayed. The mortality rate of AKI is highest in critically ill children with multiple organ failure and hemodynamically unstable patients.

  7. Nephrology Update: Acute Kidney Injury.

    Science.gov (United States)

    Sarabu, Nagaraju; Rahman, Mahboob

    2016-05-01

    Acute kidney injury (AKI) refers to any acute decrease in glomerular filtration rate, regardless of etiology. Staging of AKI has been recommended to stratify AKI patients according to severity of the condition, based on serum creatinine level and urine output. Classification of AKI into prerenal, intrinsic renal, and postrenal etiologies is helpful in differential diagnosis and management. AKI in hospitalized patients typically occurs due to decreased renal perfusion. Drug-induced, contrast-associated, postoperative, and sepsis-associated AKI also can occur. Clinical assessment of a patient with AKI involves a medical record review, thorough history and physical examination, urinary and blood tests, renal imaging, and, in some instances, renal biopsy. Contrast-induced nephropathy is a common iatrogenic etiology of AKI associated with administration of intravenous iodinated contrast media. Measures to prevent AKI should be taken before administration of intravenous iodinated contrast. AKI can result in many short- and long-term complications, including chronic kidney disease and end-stage renal disease. Appropriate treatment of AKI patients involves management of the underlying etiology, when possible, and use of nondialytic and dialytic therapies. PMID:27163760

  8. Is Progressive Chronic Kidney Disease a Slow Acute Kidney Injury?

    Science.gov (United States)

    Cowgill, Larry D; Polzin, David J; Elliott, Jonathan; Nabity, Mary B; Segev, Gilad; Grauer, Gregory F; Brown, Scott; Langston, Cathy; van Dongen, Astrid M

    2016-11-01

    International Renal Interest Society chronic kidney disease Stage 1 and acute kidney injury Grade I categorizations of kidney disease are often confused or ignored because patients are nonazotemic and generally asymptomatic. Recent evidence suggests these seemingly disparate conditions may be mechanistically linked and interrelated. Active kidney injury biomarkers have the potential to establish a new understanding for traditional views of chronic kidney disease, including its early identification and possible mediators of its progression, which, if validated, would establish a new and sophisticated paradigm for the understanding and approach to the diagnostic evaluation, and treatment of urinary disease in dogs and cats. PMID:27593574

  9. Role of ellagic acid against cisplatin-induced nephrotoxicity and oxidative stress in rats.

    Science.gov (United States)

    Ateşşahín, Ahmet; Ceríbaşi, Ali Osman; Yuce, Abdurrauf; Bulmus, Ozgür; Cikim, Gürkan

    2007-02-01

    The aim of this study was to investigate the possible protective role of antioxidant treatment with ellagic acid on cisplatin-induced nephrotoxicity using biochemical and histopatological approaches. Adult male Sprague-Dawley rats were randomly divided into four groups. The control group received 0.9% saline; animals in the ellagic acid group received only ellagic acid (10 mg/kg); animals in the cisplatin group received only cisplatin (7 mg/kg); animals in the cisplatin + ellagic acid group received ellagic acid for 10 days after cisplatin. The effects of ellagic acid on cisplatin-induced nephrotoxicity were evaluated by plasma creatinine, urea, sodium and calcium concentrations; kidney tissue malondialdehyde, reduced glutathione (GSH), glutathione peroxidase (GSH peroxidase) and catalase activities and histopatological examinations. Administration of cisplatin to rats induced a marked renal failure, characterized by significant increases in plasma creatinine, urea and calcium concentrations. Cisplatin also induced oxidative stress, as indicated by increased kidney tissue concentrations of malondialdehyde, and reduced activities of GSH peroxidase and catalase. Furthermore, treatment with cisplatin caused a marked tubular necrosis, degeneration and desquamation, luminal cast formation, karyomegaly, tubular dilatation, interstitial mononuclear cell infiltration and inter-tubular haemorrhagia. Ellagic acid markedly reduced elevated plasma creatinine, urea and calcium levels and counteracted the deleterious effects of cisplatin on oxidative stress markers. In the same way, ellagic acid ameliorated cisplatin-induced pathological changes including tubular necrosis, degeneration, karyomegaly, tubular dilatation when compared to the cisplatin alone group. These results indicate that the antioxidant ellagic acid might have a protective effect against cisplatin-induced nephrotoxicity and oxidative stress in rat, but not enough to inhibit cisplatin-induced renal dysfunction.

  10. Hydrogen sulfide: A novel nephroprotectant against cisplatin-induced renal toxicity.

    Science.gov (United States)

    Dugbartey, George J; Bouma, Hjalmar R; Lobb, Ian; Sener, Alp

    2016-07-01

    Cisplatin is a potent chemotherapeutic agent for the treatment of various solid-organ cancers. However, a plethora of evidence indicates that nephrotoxicity is a major side effect of cisplatin therapy. While the antineoplastic action of cisplatin is due to formation of cisplatin-DNA cross-links, which damage rapidly dividing cancer cells upon binding to DNA, its nephrotoxic effect results from metabolic conversion of cisplatin into a nephrotoxin and production of reactive oxygen species, causing oxidative stress leading to renal tissue injury and potentially, kidney failure. Despite therapeutic targets in several pre-clinical and clinical studies, there is still incomplete protection against cisplatin-induced nephrotoxicity. Hydrogen sulfide (H2S), the third discovered gasotransmitter next to nitric oxide and carbon monoxide, has recently been identified in several in vitro and in vivo studies to possess specific antioxidant, anti-inflammatory and anti-apoptotic properties that modulate several pathogenic pathways involved in cisplatin-induced nephrotoxicity. The current article reviews the molecular mechanisms underlying cisplatin-induced nephrotoxicity and displays recent findings in the H2S field that could disrupt such mechanisms to ameliorate cisplatin-induced renal injury.

  11. Contrast-associated Acute Kidney Injury.

    Science.gov (United States)

    Weisbord, Steven D; Palevsky, Paul M

    2015-10-01

    Contrast-associated acute kidney injury (CAAKI) is a common iatrogenic condition. The principal risk factors for CAAKI are underlying renal impairment; diabetes in the setting of kidney disease; and intravascular volume depletion, effective or absolute. CAAKI is associated with serious adverse short-term and long-term outcomes, including mortality and more rapidly progressive chronic kidney disease, although the causal nature of these associations remains unproved. Patients with chronic kidney disease and other risk factors for CAAKI who present with acute coronary syndrome should undergo indicated angiographic procedures.

  12. Long-term aerobic exercise protects against cisplatin-induced nephrotoxicity by modulating the expression of IL-6 and HO-1.

    Directory of Open Access Journals (Sweden)

    Mariana Yasue Saito Miyagi

    Full Text Available Nephrotoxicity is substantial side effect for 30% of patients undergoing cancer therapy with cisplatin and may force them to change or even abandon the treatment. Studies regarding aerobic exercise have shown its efficacy for the treatment of many types of diseases and its capacity to reduce tumors. However, little is known about the impact of physical exercise on cisplatin-induced acute kidney injury (AKI. In the present study, our aim was to investigate the role of physical exercise in AKI induced by cisplatin. We submitted C57Bl6 male mice to seven weeks of chronic exercise on a training treadmill and treated them with single i.p. injection of cisplatin (20 mg/kg in the last week. Exercise efficacy was confirmed by an increased capillary-to-fiber ratio in the gastrocnemius muscle of exercised groups (EX and CIS-EX. The group submitted to exercise before cisplatin administration (CIS-EX exhibited less weight loss and decreased serum urea levels compared to the cisplatin group (CIS. Exercise also showed a protective role against cisplatin-induced cell death in the kidney. The CIS-EX group showed a lower inflammatory response, with less TNF and IL-10 expression in the kidney and serum. In the same group, we observed an increase of IL-6 and HO-1 expression in the kidney. Taken together, our results indicate that chronic aerobic exercise is able to attenuate AKI by inducing IL-6 and HO-1 production, which results in lower inflammatory and apoptotic profiles in the kidney.

  13. Acute Kidney Injury due to Crescentic Glomerulonephritis in a Patient with Polycystic Kidney Disease

    OpenAIRE

    Maggard, Reuben; Makary, Raafat; Monteiro, Carmela l.; James, Leighton R.

    2013-01-01

    Polycystic kidney disease is an inherited condition, characterized by the development of cysts in the kidney, as well as in other organs. Patients with polycystic kidney can suffer from the same causes of acute kidney injury as the general population. Nephritic syndrome is an uncommon cause of acute kidney injury in the general population and less common in patients with polycystic kidney disease. We report the second case of crescentic glomerulonephritis, causing acute kidney injury, in a pa...

  14. Cisplatin-induced anorexia and ghrelin.

    Science.gov (United States)

    Hattori, Tomohisa; Yakabi, Koji; Takeda, Hiroshi

    2013-01-01

    Cisplatin, a formidable anticancer treatment, is used for several varieties of cancer. There are, however, many cases in which treatment must be abandoned due to a decrease in the patient's quality of life from loss of appetite associated with vomiting and nausea. There is a moderate degree of improvement in prevention of cisplatin-induced nausea and vomiting when serotonin (5-HT) 3 receptor antagonists, neurokinin 1 receptor antagonists, and steroids-either alone or in combination-are administered. The mechanism of action for anorexia, which continues during or after treatment, is, however, still unclear. This anorexia is, similar to the onset of vomiting and nausea, caused by the action of large amounts of 5-HT released as a result of cisplatin administration on tissue 5-HT receptors. Among the 5-HT receptors, the activation of 5-HT2b and 5-HT2c receptors, in particular, seems to play a major role in cisplatin-induced anorexia. Following activation of these two receptors, there is reduced gastric and hypothalamic secretion of the appetite-stimulating hormone ghrelin. There is ample evidence of the usefulness of exogenous ghrelin, synthetic ghrelin agonists, and the endogenous ghrelin signal-enhancer rikkunshito, which are expected to play significant roles in the clinical treatment and prevention of anorexia in future.

  15. Cellular Responses to Cisplatin-Induced DNA Damage

    Directory of Open Access Journals (Sweden)

    Alakananda Basu

    2010-01-01

    Full Text Available Cisplatin is one of the most effective anticancer agents widely used in the treatment of solid tumors. It is generally considered as a cytotoxic drug which kills cancer cells by damaging DNA and inhibiting DNA synthesis. How cells respond to cisplatin-induced DNA damage plays a critical role in deciding cisplatin sensitivity. Cisplatin-induced DNA damage activates various signaling pathways to prevent or promote cell death. This paper summarizes our current understandings regarding the mechanisms by which cisplatin induces cell death and the bases of cisplatin resistance. We have discussed various steps, including the entry of cisplatin inside cells, DNA repair, drug detoxification, DNA damage response, and regulation of cisplatin-induced apoptosis by protein kinases. An understanding of how various signaling pathways regulate cisplatin-induced cell death should aid in the development of more effective therapeutic strategies for the treatment of cancer.

  16. The innate immune response in ischemic acute kidney injury

    OpenAIRE

    Jang, Hye Ryoun; Rabb, Hamid

    2008-01-01

    Kidney ischemia reperfusion injury is a major cause of morbidity in both allograft and native kidneys. Ischemia reperfusion-induced acute kidney injury is characterized by early, allo-antigen independent inflammation. Major components of the innate immune system are activated and participate in the pathogenesis of acute kidney injury, plus prime the allograft kidney for rejection. Soluble members of innate immunity implicated in acute kidney injury include the complement system, cytokines, an...

  17. New biomarkers of acute kidney injury

    Directory of Open Access Journals (Sweden)

    Ruya Ozelsancak

    2013-04-01

    Full Text Available Acute kidney injury is a clinical syndrome which is generally defined as an abrupt decline in glomerular filtration rate causing accumulation of nitrogenous products and rapid development of fluid, electrolyte and acid-base disorders. It is an important clinical problem increasing mortality in patient with several co-morbid conditions. The frequency of acute kidney injury occurrence varies from 5% on the inpatients wards to 30-50% in patients from intensive care units. Serial measurement of creatinine and urine volume do not make it possible to diagnose acute kidney injury at early stages. Serum creatinine may be influenced by age, weight, hydration status and become apparent only when the kidneys have lost 50% of their function. For that reasons we need new markers. Here, we are reviewing the most promising new acute kidney injury markers, neutrophil gelatinase associated lipocalin, cystatin-C, kidney injury molecule-1, liver fatty acid binding proteins and IL-18. [Archives Medical Review Journal 2013; 22(2.000: 221-229

  18. Ritonavir-induced acute kidney injury: kidney biopsy findings and review of literature

    OpenAIRE

    Shafi, T.; Choi, M.J.; Racusen, L. C.; Spacek, L. A.; Berry, C; Atta, M.; Fine, D.M.

    2011-01-01

    Ritonavir therapy is not generally considered nephrotoxic. We report a case of acute kidney injury secondary to ritonavir, with kidney biopsy demonstrating extensive acute tubular injury. This is the first report of a kidney biopsy and pathology in acute kidney injury associated with ritonavir. A review of published medical literature on the topic is also presented.

  19. Acute kidney injury and rhabdomyolysis due to multiple wasp stings

    OpenAIRE

    Hemachandar Radhakrishnan

    2014-01-01

    In most patients, wasp stings cause local reactions and rarely anaphylaxis. Acute kidney injury and rhabdomyolysis are unusual complications of wasp stings. We report a case of acute kidney injury and rhabdomyolysis secondary to multiple wasp stings. A 55-year-old farmer developed multi organ dysfunction with acute kidney injury and rhabdomyolysis 3 days after he had sustained multiple wasp stings. The etiology of acute kidney injury is probably both rhabdomyolysis and acute tubular necrosis....

  20. Acute Kidney Injury Associated with Linagliptin.

    Science.gov (United States)

    Nandikanti, Deepak K; Gosmanova, Elvira O; Gosmanov, Aidar R

    2016-01-01

    Linagliptin is a dipeptidyl peptidase-IV (DPP-IV) inhibitor that is approved for the treatment of type 2 diabetes mellitus. About 5% of linagliptin is eliminated by the kidneys and no dose adjustment is recommended in kidney impairment. We report a first case of linagliptin-associated acute kidney injury (AKI) in a patient with preexisting chronic kidney disease (CKD). We hypothesize that AKI was due to renal hypoperfusion from linagliptin-induced natriuresis and intravascular volume contraction in the setting of concomitant lisinopril use, which is known to impair autoregulation and potentiate hypotension-induced AKI. It may be prudent to exert caution and closely monitor kidney function when initiating linagliptin in combination with ACE-inhibitors in CKD patients. PMID:26981294

  1. Acute Kidney Injury Associated with Linagliptin

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    Deepak K. Nandikanti

    2016-01-01

    Full Text Available Linagliptin is a dipeptidyl peptidase-IV (DPP-IV inhibitor that is approved for the treatment of type 2 diabetes mellitus. About 5% of linagliptin is eliminated by the kidneys and no dose adjustment is recommended in kidney impairment. We report a first case of linagliptin-associated acute kidney injury (AKI in a patient with preexisting chronic kidney disease (CKD. We hypothesize that AKI was due to renal hypoperfusion from linagliptin-induced natriuresis and intravascular volume contraction in the setting of concomitant lisinopril use, which is known to impair autoregulation and potentiate hypotension-induced AKI. It may be prudent to exert caution and closely monitor kidney function when initiating linagliptin in combination with ACE-inhibitors in CKD patients.

  2. Thalidomide ameliorates cisplatin-induced nephrotoxicity by inhibiting renal inflammation in an experimental model.

    Science.gov (United States)

    Amirshahrokhi, Keyvan; Khalili, Ali-Reza

    2015-04-01

    Cisplatin is a platinum-based chemotherapy drug. However, its chemotherapeutic use is restricted by serious side effects, especially nephrotoxicity. Inflammatory mechanisms have a significant role in the pathogenesis of cisplatin-induced nephrotoxicity. Thalidomide is an immunomodulatory and anti-inflammatory agent and is used for the treatment of various inflammatory diseases. The purpose of this study was to investigate the potential nephroprotective effect of thalidomide in a mouse model of cisplatin-induced nephrotoxicity. Nephrotoxicity was induced in mice by a single injection of cisplatin (15 mg/kg, i.p.) and treated with thalidomide (50 and 100 mg/kg/day, orally) for 4 days, beginning 24 h prior to the cisplatin injection. Renal toxicity induced by cisplatin was demonstrated by increasing plasma levels of creatinine and blood urea nitrogen (BUN). Cisplatin increased the renal production of the proinflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and transforming growth factor (TGF)-β1. In addition, kidney levels of malondialdehyde (MDA), myeloperoxidase (MPO), and nitric oxide (NO) were increased by cisplatin. Biochemical results showed that thalidomide reduced cisplatin-induced increase in plasma creatinine and BUN. Thalidomide treatment also significantly reduced tissue levels of the proinflammatory cytokines, MDA, MPO, and NO and increased anti-inflammatory cytokine IL-10. Furthermore, histological examination indicated that thalidomide ameliorated renal damage caused by cisplatin. These data suggest that thalidomide attenuates cisplatin-induced nephrotoxicity possibly by inhibition of inflammatory reactions. Taken together, our findings indicate that thalidomide might be a valuable candidate for the prevention of nephrotoxicity in patients receiving cisplatin.

  3. Flavonoids, the emerging dietary supplement against cisplatin-induced nephrotoxicity.

    Science.gov (United States)

    Athira, K V; Madhana, Rajaram Mohanrao; Lahkar, Mangala

    2016-03-25

    The letter illustrates the emerging potential of flavonoids as dietary supplement to ameliorate cisplatin-induced nephrotoxicity and refers to the recent article on ''Anti-apoptotic and anti-inflammatory effects of naringin on cisplatin-induced renal injury in the rat'' by Chtourou et al. They demonstrated that supplementation of naringin, a flavanone glycoside, found in grape and citrus fruit species, can attenuate cisplatin-induced renal dysfunction via restoration of redox balance and suppression of inflammation, NF-κB activation and apoptosis. The chemotherapeutic efficacy of cisplatin has always compelled the researchers to find solution to ameliorate its side effects. In recent years, numerous candidates have been evaluated for their protective potential against cisplatin-induced nephrotoxicity and flavonoids have come up with promising results. The future prospects might be promising with a proper refinement and collective integration of the preclinical and clinical research in the field of flavonoid supplementation to cisplatin therapy. PMID:26876905

  4. Acute kidney injury following isotretinoin treatment

    OpenAIRE

    Armaly, Zaher; Haj, Shehadeh; Bowirrat, Abdalla; Alhaj, Mohammed; Jabbour, Adel; Fahoum, Yumna; Abassi, Zaid

    2013-01-01

    Patient: Female, 17 Final Diagnosis: Acute kidney injury Symptoms: Flank pain • nausea • vomiting Medication: Isotretinoin Clinical Procedure: Acne treatment Specialty: Nephrology Objective: Unknown etiology Background: Isotretinoin is widely used for the treatment of acne that is unresponsive to topical therapy. Despite its efficacy, isotretinoin has various adverse effects, including cheilitis, increased risk of cutaneous Staphylococcus aureus infections, and liver function abnormalities. C...

  5. Protective effects of pine bark extract against cisplatin-induced hepatotoxicity and oxidative stress in rats.

    Science.gov (United States)

    Ko, Je-Won; Lee, In-Chul; Park, Sung-Hyuk; Moon, Changjong; Kang, Seong-Soo; Kim, Sung-Ho; Kim, Jong-Choon

    2014-12-01

    We investigated the protective effects of pine bark extract (pycnogenol®, PYC) against cisplatin-induced hepatotoxicity and oxidative stress in rats. Twenty-four male rats were divided into the following four groups: (1) vehicle control, (2) cisplatin (7.5 mg/kg), (3) cisplatin & PYC 10 (10 mg/kg/day), and (4) cisplatin & PYC 20 (20 mg/kg/day). A single intraperitoneal injection of cisplatin induced hepatotoxicity, as evidenced by an increase in serum aminotransferase and histopathological alterations, including degeneration/necrosis of hepatocytes, vacuolation, and sinusoidal dilation. In addition, an increase in the malondialdehyde (MDA) concentration and a decrease in the reduced glutathione (GSH) content and catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST) activities were observed in the cisplatin-treated rat hepatic tissues. In contrast, PYC treatment effectively prevented cisplatin-induced hepatotoxicity, including the elevation of aminotransferase and histopathological lesions, in a dosedependent manner. Moreover, PYC treatment also induced antioxidant activity by decreasing MDA level and increasing GSH content and SOD and GST activities in liver tissues. These results indicate that PYC has a protective effect against acute hepatotoxicity induced by cisplatin in rats, and that the protective effects of PYC may be due to inhibiting lipid peroxidation and increasing antioxidant activity. PMID:25628728

  6. Cetuximab intensifies cisplatin-induced testicular toxicity.

    Science.gov (United States)

    Levi, Mattan; Popovtzer, Aron; Tzabari, Moran; Mizrachi, Aviram; Savion, Naphtali; Stemmer, Salomon M; Shalgi, Ruth; Ben-Aharon, Irit

    2016-07-01

    Epidermal growth factor receptor (EGFR) has proliferative properties in the testis. Cetuximab, an anti-EGFR, is administered together with chemotherapy to patients with various types of cancer. This studies aim was to investigate the effect of cetuximab on testicular function. Adult male mice were injected with cetuximab (10 mg/kg), cisplatin (8 mg/kg) or a combination of both, and killed one week or one month later. The doses were chosen by human equivalent dose calculation. Testicular function was evaluated by epididymal-spermatozoa total motile count and sperm motility, weights of testes and epididymides, and the level of anti-Müllerian hormone (AMH) in the serum. Immunohistochemistry was performed to examine germ cell proliferation (Ki-67), apoptosis (Terminal transferase-mediated deoxyuridine 5-triphosphate nick-end labelling), reserve (DAZL-Deleted in azoospermia-like, Promyelocytic leukaemia zinc-finger), blood vessels (CD34) and Sertoli cells (GATA-4). Administration of cetuximab alone increased testicular apoptosis and decreased epididymal-spermatozoa total motile count over time. When added to cisplatin, cetuximab exacerbated most of the recorded testicular parameters, compared with the effect of cisplatin alone, including testis and epididymis weights, epididymal-spermatozoa total motile count, AMH concentration, meiosis and apoptosis. In conclusion, cetuximab has only a mild effect on testicular reserve, but when added to cisplatin, it exacerbates cisplatin-induced testicular toxicity. PMID:27184186

  7. Melatonin suppresses cisplatin-induced nephrotoxicity via activation of Nrf-2/HO-1 pathway

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    Kilic Ulkan

    2013-01-01

    Full Text Available Abstract Background Cisplatin, one of the most effective and potent anticancer drugs, is used in the treatment of a wide variety of both pediatric and adult malignancies. However, the chemotherapeutic use of cisplatin is limited by its serious side-effects such as nephrotoxicity and ototoxicity. Cisplatin chemotherapy induces a reduction in the antioxidant status, leading to a failure of the antioxidant defense against free-radical damage generated by antitumor drugs. Cisplatin-induced oxidative stress in the kidney was partially prevented by antioxidant treatments using superoxide dismutase, glutathione, selenium and flavonoids. Melatonin and its metabolites possess free-radical scavenging activity and it has been shown that they protect against cisplatin toxicity. However, the mechanism of the protective effects of melatonin against cisplatin-induced nephrotoxicity is still essentially unknown. We therefore designed this study to investigate the underlying mechanism of the protective effect of melatonin against cisplatin-induced renal damage in a rat nephrotoxicity model in vivo. Methods Twenty eight 8-week-old male Wistar rats were divided into four groups of control, melatonin treatment (4 mg/kg b.w i.p. for 10 days, cisplatin treatment (7 mg/kg b.w., i.p. and melatonin and cisplatin combination treatment. Serum urea nitrogen (urea-N and creatinine levels were measured. Histopathological changes were evaluated. In addition, we analyzed the expression levels of HO-1, Nrf2, NF-κB and AP-1 in Western blot analysis. Results Both serum creatinine and urea nitrogen increased significantly following cisplatin administration alone; these values decreased significantly with melatonin co-treatment of cisplatin-treated rats. Histological analysis showed that cisplatin caused damage in the proximal tubular cells in the kidneys of cisplatin-treated rats; these changes were reversed by melatonin co-treatment. Upon Western blot analysis, melatonin

  8. Ethanolic extract of Trigonella Foenum Graecum attenuates cisplatin-induced nephro- and hepatotoxicities in rats.

    Science.gov (United States)

    Hegazy, Marwa G A; Emam, Manal A

    2015-01-01

    Nephro-and hepatotoxicities are important complications in cancer patients undergoing cisplatin (CP) therapy. We aimed to study the protective effect of fenugreek (FG) on CP induced renal and hepatic injuries in rats. Cisplatin intoxication resulted in structural and functional renal and hepatic impairments, which were revealed by massive histopathological changes and elevated kidney and liver function tests. However, it was associated with oxidative stress and lipid peroxidation as evident by increased reactive oxygen species (ROS) and malondialdehyde (MDA) with decreased levels of total antioxidant activity. Cisplatin administration triggered inflammatory responses and apoptosis in rat livers and kidneys as evident by increased expression of pro-inflammatory cytokine, tumor necrosis factor- α (TNF-α) and apoptotic marker p38 mitogen-activated protein kinase (p38 MAPK) as results of overproduction of ROS. FG significantly attenuated the cisplatin-induced biochemical and histopathological alterations, inflammation and apoptosis in rat livers and kidneys. Results suggested that fenugreek co-administration has a powerful antioxidant effect and may serves as a novel and promising preventive strategy against cisplatin-induced nephron- and hepatotoxicities. PMID:26612737

  9. Acute kidney injury: A rare cause.

    Science.gov (United States)

    Mendonca, Satish; Barki, Satish; Mishra, Mayank; Kumar, R S V; Gupta, Devika; Gupta, Pooja

    2015-09-01

    We present a young lady who consumed hair dye, which contained paraphenylene diamine (PPD), as a means of deliberate self-harm. This resulted in severe angio-neurotic edema for which she had to be ventilated, and thereafter developed rhabdomyolysis leading to acute kidney injury (AKI). The unusual aspect was that the patient continued to have flaccid quadriparesis and inability to regain kidney function. Renal biopsy performed 10 weeks after the dye consumption revealed severe acute tubular necrosis with myoglobin pigment casts. This suggests that PPD has a long-term effect leading to ongoing myoglobinuria, causing flaccid paralysis to persist and preventing the recovery of AKI. In such instances, timely treatment to prevent AKI in the form alkalinization of urine should be initiated promptly. Secondly, because PPD is a nondialyzable toxin, and its long-term effect necessitates its speedy removal, hemoperfusion might be helpful and is worth considering. PMID:26354573

  10. Acute kidney injury: A rare cause

    Directory of Open Access Journals (Sweden)

    Satish Mendonca

    2015-01-01

    Full Text Available We present a young lady who consumed hair dye, which contained paraphenylene diamine (PPD, as a means of deliberate self-harm. This resulted in severe angio-neurotic edema for which she had to be ventilated, and thereafter developed rhabdomyolysis leading to acute kidney injury (AKI. The unusual aspect was that the patient continued to have flaccid quadriparesis and inability to regain kidney function. Renal biopsy performed 10 weeks after the dye consumption revealed severe acute tubular necrosis with myoglobin pigment casts. This suggests that PPD has a long-term effect leading to ongoing myoglobinuria, causing flaccid paralysis to persist and preventing the recovery of AKI. In such instances, timely treatment to prevent AKI in the form alkalinization of urine should be initiated promptly. Secondly, because PPD is a nondialyzable toxin, and its long-term effect necessitates its speedy removal, hemoperfusion might be helpful and is worth considering

  11. Acute kidney injury: current concepts and new insights

    OpenAIRE

    Yavuzer Koza

    2016-01-01

    Abstract: Background: Acute kidney injury, which was previously named as acute renal failure, is a complex clinical disorder and continues to be associated with poor outcomes. It is frequently seen in hospitalized patients, especially in critically ill patients. The primary causes of acute kidney injury are divided into three categories: prerenal, intrinsic renal and postrenal. The definition and staging of acute kidney injury are mainly based on the risk, injury, failure, loss, end-stage kid...

  12. Mediators of Inflammation in Acute Kidney Injury

    OpenAIRE

    Ali Akcay; Quocan Nguyen; Edelstein, Charles L.

    2010-01-01

    Acute kidney injury (AKI) remains to be an independent risk factor for mortality and morbidity. Inflammation is now believed to play a major role in the pathopathophysiology of AKI. It is hypothesized that in ischemia, sepsis and nephrotoxic models that the initial insult results in morphological and/or functional changes in vascular endothelial cells and/or in tubular epithelium. Then, leukocytes including neutrophils, macrophages, natural killer cells, and lymphocytes infiltrate into the in...

  13. Protective effects of ghrelin on cisplatin-induced nephrotoxicity in mice.

    Science.gov (United States)

    Nojiri, Takashi; Hosoda, Hiroshi; Kimura, Toru; Tokudome, Takeshi; Miura, Koichi; Takabatake, Hiroyuki; Miyazato, Mikiya; Okumura, Meinoshin; Kangawa, Kenji

    2016-08-01

    Cisplatin is a potent chemotherapeutic agent that has activity against malignant tumors. However, cisplatin causes various adverse effects, such as nephrotoxicity, which are associated with high morbidity and mortality. Recent studies have revealed that the mechanism of cisplatin nephrotoxicity includes a robust inflammatory response. Since ghrelin has been shown to have anti-inflammatory properties, we hypothesized that ghrelin might have protective effects against cisplatin nephrotoxicity. Mice were randomly divided into three groups: control, cisplatin with vehicle, and cisplatin with ghrelin. Ghrelin (0.8μg/kg/min via osmotic-pump, subcutaneously) or vehicle administration was started one day before cisplatin injection. At 72h after cisplatin administration (20mg/kg, intraperitoneally), we measured serum blood urea nitrogen and creatinine, urine albumin/creatinine, renal mRNA levels of monocyte chemoattractant protein-1, interleukin-6, tumor necrosis factor-α, interleukin-1β, kidney injury molecule-1, and neutrophil gelatinase-associated lipocalin by real-time polymerase chain reaction, and histological changes. Ghrelin significantly attenuated the increase in serum blood urea nitrogen and creatinine induced by cisplatin. Ghrelin tended to attenuate the increase in urine albumin/creatinine, although not significantly. Cisplatin-induced renal tubular injury and apoptosis were significantly attenuated by ghrelin pretreatment. Consequently, ghrelin significantly attenuated renal mRNA levels of monocyte chemoattractant protein-1, interleukin-6, kidney injury molecule-1, and neutrophil gelatinase-associated lipocalin. In conclusion, ghrelin produces protective effects in cisplatin-induced nephrotoxicity through inhibition of inflammatory reactions. Pretreatment with ghrelin may become a new prophylactic candidate for cisplatin-induced nephrotoxicity. PMID:27298204

  14. Mechanisms of cisplatin-induced muscle atrophy

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    Sakai, Hiroyasu, E-mail: sakai@hoshi.ac.jp [Department of Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Division of Pharmacy Professional Development and Research, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Sagara, Atsunobu; Arakawa, Kazuhiko; Sugiyama, Ryoto; Hirosaki, Akiko; Takase, Kazuhide; Jo, Ara [Department of Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Sato, Ken [Department of Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Division of Pharmacy Professional Development and Research, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Chiba, Yoshihiko [Department of Biology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Yamazaki, Mitsuaki [Department of Anesthesiology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 9300194 (Japan); Matoba, Motohiro [Department of Palliative Medicine and Psychooncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 1040045 (Japan); Narita, Minoru, E-mail: narita@hoshi.ac.jp [Department of Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan)

    2014-07-15

    Fatigue is the most common side effect of chemotherapy. However, the mechanisms of “muscle fatigue” induced by anti-cancer drugs are not fully understood. We therefore investigated the muscle-atrophic effect of cisplatin, a platinum-based anti-cancer drug, in mice. C57BL/6J mice were treated with cisplatin (3 mg/kg, i.p.) or saline for 4 consecutive days. On Day 5, hindlimb and quadriceps muscles were isolated from mice. The loss of body weight and food intake under the administration of cisplatin was the same as those in a dietary restriction (DR) group. Under the present conditions, the administration of cisplatin significantly decreased not only the muscle mass of the hindlimb and quadriceps but also the myofiber diameter, compared to those in the DR group. The mRNA expression levels of muscle atrophy F-box (MAFbx), muscle RING finger-1 (MuRF1) and forkhead box O3 (FOXO3) were significantly and further increased by cisplatin treated group, compared to DR. Furthermore, the mRNA levels of myostatin and p21 were significantly upregulated by the administration of cisplatin, compared to DR. On the other hand, the phosphorylation of Akt and FOXO3a, which leads to the blockade of the upregulation of MuRF1 and MAFbx, was significantly and dramatically decreased by cisplatin. These findings suggest that the administration of cisplatin increases atrophic gene expression, and may lead to an imbalance between protein synthesis and protein degradation pathways, which would lead to muscle atrophy. This phenomenon could, at least in part, explain the mechanism of cisplatin-induced muscle fatigue. - Highlights: • Cisplatin decreased mass and myofiber diameter in quadriceps muscle. • The mRNA of MAFbx, MuRF1 and FOXO3 were increased by the cisplatin. • The mRNA of myostatin and p21 were upregulated by cisplatin. • The phosphorylation of Akt and FOXO3a was decreased by cisplatin.

  15. [Hyperhydration and dialysis in acute kidney failure].

    Science.gov (United States)

    Saner, Fuat H; Bienholz, Anja; Tyczynski, Bartosz; Kribben, Andreas; Feldkamp, Thorsten

    2015-05-01

    Despite the advances in critical care medicine, the hospital mortality in patients with acute kidney injury (AKI) requiring dialysis remains high. Depending on the underlying disease the in-house mortality is reported to be up to 80%. Several observational studies demonstrated an association between mortality and fluid overload. A primary mechanism of interest is that fluid overload causes tissue edema and subsequent reduction of perfusion, oxygenation and nutrient delivery. This results in further renal damage. In addition, fluid overload-related dilution within the extracellular space causes artificially low serum creatinine, which masks AKI diagnosis. As a consequence, renal protective management strategies are deferred, which further aggravates kidney injury. This aggravation of renal damage subsequently increases the mortality. This review discusses the role of fluid overload for outcomes in critically ill patients as described in the current literature and assesses criteria for the initiation of renal replacement therapy in this critically ill population. PMID:25970415

  16. Acute Kidney Injury – An Update

    Directory of Open Access Journals (Sweden)

    Matt Varrier

    2015-07-01

    Full Text Available The syndrome of acute kidney injury (AKI occurs frequently in hospitalised patients, leading to increased morbidity, mortality, and healthcare expenditure. In the context of a precipitating insult, disturbances in both global and microcirculatory renal blood flow, tubular cell damage, and activation of pro- inflammatory pathways lead to impairment of numerous elements of renal function. Classification systems, including the recent ‘Kidney Disease: Improving Global Outcomes’ (KDIGO classification, typically define and stage AKI in terms of the magnitude of rise in serum creatinine (SCr and the presence of oliguria. At present there is no cure for AKI and the key principles of its management include early recognition, haemodynamic optimisation, correction of hypovolaemia, ceasing and avoidance of nephrotoxic medications, and treatment of the underlying cause. Recent data show that the type and volume of fluid therapy can affect renal function and that further guidance is required. In the future it is hoped that novel technologies, including biomarkers and real-time measurement of glomerular filtration rate will allow the earlier identification of patients with AKI, whilst a greater understanding of the pathogenesis of AKI will lead to the identification of new therapeutic targets. Despite SCr usually recovering after an episode of AKI, there is growing recognition that survivors of AKI are at an increased risk of subsequent chronic kidney disease, including end-stage renal failure and premature death.

  17. Differential effects of kidney-lung cross-talk during acute kidney injury and bacterial pneumonia

    OpenAIRE

    Singbartl, Kai; Bishop, Jeffery; Wen, Xiaoyan; Murugan, Raghavan; Chandra, Saurabh; Filippi, Marie-Dominique; John A Kellum

    2011-01-01

    Acute kidney injury (AKI) and acute lung injury (ALI) represent serious, complex clinical problems. The combination of AKI and ALI drastically decreases survival. However, detailed knowledge about the interactions between these two organs is scarce.

  18. Laboratory test surveillance following acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Michael E Matheny

    Full Text Available BACKGROUND: Patients with hospitalized acute kidney injury (AKI are at increased risk for accelerated loss of kidney function, morbidity, and mortality. We sought to inform efforts at improving post-AKI outcomes by describing the receipt of renal-specific laboratory test surveillance among a large high-risk cohort. METHODS: We acquired clinical data from the Electronic health record (EHR of 5 Veterans Affairs (VA hospitals to identify patients hospitalized with AKI from January 1st, 2002 to December 31st, 2009, and followed these patients for 1 year or until death, enrollment in palliative care, or improvement in renal function to estimated GFR (eGFR ≥ 60 L/min/1.73 m(2. Using demographic data, administrative codes, and laboratory test data, we evaluated the receipt and timing of outpatient testing for serum concentrations of creatinine and any as well as quantitative proteinuria recommended for CKD risk stratification. Additionally, we reported the rate of phosphorus and parathyroid hormone (PTH monitoring recommended for chronic kidney disease (CKD patients. RESULTS: A total of 10,955 patients admitted with AKI were discharged with an eGFR<60 mL/min/1.73 m2. During outpatient follow-up at 90 and 365 days, respectively, creatinine was measured on 69% and 85% of patients, quantitative proteinuria was measured on 6% and 12% of patients, PTH or phosphorus was measured on 10% and 15% of patients. CONCLUSIONS: Measurement of creatinine was common among all patients following AKI. However, patients with AKI were infrequently monitored with assessments of quantitative proteinuria or mineral metabolism disorder, even for patients with baseline kidney disease.

  19. Acute liver failure and acute kidney injury: Definitions, prognosis, and outcome

    OpenAIRE

    Włodzimirow, K.A.

    2013-01-01

    The objective of this thesis was to investigate definitions, prognostic indicators and their association with adverse events, mainly mortality for acute liver failure (ALF), acute-on-chronic liver failure (ACLF) and acute kidney injury (AKI).

  20. Reflex anuria: a rare cause of acute kidney injury

    OpenAIRE

    Dhakarwal, Pradeep; Adediran, Samuel

    2014-01-01

    Background: Acute Kidney Injury results from pre renal, post renal or intrinsic renal causes. Reflex anuria is a very rare cause of renal impairment which happens due to irritation or trauma to one kidney or ureter, or severely painful stimuli to other nearby organs.Case Presentation: Here we present a case of acute kidney injury secondary to reflex anuria in a patient who underwent extensive gynecological surgery along with ureteral manipulation which recovered spontaneously.Conclusion: Refl...

  1. Effect of aqueous extract of Rheum ribes on cisplatin-induced nephrotoxicity in rat

    Directory of Open Access Journals (Sweden)

    Mousa-Al-Reza Hadjzadeh

    2013-01-01

    Full Text Available Objective: The purpose of the present study was to examine whether Rheum ribes extract prevents cisplatin-induced nephrotoxicity. Materials and Methods: The animals were divided into three groups: Group A considered as control group, group B were treated with cisplatin (3 mg/kg B.W. for 3 alternative days, and group C further to cisplatin received the aqueous extract of Rheum ribes (150 mg/rat. Results: Blood urea nitrogen (BUN level increased in group B on days 14 and 42 compared to day 0 ( P < 0.001; it was also increased in group B vs. group A on day 14 ( P < 0.001. Rheum ribes extract decreased the serum BUN level on day 14 compared to group B ( P < 0.001. Serum creatinine level in group B had a similar profile as serum BUN level but Rheum ribes had no effect on blood creatinine level. Serum cholesterol level was increased in group B on days 14 and 42 compared to day 0 ( P < 0.001. Also, cholesterol level was significantly increased in group B when compared to group A on day 14 ( P < 0.001. Rheum ribes decreased the blood cholesterol level on day 42 in comparison to group B ( P < 0.001. Serum glucose level was increased in group B on days 14 and 42 vs. day 0 ( P < 0.001. Also, glucose level was significantly increased in group B when compared to group A on day 42 ( P < 0.001. Rheum ribes increased the serum glucose level on days 14 and 42 compared to day 0 ( P < 0.05. Histology of kidneys exposed to cisplatin showed renal injury, but Rheum ribes had no effect on the kidney architecture. Conclusion: Cisplatin-induced nephrotoxicity was confirmed in our study. Although Rheum ribes had some effects on biochemical parameters; its effect on renal histology in injured kidney was insignificant.

  2. Molecular determinants of acute kidney injury

    Directory of Open Access Journals (Sweden)

    Holger Husi

    2015-07-01

    Full Text Available Abstract: Background: Acute kidney injury (AKI is a condition that leads to a rapid deterioration of renal function associated with impairment to maintain electrolyte and acid balance, and, if left untreated, ultimately irreversible kidney damage and renal necrosis. There are a number of causes that can trigger AKI, ranging from underlying conditions as well as trauma and surgery. Specifically, the global rise in surgical procedures led to a substantial increase of AKI incidence rates, which in turn impacts on mortality rates, quality of life and economic costs to the healthcare system. However, no effective therapy for AKI exists. Current approaches, such as pharmacological intervention, help in alleviating symptoms in slowing down the progression, but do not prevent or reverse AKI-induced organ damage. Methods: An in-depth understanding of the molecular machinery involved in and modulated by AKI induction and progression is necessary to specifically pharmacologically target key molecules. A major hurdle to devise a successful strategy is the multifactorial and complex nature of the disorder itself, whereby the activation of a number of seemingly independent molecular pathways in the kidney leads to apoptotic and necrotic events. Results: The renin-angiotensin-aldosterone-system (RAAS axis appears to be a common element, leading to downstream events such as triggers of immune responses via the NFB pathway. Other pathways intricately linked with AKI-induction and progression are the tumor necrosis factor alpha(TNF and transforming growth factor beta (TGF signaling cascades, as well as a number of other modulators. Surprisingly, it has been shown that the involvement of the glutamatergic axis, believed to be mainly a component of the neurological system, is also a major contributor. Conclusions: Here we address the current understanding of the molecular pathways evoked in AKI, their interplay, and the potential to pharmacologically

  3. Acute kidney injury in asphyxiated neonates

    Directory of Open Access Journals (Sweden)

    Roy Amardiyanto

    2013-07-01

    Full Text Available Background Asphyxia neonatorum may result in multiorgan dysfunction including renal involvement. There is no consensus on the determination of acute kidney injury (AKI in neonates making establishment of the diagnosis and its management becomes difficult. The Acute Kidney Injury Network (AKIN recommends AKI criteria based on increased serum creatinine level and reduced urine output. Objectives To identify the prevalence of AKI in asphyxiated neonates using the AKIN criteria, to compare the difference of AKI stages, and the glomerular filtration rates (GFR between moderate and severe asphyxia. Methods This was a cross-sectional analytical study conducted between July 2012 and January 2013. Subjects were all asphyxiated neonates (Apgar score 35 weeks delivered and hospitalized in Cipto Mangunkusumo Hospital and Koja District Hospital, Jakarta, Indonesia. Glomerular filtration rate was calculated using the components of urine creatinine, serum creatinine, and urine output; while AKI stages were determined according to AKIN criteria. Urinary output was measured via urethral catheterization. Results Of 94 subjects, there were 70 neonates with moderate and 24 neonates with severe asphyxia, with the prevalence of AKI was 63%. Twenty one out of 24 neonates with severe asphyxia experienced AKI, while neonates with moderate asphyxia who experienced AKI was 38 out of 70 subjects (54%. Two third of neonates with severe asphyxia who experienced AKI had stage 3 of AKI. More severe AKI stages and lower median GFR were found in neonates with severe compared to moderate asphyxia (P<0.001. Conclusion The prevalence of AKI in neonatal asphyxia is high (63%. The more severe degree of neonatal asphyxia, the more severe AKI stage and the lower median GFR. [Paediatr Indones. 2013;53:232-8.].

  4. ACUTE KIDNEY INJURY: HISTORICAL ASPECTS AND DIAGNOSTIC CRITERIA

    Directory of Open Access Journals (Sweden)

    J. V. Kopylova

    2010-01-01

    Full Text Available The in-depth review is dedicated to the acute kidney injury. This conception is wider than acute renal failure. Even minor decline of renal function bias outcomes, so early diagnosis of acute renal injury is exceedingly important. The new markers of kidney injury are actively investigated. RIFLE criteria provide universal approach to a problem at first, and allow comparison of study results at second. 

  5. Acute Kidney Disease After Liver and Heart Transplantation.

    Science.gov (United States)

    Rossi, Ana P; Vella, John P

    2016-03-01

    After transplantation of nonrenal solid organs, an acute decline in kidney function develops in the majority of patients. In addition, a significant number of nonrenal solid organ transplant recipients develop chronic kidney disease, and some develop end-stage renal disease, requiring renal replacement therapy. The incidence varies depending on the transplanted organ. Acute kidney injury after nonrenal solid organ transplantation is associated with prolonged length of stay, cost, increased risk of death, de novo chronic kidney disease, and end-stage renal disease. This overview focuses on the risk factors for posttransplant acute kidney injury after liver and heart transplantation, integrating discussion of proteinuria and chronic kidney disease with emphasis on pathogenesis, histopathology, and management including the use of mechanistic target of rapamycin inhibition and costimulatory blockade.

  6. Acute Kidney Injury:Global Health Alert

    Institute of Scientific and Technical Information of China (English)

    Philip Kam TaoLi; Emmanuel A Burdmann; Ravindra L Mehta

    2013-01-01

    Acute kidney injury (AKI) is increasingly prevalent in developing and developed countries and is associated with severe morbidity and mortality.Most etiologies of AKI can be prevented by interventions at the individual,community,regional and in-hospital levels.Effective measures must include community-wide efforts to increase an awareness of the devastating effects of AKI and provide guidance on preventive strategies,as well as early recognition and management.Efforts should be focused on minimizing causes of AKI,increasing awareness of the importance of serial measurements of serum creatinine in high risk patients,and documenting urine volume in acutely ill people to achieve early diagnosis; there is as yet no definitive role for alternative biomarkers.Protocols need to be developed to systematically manage prerenal conditions and specific infections.More accurate data about the true incidence and clinical impact of AKI will help to raise the importance of the disease in the community,increase awareness of AKI by governments,the public,general and family physicians and other health care professionals to help prevent the disease.Prevention is the key to avoid the heavy burden of mortality and morbidity associated with AKI.

  7. Acute Kidney Injury Predicts Mortality after Charcoal Burning Suicide.

    Science.gov (United States)

    Chen, Yu-Chin; Tseng, Yi-Chia; Huang, Wen-Hung; Hsu, Ching-Wei; Weng, Cheng-Hao; Liu, Shou-Hsuan; Yang, Huang-Yu; Chen, Kuan-Hsin; Chen, Hui-Ling; Fu, Jen-Fen; Lin, Wey-Ran; Wang, I-Kuan; Yen, Tzung-Hai

    2016-01-01

    A paucity of literature exists on risk factors for mortality in charcoal burning suicide. In this observational study, we analyzed the data of 126 patients with charcoal burning suicide that seen between 2002 and 2013. Patients were grouped according to status of renal damage as acute kidney injury (N = 49) or non-acute kidney injury (N = 77). It was found that patients with acute kidney injury suffered severer complications such as respiratory failure (P = 0.002), myocardial injury (P = 0.049), hepatic injury (P acute kidney injury. Moreover, patients with acute kidney injury suffered longer hospitalization duration (16.9 ± 18.3 versus 10.7 ± 10.9, P = 0.002) and had higher mortality rate (8.2% versus 0%, P = 0.011) than patients without injury. In a multivariate Cox regression model, it was demonstrated that serum creatinine level (P = 0.019) and heart rate (P = 0.022) were significant risk factors for mortality. Finally, Kaplan-Meier analysis revealed that patients with acute kidney injury suffered lower cumulative survival than without injury (P = 0.016). In summary, the overall mortality rate of charcoal burning suicide population was 3.2%, and acute kidney injury was a powerful predictor of mortality. Further studies are warranted. PMID:27430168

  8. Protective Effect of Minocycline Against Cisplatin-induced Ototoxicity

    OpenAIRE

    Lee, Chi-Kyou; Shin, Jang-In; Cho, Yang-Sun

    2011-01-01

    Objectives Cisplatin, a widely used chemotherapeutic agent, has serious side effects, including nephrotoxicity and ototoxicity. Minocycline is a semisynthetic second-generation tetracycline that exerts anti-inflammatory and neuroprotective effects. The purpose of this study was to elucidate the protective effect of minocycline against cisplatin-induced ototoxicity in the auditory hair cell. Methods The House Ear Institute-Organ of Corti 1 (HEI-OC1) cell line and guinea pigs were used for in v...

  9. Malarial acute kidney injury: Prognostic markers

    Directory of Open Access Journals (Sweden)

    Ruhi Khan

    2013-01-01

    Full Text Available Background: Malaria has protean clinical manifestations and acute kidney injury (AKI is one of its serious and life threatening complications. This study was carried out to describe the clinical characteristics, and factors associated with adverse outcomes, in patients with malarial AKI. Materials and Methods: Data of 100 patients with AKI and smear positive malaria was retrospectively analyzed to evaluate the incidence, clinical profile, outcome and predictors of mortality among all cases presented to us at the Nephrology unit of Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh between November 2010 to October 2011. Results were expressed as mean, standard deviation (SD and range. Results: One hundred (22.1% (68 males, 32 females cases of malaria induced AKI, amongst 452 total cases of AKI, were evaluated. The mean age (± SD was 30 ± 11.23 years. Male to female ratio was 3.3:1. Plasmodium falciparum was reported in 76%, P. vivax in 11%, and both in 13% patients. The mean serum creatinine was 8.7 ± 3.7 mg%, and oligo/anuria was present in 84% of the patients. 78% of the patients required hemodialysis. 67% of the patients recovered completely, 12% did not show full recovery, and 6% developed chronic kidney failure. Mortality occurred in 15% of the patients. Conclusion : Malarial AKI most commonly occurs in patients infected by Plasmodium Falciparum. Falciparum malaria associated with AKI is a life threatening condition. Prolonged disease duration, low hemoglobin, oligo/anuria on admission, hyperbilirubinemia, cerebral malaria, disseminated intravascular coagulation, and high serum creatinine were the main predictors of mortality in our study.

  10. Contrast-Induced Acute Kidney Injury: An Update.

    Science.gov (United States)

    Chalikias, George; Drosos, Ioannis; Tziakas, Dimitrios N

    2016-04-01

    Contrast-induced acute kidney injury (CI-AKI) is defined as an abrupt deterioration in renal function associated with the administration of iodinated contrast media. This type of acute kidney injury is frequently encountered as a complication of percutaneous coronary intervention (PCI) and is associated with adverse short- and long-term outcomes including mainly mortality, cardiovascular morbidity and prolongation of hospitalization. The incidence of CI-AKI after PCI ranges from 2 to 20 % according to baseline kidney function. It may also range according to the clinical setting, being higher after emergency PCI. The primary manifestation is a small decline in kidney function, occurring 1 to 3 days after the procedure. Kidney function usually returns to preexisting levels within 7 days. Incidence of acute renal failure requiring dialysis following PCI is rare (hospital epidemic. PMID:26780748

  11. Coronary heart disease is not significantly linked to acute kidney injury identified using Acute Kidney Injury Group criteria

    OpenAIRE

    Yayan J

    2012-01-01

    Josef YayanDepartment of Internal Medicine, Vinzentius Hospital, Landau, GermanyBackground: Patients with unstable angina or myocardial infarction are at risk of acute kidney injury, which may be aggravated by the iodine-containing contrast agent used during coronary angiography; however, the relationship between these two conditions remains unclear.Objective: The current study investigated the relationship between acute kidney injury and coronary heart disease prior to coronary angiography.M...

  12. Cisplatin induces resistance by triggering differentiation of testicular embryonal carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Paolo B Abada

    Full Text Available Although testicular germ cell tumors are generally quite responsive to treatment with cisplatin, a small fraction of them acquire resistance during therapy. Even when cisplatin treatment is successful the patient is often left with a residual teratoma at the site of the primary tumor suggesting that cisplatin may trigger differentiation in some tumors. Using the human embryonal carcinoma cell line NTera2/D1, we confirmed that exposure to the differentiating agent retinoic acid produced a reduction in pluripotency markers NANOG and POU5F1 (Oct3/4 and an acute concentration-dependent increase in resistance to both cisplatin and paclitaxel that reached as high as 18-fold for cisplatin and 61-fold for paclitaxel within four days. A two day exposure to cisplatin also produced a concentration-dependent decrease in the expression of the NANOG and POU5F1 and increased expression of three markers whose levels increase with differentiation including Nestin, SCG10 and Fibronectin. In parallel, exposure to cisplatin induced up to 6.2-fold resistance to itself and 104-fold resistance to paclitaxel. Paclitaxel did not induce differentiation or resistance to either itself or cisplatin. Neither retinoic acid nor cisplatin induced resistance in cervical or prostate cancer cell lines or other germ cell tumor lines in which they failed to alter the expression of NANOG and POU5F1. Forced expression of NANOG prevented the induction of resistance to cisplatin by retinoic acid. We conclude that cisplatin can acutely induce resistance to itself and paclitaxel by triggering a differentiation response in pluripotent germ cell tumor cells.

  13. Cisplatin induces resistance by triggering differentiation of testicular embryonal carcinoma cells.

    Science.gov (United States)

    Abada, Paolo B; Howell, Stephen B

    2014-01-01

    Although testicular germ cell tumors are generally quite responsive to treatment with cisplatin, a small fraction of them acquire resistance during therapy. Even when cisplatin treatment is successful the patient is often left with a residual teratoma at the site of the primary tumor suggesting that cisplatin may trigger differentiation in some tumors. Using the human embryonal carcinoma cell line NTera2/D1, we confirmed that exposure to the differentiating agent retinoic acid produced a reduction in pluripotency markers NANOG and POU5F1 (Oct3/4) and an acute concentration-dependent increase in resistance to both cisplatin and paclitaxel that reached as high as 18-fold for cisplatin and 61-fold for paclitaxel within four days. A two day exposure to cisplatin also produced a concentration-dependent decrease in the expression of the NANOG and POU5F1 and increased expression of three markers whose levels increase with differentiation including Nestin, SCG10 and Fibronectin. In parallel, exposure to cisplatin induced up to 6.2-fold resistance to itself and 104-fold resistance to paclitaxel. Paclitaxel did not induce differentiation or resistance to either itself or cisplatin. Neither retinoic acid nor cisplatin induced resistance in cervical or prostate cancer cell lines or other germ cell tumor lines in which they failed to alter the expression of NANOG and POU5F1. Forced expression of NANOG prevented the induction of resistance to cisplatin by retinoic acid. We conclude that cisplatin can acutely induce resistance to itself and paclitaxel by triggering a differentiation response in pluripotent germ cell tumor cells. PMID:24475288

  14. Biomarkers in acute kidney injury: Evidence or paradigm?

    Science.gov (United States)

    Lombi, Fernando; Muryan, Alexis; Canzonieri, Romina; Trimarchi, Hernán

    2016-01-01

    Acute kidney injury in the critically ill represents an independent risk factor of morbidity and mortality in the short and long terms, with significant economic impacts in terms of public health costs. Currently its diagnosis is still based on the presence of oliguria and/or a gradual increase in serum creatinine, which make the diagnosis a delayed event and to detriment of the so-called 'therapeutic window'. The appearance of new biomarkers of acute kidney injury could potentially improve this situation, contributing to the detection of 'subclinical acute kidney injury', which could allow the precocious employment of multiple treatment strategies in order to preserve kidney function. However these new biomarkers display sensitive features that may threaten their full capacity of action, which focus specifically on their additional contribution in the early approach of the situation, given the lack of specific validated treatments for acute kidney injury. This review aims to analyze the strengths and weaknesses of these new tools in the early management of acute kidney injury.

  15. Acute rejection episodes after kidney transplantation

    Directory of Open Access Journals (Sweden)

    Hamida Fethi

    2009-01-01

    Full Text Available Acute rejection episodes (AREs are a major determinant of renal allograft survival. The incorporation of new immunosuppressive agents explains, at least partially, the improvement seen in the results of transplantation in recent years. The objectives of this study are to analyze the incidence and severity of AREs, their risk factors and their influence on graft and patient survival. We retrospectively studied 280 kidney transplants performed in adults at the Charles Nicolle Hospital, Tunis, between 1986 and 2004. The diagnosis of ARE was based on clinical data and response to treatment. Allograft biopsies were performed in ten cases. The treatment of AREs consisted of pulse methylprednisolone and anti-thymocyte globulin. There were 186 males (66.4% and 94 females (33.6%, and their mean age was 31 ± 8.9 years. Overall, the 280 study patients experienced a total of 113 AREs. Of them, 85 had only one ARE, 28 had two to three and none had more than three AREs. A total of 68 AREs were completely re-versible, 42 were partially reversible while three could not be reversed with treatment. The mean inci-dence of AREs was 40.4%. The incidence was > 45% between 1986 and 1997, decreased to 20.5% between 1998 and 2000 and to 9% between 2001 and 2004. Graft survival rates in patients with and without AREs were respectively 91% and 93% at three years, 82% and 90% at five years and 73% and 83% at 10 years. We found a decrease in the incidence of AREs in recent years in our study patients, and this was related to the introduction of sensitized cross-match and the newer immunosuppressive agents, particularly MMF. Additionally, AREs had a deleterious impact on late graft survival in our study population.

  16. Preliminary Experience of Integrative Medicine in Acute Kidney Injury

    Institute of Scientific and Technical Information of China (English)

    RAO Xiang-rong

    2010-01-01

    @@ Acute kidney injury (AKI), a concept that replaces the traditional concept known as acute renal failure (ARF),has been adopted by more and more nephrologists and intensive-care specialists in recent years. The definition and diagnostic criteria of AKI are quite different from thoseof ARF(1).

  17. Predicting outcome of acute kidney transplant rejection using

    NARCIS (Netherlands)

    Rekers, Niels Vincent

    2014-01-01

    Acute kidney transplant rejection is an important risk factors for adverse graft outcome. Once diagnosed, it remains difficult to predict the risk of graft loss and the response to anti-rejection treatment. The aim of this thesis was to identify biomarkers during acute rejection, which predict the r

  18. EFFECT OF ANTHOCYANIN FRACTION ON CISPLATIN-INDUCED NEPHROTOXICITY

    OpenAIRE

    Adikay Sreedevi; Belide Pavani

    2012-01-01

    Present study was designed to evaluate the effect of anthocyanin fraction of Syzygium cumini on cisplatin-induced nephrotoxicity in male Albino rats. Anthocyanin fraction was administered by gastric intubation at two dose levels. Animals were divided into 5 groups. Group I animals received vehicle. On day 1, Group II animals received cisplatin (6 mg/kg, i,p., single dose). Group III (7.5mg/kg) and IV (15mg/kg) received anthocyanin fraction respectively at 1 hr before, 24 hr and 48 hr after ci...

  19. Acute kidney injury secondary to lymphomatous infiltration and the roleof kidney biopsy

    International Nuclear Information System (INIS)

    We report a 47-year-old male patient who developed acute kidney injuryrequiring hemodialysis, associated with massive enlargement of both kidneys.A part from intra-abdominal lymphadenopathy, there was no other organ orlymph node involvement. A kidney biopsy established the diagnosis ofnon-Hodgkin's lymphoma. The patient received chemotherapy with good response.This case demonstrates that the kidney could be the primary organ involved inthe non-Hodgkin's lymphoma. In addition, we have shown that renal biopsy isadequate to make a diagnosis of lymphoma without the need to do more invasivetesting. (author)

  20. Severe but reversible acute kidney injury resulting from Amanita punctata poisoning

    OpenAIRE

    Kang, Eunjung; Cheong, Ka-Young; Lee, Min-Jeong; Kim, Seirhan; Shin, Gyu-Tae; Kim, Heungsoo; Park, In-Whee

    2015-01-01

    Mushroom-related poisoning can cause acute kidney injury. Here we report a case of acute kidney injury after ingestion of Amanita punctata, which is considered an edible mushroom. Gastrointestinal symptoms occurred within 24 hours from the mushroom intake and were followed by an asymptomatic period, acute kidney injury, and elevation of liver and pancreatic enzymes. Kidney function recovered with supportive care. Nephrotoxic mushroom poisoning should be considered as a cause of acute kidney i...

  1. Walnut consumption protects rats against cisplatin-induced neurotoxicity.

    Science.gov (United States)

    Shabani, Mohammad; Nazeri, Masoud; Parsania, Shahrnaz; Razavinasab, Moazamehosadat; Zangiabadi, Nasser; Esmaeilpour, Khadije; Abareghi, Fatemeh

    2012-10-01

    Walnut is extensively used in traditional medicine for treatment of various ailments. It is described as an anticancer, anti-inflammatory, blood purifier and antioxidant agent. In this study, we investigated whether or not Walnut could protect neurons against cisplatin-induced neurotoxicity in rats. Dietary walnut (6%) was assessed for its neuroprotective effects through the alteration in performance of hippocampus- and cerebellum-related behaviors following chronic cisplatin treatment (5 mg/kg/week for 5 consecutive weeks) in male rats. We also evaluated the effect of cisplatin and walnut administration on nociception. We showed that exposure of adolescent rats to cisplatin resulted in significant decrease in explorative behaviors and memory retention. Walnut consumption improved memory and motor abilities in cisplatin treated rats, while walnut alone did not show any significant changes in these abilities compared to saline. Cisplatin increased latency of response to nociception, and walnut reversed this effect of cisplatin. We conclude that walnuts in the diet following anticancer drugs such as cisplatin might have a protective effect against cisplatin-induced disruptions in motor and cognitive function. However, further studies are needed to elucidate the exact mechanisms of this protective effect of walnut and to explore underlying mechanisms. PMID:22935099

  2. Tempol, a superoxide dismutase mimetic agent, ameliorates cisplatin-induced nephrotoxicity through alleviation of mitochondrial dysfunction in mice.

    Directory of Open Access Journals (Sweden)

    Lamiaa A Ahmed

    Full Text Available Mitochondrial dysfunction is a crucial mechanism by which cisplatin, a potent chemotherapeutic agent, causes nephrotoxicity where mitochondrial electron transport complexes are shifted mostly toward imbalanced reactive oxygen species versus energy production. In the present study, the protective role of tempol, a membrane-permeable superoxide dismutase mimetic agent, was evaluated on mitochondrial dysfunction and the subsequent damage induced by cisplatin nephrotoxicity in mice.Nephrotoxicity was assessed 72 h after a single i.p. injection of cisplatin (25 mg/kg with or without oral administration of tempol (100 mg/kg/day. Serum creatinine and urea as well as glucosuria and proteinuria were evaluated. Both kidneys were isolated for estimation of oxidative stress markers, adenosine triphosphate (ATP content and caspase-3 activity. Moreover, mitochondrial oxidative phosphorylation capacity, complexes I-IV activities and mitochondrial nitric oxide synthase (mNOS protein expression were measured along with histological examinations of renal tubular damage and mitochondrial ultrastructural changes. Tempol was effective against cisplatin-induced elevation of serum creatinine and urea as well as glucosuria and proteinuria. Moreover, pretreatment with tempol notably inhibited cisplatin-induced oxidative stress and disruption of mitochondrial function by restoring mitochondrial oxidative phosphorylation, complexes I and III activities, mNOS protein expression and ATP content. Tempol also provided significant protection against apoptosis, tubular damage and mitochondrial ultrastructural changes. Interestingly, tempol did not interfere with the cytotoxic effect of cisplatin against the growth of solid Ehrlich carcinoma.This study highlights the potential role of tempol in inhibiting cisplatin-induced nephrotoxicity without affecting its antitumor activity via amelioration of oxidative stress and mitochondrial dysfunction.

  3. Anti-apoptotic and anti-inflammatory effects of naringin on cisplatin-induced renal injury in the rat.

    Science.gov (United States)

    Chtourou, Yassine; Aouey, Baktha; Aroui, Sonia; Kebieche, Mohammed; Fetoui, Hamadi

    2016-01-01

    Nephrotoxicity is a common complication of cisplatin chemotherapy and thus limits the use of cisplatin in clinic. Naringin, a natural flavonoid, plays important roles in inflammation and apoptosis in some inflammatory diseases; however, its roles in cisplatin-induced nephrotoxicity remain unclear. In this study, we first assessed the involvement of ROS overproduction and inflammation in cisplatin-induced nephrotoxicity in aged rats, and then we investigated the changes of renal function, histological injury, inflammatory response, and apoptosis in renal tissues after treatment with naringin (20, 50 or 100 mg/kg body weight). Cisplatin resulted in an increase of renal markers, lipid peroxidation, protein and DNA oxidation, and ROS formation. Renal tumor necrosis factor-α (TNF-α) and nitrite levels were also elevated. Expressions of nuclear factor-kappa B (NF-κB), inductible nitric oxide synthase (iNOS), caspase-3 and p53 were up-regulated in renal tissues of Cis-treated rats compared with the normal control group. Histopathological changes were also observed in cisplatin group. Adminstration of naringin at different doses (25, 50 and 100 mg/kg) was able to protect against the deterioration in kidney function, abrogate the decline in antioxidant enzyme activities and suppressed the increase in TBARS, nitrite and TNF-α concentrations. Moreover, naringin inhibited NF-κB and iNOS pathways, caspase-3 and p53 activation and improved the histological changes induced by cisplatin. In conclusion, our studies suggest that oxidative stress and inflammation might play important roles in the development of cisplatin-induced nephrotoxicity and naringin might become an effective therapeutic strategy for this disease. PMID:26612654

  4. Microvesicles derived from mesenchymal stem cells enhance survival in a lethal model of acute kidney injury.

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    Stefania Bruno

    Full Text Available Several studies demonstrated that treatment with mesenchymal stem cells (MSCs reduces cisplatin mortality in mice. Microvesicles (MVs released from MSCs were previously shown to favor renal repair in non lethal toxic and ischemic acute renal injury (AKI. In the present study we investigated the effects of MSC-derived MVs in SCID mice survival in lethal cisplatin-induced AKI. Moreover, we evaluated in vitro the effect of MVs on cisplatin-induced apoptosis of human renal tubular epithelial cells and the molecular mechanisms involved. Two different regimens of MV injection were used. The single administration of MVs ameliorated renal function and morphology, and improved survival but did not prevent chronic tubular injury and persistent increase in BUN and creatinine. Multiple injections of MVs further decreased mortality and at day 21 surviving mice showed normal histology and renal function. The mechanism of protection was mainly ascribed to an anti-apoptotic effect of MVs. In vitro studies demonstrated that MVs up-regulated in cisplatin-treated human tubular epithelial cells anti-apoptotic genes, such as Bcl-xL, Bcl2 and BIRC8 and down-regulated genes that have a central role in the execution-phase of cell apoptosis such as Casp1, Casp8 and LTA. In conclusion, MVs released from MSCs were found to exert a pro-survival effect on renal cells in vitro and in vivo, suggesting that MVs may contribute to renal protection conferred by MSCs.

  5. Functional Magnetic Resonance Imaging in Acute Kidney Injury: Present Status

    OpenAIRE

    Hai Ying Zhou; Tian Wu Chen; Xiao Ming Zhang

    2016-01-01

    Acute kidney injury (AKI) is a common complication of hospitalization that is characterized by a sudden loss of renal excretory function and associated with the subsequent development of chronic kidney disease, poor prognosis, and increased mortality. Although the pathophysiology of renal functional impairment in the setting of AKI remains poorly understood, previous studies have identified changes in renal hemodynamics, perfusion, and oxygenation as key factors in the development and progres...

  6. Perioperative aspirin and clonidine and risk of acute kidney injury

    DEFF Research Database (Denmark)

    Garg, Amit X; Kurz, Andrea; Sessler, Daniel I;

    2014-01-01

    IMPORTANCE: Acute kidney injury, a common complication of surgery, is associated with poor outcomes and high health care costs. Some studies suggest aspirin or clonidine administered during the perioperative period reduces the risk of acute kidney injury; however, these effects are uncertain...... and each intervention has the potential for harm. OBJECTIVE: To determine whether aspirin compared with placebo, and clonidine compared with placebo, alters the risk of perioperative acute kidney injury. DESIGN, SETTING, AND PARTICIPANTS: A 2 × 2 factorial randomized, blinded, clinical trial of 6905...... patients undergoing noncardiac surgery from 88 centers in 22 countries with consecutive patients enrolled between January 2011 and December 2013. INTERVENTIONS: Patients were assigned to take aspirin (200 mg) or placebo 2 to 4 hours before surgery and then aspirin (100 mg) or placebo daily up to 30 days...

  7. Amelioration of cisplatin induced nephrotoxicity in Swiss albino mice by Rubia cordifolia extract

    Directory of Open Access Journals (Sweden)

    Joy Jisha

    2008-01-01

    Full Text Available Background: Cisplatin is one of the most effective chemotherapeutics against a wide range of cancers including head, neck, ovarian and lung cancers. But its usefulness is limited by its toxicity to normal tissues, including cells of the kidney proximal tubule. The purpose of the present study is to investigate whether the hydro-alcoholic extract of Rubia cordifolia could decrease the intensity of toxicity in Swiss albino mice. Materials and Methods: Cisplatin at a dose of 12 mg/kg body wt was administered intraperitoneally to Swiss albino mice. Another set of animals was given hydro-alcoholic extract of Rubia cordifolia at different doses along with cisplatin treatment. The antioxidant levels, serum creatinine, serum urea etc. were analyzed. Results: The extract could significantly decrease the cisplatin induced nephrotoxicity as inferred from the tissue antioxidant status in the drug administered animals. Remarkable change was observed in serum creatinine and urea levels. Lipid peroxidation in the kidney and liver tissues was also considerably reduced in Rubia cordifolia extract treated animals. Conclusion: Hydro-alcoholic extracts of Rubia cordifolia are effective in reducing the renal damage caused by the cancer chemotherapeutic drug cisplatin. Since Rubia cordifolia has been in use as an important ingredient in the traditional Ayurvedic system of medicine, it could be safe and beneficial to use this herbal extract as an adjuvant to ameliorate renal damage in patients undergoing cancer chemotherapy with cisplatin.

  8. An analysis of clinical characteristics of septic acute kidney injury by using criteria of Kidney Disease:Improving Global Outcomes

    Institute of Scientific and Technical Information of China (English)

    臧芝栋

    2013-01-01

    Objective To evaluate the value of kidney Disease:Improving Global Outcomes(KDIGO) criteria in investigating clinical feature and prognosis of acute kidney injury(AKI) patients with sepsis in ICU.Methods

  9. Acute kidney injury in sepsis: transient or intrinsic?

    Science.gov (United States)

    Jörres, Achim

    2013-11-20

    The negative prediction of intrinsic versus transient acute kidney injury (AKI) in septic patients may be facilitated by combined assessment of fractional excretion of sodium and urea. If both excretions are high this would signal the presence of transient AKI and suggest that successful restoration of diuresis by conservative therapy is likely, thus supporting a wait-and-watch approach regarding the initiation of acute renal replacement therapy.

  10. Infrasound sensitizes human glioblastoma cells to cisplatin-induced apoptosis.

    Science.gov (United States)

    Rachlin, Kenneth; Moore, Dan H; Yount, Garret

    2013-11-01

    The development of nontoxic agents that can selectively enhance the cytotoxicity of chemotherapy is an important aim in oncology. This study evaluates the ability of infrasound exposure to sensitize glioblastoma cells to cisplatin-induced apoptosis. The infrasound was delivered using a device designed to replicate the unique infrasound emissions measured during external Qigong treatments. Human glioblastoma cell lines harboring wild-type p53 (U87) or mutant p53 (U251, SF210, and SF188) were treated in culture with cisplatin, infrasound emissions, or the combination of the 2 agents. Induction of apoptosis was quantified after 24 hours by flow cytometry following annexin V/propidium iodide staining. Infrasound emissions alone, delivered at moderate levels (~10 mPa) with dynamic frequency content (7-13 Hz), did not induce apoptosis, yet combining infrasound with cisplatin augmented the induction of apoptosis by cisplatin in all the 4 cell lines (P infrasound exposure was quantified by fluorescence microscopy as well as flow cytometry, demonstrating increased cell membrane permeability. The 4 cell lines differed in the degree to which infrasound exposure increased calcein uptake, and these differences were predictive of the extent to which infrasound enhanced cisplatin-induced apoptosis. When exposed to specific frequencies, membrane permeabilization also appeared to be differentially responsive for each cell line, suggesting the potential for selective targeting of tissue types using isolated infrasonic frequencies. Additionally, the pressure amplitudes used in this study were several orders of magnitude less than those used in similar studies involving ultrasound and shock waves. The results of this study provide support for using infrasound to enhance the chemotherapeutic effects of cisplatin in a clinical setting. PMID:23165942

  11. Pathophysiology and Clinical Work-Up of Acute Kidney Injury.

    Science.gov (United States)

    Meola, Mario; Nalesso, Federico; Petrucci, Ilaria; Samoni, Sara; Ronco, Claudio

    2016-01-01

    Acute kidney injury (AKI), also known in the past as acute renal failure, is a syndrome characterized by the rapid loss of kidney excretory function. It is usually diagnosed by the accumulation of end products of nitrogen metabolism (urea and creatinine) or decreased urine output or both. AKI is the clinical consequence of several disorders that acutely affect the kidney, causing electrolytes and acid-base imbalance, hyperhydration and loss of depurative function. AKI is common in critical care patients in whom it is often secondary to extrarenal events. No specific therapies can attenuate AKI or accelerate renal function recovery; thus, the only treatment is supportive. New diagnostic techniques such as renal biomarkers might improve early diagnosis. Also ultrasonography helps nephrologists in AKI diagnosis, in order to describe and follow kidney alterations and find possible causes of AKI. Renal replacement therapy is a life-saving treatment if AKI is severe. If patients survive to AKI, and did not have previous chronic kidney disease (CKD), they typically recover to dialysis independence. However, evidence suggests that patients who have had AKI are at increased risk of subsequent CKD. PMID:27169469

  12. Acute Kidney Injury Induced by Herbal Products: A Case Report

    Directory of Open Access Journals (Sweden)

    Erhan TATAR

    2014-09-01

    Full Text Available Recently, consumption of herbal products has become widespread both in Turkey and worldwide. However, the safety of these products is substantially controversial. We here present a case of acute kidney injury in a patient with excessive use of herbal products for cardio-protective purposes.

  13. Recurrence of Acute Page Kidney in a Renal Transplant Allograft

    Science.gov (United States)

    Zayas, Carlos; Mulloy, Laura; Jagadeesan, Muralidharan

    2016-01-01

    Acute Page Kidney (APK) phenomenon is a rare cause of secondary hypertension, mediated by activation of renin-angiotensin-aldosterone system (RAAS). Timely intervention is of great importance to prevent any end organ damage from hypertension. We present a unique case of three episodes of APK in the same renal transplant allograft. PMID:27725836

  14. Recurrence of Acute Page Kidney in a Renal Transplant Allograft

    Directory of Open Access Journals (Sweden)

    Rajan Kapoor

    2016-01-01

    Full Text Available Acute Page Kidney (APK phenomenon is a rare cause of secondary hypertension, mediated by activation of renin-angiotensin-aldosterone system (RAAS. Timely intervention is of great importance to prevent any end organ damage from hypertension. We present a unique case of three episodes of APK in the same renal transplant allograft.

  15. Acute kidney injury in imported Plasmodium falciparum malaria

    NARCIS (Netherlands)

    L.C. Koopmans, L.C. (Liese); M.E. van Wolfswinkel (Marlies); D.A. Hesselink (Dennis); E.J. Hoorn (Ewout); R. Koelewijn (Rob); J.J. van Hellemond (Jaap); P.J. van Genderen (P.)

    2015-01-01

    textabstractBackground: Acute kidney injury (AKI) is a known complication of malaria, and is reported to occur in up to 40 % of adult patients with a severe Plasmodium falciparum infection in endemic regions. To gain insight in the incidence and risk factors of AKI in imported P. falciparum malaria,

  16. Clinical analysis on 624 elderly patients with acute kidney injury

    Institute of Scientific and Technical Information of China (English)

    邹琴

    2012-01-01

    Objective To investigate the pathogens, clinical characteristic and therapeutic method of acute kidney injury(AKI).Methods The morbidity,composition of pathogeny,staging and prognosis of 624 cases with AKI recruited by our department from January 1999 to December 2009.

  17. Acute kidney injury and hepatorenal syndrome in cirrhosis

    DEFF Research Database (Denmark)

    Egerod Israelsen, Mads; Gluud, Lise Lotte; Krag, Aleksander

    2015-01-01

    Cirrhosis is the eighth leading cause of "years of lost life" in the United States and accounts for approximately 1% to 2% of all deaths in Europe. Patients with cirrhosis have a high risk of developing acute kidney injury. The clinical characteristics of hepatorenal syndrome (HRS) are similar...

  18. Hypothyroidism causing paralytic ileus and acute kidney injury - case report

    Directory of Open Access Journals (Sweden)

    Rodrigo Chaturaka

    2011-02-01

    Full Text Available Abstract We present a patient with severe hypothyroidism complicated by paralytic ileus and acute kidney injury. A 65 year old male patient, diagnosed with hypothyroidism one year ago was transferred to our unit in a state of drowsiness and confusion. He was severely hypothyroid and had paralytic ileus and impaired renal function at the time of transfer. Hypokalaemia was present, and was likely to have contributed to the paralytic ileus and this together with dehydration was likely to have contributed to renal injury. Nonetheless, hypothyroidism is very likely to have been the principal precipitant of both these complications, and both paralytic ileus and acute kidney injury improved with thyroxine replacement. Unfortunately, the patient died unexpectedly eight days after admission to the unit. Hypothyroidism may induce de novo acute kidney injury or it may exacerbate ongoing chronic kidney disease. This rare complication is assumed to be due to the hypodynamic circulatory state created by thyroid hormone deficiency. Paralytic ileus is an even rarer fatal manifestation of hypothyroidism and is thought to be due to an autonomic neuropathy affecting the intestines that is reversible with thyroxine replacement. To our knowledge, both these complications have not been observed in a single patient so far. It is important that clinicians are aware of these rare manifestations of hypothyroidism as in most occasions, thyroxine deficiency may be missed, and treatment can reverse the complications.

  19. Assessment of the possible role of iron and copper in cisplatin-induced nephrotoxicity in the rat.

    Science.gov (United States)

    Goudie, J; Chandra, M; Lawrence, G D; Williams, P

    1994-01-01

    Nephrotoxic lesions induced by cisplatin in rats are characterized by acute tubular necrosis in the outer stripe of the medulla. The purpose of this study was to examine the potential role of changes in metal binding proteins, and iron and copper content in urine and renal tissue in cisplatin-induced nephrotoxicity. Cisplatin was administered intravenously to groups of 20 rats at single doses of 0, 1, 2.5, and 5 mg/kg and rats were sacrificed at 1, 2, 3 and 6 days after treatment. Increased serum BUN and creatinine were observed at a dose of 5 mg/kg cisplatin on day 2 through day 6. Increased urinary copper excretion coincided with necrosis and increased BUN and creatinine on day 3 in the high-dose group. Evidence of renal injury was apparent histologically as karyomegaly at all dose levels as early as 48 hours after injection of cisplatin, prior to increases in urinary copper levels. No change in the distribution of metal binding proteins (transferrin, ferritin, ceruloplasmin, and metallothionein) evaluated by immunohistochemical staining, was seen. Based upon these results, it is unlikely that changes in metal excretion play a primary role in cisplatin-induced nephrotoxicity however, changes in nuclear function indicated by karyomegaly may be involved in early renal injury.

  20. Novel synthetic protective compound, KR-22335, against cisplatin-induced auditory cell death.

    Science.gov (United States)

    Shin, Yoo Seob; Song, Suk Jin; Kang, Sungun; Hwang, Hye Sook; Jung, Young-Sik; Kim, Chul-Ho

    2014-02-01

    Cisplatin [cis-diammine-dichloroplatinum (II)] is a widely used chemotherapeutic agent, and one of its most severe side effects is ototoxicity. In the course of developing a new protective agent against cisplatin-induced ototoxicity, we have been interested in a novel synthetic compound, 3-Amino-3-(4-fluoro-phenyl)-1H-quinoline-2,4-dione (KR-22335). We evaluated the effectiveness of KR-22335 as an otoprotective agent against cisplatin-induced toxicity. The otoprotective effect of KR-22335 against cisplatin was tested in vitro in cochlear organs of Corti-derived cell lines, HEI-OC1, and in vivo in a zebrafish (Danio rerio) model. Cisplatin-induced apoptosis, cell cycle arrest and an increase in intracellular reactive oxygen species (ROS) generation were demonstrated in HEI-OC1 cells. KR-22335 inhibited cisplatin-induced apoptosis and mitochondrial injury in HEI-OC1 cells. KR-22335 inhibited cisplatin-induced activation of JNK, p-38, caspase-3 and PARP in HEI-OC1 cells. Scanning and transmission electron micrographs showed that KR-22335 prevented cisplatin-induced destruction of kinocilium and stereocilia in zebrafish neuromasts. Tissue TUNEL of neuromasts in zebrafish demonstrated that KR-22335 blocked cisplatin-induced TUNEL positive hair cells in neuromasts. The results of this study suggest that KR-22335 may prevent ototoxicity caused by the administration of cisplatin through the inhibition of mitochondrial dysfunction and suppression of ROS generation. KR-22335 may be considered as a potential candidate for protective agents against cisplatin-induced ototoxicity.

  1. Anthocyanin - Rich Red Dye of Hibiscus Sabdariffa Calyx Modulates Cisplatin-induced Nephrotoxicity and Oxidative Stress in Rats.

    Science.gov (United States)

    Ademiluyi, Adedayo O; Oboh, Ganiyu; Agbebi, Oluwaseun J; Akinyemi, Ayodele J

    2013-12-01

    This study sought to investigate the protective effect of dietary inclusion of Hibiscus sabdariffa calyx red dye on cisplatin-induced nephrotoxicity and antioxidant status in rats. Adult male rats were randomly divided into four groups of six animals each. Groups I and II were fed basal diet while groups III and IV were fed diets containing 0.5% and 1% of the dye respectively for 20 days prior to cisplatin administration. Nephrotoxicity was induced by a single dose intraperitoneal administration of cisplatin (7 mg/kg b.w) and the experiment was terminated 3 days after. The kidney and plasma were studied for nephrotoxicity and oxidative stress indices. Cisplatin administration caused a significant (Psabdariffa dye could be attributed to its anthocyanin content. PMID:24711761

  2. Inflammatory Mechanisms of Organ Crosstalk during Ischemic Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    Laura E. White

    2012-01-01

    Full Text Available Acute kidney injury (AKI is a common complication during inpatient hospitalization, and clinical outcomes remain poor despite advancements in renal replacement therapy. AKI in the setting of multiple organ failure (MOF remains a formidable challenge to clinicians and incurs an unacceptably high mortality rate. Kidney ischemia-reperfusion injury (IRI incites a proinflammatory cascade and releases cellular and soluble mediators with systemic implications for remote organ injury. Evidence from preclinical models cites mechanisms of organ crosstalk during ischemic AKI including the expression of cellular adhesion molecules, lymphocyte trafficking, release of proinflammatory cytokines and chemokines, and modification of the host innate and adaptive immune response systems. In this paper, the influence of kidney IRI on systemic inflammation and distant organ injury will be examined. Recent experimental data and evolving concepts of organ crosstalk during ischemic AKI will also be discussed in detail.

  3. Acute Kidney Injury Classification in Neuro-ICU Patient Group

    Directory of Open Access Journals (Sweden)

    Canan Akıncı

    2012-12-01

    Full Text Available Objective: To investigate the role of acute kidney injury (AKI classification system for kidney injury outcome in neuro-Intensive care unit (ICU patients. Material and Method: Total 432 patients who admitted to ICU between 2005 and 2009 evaluated in this study. All patients’ AKI stage, Acute Physiology and Chronic Health Evaluation (APACHE-II, Sequential Organ Failure Assessment Score (SOFA, Glasgow Coma Score (GCS, Glasgow Outcome Score (GOS, mortality rate, length of ICU stay, need for intubation, and mechanical ventilation were recorded. Results: AKI was found in 24 of all 432 patents’ (5.5%. We found that, patients with AKI had higher APHACE-II score, SOFA score and mortality rates; longer ICU stay, duration of mechanical ventilation and intubation and lower GCS and GOS than without AKI group. Conclusion: Length of ICU stay and mortality rate were higher in AKI positive group.

  4. Recently published papers: Acute kidney injury – diagnosis and treatment

    OpenAIRE

    Lee, Jasmine BL; Forni, Lui G

    2009-01-01

    When faced with the management of the patient on intensive care with acute kidney injury, the clinician has various choices to consider. The conventional therapy, where appropriate, is renal replacement therapy. This technique used to be relatively straightforward but now a relative feast of alternatives is available, not least in choice of buffer and anticoagulant. Two recent studies add to the growing body of literature concerning alternative anticoagulant regimes, and one in particular sho...

  5. Genetic deficiency of adiponectin protects against acute kidney injury

    OpenAIRE

    Jin, Xiaogao; Chen, Jiyuan; Hu, Zhaoyong; Chan, Lawrence; Wang, Yanlin

    2013-01-01

    Adiponectin is a multifunctional cytokine that has a role in regulating inflammation. Here we determined if adiponectin modulates ischemic acute kidney injury. Compared with wild-type mice, adiponectin knockout mice were found to have lower serum creatinine and less tubular damage or apoptosis following ischemia/reperfusion injury. This latter process was associated with decreased Bax and reduced activation of p53 and caspase-3. Targeted disruption of adiponectin was also found to inhibit the...

  6. Iron, hormesis, and protection in acute kidney injury.

    Science.gov (United States)

    Swaminathan, Sundararaman

    2016-07-01

    Iron is critical for cellular, organismal, and possibly universal existence. Use of iron complexes to treat human diseases is ancient and is described in detail in Ayurveda/Siddha systems of medicine. Old aphorisms from Siddha medicine ("Alavukku Minjinal Amirdhamum Nanjagum," an elixir turns poisonous when taken in excess) and Paracelsus ("Die Dosis macht das Gift," the dose makes the poison) are of practical relevance in understanding the role of this ancient metal in acute kidney injury. PMID:27312440

  7. [Uncaria tomentosa and acute ischemic kidney injury in rats].

    Science.gov (United States)

    de Fátima Fernandes Vattimo, Maria; da Silva, Natalia Oliveira

    2011-03-01

    The objective of this study was to evaluate the renoprotective effects of Uncaria Tomentosa (cat's claw) on ischemic acute kidney injury induced by renal clamping in rats. The hypoxia and hypoperfusion increase the production of reactive species already present in the inflammatory process. Results showed that the renal function evaluated by creatinine clearance, the urinary excretion of peroxides and malondealdehyde indexes demonstrated that UT induced renoprotection, probably related to its antioxidant activities.

  8. Update on the diagnosis and management of acute kidney injury

    OpenAIRE

    Ali Akcay; Kultigin Turkmen; DongWon Lee; et al, ...

    2010-01-01

    Ali Akcay, Kultigin Turkmen, DongWon Lee, Charles L EdelsteinDivision of Renal Diseases and Hypertension, University of Colorado and the Health Sciences Center, Aurora, Colorado, USAAbstract: Acute kidney injury (AKI) is an independent risk factor for morbidity and mortality. This review provides essential information for the diagnosis and management of AKI. Blood urea nitrogen and serum creatinine are used for the diagnosis of AKI. The review also focuses on recent studies on the diagnosis o...

  9. 5-Aminolevulinic acid protects against cisplatin-induced nephrotoxicity without compromising the anticancer efficiency of cisplatin in rats in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Yoshio Terada

    Full Text Available BACKGROUND/AIMS: Nephrotoxicity is a frequent and major limitation in cisplatin (CDDP-based chemotherapy. 5-Aminolevulinic acid (ALA is widely distributed in animal cells, and it is a precursor of tetrapyrole compounds such as heme that is fundamentally important in aerobic energy metabolism. The aim of this study is to evaluate the protective role of ALA in CDDP-induced acute kidney injury (AKI. METHOD: We used CDDP-induced AKI rat model and cultured renal tubular cells (NRK-52E. We divided four groups of rats: control, CDDP only, CDDP + ALA(post;(ALA 10 mg/kg + Fe in drinking water after CDDP, CDDP + ALA(pre & post. RESULT: CDDP increased Cr up to 6.5 mg/dl, BUN up to 230 mg/dl, and ALA significantly reduced these changes. ALA ameliorates CDDP-induced morphological renal damages, and reduced tubular apoptosis evaluated by TUNEL staining and cleaved caspase 3. Protein and mRNA levels of ATP5α, complex(COX IV, UCP2, PGC-1α in renal tissue were significantly decreased by CDDP, and ALA ameliorates reduction of these enzymes. In contrast, Heme Oxigenase (HO-1 level is induced by CDDP treatment, and ALA treatment further up-regulates HO-1 levels. In NRK-52E cells, the CDDP-induced reduction of protein and mRNA levels of mitochondrial enzymes was significantly recovered by ALA + Fe. CDDP-induced apoptosis were ameliorated by ALA + Fe treatment. Furthermore, we evaluated the size of transplantated bladder carcinoma to the rat skin, and ALA did not change the anti cancer effects of CDDP. CONCLUSION: These data suggested that the protective role of ALA in cisplatin-induced AKI is via protection of mitochondrial viability and prevents tubular apoptosis. Also there are no significant effects of ALA on anticancer efficiency of CDDP in rats. Thus, ALA has the potential to prevent CDDP nephrotoxicity without compromising its anticancer efficacy.

  10. Acute Kidney Injury: Epidemiology, Diagnosis, Prognosis, and Future Directions

    Directory of Open Access Journals (Sweden)

    Joana Briosa Neves

    2015-07-01

    Full Text Available Acute kidney injury (AKI is a common problem highly associated with hospitalisation. AKI is the cause of harmful short-term consequences: longer hospital stays, greater disability after discharge, and greater risk of in-hospital mortality, as well as adverse long-term outcomes, such as progression to chronic kidney disease, development of cardiovascular disease, and increased risk of long-term mortality. The concept of AKI has changed since the introduction of the ‘Risk, Injury, Failure, Loss of kidney function, End-stage kidney disease’ (RIFLE classification. More recently, the ‘Kidney Disease Improving Global Outcomes’ (KDIGO classification appears to have provided increased diagnostic sensitivity and outcome-prediction capability. Novel biomarkers and further research on the role of the immune system in AKI may help improve the diagnosis, severity, outcome evaluation, and treatment of the condition. In this review we describe the epidemiology, diagnosis, and prognosis of AKI, as well as possible future directions for its clinical management.

  11. Biomarkers of delayed graft function as a form of acute kidney injury in kidney transplantation.

    Science.gov (United States)

    Malyszko, Jolanta; Lukaszyk, Ewelina; Glowinska, Irena; Durlik, Magdalena

    2015-01-01

    Renal transplantation ensures distinct advantages for patients with end-stage kidney disease. However, in some cases early complications can lead to allograft dysfunction and consequently graft loss. One of the most common early complications after kidney transplantation is delayed graft function (DGF). Unfortunately there is no effective treatment for DGF, however early diagnosis of DGF and therapeutic intervention (eg modification of immunosuppression) may improve outcome. Therefore, markers of acute kidney injury are required. Creatinine is a poor biomarker for kidney injury due principally to its inability to help diagnose early acute renal failure and complete inability to help differentiate among its various causes. Different urinary and serum proteins have been intensively investigated as possible biomarkers in this setting. There are promising candidate biomarkers with the ability to detect DGF. We focused on emerging biomarkers of DGF with NGAL is being the most studied followed by KIM-1, L-FABP, IL-18, and others. However, large randomized studies are needed to establish the value of new, promising biomarkers, in DGF diagnosis, prognosis and its cost-effectiveness. PMID:26175216

  12. Pharmacological Strategies to Prevent Contrast-Induced Acute Kidney Injury

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    Pattharawin Pattharanitima

    2014-01-01

    Full Text Available Contrast-induced acute kidney injury (CI-AKI is the most common iatrogenic cause of acute kidney injury after intravenous contrast media administration. In general, the incidence of CI-AKI is low in patients with normal renal function. However, the rate is remarkably elevated in patients with preexisting chronic kidney disease, diabetes mellitus, old age, high volume of contrast agent, congestive heart failure, hypotension, anemia, use of nephrotoxic drug, and volume depletion. Consequently, CI-AKI particularly in high risk patients contributes to extended hospitalizations and increases long-term morbidity and mortality. The pathogenesis of CI-AKI involves at least three mechanisms; contrast agents induce renal vasoconstriction, increase of oxygen free radicals through oxidative stress, and direct tubular toxicity. Several strategies to prevent CI-AKI have been evaluated in experimental studies and clinical trials. At present, intravascular volume expansion with either isotonic saline or sodium bicarbonate solutions has provided more consistent positive results and was recommended in the prevention of CI-AKI. However, the proportion of patients with risk still develops CI-AKI. This review critically evaluated the current evidence for pharmacological strategies to prevent CI-AKI in patients with a risk of developing CI-AKI.

  13. Acute kidney injury in pregnancy-current status.

    Science.gov (United States)

    Acharya, Anjali; Santos, Jolina; Linde, Brian; Anis, Kisra

    2013-05-01

    Pregnancy-related acute kidney injury (PR-AKI) causes significant maternal and fetal morbidity and mortality. Management of PR-AKI warrants a thorough understanding of the physiologic adaptations in the kidney and the urinary tract. Categorization of etiologies of PR-AKI is similar to that of acute kidney injury (AKI) in the nonpregnant population. The causes differ between developed and developing countries, with thrombotic microangiopathies (TMAs) being common in the former and septic abortion and puerperal sepsis in the latter. The incidence of PR-AKI is reported to be on a decline, but there is no consensus on the exact definition of the condition. The physiologic changes in pregnancy make diagnosis of PR-AKI difficult. Newer biomarkers are being studied extensively but are not yet available for clinical use. Early and accurate diagnosis is necessary to improve maternal and fetal outcomes. Timely identification of "at-risk" individuals and treatment of underlying conditions such as sepsis, preeclampsia, and TMAs remain the cornerstone of management. Questions regarding renal replacement therapy such as modality, optimal prescription, and timing of initiation in PR-AKI remain unclear. There is a need to systematically explore these variables to improve care of women with PR-AKI. PMID:23928385

  14. Acute kidney injury in critically ill cancer patients: an update.

    Science.gov (United States)

    Lameire, Norbert; Vanholder, Raymond; Van Biesen, Wim; Benoit, Dominique

    2016-01-01

    Patients with cancer represent a growing group among actual ICU admissions (up to 20 %). Due to their increased susceptibility to infectious and noninfectious complications related to the underlying cancer itself or its treatment, these patients frequently develop acute kidney injury (AKI). A wide variety of definitions for AKI are still used in the cancer literature, despite existing guidelines on definitions and staging of AKI. Alternative diagnostic investigations such as Cystatin C and urinary biomarkers are discussed briefly. This review summarizes the literature between 2010 and 2015 on epidemiology and prognosis of AKI in this population. Overall, the causes of AKI in the setting of malignancy are similar to those in other clinical settings, including preexisting chronic kidney disease. In addition, nephrotoxicity induced by the anticancer treatments including the more recently introduced targeted therapies is increasingly observed. However, data are sometimes difficult to interpret because they are often presented from the oncological rather than from the nephrological point of view. Because the development of the acute tumor lysis syndrome is one of the major causes of AKI in patients with a high tumor burden or a high cell turnover, the diagnosis, risk factors, and preventive measures of the syndrome will be discussed. Finally, we will briefly discuss renal replacement therapy modalities and the emergence of chronic kidney disease in the growing subgroup of critically ill post-AKI survivors. PMID:27480256

  15. Acute kidney injury: changing lexicography, definitions, and epidemiology.

    Science.gov (United States)

    Himmelfarb, J; Ikizler, T A

    2007-05-01

    In recent years, there have been numerous advances in understanding the molecular determinants of functional kidney injury after ischemic and/or toxic exposure. However, translation of successful novel therapies designed to attenuate kidney functional injury from animal models to the clinical sphere has had modest results. This lack of translatability is at least in part due to lack of sufficient standardization in definitions and classification of cases of acute kidney injury (AKI), an incomplete understanding of the natural history of human AKI, and a limited understanding of how kidney injury interacts with other organ system failure in the context of systemic metabolic abnormalities. A concerted effort is now being made by nephrologists and intensivists to arrive at standardized terminology and classification of AKI. There have also been dramatic advances in our understanding of the epidemiology and natural history of AKI, particularly in the hospital and intensive care unit setting. Promising strategies are now being developed which may ultimately lead to improved outcomes for patients at risk for or who have developed AKI, which should be readily testable in the coming decade.

  16. PLASMA NEUTROPHIL GELATINASE ASSOCIATED LIPOCALIN AS AN EARLY BIOMARKER OF ACUTE KIDNEY INJURY IN SNAKE BITE

    OpenAIRE

    Thamarai; Sivakumar,

    2014-01-01

    INTRODUCTION: Acute kidney injury due to snake bite represents a frequent and devastating problem. Currently, Acute Kidney Injury is diagnosed by biochemical monitoring of increase in serum creatinine. Increase in serum creatinine represents a late indication of a functional change in glomerular function rate. Studies have shown that Neutrophil Gelatinase Associated Lipocalin has been found to be very useful for the detection of acute kidney injury within few hours of neph...

  17. Biomarkers of acute kidney injury and associations with short- and long-term outcomes

    OpenAIRE

    Schaub, Jennifer A.; Parikh, Chirag R.

    2016-01-01

    Acute kidney injury is strongly associated with increased mortality and other adverse outcomes. Medical researchers have intensively investigated novel biomarkers to predict short- and long-term outcomes of acute kidney injury in many patient care settings, such as cardiac surgery, intensive care units, heart failure, and transplant. Future research should focus on leveraging this relationship to improve enrollment for clinical trials of acute kidney injury.

  18. Ondansetron Can Enhance Cisplatin-Induced Nephrotoxicity via Inhibition of Multiple Toxin and Extrusion Proteins (MATEs)

    Science.gov (United States)

    Li, Qing; Guo, Dong; Dong, Zhongqi; Zhang, Wei; Zhang, Lei K.; Huang, Shiew-Mei; Polli, James E.; Shu, Yan

    2013-01-01

    The nephrotoxicity limits the clinical application of cisplatin. Human organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins (MATEs) work in concert in the elimination of cationic drugs such as cisplatin from the kidney. We hypothesized that co-administration of ondansetron would have an effect on cisplatin nephrotoxicity by altering the function of cisplatin transporters. The inhibitory potencies of ondansetron on metformin accumulation mediated by OCT2 and MATEs were determined in the stable HEK-293 cells expressing these transporters. The effects of ondansetron on drug disposition in vivo were examined by conducting the pharmacokinetics of metformin, a classical substrate for OCTs and MATEs, in wild-type and Mate1−/− mice. The nephrotoxicity was assessed in the wild-type and Mate1−/− mice received cisplatin with and without ondansetron. Both MATEs, including human MATE1, human MATE2-K, and mouse Mate1, and OCT2 (human and mouse) were subject to ondansetron inhibition, with much greater potencies by ondansetron on MATEs. Ondansetron significantly increased tissue accumulation and pharmacokinetic exposure of metformin in wild-type but not in Mate1−/− mice. Moreover, ondansetron treatment significantly enhanced renal accumulation of cisplatin and cisplatin-induced nephrotoxicity which were indicated by increased levels of biochemical and molecular biomarkers and more severe pathohistological changes in mice. Similar increases in nephrotoxicity were caused by genetic deficiency of MATE function in mice. Therefore, the potent inhibition of MATEs by ondansetron enhances the nephrotoxicity associated with cisplatin treatment in mice. Potential nephrotoxic effects of combining the chemotherapeutic cisplatin and the antiemetic 5-hydroxytryptamine-3 (5-HT3) receptor antagonists, such as ondansetron, should be investigated in patients. PMID:24001450

  19. Acute kidney injury in severe acute pancreatitis: An experience from a tertiary care center

    OpenAIRE

    Ravindra Kumar; Naresh Pahwa; Neeraj Jain

    2015-01-01

    Acute kidney injury (AKI) is an important cause of morbidity and mortality in severe acute pancreatitis (SAP). We aimed in our study to explore the risk factors of AKI in patients with SAP and assess the prognosis of patients with SAP and AKI. This is a retrospective study consisting of analysis of outcome and complications encountered in 72 severe acute pancreatitis patients admitted to a tertiary care center at Indore, India, from May 2011 to April 2012. We encountered 14 AKI cases in the S...

  20. Losartan reduces ensuing chronic kidney disease and mortality after acute kidney injury

    Science.gov (United States)

    Cheng, Shun-Yang; Chou, Yu-Hsiang; Liao, Fang-Ling; Lin, Chi-Chun; Chang, Fan-Chi; Liu, Chia-Hao; Huang, Tao-Min; Lai, Chun-Fu; Lin, Yu-Feng; Wu, Vin-Cent; Chu, Tzong-Shinn; Wu, Ming-Shiou; Lin, Shuei-Liong

    2016-01-01

    Acute kidney injury (AKI) is an important risk factor for incident chronic kidney disease (CKD). Clinical studies disclose that ensuing CKD progresses after functional recovery from AKI, but the underlying mechanisms remain illusive. Using a murine model representing AKI-CKD continuum, we show angiotensin II type 1a (AT1a) receptor signaling as one of the underlying mechanisms. Male adult CD-1 mice presented severe AKI with 20% mortality within 2 weeks after right nephrectomy and left renal ischemia-reperfusion injury. Despite functional recovery, focal tubular atrophy, interstitial cell infiltration and fibrosis, upregulation of genes encoding angiotensinogen and AT1a receptor were shown in kidneys 4 weeks after AKI. Thereafter mice manifested increase of blood pressure, albuminuria and azotemia progressively. Drinking water with or without losartan or hydralazine was administered to mice from 4 weeks after AKI. Increase of mortality, blood pressure, albuminuria, azotemia and kidney fibrosis was noted in mice with vehicle administration during the 5-month experimental period. On the contrary, these parameters in mice with losartan administration were reduced to the levels shown in control group. Hydralazine did not provide similar beneficial effect though blood pressure was controlled. These findings demonstrate that losartan can reduce ensuing CKD and mortality after functional recovery from AKI. PMID:27677327

  1. Chronic kidney disease-induced HMGB1 elevation worsens sepsis and sepsis-induced acute kidney injury

    OpenAIRE

    Leelahavanichkul, Asada; Huang, Yuning; Hu, Xuzhen; Zhou, Hua; Tsuji, Takayuki; Chen, Richard; Jeffrey B Kopp; Schnermann, Jürgen; Yuen, Peter S.T.; Star, Robert A.

    2011-01-01

    We previously showed that kidney dysfunction/interstitial fibrosis by folate predisposes mice to sepsis mortality (normal/sepsis: 15%; folate/sepsis: 90%); agents that increased survival in normal septic mice were ineffective in the two-stage model. We used a recently characterized 5/6 nephrectomy (Nx) mouse model of progressive chronic kidney disease (CKD) to study how CKD impacts sepsis and acute kidney injury (AKI) induced by cecal ligation-puncture (CLP). CKD intensified sepsis severity (...

  2. Kidney Disease and the Nexus of Chronic Kidney Disease and Acute Kidney Injury: The Role of Novel Biomarkers as Early and Accurate Diagnostics.

    Science.gov (United States)

    Yerramilli, Murthy; Farace, Giosi; Quinn, John; Yerramilli, Maha

    2016-11-01

    Chronic kidney disease (CKD) and acute kidney injury (AKI) are interconnected and the presence of one is a risk for the other. CKD is an important predictor of AKI after exposure to nephrotoxic drugs or major surgery, whereas persistent or repetitive injury could result in the progression of CKD. This brings new perspectives to the diagnosis and monitoring of kidney diseases highlighting the need for a panel of kidney-specific biomarkers that reflect functional as well as structural damage and recovery, predict potential risk and provide prognosis. This article discusses the kidney-specific biomarkers, symmetric dimethylarginine (SDMA), clusterin, cystatin B, and inosine. PMID:27485279

  3. An Unusual Complication of Foam Sclerotherapy: Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    Müge EREK

    2014-09-01

    Full Text Available Sclerotherapy, in which an irritant solution is administered, is a method used to treat venous failure that results in complete venous destruction due to endothelial reaction and fibrosis. In recent years, foam sclerotherapy, in which a sclerosing agent (aethyl sclerole and air are mixed until they turn into foam and the resultant mixture is injected into noticeable veins directly and into other veins under ultrasonography in doses depending on the diameters of the varices, has been introduced. The drugs or gases used in foam sclerotherapy can cause local or systemic complications. Foam affects vessel endothelial cells and causes severe spasm in the vessel. It has been reported that endothelin-1 levels are high after foam sclerotherapy compared to the initial levels and that neurological complications vary with the endothelin levels. In this report, we present a case of acute kidney injury due to acute tubular necrosis probably caused by endothelin release following foam sclerotherapy.

  4. Metformin-Associated Acute Kidney Injury and Lactic Acidosis

    Directory of Open Access Journals (Sweden)

    David Arroyo

    2011-01-01

    Full Text Available Objectives. Metformin is the preferred oral antidiabetic agent for type 2 diabetes. Lactic acidosis is described as a rare complication, usually during an acute kidney injury (AKI. Material and Methods. We conducted a prospective observational study of metformin-associated AKI cases during four years. 29 cases were identified. Previous renal function, clinical data, and outcomes were recorded. Results. An episode of acute gastroenteritis precipitated the event in 26 cases. Three developed a septic shock. Three patients died, the only related factor being liver dysfunction. More severe metabolic acidosis hyperkalemia and anemia were associated with higher probabilities of RRT requirement. We could not find any relationship between previous renal dysfunction and the outcome of the AKI. Conclusions. AKI associated to an episode of volume depletion due to gastrointestinal losses is a serious complication in type 2 diabetic patients on metformin. Previous renal dysfunction (mild-to-moderate CKD has no influence on the severity or outcome.

  5. Central Diabetes Insipidus and Cisplatin-Induced Renal Salt Wasting Syndrome: A Challenging Combination.

    Science.gov (United States)

    Cortina, Gerard; Hansford, Jordan R; Duke, Trevor

    2016-05-01

    We describe a 2-year-old female with a suprasellar primitive neuroectodermal tumor and central diabetes insipidus (DI) who developed polyuria with natriuresis and subsequent hyponatremia 36 hr after cisplatin administration. The marked urinary losses of sodium in combination with a negative sodium balance led to the diagnosis of cisplatin-induced renal salt wasting syndrome (RSWS). The subsequent clinical management is very challenging. Four weeks later she was discharged from ICU without neurological sequela. The combination of cisplatin-induced RSWS with DI can be confusing and needs careful clinical assessment as inaccurate diagnosis and management can result in increased neurological injury.

  6. Protective effects of pine bark extract against cisplatin-induced hepatotoxicity and oxidative stress in rats

    OpenAIRE

    Ko, Je-Won; Lee, In-Chul; Park, Sung-Hyuk; Moon, Changjong; Kang, Seong-Soo; Kim, Sung-Ho; Kim, Jong-Choon

    2014-01-01

    We investigated the protective effects of pine bark extract (pycnogenol®, PYC) against cisplatin-induced hepatotoxicity and oxidative stress in rats. Twenty-four male rats were divided into the following four groups: (1) vehicle control, (2) cisplatin (7.5 mg/kg), (3) cisplatin & PYC 10 (10 mg/kg/day), and (4) cisplatin & PYC 20 (20 mg/kg/day). A single intraperitoneal injection of cisplatin induced hepatotoxicity, as evidenced by an increase in serum aminotransferase and histopathological al...

  7. Acute kidney injury: Renal disease in the ICU.

    Science.gov (United States)

    Seller-Pérez, G; Más-Font, S; Pérez-Calvo, C; Villa-Díaz, P; Celaya-López, M; Herrera-Gutiérrez, M E

    2016-01-01

    Acute kidney injury (AKI) in the ICU frequently requires costly supportive therapies, has high morbidity, and its long-term prognosis is not as good as it has been presumed so far. Consequently, AKI generates a significant burden for the healthcare system. The problem is that AKI lacks an effective treatment and the best approach relies on early secondary prevention. Therefore, to facilitate early diagnosis, a broader definition of AKI should be established, and a marker with more sensitivity and early-detection capacity than serum creatinine - the most common marker of AKI - should be identified. Fortunately, new classification systems (RIFLE, AKIN or KDIGO) have been developed to solve these problems, and the discovery of new biomarkers for kidney injury will hopefully change the way we approach renal patients. As a first step, the concept of renal failure has changed from being a "static" disease to being a "dynamic process" that requires continuous evaluation of kidney function adapted to the reality of the ICU patient. PMID:27388683

  8. Acute Kidney Injury in Lymphoma: A Single Centre Experience

    Directory of Open Access Journals (Sweden)

    Muhammad Abdul Mabood Khalil

    2014-01-01

    Full Text Available Background. Acute kidney injury (AKI is a common but least studied complication of lymphoma. Objective. To determine the frequency and predictors of AKI in lymphoma and to study the impact of AKI on hospital stay and mortality. Methods. Retrospective review of medical records of hospitalized lymphoma patients aged ≥14 years between January 2008 and December 2011 was done. Results. Out of 365 patients, AKI was present in 31.8% (116/365. Multivariate logistic regression analysis showed that independent predictors for AKI included sepsis (odds ratio (OR 3.76; 95% CI 1.83–7.72, aminoglycosides (OR 4.75; 95% CI 1.15–19.52, diuretics (OR 2.96; 95% CI 1.31–6.69, tumor lysis syndrome (OR 3.85; 95% CI 1.54–9.59, and R-CVP regimen (OR 4.70; 95% CI 1.20–18.36. AKI stages 2 and 3 was associated with increased hospital stay (OR 2.01; 95% CI 1.19–3.40. Conclusion. AKI was significantly associated with sepsis, aminoglycoside, diuretics, presence of tumor lysis syndrome, and use of R-CVP regimen. Presence of AKIN (Acute Kidney Injury Network stages 2 and 3 AKI had increased hospital stay. AKI was also associated with increased mortality.

  9. Autophagy, Innate Immunity and Tissue Repair in Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    Pu Duann

    2016-05-01

    Full Text Available Kidney is a vital organ with high energy demands to actively maintain plasma hemodynamics, electrolytes and water homeostasis. Among the nephron segments, the renal tubular epithelium is endowed with high mitochondria density for their function in active transport. Acute kidney injury (AKI is an important clinical syndrome and a global public health issue with high mortality rate and socioeconomic burden due to lack of effective therapy. AKI results in acute cell death and necrosis of renal tubule epithelial cells accompanied with leakage of tubular fluid and inflammation. The inflammatory immune response triggered by the tubular cell death, mitochondrial damage, associative oxidative stress, and the release of many tissue damage factors have been identified as key elements driving the pathophysiology of AKI. Autophagy, the cellular mechanism that removes damaged organelles via lysosome-mediated degradation, had been proposed to be renoprotective. An in-depth understanding of the intricate interplay between autophagy and innate immune response, and their roles in AKI pathology could lead to novel therapies in AKI. This review addresses the current pathophysiology of AKI in aspects of mitochondrial dysfunction, innate immunity, and molecular mechanisms of autophagy. Recent advances in renal tissue regeneration and potential therapeutic interventions are also discussed.

  10. Protective effect of cysteine and vitamin E, Crocus sativus and Nigella sativa extracts on cisplatin-induced toxicity in rats.

    Science.gov (United States)

    el Daly, E S

    1998-01-01

    Cisplatin [cis-dichlorodiammineplatinum (II)] is a widely used chemotherapeutic drug that is toxic to the kidney. Concurrent administration of cysteine together with vitamin E, Crocus sativus and Nigella sativa reduced the toxicity of cisplatin in rats. When administered i.p. for 5 alternate days with 3 mg/kg cisplatin, cysteine (20 mg/kg) together with vitamin E (2 mg/rat) an extract of Crocus sativus stigmas (50 mg/kg) and Nigella sativa seed (50 mg/kg) significantly reduced blood urea nitrogen (BUN) and serum creatinine levels as well as cisplatin-induced serum total lipids increases. In contrast, the protective agents given together with cisplatin led to an even greater decrease in blood glucose than that seen with cisplatin alone. The serum activities of alkaline phosphatase, lactate dehydrogenase, malate dehydrogenase, aspartate aminotransferase and alanine aminotransferase of cisplatin-treated rats were significantly decreased, whereas the activities of glutathione reductase and isocitrate dehydrogenase were significantly increased. Addition of cysteine and vitamin E, Crocus sativus and Nigella sativa in combination with cisplatin partially prevented many changes in the activities of serum enzymes. In cisplatin-treated rats, the liver activities of isocitrate dehydrogenase and aspartate aminotransferase were significantly increased, whereas much greater changes were found in the kidneys, with increased activity of glucose-6-phosphate dehydrogenase and decreased activities of alkaline phosphatase, isocitrate dehydrogenase, malate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, sorbitol dehydrogenase and gamma-glutamyl transferase, as well as a decreased phosphorylation to oxidation ratio in the mitochondria, indicating reduced adenosine triphosphate production. Also, administration of cysteine and vitamin E, Crocus sativus and Nigella sativa together with cisplatin partially reversed many of the kidney enzymes changes induced by cisplatin

  11. Metabolomics as an extension of proteomic analysis: study of acute kidney injury.

    Science.gov (United States)

    Portilla, Didier; Schnackenberg, Laura; Beger, Richard D

    2007-11-01

    Although proteomics studies the global expression of proteins, metabolomics characterizes and quantifies their end products: the metabolites, produced by an organism under a certain set of conditions. From this perspective it is apparent that proteomics and metabolomics are complementary and when joined allow a fuller appreciation of an organism's phenotype. Our studies using (1)H-nuclear magnetic resonance spectroscopic analysis showed the presence of glucose, amino acids, and trichloroacetic acid cycle metabolites in the urine after 48 hours of cisplatin administration. These metabolic alterations precede changes in serum creatinine. Biochemical studies confirmed the presence of glucosuria, but also showed the accumulation of nonesterified fatty acids, and triglycerides in serum, urine, and kidney tissue, despite increased levels of plasma insulin. These metabolic alterations were ameliorated by the use of fibrates. We propose that the injury-induced metabolic profile may be used as a biomarker of cisplatin-induced nephrotoxicity. These studies serve to illustrate that metabolomic studies add insight into pathophysiology not provided by proteomic analysis alone.

  12. Acute kidney injury is independently associated with higher mortality after cardiac surgery

    DEFF Research Database (Denmark)

    Kandler, Kristian; Jensen, Mathias E; Nilsson, Jens C;

    2014-01-01

    , previous nephrectomy, preoperative sCr >2.26 mg/dL and selective cerebral perfusion during cardiopulmonary bypass were used as exclusion criteria. Acute kidney injury was defined, using the Acute Kidney Injury Network (AKIN) criteria. Six hundred eight patients were included in the study. Mean age was 68...

  13. Acute kidney injury in burns: a story of volume and inflammation

    OpenAIRE

    COLPAERT, KIRSTEN; Hoste, Eric A

    2008-01-01

    Acute kidney injury occurs in approximately one-quarter to one-third of patients with major burn injury. Apart from the usual suspects – such as older age, severity of burn injury, sepsis and multiple organ dysfunction – volume overload probably has an important role in the pathogenesis of acute kidney injury.

  14. Vitamin D deficiency aggravates chronic kidney disease progression after ischemic acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Janaína Garcia Gonçalves

    pathways and involvement of TGF-β1 growth factor, VDD could be considered as an aggravating factor for tubulointerstitial damage and fibrosis progression following acute kidney injury induced by ischemia/reperfusion.

  15. Gene Expression Profiling on Acute Rejected Transplant Kidneys with Microarray

    Institute of Scientific and Technical Information of China (English)

    Deping LI; Kang WANG; Yong DAI; Tianyu LV

    2008-01-01

    To investigate the gene expression profiles in acute allograft rejection of renal trans- plantation, and identify the markers for the early diagnosis of acute rejection, heterotopic kidney transplantation was performed by using F344 or Lewis donors and Lewis recipients. No immunosup- pressant was used. Renal grafts were harvested on days 3, 7, and 14. A commercial microarray was used to measure gene expression levels in day-7 grafts. The expression levels of 48 genes were up-regulated in the allograft in comparison with the isograft control, and interferon-y-induced GTPase gene was most significantly up-regulated in allografts. It is concluded that a variety of pathways are involved in organ transplant rejection which is dynamic and non-balanced. IFN-inducible genes, such as IGTP, may play an important role in the rejection. A lot of important factors involved in acute re- jection are unnecessary but sufficient conditions for the rejection. We are led to conclude that it is virtually impossible to make an early diagnosis based on a single gene marker, but it could he achieved on the basis of a set of markers.

  16. Antiemetic role of thalidomide in a rat model of cisplatin-induced emesis.

    Science.gov (United States)

    Han, Zheng-xiang; Xu, Jie; Wang, Hong-mei; Ma, Jan; Sun, Xuan; Du, Xiu-ping

    2014-09-01

    The efficacy of thalidomide to attenuate cisplatin-induced emesis was evaluated in a rat model. Four groups were utilized: control group (peritoneal injection and gastric lavage with normal saline), cisplatin group (peritoneal injection of cisplatin at 10 mg/kg and gastric lavage with normal saline), thalidomide group (cisplatin as above and gastric lavage with thalidomide at 10 mg/kg), and granisetron group (positive control for antiemetic effects; cisplatin given as above and gastric lavage done with granisetron at 0.5 mg/kg). The cisplatin-induced kaolin consumption (pica behavior) was used as a model of emesis in patients. The animals' kaolin and food intakes were measured. Further, medulla and gastric tissues were obtained 5 and 33 h after peritoneal injections to quantify the levels of Substance P and Neurokinin-1 receptor (NK-1R). The cisplatin-induced kaolin consumption was significantly (p thalidomide 72 h after the injection. The levels of Substance P in the medulla and gastric tissue were increased 5 h after the injection in both cisplatin and thalidomide groups, however, returned faster to normal levels in the thalidomide group (p thalidomide, and granisetron group were significantly increased at both 5 and 33 h (p thalidomide attenuates animal equivalent of cisplatin-induced emesis, and this beneficial effect is associated with decreased levels of Substance P levels in the medulla and gastric tissue.

  17. [Epidemiology of acute kidney injury in hospitalized patients in China].

    Science.gov (United States)

    Lang, Xiabing; Yang, Yi; Chen, Jianghua

    2016-03-01

    Acute kidney injury (AKI) is a disease spectrum ranging from minimal elevation of serum creatinine to complete renal failure. It is significantly associated with increased mortality, length of hospital stay and medical care cost. With the increasing awareness of the importance of AKI, several high quality and multicenter epidemiological studies have been published recently in China. However, the results differ a lot due to the differences in regional economic development, the selection of target population and testing indicators, the disease definition and study strategies. The reported incidence of AKI in China is much lower than that in the developed countries. This article will analyze the current status and the problems facing AKI epidemiological studies of hospitalized patients with our own data and those from literature. The article intends to clarify the burden of AKI,to increase the awareness of AKI among clinicians and policy makers for achieving the goal of "zero by 2025" in China. PMID:27273996

  18. Recurrent acute kidney injury associated with metastatic bronchial carcinoid.

    Science.gov (United States)

    Barton, James C; Barton, J Clayborn; Bertoli, Luigi F

    2012-01-01

    Acute kidney injury (AKI) is a rare complication of carcinoid syndrome. A 61-year-old man developed carcinoid syndrome 51 months after pneumonectomy for bronchial carcinoid, and 8 episodes of AKI 101 to 118 months after pneumonectomy. Serum chromogranin A and urine 5-hydroxyindoleacetic acid levels were elevated for more than 1 year before AKI occurred. Each episode was characterized by flushing, facial edema, mild diarrhea, necrosis of hepatic metastatic nodules, mild oliguria, hyponatremia, acidosis, hypokalemia, hypomagnesemia and hyperphosphatemia. He did not have elevated urine sodium levels or osmolality, hypotension or hypertension. Plasma levels of dopamine, epinephrine and norepinephrine, measured during a single episode, were markedly elevated. Serum creatinine levels returned to normal after most episodes. Hyponatremia persisted but was more severe during AKI. Elevated plasma levels of vasoactive substances other than 5-hydroxytryptamine, perhaps dopamine or other catecholamines, could explain recurrent AKI. The natriuretic effect of elevated plasma dopamine levels could explain chronic hyponatremia. PMID:22008780

  19. Predictors of Renal Replacement Therapy in Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    Michael J. Koziolek

    2012-09-01

    Full Text Available Backgrounds: Criteria that may guide early renal replacement therapy (RRT initiation in patients with acute kidney injury (AKI currently do not exist. Methods: In 120 consecutive patients with AKI, clinical and laboratory data were analyzed on admittance. The prognostic power of those parameters which were significantly different between the two groups was analyzed by receiver operator characteristic curves and by leave-1-out cross validation. Results: Six parameters (urine albumin, plasma creatinine, blood urea nitrogen, daily urine output, fluid balance and plasma sodium were combined in a logistic regression model that estimates the probability that a particular patient will need RRT. Additionally, a second model without daily urine output was established. Both models yielded a higher accuracy (89 and 88% correct classification rate, respectively than the best single parameter, cystatin C (correct classification rate 74%. Conclusions: The combined models may help to better predict the necessity of RRT using clinical and routine laboratory data in patients with AKI.

  20. Expanding the pool of kidney donors: use of kidneys with acute renal dysfunction.

    Science.gov (United States)

    Matos, Ana Cristina Carvalho de; Requião-Moura, Lúcio Roberto; Clarizia, Gabriela; Durão Junior, Marcelino de Souza; Tonato, Eduardo José; Chinen, Rogério; Arruda, Érika Ferraz de; Filiponi, Thiago Corsi; Pires, Luciana Mello de Mello Barros; Bertocchi, Ana Paula Fernandes; Pacheco-Silva, Alvaro

    2015-01-01

    Given the shortage of organs transplantation, some strategies have been adopted by the transplant community to increase the supply of organs. One strategy is the use of expanded criteria for donors, that is, donors aged >60 years or 50 and 59 years, and meeting two or more of the following criteria: history of hypertension, terminal serum creatinine >1.5mg/dL, and stroke as the donor´s cause of death. In this review, emphasis was placed on the use of donors with acute renal failure, a condition considered by many as a contraindication for organ acceptance and therefore one of the main causes for kidney discard. Since these are well-selected donors and with no chronic diseases, such as hypertension, renal disease, or diabetes, many studies showed that the use of donors with acute renal failure should be encouraged, because, in general, acute renal dysfunction is reversible. Although most studies demonstrated these grafts have more delayed function, the results of graft and patient survival after transplant are very similar to those with the use of standard donors. Clinical and morphological findings of donors, the use of machine perfusion, and analysis of its parameters, especially intrarenal resistance, are important tools to support decision-making when considering the supply of organs with renal dysfunction. PMID:26154553

  1. Functional Magnetic Resonance Imaging in Acute Kidney Injury: Present Status

    Directory of Open Access Journals (Sweden)

    Hai Ying Zhou

    2016-01-01

    Full Text Available Acute kidney injury (AKI is a common complication of hospitalization that is characterized by a sudden loss of renal excretory function and associated with the subsequent development of chronic kidney disease, poor prognosis, and increased mortality. Although the pathophysiology of renal functional impairment in the setting of AKI remains poorly understood, previous studies have identified changes in renal hemodynamics, perfusion, and oxygenation as key factors in the development and progression of AKI. The early assessment of these changes remains a challenge. Many established approaches are not applicable to humans because of their invasiveness. Functional renal magnetic resonance (MR imaging offers an alternative assessment tool that could be used to evaluate renal morphology and function noninvasively and simultaneously. Thus, the purpose of this review is to illustrate the principle, application, and role of the techniques of functional renal MR imaging, including blood oxygen level-dependent imaging, arterial spin labeling, and diffusion-weighted MR imaging, in the management of AKI. The use of gadolinium in MR imaging may exacerbate renal impairment and cause nephrogenic systemic fibrosis. Therefore, dynamic contrast-enhanced MR imaging will not be discussed in this paper.

  2. Functional Magnetic Resonance Imaging in Acute Kidney Injury: Present Status.

    Science.gov (United States)

    Zhou, Hai Ying; Chen, Tian Wu; Zhang, Xiao Ming

    2016-01-01

    Acute kidney injury (AKI) is a common complication of hospitalization that is characterized by a sudden loss of renal excretory function and associated with the subsequent development of chronic kidney disease, poor prognosis, and increased mortality. Although the pathophysiology of renal functional impairment in the setting of AKI remains poorly understood, previous studies have identified changes in renal hemodynamics, perfusion, and oxygenation as key factors in the development and progression of AKI. The early assessment of these changes remains a challenge. Many established approaches are not applicable to humans because of their invasiveness. Functional renal magnetic resonance (MR) imaging offers an alternative assessment tool that could be used to evaluate renal morphology and function noninvasively and simultaneously. Thus, the purpose of this review is to illustrate the principle, application, and role of the techniques of functional renal MR imaging, including blood oxygen level-dependent imaging, arterial spin labeling, and diffusion-weighted MR imaging, in the management of AKI. The use of gadolinium in MR imaging may exacerbate renal impairment and cause nephrogenic systemic fibrosis. Therefore, dynamic contrast-enhanced MR imaging will not be discussed in this paper. PMID:26925411

  3. Acute kidney injury in septua- and octogenarians after cardiac surgery

    Directory of Open Access Journals (Sweden)

    Schmid Christof

    2011-08-01

    Full Text Available Abstract Background An increasing number of septua- and octogenarians undergo cardiac surgery. Acute kidney injury (AKI still is a frequent complication after surgery. We examined the incidence of AKI and its impact on 30-day mortality. Methods A retrospective study between 01/2006 and 08/2009 with 299 octogenarians, who were matched for gender and surgical procedure to 299 septuagenarians at a university hospital. Primary endpoint was AKI after surgery as proposed by the RIFLE definition (Risk, Injury, Failure, Loss, End-stage kidney disease. Secondary endpoint was 30-day mortality. Perioperative mortality was predicted with the logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE. Results Octogenarians significantly had a mean higher logistic EuroSCORE compared to septuagenarians (13.2% versus 8.5%; p -1 × 1.73 m-2. In contrast, septuagenarians showed a slightly higher median body mass index (28 kg × m-2 versus 26 kg × m-2 and were more frequently active smoker at time of surgery (6.4% versus 1.6%, p The RIFLE classification provided accurate risk assessment for 30-day mortality and fair discriminatory power. Conclusions The RIFLE criteria allow identifying patients with AKI after cardiac surgery. The high incidence of AKI in septua- and octogenarians after cardiac surgery should prompt the use of RIFLE criteria to identify patients at risk and should stimulate institutional measures that target AKI as a quality improvement initiative for patients at advanced age.

  4. Acute kidney injury: from clinical to molecular diagnosis.

    Science.gov (United States)

    Ronco, Claudio

    2016-01-01

    The RIFLE classification was introduced in 2004 to describe the presence of acute kidney injury (AKI) and to define its clinical stage, based upon the serum creatinine level and urine output. The same criteria, although slightly modified, are used in the other scoring systems AKIN and KDIGO. Mortality and morbidity remain high in AKI, suggesting that current diagnostic methods are suboptimal, poorly accurate, and often timely inadequate in detecting the presence of early kidney injury. Conversely, a growing body of evidence indicates that new AKI biomarkers can be used to both rule out AKI and to assess high-risk conditions or the presence of subclinical forms. Neutrophil gelatinase-associated lipocalin or cell cycle arrest biomarkers seem to be sensitive and specific enough to be used in conjunction with existing markers of AKI for better classifying renal injury as well as dysfunction. Improvements in diagnosis, risk identification, stratification, prognosis, and therapeutic monitoring may improve prevention and protection from organ damage and help to identify patients at risk, allowing individualized therapy. In this view, we may say that AKI diagnosis has finally moved from clinical to molecular level with potential benefits for the patients because similar progress has been shown in other disciplines. PMID:27384344

  5. Biomarkers of acute kidney injury in neonatal encephalopathy.

    LENUS (Irish Health Repository)

    Sweetman, D U

    2013-03-01

    Acute kidney injury (AKI) is a common complication of neonatal encephalopathy (NE). The accurate diagnosis of neonatal AKI, irrespective of the cause, relies on suboptimal methods such as identification of rising serum creatinine, decreased urinary output and glomerular filtration rate. Studies of AKI biomarkers in adults and children have shown that biomarkers can improve the early diagnosis of AKI. Hypoxia-ischaemia is the proposed aetiological basis of AKI in both NE and cardiopulmonary bypass (CPB). However, there is a paucity of studies examining the role of AKI biomarkers specifically in NE. Urinary cystatin C (CysC), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18, kidney injury molecule-1, liver-type fatty acid-binding protein, serum CysC and serum NGAL all show good ability to predict early AKI in a heterogeneous critically ill neonatal population including infants post-CPB. Moreover, serum and urinary NGAL and urinary CysC are early predictors of AKI secondary to NE. These findings are promising and open up the possibility of biomarkers playing a significant role in the early diagnosis and treatment of NE-related AKI. There is an urgent need to explore the role of AKI biomarkers in infants with NE as establishing the diagnosis of AKI earlier may allow more timely intervention with potential for improving long-term outcome.

  6. Acute kidney injury in severe acute pancreatitis: An experience from a tertiary care center

    Directory of Open Access Journals (Sweden)

    Ravindra Kumar

    2015-01-01

    Full Text Available Acute kidney injury (AKI is an important cause of morbidity and mortality in severe acute pancreatitis (SAP. We aimed in our study to explore the risk factors of AKI in patients with SAP and assess the prognosis of patients with SAP and AKI. This is a retrospective study consisting of analysis of outcome and complications encountered in 72 severe acute pancreatitis patients admitted to a tertiary care center at Indore, India, from May 2011 to April 2012. We encountered 14 AKI cases in the SAP study patients. There was a significant association of diabetes and alcohol with AKI in patients with SAP. Alcohol was found to be an independent significant risk factor for AKI in SAP. All the eight patients with SAP who expired had AKI. None of the patients of SAP without AKI expired during the study. We conclude that the patients with SAP with AKI have a greater mortality rate as compared with the SAP patients without AKI.

  7. CXCR2 knockout mice are protected against DSS-colitis-induced acute kidney injury and inflammation.

    Science.gov (United States)

    Ranganathan, Punithavathi; Jayakumar, Calpurnia; Manicassamy, Santhakumar; Ramesh, Ganesan

    2013-11-15

    Organ cross talk exists in many diseases of the human and animal models of human diseases. A recent study demonstrated that inflammatory mediators can cause acute kidney injury and neutrophil infiltration in a mouse model of dextran sodium sulfate (DSS)-colitis. However, the chemokines and their receptors that may mediate distant organ effects in colitis are unknown. We hypothesized that keratinocyte chemoattractant (KC)/IL-8 receptor chemokine (C-X-C motif) ligand 2 (CXCL2) mediates DSS-colitis-induced acute kidney injury. Consistent with our hypothesis, wild-type (WT) mice developed severe colitis with DSS treatment, which was associated with inflammatory cytokine and chemokine expression and neutrophil infiltration in the colon. DSS-colitis in WT was accompanied by acute kidney injury and enhanced expression of inflammatory cytokines in the kidney. However, CXCR2 knockout mice were protected against DSS-colitis as well as acute kidney injury. Moreover, the expression of cytokines and chemokines and neutrophil infiltration was blunted in CXCR2 knockout mice in the colon and kidney. Administration of recombinant KC exacerbated DSS-colitis-induced acute kidney injury. Our results suggest that KC/IL-8 and its receptor CXCR2 are critical and major mediators of organ cross talk in DSS colitis and neutralization of CXCR2 will help to reduce the incidence of acute kidney injury due to ulcerative colitis and Crohn's disease in humans.

  8. Relation between acute kidney injury and pregnancy-related factors

    Institute of Scientific and Technical Information of China (English)

    Monchai Siribamrungwong; Pawadee Chinudomwong

    2016-01-01

    Acute kidney injury (AKI) is a serious problem during pregnancy. Once occurred, it brings about devastating maternal and fetal outcomes. Among developed nations, the trend of pregnancy-related AKI (PRAKI) is on a decline due to the advances in obstetrics care and the legality of abortion. On the contrary, this situation remains one of the major health problems in the developing countries. Though some improvements have been observed, PRAKI still causes high maternal morbidity and mortality, leading to fetal losses. This article aims to review current studies with regards to obstetrics related AKI. Most of the studies in this review were carried out in observational, both prospective and retrospective, studies. Results demonstrated a variety of major PRAKI causes such as hypertensive disorders in pregnancy, obstetric hemorrhage, sepsis, thrombotic micro-angiopathy and acute fatty liver in pregnancy. Aside from awareness of the etiologies of PRAKI, understanding the physiological renal adaptation during pregnancy is crucial for early detection, diagnosis, and proper management to prevent the obstetric complications.

  9. Acute Kidney Injury and Atypical Features during Pediatric Poststreptococcal Glomerulonephritis

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    Rose M. Ayoob

    2016-01-01

    Full Text Available The most common acute glomerulonephritis in children is poststreptococcal glomerulonephritis (PSGN usually occurring between 3 and 12 years old. Hypertension and gross hematuria are common presenting symptoms. Most PSGN patients do not experience complications, but rapidly progressive glomerulonephritis and hypertensive encephalopathy have been reported. This paper reports 17 patients seen in 1 year for PSGN including 4 with atypical PSGN, at a pediatric tertiary care center. Seventeen children (11 males, mean age of 8 years, were analyzed. Ninety-four percent had elevated serum BUN levels and decreased GFR. Four of the hospitalized patients had complex presentations that included AKI along with positive ANA or ANCAs. Three patients required renal replacement therapy and two were thrombocytopenic. PSGN usually does not occur as a severe nephritis. Over the 12-month study period, 17 cases associated with low serum albumin in 53%, acute kidney injury in 94%, and thrombocytopenia in 18% were treated. The presentation of PSGN may be severe and in a small subset have associations similar to SLE nephritis findings including AKI, positive ANA, and hematological anomalies.

  10. Relation between acute kidney injury and pregnancy-related factors

    Directory of Open Access Journals (Sweden)

    Monchai Siribamrungwong

    2016-01-01

    Full Text Available Acute kidney injury (AKI is a serious problem during pregnancy. Once occurred, it brings about devastating maternal and fetal outcomes. Among developed nations, the trend of pregnancy-related AKI (PRAKI is on a decline due to the advances in obstetrics care and the legality of abortion. On the contrary, this situation remains one of the major health problems in the developing countries. Though some improvements have been observed, PRAKI still causes high maternal morbidity and mortality, leading to fetal losses. This article aims to review current studies with regards to obstetrics related AKI. Most of the studies in this review were carried out in observational, both prospective and retrospective, studies. Results demonstrated a variety of major PRAKI causes such as hypertensive disorders in pregnancy, obstetric hemorrhage, sepsis, thrombotic microangiopathy and acute fatty liver in pregnancy. Aside from awareness of the etiologies of PRAKI, understanding the physiological renal adaptation during pregnancy is crucial for early detection, diagnosis, and proper management to prevent the obstetric complications.

  11. Ondansetron can enhance cisplatin-induced nephrotoxicity via inhibition of multiple toxin and extrusion proteins (MATEs)

    Energy Technology Data Exchange (ETDEWEB)

    Li, Qing [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States); Institute of Clinical Pharmacology, Central South University, Hunan 410078 (China); Guo, Dong [Institute of Clinical Pharmacology, Central South University, Hunan 410078 (China); Dong, Zhongqi [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States); Zhang, Wei [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States); Institute of Clinical Pharmacology, Central South University, Hunan 410078 (China); Zhang, Lei; Huang, Shiew-Mei [Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD (United States); Polli, James E. [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States); Shu, Yan, E-mail: yshu@rx.umaryland.edu [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States)

    2013-11-15

    The nephrotoxicity limits the clinical application of cisplatin. Human organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins (MATEs) work in concert in the elimination of cationic drugs such as cisplatin from the kidney. We hypothesized that co-administration of ondansetron would have an effect on cisplatin nephrotoxicity by altering the function of cisplatin transporters. The inhibitory potencies of ondansetron on metformin accumulation mediated by OCT2 and MATEs were determined in the stable HEK-293 cells expressing these transporters. The effects of ondansetron on drug disposition in vivo were examined by conducting the pharmacokinetics of metformin, a classical substrate for OCTs and MATEs, in wild-type and Mate1−/− mice. The nephrotoxicity was assessed in the wild-type and Mate1−/− mice received cisplatin with and without ondansetron. Both MATEs, including human MATE1, human MATE2-K, and mouse Mate1, and OCT2 (human and mouse) were subject to ondansetron inhibition, with much greater potencies by ondansetron on MATEs. Ondansetron significantly increased tissue accumulation and pharmacokinetic exposure of metformin in wild-type but not in Mate1−/− mice. Moreover, ondansetron treatment significantly enhanced renal accumulation of cisplatin and cisplatin-induced nephrotoxicity which were indicated by increased levels of biochemical and molecular biomarkers and more severe pathohistological changes in mice. Similar increases in nephrotoxicity were caused by genetic deficiency of MATE function in mice. Therefore, the potent inhibition of MATEs by ondansetron enhances the nephrotoxicity associated with cisplatin treatment in mice. Potential nephrotoxic effects of combining the chemotherapeutic cisplatin and the antiemetic 5-hydroxytryptamine-3 (5-HT{sub 3}) receptor antagonists, such as ondansetron, should be investigated in patients. - Highlights: • Nephrotoxicity significantly limits clinical use of the chemotherapeutic

  12. Energy and Oxygen Metabolism Disorder During Septic Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    Rong-li Yang

    2014-08-01

    Full Text Available Background/Aims: Acute kidney injury (AKI during septic shock, which is one of the most common clinical syndromes in the intensive care unit (ICU, has a high mortality rate and poor prognosis, partly because of a poor understanding of the pathogenesis of renal dysfunction during septic shock. Although ischemic injury of the kidney has been reported to result from adenosine triphosphate (ATP depletion, increasing evidence has demonstrated that AKI occurs in the absence of renal hypoperfusion and even occurs during normal or increased renal blood flow (RBF; nevertheless, whether energy metabolism disorder is involved in septic AKI and whether it changes according to renal hemodynamics have not been established. Moreover, tubular cell apoptosis, which is closely related to ATP depletion, rather than necrosis, has been shown to be the major form of cell injury during AKI. Methods: We used canine endotoxin shock models to investigate the hemodynamics, renal energy metabolism, renal oxygen metabolism, and pathological changes during septic AKI and to explore the underlying mechanisms of septic AKI. Results: The present results revealed that the nicotinamide adenine dinucleotide (NAD+ pool and the ATP/adenosine diphosphate (ADP ratio were significantly decreased during the early phase of septic AKI, which is accompanied by a decreased renal oxygen extraction ratio (O2ER% and decreased renal oxygen consumption (VO2. Furthermore, significant apoptosis was observed following renal dysfunction. RBF and renal oxygen delivery were not significantly altered. Conclusion: These results suggest that imbalanced energy metabolism, rather than tubular cell apoptosis, may be the initiator of renal dysfunction during septic shock.

  13. Herbal Medicines for Acute Kidney Injury: Evidence, Gaps and Frontiers

    Directory of Open Access Journals (Sweden)

    Valérian Bunel

    2015-07-01

    Full Text Available Acute kidney injury (AKI is a major health threat worldwide. The literature on herbal intervention in AKI was searched from English and Chinese databases and reports were critically analyzed in terms of preventing AKI, promoting repair and regeneration, enhancing extrarenal clearance of uremic toxins, and preventing progression to chronic kidney disease (CKD. Altogether, 16 herbal formulae and a few extracts derived from individual herbs were reported to prevent or mitigate AKI in animal models induced by renal ischemia/reperfusion, cisplastin, gentamicin, glycerol, adenine, sepsis or physical exhaustion. Four formulae and six individual herbs were reported to accelerate recovery and/or to prevent CKD in established AKI animal models. Intrarectal herbal medicines, with or without simultaneous oral administration, were reported in six clinical trials and in an animal model to increase extrarenal clearance of uremic toxins. Additional 13 clinical trials reported oral or intravenous herbal interventions in AKI of different etiologies. Despite recurring problems, notably poor compliance with good practice guidelines for clinical trials and for authentication, naming and quality control of herbal materials, accumulating experimental data on the preventive effects of herbal medicines in AKI look encouraging and urge for better, definitive trials to guide clinical practice. Herbal enemas promoting extrarenal clearance of uremic toxins seem cost-effective, but better clinical evidence is certainly needed before any affirmative recommendation be made for AKI patients without access to dialysis. New frontiers, however, lie in those herbal remedies that promote repair/regeneration and prevent chronicity after AKI. Recent experimental data suggest that this may be possible.

  14. Update in sepsis and acute kidney injury 2014.

    Science.gov (United States)

    Schortgen, Frédérique; Asfar, Pierre

    2015-06-01

    Sepsis and acute kidney injury (AKI) represent an important burden in intensive care unit clinical practices. The Journal published important contributions in sepsis for novel therapeutic approaches suggesting that combined molecular targets (e.g., dual inhibition of IL-1β and IL-18, and coadministration of endothelial progenitor cells and stromal cell-derived factor-1α analog) could perform better. The clinical effectiveness of 1,25-dihydroxyvitamin D was reported in a double-blind, randomized, placebo-controlled trial. Although its experimental properties appeared favorable in the pro- and antiinflammatory cytokine balance, 1,25-dihydroxyvitamin D failed to improve survival. Strategies for decreasing antimicrobial resistances are of particular importance. Effective (aerosolized antibiotics for ventilator-associated pneumonia) and ineffective (procalcitonin algorithm for antibiotic deescalation) approaches were published. In 2014, several publications raised an important point shared by survivors from sepsis and/or AKI. The increased number of survivors over time brought out long-term sequelae, leading to a poor outcome after hospital discharge. Among them, cardiovascular events and chronic kidney disease may explain the significant increase in the risk of death, which can persist up to 10 years and significantly increases the use of health care. Postdischarge survival represents a new target for future research in sepsis and AKI to find how we can prevent and manage long-term sequelae. A milestone of the year was the Ebola outbreak. The Journal contributed to our better understanding of Ebola virus disease with a paper underlying the crucial role of a large implementation of pragmatic supportive care, including fluid infusion and correction of metabolic abnormalities, to save more lives. PMID:26029837

  15. Antioxidantes da dieta como inibidores da nefrotoxicidade induzida pelo antitumoral cisplatina Dietary antioxidants as inhibitors of cisplatin-induced nephrotoxicity

    Directory of Open Access Journals (Sweden)

    Lusânia Maria Greggi Antunes

    2004-03-01

    Full Text Available A cisplatina é uma droga antineoplásica altamente efetiva contra vários tipos de cânceres humanos, tais como tumores do testículo e ovário, câncer da cabeça e pescoço e câncer do pulmão. Entretanto, a nefrotoxicidade é um dos principais efeitos colaterais da terapia com a cisplatina. A gravidade da nefrotoxicidade induzida pela cisplatina está relacionada com a concentração de platina nos rins. As evidências mostram que a nefrotoxicidade induzida pela cisplatina é atribuída ao dano oxidativo resultante da geração de radicais livres, e que a administração de antioxidantes é eficiente na inibição destes efeitos colaterais. Uma abordagem alternativa para proteger os roedores dos efeitos colaterais da cisplatina é o uso de conhecidos antioxidantes da dieta. Alguns estudos têm sido realizados para diminuir a peroxidação lipídica e os efeitos citotóxicos induzidos pela cisplatina, com o emprego de antioxidantes da dieta, tais como, selenito de sódio, vitaminas C e E, curcumina e o carotenóide bixina. Nós sugerimos que aqueles antioxidantes da dieta têm efeito nefroprotetor, e que os mecanismos antioxidantes destes compostos deveriam ser explorados durante a quimioterapia com a cisplatina.Cisplatin is a highly effective antineoplastic drug used against several types of human cancers, such as testicular and ovarian tumors; head and neck; and lung cancer. However, nephrotoxicity is one of the most important side-effects of cisplatin therapy. The severity of cisplatin nephrotoxicity is related to platinum concentration in the kidneys. There is a growing amount of evidence that cisplatin-induced nephrotoxicity is ascribed to oxidative damage resulting from free radical generation and that the administration of antioxidants is efficient in inhibiting these side effects. An alternative approach aiming to protect rodents against cisplatin side-effects is the introduction of known dietary antioxidants. Some studies have been

  16. Decursin Mediated Protection on Cisplatin-induced Nephrotoxicity in SD Rats and BDF1 Mice

    Institute of Scientific and Technical Information of China (English)

    Jiang Cheng-zhe; Han Ilhyun; Choung Seyoung

    2012-01-01

    Tisplatin is one of the valuable icancer agents against several types of neoplasm. However, nephrotoxicity is the major adverse effect representing in cisplatin therapy. In this study, the animal tests detecting protective effects of a natural compound, Decursin, on cisplatin-induced nephrotoxicity were examined by using in vivo model. Pretreatment Decursin 10, 20 and 40 mg · kg^-1 at 48, 24 and 6 h, and administration of a single dose of Cisplatin 5.2 mg · kg^-1. Nephrotoxicity was evaluated by serum BUN and creatinine examination. There was significant difference in body weights, serum BUN and creatinine levels of the normal group. Based on the new understanding of the protective mechanisms of cisplatin-induced nephrotocivity, new strategies can be developed to prevent renal injury or to enhance recovery after cisplatin treatment.

  17. Acute kidney injury in stable COPD and at exacerbation

    Directory of Open Access Journals (Sweden)

    Barakat MF

    2015-09-01

    Full Text Available MF Barakat,1 HI McDonald,1 TJ Collier,1 L Smeeth,1 D Nitsch,1 JK Quint1,2 1Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, 2Department of Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College London, London, UK Background: While acute kidney injury (AKI alone is associated with increased mortality, the incidence of hospital admission with AKI among stable and exacerbating COPD patients and the effect of concurrent AKI at COPD exacerbation on mortality is not known.Methods: A total of 189,561 individuals with COPD were identified from the Clinical Practice Research Datalink. Using Poisson and logistic regressions, we explored which factors predicted admission for AKI (identified in Hospital Episode Statistics in this COPD cohort and concomitant AKI at a hospitalization for COPD exacerbation. Using survival analysis, we investigated the effect of concurrent AKI at exacerbation on mortality (n=36,107 and identified confounding factors.Results: The incidence of AKI in the total COPD cohort was 128/100,000 person-years. The prevalence of concomitant AKI at exacerbation was 1.9%, and the mortality rate in patients with AKI at exacerbation was 521/1,000 person-years. Male sex, older age, and lower glomerular filtration rate predicted higher risk of AKI or death. There was a 1.80 fold (95% confidence interval: 1.61, 2.03 increase in adjusted mortality within the first 6 months post COPD exacerbation in patients suffering from AKI and COPD exacerbation compared to those who were AKI free.Conclusion: In comparison to previous studies on general populations and hospitalizations, the incidence and prevalence of AKI is relatively high in COPD patients. Coexisting AKI at exacerbation is prognostic of poor outcome. Keywords: acute renal failure, mortality, emphysema, chronic bronchitis, prognosis

  18. Electronic Medical Record-Based Predictive Model for Acute Kidney Injury in an Acute Care Hospital.

    Science.gov (United States)

    Laszczyńska, Olga; Severo, Milton; Azevedo, Ana

    2016-01-01

    Patients with acute kidney injury (AKI) are at risk for increased morbidity and mortality. Lack of specific treatment has meant that efforts have focused on early diagnosis and timely treatment. Advanced algorithms for clinical assistance including AKI prediction models have potential to provide accurate risk estimates. In this project, we aim to provide a clinical decision supporting system (CDSS) based on a self-learning predictive model for AKI in patients of an acute care hospital. Data of all in-patient episodes in adults admitted will be analysed using "data mining" techniques to build a prediction model. The subsequent machine-learning process including two algorithms for data stream and concept drift will refine the predictive ability of the model. Simulation studies on the model will be used to quantify the expected impact of several scenarios of change in factors that influence AKI incidence. The proposed dynamic CDSS will apply to future in-hospital AKI surveillance in clinical practice. PMID:27577501

  19. Migfilin sensitizes cisplatin-induced apoptosis in human glioma cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Jing FAN; Yun-wei OU; Chuan-yue WU; Chun-jiang YU; Yong-mei SONG; Qi-min ZHAN

    2012-01-01

    Aim:Filamin binding LIM protein 1,also known as migfilin,is a skeleton organization protein that binds to mitogen-inducible gene 2 at cell-extracellular matrix adhesions.The aim of this study was to investigate the role of migfilin in cisplatin-induced apoptosis in human glioma cells,to determine the functional domains of migfilin,and to elucidate the molecular mechanisms underlying the regulation of cisplatin-related chemosensitivity.Methods:The human glioma cell lines Hs683,H4,and U-87 MG were transfected with pEGFP-C2-migfilin to elevate the expression level of migfilin.RNA interference was used to reduce the expression of migfilin.To determine the functional domains of migfilin,U-87 MG cells were transfected with plasmids of migfilin deletion mutants.After treatment with cisplatin (40 μmol/L) for 24 h,the cell viability was assessed using the MTS assay,and the cell apoptotic was examined using the DAPI staining assay and TUNEL analysis.Expression levels of apoptosis-related proteins were detected by Western blot analysis.Results:Overexpression of migfilin significantly enhanced cisplatin-induced apoptosis in Hs683,H4,and U-87 MG cells,whereas downregulation of migfilin expression inhibited the chemosensitivity of these cell lines.The N-terminal region of migfilin alone was able to enhance the cisplatin-induced apoptosis.However,despite the existence of the N-terminal region,mutants of migfilin with any one of three LIM domains deleted led to a function loss.Furthermore,apoptotic proteins (PARP and caspase-3) and the anti-apoptotic protein Bcl-xL were modulated by the expression level of migfilin in combination with cisplatin.Conclusion:The LIM1-3 domains of migfilin play a key role in sensitizing glioma cells to cisplatin-induced apoptosis through regulation of apoptosis-related proteins.

  20. Ondansetron compared with ondansetron plus metoclopramide in the prevention of cisplatin-induced emesis.

    OpenAIRE

    Lee, C. W.; Suh, C. W.; Lee, J. S.; Lee, K. H.; Cho, G. Y.; Kim, S.W.; Kim, S H

    1994-01-01

    To determine the contribution of metoclopramide to the efficacy of ondansetron in control of cisplatin-induced emesis, ondansetron was compared with ondansetron plus metoclopramide for antiemetic efficacy in a randomized double-blind trial. Enrolled 66 patients were treated with cisplatin(60mg/m2) in combination with etoposide, flourouracil, or vinblastine, and randomized to receive either ondansetron alone or ondansetron plus metoclopramide. Sixty patients were evaluable. Complete or major c...

  1. Voluntary exercise prevents cisplatin-induced muscle wasting during chemotherapy in mice

    DEFF Research Database (Denmark)

    Hojman, Pernille; Fjelbye, Jonas; Zerahn, Bo;

    2014-01-01

    % (Panorexia and impairments in Akt and protein degradation signalling. Cisplatin-induced muscular inflammation was not prevented by voluntary wheel running, nor was glucose tolerance improved. Exercise training may......, food intake as well as muscle mass, strength and signalling. Mice were treated weekly with 4 mg/kg cisplatin or saline for 6 weeks, and randomized to voluntary wheel running or not. Cisplatin treatment induced loss of body weight (29.8%, Panorexia...

  2. Rikkunshito, a traditional Japanese medicine, suppresses cisplatin-induced anorexia in humans

    OpenAIRE

    Ohno T; Yanai M; Ando H; Toyomasu Y; Ogawa A; Morita H; Ogata K; Mochiki E; Asao T; Kuwano H

    2011-01-01

    Tetsuro Ohno, Mitsuhiro Yanai, Hiroyuki Ando, Yoshitaka Toyomasu, Atsushi Ogawa, Hiroki Morita, Kyoichi Ogata, Erito Mochiki, Takayuki Asao, Hiroyuki KuwanoDepartment of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, JapanBackground: The aim of this study was to investigate the effects of Rikkunshito on ghrelin secretion and on cisplatin-induced anorexia in humans.Methods: The study was performed as a crossover design, and ten unresectable or relapsed gastri...

  3. Metformin Prevents Cisplatin-Induced Cognitive Impairment and Brain Damage in Mice.

    Directory of Open Access Journals (Sweden)

    Wenjun Zhou

    Full Text Available Chemotherapy-induced cognitive impairment, also known as 'chemobrain', is now widely recognized as a frequent adverse side effect of cancer treatment that often persists into survivorship. There are no drugs available to prevent or treat chemotherapy-induced cognitive deficits. The aim of this study was to establish a mouse model of cisplatin-induced cognitive deficits and to determine the potential preventive effects of the anti-diabetic drug metformin.Treatment of C57/BL6J mice with cisplatin (cumulative dose 34.5 mg/kg impaired performance in the novel object and place recognition task as well as in the social discrimination task indicating cognitive deficits. Co-administration of metformin prevented these cisplatin-induced cognitive impairments. At the structural level, we demonstrate that cisplatin reduces coherency of white matter fibers in the cingulate cortex. Moreover, the number of dendritic spines and neuronal arborizations as quantified on Golgi-stained brains was reduced after cisplatin treatment. Co-administration of metformin prevented all of these structural abnormalities in cisplatin-treated mice. In contrast to what has been reported in other models of chemobrain, we do not have evidence for persistent microglial or astrocyte activation in the brains of cisplatin-treated mice. Finally, we show that co-administration of metformin also protects against cisplatin-induced peripheral neuropathy.In summary, we show here for the first time that treatment of mice with cisplatin induces cognitive deficits that are associated with structural abnormalities in the brain. Moreover, we present the first evidence that the widely used and safe anti-diabetic drug metformin protects against these deleterious effects of cancer treatment. In view of the ongoing clinical trials to examine the potential efficacy of metformin as add-on therapy in patients treated for cancer, these findings should allow rapid clinical translation.

  4. Antioxidant protection of statins in acute kidney injury induced by sepsis

    Directory of Open Access Journals (Sweden)

    Franciele do Nascimento Santos

    2014-10-01

    Full Text Available Objective Evaluating the effect of preconditioning with simvastatin in acute kidney injury induced by sepsis. Method Male adult Wistar rats were divided into the following groups: SHAM (control; SHAM+Statin (0.5 mg/kg simvastatin, orally; Sepsis (cecal puncture ligation – CPL; Sepsis+Statin. Physiological parameters, peritoneal fluid culture, renal function, oxidative metabolites, severity of acute kidney injury and animal survival were evaluated. Results The treatment with simvastatin in induced sepsis showed elevation of creatinine clearance with attenuation of generation of oxidative metabolites, lower severity of acute kidney injury and reduced mortality. Conclusion This investigation confirmed the renoprotection with antioxidant principle of the simvastatin in acute kidney injury induced by sepsis in an experimental model.

  5. Challenges of treating a 466-kilogram man with acute kidney injury.

    Science.gov (United States)

    Friedman, Allon N; Decker, Brian; Seele, Louis; Hellman, Richard N

    2008-07-01

    Caring for super obese patients (body mass index > 50 kg/m(2)) presents a number of complex and unique clinical challenges, particularly when acute kidney injury is present. We describe our experience treating the heaviest individual with acute kidney injury requiring renal replacement therapy reported to date. A 24-year-old black man was admitted to our hospital with fever, vomiting, progressive weakness, shortness of breath, and hemoptysis. Admission weight was 1,024 lbs (466 kg), height was 6 ft 4 in (1.9 m), and body mass index was 125 kg/m(2). During hospitalization, the patient experienced oligoanuric acute kidney injury and required initiation of continuous and subsequently intermittent renal replacement therapy. This clinical scenario identifies the many challenges involved in caring for super obese patients with acute kidney injury and may be a harbinger of what awaits the nephrology community in the obesity pandemic era.

  6. Diagnostic Value of Urine Microscopy for Differential Diagnosis of Acute Kidney Injury in Hospitalized Patients

    OpenAIRE

    Perazella, Mark A.; Coca, Steven G.; Kanbay, Mehmet; Brewster, Ursula C.; Parikh, Chirag R.

    2008-01-01

    Background and objectives: Urine microscopy is the oldest and one of the most commonly used tests for differential diagnosis of acute kidney injury (AKI), but its performance has not been adequately studied in the setting of AKI.

  7. Unusual presentations of acute kidney injury and neurologic complications due to snake bite

    OpenAIRE

    Hamid Noshad; Reza Rikhtegar; Mehdi Hagdoost; Masood Dinevari; Hosein Mahmoodi

    2015-01-01

    Introduction: Vascularity of kidneys is very high, so these organs are potentially susceptible to be affected with toxins including snake venom. Hypersensitivity to snake venous could cause some neurological problem. Case Report: We present a 14-year-old boy with acute kidney injury (AKI) due to snake bite. After a few days, kidney failure with hematuria was developed. His serum creatinine level rose to 3 mg/dl and following 2 weeks gradually and d...

  8. Effect of Camel's Milk on Cisplatin-Induced Nephrotoxicity in Swiss Albino Mice

    Directory of Open Access Journals (Sweden)

    Mohamed M.E. Afifi

    2010-01-01

    Full Text Available Problem statement: Nephrotoxicity is a major complication and a dose limiting factor for cisplatin therapy. Cisplatin mediated nephrotoxicity is remarkably documented by reactive oxygen species. Camel's milk has good nutritive value, antigenotoxic and anticytotoxic effects. The aim of the present study was to assess the protective effect of camel's milk against Cisplatin-induced renal oxidative stress in mice. Approach: Forty mal Swiss albino mice were randomly divided into four groups (n = 10. Group I, control group. Group II was received cisplatin (12 mg kg-1 for 5 alternate days. Group III was received camel's milk (33 mL kg-1 for consecutive 30 days. Group IV was received camel's milk (33 mL kg-1 for consecutive 30 days before administration of Cisplatin. Results: Cisplatin-induced oxidative stress was indicated by increased level of tissue Malondialdehyde (MDA, serum creatinine and urea, decreased the concentration of reduced Glutathione (GSH, Vitamin C (Vit. C and Vitamin E (Vit. E and decreased both activities and gene expression of Superoxid Dismutase (SOD, Catalase (CAT, Glutathione Raductase (GR and Glutathione Peroxidase (GPx. Camel's milk reduced these biochemical changes and counteracted the deleterious effects of cisplatin Conclusion: The present study demonstrated the renoprotective potential of camel's milk against cisplatin-induced oxidative stress and renal dysfunction in mice. Hence, camel's milk has a potential to be used as therapeutic adjuvant in cisplatin nephrotoxicity.

  9. Metabonomics of acute kidney injury in children after cardiac surgery.

    Science.gov (United States)

    Beger, Richard D; Holland, Ricky D; Sun, Jinchun; Schnackenberg, Laura K; Moore, Page C; Dent, Catherine L; Devarajan, Prasad; Portilla, Didier

    2008-06-01

    Acute kidney injury (AKI) is a major complication in children who undergo cardiopulmonary bypass surgery. We performed metabonomic analyses of urine samples obtained from 40 children that underwent cardiac surgery for correction of congenital cardiac defects. Serial urine samples were obtained from each patient prior to surgery and at 4 h and 12 h after surgery. AKI, defined as a 50% or greater rise in baseline level of serum creatinine, was noted in 21 children at 48-72 h after cardiac surgery. The principal component analysis of liquid chromatography/mass spectrometry (LC/MS) negative ionization data of the urine samples obtained 4 h and 12 h after surgery from patients who develop AKI clustered away from patients who did not develop AKI. The LC/MS peak with mass-to-charge ratio (m/z) 261.01 and retention time (tR) 4.92 min was further analyzed by tandem mass spectrometry (MS/MS) and identified as homovanillic acid sulfate (HVA-SO4), a dopamine metabolite. By MS single-reaction monitoring, the sensitivity was 0.90 and specificity was 0.95 for a cut-off value of 24 ng/microl for HVA-SO4 at 12 h after surgery. We concluded that urinary HVA-SO4 represents a novel, sensitive, and predictive early biomarker of AKI after pediatric cardiac surgery.

  10. Acute kidney injury in children: Enhancing diagnosis with novel biomarkers

    Directory of Open Access Journals (Sweden)

    Samuel Nkachukwu Uwaezuoke

    2016-07-01

    Full Text Available This narrative review aims to appraise the sensitivity and specificity of novel biomarkers in identifying acute kidney injury (AKI in children. Serum creatinine represents a poor traditional biomarker for AKI due to some limitations. Although alternative reliable biomarkers that would better identify individuals at high risk for developing AKI, identify AKI early enough, monitor its progression and patients' recovery, as well as identify those patients at higher risk for poor outcomes are not yet available in renal care, the search-light has recently been focused on various novel biomarkers, some of which could provide this information in time ahead. Several studies have established their predictive value. However, none of them could solely fulfill all the criteria of the ideal biomarker. Therefore, to increase their sensitivity and specificity and enhance the diagnosis of AKI, constellations of different biomarkers with specific features are probably required. In future, the diagnostic evaluation of AKI in intensive care units will have to undergo a paradigm shift from serum creatinine as the traditional biomarker to tissue-specific injury biomarkers. A panel of these novel biomarkers employed at the bedside setting will ultimately revolutionize the diagnosis and prognostication of AKI in children.

  11. Sepsis-induced acute kidney injury in patients with cirrhosis.

    Science.gov (United States)

    Angeli, Paolo; Tonon, Marta; Pilutti, Chiara; Morando, Filippo; Piano, Salvatore

    2016-01-01

    Acute kidney injury (AKI) is a common and life-threatening complication in patients with cirrhosis. Recently, new criteria for the diagnosis of AKI have been proposed in patients with cirrhosis by the International Club of Ascites. Almost all types of bacterial infections can induce AKI in patients with cirrhosis representing its most common precipitating event. The bacterial infection-induced AKI usually meets the diagnostic criteria of hepatorenal syndrome (HRS). Well in keeping with the "splanchnic arterial vasodilation hypothesis", it has been stated that HRS develops as a consequence of a severe reduction of effective circulating volume related to splanchnic arterial vasodilation and to an inadequate cardiac output. Nevertheless, the role of bacterial infections in precipitating organ failures, including renal failure, is enhanced when their course is characterized by the development of a systemic inflammatory response syndrome (SIRS), thus, when sepsis occurs. Sepsis has been shown to be capable to induce "per se" AKI in animals as well as in patients conditioning also the features of renal damage. This observation suggests that when precipitated by sepsis, the pathogenesis and the clinical course of AKI also in patients with cirrhosis may differentiate to a certain extent from AKI with another or no precipitating factor. The purpose of this review is to describe the features of AKI precipitated by bacterial infections and to highlight whether infection and/or the development of SIRS may influence its clinical course, and, in particular, the response to treatment.

  12. Hyperglycemia and Acute Kidney Injury During the Perioperative Period.

    Science.gov (United States)

    Mendez, Carlos E; Der Mesropian, Paul J; Mathew, Roy O; Slawski, Barbara

    2016-01-01

    Hyperglycemia and acute kidney injury (AKI) are frequently observed during the perioperative period. Substantial evidence indicates that hyperglycemia increases the prevalence of AKI as a surgical complication. Patients who develop hyperglycemia and AKI during the perioperative period are at significantly elevated risk for poor outcomes such as major adverse cardiac events and all-cause mortality. Early observational and interventional trials demonstrated that the use of intensive insulin therapy to achieve strict glycemic control resulted in remarkable reductions of AKI in surgical populations. However, more recent interventional trials and meta-analyses have produced contradictory evidence questioning the renal benefits of strict glycemic control. Although the exact mechanisms through which hyperglycemia increases the risk of AKI have not been elucidated, multiple pathophysiologic pathways have been proposed. Hypoglycemia and glycemic variability may also play a significant role in the development of AKI. In this literature review, the complex relationship between hyperglycemia and AKI as well as its impact on clinical outcomes during the perioperative period is explored.

  13. Prediction and Prevention of Acute Kidney Injury after Cardiac Surgery

    Directory of Open Access Journals (Sweden)

    Su Rin Shin

    2016-01-01

    Full Text Available The incidence of acute kidney injury after cardiac surgery (CS-AKI ranges from 33% to 94% and is associated with a high incidence of morbidity and mortality. The etiology is suggested to be multifactorial and related to almost all aspects of perioperative management. Numerous studies have reported the risk factors and risk scores and novel biomarkers of AKI have been investigated to facilitate the subclinical diagnosis of AKI. Based on the known independent risk factors, many preventive interventions to reduce the risk of CS-AKI have been tested. However, any single preventive intervention did not show a definite and persistent benefit to reduce the incidence of CS-AKI. Goal-directed therapy has been considered to be a preventive strategy with a substantial level of efficacy. Many pharmacologic agents were tested for any benefit to treat or prevent CS-AKI but the results were conflicting and evidences are still lacking. The present review will summarize the current updated evidences about the risk factors and preventive strategies for CS-AKI.

  14. The potential of alkaline phosphatase as a treatment for sepsis-associated acute kidney injury

    NARCIS (Netherlands)

    Peters, Esther; Masereeuw, R.; Pickkers, Peter

    2014-01-01

    Sepsis-associated acute kidney injury (AKI) is associated with a high attributable mortality and an increased risk of developing chronic kidney failure in survivors. As a successful therapy is, as yet, unavailable, a pharmacological treatment option is clearly warranted. Recently, two small phase II

  15. Contribution of bone marrow-derived cells in renal repair after acute kidney injury.

    NARCIS (Netherlands)

    Masereeuw, R.

    2009-01-01

    Acute kidney injury (AKI) is a frequent clinical problem with a high mortality rate, generally caused by ischemic insults. Nevertheless, the kidney has a remarkably high capacity to regenerate after ischemic injury. Tubular cells can restore renal function by proliferation and dedifferentiation into

  16. Renal cell carcinoma in an ectopic pelvic kidney in a patient presenting with acute urinary retention

    Directory of Open Access Journals (Sweden)

    Isabella Dash

    2010-12-01

    Full Text Available The incidence of renal cell carcinoma in a pelvic kidney is rare, and has only been described in a very small number of cases. We describe a case where an incidental ectopic kidney with invasive renal cell carcinoma was diagnosed during a separate emergency admission for acute urinary retention.

  17. Incidence and Outcome of Early Acute Kidney Injury in Critically-Ill Trauma Patients

    OpenAIRE

    Amber S Podoll; Kozar, Rosemary; Holcomb, John B; Kevin W Finkel

    2013-01-01

    Objective To determine the incidence and effect on mortality of early acute kidney injury in severely injured trauma patients using the Acute Kidney Injury Network creatinine criteria. Design A retrospective cohort study of severely injured trauma patients admitted to the shock trauma intensive care unit. Setting Texas Trauma Institute, a state designated level I trauma unit certified by the American College of Surgeons Committee on Trauma. Patients 901 severely injured trauma patients admitt...

  18. Plant-Derived Agents for Counteracting Cisplatin-Induced Nephrotoxicity

    Science.gov (United States)

    Venkataraman, Balaji; Kurdi, Amani; Mahgoub, Eglal; Sadek, Bassem

    2016-01-01

    Cisplatin (CSP) is a chemotherapeutic agent commonly used to treat a variety of malignancies. The major setback with CSP treatment is that its clinical efficacy is compromised by its induction of organ toxicity, particular to the kidneys and ears. Despite the significant strides that have been made in understanding the mechanisms underlying CSP-induced renal toxicity, advances in developing renoprotective strategies are still lacking. In addition, the renoprotective approaches described in the literature reveal partial amelioration of CSP-induced renal toxicity, stressing the need to develop potent combinatorial/synergistic agents for the mitigation of renal toxicity. However, the ideal renoprotective adjuvant should not interfere with the anticancer efficacy of CSP. In this review, we have discussed the progress made in utilizing plant-derived agents (phytochemicals) to combat CSP-induced nephrotoxicity in preclinical studies. Furthermore, we have also presented strategies to utilize phytochemicals as prototypes for the development of novel renoprotective agents for counteracting chemotherapy-induced renal damage.

  19. [Acute Kidney Injury, Type - 3 cardiorenal syndrome, Biomarkers, Renal Replacement Therapy].

    Science.gov (United States)

    Di Lullo, Luca; Bellasi, Antonio; Barbera, Vincenzo; Cozzolino, Mario; Russo, Domenico; De Pascalis, Antonio; Santoboni, Francesca; Villani, Annalisa; De Rosa, Silvia; Colafelice, Marco; Russo, Luigi; Ronco, Claudio

    2016-01-01

    Cardiovascular disease and major cardiovascular events represent main cause of death in both acute and chronic kidney disease patients. Kidney and heart failure are common and frequently co-exist This organ-organ interaction, also called organ cross-talk, leads to well-known definition of cardiorenal syndrome (CRS). Here we will describe cardiovascular involvement in patients with acute kidney injury (AKI). Also known as Type-3 CRS or acute reno-cardiac CRS, it occurs when AKI contributes and/or precipitates development of acute cardiac injury. AKI may directly or indirectly produces an acute cardiac event and it can be associated with volume overload, metabolic acidosis and electrolytes disorders such as hyperkalemia and hypocalcemia, coronary artery disease, left ventricular dysfunction and fibrosis which has been also described in patients with AKI with the consequence of direct negative effects on cardiac performance. PMID:27374388

  20. Acute Renal Failure - A Serious Complication in Patients After Kidney Transplantation.

    Science.gov (United States)

    Basta-Jovanovic, G; Bogdanovic, Lj; Radunovic, M; Prostran, M; Naumovic, R; Simic-Ogrizovic, S; Radojevic-Skodric, S

    2016-01-01

    Free radical-mediated injury releases proinflammatory cytokines and activates innate immunity. It has been suggested that the early innate response and the ischemic tissue damage play roles in the development of adaptive responses, which may lead to acute kidney rejection. Various durations of hypothermic kidney storage before transplantation add to ischemic tissue damage. The final stage of ischemic injury occurs during reperfusion that develops hours or days after the initial insult. Repair and regeneration processes occur together with cellular apoptosis, autophagy and necrosis and a favorable outcome is expected if regeneration prevails. Along the entire transplantation time course, there is a great demand for novel immune and nonimmune injury biomarkers. The use of these markers can be of great help in the monitoring of kidney injury in potential kidney donors, where acute kidney damage can be overlooked, in predicting acute transplant dysfunction during the early post-transplant periods, or in predicting chronic changes in long term followup. Numerous investigations have demonstrated that biomarkers that have the highest predictive value in acute kidney injury include NGAL, Cystatin C, KIM-1, IL-18, and L-FABP. Most investigations show that the ideal biomarker to fulfill all the needs in renal transplant has not been identified yet. Although, in many animal models, new biomarkers are emerging for predicting acute and chronic allograft damage, in human allograft analysis they are still not routinely accepted and renal biopsy still remains the gold standard. PMID:27498898

  1. Analyses of acute kidney injury biomarkers by ultra-high performance liquid chromatography with mass spectrometry.

    Science.gov (United States)

    Al Za'abi, Mohammed; Ali, Badreldin H; ALOthman, Zeid A; Ali, Imran

    2016-01-01

    The newly developed acute kidney injury biomarkers are very important for the early and timely detection of kidney diseases. This review contains details of the analyses of several acute kidney injury biomarkers using ultra-high performance liquid chromatography-mass spectrometry in urine and plasma samples. In this review we attempt to discuss some aspects of the types of the biomarkers, patents, sample preparation, and the analyses. Besides, efforts were also made to discuss the possible uses of superficially porous (core-shell) columns in traditional and inexpensive high-performance liquid chromatography instruments. Additionally, the challenges and the future prospects are also highlighted. The present review will be useful for the academicians, scientists, and clinicians for the early detection of acute kidney injury biomarkers.

  2. Assessment of Plasma and NGAL for the Early Prediction of Acute Kidney Injury After Cardiac Surgery in Adults Study

    Science.gov (United States)

    2016-04-11

    Acute Kidney Injury (AKI); Chronic Kidney Disease (CKD); End Stage Renal Disease (ESRD); Estimated Glomerular Filtration Rate (eGFR); Neutrophil Gelatinase-associated Lipocalin (NGAL); Serum Creatinine (SCr); Urine Creatinine (UCr); Urine Albumin (UAlb)

  3. Prevention of acute kidney injury and protection of renal function in the intensive care unit

    NARCIS (Netherlands)

    Joannidis, Michael; Druml, Wilfred; Forni, Lui G.; Groeneveld, A. B. Johan; Honore, Patrick; Oudemans-van Straaten, Heleen M.; Ronco, Claudio; Schetz, Marie R. C.; Woittiez, Arend Jan

    2010-01-01

    Acute renal failure on the intensive care unit is associated with significant mortality and morbidity. To determine recommendations for the prevention of acute kidney injury (AKI), focusing on the role of potential preventative maneuvers including volume expansion, diuretics, use of inotropes, vasop

  4. Effects of chronic kidney disease on platelet response to antiplatelet therapy in acute myocardial infarction patients

    Institute of Scientific and Technical Information of China (English)

    邓捷

    2012-01-01

    Objective To elucidate the effects of dual antiplatelet therapy on platelet response in acute myocardial infarction patients with chronic kidney disease. Methods From September 2011 to June 2012,a total of 195 acute myocardial infarction patients with drug eluting stent implanting were enrolled. Among them,133 cases had normal

  5. The Role of Eugenol in the Prevention of Acute Pancreatitis-Induced Acute Kidney Injury: Experimental Study

    OpenAIRE

    Charalampos Markakis; Alexandra Tsaroucha; Papalois, Apostolos E.; Maria Lambropoulou; Eleftherios Spartalis; Christina Tsigalou; Konstantinos Romanidis; Constantinos Simopoulos

    2016-01-01

    Aim. Acute pancreatitis is an inflammatory intra-abdominal disease, which takes a severe form in 15–20% of patients and can result in high mortality especially when complicated by acute renal failure. The aim of this study is to assess the possible reduction in the extent of acute kidney injury after administration of eugenol in an experimental model of acute pancreatitis. Materials and Methods. 106 male Wistar rats weighing 220–350 g were divided into 3 groups: (1) Sham, with sham surgery; (...

  6. Definition and Classification of Acute Kidney Injury:Contributions and Problems in the Clinical Practice

    Institute of Scientific and Technical Information of China (English)

    CHEN Yi-pu

    2010-01-01

    @@ Definition and Classification of Acute Kidney Injury Before the RIFLE classification system of acute renal failure (ARF) was proposed in the Second Conference of Acute Dialysis Quality Initiative (ADQI, an international volunteer organization mainly composed of intensivists and nephrologists in developed countries) in 2002, there were more than 35 diagnostic criteria of ARF in different literatures, which led to confusion in clinical practice and epidemiological investigation(1).

  7. Fenofibrate reduces cisplatin-induced apoptosis of renal proximal tubular cells via inhibition of JNK and p38 pathways.

    Science.gov (United States)

    Thongnuanjan, Penjai; Soodvilai, Sirima; Chatsudthipong, Varanuj; Soodvilai, Sunhapas

    2016-01-01

    Cisplatin is widely used as a standard chemotherapy for solid tumors. The major adverse effect of cisplatin is nephrotoxicity in proximal tubular cells, via oxidative stress, DNA damage, cell apoptosis, and inflammation. The aim of this study was to investigate the pharmacological effect and mechanism of fibrate drugs on cisplatin-induced renal proximal tubular cell death. Cisplatin decreased cell viability of LLC-PK1 and HK-2 cells in a dose-dependent manner. Cisplatin-induced apoptosis was attenuated by co-treatment with fenofibrate while less so with clofibrate and bezafibrate. Fenofibrate's protective effect was not complimented by co-treatment with GW6471, a PPARα antagonist, indicating the protective effect occurred via a PPARα-independent mechanism. Treating cells with cisplatin induced reactive oxygen species (ROS), c-JUN N-terminal kinase (JNK), and p38 kinase (p38), but not extracellular signal-regulated kinase (ERK). Fenofibrate reversed cisplatin-induced JNK and p38 activation, but had no effect on ROS production. The findings suggest fenofibrate's protective effect on cisplatin-induced cytotoxicity is mediated by inhibition of JNK and p38. Moreover, fenofibrate did not alter cisplatin's antitumor effect on cancer cell lines including T84, SW-480, HepG2, and SK-LU-1 cells. Therefore, fenofibrate may be a candidate agent for further development as an adjuvant to cisplatin treatment. PMID:27193727

  8. Acute Superoxide Radical Scavenging Reduces Blood Pressure but Does Not Influence Kidney Function in Hypertensive Rats with Postischemic Kidney Injury

    Directory of Open Access Journals (Sweden)

    Zoran Miloradović

    2014-01-01

    Full Text Available Acute kidney injury (AKI is associated with significant morbidity and mortality in hypertensive surroundings. We investigated superoxide radical molecules influence on systemic haemodynamic and kidney function in spontaneously hypertensive rats (SHR with induced postischemic AKI. Experiment was performed in anesthetized adult male SHR. The right kidney was removed, and left renal artery was subjected to ischemia by clamping for 40 minutes. The treated group received synthetic superoxide dismutase mimetic TEMPOL in the femoral vein 5 minutes before, during, and 175 minutes after the period of reperfusion, while the control AKI group received the vehicle via the same route. All parameters were measured 24 h after renal reperfusion. TEMPOL treatment significantly decreased mean arterial pressure and total peripheral resistance P<0.05 compared to AKI control. It also increased cardiac output and catalase activity P<0.05. Lipid peroxidation and renal vascular resistance were decreased in TEMPOL P<0.05. Plasma creatinine and kidney morphological parameters were unchanged among TEMPOL treated and control groups. Our study shows that superoxide radicals participate in haemodynamic control, but acute superoxide scavenging is ineffective in glomerular and tubular improvement, probably due to hypertension-induced strong endothelial dysfunction which neutralizes beneficial effects of O2− scavenging.

  9. Urinary Kidney Injury Molecule-1 (KIM-1 in Early Diagnosis of Acute Kidney Injury in Pediatric Critically Ill

    Directory of Open Access Journals (Sweden)

    Irma Lestari Paramastuty

    2016-04-01

    Full Text Available Acute kidney injury (AKI often associated with a high hospital morbi-mortality rate in the intensive care unit patients. Kidney injury molecule-1 (KIM-1, has many characteristics of ideal biomarker for kidney injury. The aim of this study was to compared the temporal pattern of elevation urinary KIM-1 level following critically ill children with SCr as standart biomarker of AKI. Prospective analytic observational study was conducted during October to March 2014 in the Saiful Anwar General Hospital and Physiology Laboratory Brawijaya University. There were 13 critically ill as subjects. SCr and KIM-1 levels from all subjects were measured three times ( at admission, after 1st and 6th hour. Subjects were devided into AKI - non-AKI groups by SCr level and survivor - non survivor group at the and of the observations. Results showed that there were significantly increased levels of KIM-1 in the AKI and non-AKI and survivor-non survivor group at time point. However, we found that delta KIM-1 at time point increased significant in non AKI group and survivor group. KIM-1 at admission can diagnosed AKI in critically ill children. We conclude that urinary KIM-1 is a sensitive non-invasive biomarker to diagnosed acute kidney injury in critically ill children. Increase level of KIM-1 by time shows protective and good outcome in critically ill children.

  10. The antioxidant protein PARK7 plays an important role in cell resistance to Cisplatin-induced apoptosis in case of clear cell renal cell carcinoma.

    Science.gov (United States)

    Trivedi, Rachana; Dihazi, Gry H; Eltoweissy, Marwa; Mishra, Durga P; Mueller, Gerhard A; Dihazi, Hassan

    2016-08-01

    Clear cell renal cell carcinoma (ccRCC) is the most malignant tumor in the adult kidney. Many factors are responsible for the development and progression of this tumor. Increased reactive oxygen species accumulation and altered redox status have been observed in cancer cells and this biochemical property of cancer cells can be exploited for therapeutic benefits. In earlier work we identified and characterize Protein DJ-1 (PARK7) as an oxidative stress squevenger in renal cells exposed to oxidative stress. To investigate whether the PARK7 or other oxidative stress proteins play a role in the renal cell carcinoma and its sensitivity or resistance to cytostatic drug treatment, differential proteomics analysis was performed with a cell model for clear cell renal carcinoma (Caki-2 and A498). Caki-2 cells were treated with cisplatin and differentially expressed proteins were investigated. The cisplatin treatment resulted in an increase in reactive oxygen species accumulation and ultimately apoptosis of Caki-2 and A498 cells. In parallel, the apoptotic effect was accompanied by a significant downregulation of antioxidant proteins especially PARK7. Knockdown of PARK7 using siRNA and overexpression using plasmid highlights the role of PARK7 as a key player in renal cell carcinoma response to cisplatin induced apoptosis. Overexpression of PARK7 resulted in significant decrease in apoptosis, whereas knockdown of the protein was accompanied by an increase in apoptosis in Caki-2 and A498 cells treated with cisplatin. These results highlights for the first time the important role of PARK7 in cisplatin induced apoptosis in clear renal cell carcinoma cells. PMID:27112662

  11. Effect of Matricaria chamomilla Hydroalcoholic Extract on Cisplatin-induced Neuropathy in Mice

    Institute of Scientific and Technical Information of China (English)

    A.Namvaran Abbas Abad; M.H.Kayate Nouri; A.Gharjanie; F.Tavakoli

    2011-01-01

    AIM: Cisplatin-based chemotherapy is a mainstay for the treatment of solid tumors, especially colorectal, ovarian,testicular, bladder, and lung cancer. Studies have shown that cisplatin could have painful effects on human and animal models. Matricaria chamomilla (MC) has analgesic and anti-inflammatory effects. The aim of this study was to investigate the effects of MC hydroalcoholic extract on cisplatin-induced peripheral neuropathy and to compare with morphine in mice. METHODS: Experiments were performed on 60 NMRI male mice weighed 25 g to 30 g which have been divided into 6 groups. The fast group received normal saline;the second group received MC hydroalcoholic extract; the third group received cisplatin; the fourth group received MC hydroalcoholic extract and cisplatin, 96 hours before formalin test; the fifth group received morphine and the sixth group received cisplatin and morphine. The time of injected hind paw biting and licking time were measured in 5-minute interval for an hour. RESULTS: Results showed that formalin induced significant (P<0.05) pain response (the first phase: 0-5 min and the second phase: 15-40 min after injection). Administration of MC extract before formalin injection showed significant (P<0.05) decrease of pain responses in the first and second phase. Administration of cisplatin produced significant (P<0.05) increase in pain response in both phases of formalin test.Injection of MC extract and cisplatin together have shown that MC is able to decrease the second phase of cisplatin-induced pain sig-nificantly (P<0.05). Morphine decreased cisplatin-induced pain in the first and second phase of formalin test significantly(P<0.05).In comparison morphine has analgesic effects in the first phase and MC extract has anti inflammatory effects in the second phase of formalin test significantly (P < 0.05). CONCLUSION: MC and cisplatin have analgesic and painful neuropathic respective effects, and MC hydroalcoholic extract is able to

  12. The Effect of Mirtazapine on Cisplatin-Induced Oxidative Damage and Infertility in Rat Ovaries

    OpenAIRE

    Durdu Altuner; Mine Gulaboglu; Omer Erkan Yapca; Nihal Cetin

    2013-01-01

    Cisplatin causes infertility due to ovarian toxicity. The toxicity mechanism is unknown, but evidence suggests oxidative stress. In this study, the effect of mirtazapine on cisplatin-induced infertility and oxidative stress in rats was investigated. 64 female rats were divided into 4 groups of 16. Except for the controls that received physiologic saline only, all were administered with cisplatin (5 mg/kg i.p.) and mirtazapine (15 mg/kg p.o.) or mirtazapine (30 mg/kg p.o.) for 10 days. After t...

  13. Acute Lymphoblastic Leukemia in a Young Adult Presenting as Hepatitis and Acute Kidney Injury

    Science.gov (United States)

    Heincelman, Marc; Karakala, Nithin; Rockey, Don C.

    2016-01-01

    Acute lymphoblastic leukemia (ALL) in adults is a relatively rare malignancy. The typical presentation includes signs and symptoms associated with bone marrow failure, including fevers, infections, fatigue, and excessive bruising. In this article, we report an unusual systemic presentation of ALL in a previously healthy 18-year-old man. He initially presented with several-day history of nausea and vomiting, 10-pound weight loss, and right upper quadrant abdominal pain with evidence of acute hepatocellular liver injury (elevations in aspartate aminotransferase/alanine aminotransferase) and elevation in serum creatinine. Further history revealed that he just joined the Marine Corp; in preparation, he had been lifting weights and taking protein and creatine supplements. A complete serological evaluation for liver disease was negative and creatine phosphokinase was normal. His aspartate aminotransferase and alanine aminotransferase declined, and he was discharged with expected improvement. However, he returned one week later with continued symptoms and greater elevation of aminotransferases. Liver biopsy was nondiagnostic, revealing scattered portal and lobular inflammatory cells (primarily lymphocytes) felt to be consistent with drug-induced liver injury or viral hepatitis. Given his elevated creatinine, unresponsive to aggressive volume expansion, a kidney biopsy was performed, revealing normal histology. He subsequently developed an extensive left lower extremity deep venous thrombosis. Given his deep venous thrombosis, his peripheral blood was sent for flow cytometry, which revealed lymphoblasts. Bone marrow biopsy revealed 78% blasts with markers consistent with acute B-cell lymphoblastic leukemia. This report emphasizes that right upper quadrant abdominal pain with liver test abnormalities may be the initial presentation of a systemic illness such as ALL.

  14. Acute pancreatitis induced by mycophenolate mofetil in a kidney transplant patient

    OpenAIRE

    Einollahi Behzad; Dolatimehr Fardin

    2015-01-01

    Acute pancreatitis is a rare life-threatening complication in patients after kidney transplantation. Here we described a 56-year-old man who had received a living related kidney transplant for an end-stage renal disease. In his regular follow-up, his serum creatinine was gradually increased and he underwent an allograft biopsy, which revealed an interstitial nephritis/tubular atrophy grade II. Mycophenolate mofetil (MMF) was prescribed to control chronic allograft nephropathy. He presented wi...

  15. Acute Kidney Injury after Using Contrast during Cardiac Catheterization in Children with Heart Disease

    OpenAIRE

    Hwang, Young Ju; Hyun, Myung Chul; Choi, Bong Seok; Chun, So Young; Cho, Min Hyun

    2014-01-01

    Acute kidney injury (AKI) is closely associated with the mortality of hospitalized patients and long-term development of chronic kidney disease, especially in children. The purpose of our study was to assess the evidence of contrast-induced AKI after cardiac catheterization in children with heart disease and evaluate the clinical usefulness of candidate biomarkers in AKI. A total of 26 children undergoing cardiac catheterization due to various heart diseases were selected and urine and blood ...

  16. Urinary L-FABP predicts poor outcomes in critically ill patients with early acute kidney injury

    OpenAIRE

    Parr, Sharidan K.; Clark, Amanda J.; Bian, Aihua; Shintani, Ayumi; Wickersham, Nancy E.; Ware, Lorraine B.; Ikizler, T. Alp; Siew, Edward D.

    2014-01-01

    Biomarker studies for early detection of acute kidney injury (AKI) have been limited by non-selective testing and uncertainties in using small changes in serum creatinine as a reference standard. Here we examine the ability of urine L-type fatty acid binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), Interleukin-18 (IL-18), and Kidney Injury Moledule-1 (KIM-1) to predict injury progression, dialysis, or death within 7 days in critically ill adults with early AKI. Of ...

  17. Disseminate Fungal Infection after Acute Pancreatitis in a Simultaneous Pancreas-Kidney Recipient

    OpenAIRE

    Gian Luigi Adani; Vittorio Bresadola; Pierluigi Viale; Andrea Risaliti; Dario Lorenzin; Umberto Baccarani; Anna Rossetto

    2010-01-01

    Fungal infections after kidney transplantation are a major cause of morbidity and mortality, and Candida infection of the pancreas is considered an infrequent but important agent in necrotizing pancreatitis. We report the case of a 43-year-old Caucasian patient who underwent simultaneous pancreas-kidney transplantation because of diabetes type I, and chronic renal failure with peritoneal dialysis. The postoperative course was complicated by acute pancreatitis due to the thrombosis of the sple...

  18. Preischemic targeting of HIF prolyl hydroxylation inhibits fibrosis associated with acute kidney injury

    OpenAIRE

    Kapitsinou, Pinelopi P.; Jaffe, Jonathan; Michael, Mark; Swan, Christina E.; Duffy, Kevin J.; Erickson-Miller, Connie L.; Haase, Volker H.

    2012-01-01

    Acute kidney injury (AKI) due to ischemia is an important contributor to the progression of chronic kidney disease (CKD). Key mediators of cellular adaptation to hypoxia are oxygen-sensitive hypoxia-inducible factors (HIF), which are regulated by prolyl-4-hydroxylase domain (PHD)-containing dioxygenases. While activation of HIF protects from ischemic cell death, HIF has been shown to promote fibrosis in experimental models of CKD. The impact of HIF activation on AKI-induced fibrosis has not b...

  19. Mouse model of ischemic acute kidney injury: technical notes and tricks

    OpenAIRE

    Wei, Qingqing; Zheng DONG

    2012-01-01

    Renal ischemia-reperfusion leads to acute kidney injury (AKI), a major kidney disease associated with an increasing prevalence and high mortality rates. A variety of experimental models, both in vitro and in vivo, have been used to study the pathogenic mechanisms of ischemic AKI and to test renoprotective strategies. Among them, the mouse model of renal clamping is popular, mainly due to the availability of transgenic models and the relatively small animal size for drug testing. However, the ...

  20. Increased incidence of acute kidney injury with aprotinin use during cardiac surgery detected with urinary NGAL

    DEFF Research Database (Denmark)

    Wagener, G.; Gubitosa, G.; Wang, S.;

    2008-01-01

    BACKGROUND: Use of aprotinin has been associated with acute kidney injury after cardiac surgery. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel, very sensitive marker for renal injury. Urinary NGAL may be able to detect renal injury caused by aprotinin. This study determined...... if the use of aprotinin is associated with an increased incidence of acute kidney injury and increased levels of urinary NGAL. METHODS: In this prospective, observational study 369 patients undergoing cardiac surgery were enrolled. 205 patients received aprotinin and 164 received epsilon amino-caproic acid...... intraoperatively. Urinary NGAL was measured before and immediately after cardiac surgery and 3, 18 and 24 h later. The association of aprotinin use with the incidence of acute kidney injury (increase of serum creatinine >0.5 mg/dl) and NGAL levels was determined using logistic and linear regression models. RESULTS...

  1. SODIUM BICARBONATE INFUSION: TO PREVENT CARDIAC SURGERY - ASSOCIATED ACUTE KIDNEY INJURY

    Directory of Open Access Journals (Sweden)

    Ramesh

    2015-02-01

    Full Text Available OBJECTIVES: The incidence of cardiac surgery – associated acute kidney injury is 50% of patients and is associated with increased mortality and morbidity. This study aimed to determine if perioperative urinary and plasma alkalization with sodium bicarbonate infusion re duces the incidence of cardiac surgery – associated acute kidney injury. SETTING AND DESIGN: This study is double blind randomized control trial conducted at U N Mehta Institute of Cardiology and Research Center , India. METHOD S AND RESULT: A total of 140 pat ients scheduled to undergo elective cardiac surgery , who were at increased risk of development of cardiac surgery – associated acute kidney injury using recognized risk factors. Patients were randomly allocated to receive either sodium bicarbonate (n = 70 o r sodium chloride (n = 70 infusion , commencing at the start of anesthesia , in a dose of 4 mmol/kg over 24 hour. The primary outcome measure was the number of patients with development of CSA - AKI , defined as an increase in creatinine greater than 25% from baseline to peak value within the first three postoperative days. Significant differences among the groups in both plasma and urinary pH were achieved 6 hours after commencement of the infusion , and these changes persisted for more than 24 hours. A total o f 7 out of 70(10% patients in the sodium bicarbonate group and 16 out of 70(22.85% patients in the sodium chloride group developed acute kidney injury within the first three postoperative days with p value of 0.06 which is statistically not significant . There were also no significant differences in ventilation hours , ICU or hospital length of stay , or mortality. CONCLUSIONS: Perioperative alkalization of blood and urine using an infusion of sodium bicarbonate did not result in a decrease in the incidence of acute kidney injury in patients undergoing cardiac surgery. KEYWORDS: Acute kidney injury; Cardiac surgery; Cardiopulmonary bypass; Creatinine

  2. Urinary neutrophil gelatinase-associated lipocalin and acute kidney injury after cardiac surgery

    DEFF Research Database (Denmark)

    Wagener, G.; Gubitosa, G.; Wang, S.;

    2008-01-01

    BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is proposed as an early marker of kidney injury. We report the association of urinary NGAL with indexes of intraoperative renal hypoperfusion (cardiopulmonary bypass time and aortic cross-clamp time) and acute kidney injury (AKI) after...... cardiopulmonary bypass time and aortic cross-clamp time to predict AKI were 0.592 (95% CI, 0.518 to 0.666) and 0.593 (95% CI, 0.523 to 0.665), respectively. LIMITATIONS: Limited sensitivity of changes in serum creatinine levels for kidney injury. CONCLUSIONS: Urinary NGAL has limited diagnostic accuracy to...

  3. The Preventive Effect of Oxytocin to Cisplatin-Induced Neurotoxicity: An Experimental Rat Model

    Directory of Open Access Journals (Sweden)

    Tulay Akman

    2015-01-01

    Full Text Available Peripheral neurotoxicity is a frequent dose-limiting side effect of the chemotherapeutic agent cisplatin. This study was conducted to investigate the preventive effect of oxytocin (OT on cisplatin-induced neurotoxicity in rats. Forty-four adult female rats were included in the study. Thirty-six rats were administered intraperitoneally (i.p. single dose cisplatin 10 mg/kg and divided in to 3 groups. The first group (n=12 received saline i.p., whereas the second group (n=12 and the third group (n=12 were injected with 80 µg/kg and 160 µg/kg OT, respectively, for 10 days. The remaining 8 rats served as the control group. Electromyography (EMG studies were recorded and blood samples were collected for the measurement of plasma lipid peroxidation (malondialdehyde; MDA, tumor necrosis factor (TNF-α, and glutathione (GSH levels. EMG findings revealed that compound muscle action potential amplitude was significantly decreased and distal latency was prolonged in the nontreated cisplatin-injected rats compared with the control group (P<0.005. Also, nontreated cisplatin-injected rats showed significantly higher TNF-α and MDA levels and lower GSH level than control group. The administration of OT significantly ameliorated the EMG alterations, suppressed oxidative stress and inflammatory parameters, and increased antioxidative capacity. We suggest that oxytocin may have beneficial effects against cisplatin-induced neurotoxicity.

  4. D-methionine protects against cisplatin-induced neurotoxicity in the hippocampus of the adult rat.

    Science.gov (United States)

    Hinduja, Sneha; Kraus, Kari Suzanne; Manohar, Senthilvelan; Salvi, Richard J

    2015-04-01

    The hippocampus plays an important role in memory, mood, and spatial navigation. In the dentate gyrus of the adult hippocampus, in the subgranular zone (SGZ), new cells are generated, which differentiate and mature into new neurons. Cisplatin, a highly effective antineoplastic drug with nephrotoxic and ototoxic side effects, induces apoptosis and suppresses neurogenesis in the hippocampus leading to memory impairment. Previous studies have shown that the antioxidant D-methionine protects against cisplatin-induced ototoxicity and nephrotoxicity suggesting that it might also prevent neurogenesis from being suppressed by cisplatin treatment. To test this hypothesis, rats were treated with cisplatin, D-methionine, cisplatin plus D-methionine, or saline (controls). Seven days after treatment, the rats were sacrificed, and hippocampal sections immunolabeled for doublecortin (DCX) to identify neuronal precursor cells and maturing neurons in the SGZ. Cisplatin significantly reduced the number of DCX-labeled cells (~80 %) relative to controls. In contrast, DCX cell counts in rats treated with D-methionine prior to cisplatin were similar to controls. The treatment with D-methionine alone did not affect the number of DCX cells. These results indicate that D-methionine prevents the dramatic cisplatin-induced decrease of neurogenesis.

  5. Protective effect of bixin on cisplatin-induced genotoxicity in PC12 cells.

    Science.gov (United States)

    Dos Santos, Graciela Cristina; Mendonça, Leonardo Meneghin; Antonucci, Gilmara Ausech; Dos Santos, Antonio Cardozo; Antunes, Lusânia Maria Greggi; Bianchi, Maria de Lourdes Pires

    2012-02-01

    Bixin is the main carotenoid found in annatto seeds (Bixa orellana L.) and is responsible for their reddish-orange color. The antioxidant properties of this compound are associated with its ability to scavenge free radicals, which may reduce damage and protect tissues against toxicity caused by anticancer drugs such as cisplatin. In this study, the genotoxicity and antigenotoxicity of bixin on cisplatin-induced toxicity in PC12 cells was assessed. Cytotoxicity was evaluated using the MTT assay, mutagenicity, genotoxicity, and protective effect of bixin were evaluated using the micronucleus test and comet assay. PC12 cells were treated with bixin (0.05, 0.08, and 0.10μg/mL), cisplatin (0.1μg/mL) or a combination of both bixin and cisplatin. Bixin was neither cytotoxic nor genotoxic compared to the controls. In the combined treatment bixin significantly reduced the percentage of DNA in tail and the frequency of micronuclei induced by cisplatin. This result suggests that bixin can function as a protective agent, reducing cisplatin-induced DNA damage in PC12 cells, and it is possible that this protection could also extend to neuronal cells. Further studies are being conducted to better understand the mechanisms involved in the activity of this protective agent prior to using it therapeutically. PMID:22019694

  6. Effects of Roselle and Ginger on cisplatin-induced reproductive toxicity in rats

    Institute of Scientific and Technical Information of China (English)

    Amr Amin; AlaaEldin A. Hamza

    2006-01-01

    Aim: To evaluate the protective effects of Hibiscus sabdariffa (Roselle) and Zingiber officinale (Ginger) against cisplatin-induced reproductive toxicity in rats and to study the mechanisms underlying these effects. Methods:which began 21 days before a single cisplatin I.p. Injection (10 mg/kg body weight). Results: Extracts of H. Sabdariffa and Z. Officinale reduced the extent of cisplatin-induced sperm abnormality and enhanced sperm motility. Both extracts restored the control level of malondialdehyde (MDA) (lipid peroxidation marker) in the cisplatin-treated testis.The cisplatin injection induced decline in the levels of superoxide dismutase (SOD), reduced glutathione (GSH) and catalase (CAT) were significantly reversed to control levels in groups where cisplatin was preceded by the administration of either H. Sabdariffa or Z. Officinale. Conclusion: Both H. Sabdariffa and Z. Officinale treatment increased the activities of testicular antioxidant enzymes and restored sperm motility of cisplatin-treated rats. The protective effects of tested plants are, therefore, suggested to be mediated by their potent antioxidant activities.

  7. Protective effect of speman on cisplatin-induced testicular and epididymal toxicity in mice

    Directory of Open Access Journals (Sweden)

    S B Sainath

    2011-01-01

    Full Text Available Testicular cancer is the most common cancer affecting men of reproductive age. Advances in treatment of the disease, which includes the administration of cisplatin, have brought the 5-year survival rate to over 90%. This high cure rate, coupled with young age of patients, makes elucidation of the impact of the treatment on reproduction become increasingly important. The objective of the present study was to investigate the protective effect of speman, a non-hormonal herbal formulation, on cisplatin-induced suppressed male reproductive health in mice. Male mice were treated with cisplatin or speman alone or in combination and assessed for spermatogenesis and steroidogenesis. Significant decrease in the weights of testes and epididymis was observed in cisplatin treated animals. Injection of cisplatin significantly decreased epididymal sperm count, viable sperms, motile sperms and hypo-osmotic swelling (HOS-tail coiled sperms with a significant reduction in the testicular steroidogenic enzyme activities and serum testosterone levels, whereas co-administration of speman with cisplatin showed a significant improvement in the selected reproductive parameters over cisplatin alone treated mice indicating the beneficial effect of speman to combat cisplatin-induced suppressed reproduction in male mice.

  8. Nicotinic Acetylcholine Receptor Agonists Attenuate Septic Acute Kidney Injury in Mice by Suppressing Inflammation and Proteasome Activity

    OpenAIRE

    Chatterjee, Prodyot K.; Yeboah, Michael M.; Oonagh Dowling; Xiangying Xue; Powell, Saul R.; Yousef Al-Abed; Metz, Christine N

    2012-01-01

    Sepsis is one of the leading causes of acute kidney injury (AKI). Septic patients who develop acute kidney injury (AKI) are at increased risk of death. To date there is no effective treatment for AKI or septic AKI. Based on their anti-inflammatory properties, we examined the effects of nicotinic acetylcholine receptor agonists on renal damage using a mouse model of lipopolysaccharide (LPS)-induced AKI where localized LPS promotes inflammation-mediated kidney damage. Administration of nicotine...

  9. Outpatient nephrology referral rates after acute kidney injury.

    Science.gov (United States)

    Siew, Edward D; Peterson, Josh F; Eden, Svetlana K; Hung, Adriana M; Speroff, Theodore; Ikizler, T Alp; Matheny, Michael E

    2012-02-01

    AKI associates with an increased risk for the development and progression of CKD and mortality. Processes of care after an episode of AKI are not well described. Here, we examined the likelihood of nephrology referral among survivors of AKI at risk for subsequent decline in kidney function in a US Department of Veterans Affairs database. We identified 3929 survivors of AKI hospitalized between January 2003 and December 2008 who had an estimated GFR (eGFR) <60 ml/min per 1.73 m(2) 30 days after peak injury. We analyzed time to referral considering improvement in kidney function (eGFR ≥60 ml/min per 1.73 m(2)), dialysis initiation, and death as competing risks over a 12-month surveillance period. Median age was 73 years (interquartile range, 62-79 years) and the prevalence of preadmission kidney dysfunction (baseline eGFR <60 ml/min per 1.73 m(2)) was 60%. Overall mortality during the surveillance period was 22%. The cumulative incidence of nephrology referral before dying, initiating dialysis, or experiencing an improvement in kidney function was 8.5% (95% confidence interval, 7.6-9.4). Severity of AKI did not affect referral rates. These data demonstrate that a minority of at-risk survivors are referred for nephrology care after an episode of AKI. Determining how to best identify survivors of AKI who are at highest risk for complications and progression of CKD could facilitate early nephrology-based interventions.

  10. T1-mapping for assessment of ischemia-induced acute kidney injury and prediction of chronic kidney disease in mice

    Energy Technology Data Exchange (ETDEWEB)

    Hueper, Katja; Gutberlet, Marcel; Wacker, Frank; Hartung, Dagmar [Hannover Medical School, Department of Radiology, Hannover (Germany); Hannover Medical School, REBIRTH Cluster of Excellence, Hannover (Germany); Peperhove, Matti; Tewes, Susanne; Barrmeyer, Amelie [Hannover Medical School, Department of Radiology, Hannover (Germany); Rong, Song [Hannover Medical School, Department of Nephrology, Hannover (Germany); Zunyi Medical College, Laboratory of Organ Transplantation, Zunyi (China); Gerstenberg, Jessica; Haller, Herman; Gueler, Faikah [Hannover Medical School, Department of Nephrology, Hannover (Germany); Mengel, Michael [University of Alberta, Department of Laboratory Medicine and Pathology, Edmonton (Canada); Meier, Martin [Hannover Medical School, REBIRTH Cluster of Excellence, Hannover (Germany); Hannover Medical School, Institute for Animal Science, Hannover (Germany); Chen, Rongjun [Hannover Medical School, Department of Nephrology, Hannover (Germany); Zhejiang University, The Kidney Disease Center of the First Affiliated Hospital, Hangzhou (China)

    2014-09-15

    To investigate whether T1-mapping allows assessment of acute kidney injury (AKI) and prediction of chronic kidney disease (CKD) in mice. AKI was induced in C57Bl/6N mice by clamping of the right renal pedicle for 35 min (moderate AKI, n = 26) or 45 min (severe AKI, n = 23). Sham animals served as controls (n = 9). Renal histology was assessed in the acute (day 1 + day 7; d1 + d7) and chronic phase (d28) after AKI. Furthermore, longitudinal MRI-examinations (prior to until d28 after surgery) were performed using a 7-Tesla magnet. T1-maps were calculated from a fat-saturated echoplanar inversion recovery sequence, and mean and relative T1-relaxation times were determined. Renal histology showed severe tubular injury at d1 + d7 in both AKI groups, whereas, at d28, only animals with prolonged 45-min ischemia showed persistent signs of AKI. Following both AKI severities T1-values significantly increased and peaked at d7. T1-times in the contralateral kidney without AKI remained stable. At d7 relative T1-values in the outer stripe of the outer medulla were significantly higher after severe than after moderate AKI (138 ± 2 % vs. 121 ± 3 %, p = 0.001). T1-elevation persisted until d28 only after severe AKI. Already at d7 T1 in the outer stripe of the outer medulla correlated with kidney volume loss indicating CKD (r = 0.83). T1-mapping non-invasively detects AKI severity in mice and predicts further outcome. (orig.)

  11. T1-mapping for assessment of ischemia-induced acute kidney injury and prediction of chronic kidney disease in mice

    International Nuclear Information System (INIS)

    To investigate whether T1-mapping allows assessment of acute kidney injury (AKI) and prediction of chronic kidney disease (CKD) in mice. AKI was induced in C57Bl/6N mice by clamping of the right renal pedicle for 35 min (moderate AKI, n = 26) or 45 min (severe AKI, n = 23). Sham animals served as controls (n = 9). Renal histology was assessed in the acute (day 1 + day 7; d1 + d7) and chronic phase (d28) after AKI. Furthermore, longitudinal MRI-examinations (prior to until d28 after surgery) were performed using a 7-Tesla magnet. T1-maps were calculated from a fat-saturated echoplanar inversion recovery sequence, and mean and relative T1-relaxation times were determined. Renal histology showed severe tubular injury at d1 + d7 in both AKI groups, whereas, at d28, only animals with prolonged 45-min ischemia showed persistent signs of AKI. Following both AKI severities T1-values significantly increased and peaked at d7. T1-times in the contralateral kidney without AKI remained stable. At d7 relative T1-values in the outer stripe of the outer medulla were significantly higher after severe than after moderate AKI (138 ± 2 % vs. 121 ± 3 %, p = 0.001). T1-elevation persisted until d28 only after severe AKI. Already at d7 T1 in the outer stripe of the outer medulla correlated with kidney volume loss indicating CKD (r = 0.83). T1-mapping non-invasively detects AKI severity in mice and predicts further outcome. (orig.)

  12. Procalcitonin levels predict acute kidney injury and prognosis in acute pancreatitis: a prospective study.

    Directory of Open Access Journals (Sweden)

    Hua-Lan Huang

    Full Text Available BACKGROUND: Acute kidney injury (AKI has been proposed as a leading cause of mortality for acute pancreatitis (AP patients admitted to the intensive care unit (ICU. This study investigated the predictive value of procalcitonin (PCT for AKI development and relevant prognosis in patients with AP, and compared PCT's predictive power with that of other inflammation-related variables. METHODS: Between January 2011 and March 2013, we enrolled 305 cases with acute pancreatitis admitted to ICU. Serum levels of PCT, serum amyloid A (SAA, interleukin-6 (IL-6, and C reactive protein (CRP were determined on admission. Serum PCT was tested in patients who developed AKI on the day of AKI occurrence and on either day 28 after occurrence (for survivors or on the day of death (for those who died within 28 days. RESULTS: Serum PCT levels were 100-fold higher in the AKI group than in the non-AKI group on the day of ICU admission (p<0.05. The area under the receiver-operating characteristic (ROC curve of PCT for predicting AKI was 0.986, which was superior to SAA, CRP, and IL-6 (p<0.05. ROC analysis revealed all variables tested had lower predictive performance for AKI prognosis. The average serum PCT level on day 28 (2.67 (0.89, 7.99 ng/ml was significantly (p<0.0001 lower than on the day of AKI occurrence (43.71 (19.24,65.69 ng/ml in survivors, but the serum PCT level on death (63.73 (34.22,94.30 ng/ml was higher than on the day of AKI occurrence (37.55 (18.70,74.12 ng/ml in non-survivors, although there was no significant difference between the two days in the latter group (p = 0.1365. CONCLUSION: Serum PCT is superior to CRP, IL-6, and SAA for predicting the development of AKI in patients with AP, and also can be used for dynamic evaluation of AKI prognosis.

  13. Eearly diagnostic value of urinary NGAL in acute kidney injury in critically ill patients

    Institute of Scientific and Technical Information of China (English)

    徐兴凯

    2013-01-01

    Objective To estimate the predictive value of neutrophil gelatinase-associated lipocalin in urine (uNGAL) for detection of acute kidney injury (AKI) in the intensive care unit (ICU) critically ill patients.Methods A total of 110 patients from the ICU of three general hospitals were enrolled in the study.The patients were adults

  14. Alkaline phosphatase : a possible treatment for sepsis-associated acute kidney injury in critically ill patients

    NARCIS (Netherlands)

    Peters, Esther; Heemskerk, Suzanne; Masereeuw, R.; Pickkers, Peter

    2014-01-01

    Acute kidney injury (AKI) is a common disease in the intensive care unit and accounts for high morbidity and mortality. Sepsis, the predominant cause of AKI in this setting, involves a complex pathogenesis in which renal inflammation and hypoxia are believed to play an important role. A new therapy

  15. Acute kidney injury: intravenous fluid to prevent contrast-induced AKI.

    Science.gov (United States)

    Weisbord, Steven D; Palevsky, Paul M

    2009-05-01

    Trials that compared sodium bicarbonate and sodium chloride for the prevention of contrast-induced acute kidney injury have yielded highly conflicting results. The authors of a recent meta-analysis endeavored to provide a definitive assessment of the relative efficacy of these two intravenous fluids.

  16. Arterial pressure during cardiopulmonary bypass is not associated with acute kidney injury

    DEFF Research Database (Denmark)

    Kandler, K; Jensen, M E; Nilsson, J C;

    2015-01-01

    BACKGROUND: Acute kidney injury (AKI) after cardiac surgery is common and is associated with increased mortality. We wanted to investigate if the arterial pressure or the use of norepinephrine during cardiopulmonary bypass were associated with AKI. METHODS: A retrospective analysis of patients who...

  17. Serum and urine cystatin C are poor biomarkers for acute kidney injury and renal replacement therapy.

    NARCIS (Netherlands)

    Royakkers, A.A.N.M.; Korevaar, J.C.; Suijlen, J.D.E. van; Hofstra, L.S.; Kuiper, M.A.; Spronk, P.E.; Schultz, M.J.; Bouman, C.S.C.

    2011-01-01

    Purpose : To evaluate whether cystatin C in serum (sCyC) and urine (uCyC) can predict early acute kidney injury (AKI) in a mixed heterogeneous intensive care unit (ICU), and also whether these biomarkers can predict the need for renal replacement therapy (RRT). Methods: Multicenter prospective obser

  18. Negative Regulation of TGFβ Signaling by Stem Cell Antigen-1 Protects against Ischemic Acute Kidney Injury.

    Directory of Open Access Journals (Sweden)

    Troy D Camarata

    Full Text Available Acute kidney injury, often caused by an ischemic insult, is associated with significant short-term morbidity and mortality, and increased risk of chronic kidney disease. The factors affecting the renal response to injury following ischemia and reperfusion remain to be clarified. We found that the Stem cell antigen-1 (Sca-1, commonly used as a stem cell marker, is heavily expressed in renal tubules of the adult mouse kidney. We evaluated its potential role in the kidney using Sca-1 knockout mice submitted to acute ischemia reperfusion injury (IRI, as well as cultured renal proximal tubular cells in which Sca-1 was stably silenced with shRNA. IRI induced more severe injury in Sca-1 null kidneys, as assessed by increased expression of Kim-1 and Ngal, rise in serum creatinine, abnormal pathology, and increased apoptosis of tubular epithelium, and persistent significant renal injury at day 7 post IRI, when recovery of renal function in control animals was nearly complete. Serum creatinine, Kim-1 and Ngal were slightly but significantly elevated even in uninjured Sca-1-/- kidneys. Sca-1 constitutively bound both TGFβ receptors I and II in cultured normal proximal tubular epithelial cells. Its genetic loss or silencing lead to constitutive TGFβ receptor-mediated activation of canonical Smad signaling even in the absence of ligand and to KIM-1 expression in the silenced cells. These studies demonstrate that by normally repressing TGFβ-mediated canonical Smad signaling, Sca-1 plays an important in renal epithelial cell homeostasis and in recovery of renal function following ischemic acute kidney injury.

  19. Acute kidney injury from cherry concentrate in a patient with CKD.

    Science.gov (United States)

    Luciano, Randy L

    2014-03-01

    Nutraceuticals are supplements and medical foods that offer numerous health benefits. However, these substances may have adverse effects on multiple organ systems, leading to significant morbidity. I present a patient with chronic kidney disease who experienced hemodynamically mediated acute kidney injury and hyperkalemia after daily consumption of cherry concentrate. The method of injury was most likely cyclooxygenase inhibition by the compounds in cherries that mimic the mechanism of action of nonsteroidal anti-inflammatory medications. Ceasing cherry concentrate consumption led to improvements in both the patient's hyperkalemia and kidney injury. Physicians should be aware of the potentially harmful side effects of cherry concentrate and approach the use of cherry extract or concentrate with caution in patients with underlying kidney disease. PMID:24290246

  20. Design of Clinical Trials in Acute Kidney Injury: Lessons from the Past and Future Directions.

    Science.gov (United States)

    Weisbord, Steven D; Palevsky, Paul M

    2016-01-01

    Acute kidney injury (AKI) is a common condition with multiple etiologies and variable clinical findings and pathologic manifestations. AKI is associated with serious adverse clinical outcomes, including the development of de novo chronic kidney disease, accelerated progression of pre-existing chronic kidney disease, end-stage kidney disease, and increased mortality. Past research has advanced our understanding of the pathophysiology, epidemiology, and outcomes of AKI significantly, however, little progress has been made in the development of evidence-based interventions for its prevention and treatment. In this review, we discuss key considerations in the design of clinical trials in AKI and highlight significant methodologic limitations that precluded many past studies from determining the effectiveness of preventive and therapeutic strategies for this common and serious condition.

  1. The inflammatory response in blood and in remote organs following acute kidney injury

    DEFF Research Database (Denmark)

    Brøchner, Anne Craveiro; Dagnaes-Hansen, Frederik; Højberg-Holm, Jimmy;

    2014-01-01

    In patients with acute kidney injury (AKI) mortality remains high, despite the fact that the patients are treated with continuous renal replacement therapy. The interaction between the kidney and the immune system might explain the high mortality observed in AKI. In order to elucidate the...... interaction between the kidney and immune system we developed a two-hit model of AKI and endotoxemia. Our hypothesis was that ischemia/reperfusion (I/R) of the kidney simultaneously with endotoxemia would generate a more extensive inflammatory response compared to I/R of the hind legs. Our expectation was....... The neutrophil infiltration of distant organs measured by the levels of MPO in the lung and liver also showed a significantly higher level in renal I/R compared to hind leg I/R. Renal I/R is associated with a more pronounced inflammatory response in blood and distant organs. The high cytokine levels...

  2. Effect of acute occlusion of left renal vein on the kidney: an experimental study in dogs.

    Science.gov (United States)

    Khan, S A; Ashraf, S M; Naim, M; Azfar, M

    1994-04-01

    To study the effects of acute ligation of the left renal vein an experimental study was carried out on 16 Mongrel dogs out of 18 of which 2 had died postoperatively. The right kidney served as control. Changes immediately after ligation were recorded; subsequently the dogs were sacrificed in 4 groups comprising 4 in each at intervals of 24 hours, one week, 4 weeks and 6 weeks. Both the kidneys were removed and gross and microscopic changes were noted. In all cases atrophy of the ligated kidney due to tubular atrophy and fibrosis were seen in spite of good collaterals. It is concluded that left renal vein ligation in dogs is not safe for the kidney, though it is not fatal.

  3. Acute Kidney Injury Complicated Epstein-Barr Virus Infection in Infancy

    Directory of Open Access Journals (Sweden)

    Gamze Ozgurhan

    2015-01-01

    Full Text Available Infectious mononucleosis is an acute lymphoproliferative disorder caused by the Epstein-Barr virus (EBV and seen most commonly in children and young adults. Clinical presentation of the disease is characterized by fever, tonsillopharyngitis, lymphadenopathy, and hepatosplenomegaly, whereas serological findings of this benign disorder include positive heterophilic antibody formation (transient increase in heterophilic antibodies and prominence of hematological lymphocytosis of more than 10% of atypical lymphocytes. An EBV infection is usually asymptomatic in childhood, but acute kidney injury can be a rare complication during its course. Most cases recover from the disease completely. Early recognition of EBV infection and estimation of its complication are important for its prognosis. In light of previous literature, we discuss the case evaluated as an EBV infection complicated by acute kidney injury in early childhood and results of tubulointerstitial nephritis shown on a renal biopsy that was later diagnosed as an EBV infection by serological examination.

  4. Breast cancer cells with acquired antiestrogen resistance are sensitized to cisplatin-induced cell death

    DEFF Research Database (Denmark)

    Yde, Christina Westmose; Gyrd-Hansen, Mads; Lykkesfeldt, Anne E;

    2007-01-01

    with parental MCF-7 cells. Our data show that Bcl-2 can protect antiestrogen-resistant breast cancer cells from cisplatin-induced cell death, indicating that the reduced expression of Bcl-2 in the antiestrogen-resistant cells plays a role in sensitizing the cells to cisplatin treatment.......Antiestrogens are currently used for treating breast cancer patients who have estrogen receptor-positive tumors. However, patients with advanced disease will eventually develop resistance to the drugs. Therefore, compounds effective on antiestrogen-resistant tumors will be of great importance...... for future breast cancer treatment. In this study, we have investigated the effect of the chemotherapeutic compound cisplatin using a panel of antiestrogen-resistant breast cancer cell lines established from the human breast cancer cell line MCF-7. We show that the antiestrogen-resistant cells...

  5. Pinpointing differences in cisplatin-induced apoptosis in adherent and non-adherent cancer cells

    DEFF Research Database (Denmark)

    Tastesen, Hanne Sørup; Holm, Jacob Bak; Poulsen, Kristian Arild;

    2010-01-01

    ascites tumour cells (ELA). Loss of KCl and cell shrinkage are hallmarks in apoptosis and has been shown in EATC. However, we find no reduction in cell volume and only a minor loss of K(+) which is accompanied by net uptake of Na(+) following 18 hours cisplatin exposure in ELA. Glutathione and taurine...... have previously been demonstrated to protect cells from apoptosis. We find, however, that increase or decrease in the cellular content of glutathione and taurine has no effect on cisplatin-induced cell death in EATC and ELA. Nevertheless, knock-down of the taurine transporter TauT leads...... to a significant increase in apoptosis in ELA following cisplatin exposure. We find that cytosolic accumulation of cisplatin is similar in EATC and ELA. However, the nuclear accumulation and DNA-binding of cisplatin is significant lower in ELA compared to EATC. We suggest three putative reasons for the observed...

  6. Acute Kidney Injury in Elderly Patients With Chronic Kidney Disease: Do Angiotensin-Converting Enzyme Inhibitors Carry a Risk?

    Science.gov (United States)

    Chaumont, Martin; Pourcelet, Aline; van Nuffelen, Marc; Racapé, Judith; Leeman, Marc; Hougardy, Jean-Michel

    2016-06-01

    In contrast to angiotensin receptor blockers (ARBs), mainly excreted by the liver, the dosage of angiotensin-converting enzyme (ACE) inhibitors, cleared by the kidney, must be adapted to account for renal clearance in patients with chronic kidney disease (CKD) to avoid acute kidney injury (AKI). Community-acquired AKI and the use of ACE inhibitors or ARBs in the emergency department were retrospectively assessed in 324 patients with baseline stage 3 or higher CKD. After stepwise regression analysis, the use of ACE inhibitors (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1-3.1; P=.02) and the presence of dehydration (OR, 30.8; 95% CI, 3.9-239.1) were associated with AKI. A total of 45% of patients using ACE inhibitors experienced overdosing, which causes most of the excess risk of AKI. These results suggest that dosage adjustment of ACE inhibitors to renal function or substitution of ACE inhibitors with ARBs could reduce the incidence of AKI. Moreover, ACE inhibitors and ARBs should be stopped in cases of dehydration. PMID:27080620

  7. Sepsis as a cause and consequence of acute kidney injury: Program to Improve Care in Acute Renal Disease

    OpenAIRE

    Mehta, Ravindra L; Bouchard, Josée; Soroko, Sharon B.; Ikizler, T. Alp; Paganini, Emil P.; Chertow, Glenn M.; Himmelfarb, Jonathan

    2011-01-01

    Sepsis commonly contributes to acute kidney injury (AKI); however, the frequency with which sepsis develops as a complication of AKI and the clinical consequences of this sepsis are unknown. This study examined the incidence of, and outcomes associated with, sepsis developing after AKI. We analyzed data from 618 critically ill patients enrolled in a multicenter observational study of AKI (PICARD). Patients were stratified according to their sepsis status and timing of incident sepsis relat...

  8. Sepsis as a cause and consequence of acute kidney injury: Program to Improve Care in Acute Renal Disease

    OpenAIRE

    Mehta, Ravindra L; Bouchard, Josée; Soroko, Sharon B.; Ikizler, T. Alp; Paganini, Emil P.; Chertow, Glenn M.; Himmelfarb, Jonathan; ,

    2010-01-01

    Purpose Sepsis commonly contributes to acute kidney injury (AKI); however, the frequency with which sepsis develops as a complication of AKI and the clinical consequences of this sepsis are unknown. This study examined the incidence of, and outcomes associated with, sepsis developing after AKI. Methods We analyzed data from 618 critically ill patients enrolled in a multicenter observational study of AKI (PICARD). Patients were stratified according to their sepsis status and timing of incident...

  9. Cisplatin Induces Bmi-1 and Enhances the Stem Cell Fraction in Head and Neck Cancer

    Directory of Open Access Journals (Sweden)

    Carolina Nör

    2014-02-01

    Full Text Available Recent evidence has unveiled a subpopulation of highly tumorigenic, multipotent cells capable of self-renewal in head and neck squamous cell carcinomas (HNSCCs. These unique cells, named here cancer stem cells (CSCs, proliferate slowly and might be involved in resistance to conventional chemotherapy. We have shown that CSCs are found in perivascular niches and rely on endothelial cell-secreted factors [particularly interleukin-6 (IL-6] for their survival and self-renewal in HNSCC. Here, we hypothesized that cisplatin enhances the stem cell fraction in HNSCC. To address this hypothesis, we generated xenograft HNSCC tumors with University of Michigan-squamous cell carcinoma 22B (UM-SCC-22B cells and observed that cisplatin treatment increased (P = .0013 the fraction of CSCs [i.e., aldehyde dehydrogenase activity high and cluster of differentiation 44 high (ALDHhighCD44high]. Cisplatin promoted self-renewal and survival of CSCs in vitro, as seen by an increase in the number of orospheres in ultralow attachment plates and induction in B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1 and octamer-binding transcription factor 4 expression. Cisplatin-resistant cells expressed more Bmi-1 than cisplatinsensitive cells. IL-6 potentiated cisplatin-induced orosphere formation generated when primary human HNSCC cells were sorted for ALDHhighCD44high immediately after surgery and plated onto ultralow attachment plates. IL-6-induced signal transducer and activator of transcription 3 (STAT3 phosphorylation (indicative of stemness was unaffected by treatment with cisplatin in UM-SCC-22B cells, whereas IL-6-induced extracellular signal-regulated kinase (ERK phosphorylation (indicative of differentiation processes was partially inhibited by cisplatin. Notably, cisplatin-induced Bmi-1 was inhibited by interleukin-6 receptor blockade in parental and cisplatin-resistant cells. Taken together, these results demonstrate that cisplatin enhances the fraction of CSCs

  10. Cisplatin induces Bmi-1 and enhances the stem cell fraction in head and neck cancer.

    Science.gov (United States)

    Nör, Carolina; Zhang, Zhaocheng; Warner, Kristy A; Bernardi, Lisiane; Visioli, Fernanda; Helman, Joseph I; Roesler, Rafael; Nör, Jacques E

    2014-02-01

    Recent evidence has unveiled a subpopulation of highly tumorigenic, multipotent cells capable of self-renewal in head and neck squamous cell carcinomas (HNSCCs). These unique cells, named here cancer stem cells (CSCs), proliferate slowly and might be involved in resistance to conventional chemotherapy. We have shown that CSCs are found in perivascular niches and rely on endothelial cell-secreted factors [particularly interleukin-6 (IL-6)] for their survival and self-renewal in HNSCC. Here, we hypothesized that cisplatin enhances the stem cell fraction in HNSCC. To address this hypothesis, we generated xenograft HNSCC tumors with University of Michigan-squamous cell carcinoma 22B (UM-SCC-22B) cells and observed that cisplatin treatment increased (P = .0013) the fraction of CSCs [i.e., aldehyde dehydrogenase activity high and cluster of differentiation 44 high (ALDH(high)CD44(high))]. Cisplatin promoted self-renewal and survival of CSCs in vitro, as seen by an increase in the number of orospheres in ultralow attachment plates and induction in B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) and octamer-binding transcription factor 4 expression. Cisplatin-resistant cells expressed more Bmi-1 than cisplatin-sensitive cells. IL-6 potentiated cisplatin-induced orosphere formation generated when primary human HNSCC cells were sorted for ALDH(high)CD44(high) immediately after surgery and plated onto ultralow attachment plates. IL-6-induced signal transducer and activator of transcription 3 (STAT3) phosphorylation (indicative of stemness) was unaffected by treatment with cisplatin in UM-SCC-22B cells, whereas IL-6-induced extracellular signal-regulated kinase (ERK) phosphorylation (indicative of differentiation processes) was partially inhibited by cisplatin. Notably, cisplatin-induced Bmi-1 was inhibited by interleukin-6 receptor blockade in parental and cisplatin-resistant cells. Taken together, these results demonstrate that cisplatin enhances the fraction of CSCs

  11. Cisplatin Induces Bmi-1 and Enhances the Stem Cell Fraction in Head and Neck Cancer12

    Science.gov (United States)

    Nör, Carolina; Zhang, Zhaocheng; Warner, Kristy A; Bernardi, Lisiane; Visioli, Fernanda; Helman, Joseph I; Roesler, Rafael; Nör, Jacques E

    2014-01-01

    Recent evidence has unveiled a subpopulation of highly tumorigenic, multipotent cells capable of self-renewal in head and neck squamous cell carcinomas (HNSCCs). These unique cells, named here cancer stem cells (CSCs), proliferate slowly and might be involved in resistance to conventional chemotherapy. We have shown that CSCs are found in perivascular niches and rely on endothelial cell-secreted factors [particularly interleukin-6 (IL-6)] for their survival and self-renewal in HNSCC. Here, we hypothesized that cisplatin enhances the stem cell fraction in HNSCC. To address this hypothesis, we generated xenograft HNSCC tumors with University of Michigan-squamous cell carcinoma 22B (UM-SCC-22B) cells and observed that cisplatin treatment increased (P = .0013) the fraction of CSCs [i.e., aldehyde dehydrogenase activity high and cluster of differentiation 44 high (ALDHhighCD44high)]. Cisplatin promoted self-renewal and survival of CSCs in vitro, as seen by an increase in the number of orospheres in ultralow attachment plates and induction in B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) and octamer-binding transcription factor 4 expression. Cisplatin-resistant cells expressed more Bmi-1 than cisplatinsensitive cells. IL-6 potentiated cisplatin-induced orosphere formation generated when primary human HNSCC cells were sorted for ALDHhighCD44high immediately after surgery and plated onto ultralow attachment plates. IL-6-induced signal transducer and activator of transcription 3 (STAT3) phosphorylation (indicative of stemness) was unaffected by treatment with cisplatin in UM-SCC-22B cells, whereas IL-6-induced extracellular signal-regulated kinase (ERK) phosphorylation (indicative of differentiation processes) was partially inhibited by cisplatin. Notably, cisplatin-induced Bmi-1 was inhibited by interleukin-6 receptor blockade in parental and cisplatin-resistant cells. Taken together, these results demonstrate that cisplatin enhances the fraction of CSCs and suggest

  12. Selective Cyclooxygenase-2 Inhibitor Prevents Cisplatin-induced Tumorigenesis in A/J Mice

    Directory of Open Access Journals (Sweden)

    Okada,Toshiaki

    2012-06-01

    Full Text Available Cisplatin is used to treat lung cancer;however, it is also a known carcinogen. Cyclooxygenase-2 (COX-2 inhibitors have been shown to prevent carcinogen-induced experimental tumors. We investigated the effect of a COX-2 inhibitor, celecoxib, on cisplatin-induced lung tumors. One hundred twenty 4-week-old A/J mice were divided into 6 groups:group 1, no treatment;group 2, low-dose celecoxib (150mg/kg;group 3, high-dose celecoxib (1,500mg/kg;group 4, cisplatin alone;group 5, cisplatin plus low-dose celecoxib;and group 6, cisplatin plus high-dose celecoxib. Mice in groups 4-6 were administered cisplatin (1.62mg/kg, i.p. once a week for 10 weeks between 7 and 16 weeks of age. All mice were sacrificed at week 30. Tumor incidence was 15.8% in group 1, 25% in group 2, 26.3% in group 3, 60% in group 4, 50% in group 5, and 50% in group 6. Tumor multiplicity was 0.2, 0.3, 0.3, 1.3, 1.0, and 0.6 in groups 1-6, respectively. Tumor multiplicity in the cisplatin-treated mice was reduced by celecoxib treatment in a dose-dependent manner (p<0.05, group 4 vs. group 6. Celecoxib significantly reduced COX-2 expression in cisplatin-induced tumors (p<0.01, group 4 vs. group 6.

  13. Renal endothelial injury and microvascular dysfunction in acute kidney injury.

    Science.gov (United States)

    Verma, Sudhanshu Kumar; Molitoris, Bruce A

    2015-01-01

    The kidney is comprised of heterogeneous cell populations that function together to perform a number of tightly controlled, complex and interdependent processes. Renal endothelial cells contribute to vascular tone, regulation of blood flow to local tissue beds, modulation of coagulation and inflammation, and vascular permeability. Both ischemia and sepsis have profound effects on the renal endothelium, resulting in microvascular dysregulation resulting in continued ischemia and further injury. In recent years, the concept of the vascular endothelium as an organ that is both the source of and target for inflammatory injury has become widely appreciated. Here we revisit the renal endothelium in the light of ever evolving molecular advances. PMID:25795503

  14. The role of the uncertainty of measurement of serum creatinine concentrations in the diagnosis of acute kidney injury.

    Science.gov (United States)

    Kin Tekce, Buket; Tekce, Hikmet; Aktas, Gulali; Uyeturk, Ugur

    2016-01-01

    Uncertainty of measurement is the numeric expression of the errors associated with all measurements taken in clinical laboratories. Serum creatinine concentration is the most common diagnostic marker for acute kidney injury. The goal of this study was to determine the effect of the uncertainty of measurement of serum creatinine concentrations on the diagnosis of acute kidney injury. We calculated the uncertainty of measurement of serum creatinine according to the Nordtest Guide. Retrospectively, we identified 289 patients who were evaluated for acute kidney injury. Of the total patient pool, 233 were diagnosed with acute kidney injury using the AKIN classification scheme and then were compared using statistical analysis. We determined nine probabilities of the uncertainty of measurement of serum creatinine concentrations. There was a statistically significant difference in the number of patients diagnosed with acute kidney injury when uncertainty of measurement was taken into consideration (first probability compared to the fifth p = 0.023 and first probability compared to the ninth p = 0.012). We found that the uncertainty of measurement for serum creatinine concentrations was an important factor for correctly diagnosing acute kidney injury. In addition, based on the AKIN classification scheme, minimizing the total allowable error levels for serum creatinine concentrations is necessary for the accurate diagnosis of acute kidney injury by clinicians.

  15. Molecular Ultrasound Imaging of Tissue Inflammation Using an Animal Model of Acute Kidney Injury

    Science.gov (United States)

    Hoyt, Kenneth; Warram, Jason M.; Wang, Dezhi; Ratnayaka, Sithira; Traylor, Amie; Agarwal, Anupam

    2016-01-01

    Purpose The objective of this study was to evaluate the use of molecular ultrasound (US) imaging for monitoring the early inflammatory effects following acute kidney injury. Procedures A population of rats underwent 30 min of renal ischemia (acute kidney injury, N=6) or sham injury (N=4) using established surgical methods. Animals were divided and molecular US imaging was performed during the bolus injection of a targeted microbubble (MB) contrast agent to either P-selectin or vascular cell adhesion molecule 1 (VCAM-1). Imaging was performed before surgery and 4 and 24 h thereafter. After manual segmentation of renal tissue space, the molecular US signal was calculated as the difference between time-intensity curve data before MB injection and after reaching steady-state US image enhancement. All animals were terminated after the 24 h imaging time point and kidneys excised for immunohistochemical (IHC) analysis. Results Renal inflammation was analyzed using molecular US imaging. While results using the P-selectin and VCAM-1 targeted MBs were comparable, it appears that the former was more sensitive to biomarker expression. All molecular US imaging measures had a positive correlation with IHC findings. Conclusions Acute kidney injury is a serious disease in need of improved noninvasive methods to help diagnose the extent of injury and monitor the tissue throughout disease progression. Molecular US imaging appears well suited to address this challenge and more research is warranted. PMID:25905474

  16. Early Prediction of Acute Kidney Injury by Clinical Features of Snakebite Patients at the Time of Hospital Admission

    Directory of Open Access Journals (Sweden)

    Jayanta Paul

    2012-01-01

    Full Text Available Background: Snakebite is a major health problem in India. Venomous snakebite, which is an important medical hazard in several tropical countries including India, affects thousands of people per year and some of them develop acute kidney injury (AKI. Aims: This study was performed to find out 1 early clinical predictors for acute kidney injury in snakebite patients at the time of hospital admission and 2 incidence of acute kidney injury in snakebite patients. Materials and Methods: 171 consecutively admitted non-diabetic, non-hypertensive snakebite patients were examined. Multivariate linear regression analysis with 95 percent confidence interval (CI was done for statistical analysis. Analyses were performed by software Statistical Package for the Social Sciences (SPSS (17 th version for Windows. Results: Incidence of acute kidney injury was 43.27%. Development of acute kidney injury was independently associated with 20 min whole blood clotting test (20 min WBCT (P value = 0.029; CI 95%, dark or brown color urine (P value = 0.000; CI 95%, and time interval between snakebite and anti-snake venom administration (P value = 0.000; CI 95%. Age (P value = 0.011; CI 95% and presence of neurological signs (P value = 0.000; CI 95% were negatively correlated with development of acute kidney injury. Conclusion: Incidence of acute kidney injury is slightly higher in our study than previous studies. Early prediction of acute kidney injury development in snakebite patients can be done by presence of black or brown urine, 20 min WBCT > 20 min, and increased time interval between snakebite and administration of anti-snake venom at the time of hospital admission. Young age group of snakebite patients develops acute kidney injury more commonly.

  17. The Role of M2 Macrophages in the Progression of Chronic Kidney Disease following Acute Kidney Injury.

    Directory of Open Access Journals (Sweden)

    Myung-Gyu Kim

    Full Text Available Acute kidney injury (AKI is a major risk factor in the development of chronic kidney disease (CKD. However, the mechanisms linking AKI to CKD remain unclear. We examined the alteration of macrophage phenotypes during an extended recovery period following ischemia/reperfusion injury (IRI and determine their roles in the development of fibrosis.The left renal pedicle of mice was clamped for 40 min. To deplete monocyte/macrophage, liposome clodronate was injected or CD11b-DTR and CD11c-DTR transgenic mice were used.Throughout the phase of IRI recovery, M2-phenotype macrophages made up the predominant macrophage subset. On day 28, renal fibrosis was clearly shown with increased type IV collagen and TGF-β. The depletion of macrophages induced by the liposome clodronate injection improved renal fibrosis with a reduction of kidney IL-6, type IV collagen, and TGF-β levels. Additionally, the adoptive transfer of the M2c macrophages partially reversed the beneficial effect of macrophage depletion, whereas the adoptive transfer of the M1 macrophages did not. M2 macrophages isolated from the kidneys during the recovery phase expressed 2.5 fold higher levels of TGF-β than the M1 macrophages. The injection of the diphtheria toxin into CD11b or CD11c-DTR transgenic mice resulted in lesser depletion or no change in M2 macrophages and had little impact on renal fibrosis.Although M2 macrophages are known to be indispensible for short-term recovery, they are thought to be main culprit in the development of renal fibrosis following IRI.

  18. Acute Kidney Injury Secondary to NSAID Diagnosed on 99mTc MDP Bone Scan

    Directory of Open Access Journals (Sweden)

    Özhan Özdoğan

    2013-08-01

    Full Text Available A bone scan with 99mTc MDP was obtained to rule out the presence of micro fractures in a patient with the diagnosis of idiopathic osteoporosis. There was not any sign of micro fractures, but interestingly, both kidneys were diffusely very active. A differential diagnosis of acute kidney injury secondary to the use of nonsteroidal anti-inflammatory drug was made and reported after elimination of other clinical situations. The renal functions obtained following bone scan were impaired. The anti-inflammatory drug was discontinued. The renal functions were recovered starting with the following day.

  19. The first case of atrial fibrillation-related graft kidney infarction following acute pyelonephritis.

    Science.gov (United States)

    Tsai, Shang-Feng

    2014-01-01

    Native renal infarction is uncommon in patients with atrial fibrillation (AF)-related thromboembolism. Graft infarction is also rare, with such cases mostly occurring in the main graft artery postoperatively. To date, there have been no studies of AF-related graft kidney infarction. We herein describe the first case of AF-related graft kidney infarction. The clinical manifestations of this condition mimic and follow those of acute pyelonephritis; therefore, these diseases should be differentially diagnosed as early as possible using lactic dehydrogenase testing and computed tomography. Aggressive treatment with intravascular thrombolysis should be administered, even when the diagnosis is delayed, in order to restore a viable renal function.

  20. Fungal granulomatous interstitial nephritis presenting as acute kidney injury diagnosed by renal histology including PCR assay.

    Science.gov (United States)

    Ogura, Makoto; Kagami, Shino; Nakao, Masatsugu; Kono, Midori; Kanetsuna, Yukiko; Hosoya, Tatsuo

    2012-10-01

    We describe two cases of fungal granulomatous interstitial nephritis (GIN) presenting as acute kidney injury (AKI). Increased serum creatinine was detected in Patient 1 after chemotherapy for pharyngeal cancer and in Patient 2 after steroid pulse therapy for bronchial asthma. Renal histology of both patients revealed GIN. Polymerase chain reaction (PCR)-based detection of fungal DNA sequences from kidney tissue demonstrated Trichosporon laibachii and Candida albicans, respectively. When AKI occurs in an immunocompromised host, differential diagnosis of fungal interstitial nephritis should be considered. Furthermore, PCR-based detection of fungal DNA sequences from renal specimens can be useful for rapid diagnosis.

  1. Acute pancreatitis induced by mycophenolate mofetil in a kidney transplant patient

    Directory of Open Access Journals (Sweden)

    Einollahi Behzad

    2015-04-01

    Full Text Available Acute pancreatitis is a rare life-threatening complication in patients after kidney transplantation. Here we described a 56-year-old man who had received a living related kidney transplant for an end-stage renal disease. In his regular follow-up, his serum creatinine was gradually increased and he underwent an allograft biopsy, which revealed an interstitial nephritis/tubular atrophy grade II. Mycophenolate mofetil (MMF was prescribed to control chronic allograft nephropathy. He presented with complaints of severe abdominal pain, vomiting, loss of appetite and fever requiring hospital admission twelve days later. Acute pancreatitis was diagnosed on the basis of laboratory data and imaging findings during hospital admission. There was no history of alcohol consumption in our patient. Unfortunately he died one week later and autopsy findings demonstrated acute necrotizing pancreatitis. The bladder drainage of this patients was normal. Laboratory findings in this patient did not endorse infections and other possibilities regarding the etiology of acute pancreatitis in this patient. Therefore, we concluded that acute pancreatitis in near the patient was induced by drugs and basis on our evidence, MMF is the most important suspect. This study suggests that acute pancreatitis can be considered as a side effect of MMF.

  2. Nonpharmacological Strategies to Prevent Contrast-Induced Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    Paweena Susantitaphong

    2014-01-01

    Full Text Available Contrast-induced AKI (CI-AKI has been one of the leading causes for hospital-acquired AKI and is associated with independent risk for adverse clinical outcomes including morbidity and mortality. The aim of this review is to provide a brief summary of the studies that focus on nonpharmacological strategies to prevent CI-AKI, including routine identification of at-risk patients, use of appropriate hydration regimens, withdrawal of nephrotoxic drugs, selection of low-osmolar contrast media or isoosmolar contrast media, and using the minimum volume of contrast media as possible. There is no need to schedule dialysis in relation to injection of contrast media or injection of contrast agent in relation to dialysis program. Hemodialysis cannot protect the poorly functioning kidney against CI-AKI.

  3. A new model to predict acute kidney injury requiring renal replacement therapy after cardiac surgery

    Science.gov (United States)

    Pannu, Neesh; Graham, Michelle; Klarenbach, Scott; Meyer, Steven; Kieser, Teresa; Hemmelgarn, Brenda; Ye, Feng; James, Matthew

    2016-01-01

    Background: Acute kidney injury after cardiac surgery is associated with adverse in-hospital and long-term outcomes. Novel risk factors for acute kidney injury have been identified, but it is unknown whether their incorporation into risk models substantially improves prediction of postoperative acute kidney injury requiring renal replacement therapy. Methods: We developed and validated a risk prediction model for acute kidney injury requiring renal replacement therapy within 14 days after cardiac surgery. We used demographic, and preoperative clinical and laboratory data from 2 independent cohorts of adults who underwent cardiac surgery (excluding transplantation) between Jan. 1, 2004, and Mar. 31, 2009. We developed the risk prediction model using multivariable logistic regression and compared it with existing models based on the C statistic, Hosmer–Lemeshow goodness-of-fit test and Net Reclassification Improvement index. Results: We identified 8 independent predictors of acute kidney injury requiring renal replacement therapy in the derivation model (adjusted odds ratio, 95% confidence interval [CI]): congestive heart failure (3.03, 2.00–4.58), Canadian Cardiovascular Society angina class III or higher (1.66, 1.15–2.40), diabetes mellitus (1.61, 1.12–2.31), baseline estimated glomerular filtration rate (0.96, 0.95–0.97), increasing hemoglobin concentration (0.85, 0.77–0.93), proteinuria (1.65, 1.07–2.54), coronary artery bypass graft (CABG) plus valve surgery (v. CABG only, 1.25, 0.64–2.43), other cardiac procedure (v. CABG only, 3.11, 2.12–4.58) and emergent status for surgery booking (4.63, 2.61–8.21). The 8-variable risk prediction model had excellent performance characteristics in the validation cohort (C statistic 0.83, 95% CI 0.79–0.86). The net reclassification improvement with the prediction model was 13.9% (p < 0.001) compared with the best existing risk prediction model (Cleveland Clinic Score). Interpretation: We have developed

  4. Delayed Diagnosis of Falciparum Malaria with Acute Kidney Injury.

    Science.gov (United States)

    Choi, Iee Ho; Hwang, Pyoung Han; Choi, Sam Im; Lee, Dae Yeol; Kim, Min Sun

    2016-09-01

    Prompt malaria diagnosis is crucial so antimalarial drugs and supportive care can then be rapidly initiated. A 15-year-old boy who had traveled to Africa (South Africa, Kenya, and Nigeria between January 3 and 25, 2011) presented with fever persisting over 5 days, headache, diarrhea, and dysuria, approximately 17 days after his return from the journey. Urinalysis showed pyuria and hematuria. Blood examination showed hemolytic anemia, thrombocytopenia, disseminated intravascular coagulation, and hyperbilirubinemia. Plasmapheresis and hemodialysis were performed for 19 hospital days. Falciparum malaria was then confirmed by peripheral blood smear, and antimalarial medications were initiated. The patient's condition and laboratory results were quickly normalized. We report a case of severe acute renal failure associated with delayed diagnosis of falciparum malaria, and primary use of supportive treatment rather than antimalarial medicine. The present case suggests that early diagnosis and treatment is important because untreated tropical malaria can be associated with severe acute renal failure and fatality. Physicians must be alert for correct diagnosis and proper management of imported tropical malaria when patients have travel history of endemic areas. PMID:27510397

  5. Bardoxolone methyl (BARD) ameliorates aristolochic acid (AA)-induced acute kidney injury through Nrf2 pathway

    International Nuclear Information System (INIS)

    Bardoxolone methyl (BARD) is an antioxidant modulator that acts through induction of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. This study aimed to investigate the role of BARD in protecting kidneys from aristolochic acid (AA)-induced acute kidney injury (AKI). Male C57BL/6 mice received intraperitoneal (i.p.) injections of aristolochic acid I (AAI) (5 mg/kg/day) for 5 days to produce acute AA nephropathy (AAN) model. BARD (10 mg/kg/day, i.p.) was applied for 7 consecutive days, starting 2 days prior to AAI administration. The mice in the AA group showed AKI as evidenced by worsening kidney function evaluated by blood urea nitrogen (BUN) and serum creatinine (SCr) levels, and severe tubulointerstitial injury marked by massive tubule necrosis in kidney tissues. BARD significantly reduced BUN and SCr levels which were elevated by AAI. Additionally, AAI-induced histopathological renal damage was ameliorated by BARD. Furthermore, the expression of Nrf2 was reduced, and its repressor Kelch-like ECH-associated protein 1 (Keap1) was increased significantly, whereas heme oxygenase-1 (HO-1) was upregulated and NAD(P)H quinone oxidoreductase-1 (NQO1) was barely increased in the cytoplasm of tubules in kidneys after treatment with AAI. BARD significantly upregulated renal Nrf2, NQO1 and HO-1 expression and downregulated Keap1 expression compared with those in the AA group. Moreover, it was found that Nrf2 was expressed both in the cytoplasm and nuclear of glomeruli and tubules, whereas NQO1 and HO-1 were localized in the cytoplasm of tubules only. In conclusion, AA-induced acute renal injury was associated with impaired Nrf2 activation and expression of its downstream target genes in renal tissues. BARD prevented renal damage induced by AAI, and this renoprotective effect may be exerted by activating the Nrf2 signaling pathway and increasing expression of the downstream target genes

  6. Treatment disparities in acute coronary syndromes, heart failure, and kidney disease.

    Science.gov (United States)

    McCullough, Peter A; Maynard, Robert C

    2011-01-01

    It has been consistently observed that patients with renal dysfunction have more premature, severe, complicated, and fatal cardiovascular disease than age- and sex-matched individuals with normal renal function. There have been 4 major explanations for this finding: (1) positive confounding by third variables associated with chronic kidney disease (CKD), including diabetes mellitus and hypertension; (2) therapeutic nihilism or lesser use of beneficial therapies in CKD; (3) greater toxicities of therapies, such as bleeding from anticoagulants or contrast-induced kidney injury; (4) biological factors which result directly from CKD that work to promote and accelerate cardiovascular disease. In this paper, we focus on the issue of treatment disparities or therapeutic nihilism and its contribution to poor outcomes in the setting of acute coronary syndromes and acutely decompensated heart failure. This issue is important because if we can overcome barriers to the utilization of beneficial treatments, then clinical outcomes should improve over time. PMID:21625092

  7. A feasible strategy for preventing blood clots in critically ill patients with acute kidney injury (FBI)

    DEFF Research Database (Denmark)

    Robinson, Sian I.; Zincuk, A.; Larsen, U. L.;

    2014-01-01

    BACKGROUND: Previous pharmacokinetic trials suggested that 40 mg subcutaneous enoxaparin once daily provided inadequate thromboprophylaxis for intensive care unit patients. Critically ill patients with acute kidney injury are at increased risk of venous thromboembolism and yet are often excluded...... from these trials. We hypothesized that for critically ill patients with acute kidney injury receiving continuous renal replacement therapy, a dose of 1 mg/kg enoxaparin subcutaneously once daily would improve thromboprophylaxis without increasing the risk of bleeding. In addition, we seek to utilize...... urine output prior to discontinuing dialysis, and low neutrophil gelatinase-associated lipocalin in dialysis-free intervals, as markers of renal recovery. METHODS/DESIGN: In a multicenter, double-blind randomized controlled trial in progress at three intensive care units across Denmark, we randomly...

  8. Unilateral Renal Ischemia as a Model of Acute Kidney Injury and Renal Fibrosis in Cats.

    Science.gov (United States)

    Schmiedt, C W; Brainard, B M; Hinson, W; Brown, S A; Brown, C A

    2016-01-01

    The objectives of this study were to define the acute and chronic effects of 1-hour unilateral in vivo renal ischemia on renal function and histology in cats. Twenty-one adult purpose-bred research cats were anesthetized, and 1 kidney underwent renal artery and vein occlusion for 1 hour. Serum creatinine and urea concentrations, urine protein:creatinine ratio, urine-specific gravity, glomerular filtration rate, hematocrit, platelet concentration and function, and white blood cell count were measured at baseline and variable time points after ischemia. Renal histopathology was evaluated on days 3, 6, 12, 21, 42, and 70 postischemia; changes in smooth muscle actin and interstitial collagen were examined. Following ischemia, whole animal glomerular filtration rate was significantly reduced (57% of baseline on day 6; P cats and demonstrates that ischemic acute kidney injury triggers chronic fibrosis, interstitial inflammation, and tubular atrophy in feline kidneys. These late changes are typical of those observed in cats with naturally occurring chronic kidney disease. PMID:26319781

  9. Acute kidney injury and disseminated intravascular coagulation due to mercuric chloride poisoning

    OpenAIRE

    Dhanapriya, J.; Gopalakrishnan, N; Arun, V.; Dineshkumar, T.; Sakthirajan, R.; Balasubramaniyan, T.; Haris, M

    2016-01-01

    Mercury is a toxic heavy metal and occurs in organic and inorganic forms. Inorganic mercury includes elemental mercury and mercury salts. Mercury salts are usually white powder or crystals, and widely used in indigenous medicines and folk remedies in Asia. Inorganic mercury poisoning causes acute kidney injury (AKI) and gastrointestinal manifestations and can be life-threatening. We describe a case with unknown substance poisoning who developed AKI and disseminated intravascular coagulation (...

  10. Measuring biomarkers of acute kidney injury during renal replacement therapy: wisdom or folly?

    Science.gov (United States)

    Ostermann, Marlies; Forni, Lui G

    2014-06-19

    Early data are now appearing relating to the measurement of biomarkers of acute kidney injury during renal replacement therapy. These data go some way in describing the clearance of these molecules during renal support. Understanding the potential clearance, or otherwise, of these proteins may lead to directing our therapies in the future particularly with regard to cessation of renal support. We describe a recent study which has provided data that may aid in addressing this issue.

  11. Recurrent Acute Pancreatitis and Cholangitis in a Patient with Autosomal Dominant Polycystic Kidney Disease

    OpenAIRE

    Kambiz Yazdanpanah; Navid Manouchehri; Elinaz Hosseinzadeh; Mohammad Hassan Emami; Mehdi Karami; Amir Hossein Sarrami

    2013-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder associated with multiple cyst formation in the different organs. Development of pancreatic cyst in ADPKD is often asymptomatic and is associated with no complication. A 38-year-old man with ADPKD was presented with six episodes of acute pancreatitis and two episodes of cholangitis in a period of 12 months. Various imaging studies revealed multiple renal, hepatic and pancreatic cysts, mild ectasia of pancreatic duct,...

  12. Urinary liver-type fatty acid-binding protein predicts adverse outcomes in acute kidney injury

    OpenAIRE

    Ferguson, Michael A.; Vaidya, Vishal S.; Waikar, Sushrut S.; Collings, Fitz B.; Sunderland, Kelsey E.; Gioules, Costas J.; Bonventre, Joseph V.

    2009-01-01

    Acute kidney injury (AKI) is a common condition with significant associated morbidity and mortality. The insensitivity and non-specificity of traditional markers of renal dysfunction prevent timely diagnosis, estimation of the severity of renal injury, and the administration of possible therapeutic agents. Here, we determine the prognostic ability of urinary liver-type fatty acid-binding protein (L-FABP), and further characterize its sensitivity and specificity as a biomarker of AKI. Initial ...

  13. Comparison of three early biomarkers for acute kidney injury after cardiac surgery under cardiopulmonary bypass

    OpenAIRE

    Moriyama, Takahiro; Hagihara, Shintaro; Shiramomo, Toko; Nagaoka, Misaki; Iwakawa, Shohei; Kanmura, Yuichi

    2016-01-01

    Background Acute kidney injury (AKI) is a serious complication after cardiac surgery, being associated with a high mortality. We assessed three urinary biomarkers, L-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), and angiotensinogen, which are elevated through different mechanisms, and investigated which of these biomarkers was the earliest and most useful indicator of AKI after cardiac surgery. Methods This study was a prospective observational s...

  14. Postoperative intubation time is associated with acute kidney injury in cardiac surgical patients

    OpenAIRE

    Heringlake, Matthias; Nowak, Yvonne; Schön, Julika; Trautmann, Jens; Berggreen, Astrid Ellen; Charitos, Efstratios I.; Paarmann, Hauke

    2014-01-01

    Introduction Acute kidney injury (AKI) is a frequent complication after cardiac surgery and is associated with a poor prognosis. Mechanical ventilation is an important risk factor for developing AKI in critically ill patients. Ventilation with high tidal volumes has been associated with postoperative organ dysfunction in cardiac surgical patients. No data are available about the effects of the duration of postoperative respiratory support in the immediate postoperative period on the incidence...

  15. Post Cardiac Surgery Acute Kidney Injury: A Woebegone Status Rejuvenated by the Novel Biomarkers

    OpenAIRE

    Jayaraman, Rajesh; Sunder, Sham; Sathi, Satyanand; Gupta, Vijay Kumar; Sharma, Neera; Kanchi, Prabhu; Gupta, Anurag; Daksh, Sunil Kumar; Ram, Pranith; Mohamed, Ashik

    2014-01-01

    Background: Acute kidney injury (AKI) is common after cardiac surgery, the incidence varying between 7.7% and 28.1%. It significantly increases morbidity and mortality. Creatinine considerably delays the diagnosis with its own attended demerits. Novel urinary biomarkers are emerging which help in rapid diagnosis thus reducing the morbidity and mortality. Biomarkers of our study were neutrophil gelatinase-associated lipocalin (NGAL) and Interleukin-18 (IL-18). Objectives: To find out the incid...

  16. Acute kidney injury: risk factors and management challenges in developing countries

    OpenAIRE

    Ponce, Daniela; Balbi, Andre

    2016-01-01

    Daniela Ponce, Andre Balbi Department of Medicine, Botucatu School of Medicine, Sao Paulo, Brazil Abstract: Acute kidney injury (AKI) is a major global health problem in both developed and developing nations, negatively affecting patient morbidity and responsible for an estimated 1.4 million deaths per year. Although the International Society of Nephrology set a goal of eliminating preventable deaths from AKI by 2025, implementation of this program in developing countries presents ma...

  17. Urine NGAL Predicts Severity of Acute Kidney Injury After Cardiac Surgery: A Prospective Study

    OpenAIRE

    Bennett, Michael; Dent, Catherine L; Ma, Qing; Dastrala, Sudha; Grenier, Frank; Workman, Ryan; Syed, Hina; Ali, Salman; Barasch, Jonathan; Devarajan, Prasad

    2008-01-01

    Background and objectives: The authors have previously shown that urine neutrophil gelatinase-associated lipocalin (NGAL), measured by a research ELISA, is an early predictive biomarker of acute kidney injury (AKI) after cardiopulmonary bypass (CPB). In this study, whether an NGAL immunoassay developed for a standardized clinical platform (ARCHITECT analyzer®, Abbott Diagnostics Division, Abbott Laboratories, Abbott Park, IL) can predict AKI after CPB was tested.

  18. Hypotension as a Risk Factor for Acute Kidney Injury in ICU Patients

    OpenAIRE

    Lehman, Li-Wei; Saeed, Mohammed; Moody, George; Mark, Roger

    2010-01-01

    In the context of critical illness, hypotension may be associated with acute kidney injury (AKI). Using the MIMIC II database, we studied the risk of AKI in ICU patients as a function of both the severity and duration of hypotension. Multivariate logistical regression was performed to find correlations between hypotension and AKI. Minimum mean arterial blood pressure (MAP) and the amount of time MAP was below a range of hypotension thresholds in a target 48-hour window (prior to AKI onset) we...

  19. Diagnostic accuracy of urinary neutrophil gelatinase-associated lipocalin in patients with septic acute kidney injury

    OpenAIRE

    Patel, Munna

    2016-01-01

    Munna Lal Patel,1 Rekha Sachan,2 Radhey Shyam,3 Satish Kumar,1 Ritul Kamal,4 Arvind Misra1 1Department of Medicine, 2Department of Obstetrics & Gynaecology, 3Department of Geriatric Intensive Care Unit, King George Medical University, 4Epidemiology Division, Council of Scientific and Industrial Research (CSIR-IITR), Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India Background: Sepsis is the most common cause of acute kidney injury (AKI). Very few studies have inve...

  20. Incidence, Characteristics and Risk Factors of Acute Kidney Injury among Dengue Patients: A Retrospective Analysis

    OpenAIRE

    Tauqeer Hussain Mallhi; Amer Hayat Khan; Azreen Syazril Adnan; Azmi Sarriff; Yusra Habib Khan; Fauziah Jummaat

    2015-01-01

    Background Dengue induced acute kidney injury (AKI) imposes heavy burden of illness in terms of morbidity and mortality. A retrospective study was conducted to investigate incidence, characteristics, risk factors and clinical outcomes of AKI among dengue patients. Methodology A total 667 dengue patients (2008–2013) were retrospectively evaluated and were stratified into AKI and non-AKI groups by using AKIN criteria. Two groups were compared by using appropriate statistical methods. Results Th...

  1. Admission hyperuricemia increases the risk of acute kidney injury in hospitalized patients *

    OpenAIRE

    Cheungpasitporn, Wisit; Thongprayoon, Charat; Harrison, Andrew M.; Erickson, Stephen B.

    2015-01-01

    Background The association between elevated admission serum uric acid (SUA) and risk of in-hospital acute kidney injury (AKI) is limited. The aim of this study was to assess the risk of developing AKI in all hospitalized patients with various admission SUA levels. Methods This is a single-center retrospective study conducted at a tertiary referral hospital. All hospitalized adult patients who had admission SUA available from January 2011 through December 2013 were analyzed in this study. Admi...

  2. Heterogeneity of epigenetic changes at ischemia/reperfusion- and endotoxin-induced acute kidney injury genes

    OpenAIRE

    Mar, Daniel; Gharib, Sina A; Zager, Richard A.; Johnson, Ali; Denisenko, Oleg; Bomsztyk, Karol

    2015-01-01

    Aberrant gene expression is a molecular hallmark of acute kidney injury (AKI). Since epigenetic processes control gene expression in a cell- and environment-defined manner, understanding the epigenetic pathways that regulate genes altered by AKI may open vital new insights into the complexities of disease pathogenesis and identify possible therapeutic targets. Here we used matrix chromatin immunoprecipitation and integrative analysis to study twenty key permissive and repressive epigenetic hi...

  3. Pharmacokinetics of salicylate in rabbits with acute kidney failure

    International Nuclear Information System (INIS)

    Changes in the pharmacokinetics and metabolism of sodium salicylate were studied in rabbits with acute renal failure induced by intravenous administration of uranyl nitrate hexahydrate in a dose of 0.2 mg kg-1. 14C-labelled salicylic acid, 99mTc-complex and 125I-hippuran were used to study the metabolism. The 99mTc and 125I activities were measured with a Tesla gamma counter or beta-gamma spectrometer NE 8312. The 14C activity was measured using beta spectrometer Rack beta 1219. The 99mTc activity was determined immediately after the experiment, the 14C activity was determined after 4 days. The drug concentration was determined by comparing the activities of the sample and the standard activities. (J.J.). 6 figs., 1 tab., 18 refs

  4. Outcome assessment of pregnancy-related acute kidney injury in Morocco: A national prospective study.

    Science.gov (United States)

    Kabbali, Nadia; Tachfouti, Nabil; Arrayhani, Mohammed; Harandou, Mustapha; Tagnaouti, Mounia; Bentata, Yassamine; Laouad, Inass; Ramdani, Benyounes; Bayahia, Rabia; Oualim, Zouhair; Houssaini, Tarik Sqalli

    2015-01-01

    Acute kidney injury (AKI) is a rare but life-threatening complication of pregnancy. The aim of this paper is to study the characteristics of acute AKI in pregnancy and to emphasize on its management modalities in Moroccan hospitals. This is a national prospective study performed over six months from July 1 to December 31 2010 on AKI developing in pregnant patients, both preand post-partum period. Patients with pre-existing kidney disease were excluded from the study. Outcome was considered unfavorable when complete recovery of renal function was not achieved and/or maternal death occurred. Forty-four patients were included in this study. They were 29.6 ± 6 years old and mostly illiterate (70.6%). Most AKI occurred in the post-partum period, with 66% of the cases occurring in those who did not receive antenatal care. The main etiologies were pre-eclampsia (28 cases), hemorrhagic shock (six cases) and septic events (five cases). We noted three cases of acute fatty liver, one case of obstructive kidney injury and one case of lupus nephritis. Hemodialysis was necessary in 17 (38.6%) cases. The outcome was favorable in 29 patients. The maternal mortality rate was 11.4%. Two poor prognostic factors were identified: Age over 38 years and sepsis. AKI is a severe complication of pregnancy in developing countries. Its prevention necessitates the improvement of the sanitary infrastructure and the establishment of the obligatory antenatal care. PMID:26022044

  5. Outcome assessment of pregnancy-related acute kidney injury in Morocco: A national prospective study

    Directory of Open Access Journals (Sweden)

    Nadia Kabbali

    2015-01-01

    Full Text Available Acute kidney injury (AKI is a rare but life-threatening complication of pregnancy. The aim of this paper is to study the characteristics of acute AKI in pregnancy and to emphasize on its management modalities in Moroccan hospitals. This is a national prospective study performed over six months from July 1 to December 31 2010 on AKI developing in pregnant patients, both preand post-partum period. Patients with pre-existing kidney disease were excluded from the study. Outcome was considered unfavorable when complete recovery of renal function was not achieved and/or maternal death occurred. Forty-four patients were included in this study. They were 29.6 ± 6 years old and mostly illiterate (70.6%. Most AKI occurred in the post-partum period, with 66% of the cases occurring in those who did not receive antenatal care. The main etiologies were pre-eclampsia (28 cases, hemorrhagic shock (six cases and septic events (five cases. We noted three cases of acute fatty liver, one case of obstructive kidney injury and one case of lupus nephritis. Hemodialysis was necessary in 17 (38.6% cases. The outcome was favorable in 29 patients. The maternal mortality rate was 11.4%. Two poor prognostic factors were identified: Age over 38 years and sepsis. AKI is a severe complication of pregnancy in developing countries. Its prevention necessitates the improvement of the sanitary infrastructure and the establishment of the obligatory antenatal care.

  6. Contrast-induced acute kidney injury: short- and long-term implications.

    Science.gov (United States)

    Weisbord, Steven D; Palevsky, Paul M

    2011-05-01

    The intravascular administration of iodine-based contrast media remains a common cause of acute kidney injury and a leading cause of iatrogenic renal disease. Past research has elucidated the principal risk factors for contrast-induced acute kidney injury (CIAKI) and helped to establish the efficacy of various interventions for the prevention of this condition. The importance of preventing CIAKI has been underscored by a growing number of studies showing strong associations of CIAKI with serious adverse short- and long-term outcomes. However, it remains unclear whether these associations are causal. This is important because considerable health care resources are used to prevent CIAKI. If CIAKI is a marker, but not a mediator, of serious adverse downstream outcomes, more judicious and selective use of preventive care may be appropriate. Moreover, with an increasing number of studies reporting the underuse of coronary angiography in patients with acute coronary syndrome and underlying chronic kidney disease, presumably in part because of a fear of CIAKI, a clear understanding of whether this condition directly results in adverse downstream outcomes is essential. Careful inspection of past studies that investigated the association of CIAKI with adverse short- and long-term events sheds light on their strengths and weaknesses and provides insight into how future research may be better able to characterize the short- and long-term implications of this iatrogenic condition.

  7. Difficulties in diagnosing acute kidney injury post liver transplantation using serum creatinine based diagnostic criteria

    Institute of Scientific and Technical Information of China (English)

    Banwari; Agarwal; Andrew; Davenport

    2014-01-01

    Renal function in patients with advanced cirrhosis is an important prognostic factor for survival both prior to and following liver transplantation. The importance of renal function is reflected by the introduction of the model for end stage liver disease(MELD) score, which includes serum creatinine. The MELD score has been shown to predict the short term risk of death for transplant wait listed patients and is currently used by many countries to allocate liver transplants on the basis of severity of underlying illness. Changes in serum creatinine are also used to stage acute kidney injury. However prior to liver transplantation the serum creatinine typically over estimates underlying renal function, particularly when a colorimetric Jaffe based assay is used, and paradoxically then under estimates renal function post liver transplantation, particularly when immunophyllins are started early as part of transplant immunosuppression. As acute kidney injury is defined by changes in serum creatinine, this potentially leads to over estimation of the incidence and severity of acute kidney injury in the immediate post-operative period.

  8. Oral Supplementation of Glucosamine Fails to Alleviate Acute Kidney Injury in Renal Ischemia-Reperfusion Damage

    Science.gov (United States)

    Johnsen, Marc; Späth, Martin Richard; Denzel, Martin S.; Göbel, Heike; Kubacki, Torsten; Hoyer, Karla Johanna Ruth; Hinze, Yvonne; Benzing, Thomas; Schermer, Bernhard; Antebi, Adam; Burst, Volker; Müller, Roman-Ulrich

    2016-01-01

    Acute kidney injury is a leading contributor to morbidity and mortality in the ageing population. Proteotoxic stress response pathways have been suggested to contribute to the development of acute renal injury. Recent evidence suggests that increased synthesis of N-glycan precursors in the hexosamine pathway as well as feeding of animals with aminosugars produced in the hexosamine pathway may increase stress resistance through reducing proteotoxic stress and alleviate pathology in model organisms. As feeding of the hexosamine pathway metabolite glucosamine to aged mice increased their life expectancy we tested whether supplementation of this aminosugar may also protect mice from acute kidney injury after renal ischemia and reperfusion. Animals were fed for 4 weeks ad libitum with standard chow or standard chow supplemented with 0.5% N-acetylglucosamine. Preconditioning with caloric restriction for four weeks prior to surgery served as a positive control for protective dietary effects. Whereas caloric restriction demonstrated the known protective effect both on renal function as well as survival in the treated animals, glucosamine supplementation failed to promote any protection from ischemia-reperfusion injury. These data show that although hexosamine pathway metabolites have a proven role in enhancing protein quality control and survival in model organisms oral glucosamine supplementation at moderate doses that would be amenable to humans does not promote protection from ischemia-reperfusion injury of the kidney. PMID:27557097

  9. Attenuation of cisplatin-induced emetogenesis by standardized Bacopa monnieri extracts in the pigeon: behavioral and neurochemical correlations.

    Science.gov (United States)

    Ullah, Ihsan; Subhan, Fazal; Rudd, John A; Rauf, Khalid; Alam, Javaid; Shahid, Muhammad; Sewell, Robert D E

    2014-11-01

    Nausea and vomiting are the most distressing and common side effects of cancer chemotherapy which often result in patient noncompliance. In the present study, standardized methanolic and n-butanolic fractions of Bacopa monnieri were evaluated against cisplatin-induced emesis in the pigeon in relation to their activity on central and intestinal neurotransmitters levels. Cisplatin (7.0 mg/kg, i. v.) induced reproducible emesis without lethality in healthy pigeons. The methanolic (10-40 mg/kg) and the bacoside-rich n-butanolic fractions of B. monnieri (5-20 mg/kg), as well as the antioxidant N-(2-mercaptopropionyl) glycine (10 mg/kg), attenuated cisplatin-induced emesis by 66.3% (p bacoside-rich n-butanolic fractions might be a valuable adjunct in the treatment of emetogenic chemotherapy, and this warrants further study in other models of emesis.

  10. The potential use of biomarkers in predicting contrast-induced acute kidney injury

    Science.gov (United States)

    Andreucci, Michele; Faga, Teresa; Riccio, Eleonora; Sabbatini, Massimo; Pisani, Antonio; Michael, Ashour

    2016-01-01

    Contrast-induced acute kidney injury (CI-AKI) is a problem associated with the use of iodinated contrast media, causing kidney dysfunction in patients with preexisting renal failure. It accounts for 12% of all hospital-acquired kidney failure and increases the length of hospitalization, a situation that is worsening with increasing numbers of patients with comorbidities, including those requiring cardiovascular interventional procedures. So far, its diagnosis has relied upon the rise in creatinine levels, which is a late marker of kidney damage and is believed to be inadequate. Therefore, there is an urgent need for biomarkers that can detect CI-AKI sooner and more reliably. In recent years, many new biomarkers have been characterized for AKI, and these are discussed particularly with their use in known CI-AKI models and studies and include neutrophil gelatinase-associated lipocalin, cystatin C (Cys-C), kidney injury molecule-1, interleukin-18, N-acetyl-β-d-glucosaminidase, and L-type fatty acid-binding protein (L-FABP). The potential of miRNA and metabolomic technology is also mentioned. Early detection of CI-AKI may lead to early intervention and therefore improve patient outcome, and in future any one or a combination of several of these markers together with development in technology for their analysis may prove effective in this respect. PMID:27672338

  11. Acute kidney injury in the perioperative period and in intensive care units (excluding renal replacement therapies).

    Science.gov (United States)

    Ichai, Carole; Vinsonneau, Christophe; Souweine, Bertrand; Armando, Fabien; Canet, Emmanuel; Clec'h, Christophe; Constantin, Jean-Michel; Darmon, Michaël; Duranteau, Jacques; Gaillot, Théophille; Garnier, Arnaud; Jacob, Laurent; Joannes-Boyau, Olivier; Juillard, Laurent; Journois, Didier; Lautrette, Alexandre; Muller, Laurent; Legrand, Matthieu; Lerolle, Nicolas; Rimmelé, Thomas; Rondeau, Eric; Tamion, Fabienne; Walrave, Yannick; Velly, Lionel

    2016-12-01

    Acute kidney injury (AKI) is a syndrome that has progressed a great deal over the last 20 years. The decrease in urine output and the increase in classical renal biomarkers, such as blood urea nitrogen and serum creatinine, have largely been used as surrogate markers for decreased glomerular filtration rate (GFR), which defines AKI. However, using such markers of GFR as criteria for diagnosing AKI has several limits including the difficult diagnosis of non-organic AKI, also called "functional renal insufficiency" or "pre-renal insufficiency". This situation is characterized by an oliguria and an increase in creatininemia as a consequence of a reduction in renal blood flow related to systemic haemodynamic abnormalities. In this situation, "renal insufficiency" seems rather inappropriate as kidney function is not impaired. On the contrary, the kidney delivers an appropriate response aiming to recover optimal systemic physiological haemodynamic conditions. Considering the kidney as insufficient is erroneous because this suggests that it does not work correctly, whereas the opposite is occurring, because the kidney is healthy even in a threatening situation. With current definitions of AKI, normalization of volaemia is needed before defining AKI in order to avoid this pitfall. PMID:27230984

  12. Umbilical cord mesenchymal stem cell transplantation ameliorates burn-induced acute kidney injury in rats.

    Science.gov (United States)

    Lu, Gang; Huang, Sha; Chen, Yongbin; Ma, Kui

    2013-09-01

    Excessive systemic inflammation following burns could lead to acute kidney injury (AKI). Mesenchymal stromal cells (MSCs) suppress immune cell responses and have beneficial effects in various inflammatory-related immune disorders. However, autologous MSCs are not vital enough for the treatment because of the severely burned patients' deleterious condition. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) could be a suitable substitute cell candidate but no data are available on the therapeutic effectiveness of UC-MSCs transplantation for burn injury and its consequences. In this study, UC-MSCs or ulinastatin was administered intravenously in the rats with burn trauma, and the therapeutic effects of UC-MSCs on the survival of severe burn-induced AKI rats and functional protection of kidney were analyzed. Results showed that UC-MSCs promoted the survival and prevented commitment to apoptosis of resident kidney cells and reduced organ microscopic damage in kidneys after thermal trauma. Thus, our study demonstrates that intravenously delivered UC-MSCs protected the host from death caused by kidney injury subsequent to severe burn, identifying UC-MSCs transplantation may be an attractive candidate for cell-based treatments for burns and induced organ damage. PMID:24043673

  13. A European Renal Best Practice (ERBP) position statement on the Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guidelines on Acute Kidney Injury: part 2: renal replacement therapy.

    Science.gov (United States)

    Jörres, Achim; John, Stefan; Lewington, Andrew; ter Wee, Pieter M; Vanholder, Raymond; Van Biesen, Wim; Tattersall, James

    2013-12-01

    This paper provides an endorsement of the KDIGO guideline on acute kidney injury; more specifically, on the part that concerns renal replacement therapy. New evidence that has emerged since the publication of the KDIGO guideline was taken into account, and the guideline is commented on from a European perspective. Advice is given on when to start and stop renal replacement therapy in acute kidney injury; which modalities should be preferentially be applied, and in which conditions; how to gain access to circulation; how to measure adequacy; and which dose can be recommended.

  14. The potential use of biomarkers in predicting contrast-induced acute kidney injury

    Directory of Open Access Journals (Sweden)

    Andreucci M

    2016-09-01

    Full Text Available Michele Andreucci,1 Teresa Faga,1 Eleonora Riccio,2 Massimo Sabbatini,2 Antonio Pisani,2 Ashour Michael,1 1Department of Health Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, 2Department of Public Health, University of Naples Federico II, Naples, Italy Abstract: Contrast-induced acute kidney injury (CI-AKI is a problem associated with the use of iodinated contrast media, causing kidney dysfunction in patients with preexisting renal failure. It accounts for 12% of all hospital-acquired kidney failure and increases the length of hospitalization, a situation that is worsening with increasing numbers of patients with comorbidities, including those requiring cardiovascular interventional procedures. So far, its diagnosis has relied upon the rise in creatinine levels, which is a late marker of kidney damage and is believed to be inadequate. Therefore, there is an urgent need for biomarkers that can detect CI-AKI sooner and more reliably. In recent years, many new biomarkers have been characterized for AKI, and these are discussed particularly with their use in known CI-AKI models and studies and include neutrophil gelatinase-associated lipocalin, cystatin C (Cys-C, kidney injury molecule-1, interleukin-18, N-acetyl-β-d-glucosaminidase, and L-type fatty acid-binding protein (L-FABP. The potential of miRNA and metabolomic technology is also mentioned. Early detection of CI-AKI may lead to early intervention and therefore improve patient outcome, and in future any one or a combination of several of these markers together with development in technology for their analysis may prove effective in this respect. Keywords: radiocontrast media, acute renal failure, markers, renal injury

  15. Voluntary exercise prevents cisplatin-induced muscle wasting during chemotherapy in mice.

    Directory of Open Access Journals (Sweden)

    Pernille Hojman

    Full Text Available Loss of muscle mass related to anti-cancer therapy is a major concern in cancer patients, being associated with important clinical endpoints including survival, treatment toxicity and patient-related outcomes. We investigated effects of voluntary exercise during cisplatin treatment on body weight, food intake as well as muscle mass, strength and signalling. Mice were treated weekly with 4 mg/kg cisplatin or saline for 6 weeks, and randomized to voluntary wheel running or not. Cisplatin treatment induced loss of body weight (29.8%, P < 0.001, lean body mass (20.6%, P = 0.001, as well as anorexia, impaired muscle strength (22.5% decrease, P < 0.001 and decreased glucose tolerance. In addition, cisplatin impaired Akt-signalling, induced genes related to protein degradation and inflammation, and reduced muscle glycogen content. Voluntary wheel running during treatment attenuated body weight loss by 50% (P < 0.001, maintained lean body mass (P < 0.001 and muscle strength (P < 0.001, reversed anorexia and impairments in Akt and protein degradation signalling. Cisplatin-induced muscular inflammation was not prevented by voluntary wheel running, nor was glucose tolerance improved. Exercise training may preserve muscle mass in cancer patients receiving cisplatin treatment, potentially improving physical capacity, quality of life and overall survival.

  16. Cisplatin-induced premature senescence with concomitant reduction of gap junctions in human fibroblasts

    Institute of Scientific and Technical Information of China (English)

    Wei ZHAO; Zhong Xiang LIN; Zhi Qian ZHANG

    2004-01-01

    To examine the role of gap junctions in cell senescence,the changes of gap junctions in cisplatin-induced premature senescence of primary cultured fibroblasts were studied and compared with the replicative senescent human fibroblasts.Dye transfer assay for gap junction function and immunofluorescent staining for connexin 43 protein distribution were done respectively. Furthermore,cytofluorimetry and DAPI fluorescence staining were performed for cell cycle and apoptosis analysis. p53 gene expression level was detected with indirect immunofluorescence. We found that cisplatin (10 mM) treatment could block cell growth cycle at G1 and induced premature senescence. The premature senescence changes included high frequency of apoptosis,elevation of p53 expression,loss of membranous gap junctions and reduction of dye-transfer capacity. These changes were comparable to the changes of replicative senescence of human fibroblasts. It was also concluded that cisplatin could induce premature senescence concomitant with inhibition of gap junctions in the fibroblasts. Loss of functional gap junctions from the cell membrane may account for the reduced intercellular communication in the premature senescent fibroblasts. The cell system we used may provide a model useful for the study of the gap junction thus promoting agents against premature senescence.

  17. Syzygium Cumini (L. Seeds Extract Ameliorates Cisplatin Induced Hepatotoxicity in Male Wistar Rats

    Directory of Open Access Journals (Sweden)

    R.Maheswari

    2015-02-01

    Full Text Available The discovery of cisplatin, cis-[Pt(II(NH(3(2Cl(2] ([PtCl2(NH32] or CDDP, was a corner stone which triggered the interest in platinum(II-and other metal-containing compounds as potential anticancer drugs. Cisplatin, is one of the most potent chemotherapy drugs widely used for cancer treatment. In our present study, an attempt has been made to study the effect of Cisplatin on biochemical and histopathological parameters and ameliorating effects of the Syzygium cumini (L. aqueous seeds extract or Eugena Jambolana in male wistar rats. Adult male wistar rats were divided into four different groups. Group I Served as vehicle treated normal saline (Control, Group II Rats received single intra-peritoneal (Ip injection of cisplatin (7mg/kg bw, Group III received Syzygium cumini (L. aqueous seeds extract 400mg/kg/bw orally for 7 days beginning one day prior to cisplatin (CP injection. Group IV Rats received alone Syzygium cumini (L. aqueous seeds extract (400mg/kg bw treated. Cisplatin exposure leads to adverse effects on hematological, hepatotoxic parameters including Erythrocytes (RBCs. Cisplatin induction leads to reduction in the levels of Enzymic and Non-Enzymic antioxidants levels. However, on treatment with Syzygium cumini (L. aqueous seeds extract normalized the levels of all the biochemical and hematological parameters. These findings highlight the efficacy of Syzygium cumini (L. aqueous seeds extract as protective effects Cisplatin induced hepatotoxicity.

  18. The effects of oral grape seed extract on Cisplatin-induced cytogenotoxicity in mice

    International Nuclear Information System (INIS)

    The present investigation was directed to study the possible chemoprotective activity of orally administered grape seed extract (GSE) against cisplatin-induced cytotoxicity and genotoxicity towards mouse somatic and germinal cells in vivo. Pretreatment of mice with GSE (100mg/kg/day) for 7 days and simultaneously with a single dose of cisplatin (2.2 or 5.5 mg/kg, i.p.) for another day, significantly reduced the frequency of bone marrow micronucleated polychromatic erythrocytes by factors of 1.9 and 1.28, respectively. Furthermore, GSF caused a reduction in bone marrow suppression induced by cisplatin treatment, particularly before the lower dose. In mail germline, orally administration of GSE (100mg/kg/day) for 7 consecutive days before and 7 consecutives days after treatment with a single dose of cisplatin (2.2 or 5.5 mg/kg, i.p.), significantly elevated the levels of sperm motility reduced by cisplatin treatment. Furthermore, GSE significantly decreased the elevated levels sperm head abnormality induced with cisplatin by factors of 1.6 and 1.2, respectively. Our results indicate that GSE plays a role in attenuating the genotoxicity induced by cisplatin and many provide the development of secondary malignancy and abnormal reproductive outcomes risk. (author)

  19. CYSTATIN C AS A SURROGATE MARKER FOR EVALUATING GLOMERULAR FILTRATION RATE IN ACUTE KIDNEY INJURY

    Directory of Open Access Journals (Sweden)

    Davendra

    2016-07-01

    Full Text Available BACKGROUND The gold standard for measuring GFR has practical limitations in clinical practice; instead it is estimated by use of the serum concentration of endogenous filtration markers. The objective of this research was to compare serum cystatin C with serum creatinine for Estimating Glomerular Filtration Rate (eGFR in acute kidney injury and to determine whether elevated serum cystatin C has an impact on mortality in the presence of kidney injury. METHODS This prospective observation study was carried out for 18 months in our institution. It included all indoor Acute Kidney Injury (AKI patients more than 18 years, admitted in the Department of Medicine of our tertiary care centre. The renal function of the patients was evaluated by testing for serum creatinine and serum cystatin C. Serum creatinine based Cockcroft and Gault (CG equation and Estimated GFR (e-GFR with Modification of Diet in Renal Disease (MDRD equation were compared with serum cystatin C based e-GFR Hoek and Larsson equations. All-cause mortality was ascertained by examination of death certificates, inpatient hospital records. RESULTS A total of 90 patients were enrolled during the study. The mean serum creatinine (mg/dL 3.455±1.77, serum cystatin (mg/L 2.932±1.13, and creatinine clearance (CG 27.16±16.96, eGFR-MDRD (mL/min. 24.94±17.95, eGFR-Larsson 31.60±17.36 and eGFRHoek 29.00±17.39. The correlation of the Larsson and Hoek cystatin C based GFR estimates (r= 0.94; p=<0.001 and MDRD and CG serum creatinine based GFR estimates (r=-0.93; p<0.001 were highly significant. In multiple logistic regression analysis which included age, serum creatinine and serum cystatin C as variables, only serum cystatin C (p=0. 046 was found to be a significant factor influencing mortality in acute kidney injury. CONCLUSIONS The present study suggests that the cystatin C-based prediction equation achieved a diagnostic performance that was at least as good as the creatinine based formulas

  20. Biomarkers in the assessment of acute and chronic kidney diseases in the dog and cat.

    Science.gov (United States)

    Cobrin, A R; Blois, S L; Kruth, S A; Abrams-Ogg, A C G; Dewey, C

    2013-12-01

    In both human and veterinary medicine, diagnosing and staging renal disease can be difficult. Measurement of glomerular filtration rate is considered the gold standard for assessing renal function but methods for its assessment can be technically challenging and impractical. The main parameters used to diagnose acute and chronic kidney disease include circulating creatinine and urea concentrations, and urine-specific gravity. However, these parameters can be insensitive. Therefore, there is a need for better methods to diagnose and monitor patients with renal disease. The use of renal biomarkers is increasing in human and veterinary medicine for the diagnosis and monitoring of acute and chronic kidney diseases. An ideal biomarker would identify site and severity of injury, and correlate with renal function, among other qualities. This article will review the advantages and limitations of renal biomarkers that have been used in dogs and cats, as well as some markers used in humans that may be adapted for veterinary use. In the future, measuring a combination of biomarkers will likely be a useful approach in the diagnosis of kidney disorders. PMID:24152019

  1. Design of clinical trials in acute kidney injury: report from an NIDDK workshop on trial methodology.

    Science.gov (United States)

    Palevsky, Paul M; Molitoris, Bruce A; Okusa, Mark D; Levin, Adeera; Waikar, Sushrut S; Wald, Ron; Chertow, Glenn M; Murray, Patrick T; Parikh, Chirag R; Shaw, Andrew D; Go, Alan S; Faubel, Sarah G; Kellum, John A; Chinchilli, Vernon M; Liu, Kathleen D; Cheung, Alfred K; Weisbord, Steven D; Chawla, Lakhmir S; Kaufman, James S; Devarajan, Prasad; Toto, Robert M; Hsu, Chi-yuan; Greene, Tom; Mehta, Ravindra L; Stokes, John B; Thompson, Aliza M; Thompson, B Taylor; Westenfelder, Christof S; Tumlin, James A; Warnock, David G; Shah, Sudhir V; Xie, Yining; Duggan, Emily G; Kimmel, Paul L; Star, Robert A

    2012-05-01

    Acute kidney injury (AKI) remains a complex clinical problem associated with significant short-term morbidity and mortality and lacking effective pharmacologic interventions. Patients with AKI experience longer-term risks for progressive chronic ESRD, which diminish patients' health-related quality of life and create a larger burden on the healthcare system. Although experimental models have yielded numerous promising agents, translation into clinical practice has been unsuccessful, possibly because of issues in clinical trial design, such as delayed drug administration, masking of therapeutic benefit by adverse events, and inadequate sample size. To address issues of clinical trial design, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored a workshop titled "Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers" in December 2010. Workshop participants included representatives from academia, industry, and government agencies whose areas of expertise spanned basic science, clinical nephrology, critical care medicine, biostatistics, pharmacology, and drug development. This document summarizes the discussions of collaborative workgroups that addressed issues related to patient selection, study endpoints, the role of novel biomarkers, sample size and power calculations, and adverse events and pilot/feasibility studies in prevention and treatment of AKI. Companion articles outline the discussions of workgroups for model trials related to prevention or treatment of established AKI in different clinical settings, such as in patients with sepsis.

  2. Resveratrol attenuates acute kidney injury by inhibiting death receptor‑mediated apoptotic pathways in a cisplatin‑induced rat model.

    Science.gov (United States)

    Hao, Qiufa; Xiao, Xiaoyan; Zhen, Junhui; Feng, Jinbo; Song, Chun; Jiang, Bei; Hu, Zhao

    2016-10-01

    Acute kidney injury is a clinical syndrome characterized by a loss of renal function and acute tubular necrosis. Resveratrol exerts a wide range of pharmacological effects based on its anti‑inflammatory, antioxidant and cytoprotective properties. The present study aimed to evaluate whether resveratrol attenuates acute kidney injury in a cisplatin‑induced rat model and to investigate the potential mechanisms involved. Rats were randomly divided into four treatment groups: control, cisplatin, resveratrol, and cisplatin plus resveratrol. Rats exposed to cisplatin displayed acute kidney injury, identified by analysis of renal function and histopathological observation. Resveratrol significantly ameliorated the increased serum creatinine, blood urea nitrogen, renal index and histopathological damage induced by cisplatin. Furthermore, compared with untreated control animals, cisplatin lead to significantly increased expression of Fas ligand, tumor necrosis factor‑α (TNF‑α), caspase‑8 and Bcl‑2 associated protein X apoptosis regulator (Bax), and decreased expression of anti‑apoptosis regulators, BH3 interacting domain death agonist (BID) and B cell lymphoma 2 apoptosis regulator (Bcl‑2). Administration of resveratrol significantly reversed the cisplatin‑induced alteration in these apoptosis‑associated proteins. In conclusion, these findings suggest that resveratrol attenuates cisplatin‑induced acute kidney injury through inactivation of the death receptor‑mediated apoptotic pathway, and may provide a new therapeutic strategy to ameliorate the process of acute kidney injury. PMID:27600998

  3. BLOOD LEVELS OF INTERLEUKIN-6 AND INTERLEUKIN-10 IN SERUM AND BIOMARKERS OF ACUTE KIDNEY INJURY IN ACUTE CORONARY SYNDROME

    Directory of Open Access Journals (Sweden)

    M. A. Shalenkova

    2015-01-01

    Full Text Available Certain correlations between changes of cytokine levels and kidney dysfunction, as well as their prognostic significance for development of acute kidney injury (АКI in different clinical forms of ischemic heart disease (IHD seem to be worth of further studies. The levels of IL-6 and IL-10 and their correlation with serum creatinine (sCr and lipocalin levels in urine (u-NGAL were studied in 98 IHD patients, of them 93 presented with acute coronary syndrome (ACS and 5, with stable angina pectoris. ACS patients were found to have increased levels of IL-6, IL-10, sCr, u-NGAL. IL-6 and IL-10 contents proved to be increased in cases of non-ST-segment elevation ACS (NSTE-ACS, and during AKI development. According to serum creatinin levels, AKI was more frequently revealed in patients with NSTE-ACS. Urinary NGAL levels were found to be higher in ACS with ST segment elevation. 

  4. Adipose Tissue-Derived Stem Cells Reduce Acute and Chronic Kidney Damage in Mice.

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    Marina Burgos-Silva

    Full Text Available Acute and chronic kidney injuries (AKI and CKI constitute syndromes responsible for a large part of renal failures, and are today still associated with high mortality rates. Given the lack of more effective therapies, there has been intense focus on the use stem cells for organ protective and regenerative effects. Mesenchymal stem cells (MSCs have shown great potential in the treatment of various diseases of immune character, although there is still debate on its mechanism of action. Thus, for a greater understanding of the role of MSCs, we evaluated the effect of adipose tissue-derived stem cells (AdSCs in an experimental model of nephrotoxicity induced by folic acid (FA in FVB mice. AdSC-treated animals displayed kidney functional improvement 24h after therapy, represented by reduced serum urea after FA. These data correlated with cell cycle regulation and immune response modulation via reduced chemokine expression and reduced neutrophil infiltrate. Long-term analyses, 4 weeks after FA, indicated that AdSC treatment reduced kidney fibrosis and chronic inflammation. These were demonstrated by reduced interstitial collagen deposition and tissue chemokine and cytokine expression. Thus, we concluded that AdSC treatment played a protective role in the framework of nephrotoxic injury via modulation of inflammation and cell cycle regulation, resulting in reduced kidney damage and functional improvement, inhibiting organ fibrosis and providing long-term immune regulation.

  5. Unusual presentations of acute kidney injury and neurologic complications due to snake bite

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    Hamid Noshad

    2015-06-01

    Full Text Available Introduction: Vascularity of kidneys is very high, so these organs are potentially susceptible to be affected with toxins including snake venom. Hypersensitivity to snake venous could cause some neurological problem. Case Report: We present a 14-year-old boy with acute kidney injury (AKI due to snake bite. After a few days, kidney failure with hematuria was developed. His serum creatinine level rose to 3 mg/dl and following 2 weeks gradually and decreased to normal level without any special treatment except for anti-venom, which was not prescribed inappropriate time (this type of AKI is not reported previously. He had seizure attacks, which were according to magnetic resonance imaging due to posterior reversible encephalopathy syndrome (PRES (This neurologic complication has been seen in other kidney injuries but up to now it was not reported in snake bite victims. Conclusion: Sanke venom could cause PRES due to AKI and seizure could be one of the most important complications in snake bite.

  6. Interleukin-19 mediates tissue damage in murine ischemic acute kidney injury.

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    Yu-Hsiang Hsu

    Full Text Available Inflammation and renal tubular injury are major features of acute kidney injury (AKI. Many cytokines and chemokines are released from injured tubular cells and acts as proinflammatory mediators. However, the role of IL-19 in the pathogenesis of AKI is not defined yet. In bilateral renal ischemia/reperfusion injury (IRI-induced and HgCl2-induced AKI animal models, real-time quantitative (RTQ-PCR showed that the kidneys, livers, and lungs of AKI mice expressed significantly higher IL-19 and its receptors than did sham control mice. Immunohistochemical staining showed that IL-19 and its receptors were strongly stained in the kidney, liver, and lung tissue of AKI mice. In vitro, IL-19 upregulated MCP-1, TGF-β1, and IL-19, and induced mitochondria-dependent apoptosis in murine renal tubular epithelial M-1 cells. IL-19 upregulated TNF-α and IL-10 in cultured HepG2 cells, and it increased IL-1β and TNF-α expression in cultured A549 cells. In vivo, after renal IRI or a nephrotoxic dose of HgCl2 treatment, IL-20R1-deficient mice (the deficiency blocks IL-19 signaling showed lower levels of blood urea nitrogen (BUN in serum and less tubular damage than did wild-type mice. Therefore, we conclude that IL-19 mediates kidney, liver, and lung tissue damage in murine AKI and that blocking IL-19 signaling may provide a potent therapeutic strategy for treating AKI.

  7. ACUTE RENAL FAILURE WITH NORMAL PLASMA UREA LEVEL SECONDARY TO ACUTE PYELONEPHITIS IN A SINGLE KIDNEY PATIENT

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    Algranati L

    2007-04-01

    Full Text Available SUMMARY: Acute renal failure is a syndrome that usually runs with an increase in creatinine and urea plasma levels. However, there are clinical situations in which this syndrome may run with an increase in plasma creatinine keeping normal the urea one. In this report we present a case of acute renal failure with normal plasma urea level secondary to an acute pyelonephritis in a single kidney patient. The patient had an increased fractional excretion of urea which could explain the normal plasma urea levels found despite of his reduced glomerular filtration. This increased urea excretion state was interpreted as a consequence of the nephrogenic diabetes insipidus and alteration of the intra-renal urea reciclying process that the acute pyelonephritis induced. In conclusion: Acute pyelonephritis in a single kidney patient can appear as a pattern of acute renal failure with normal plasma urea levels.RESUMEN: La insuficiencia renal aguda es un sindrome que característicamente cursa con niveles plasmáticos elevados de urea y creatinina. Sin embargo, hay situaciones clínicas en las cuales este sindrome puede cursar con un incremento de la creatininemia sin presentar elevación de la uremia. En este reporte presentamos un caso clínico de una insuficiencia renal aguda con uremia normal secundaria a una pielonefritis aguda en un paciente con riñón único. El paciente presentaba una elevada excreción fraccional de urea lo cual podía explicar su uremia normal pese a estar cursando una caída del filtrado gomerular. Dicha excreción de urea elevada fue interpretada como secundaria a una diabetes insipida nefrogénica y una alteración en el recirculado intra-renal de la urea ambos producto de la pielonefritis aguda. Concluimos que la pielonefritis aguda en un paciente mono-reno puede presentarse con un patrón de insuficiencia renal aguda con uremia normal.

  8. An educational approach to improve outcomes in acute kidney injury (AKI): report of a quality improvement project

    OpenAIRE

    Xu, Gang; Baines, Richard; Westacott, Rachel; Selby, Nick; Carr, Susan

    2014-01-01

    Objective To assess the impact of a quality improvement project that used a multifaceted educational intervention on how to improve clinician's knowledge, confidence and awareness of acute kidney injury (AKI). Setting 2 large acute teaching hospitals in England, serving a combined population of over 1.5 million people. Participants All secondary care clinicians working in the clinical areas were targeted, with a specific focus on clinicians working in acute admission areas. Interventions A mu...

  9. Contrast-Induced Acute Kidney Injury: Short and Long-term Implications

    Science.gov (United States)

    Weisbord, Steven D.; Palevsky, Paul M.

    2011-01-01

    The intravascular administration of iodine-based contrast media remains a common cause of acute kidney injury and a leading cause of iatrogenic renal disease. Past research has elucidated the principal risk factors for contrast-induced acute kidney injury (CIAKI) and helped to establish the efficacy of various interventions for the prevention of this condition. The importance of preventing CIAKI has been underscored by a growing number of studies demonstrating strong associations of CIAKI with serious, adverse short and long-term outcomes. However, it remains unclear whether these associations are causal. This is important as considerable healthcare resources are used to prevent CIAKI. If CIAKI is a marker, but not a mediator, of serious, adverse downstream outcomes, more judicious and selective utilization of preventive care may be appropriate. Moreover, with an increasing number of studies reporting the under-utilization of coronary angiography in patients with acute coronary syndrome and underlying CKD, presumably due in part out of a fear of CIAKI, a clear understanding of whether this condition directly results in adverse downstream outcomes is essential. Careful inspection of past studies that investigated the association of CIAKI with adverse short and long-term events sheds light on their strengths and weaknesses and provides insight into how future research may be better able to characterize the short and long-term implications of this iatrogenic condition. PMID:21784279

  10. MORPHOLOGICAL AND IMMUNOHISTOCHEMICAL MANIFESTATIONS OF DIFFERENT VARIANTS OF ACUTE KIDNEY ALLOGRAFT REJECTION

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    A.V Trailin

    2009-01-01

    Full Text Available The aim of this study was morphological characteristics of peculiar properties of acute T-cells- (ATMR and antibody-mediated kidney allograft rejection (AAMR. Histological slices of kidney allograft biopsies were examined after coloration by routine methods and immunohistochemical proceeding for C4d, CD45R0 T-lymphocytes antigen and CD68 macrophages antigen. We’ve determined that the key features of ATMR are: increasing of T-lymphocytes interstitial infi ltration with the same level of macrophages infi ltration comparing with implantation biopsies, mild mononuclear glomerulitis and capillaritis; tubulitis. Morphological traits of AAMR are neutrophilic and T-lymphocytes glomerulitis, diffuse capillaritis, capillaries dilatation and margination of mononuclear cells with admixture of neutrophils, macrophagal interstitial infi ltration under semiquantitative evaluation, as well as, more pronounced, than in ATMR, T-lymphoctes and macrophages interstitial infi ltration under quantitative evaluation.

  11. Non-Hodgkin's Lymphoma Primarily Presenting with Fanconi Syndrome and Acute Kidney Injury

    Institute of Scientific and Technical Information of China (English)

    Wen-ling Ye; Bing Han; Bing-yan Liu; Chan Meng; Wei Ye; Yu-bing Wen; Hang Li; Xue-mei Li

    2010-01-01

    @@ KIDNEY involvement is common in non-Hodg-kin's lymphoma (NHL) with incidence up to 30%-40% in autopsy studies. However, it us-ually occurs late in the course of the disease and is clinically silent. Clinically overt renal disease in-cluding acute kidney injury (AKI) as its primary manifes-tation is rarely reported, moreover, Fanconi syndrome (FS) is extremely rare as the main manifestation in NHL. In this report, we presented a case of NHL primarily presenting with FS and AKI due to diffuse interstitial infiltration of NHL cells and emphasized the important role of renal biopsy, especially renal immunohistochemical analysis in the di-agnosis of renal diffuse lymphoma.

  12. Rikkunshito, a traditional Japanese medicine, suppresses cisplatin-induced anorexia in humans

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    Ohno T

    2011-12-01

    Full Text Available Tetsuro Ohno, Mitsuhiro Yanai, Hiroyuki Ando, Yoshitaka Toyomasu, Atsushi Ogawa, Hiroki Morita, Kyoichi Ogata, Erito Mochiki, Takayuki Asao, Hiroyuki KuwanoDepartment of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, JapanBackground: The aim of this study was to investigate the effects of Rikkunshito on ghrelin secretion and on cisplatin-induced anorexia in humans.Methods: The study was performed as a crossover design, and ten unresectable or relapsed gastric cancer patients were randomly divided into two groups. Group A (n = 5 was started on Rikkunshito (2.5 g three times daily, orally from the first course of chemotherapy and followed by a second course without Rikkunshito. A treatment with reversed order was performed for Group B (n = 5. All patients received combined chemotherapy with S-1 plus cisplatin. The primary endpoint was the amount of oral intake, and the categories of scales of anorexia, nausea, and vomiting; secondary endpoints included the plasma concentration of acylated ghrelin.Results: In the Rikkunshito-on period, no decrease of the plasma concentration of acylated ghrelin induced by cisplatin was observed. The average oral intake in the Rikkunshito-on period was significantly larger than that in the Rikkunshito-off period, and the grade of anorexia was significantly lower in the Rikkunshito-on period than in the Rikkunshito-off period.Conclusion: Rikkunshito appeared to prevent anorexia induced by cisplatin, resulting in effective prophylactic administration of chemotherapy with cisplatin, and patients could continue their treatments on schedule.Keywords: Rikkunshito, cisplatin, ghrelin, anorexia, stomach cancer

  13. Chronic low vitamin intake potentiates cisplatin-induced intestinal epithelial cell apoptosis in WNIN rats

    Institute of Scientific and Technical Information of China (English)

    Bodiga Vijayalakshmi; Boindala Sesikeran; Putcha Udaykumar; Subramaniam Kalyanasundaram; Manchala Raghunath

    2006-01-01

    AIM: To investigate if cisplatin alters vitamin status and if VR modulates cisplatin induced intestinal apoptosis and oxidative stress in Wistar/NIN (WNIN) male rats.METHODS: Weanling, WNIN male rats (n = 12 per group) received adlibitum for 17 wk: control diet (20%protein) or the same with 50% vitamin restriction. They were then sub-divided into two groups of six rats each and administered cisplatin (2.61 mg/kg bodyweight)once a week for three wk or PBS (vehicle control).Intestinal epithelial cell (IEC) apoptosis was monitored by morphometry, Annexin-V binding, M30 cytodeath assay and DNA fragmentation. Structural and functional integrity of the villus were assessed by villus height /crypt depth ratio and activities of alkaline phosphatase,lys, ala-dipeptidyl amino-peptidase, respectively. To assess the probable mechanism(s) of altered apoptosis,oxidative stress parameters, caspase-3 activity, and expression of Bcl-2 and Bax were determined.RESULTS: Cisplatin per se decreased plasma vitamin levels and they were the lowest in VR animals treated with cisplatin. As expected VR increased only villus apoptosis, whereas cisplatin increased stem cell apoptosis in the crypt. However, cisplatin treatment of VR rats increased apoptosis both in villus and crypt regions and was associated with higher levels of TBARS,protein carbonyls and caspase-3 activity, but lower GSH concentrations. VR induced decrease in Bcl-2 expression was further lowered by cisplatin. Bax expression,unaffected by VR was increased on cisplatin treatment.Mucosal functional integrity was severely compromised in cisplatin treated VR-rats.CONCLUSION: Low intake of vitamins increases the sensitivity of rats to cisplatin and promotes intestinal epithelial cell apoptosis.

  14. Hepatoprotective effect of Ficus religiosa latex on cisplatin induced liver injury in Wistar rats

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    Yogesh C. Yadav

    2015-06-01

    Full Text Available AbstractFicus religiosa L., Moraceae, is widely planted in the tropics. The chemical constituents of F. religiosa include tannin, saponin gluanol acetate, β-sitosterol, leucoanthocyanidin, and leucoanthocyanin. These are used for the treatment of pain, inflammation, impotence, menstrual disturbances, and urine related problems, and as uterine tonic. The present study aimed to evaluate hepatoprotective effects of F. religiosa latex on cisplatin induced liver injury in Wistar rats. In experimental protocol contained five groups of rats (n = 6. In which, group I (control was administered acacia (2%, w/v of 5 ml/kg throughout the experiment for 16 days. The group II (cisplatin treated was administered single dose of cisplatin (7.5 mg/kg i.p. on 1st day. Group III (extract control was administered 300 mg/kg p.o. of extract for 1stto 10th day. Group IV (Protective was administered extract (300 mg/kg p.o. of F. religiosa latex for 1st to 10th day and administered single dose of cisplatin (7.5 mg/kg i.p. on 11th day and group V (Curative received single dose of cisplatin (7.5 mg/kg i.p. on day 1st, and administered extract (300 mg/kg p.o. from 7th to 16thdays. On the 6th day in cisplatin treated, 10th day in extract control and 16th day in control, protective and curative, blood withdrawn from retro-orbital sinus of rats for biochemical estimation for serum and dissected out the livers for estimation of antioxidant enzymes and histopathological works. The cisplatin-treated group 2 showed a significant increase in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and hepatocytes cells degeneration inflammatory infiltrate and necrosis it's were significantly (**p < 0.01 alleviates by protective groups.

  15. Effects of Delta-9-Tetrahydrocannabinol and Cannabidiol on Cisplatin-Induced Neuropathy in Mice.

    Science.gov (United States)

    Harris, Hannah M; Sufka, Kenneth J; Gul, Waseem; ElSohly, Mahmoud A

    2016-08-01

    Sativex, a cannabinoid extract with a 1 : 1 ratio of tetrahydocannabinol and cannabidiol, has been shown to alleviate neuropathic pain associated with chemotherapy. This research examined whether tetrahydocannabinol or cannabidiol alone could attenuate or prevent cisplatin-induced tactile allodynia. In experiment 1, mice (C57BL/6) received eight administrations of 2.3 mg/kg cisplatin or saline solution IP every other day to induce tactile allodynia. Mice were then administered vehicle, 100 mg/kg gabapentin, 2 mg/kg tetrahydocannabinol, or 2 mg/kg cannabidiol IP and tested 60 min later on an electronic Von Frey. In experiment 2, prevention studies, cannabidiol (0.0, 0.5, 1.0, and 2.0 mg/kg) or tetrahydocannabinol (0.0, 0.5, 1.0, and 2.0 mg/kg) was given IP 30 min prior to cisplatin administration (2.3 or 1.0 mg/kg) utilizing a six-dose alternate day protocol. In both studies, tactile responses to the hind paws were quantified in g of force using an electronic Von Frey prior to and after the cisplatin administration protocol. Cisplatin produced a reduction in g of force indicative of neuropathy that was attenuated by gabapentin, tetrahydocannabinol, and cannabidiol but not prevented by either cannabinoid. These data demonstrate that each of the major constituents of Sativex alone can achieve analgesic effects against cisplatin neuropathy. PMID:27214593

  16. Acute kidney injury: risk factors and management challenges in developing countries.

    Science.gov (United States)

    Ponce, Daniela; Balbi, Andre

    2016-01-01

    Acute kidney injury (AKI) is a major global health problem in both developed and developing nations, negatively affecting patient morbidity and responsible for an estimated 1.4 million deaths per year. Although the International Society of Nephrology set a goal of eliminating preventable deaths from AKI by 2025, implementation of this program in developing countries presents major challenges not only because of the lack of resources but also because of the scarce data addressing the epidemiology and causes of AKI in developing countries, the limited health care resources to diagnose and treat AKI, and the poor awareness of the impact of AKI on patient outcomes. PMID:27578995

  17. Role of markers for acute kidney injury in surgical management of patients with renal cancer

    OpenAIRE

    O I Kit; E. M. Frantsiyants; S. N. Dimitriadi; I. V. Kaplieva; L. K. Trepitaki; N. D. Cheryarina; Yu. A. Pogorelova

    2015-01-01

    The paper gives the results of studying the urinary levels of markers of acute kidney injury (AKI) in 46 patients with renal cancer during separate ureteral catheterization before the surgery and 24 hours after laparoscopic partial nephrectomy performed due to elective indications under warm ischemia. The levels of cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP), and interleukin-18 were examined by enzyme immunoassay. It has been e...

  18. Rhabdomyolysis, acute kidney injury and transverse myelitis due to naive heroin exposure

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    Ankur Gupta

    2011-01-01

    Full Text Available Heroin exposure can cause various complications like seizures, stroke, spongiform encephalopathy, transverse myelopathy, plexopathy, compartment syndrome, rhabdomyolysis and renal failure due to various mechanisms. We report here a young male who smoked heroin for the first time and developed transverse myelitis, rhabdomyolysis and acute kidney injury requiring dialysis. His renal recovery was complete by four weeks, while neurological improvement occurred 8 to 12 weeks later. This case suggests a common pathogenic mechanism of heroin intoxication involving multiple systems of the body.

  19. Acute kidney injury as first presentation of lymphoma: the role of renal biopsy

    OpenAIRE

    On, Wei; Udberg, Martin

    2013-01-01

    A 65-year-old man with an insidious history of being generally unwell with weight loss, a poor appetite and night sweats was transferred to a tertiary nephrology unit after being found to be in acute kidney injury (AKI). A renal biopsy was performed on the same day which revealed lymphomatous infiltration of the renal parenchyma. He required temporary haemodialysis as he was oliguric and was started on chemotherapy. His renal function improved to baseline 3 weeks after treatment. This case il...

  20. Acute Cerebral Infarction after FK 506 Administration in a Kidney Transplantation Recipient: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Ji Kyung; Byun, Woo Mok; Kim, Jae Woon [Yeungnam University College of Medicine, Daegu (Korea, Republic of)

    2011-02-15

    FK506 is widely used as a potent immunosuppressive agent following organ transplantation. However, the use of FK506 is associated with a wide spectrum of neurotoxicity. FK506-induced cerebral infarctions have rarely been reported. We report here on a case of the acute cerebral infarction caused by vasospasm after FK506 administration in a kidney transplantation recipient. There were areas with increased signal intensity on the diffusion-weighted image. The areas showing increased signal intensity on the diffusion- and T2-weighted images demonstrated decreased signal intensity on the apparent diffusion coefficient mapping. MR angiography showed diffuse stenosis in both the anterior and middle cerebral arteries

  1. Acute kidney injury on admission to the intensive care unit: where to go from here?

    Science.gov (United States)

    Ostermann, Marlies

    2008-01-01

    Acute kidney injury (AKI) is a common problem, especially in critically ill patients. In Critical Care, Kolhe and colleagues report that 6.3% of 276,731 patients in 170 intensive care units (ICUs) in the UK had evidence of severe AKI within the first 24 hours of admission to ICU. ICU and hospital mortality as well as length of stay in hospital were significantly increased. In light of this serious burden on individuals and the health system in general, the following commentary discusses the current state of knowledge of AKI in ICU and calls for more attention to preventive strategies.

  2. EARLY ALLOGRAFT DYSFUNCTION AND ACUTE KIDNEY INJURY AFTER LIVER TRANSPLANTATION: DEFINITIONS, RISK FACTORS AND CLINICAL SIGNIFICANCE

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    L. Y. Moysyuk

    2012-01-01

    Full Text Available This review discusses issues related to intensive care in recipients of transplanted liver in the early postoperative period, with an emphasis on contemporary conditions and attitudes that are specific for this group of patients. Early allograft dysfunction (EAD requires immediate diagnosis and appropriate treatment in case. The causes of the EAD and therapeutic tactics are discussed. Acute kidney injury (AKI and renal failure are common in patients after transplantation. We consider etiology, risk factors, diagnosis and treatment guidelines for AKI. The negative impact of EAD and AKI on the grafts survival and recipients is demonstrated. 

  3. AKI and Genetics: Evolving Concepts in the Genetics of Acute Kidney Injury: Implications for Pediatric AKI.

    Science.gov (United States)

    Lee-Son, Kathy; Jetton, Jennifer G

    2016-03-01

    In spite of recent advances in the field of acute kidney injury (AKI) research, morbidity and mortality remain high for AKI sufferers. The study of genetic influences in AKI pathways is an evolving field with potential for improving outcomes through the identification of risk and protective factors at the individual level that may in turn allow for the development of rational therapeutic interventions. Studies of single nucleotide polymorphisms, individual susceptibility to nephrotoxic medications, and epigenetic factors comprise a growing body of research in this area. While promising, this field is still only emerging, with a small number of studies in humans and very little data in pediatric patients. PMID:27617143

  4. Radiographic Contrast-Media-Induced Acute Kidney Injury: Pathophysiology and Prophylactic Strategies

    International Nuclear Information System (INIS)

    Contrast-induced acute kidney injury (CI-AKI) is one of the most widely discussed and debated topics in cardiovascular medicine. With increasing number of contrast-media- (CM-) enhanced imaging studies being performed and growing octogenarian population with significant comorbidities, incidence of CI-AKI remains high. In this review, pathophysiology of CI-AKI, its relationship with different types of CM, role of serum and urinary biomarkers for diagnosing CI-AKI, and various prophylactic strategies used for nephroprotection against CI-AKI are discussed in detail

  5. Cost-effectiveness analysis of acute kidney injury biomarkers in pediatric cardiac surgery

    OpenAIRE

    Petrovic, Stanislava; Bogavac-Stanojevic, Natasa; Lakic, Dragana; Peco-Antic, Amira; Vulicevic, Irena; Ivanisevic, Ivana; Kotur-Stevuljevic, Jelena; Jelic-Ivanovic, Zorana

    2015-01-01

    Introduction: Acute kidney injury (AKI) is significant problem in children with congenital heart disease (CHD) who undergo cardiac surgery. The economic impact of a biomarker-based diagnostic strategy for AKI in pediatric populations undergoing CHD surgery is unknown. The aim of this study was to perform the cost effectiveness analysis of using serum cystatin C (sCysC), urine neutrophil gelatinase-associated lipocalin (uNGAL) and urine liver fatty acid-binding protein (uL-FABP) for the diagno...

  6. Cost-effectiveness analysis of acute kidney injury biomarkers in pediatric cardiac surgery

    OpenAIRE

    Petrovic, Stanislava; Bogavac-Stanojevic, Natasa; Lakic, Dragana; Peco-Antic, Amira; Vulicevic, Irena; Ivanisevic, Ivana; Kotur-Stevuljevic, Jelena; Jelic-Ivanovic, Zorana

    2015-01-01

    Introduction Acute kidney injury (AKI) is significant problem in children with congenital heart disease (CHD) who undergo cardiac surgery. The economic impact of a biomarker-based diagnostic strategy for AKI in pediatric populations undergoing CHD surgery is unknown. The aim of this study was to perform the cost effectiveness analysis of using serum cystatin C (sCysC), urine neutrophil gelatinase-associated lipocalin (uNGAL) and urine liver fatty acid-binding protein (uL-FABP) for the diagnos...

  7. Role of TRPV1 channels in ischemia/reperfusion-induced acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Lan Chen

    Full Text Available OBJECTIVES: Transient receptor potential vanilloid 1 (TRPV1 -positive sensory nerves are widely distributed in the kidney, suggesting that TRPV1-mediated action may participate in the regulation of renal function under pathophysiological conditions. Stimulation of TRPV1 channels protects against ischemia/reperfusion (I/R-induced acute kidney injury (AKI. However, it is unknown whether inhibition of these channels is detrimental in AKI or not. We tested the role of TRPV1 channels in I/R-induced AKI by modulating these channels with capsaicin (TRPV1 agonist, capsazepine (TRPV1 antagonist and using Trpv1-/- mice. METHODS AND RESULTS: Anesthetized C57BL/6 mice were subjected to 25 min of renal ischemia and 24 hrs of reperfusion. Mice were pretreated with capsaicin (0.3 mg/kg body weight or capsazepine (50 mg/kg body weight. Capsaicin ameliorated the outcome of AKI, as measured by serum creatinine levels, tubular damage,neutrophil gelatinase-associated lipocalin (NGAL abundance and Ly-6B.2 positive polymorphonuclear inflammatory cells in injured kidneys. Neither capsazepine nor deficiency of TRPV1 did deteriorate renal function or histology after AKI. Measurements of endovanilloids in kidney tissue indicate that 20-hydroxyeicosatetraeonic acid (20-HETE or epoxyeicosatrienoic acids (EETs are unlikely involved in the beneficial effects of capsaicin on I/R-induced AKI. CONCLUSIONS: Activation of TRPV1 channels ameliorates I/R-induced AKI, but inhibition of these channels does not affect the outcome of AKI. Our results may have clinical implications for long-term safety of renal denervation to treat resistant hypertension in man, with respect to the function of primary sensory nerves in the response of the kidney to ischemic stimuli.

  8. Using pRIFLE criteria for acute kidney injury in critically ill children

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    Rina Amalia C. Saragih

    2013-01-01

    Full Text Available Background Incidence of acute kidney injury (AKI in critically ill children and its mortality rate is high. The lack of a uniform definition for AKI leads to failure in determining kidney injury, delayed treatment, and the inability to generalize research results. Objectives To evaluate the pediatric RIFLE (pRIFLE criteria (risk for renal dysfunction, injury to the kidney, failure of kidney function, loss of kidney function, and end-stage renal disease for diagnosing and following the clinical course of AKI in critically ill children. We also aimed to compare AKI severity on days 1 and 3 of pediatric intensive care unit (PICUu stay in critically ill pediatric patients. Methods This prospective cohort study was performed in PICU patients. Urine output (UOP, serum creatinine (SCr, and glomerular filtration rate on days 1 and 3 of PICU stay were recorded. Classification of AKI was determined according to pRIFLE criteria. We also recorded subjects’ immune status, pediatric logistic organ dysfunction (PELOD score, admission diagnosis, the use of vasoactive medications, diuretics, and ventilators, as well as PICU length of stay and mortality. Results Forty patients were enrolled in this study. AKI was found in 13 patients (33%. A comparison of AKI severity on day 1 and day 3 revealed no statistically significant differences for attainment of pRIFLE criteria by urine output only (pRIFLE UOP; P=0.087 and by both UOP and SCr (pRIFLECr+UOP; P=0.577. However, attainment of pRIFLE criteria by SCr only (pRIFLECr was significantly improved between days 1 and 3 (P=0.026. There was no statistically significant difference in mortality or length of stay between subjects with AKI and those without AKI. Conclusion The pRIFLE criteria is feasible for use in diagnosing and following the clinical course of AKI in critically ill children.[Paediatr Indones. 2013;53:32-6.

  9. P2X7 receptor blockade protects against cisplatin-induced nephrotoxicity in mice by decreasing the activities of inflammasome components, oxidative stress and caspase-3

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yuanyuan; Yuan, Fahuan; Cao, Xuejiao [Department of Nephrology, Xinqiao Hospital, PLA, Third Military Medical University, Chongqing 400037 (China); Zhai, Zhifang [Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Gang Huang [Department of Medical Genetics, Third Military Medical University, Chongqing 430038 (China); Du, Xiang; Wang, Yiqin; Zhang, Jingbo; Huang, Yunjian; Zhao, Jinghong [Department of Nephrology, Xinqiao Hospital, PLA, Third Military Medical University, Chongqing 400037 (China); Hou, Weiping, E-mail: hwp0518@aliyun.com [Department of Nephrology, Xinqiao Hospital, PLA, Third Military Medical University, Chongqing 400037 (China)

    2014-11-15

    Nephrotoxicity is a common complication of cisplatin chemotherapy and thus limits the use of cisplatin in clinic. The purinergic 2X7 receptor (P2X7R) plays important roles in inflammation and apoptosis in some inflammatory diseases; however, its roles in cisplatin-induced nephrotoxicity remain unclear. In this study, we first assessed the expression of P2X7R in cisplatin-induced nephrotoxicity in C57BL/6 mice, and then we investigated the changes of renal function, histological injury, inflammatory response, and apoptosis in renal tissues after P2X7R blockade in vivo using an antagonist A-438079. Moreover, we measured the changes of nod-like receptor family, pyrin domain containing proteins (NLRP3) inflammasome components, oxidative stress, and proapoptotic genes in renal tissues in cisplatin-induced nephrotoxicity after treatment with A-438079. We found that the expression of P2X7R was significantly upregulated in the renal tubular epithelial cells in cisplatin-induced nephrotoxicity compared with that of the normal control group. Furthermore, pretreatment with A-438079 markedly attenuated the cisplatin-induced renal injury while lightening the histological damage, inflammatory response and apoptosis in renal tissue, and improved the renal function. These effects were associated with the significantly reduced levels of NLRP3 inflammasome components, oxidative stress, p53 and caspase-3 in renal tissues in cisplatin-induced nephrotoxicity. In conclusions, our studies suggest that the upregulated activity of P2X7R might play important roles in the development of cisplatin-induced nephrotoxicity, and P2X7R blockade might become an effective therapeutic strategy for this disease. - Highlights: • The P2X7R expression was markedly upregulated in cisplatin-induced nephrotoxicity. • P2X7R blockade significantly attenuated the cisplatin-induced renal injury. • P2X7R blockade reduced activities of NLRP3 inflammasome components in renal tissue. • P2X7R blockade

  10. Recurrent acute pancreatitis and cholangitis in a patient with autosomal dominant polycystic kidney disease

    Directory of Open Access Journals (Sweden)

    Kambiz Yazdanpanah

    2013-01-01

    Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is an inherited disorder associated with multiple cyst formation in the different organs. Development of pancreatic cyst in ADPKD is often asymptomatic and is associated with no complication. A 38-year-old man with ADPKD was presented with six episodes of acute pancreatitis and two episodes of cholangitis in a period of 12 months. Various imaging studies revealed multiple renal, hepatic and pancreatic cysts, mild ectasia of pancreatic duct, dilation of biliary system and absence of biliary stone. He was managed with conservative treatment for each attack. ADPKD should be considered as a potential risk factor for recurrent acute and/or chronic pancreatitis and cholangitis.

  11. Acute kidney injury associated with androgenic steroids and nutritional supplements in bodybuilders†

    Science.gov (United States)

    Almukhtar, Safa E.; Abbas, Alaa A.; Muhealdeen, Dana N.; Hughson, Michael D.

    2015-01-01

    Four bodybuilders who injected anabolic steroids and ingested commercial protein (78–104 g/day) and creatine (15 g/day) products presented with serum creatinine levels between 229.84 and 335.92 µmol/L (2.6–3.8 mg/dL). Renal biopsies revealed acute tubular necrosis. Four weeks after discontinuing injections and supplements, serum creatinine was in the normal range and estimated glomerular filtration rate > 1.00 mL/s (60 mL/min), including two patients with biopsies showing >30% interstitial fibrosis and tubular atrophy. The findings highlight a risk for acute and potentially chronic kidney injury among young men abusing anabolic steroids and using excessive amounts of nutritional supplements. PMID:26251708

  12. Acute kidney injury biomarkers for patients in a coronary care unit: a prospective cohort study.

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    Tien-Hsing Chen

    Full Text Available BACKGROUND: Renal dysfunction is an established predictor of all-cause mortality in intensive care units. This study analyzed the outcomes of coronary care unit (CCU patients and evaluated several biomarkers of acute kidney injury (AKI, including neutrophil gelatinase-associated lipocalin (NGAL, interleukin-18 (IL-18 and cystatin C (CysC on the first day of CCU admission. METHODOLOGY/PRINCIPAL FINDINGS: Serum and urinary samples collected from 150 patients in the coronary care unit of a tertiary care university hospital between September 2009 and August 2010 were tested for NGAL, IL-18 and CysC. Prospective demographic, clinical and laboratory data were evaluated as predictors of survival in this patient group. The most common cause of CCU admission was acute myocardial infarction (80%. According to Acute Kidney Injury Network criteria, 28.7% (43/150 of CCU patients had AKI of varying severity. Cumulative survival rates at 6-month follow-up following hospital discharge differed significantly (p<0.05 between patients with AKI versus those without AKI. For predicting AKI, serum CysC displayed an excellent areas under the receiver operating characteristic curve (AUROC (0.895 ± 0.031, p < 0.001. The overall 180-day survival rate was 88.7% (133/150. Multiple Cox logistic regression hazard analysis revealed that urinary NGAL, serum IL-18, Acute Physiology, Age and Chronic Health Evaluation II (APACHE II and sodium on CCU admission day one were independent risk factors for 6-month mortality. In terms of 6-month mortality, urinary NGAL had the best discriminatory power, the best Youden index, and the highest overall correctness of prediction. CONCLUSIONS: Our data showed that serum CysC has the best discriminative power for predicting AKI in CCU patients. However, urinary NGAL and serum IL-18 are associated with short-term mortality in these critically ill patients.

  13. Topiramate as a rare cause of reversible Fanconi syndrome and acute kidney injury: a case report and literature review.

    Science.gov (United States)

    Meseeha, Marcelle G; Attia, Maximos N; Kolade, Victor O

    2016-01-01

    Topiramate (TPM) is a sulfa-derivative monosaccharide that has been used for multiple indications in the last several years. We describe a 53-year-old woman with known chronic kidney disease stage 2 and baseline creatinine of 1 mg/dL who developed acute kidney injury and proximal renal tubular dysfunction while on TPM for depression. The Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship (score of 6) between TPM and acute kidney injury as well as proximal tubular dysfunction; these renal conditions resolved on withdrawal of TPM. To our knowledge, this is the first report of such a scenario. Patients receiving TPM therapy should be closely monitored for evidence of kidney dysfunction and electrolyte abnormalities. PMID:26908388

  14. Topiramate as a rare cause of reversible Fanconi syndrome and acute kidney injury: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Marcelle G. Meseeha

    2016-02-01

    Full Text Available Topiramate (TPM is a sulfa-derivative monosaccharide that has been used for multiple indications in the last several years. We describe a 53-year-old woman with known chronic kidney disease stage 2 and baseline creatinine of 1 mg/dL who developed acute kidney injury and proximal renal tubular dysfunction while on TPM for depression. The Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship (score of 6 between TPM and acute kidney injury as well as proximal tubular dysfunction; these renal conditions resolved on withdrawal of TPM. To our knowledge, this is the first report of such a scenario. Patients receiving TPM therapy should be closely monitored for evidence of kidney dysfunction and electrolyte abnormalities.

  15. Prevention of iodinated contrast induced acute kidney injury (ICI--AKI) - what have we learnt so far?

    OpenAIRE

    Asim Muhammad

    2009-01-01

    The use of imaging modalities and endovascular procedures has escalated phenol-menally in the last two decades. In view of increasing number of elderly patients, rising incidence of chronic kidney disease and diabetes along with the complication of nephrogenic systemic fibrosis with gadolinium, a large patient population will be at risk of developing iodinated contrast induced acute kidney injury (ICI-AKI) which is associated with significant morbidity and mortality and increased health care ...

  16. Value of joint detecion of multiple biomarkers on early diagnosis of acute kidney injury in critical patients

    Institute of Scientific and Technical Information of China (English)

    许光银

    2014-01-01

    Objective To assess the value of joint detection of serum cysteine proteinase inhibitors C(sCys-C),urinary kidney injury molecule 1(uKIM-1),urinary neutrophil gelatinase-associated lipocalin(uNGAL)and urinary interleukin 18(uIL-18)for early diagnosis of acute kidney injury(AKI)in critically ill patients.Methods A total of256 adult patients who stayed in Intensive Care Unit for

  17. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury.

    Science.gov (United States)

    Palevsky, Paul M; Liu, Kathleen D; Brophy, Patrick D; Chawla, Lakhmir S; Parikh, Chirag R; Thakar, Charuhas V; Tolwani, Ashita J; Waikar, Sushrut S; Weisbord, Steven D

    2013-05-01

    In response to the recently released 2012 KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for acute kidney injury (AKI), the National Kidney Foundation organized a group of US experts in adult and pediatric AKI and critical care nephrology to review the recommendations and comment on their relevancy in the context of current US clinical practice and concerns. The first portion of the KDIGO guideline attempts to harmonize earlier consensus definitions and staging criteria for AKI. While the expert panel thought that the KDIGO definition and staging criteria are appropriate for defining the epidemiology of AKI and in the design of clinical trials, the panel concluded that there is insufficient evidence to support their widespread application to clinical care in the United States. The panel generally concurred with the remainder of the KDIGO guidelines that are focused on the prevention and pharmacologic and dialytic management of AKI, although noting the dearth of clinical trial evidence to provide strong evidence-based recommendations and the continued absence of effective therapies beyond hemodynamic optimization and avoidance of nephrotoxins for the prevention and treatment of AKI.

  18. Acute kidney injury after using contrast during cardiac catheterization in children with heart disease.

    Science.gov (United States)

    Hwang, Young Ju; Hyun, Myung Chul; Choi, Bong Seok; Chun, So Young; Cho, Min Hyun

    2014-08-01

    Acute kidney injury (AKI) is closely associated with the mortality of hospitalized patients and long-term development of chronic kidney disease, especially in children. The purpose of our study was to assess the evidence of contrast-induced AKI after cardiac catheterization in children with heart disease and evaluate the clinical usefulness of candidate biomarkers in AKI. A total of 26 children undergoing cardiac catheterization due to various heart diseases were selected and urine and blood samples were taken at 0 hr, 6 hr, 24 hr, and 48 hr after cardiac catheterization. Until 48 hr after cardiac catheterization, there was no significant increase in serum creatinine level in all patients. Unlike urine kidney injury molecule-1, IL-18 and neutrophil gelatinase-associated lipocalin, urine liver-type fatty acid-binding protein (L-FABP) level showed biphasic pattern and the significant difference in the levels of urine L-FABP between 24 and 48 hr. We suggest that urine L-FABP can be one of the useful biomarkers to detect subclinical AKI developed by the contrast before cardiac surgery.

  19. High prevalence of and potential mechanisms for chronic kidney disease in patients with acute intermittent porphyria.

    Science.gov (United States)

    Pallet, Nicolas; Mami, Iadh; Schmitt, Caroline; Karim, Zoubida; François, Arnaud; Rabant, Marion; Nochy, Dominique; Gouya, Laurent; Deybach, Jean-Charles; Xu-Dubois, Yichum; Thervet, Eric; Puy, Hervé; Karras, Alexandre

    2015-08-01

    Acute intermittent porphyria (AIP) is a genetic disorder of the synthesis of heme caused by a deficiency in hydroxymethylbilane synthase (HMBS), leading to the overproduction of the porphyrin precursors δ-aminolevulinic acid and porphobilinogen. The aim of this study is to describe the clinical and biological characteristics, the renal pathology, and the cellular mechanisms of chronic kidney disease associated with AIP. A total of 415 patients with HMBS deficiency followed up in the French Porphyria Center were enrolled in 2003 in a population-based study. A follow-up study was conducted in 2013, assessing patients for clinical, biological, and histological parameters. In vitro models were used to determine whether porphyrin precursors promote tubular and endothelial cytotoxicity. Chronic kidney disease occurred in up to 59% of the symptomatic AIP patients, with a decline in the glomerular filtration rate of ~1 ml/min per 1.73 m(2) annually. Proteinuria was absent in the vast majority of the cases. The renal pathology was a chronic tubulointerstitial nephropathy, associated with a fibrous intimal hyperplasia and focal cortical atrophy. Our experimental data provide evidence that porphyrin precursors promote endoplasmic reticulum stress, apoptosis, and epithelial phenotypic changes in proximal tubular cells. In conclusion, the diagnosis of chronic kidney disease associated with AIP should be considered in cases of chronic tubulointerstitial nephropathy and/or focal cortical atrophy with severe proliferative arteriosclerosis.

  20. Over-diuresis or cardiac tamponade? An unusual case of acute kidney injury and early closure

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    Gurkeerat Singh

    2016-04-01

    Full Text Available An 84-year-old man with hypertension and a history of deep venous thrombosis (on warfarin was admitted with shortness of breath presumed to be due to congestive heart failure. Echocardiogram performed the following day showed a low-normal ejection fraction with signs of elevated right-sided pressures but was otherwise normal. He improved with diuretic therapy but after a few days was found to be hypotensive with a concomitant rise in creatinine with decreased urine output. This was felt to be secondary to over-diuresis but he did not respond to small boluses of intravenous fluids as his kidney function continued to worsen and hypotension persisted. He was transferred to the intermediate care unit where a rapid, bedside ultrasound revealed a new, moderate-sized pericardial effusion with tamponade physiology. Pericardiocentesis, with removal of 750 cc of frank blood, led to dramatic improvement in blood pressure, kidney function, and urine output. Here, we demonstrate the utility of point-of-care ultrasound in a community hospital setting where urgent echocardiogram is not routinely available. We also report acute kidney injury due to pericardial tamponade reversed with therapeutic pericardiocentesis.

  1. Kidney and lung injury in irradiated rats protected from acute death by partial-body shielding

    International Nuclear Information System (INIS)

    Ninety-six CD-1 male rats were exposed to gamma-ray doses (0-25 Gy) in increments of 5 Gy. One femur, the surgically exteriorized GI tract, and the oral cavity were shielded during irradiation to protect against acute mortality from injury to the hematopoietic system, small intestine, and oral cavity. In addition, the thoraxes of half of the animals from each dose group were shielded. At approximately monthly intervals from 2 to 10 months after irradiation the hematocrit, plasma urea nitrogen (PUN), and 51Cr-EDTA clearance were measured. During the study 20 thorax-shielded and 19 thorax-irradiated animals died. All rats whose thoraxes received 25 Gy irradiation and three out of seven rats whose thoraxes received 20 Gy died 1 to 3 months postirradiation with massive pleural fluid accumulation. Shielding the thoraxes prevented this mode of death at these doses. Kidney injury was judged to be the primary cause of death of all thorax-shielded animals and 15- and 20-Gy thorax-irradiated animals. Animals with kidney damage had elevated PUN and reduced 51Cr-EDTA clearance and hematocrits. The relative merits of each of these end points in assessing radiation-induced kidney injury after total-body exposure are discussed

  2. Cortex perfusion index: a sensitive detector of acute rejection crisis in transplanted kidneys

    Energy Technology Data Exchange (ETDEWEB)

    Anaise, D.; Oster, Z.H.; Atkins, H.L.; Arnold, A.N.; Weis, S.; Waltzer, W.C.; Rapaport, F.T.

    1986-11-01

    Damage to the renal cortical microcirculation, an early event in the course of acute rejection crisis (ARC), usually precedes measurable functional derangements in the transplanted kidney. Direct assessment of cortical blood flow by radionuclide renography may provide a sensitive and reliable index to the diagnosis of ARC, with particular regard to the differential diagnosis of ARC and ATN. Computer generated time-activity curves of global, cortical, and medullary renal blood flow were analyzed in 67 instances (35 patients) of renal allograft dysfunction and correlated with needle biopsy of these kidneys. No increase in cortex perfusion index (CPI), i.e., decrease in cortical perfusion, was found when the patients were suffering from ureteral obstruction or drug and viral nephropathy (mean perfusion index (PI) increase (8%). In contrast, a marked increase in CPI of 193% was noted in ARC. Global and medullary PI increased only 116%. As a result, global and medullary PI were capable of diagnosing ARC in only 73% and 55% of the cases, respectively, whereby cortex PI correctly diagnosed ARC in 94% of the cases. Selective analysis of cortical perfusion may thus enhance the accuracy of (99mTc)DTPA scans (radionuclide renograph) for the early detection of ARC and in differentiating ARC from nonimmunological causes of kidney allograft dysfunction.

  3. Classical and remote post-conditioning effects on ischemia/reperfusion-induced acute oxidant kidney injury.

    Science.gov (United States)

    Kadkhodaee, Mehri; Najafi, Atefeh; Seifi, Behjat

    2014-11-01

    The present study aimed to analyze and compare the effects of classical and remote ischemic postconditioning (POC) on rat renal ischemia/reperfusion (IR)-induced acute kidney injury. After right nephrectomy, male rats were randomly assigned into four groups (n = 8). In the IR group, 45 min of left renal artery occlusion was induced followed by 24 h of reperfusion. In the classical POC group, after induction of 45 min ischemia, 4 cycles of 10 s of intermittent ischemia and reperfusion were applied to the kidney before complete restoring of renal blood. In the remote POC group, 4 cycles of 5 min ischemia and reperfusion of left femoral artery were applied after 45 min renal ischemia and right at the time of renal reperfusion. There was a reduction in renal function (increase in blood urea and creatinine) in the IR group. Application of both forms of POC prevented the IR-induced reduction in renal function and histology. There were also significant improvements in kidney oxidative stress status in both POC groups demonstrated by a reduction in malondialdehyde (MDA) formation and preservation of antioxidant levels comparing to the IR group. We concluded that both methods of POC have protective effects on renal function and histology possibly by a reduction in IR-induced oxidative stress.

  4. Autophagy Limits Endotoxemic Acute Kidney Injury and Alters Renal Tubular Epithelial Cell Cytokine Expression.

    Science.gov (United States)

    Leventhal, Jeremy S; Ni, Jie; Osmond, Morgan; Lee, Kyung; Gusella, G Luca; Salem, Fadi; Ross, Michael J

    2016-01-01

    Sepsis related acute kidney injury (AKI) is a common in-hospital complication with a dismal prognosis. Our incomplete understanding of disease pathogenesis has prevented the identification of hypothesis-driven preventive or therapeutic interventions. Increasing evidence in ischemia-reperfusion and nephrotoxic mouse models of AKI support the theory that autophagy protects renal tubular epithelial cells (RTEC) from injury. However, the role of RTEC autophagy in septic AKI remains unclear. We observed that lipopolysaccharide (LPS), a mediator of gram-negative bacterial sepsis, induces RTEC autophagy in vivo and in vitro through TLR4-initiated signaling. We modeled septic AKI through intraperitoneal LPS injection in mice in which autophagy-related protein 7 was specifically knocked out in the renal proximal tubules (ATG7KO). Compared to control littermates, ATG7KO mice developed more severe renal dysfunction (24hr BUN 100.1mg/dl +/- 14.8 vs 54.6mg/dl +/- 11.3) and parenchymal injury. After injection with LPS, analysis of kidney lysates identified higher IL-6 expression and increased STAT3 activation in kidney lysates from ATG7KO mice compared to controls. In vitro experiments confirmed an altered response to LPS in RTEC with genetic or pharmacological impairment of autophagy. In conclusion, RTEC autophagy protects against endotoxin induced injury and regulates downstream effects of RTEC TLR4 signaling.

  5. Autophagy Limits Endotoxemic Acute Kidney Injury and Alters Renal Tubular Epithelial Cell Cytokine Expression.

    Directory of Open Access Journals (Sweden)

    Jeremy S Leventhal

    Full Text Available Sepsis related acute kidney injury (AKI is a common in-hospital complication with a dismal prognosis. Our incomplete understanding of disease pathogenesis has prevented the identification of hypothesis-driven preventive or therapeutic interventions. Increasing evidence in ischemia-reperfusion and nephrotoxic mouse models of AKI support the theory that autophagy protects renal tubular epithelial cells (RTEC from injury. However, the role of RTEC autophagy in septic AKI remains unclear. We observed that lipopolysaccharide (LPS, a mediator of gram-negative bacterial sepsis, induces RTEC autophagy in vivo and in vitro through TLR4-initiated signaling. We modeled septic AKI through intraperitoneal LPS injection in mice in which autophagy-related protein 7 was specifically knocked out in the renal proximal tubules (ATG7KO. Compared to control littermates, ATG7KO mice developed more severe renal dysfunction (24hr BUN 100.1mg/dl +/- 14.8 vs 54.6mg/dl +/- 11.3 and parenchymal injury. After injection with LPS, analysis of kidney lysates identified higher IL-6 expression and increased STAT3 activation in kidney lysates from ATG7KO mice compared to controls. In vitro experiments confirmed an altered response to LPS in RTEC with genetic or pharmacological impairment of autophagy. In conclusion, RTEC autophagy protects against endotoxin induced injury and regulates downstream effects of RTEC TLR4 signaling.

  6. Acute kidney injury and hyperbilirubinemia in a young male after ingestion of Tribulus terrestris.

    Science.gov (United States)

    Ryan, Margaret; Lazar, Ira; Nadasdy, Gyongyi M; Nadasdy, Tibor; Satoskar, Anjali A

    2015-03-01

    Acute tubular necrosis (ATN), especially from toxic injury is frequently accompanied by tubular casts and crystals. Myeloma casts, myoglobin, red blood cell and granular casts are well described. However, bile casts in tubules are rarely seen. We describe a case of Tribulus terrestris toxicity in a young healthy male, presenting with severe hyperbilirubinemia followed by acute renal failure and bile containing casts in the tubules. Tribulus terrestris is an herb often used by athletes as a nutritional supplement for performance enhancement. Although it is thought to be relatively safe, serious side effects have been reported before. Our aim is to increase awareness of the potential toxicities of performance enhancing herbal medications. These are often sold over-the-counter and therefore casually used, especially by young healthy individuals. Beneficial effects are controversial. Under-reporting by patients and infrequent documentation by health-care providers can delay diagnosis. We elaborately describe the kidney biopsy findings in Tribulus terrestris toxicity, and also provide a concise overview of the spectrum of tubular casts and their staining patterns, found in various kidney diseases. PMID:25295577

  7. Multidimensional Approach to Adequacy of Renal Replacement Therapy in Acute Kidney Injury.

    Science.gov (United States)

    Villa, Gianluca; Ricci, Zaccaria; Romagnoli, Stefano; Ronco, Claudio

    2016-01-01

    Acute kidney injury (AKI) is frequently observed among hospitalized and critical care patients. In the absence of any effective therapies aiming to actively restore kidney function, AKI is usually managed through acute renal replacement therapy (ARRT). 'Optimization' of ARRT may reduce the mortality of patients with AKI. Although several studies have tried to identify the most adequate approach to ARRT in terms of dose, treatment modality and all other important dimensions, the literature has provided controversial results. Nowadays, adequate ARRT still appears difficult to dose, prescribe, deliver and monitor among different critical care patients. The identification of the major elements involved for a multidimensional approach to adequacy of ARRT in patients with AKI should consider the patient, the applied technology and the environment. All these aspects should be carefully evaluated and adequately applied in clinical practice through a patient-oriented approach. Adequacy of ARRT imposes the concomitant consideration of more complex issues, such as the timing, modality and technique of ARRT delivery; anticoagulation and substitution fluid choice; membrane selection; monitor accuracy; the role of fluid overload; and other patient comorbidities. The capacity of clinicians to consider all these aspects through a multidimensional approach, adapting the different dimensions of ARRT to actual patients' needs, might be the fundamental missing element in the pathway toward significant outcome improvements among critically ill patients with AKI. This narrative review provides a systematic approach to the major dimensions of ARRT and their multidimensional rationalization for adequate treatment prescription, monitoring and evaluation. PMID:26881756

  8. Loxosceles gaucho venom-induced acute kidney injury--in vivo and in vitro studies.

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    Rui V Lucato

    Full Text Available BACKGROUND: Accidents caused by Loxosceles spider may cause severe systemic reactions, including acute kidney injury (AKI. There are few experimental studies assessing Loxosceles venom effects on kidney function in vivo. METHODOLOGY/PRINCIPAL FINDINGS: In order to test Loxosceles gaucho venom (LV nephrotoxicity and to assess some of the possible mechanisms of renal injury, rats were studied up to 60 minutes after LV 0.24 mg/kg or saline IV injection (control. LV caused a sharp and significant drop in glomerular filtration rate, renal blood flow and urinary output and increased renal vascular resistance, without changing blood pressure. Venom infusion increased significantly serum creatine kinase and aspartate aminotransferase. In the LV group renal histology analysis found acute epithelial tubular cells degenerative changes, presence of cell debris and detached epithelial cells in tubular lumen without glomerular or vascular changes. Immunohistochemistry disclosed renal deposition of myoglobin and hemoglobin. LV did not cause injury to a suspension of fresh proximal tubules isolated from rats. CONCLUSIONS/SIGNIFICANCE: Loxosceles gaucho venom injection caused early AKI, which occurred without blood pressure variation. Changes in glomerular function occurred likely due to renal vasoconstriction and rhabdomyolysis. Direct nephrotoxicity could not be demonstrated in vitro. The development of a consistent model of Loxosceles venom-induced AKI and a better understanding of the mechanisms involved in the renal injury may allow more efficient ways to prevent or attenuate the systemic injury after Loxosceles bite.

  9. Disseminate Fungal Infection after Acute Pancreatitis in a Simultaneous Pancreas-Kidney Recipient

    Directory of Open Access Journals (Sweden)

    Anna Rossetto

    2010-01-01

    Full Text Available Fungal infections after kidney transplantation are a major cause of morbidity and mortality, and Candida infection of the pancreas is considered an infrequent but important agent in necrotizing pancreatitis. We report the case of a 43-year-old Caucasian patient who underwent simultaneous pancreas-kidney transplantation because of diabetes type I, and chronic renal failure with peritoneal dialysis. The postoperative course was complicated by acute pancreatitis due to the thrombosis of the splenic artery of the graft, the subsequent acute rupture of the external iliac artery caused by fungal arteritis (Candida glabrata, and peritonitis a few days later caused by sigmoid perforation with detection of Candida glabrata infection of the resected intestinal tract. The present case remarks that awareness and prevention of fungal infection are major issues in the transplant field. Important information can be added by systematic culture of conservation perfusates but, probably, the best way for early recognition of a critical level of infectious risk remains the routine application of the colonization index screening. In cases of positive results, preemptive antifungal therapy could be warranted.

  10. Melatonin protects kidney against apoptosis induced by acute unilateral ureteral obstruction in rats

    Science.gov (United States)

    Badem, Hüseyin; Cakmak, Muzaffer; Yilmaz, Hakki; Kosem, Bahadir; Karatas, Omer Faruk; Bayrak, Reyhan; Cimentepe, Ersin

    2016-01-01

    Introduction To investigate whether there was a protective effect of melatonin on apoptotic mechanisms after an acute unilateral obstruction of the kidney. Material and methods A total of 25 rats consisting of five groups were used in the study, designated as follows: Group 1: control, Group 2: sham, Group 3: unilateral ureteral obstruction treated with only saline, Group 4: unilateral ureteral obstruction treated with melatonin immediately, and Group 5: unilateral obstruction treated with melatonin one day after obstruction. Melatonin was administered as a 10 mg/kg dose intraperitoneally. The kidneys were evaluated according to the apoptotic index and Ki-67 scores. Results Comparison of all obstruction groups (Group 3, 4, and 5), revealed that the apoptotic index was significantly higher in Groups 1 and 2. Despite melatonin reduced apoptotic mechanisms in Groups 4 and 5, there was no significant difference between Groups 4 and 5 in terms of the reduction of apoptosis. However, the reduction of apoptosis in the melatonin treated group did not decrease to the level of Groups 1 and 2. Conclusions Despite melatonin administration, which significantly reduces the apoptotic index occurring after acute unilateral ureteral obstruction, the present study did not observe a return to normal renal histology in the obstruction groups. PMID:27551563

  11. Ulinastatin Protects against Acute Kidney Injury in Infant Piglets Model Undergoing Surgery on Hypothermic Low-Flow Cardiopulmonary Bypass.

    Directory of Open Access Journals (Sweden)

    Xiaocou Wang

    Full Text Available Infants are more vulnerable to kidney injuries induced by inflammatory response syndrome and ischemia-reperfusion injury following cardiopulmonary bypass especially with prolonged hypothermic low-flow (HLF. This study aims to evaluate the protective role of ulinastatin, an anti-inflammatory agent, against acute kidney injuries in infant piglets model undergoing surgery on HLF cardiopulmonary bypass.Eighteen general-type infant piglets were randomly separated into the ulinastatin group (Group U, n = 6, the control group (Group C, n = 6, and the sham operation group (Group S, n = 6, and anaesthetized. The groups U and C received following experimental procedure: median thoracotomy, routine CPB and HLF, and finally weaned from CPB. The group S only underwent sham median thoracotomy. Ulinastatin at a dose of 5,000 units/kg body weight and a certain volume of saline were administrated to animals of the groups U and C at the beginning of CPB and at aortic declamping, respectively. Venous blood samples were collected at 3 different time points: after anesthesia induction in all experimental groups, 5 minutes, and 120 minutes after CPB in the Groups U and C. Markers for inflammation and acute kidney injury were tested in the collected plasma. N-acetyl-β-D-glucosaminidase (NAG from urine, markers of oxidative stress injury and TUNEL-positive cells in kidney tissues were also detected.The expressions of plasma inflammatory markers and acute kidney injury markers increased both in Group U and Group C at 5 min and 120 min after CPB. Also, numbers of TUNEL-positive cells and oxidative stress markers in kidney rose in both groups. At the time point of 120-min after CPB, compared with the Group C, some plasma inflammatory and acute kidney injury markers as well as TUNEL-positive cells and oxidative stress markers in kidney were significantly reduced in the Group U. Histologic analyses showed that HLF promoted acute tubular necrosis and dilatation

  12. Ulinastatin Protects against Acute Kidney Injury in Infant Piglets Model Undergoing Surgery on Hypothermic Low-Flow Cardiopulmonary Bypass

    Science.gov (United States)

    Wang, Xiaocou; Xue, Qinghua; Yan, Fuxia; Liu, Jinping; Li, Shoujun; Hu, Shengshou

    2015-01-01

    Objective Infants are more vulnerable to kidney injuries induced by inflammatory response syndrome and ischemia-reperfusion injury following cardiopulmonary bypass especially with prolonged hypothermic low-flow (HLF). This study aims to evaluate the protective role of ulinastatin, an anti-inflammatory agent, against acute kidney injuries in infant piglets model undergoing surgery on HLF cardiopulmonary bypass. Methods Eighteen general-type infant piglets were randomly separated into the ulinastatin group (Group U, n = 6), the control group (Group C, n = 6), and the sham operation group (Group S, n = 6), and anaesthetized. The groups U and C received following experimental procedure: median thoracotomy, routine CPB and HLF, and finally weaned from CPB. The group S only underwent sham median thoracotomy. Ulinastatin at a dose of 5,000 units/kg body weight and a certain volume of saline were administrated to animals of the groups U and C at the beginning of CPB and at aortic declamping, respectively. Venous blood samples were collected at 3 different time points: after anesthesia induction in all experimental groups, 5 minutes, and 120 minutes after CPB in the Groups U and C. Markers for inflammation and acute kidney injury were tested in the collected plasma. N-acetyl-β-D-glucosaminidase (NAG) from urine, markers of oxidative stress injury and TUNEL-positive cells in kidney tissues were also detected. Results The expressions of plasma inflammatory markers and acute kidney injury markers increased both in Group U and Group C at 5 min and 120 min after CPB. Also, numbers of TUNEL-positive cells and oxidative stress markers in kidney rose in both groups. At the time point of 120-min after CPB, compared with the Group C, some plasma inflammatory and acute kidney injury markers as well as TUNEL-positive cells and oxidative stress markers in kidney were significantly reduced in the Group U. Histologic analyses showed that HLF promoted acute tubular necrosis and dilatation

  13. Epidemiology of acute kidney injury in intensive care septic patients based on the KDIGO guidelines

    Institute of Scientific and Technical Information of China (English)

    Peng Qianyi; Zhang Lina; Ai Yuhang; Zhang Lemeng

    2014-01-01

    Background Acute kidney injury (AKI) is a common complication of sepsis,which is associated with higher risks of adverse outcomes.Recently,kidney disease:improving global outcomes (KDIGO) recommended a new guideline forAKI,including a little modification on the AKI staging criteria.Methods This retrospective study included 211 septic patients admitted to the intensive care unit (ICU) at Xiangya Hospital,Central South University from January 2008 to January 2011.AKI was diagnosed and classified according to the KDIGO or acute kidney injury network (AKIN) criteria.Differences between the AKI and non-AKI groups for baseline characteristics,laboratory examinations,etiology,outcomes,as well as the risk factors for AKI and 28-day mortality were analyzed.The reliability of the KDIGO criteria was also evaluated by comparing it with the AKIN criteria.Results The overall incidence of AKI in septic patients was 47.9%,and the 28-day mortality was 32.7%.The incidence of AKI was significantly higher in patients with more severe sepsis.Indicators of hepatic and respiratory function were significantly worse in the AKI group.Furthermore,a higher proportion of patients were infected with Enterobacter cloacae in the AKI group.The independent risk factors for AKI were shock,the number of organ failures,blood urea nitrogen (BUN)levels,and the use of vasopressors.The independent risk factors for mortality were BUN and creatine kinase-MB (CK-MB)levels.Both the KDIGO criteria and the AKIN criteria were significantly associated with 28-day mortality.Conclusions The incidence and 28-day mortality of AKI were very high in ICU septic patients.Greater attention should be paid to AKI-induced hepatic and respiratory dysfunction in clinical practice.Patients with an intra-abdominal source of infection were more likely to develop AKI.KDIGO criteria are reliable in AKI staging.

  14. Pyridoxamine reduces postinjury fibrosis and improves functional recovery after acute kidney injury.

    Science.gov (United States)

    Skrypnyk, Nataliya I; Voziyan, Paul; Yang, Haichun; de Caestecker, Christian R; Theberge, Marie-Claude; Drouin, Mathieu; Hudson, Billy; Harris, Raymond C; de Caestecker, Mark P

    2016-08-01

    Acute kidney injury (AKI) is a common and independent risk factor for death and chronic kidney disease (CKD). Despite promising preclinical data, there is no evidence that antioxidants reduce the severity of injury, increase recovery, or prevent CKD in patients with AKI. Pyridoxamine (PM) is a structural analog of vitamin B6 that interferes with oxidative macromolecular damage via a number of different mechanisms and is in a phase 3 clinical efficacy trial to delay CKD progression in patients with diabetic kidney disease. Because oxidative stress is implicated as one of the main drivers of renal injury after AKI, the ability of PM to interfere with multiple aspects of oxidative damage may be favorable for AKI treatment. In these studies we therefore evaluated PM treatment in a mouse model of AKI. Pretreatment with PM caused a dose-dependent reduction in acute tubular injury, long-term postinjury fibrosis, as well as improved functional recovery after ischemia-reperfusion AKI (IR-AKI). This was associated with a dose-dependent reduction in the oxidative stress marker isofuran-to-F2-isoprostane ratio, indicating that PM reduces renal oxidative damage post-AKI. PM also reduced postinjury fibrosis when administered 24 h after the initiating injury, but this was not associated with improvement in functional recovery after IR-AKI. This is the first report showing that treatment with PM reduces short- and long-term injury, fibrosis, and renal functional recovery after IR-AKI. These preclinical findings suggest that PM, which has a favorable clinical safety profile, holds therapeutic promise for AKI and, most importantly, for prevention of adverse long-term outcomes after AKI. PMID:27194713

  15. PLASMA NEUTROPHIL GELATINASE ASSOCIATED LIPOCALIN AS AN EARLY BIOMARKER OF ACUTE KIDNEY INJURY IN SNAKE BITE

    Directory of Open Access Journals (Sweden)

    Thamarai

    2014-12-01

    Full Text Available INTRODUCTION: Acute kidney injury due to snake bite represents a frequent and devastating problem. Currently, Acute Kidney Injury is diagnosed by biochemical monitoring of increase in serum creatinine. Increase in serum creatinine represents a late indication of a functional change in glomerular function rate. Studies have shown that Neutrophil Gelatinase Associated Lipocalin has been found to be very useful for the detection of acute kidney injury within few hours of nephrotoxic insult. Limited information, however, is available regarding the study of plasma Neutrophil Gelatinase-Associated Lipocalin in snake bite. AIM: The purpose of the study was to estimate the diagnostic accuracy of plasma Neutrophil Gelatinase-Associated Lipocalin as an early biomarker of Acute Kidney Injury in patients with snake bite and to correlate with serum creatinine. If early detection of Acute Kidney Injury occurs, it can be followed by effective treatment modalities to abort the development or limit the severity of AKI. Therefore this study was designed to explore the importance of pNGAL in cases of snake bite induced AKI. MATERIALS AND METHODS: A prospective observational study was designed to study the patients admitted for the treatment of snakebite within 6 hours in a tertiary care hospital. Patients admitted for snake bite were followed by estimation of pNGAL on day 1 and serum creatinine from the period of admission for up to 5 days. A total of 130 snake bite patients were enrolled and 100 were included in the final study. Snake bite patients were classified into two groups based on the occurrence and absence of AKI. Plasma NGAL and serum creatinine was estimated by solid phase Enzyme Linked Immunosorbent Assay method and Jaffe`s method respectively. Data were entered into the excel sheet and analyzed statistically using statistical package for the social sciences (SPSS version 17. RESULTS:Among 100 snake bite patients 64 individuals had elevated p

  16. Immune Complex Mediated Glomerulonephritis with Acute Thrombotic Microangiopathy following Newly Detected Hepatitis B Virus Infection in a Kidney Transplant Recipient

    Science.gov (United States)

    Burton, Hannah; Douthwaite, Sam; Newsholme, William; Horsfield, Catherine

    2016-01-01

    Hepatitis B virus (HBV) presents a risk to patients and staff in renal units. To minimise viral transmission, there are international and UK guidelines recommending HBV immunisation for patients commencing renal replacement therapy (RRT) and HBV surveillance in kidney transplant recipients. We report the case of a 56-year-old male who was immunised against HBV before starting haemodialysis. He received a deceased donor kidney transplant three years later, at which time there was no evidence of HBV infection. After a further six years he developed an acute kidney injury; allograft biopsy revealed an acute thrombotic microangiopathy (TMA) with glomerulitis, peritubular capillaritis, and C4d staining. Due to a “full house” immunoprofile, tests including virological screening were undertaken, which revealed acute HBV infection. Entecavir treatment resulted in an improvement in viral load and kidney function. HBV genotyping demonstrated a vaccine escape mutant, suggesting “past resolved” infection that reactivated with immunosuppression, though posttransplant acquisition cannot be excluded. This is the first reported case of acute HBV infection associated with immune complex mediated glomerulonephritis and TMA. Furthermore, it highlights the importance of HBV surveillance in kidney transplant recipients, which although addressed by UK guidelines is not currently practiced in all UK units.

  17. Immune Complex Mediated Glomerulonephritis with Acute Thrombotic Microangiopathy following Newly Detected Hepatitis B Virus Infection in a Kidney Transplant Recipient

    Directory of Open Access Journals (Sweden)

    Tracey Salter

    2016-01-01

    Full Text Available Hepatitis B virus (HBV presents a risk to patients and staff in renal units. To minimise viral transmission, there are international and UK guidelines recommending HBV immunisation for patients commencing renal replacement therapy (RRT and HBV surveillance in kidney transplant recipients. We report the case of a 56-year-old male who was immunised against HBV before starting haemodialysis. He received a deceased donor kidney transplant three years later, at which time there was no evidence of HBV infection. After a further six years he developed an acute kidney injury; allograft biopsy revealed an acute thrombotic microangiopathy (TMA with glomerulitis, peritubular capillaritis, and C4d staining. Due to a “full house” immunoprofile, tests including virological screening were undertaken, which revealed acute HBV infection. Entecavir treatment resulted in an improvement in viral load and kidney function. HBV genotyping demonstrated a vaccine escape mutant, suggesting “past resolved” infection that reactivated with immunosuppression, though posttransplant acquisition cannot be excluded. This is the first reported case of acute HBV infection associated with immune complex mediated glomerulonephritis and TMA. Furthermore, it highlights the importance of HBV surveillance in kidney transplant recipients, which although addressed by UK guidelines is not currently practiced in all UK units.

  18. Cisplatin-induced renal toxicity via tumor necrosis factor-α, interleukin 6, tumor suppressor P53, DNA damage, xanthine oxidase, histological changes, oxidative stress and nitric oxide in rats: protective effect of ginseng.

    Science.gov (United States)

    Yousef, Mokhtar I; Hussien, Hend M

    2015-04-01

    Cisplatin is an effective chemotherapeutic agent successfully used in the treatment of a wide range of solid tumors, while its usage is limited due to its nephrotoxicity. The present study was undertaken to examine the effectiveness of ginseng to ameliorate the renal nephrotoxicity, damage in kidney genomic DNA, tumor necrosis factor-α, interleukin 6, tumor suppressor P53, histological changes and oxidative stress induced by cisplatin in rats. Cisplatin caused renal damage, including DNA fragmentation, upregulates gene expression of tumor suppressor protein p53 and tumor necrosis factor-α and IL-6. Cisplatin increased the levels of kidney TBARS, xanthine oxidase, nitric oxide, serum urea and creatinine. Cisplatin decreased the activities of antioxidant enzymes (GST, GPX, CAT and SOD), ATPase and the levels of GSH. A microscopic examination showed that cisplatin caused kidney damage including vacuolization, severe necrosis and degenerative changes. Ginseng co-treatment with cisplatin reduced its renal damage, oxidative stress, DNA fragmentation and induced DNA repair processes. Also, ginseng diminished p53 activation and improved renal cell apoptosis and nephrotoxicity. It can be concluded that, the protective effects of ginseng against cisplatin induced-renal damage was associated with the attenuation of oxidative stress and the preservation of antioxidant enzymes.

  19. Comparison of Plasma and Urine Biomarker Performance in Acute Kidney Injury

    Science.gov (United States)

    Schley, Gunnar; Köberle, Carmen; Manuilova, Ekaterina; Rutz, Sandra; Forster, Christian; Weyand, Michael; Formentini, Ivan; Kientsch-Engel, Rosemarie; Eckardt, Kai-Uwe; Willam, Carsten

    2015-01-01

    Background New renal biomarkers measured in urine promise to increase specificity for risk stratification and early diagnosis of acute kidney injury (AKI) but concomitantly may be altered by urine concentration effects and chronic renal insufficiency. This study therefore directly compared the performance of AKI biomarkers in urine and plasma. Methods This single-center, prospective cohort study included 110 unselected adults undergoing cardiac surgery with cardiopulmonary bypass between 2009 and 2010. Plasma and/or urine concentrations of creatinine, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), liver fatty acid-binding protein (L-FABP), kidney injury molecule 1 (KIM1), and albumin as well as 15 additional biomarkers in plasma and urine were measured during the perioperative period. The primary outcome was AKI defined by AKIN serum creatinine criteria within 72 hours after surgery. Results Biomarkers in plasma showed markedly better discriminative performance for preoperative risk stratification and early postoperative (within 24h after surgery) detection of AKI than urine biomarkers. Discriminative power of urine biomarkers improved when concentrations were normalized to urinary creatinine, but urine biomarkers had still lower AUC values than plasma biomarkers. Best diagnostic performance 4h after surgery had plasma NGAL (AUC 0.83), cystatin C (0.76), MIG (0.74), and L-FAPB (0.73). Combinations of multiple biomarkers did not improve their diagnostic power. Preoperative clinical scoring systems (EuroSCORE and Cleveland Clinic Foundation Score) predicted the risk for AKI (AUC 0.76 and 0.71) and were not inferior to biomarkers. Preexisting chronic kidney disease limited the diagnostic performance of both plasma and urine biomarkers. Conclusions In our cohort plasma biomarkers had higher discriminative power for risk stratification and early diagnosis of AKI than urine biomarkers. For preoperative risk stratification of AKI clinical models showed

  20. Comparison of Plasma and Urine Biomarker Performance in Acute Kidney Injury.

    Directory of Open Access Journals (Sweden)

    Gunnar Schley

    Full Text Available New renal biomarkers measured in urine promise to increase specificity for risk stratification and early diagnosis of acute kidney injury (AKI but concomitantly may be altered by urine concentration effects and chronic renal insufficiency. This study therefore directly compared the performance of AKI biomarkers in urine and plasma.This single-center, prospective cohort study included 110 unselected adults undergoing cardiac surgery with cardiopulmonary bypass between 2009 and 2010. Plasma and/or urine concentrations of creatinine, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL, liver fatty acid-binding protein (L-FABP, kidney injury molecule 1 (KIM1, and albumin as well as 15 additional biomarkers in plasma and urine were measured during the perioperative period. The primary outcome was AKI defined by AKIN serum creatinine criteria within 72 hours after surgery.Biomarkers in plasma showed markedly better discriminative performance for preoperative risk stratification and early postoperative (within 24h after surgery detection of AKI than urine biomarkers. Discriminative power of urine biomarkers improved when concentrations were normalized to urinary creatinine, but urine biomarkers had still lower AUC values than plasma biomarkers. Best diagnostic performance 4h after surgery had plasma NGAL (AUC 0.83, cystatin C (0.76, MIG (0.74, and L-FAPB (0.73. Combinations of multiple biomarkers did not improve their diagnostic power. Preoperative clinical scoring systems (EuroSCORE and Cleveland Clinic Foundation Score predicted the risk for AKI (AUC 0.76 and 0.71 and were not inferior to biomarkers. Preexisting chronic kidney disease limited the diagnostic performance of both plasma and urine biomarkers.In our cohort plasma biomarkers had higher discriminative power for risk stratification and early diagnosis of AKI than urine biomarkers. For preoperative risk stratification of AKI clinical models showed similar discriminative performance

  1. Sodium selenosulfate at an innocuous dose markedly prevents cisplatin-induced gastrointestinal toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jun; Sun, Kang [School of Tea and Food Science, Anhui Agricultural University, Hefei 230036, Anhui (China); Ni, Lijuan; Wang, Xufang [School of Chemistry and Materials of Science, University of Science and Technology of China, Hefei 230052, Anhui (China); Wang, Dongxu [School of Tea and Food Science, Anhui Agricultural University, Hefei 230036, Anhui (China); Zhang, Jinsong, E-mail: zjs@ahau.edu.cn [School of Tea and Food Science, Anhui Agricultural University, Hefei 230036, Anhui (China)

    2012-02-01

    Our previous studies in mice revealed that two weeks short-term toxicity of sodium selenosulfate was significantly lower than that of sodium selenite, but selenium repletion efficacy of both compounds was equivalent. In addition, we showed that sodium selenosulfate reduced nephrotoxicity of cisplatin (CDDP) without compromising its anticancer activity, thus leading to a dramatic increase of cancer cure rate from 25% to 75%. Hydration has been used in clinical practice to reduce CDDP-induced nephrotoxicity, but it cannot mitigate CDDP-induced gastrointestinal toxicity. The present work investigated whether sodium selenosulfate is a potential preventive agent for the gastrointestinal toxicity. In tumor-bearing mice, sodium selenosulfate was administered at a dose of 9.5 μmol/kg daily for 11 days, CDDP alone resulted in diarrhea by 88% on day 12, whereas the co-administration of CDDP and sodium selenosulfate dramatically reduced diarrhea to 6% (p < 0.0001). Such a prominent protective effect promoted us to evaluate the safety potential of long-term sodium selenosulfate application. Mice were administered with sodium selenosulfate or sodium selenite for 55 days at the doses of 12.7 and 19 μmol/kg. The low-dose sodium selenite caused growth suppression and hepatotoxicity which were aggravated by the high-dose, leading to 40% mortality rate, but no toxic symptoms were observed in the two sodium selenosulfate groups. Altogether these results clearly show that sodium selenosulfate at an innocuous dose can markedly prevent CDDP-induced gastrointestinal toxicity. -- Highlights: ►Cisplatin resulted in diarrhea in mice by 88%. ►i.p. selenosulfate at 9.5 μmol/kg daily for 11 days reduced diarrhea to 6%. ►i.p. selenosulfate at 19 μmol/kg daily for 55 days was not toxic. ►i.p. selenite at 19 μmol/kg daily for 55 days was lethal. ►Innocuous dose of selenosulfate greatly prevents cisplatin-induced diarrhea.

  2. Impact of onset time of acute kidney injury on outcomes in patients with acute decompensated heart failure.

    Science.gov (United States)

    Takaya, Yoichi; Yoshihara, Fumiki; Yokoyama, Hiroyuki; Kanzaki, Hideaki; Kitakaze, Masafumi; Goto, Yoichi; Anzai, Toshihisa; Yasuda, Satoshi; Ogawa, Hisao; Kawano, Yuhei

    2016-01-01

    Since acute kidney injury (AKI) is not always related to mortality in patients with acute decompensated heart failure (ADHF), the aim of this study was to focus on onset time of AKI and its clinical importance. A total of 371 ADHF patients were included. The impact of AKI (≥ 0.3 mg/dl or 1.5-fold increase in serum creatinine level within 48 h) with early onset (≤ 4 days from admission) or late onset (≥ 5 days from admission) was assessed. AKI occurred in 99 patients, who were divided into two groups according to the median onset time of AKI: 50 with early onset of AKI and 49 with late onset of AKI. The maximum increase in serum creatinine level from admission was greater in patients with late onset of AKI than in patients with early onset of AKI (p = 0.012). Patients with late onset of AKI had a higher 12-month mortality rate than that in patients with early onset of AKI (log-rank test, p = 0.014). Late onset of AKI was an independent predictor of mortality (hazard ratio: 3.39, 95 % confidence interval: 1.84-6.18, p time of AKI may be useful for risk stratification of mortality in ADHF patients developing AKI.

  3. SIRT1 overexpression decreases cisplatin-induced acetylation of NF-{kappa}B p65 subunit and cytotoxicity in renal proximal tubule cells

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Yu Jin; Lee, Jung Eun; Lee, Ae Sin [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Kang, Kyung Pyo; Lee, Sik; Park, Sung Kwang [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Lee, Sang Yong [Department of Diagnostic Radiology, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Han, Myung Kwan [Department of Microbiology, Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Kim, Duk Hoon [Division of Forensic Medicine, National Forensic Service, Seoul (Korea, Republic of); Kim, Won, E-mail: kwon@jbnu.ac.kr [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju (Korea, Republic of)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer Cisplatin increases acetylation of NF-{kappa}B p65 subunit in HK2 cells. Black-Right-Pointing-Pointer SIRT1 overexpression decreases cisplatin-induced p65 acetylation and -cytotoxicity. Black-Right-Pointing-Pointer Resveratrol decreased cisplatin-induced cell viability through deacetylation of p65. -- Abstract: As the increased acetylation of p65 is linked to nuclear factor-{kappa}B (NF-{kappa}B) activation, the regulation of p65 acetylation can be a potential target for the treatment of inflammatory injury. Cisplatin-induced nephrotoxicity is an important issue in chemotherapy of cancer patients. SIRT1, nicotinamide adenine dinucleotide (NAD{sup +})-dependent protein deacetylase, has been implicated in a variety of cellular processes such as inflammatory injury and the control of multidrug resistance in cancer. However, there is no report on the effect of SIRT1 overexpression on cisplatin-induced acetylation of p65 subunit of NF-{kappa}B and cell injury. To investigate the effect of SIRT1 in on cisplatin-induced acetylation of p65 subunit of NF-{kappa}B and cell injury, HK2 cells were exposed with SIRT1 overexpression, LacZ adenovirus or dominant negative adenovirus after treatment with cisplatin. While protein expression of SIRT1 was decreased by cisplatin treatment compared with control buffer treatment, acetylation of NF-{kappa}B p65 subunit was significantly increased after treatment with cisplatin. Overexpression of SIRT1 ameliorated the increased acetylation of p65 of NF-{kappa}B during cisplatin treatment and cisplatin-induced cytotoxicity. Further, treatment of cisplatin-treated HK2 cells with resveratrol, a SIRT1 activator, also decreased acetylation of NF-{kappa}B p65 subunit and cisplatin-induced increase of the cell viability in HK2 cells. Our findings suggests that the regulation of acetylation of p65 of NF-{kappa}B through SIRT1 can be a possible target to attenuate cisplatin-induced renal cell damage.

  4. The relationship between hyperuricemia and the risk of contrast-induced acute kidney injury after percutaneous coronary intervention in patients with relatively normal serum creatinine

    OpenAIRE

    Yong Liu; Ning Tan; Jiyan Chen; Yingling Zhou; Liling Chen; Shiqun Chen; Zhujun Chen; Liwen Li

    2013-01-01

    OBJECTIVES: Hyperuricemia is a risk factor for contrast-induced acute kidney injury in patients with chronic kidney disease. This study evaluated the value of hyperuricemia for predicting the risk of contrast-induced acute kidney injury in patients with relatively normal serum creatinine who were undergoing percutaneous coronary interventions. METHODS AND RESULTS: A total of 788 patients with relatively normal baseline serum creatinine (7 mg/ dL in males and >6 mg/dL in females. The incidence...

  5. miR-203 inhibits cell proliferation and promotes cisplatin induced cell death in tongue squamous cancer.

    Science.gov (United States)

    Lin, Jiong; Lin, Yao; Fan, Li; Kuang, Wei; Zheng, Liwei; Wu, Jiahua; Shang, Peng; Wang, Qiaofeng; Tan, Jiali

    2016-04-29

    Oral squamous cell carcinoma (OSCC) is one of the most common types of the head and neck cancer. Chemo resistance of OSCC has been identified as a substantial therapeutic hurdle. In this study, we analyzed the role of miR-203 in the OSCC and its effects on cisplatin-induced cell death in an OSCC cell line, Tca8113. There was a significant decrease of miR-203 expression in OSCC samples, compared with the adjacent normal, non-cancerous tissue. After 3 days cisplatin treatment, the survived Tca8113 cells had a lower expression of miR-203 than that in the untreated control group. In contrast, PIK3CA showed an inverse expression in cancer and cisplatin survived Tca8113 cells. Transfection of Tca8113 cells with miR-203 mimics greatly reduced PIK3CA expression and Akt activation. Furthermore, miR-203 repressed PIK3CA expression through targeting the 3'UTR. Restoration of miR-203 not only suppressed cell proliferation, but also sensitized cells to cisplatin induced cell apoptosis. This effect was absent in cells that were simultaneously treated with PIK3CA RNAi. In summary, these findings suggest miR-203 plays an important role in cisplatin resistance in OSCC, and furthermore delivery of miR-203 analogs may serve as an adjuvant therapy for OSCC.

  6. Aspirin-triggered resolvin D1 down-regulates inflammatory responses and protects against endotoxin-induced acute kidney injury

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jiao [Center for Research on Environmental Disease, University of Kentucky, Lexington, KY 40536 (United States); Shetty, Sreerama [Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, TX 75708 (United States); Zhang, Ping [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041 (China); Gao, Rong; Hu, Yuxin [Center for Research on Environmental Disease, University of Kentucky, Lexington, KY 40536 (United States); Wang, Shuxia [Graduate Center for Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Li, Zhenyu [Division of Cardiovascular Medicine, University of Kentucky, Lexington, KY 40536 (United States); Fu, Jian, E-mail: jian.fu@uky.edu [Center for Research on Environmental Disease, University of Kentucky, Lexington, KY 40536 (United States); Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States)

    2014-06-01

    The presence of endotoxin in blood can lead to acute kidney injury (AKI) and septic shock. Resolvins, the endogenous lipid mediators derived from docosahexaenoic acid, have been reported to exhibit potent anti-inflammatory action. Using a mouse model of lipopolysaccharide (LPS)-induced AKI, we investigated the effects of aspirin-triggered resolvin D1 (AT-RvD1) on inflammatory kidney injury. Administration of AT-RvD1 1 h after LPS challenge protected the mice from kidney injury as indicated by the measurements of blood urea nitrogen, serum creatinine, and morphological alterations associated with tubular damage. The protective effects were evidenced by decreased neutrophil infiltration in the kidney indicating reduction in inflammation. AT-RvD1 treatment restored kidney cell junction protein claudin-4 expression, which was otherwise reduced after LPS challenge. AT-RvD1 treatment inhibited endotoxin-induced NF-κB activation and suppressed LPS-induced ICAM-1 and VCAM-1 expression in the kidney. Moreover, AT-RvD1 treatment markedly decreased LPS-induced IL-6 level in the kidney and blocked IL-6-mediated signaling including STAT3 and ERK phosphorylation. Our findings demonstrate that AT-RvD1 is a potent anti-inflammatory mediator in LPS-induced kidney injury, and AT-RvD1 has therapeutic potential against AKI during endotoxemia.

  7. Aspirin-triggered resolvin D1 down-regulates inflammatory responses and protects against endotoxin-induced acute kidney injury

    International Nuclear Information System (INIS)

    The presence of endotoxin in blood can lead to acute kidney injury (AKI) and septic shock. Resolvins, the endogenous lipid mediators derived from docosahexaenoic acid, have been reported to exhibit potent anti-inflammatory action. Using a mouse model of lipopolysaccharide (LPS)-induced AKI, we investigated the effects of aspirin-triggered resolvin D1 (AT-RvD1) on inflammatory kidney injury. Administration of AT-RvD1 1 h after LPS challenge protected the mice from kidney injury as indicated by the measurements of blood urea nitrogen, serum creatinine, and morphological alterations associated with tubular damage. The protective effects were evidenced by decreased neutrophil infiltration in the kidney indicating reduction in inflammation. AT-RvD1 treatment restored kidney cell junction protein claudin-4 expression, which was otherwise reduced after LPS challenge. AT-RvD1 treatment inhibited endotoxin-induced NF-κB activation and suppressed LPS-induced ICAM-1 and VCAM-1 expression in the kidney. Moreover, AT-RvD1 treatment markedly decreased LPS-induced IL-6 level in the kidney and blocked IL-6-mediated signaling including STAT3 and ERK phosphorylation. Our findings demonstrate that AT-RvD1 is a potent anti-inflammatory mediator in LPS-induced kidney injury, and AT-RvD1 has therapeutic potential against AKI during endotoxemia

  8. Effects of Schizolobium parahyba extract on experimental Bothrops venom-induced acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Monique Silva Martines

    Full Text Available BACKGROUND: Venom-induced acute kidney injury (AKI is a frequent complication of Bothrops snakebite with relevant morbidity and mortality. The aim of this study was to assess the effects of Schizolobium parahyba (SP extract, a natural medicine with presumed anti-Bothrops venom effects, in an experimental model of Bothrops jararaca venom (BV-induced AKI. METHODOLOGY: Groups of 8 to 10 rats received infusions of 0.9% saline (control, C, SP 2 mg/kg, BV 0.25 mg/kg and BV immediately followed by SP (treatment, T in the doses already described. After the respective infusions, animals were assessed for their glomerular filtration rate (GFR, inulin clearance, renal blood flow (RBF, Doppler, blood pressure (BP, intra-arterial transducer, renal vascular resistance (RVR, urinary osmolality (UO, freezing point, urinary neutrophil gelatinase-associated lipocalin (NGAL, enzyme-linked immunosorbent assay [ELISA], lactate dehydrogenase (LDH, kinetic method, hematocrit (Hct, microhematocrit, fibrinogen (Fi, Klauss modified and blinded renal histology (acute tubular necrosis score. PRINCIPAL FINDINGS: BV caused significant decreases in GFR, RBF, UO, HcT and Fi; significant increases in RVR, NGAL and LDH; and acute tubular necrosis. SP did not prevent these changes; instead, it caused a significant decrease in GFR when used alone. CONCLUSION: SP administered simultaneously with BV, in an approximate 10∶1 concentration, did not prevent BV-induced AKI, hemolysis and fibrinogen consumption. SP used alone caused a decrease in GFR.

  9. STUDY OF ACUTE KIDNEY INJURY IN CHILDREN: ITS AETIOLOGY, CLINICAL PROFILE AND OUTCOME

    Directory of Open Access Journals (Sweden)

    Garuda

    2015-03-01

    Full Text Available OBJECTIVES : To determine the incidence , age & sex ratio , analyse the spectrum of Acute Kidney Injury (AKI in its aetiopathology , complications including mortality , prognostic factors and the role of dialysis in the management. METHODS : This prospective observational study was conducted on serial cases of 30 patients a dmitted in Paediatrics department from Feb 2012 - Aug 2014 (30 months. RESULTS : The incidence of AKI was 0.44%. Children in age group of 0 - 4 yrs were affected most , predominantly males. Distribution of AKI according to aetiopathogenesis was Acute Tubular Necrosis (ATN 50% , Haemolytic Uraemic Syndrome (HUS 19.8% , Glomerulonephritis (GN 13.2% , Obstructive uropathy 9.9% and Acute on Chronic renal failure (CRF 6.6%. Dialysis was required in 53.3% of patients. Mortality was 57%. Patients with complications of sepsis , neurological & respiratory problems , hyperkalemia , metabolic acidosis and gastrointestinal bleeding were associated with high mortality. CONCLUSIONS : AKI is a common life threatening condition seen in childhood. Early referral , proper assessment , adequate & timely treatment and prompt institution of dialysis helps in decreasing mortality.

  10. Plasma levels of microRNA in chronic kidney disease: patterns in acute and chronic exercise.

    Science.gov (United States)

    Van Craenenbroeck, Amaryllis H; Ledeganck, Kristien J; Van Ackeren, Katrijn; Jürgens, Angelika; Hoymans, Vicky Y; Fransen, Erik; Adams, Volker; De Winter, Benedicte Y; Verpooten, Gert A; Vrints, Christiaan J; Couttenye, Marie M; Van Craenenbroeck, Emeline M

    2015-12-15

    Exercise training is an effective way to improve exercise capacity in chronic kidney disease (CKD), but the underlying mechanisms are only partly understood. In healthy subjects (HS), microRNA (miRNA or miR) are dynamically regulated following exercise and have, therefore, been suggested as regulators of cardiovascular adaptation to exercise. However, these effects were not studied in CKD before. The effect of acute exercise (i.e., an acute exercise bout) was assessed in 32 patients with CKD and 12 age- and sex-matched HS (study 1). miRNA expression in response to chronic exercise (i.e., a 3-mo exercise training program) was evaluated in 40 CKD patients (study 2). In a subgroup of study 2, the acute-exercise induced effect was evaluated at baseline and at follow-up. Plasma levels of a preselected panel miRNA, involved in exercise adaptation processes such as angiogenesis (miR-126, miR-210), inflammation (miR-21, miR-146a), hypoxia/ischemia (miR-21, miR-210), and progenitor cells (miR-150), were quantified by RT-PCR. Additionally, seven miRNA involved in similar biological processes were quantified in the subgroup of study 2. Baseline, studied miRNA were comparable in CKD and HS. Following acute exercise, miR-150 levels increased in both CKD (fold change 2.12 ± 0.39, P = 0.002; and HS: fold change 2.41 ± 0.48 P = 0.018, P for interaction > 0.05). miR-146a acutely decreased in CKD (fold change 0.92 ± 0.13, P = 0.024), whereas it remained unchanged in HS. Levels of miR-21, miR-126, and miR-210 remained unaltered. Chronic exercise did not elicit a significant change in the studied miRNA levels. However, an acute exercise-induced decrease in miR-210 was observed in CKD patients, only after training (fold change 0.76 ± 0.15). The differential expression in circulating miRNA in response to acute and chronic exercise may point toward a physiological role in cardiovascular adaptation to exercise, also in CKD. PMID:26475583

  11. Coupled plasma filtration adsorption for the treatment of a patient with acute respiratory distress syndrome and acute kidney injury: a case report.

    Science.gov (United States)

    Lucisano, Gaetano; Capria, Maria; Matera, Giovanni; Presta, Pierangela; Comi, Nicolino; Talarico, Roberta; Rametti, Linda; Quirino, Angela; Giancotti, Aida; Fuiano, Giorgio

    2011-10-01

    Coupled plasma filtration adsorption (CPFA) is an extracorporeal blood purification therapy based on non-specific pro- and anti-inflammatory mediator adsorption on a special resin cartridge coupled with continuous veno-venous haemofiltration or continuous veno-venous haemodiafiltration and is one of the emerging treatments for septic patients. However, in the literature, there are limited data about its efficacy in treating patients with acute diseases but without the traditional criteria for sepsis. We describe the case of a 43-year-old male who developed acute respiratory distress syndrome secondary to pneumonia and acute kidney injury, whose clinical conditions rapidly improved after early CPFA therapy.

  12. N-octanoyl dopamine treatment exerts renoprotective properties in acute kidney injury but not in renal allograft recipients

    NARCIS (Netherlands)

    Klotz, Sarah; Pallavi, Prama; Tsagogiorgas, Charalambos; Zimmer, Fabian; Zoellner, Frank G.; Binzen, Uta; Greffrath, Wolfgang; Treede, Rolf-Detlef; Walter, Jakob; Harmsen, Martin C.; Kraemer, Bernhard K.; Hafner, Mathias; Yard, Benito A.; Hoeger, Simone

    2016-01-01

    N-octanoyl dopamine (NOD) treatment improves renal function when applied to brain dead donors and in the setting of warm ischaemia-induced acute kidney injury (AKI). Because it also activates transient receptor potential vanilloid type 1 (TRPV1) channels, we first assessed if NOD conveys its renopro

  13. A comparison of early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury

    DEFF Research Database (Denmark)

    2011-01-01

    Introduction: Our aim was to investigate the impact of early versus late initiation of renal replacement therapy (RRT) on clinical outcomes in critically ill patients with acute kidney injury (AKI). Methods: Systematic review and meta-analysis were used in this study. PUBMED, EMBASE, SCOPUS, Web...

  14. A Meta-analysis of the Association of Estimated GFR, Albuminuria, Age, Race, and Sex With Acute Kidney Injury

    NARCIS (Netherlands)

    Grams, Morgan E.; Sang, Yingying; Ballew, Shoshana H.; Gansevoort, Ron T.; Kimm, Heejin; Kovesdy, Csaba P.; Naimark, David; Oien, Cecilia; Smith, David H.; Coresh, Josef; Sarnak, Mark J.; Stengel, Benedicte; Tonelli, Marcello; de Zeeuw, Dick; Bakker, Stephan J. L.; van der Harst, Pim; Heerspink, Hiddo J.; Hillege, Hans L.

    2015-01-01

    Background: Acute kidney injury (AKI) is a serious global public health problem. We aimed to quantify the risk of AKI associated with estimated glomerular filtration rate (eGFR), albuminuria (albumin-creatinine ratio [ACR]), age, sex, and race (African American and white). Study Design: Collaborativ

  15. Dialysis-requiring acute kidney injury in Denmark 2000-2012: time trends of incidence and prevalence of risk factors

    DEFF Research Database (Denmark)

    Carlson, Nicholas; Hommel, Kristine; Olesen, Jonas Bjerring;

    2016-01-01

    INTRODUCTION: Dialysis-requiring acute kidney injury is a severe illness associated with poor prognosis. However, information pertaining to incidence rates and prevalence of risk factors remains limited in spite of increasing focus. We evaluate time trends of incidence rates and changing patterns...

  16. Trends in one-year outcomes of dialysis-requiring acute kidney injury in Denmark 2005-2012

    DEFF Research Database (Denmark)

    Carlson, Nicholas; Hommel, Kristine; Olesen, Jonas Bjerring;

    2016-01-01

    BACKGROUND: Dialysis-requiring acute kidney injury (AKI) is associated with substantial mortality and risk of end-stage renal disease (ESRD). Despite considerable growth in incidence of severe AKI, information pertaining to trends in outcomes remains limited. We evaluated time trends in one year ...

  17. Serum and urine cystatin C are poor biomarkers for acute kidney injury and renal replacement therapy

    NARCIS (Netherlands)

    A.A.N.M. Royakkers; J.C. Korevaar; J.D.E. van Suijlen; L.S. Hofstra; M.A. Kuiper; P.E. Spronk; M.J. Schultz; C.S.C. Bouman

    2011-01-01

    To evaluate whether cystatin C in serum (sCyC) and urine (uCyC) can predict early acute kidney injury (AKI) in a mixed heterogeneous intensive care unit (ICU), and also whether these biomarkers can predict the need for renal replacement therapy (RRT). Multicenter prospective observational cohort stu

  18. First presentation of Addison's disease as hyperkalaemia in acute kidney injury.

    Science.gov (United States)

    Maki, Sara; Kramarz, Caroline; Maria Heister, Paula; Pasha, Kamran

    2016-01-01

    Addison's disease is a rare endocrine disorder that frequently presents with non-specific symptoms, but may deteriorate rapidly into life-threatening Addisonian crisis if left untreated. Diagnosis can be difficult in patients without a suggestive medical history. We describe a case of a 37-year-old man who was admitted with acute kidney injury and hyperkalaemia, resistant to treatment with insulin/dextrose and calcium gluconate. On clinical examination, he was found to be hyperpigmented; a subsequent random serum cortisol of 49 nmol/L affirmed the preliminary diagnosis of Addison's disease. The patient's hyperkalaemia improved on treatment with hydrocortisone, and a follow-up morning adrenocorticotropic hormone of 1051 ng/L confirmed the diagnosis. PMID:27170604

  19. The Regulation of Inflammatory Mediators in Acute Kidney Injury via Exogenous Mesenchymal Stem Cells

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    Tao Du

    2014-01-01

    Full Text Available Acute kidney injury (AKI remains to be an independent risk factor for mortality and morbidity. Inflammation is believed to play a major role in the pathophysiology of AKI. Exogenous mesenchymal stem cells (MSCs are now under extensive investigation as a potential therapy for AKI. Various preclinical studies indicated the beneficial effects of MSCs in alleviating renal injury and accelerating tissue repair. However the mechanisms responsible for these effects are incompletely understood. In the recent years, anti-inflammatory/immunoregulatory properties of MSCs have become one of the important issues in the treatment of AKI. This review will summarize the current literature on the regulation of inflammatory mediators via exogenous MSCs contributing to the recovery from AKI.

  20. Care of the Critically Ill Emergency Department Patient with Acute Kidney Injury

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    Jennifer Joslin

    2012-01-01

    Full Text Available Introduction. Acute Kidney Injury (AKI is common and associated with significant mortality and complications. Exact data on the epidemiology of AKI in the Emergency Department (ED are sparse. This review aims to summarise the key principles for managing AKI patients in the ED. Principal Findings. Timely resuscitation, goal-directed correction of fluid depletion and hypotension, and appropriate management of the underlying illness are essential in preventing or limiting AKI. There is no specific curative therapy for AKI. Key principles of secondary prevention are identification of patients with early AKI, discontinuation of nephrotoxic medication where possible, attention to fluid resuscitation, and awareness of the risks of contrast-induced nephropathy. In patients with advanced AKI, arrangements for renal replacement therapy need to be made before the onset of life-threatening uraemic complications. Conclusions. Research and guidelines regarding AKI in the ED are lacking and AKI practice from critical care departments should be adopted.

  1. Toll‑like receptor 4 contributes to acute kidney injury after cardiopulmonary resuscitation in mice.

    Science.gov (United States)

    Zhang, Qingsong; Li, Gang; Xu, Li; Li, Qian; Wang, Qianyan; Zhang, Yue; Zhang, Qing; Sun, Peng

    2016-10-01

    Toll-like receptor 4 (TLR4) activation mediates renal injury in regional ischemia and reperfusion (I/R) models generated by clamping renal pedicles. However, it remains unclear whether TLR4 is causal in the kidney injury following global I/R induced by cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). The present study used wild‑type (C3H/HeN) and TLR4‑mutant (C3H/HeJ) mice to produce the CA/CPR model. CA was induced by injection of cold KCl and left untreated for different time periods. After resuscitation (72 h), the level of blood urea nitrogen (BUN) and serum creatinine (Scr), as well as histological changes in renal tissue were assessed to evaluate the severity of acute kidney injury (AKI). The expression of TLR4, intercellular adhesion molecule‑1 (ICAM‑1), myeloperoxidase (MPO) and growth‑regulated oncogene‑β (GRO‑β) in kidney tissues was detected. The results demonstrated that the levels of Scr and BUN increased significantly in C3H/HeN and C3H/HeJ mice after CPR. CPR also resulted in increased expression of TLR4, ICAM‑1, GRO‑β and MPO in a CA‑duration dependent manner. However, there was decreased expression of ICAM‑1, GRO‑β and MPO in C3H/HeJ mice compared with that in C3H/HeN mice. C3H/HeJ mice were resistant to AKI as demonstrated by the minor changes in renal histology and function following CPR. In conclusion, mice suffered from AKI after successful CPR and severe AKI occurred in mice with prolonged CA duration. TLR4 and its downstream signaling events that promote neutrophil infiltration via ICAM‑1 and GRO‑β may be important in mediating inflammatory responses to renal injury after CPR. PMID:27510583

  2. Vitamin D deficiency contributes to vascular damage in sustained ischemic acute kidney injury.

    Science.gov (United States)

    de Bragança, Ana C; Volpini, Rildo A; Mehrotra, Purvi; Andrade, Lúcia; Basile, David P

    2016-07-01

    Reductions in renal microvasculature density and increased lymphocyte activity may play critical roles in the progression of chronic kidney disease (CKD) following acute kidney injury (AKI) induced by ischemia/reperfusion injury (IRI). Vitamin D deficiency is associated with tubulointerstitial damage and fibrosis progression following IRI-AKI We evaluated the effect of vitamin D deficiency in sustained IRI-AKI, hypothesizing that such deficiency contributes to the early reduction in renal capillary density or alters the lymphocyte response to IRI Wistar rats were fed vitamin D-free or standard diets for 35 days. On day 28, rats were randomized into four groups: control, vitamin D deficient (VDD), bilateral IRI, and VDD+IRI Indices of renal injury and recovery were evaluated for up to 7 days following the surgical procedures. VDD rats showed reduced capillary density (by cablin staining), even in the absence of renal I/R. In comparison with VDD and IRI rats, VDD+IRI rats manifested a significant exacerbation of capillary rarefaction as well as higher urinary volume, kidney weight/body weight ratio, tissue injury scores, fibroblast-specific protein-1, and alpha-smooth muscle actin. VDD+IRI rats also had higher numbers of infiltrating activated CD4(+) and CD8(+) cells staining for interferon gamma and interleukin-17, with a significant elevation in the Th17/T-regulatory cell ratio. These data suggest that vitamin D deficiency impairs renal repair responses to I/R injury, exacerbates changes in renal capillary density, as well as promoting fibrosis and inflammation, which may contribute to the transition from AKI to CKD.

  3. Toll-like receptor 4 contributes to acute kidney injury after cardiopulmonary resuscitation in mice

    Science.gov (United States)

    Zhang, Qingsong; Li, Gang; Xu, Li; Li, Qian; Wang, Qianyan; Zhang, Yue; Zhang, Qing; Sun, Peng

    2016-01-01

    Toll-like receptor 4 (TLR4) activation mediates renal injury in regional ischemia and reperfusion (I/R) models generated by clamping renal pedicles. However, it remains unclear whether TLR4 is causal in the kidney injury following global I/R induced by cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). The present study used wild-type (C3H/HeN) and TLR4-mutant (C3H/HeJ) mice to produce the CA/CPR model. CA was induced by injection of cold KCl and left untreated for different time periods. After resuscitation (72 h), the level of blood urea nitrogen (BUN) and serum creatinine (Scr), as well as histological changes in renal tissue were assessed to evaluate the severity of acute kidney injury (AKI). The expression of TLR4, intercellular adhesion molecule-1 (ICAM-1), myeloperoxidase (MPO) and growth-regulated oncogene-β (GRO-β) in kidney tissues was detected. The results demonstrated that the levels of Scr and BUN increased significantly in C3H/HeN and C3H/HeJ mice after CPR. CPR also resulted in increased expression of TLR4, ICAM-1, GRO-β and MPO in a CA-duration dependent manner. However, there was decreased expression of ICAM-1, GRO-β and MPO in C3H/HeJ mice compared with that in C3H/HeN mice. C3H/HeJ mice were resistant to AKI as demonstrated by the minor changes in renal histology and function following CPR. In conclusion, mice suffered from AKI after successful CPR and severe AKI occurred in mice with prolonged CA duration. TLR4 and its downstream signaling events that promote neutrophil infiltration via ICAM-1 and GRO-β may be important in mediating inflammatory responses to renal injury after CPR. PMID:27510583

  4. The Effects of Vitamin D on Gentamicin-Induced Acute Kidney Injury in Experimental Rat Model

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    Ender Hur

    2013-01-01

    Full Text Available Introduction. Acute kidney injury (AKI pathogenesis is complex. Findings of gentamicin nephrotoxicity are seen in 30% of the AKI patients. Vitamin D has proven to be effective on renin expression, inflammatory response, oxidative stress, apoptosis, and atherosclerosis. We aimed to investigate the effect of vitamin D in an experimental rat model of gentamicin-induced AKI. Methods. Thirty nonuremic Wistar albino rats were divided into 3 groups: Control group, 1 mL saline intramuscular (im daily; Genta group, gentamicin 100 mg/kg/day (im; Genta + vitamin D, gentamicin 100 mg/kg/day (im in addition to 1α, 25 (OH2D3 0.4 mcg/kg/day subcutaneously for 8 days. Blood pressures and 24-hour urine were measured. Blood urea and creatinine levels and urine tubular injury markers were measured. Renal histology was semiquantitatively assessed. Results. Urea, creatinine and urine neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 were all increased in Genta group indicating AKI model. Systolic blood pressure decreased, but urine volume and glutathione increased in Genta + Vit D group compared to Control group. Histological scores indicating tubular injury increased in Genta and Genta + Vit D groups. Conclusions. Vitamin D does not seem to be effective on histological findings although it has some beneficial effects via RAS system and a promising effect on antioxidant system.

  5. Acute kidney injury following cardiac surgery: current understanding and future directions.

    Science.gov (United States)

    O'Neal, Jason B; Shaw, Andrew D; Billings, Frederic T

    2016-01-01

    Acute kidney injury (AKI) complicates recovery from cardiac surgery in up to 30 % of patients, injures and impairs the function of the brain, lungs, and gut, and places patients at a 5-fold increased risk of death during hospitalization. Renal ischemia, reperfusion, inflammation, hemolysis, oxidative stress, cholesterol emboli, and toxins contribute to the development and progression of AKI. Preventive strategies are limited, but current evidence supports maintenance of renal perfusion and intravascular volume while avoiding venous congestion, administration of balanced salt as opposed to high-chloride intravenous fluids, and the avoidance or limitation of cardiopulmonary bypass exposure. AKI that requires renal replacement therapy occurs in 2-5 % of patients following cardiac surgery and is associated with 50 % mortality. For those who recover from renal replacement therapy or even mild AKI, progression to chronic kidney disease in the ensuing months and years is more likely than for those who do not develop AKI. Cardiac surgery continues to be a popular clinical model to evaluate novel therapeutics, off-label use of existing medications, and nonpharmacologic treatments for AKI, since cardiac surgery is fairly common, typically elective, provides a relatively standardized insult, and patients remain hospitalized and monitored following surgery. More efficient and time-sensitive methods to diagnose AKI are imperative to reduce this negative outcome. The discovery and validation of renal damage biomarkers should in time supplant creatinine-based criteria for the clinical diagnosis of AKI. PMID:27373799

  6. Serum metabolomic profiles from patients with acute kidney injury: a pilot study.

    Science.gov (United States)

    Sun, Jinchun; Shannon, Melissa; Ando, Yosuke; Schnackenberg, Laura K; Khan, Nasim A; Portilla, Didier; Beger, Richard D

    2012-04-15

    Low sensitivity of current clinical markers (serum creatinine and blood urea nitrogen (BUN)) in early stages of the development of acute kidney injury (AKI) limits their utility. Rapid LC/MS-based metabolic profiling of serum demonstrated in a pilot study that metabolomics could provide novel indicators of AKI. Metabolic profiles of serum samples from seventeen hospitalized patients with newly diagnosed AKI were compared with the profiles of serum from age-matched subjects with normal kidney function. Increases in acylcarnitines and amino acids (methionine, homocysteine, pyroglutamate, asymmetric dimethylarginine (ADMA), and phenylalanine) and a reduction in serum levels of arginine and several lysophosphatidyl cholines were observed in patients with AKI compared to healthy subjects. Increases in homocysteine, ADMA and pyroglutamate have been recognized as biomarkers of cardiovascular and renal disease, and acylcarnitines represent biomarkers of defective fatty acid oxidation. The results of this pilot study demonstrate the utility of metabolomics in the discovery of novel serum biomarkers that can facilitate the diagnosis and determine prognosis of AKI in hospitalized patients.

  7. The Phenotypic Fate of Bone Marrow-Derived Stem Cells in Acute Kidney Injury

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    Guowei Feng

    2013-11-01

    Full Text Available Background: Despite increasing attention on the role of bone marrow derived stem cells in repair or rejuvenation of tissues and organs, cellular mechanisms of such cell-based therapy remain poorly understood. Methods: We reconstituted hematopoiesis in recipient C57BL/6J mice by transplanting syngeneic GFP+ bone marrow (BM cells. Subsequently, the recipients received subcutaneous injection of granulocyte-colony stimulating factor (G-CSF and were subjected to acute renal ischemic injury. Flow cytometry and immunostaining were performed at various time points to assess engraftment and phenotype of BM derived stem cells. Results: Administration of G-CSF increased the release of BM derived stem cells into circulation and enhanced the ensuing recruitment of BM derived stem cells into injured kidney. During the second month post injury, migrated BM derived stem cells lost hematopoietic phenotype (CD45 but maintained the expression of other markers (Sca-1, CD133 and CD44, suggesting their potential of transdifferentiation into renal stem cells. Moreover, G-CSF treatment enhanced the phenotypic conversion. Conclusion: Our work depicted a time-course dependent transition of phenotypic characteristics of BM derived stem cells, demonstrated the existence of BM derived stem cells in damaged kidney and revealed the effects of G-CSF on cell transdifferentiation.

  8. Preischemic targeting of HIF prolyl hydroxylation inhibits fibrosis associated with acute kidney injury.

    Science.gov (United States)

    Kapitsinou, Pinelopi P; Jaffe, Jonathan; Michael, Mark; Swan, Christina E; Duffy, Kevin J; Erickson-Miller, Connie L; Haase, Volker H

    2012-05-01

    Acute kidney injury (AKI) due to ischemia is an important contributor to the progression of chronic kidney disease (CKD). Key mediators of cellular adaptation to hypoxia are oxygen-sensitive hypoxia-inducible factors (HIF), which are regulated by prolyl-4-hydroxylase domain (PHD)-containing dioxygenases. While activation of HIF protects from ischemic cell death, HIF has been shown to promote fibrosis in experimental models of CKD. The impact of HIF activation on AKI-induced fibrosis has not been defined. Here, we investigated the role of pharmacologic HIF activation in AKI-associated fibrosis and inflammation. We found that pharmacologic inhibition of HIF prolyl hydroxylation before AKI ameliorated fibrosis and prevented anemia, while inhibition of HIF prolyl hydroxylation in the early recovery phase of AKI did not affect short- or long-term clinical outcome. Therefore, preischemic targeting of the PHD/HIF pathway represents an effective therapeutic strategy for the prevention of CKD resulting from AKI, and it warrants further investigation in clinical trials. PMID:22262480

  9. Severe metabolic alkalosis and recurrent acute on chronic kidney injury in a patient with Crohn's disease

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    Schmid Axel

    2010-04-01

    Full Text Available Abstract Background Diarrhea is common in patients with Crohn's disease and may be accompanied by acid base disorders, most commonly metabolic acidosis due to intestinal loss of bicarbonate. Case Presentation Here, we present a case of severe metabolic alkalosis in a young patient suffering from M. Crohn. The patient had undergone multiple resections of the intestine and suffered from chronic kidney disease. He was now referred to our clinic for recurrent acute kidney injury, the nature of which was pre-renal due to profound volume depletion. Renal failure was associated with marked hypochloremic metabolic alkalosis which only responded to high volume repletion and high dose blockade of gastric hypersecretion. Intestinal failure with stomal fluid losses of up to 5.7 litres per day required port implantation to commence parenteral nutrition. Fluid and electrolyte replacement rapidly improved renal function and acid base homeostasis. Conclusions This case highlights the important role of gastrointestinal function to maintain acid base status in patients with Crohn's disease.

  10. The multifaceted role of the renal microvasculature during acute kidney injury.

    Science.gov (United States)

    Maringer, Katherine; Sims-Lucas, Sunder

    2016-08-01

    Pediatric acute kidney injury (AKI) represents a complex disease process for clinicians as it is multifactorial in cause and only limited treatment or preventatives are available. The renal microvasculature has recently been implicated in AKI as a strong therapeutic candidate involved in both injury and recovery. Significant progress has been made in the ability to study the renal microvasculature following ischemic AKI and its role in repair. Advances have also been made in elucidating cell-cell interactions and the molecular mechanisms involved in these interactions. The ability of the kidney to repair post AKI is closely linked to alterations in hypoxia, and these studies are elucidated in this review. Injury to the microvasculature following AKI plays an integral role in mediating the inflammatory response, thereby complicating potential therapeutics. However, recent work with experimental animal models suggests that the endothelium and its cellular and molecular interactions are attractive targets to prevent injury or hasten repair following AKI. Here, we review the cellular and molecular mechanisms of the renal endothelium in AKI, as well as repair and recovery, and potential therapeutics to prevent or ameliorate injury and hasten repair. PMID:26493067

  11. Urine neutrophil gelatinase-associated lipocalin (NGAL as a biomarker for acute canine kidney injury

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    Lee Ya-Jane

    2012-12-01

    Full Text Available Abstract Background Biomarkers for the early prediction of canine acute kidney injury (AKI are clinically important. Recently, neutrophil gelatinase-associated lipocalin (NGAL was found to be a sensitive biomarker for the prediction of human AKI at a very early stage and the development of AKI after surgery. However, NGAL has not yet been studied with respect to dog kidney diseases. The application of NGAL canine AKI was investigated in this study. Results The canine NGAL gene was successfully cloned and expressed. Polyclonal antibodies against canine NGAL were generated and used to develop an ELISA for measuring NGAL protein in serum and urine samples that were collected from 39 dogs at different time points after surgery. AKI was defined by the standard method, namely a serum creatinine increase of greater than or equal to 26.5 μmol/L from baseline within 48 h. At 12 h after surgery, compared to the group without AKI (12 dogs, the NGAL level in the urine of seven dogs with AKI was significantly increased (median 178.4 pg/mL vs. 88.0 pg/mL, and this difference was sustained to 72 h. Conclusion As the increase in NGAL occurred much earlier than the increase in serum creatinine, urine NGAL seems to be able to serve as a sensitive and specific biomarker for the prediction of AKI in dogs.

  12. Defining the cause of death in hospitalised patients with acute kidney injury.

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    Nicholas M Selby

    Full Text Available BACKGROUND: The high mortality rates that follow the onset of acute kidney injury (AKI are well recognised. However, the mode of death in patients with AKI remains relatively under-studied, particularly in general hospitalised populations who represent the majority of those affected. We sought to describe the primary cause of death in a large group of prospectively identified patients with AKI. METHODS: All patients sustaining AKI at our centre between 1(st October 2010 and 31(st October 2011 were identified by real-time, hospital-wide, electronic AKI reporting based on the Acute Kidney Injury Network (AKIN diagnostic criteria. Using this system we are able to generate a prospective database of all AKI cases that includes demographic, outcome and hospital coding data. For those patients that died during hospital admission, cause of death was derived from the Medical Certificate of Cause of Death. RESULTS: During the study period there were 3,930 patients who sustained AKI; 62.0% had AKI stage 1, 20.6% had stage 2 and 17.4% stage 3. In-hospital mortality rate was 21.9% (859 patients. Cause of death could be identified in 93.4% of cases. There were three main disease categories accounting for three quarters of all mortality; sepsis (41.1%, cardiovascular disease (19.2% and malignancy (12.9%. The major diagnosis leading to sepsis was pneumonia, whilst cardiovascular death was largely a result of heart failure and ischaemic heart disease. AKI was the primary cause of death in only 3% of cases. CONCLUSIONS: Mortality associated with AKI remains high, although cause of death is usually concurrent illness. Specific strategies to improve outcomes may therefore need to target not just the management of AKI but also the most relevant co-existing conditions.

  13. INTRA-ABDOMINAL HYPERTENSION AS A RISK FACTOR FOR ACUTE KIDNEY INJURY IN CRITICALLY ILL PATIENTS

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    Sreelatha

    2016-05-01

    Full Text Available BACKGROUND AND AIMS Increased intra-abdominal pressure (IAP, also referred to as intra-abdominal hypertension (IAH, affects organ function in critically ill patients. The prevalence of IAH is between 32% - 65% in intensive care units. Normal IAP is ≈ 5–7 mmHg. According to WSACS definition, IAH = IAP ≥12 mmHg and is divided into 4 grades. They are Grade I (12-15 mmHg, Grade II (16-20 mmHg, Grade III (21-25 mmHg, Grade IV (>25 mmHg. Transvesical measurement of IAP currently is the most popular technique. Several systems with or without the need for electronic equipment are available that allow IAP measurement. The aim is to study the incidence of IAH in critically ill patients, to assess the risk factors for development of IAH, to study the role of IAH as a risk factor for Acute Kidney Injury (AKI, to assess the role of IAH as a risk factor for increased (Intensive Care Unit ICU mortality. SUBJECTS AND METHODS This is a prospective observational study. Study period was six months. The study included 52 patients admitted to Medical ICU in Government Medical College, Kozhikode, Kerala. RESULTS AND CONCLUSION There was a very high incidence of intra-abdominal hypertension in critically ill patients. IAH was significantly associated with risk factors like sepsis, mechanical ventilation, pancreatitis, capillary leak, ascites, cumulative fluid balance and cirrhosis. IAH is an independent risk factor for development of acute kidney injury. IAH is an independent predictor of mortality in critically ill patients.

  14. Long-term follow-up of patients after acute kidney injury: patterns of renal functional recovery.

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    Etienne Macedo

    Full Text Available BACKGROUND AND OBJECTIVES: Patients who survive acute kidney injury (AKI, especially those with partial renal recovery, present a higher long-term mortality risk. However, there is no consensus on the best time to assess renal function after an episode of acute kidney injury or agreement on the definition of renal recovery. In addition, only limited data regarding predictors of recovery are available. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: From 1984 to 2009, 84 adult survivors of acute kidney injury were followed by the same nephrologist (RCRMA for a median time of 4.1 years. Patients were seen at least once each year after discharge until end stage renal disease (ESRD or death. In each consultation serum creatinine was measured and glomerular filtration rate estimated. Renal recovery was defined as a glomerular filtration rate value ≥60 mL/min/1.73 m2. A multiple logistic regression was performed to evaluate factors independently associated with renal recovery. RESULTS: The median length of follow-up was 50 months (30-90 months. All patients had stabilized their glomerular filtration rates by 18 months and 83% of them stabilized earlier: up to 12 months. Renal recovery occurred in 16 patients (19% at discharge and in 54 (64% by 18 months. Six patients died and four patients progressed to ESRD during the follow up period. Age (OR 1.09, p<0.0001 and serum creatinine at hospital discharge (OR 2.48, p = 0.007 were independent factors associated with non renal recovery. The acute kidney injury severity, evaluated by peak serum creatinine and need for dialysis, was not associated with non renal recovery. CONCLUSIONS: Renal recovery must be evaluated no earlier than one year after an acute kidney injury episode. Nephrology referral should be considered mainly for older patients and those with elevated serum creatinine at hospital discharge.

  15. Effect of tunicamycin on cisplatin induced apoptosis of HeLa cells

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    Ye XU

    2013-04-01

    Full Text Available Objective  To investigate the effect of endoplasmic reticulum stress (ER stress in cisplatin-induced apoptosis of human cervical cancer HeLa cells. Methods  HeLa cells were used as the study object which were divided into four groups: TUNI (5mg/L group, cisplatin (6mg/L group, TUNI(5mg/L+cisplatin(6mg/L group, and negative control group (no drug treatment. MTT assay was employed to examine the growth status of the cells. Hoechst staining was used to observe the morphological change in the nucleus. Immunoblotting was used to detect the activation of apoptotic proteins, caspase-3 and caspase-4. Indirect immunofluorescence was used to assess the expression of the protein disulfide isomerase (PDI and phosphorylated histone H2AX (γ-H2AX. Results  MTT assay showed that the growth inhibition rates were 2.65%±2.71%, 19.60%±4.34%, 44.69%±7.07% and 0% in TUNI group, cisplatin group, TUNI+cisplatin group and control group, respectively (P<0.05. Cisplatin showed a significant inhibitory effect on the growth of HeLa cells, and TUNI enhanced the effect of cisplatin. Statistical significance was found between TUNI+cisplatin group and cisplatin group (P<0.05. Hoechst staining showed that the fluorescence of the nucleus in control group was weak and well-distributed. At 12h after treatment, the nuclei in some HeLa cells in cisplatin group and TUNI+cisplatin group diminished in size, thus showing dense hyperfluorescence, and some of them were broken. The proportion of karyorrhexis cells in TUNI+cisplatin group (44.5%±5.1% was significantly higher than that in cisplatin group (22.7%±3.9%, P<0.05. Immunoblotting showed the expressions of activated caspase-3 and caspase-4 were up-regulated obviously in cisplatin group. Compared to cisplatin group, the expressions of those proteins significantly increased in TUNI+cisplatin group (P<0.05. Indirect immunofluorescence staining showed no PDI expression and weak fluorescence was found in control group. PDI

  16. Predictors and in-hospital outcomes of preoperative acute kidney injury in patients with type A acute aortic dissection

    Science.gov (United States)

    Wang, Xiao; Ren, Hong-Mei; Hu, Chun-Yan; Que, Bin; Ai, Hui; Wang, Chun-Mei; Sun, Li-Zhong; Nie, Shao-Ping

    2016-01-01

    Background Acute kidney injury (AKI) is common after surgery for acute aortic dissection (AAD) and increases in-hospital and long-term mortality. However, few data exist on the clinical and prognostic relevance of early preoperative AKI in patients with type A AAD. We aimed to determine the incidence and predictors of preoperative AKI and the impact of AKI on in-hospital outcomes in patients with type A AAD. Methods From May 2009 to June 2014, we retrospectively enrolled 178 patients admitted to our hospital within 48 h from symptom onset and receiving open surgery for type A AAD. The patients were divided into no AKI and AKI groups and staged with AKI severity according to the KDIGO criteria before surgery. Results AKI occurred in 41 patients (23.0%). The incidence of in-hospital complications was significantly higher in patients with preoperative AKI compared to no AKI (41.5% vs. 9.5%, P < 0.001), including renal infarction (7.3% vs. 0, P = 0.012), and it increased with AKI severity (Ptrend < 0.001). Patients with AKI had higher in-hospital mortality compared with patients without AKI, although no significant difference was found (14.6% vs. 5.1%, P = 0.079). Multivariate analysis indicated that male gender, diastolic blood pressure on admission and bilateral renal artery involvement were independent predictors of preoperative AKI in patients with type A AAD. Conclusions Early AKI before surgery was common in patients with type A AAD, and was associated with increased in-hospital complications. Male gender, diastolic blood pressure on admission and bilateral renal artery involvement were major predictors for preoperative AKI. PMID:27781058

  17. Effect of Insulin-Like Growth Factor II on Protecting Myoblast Cells Against Cisplatin-Induced Apoptosis Through p70 S6 Kinase Pathway

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    Xiaolin Wan

    2002-01-01

    Full Text Available Insulin-like growth factor. (IGF-II is overexpressed in a variety of human tumors and has both mitogenic and antiapoptotic activity. Although the mechanisms of IGFII-induced proliferation have been well studied, the mechanisms underlying its survival signaling have been less well characterized. In this report, we investigated the role of IGF-II on cisplatin-induced apoptosis. We found that IGF-II overexpression was associated with an increase in p70 ribosomal protein S6 kinase. (p70 S6K. Cisplatin treatment of. (321312 mouse myoblasts led to cell death associated with an inhibition of p70 S6K activity. Endogenous or exogenous IGF-II addition to. (321312 cells caused protection to cisplatin-induced apoptosis. This protection was associated in both cases with an increase in p70 S6K basal activity as well as resistance to cisplatin-induced decreased activity. Blockade of p70 S6K activation by rapamycin abrogated the IGF-II-mediated protection of cells to cisplatininduced apoptosis. Furthermore, treatment of IGF-IIoverexpressing Rh30 and CTR rhabdomyosarcoma cells with rapamycin restored sensitivity to cisplatininduced apoptosis. These data together suggest that IGF-II-associated protection to cisplatin-induced apoptosis is mediated through an activation of the p70 S6K pathway. Thus, inhibition of the p70 S6 pathway may enhance chemotherapy-induced apoptosis in the treatment of IGF-II-overexpressing tumors.

  18. Risk Factors for Acute Kidney Injury in Older Adults With Critical Illness: A Retrospective Cohort Study

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    Kane-Gill, Sandra L.; Sileanu, Florentina E.; Murugan, Raghavan; Trietley, Gregory S.; Handler, Steven M.; Kellum, John A.

    2014-01-01

    Background Risk for acute kidney injury (AKI) in older adults has not been systematically evaluated. We sought to delineate the determinants of risk for AKI in older compared to younger adults. Study Design Retrospective analysis of patients hospitalized in July 2000–September 2008. Setting & Participants We identified all adult patients admitted to an intensive care unit (ICU) (n=45,655) in a large tertiary care university hospital system. We excluded patients receiving dialysis or kidney transplant prior to hospital admission, and patients with baseline creatinine ≥ 4 mg/dl, liver transplantation, indeterminate AKI status, or unknown age, leaving 39,938 patients. Predictor We collected data on multiple susceptibilities and exposures including age, sex, race, body mass, comorbid conditions, severity of illness, baseline kidney function, sepsis, and shock. Outcomes We defined AKI according to KDIGO (Kidney Disease: Improving Global Outcomes) criteria. We examined susceptibilities and exposures across age strata for impact on development of AKI. Measurements We calculated area under the receiver operating characteristic curve (AUC) for prediction of AKI across age groups. Results 25,230 patients (63.2%) were aged 55 years or older. Overall 25,120 patients (62.9%) developed AKI (69.2% aged 55 years or older). Examples of risk factors for AKI in the oldest age category (75 years or older) were drugs (vancomycin, aminoglycosides, nonsteroidal anti-inflammatories), history of hypertension (OR, 1.13; 95% CI, 1.02–1.25) and sepsis (OR, 2.12; 95% CI, 1.68–2.67). Fewer variables remained predictive of AKI as age increased and the model for older patients was less predictive (p<0.001). For the age categories 18–54, 55–64, 65–74, and 75 years or older, the AUCs were 0.744 (95% CI, 0.735–0.752), 0.714 (95% CI, 0.702–0.726), 0.706 (95% CI, 0.693–0.718), and 0.673 (95% CI, 0.661–0.685), respectively. Limitations Analysis may not apply to non-ICU patients

  19. Injuria renal aguda en la sepsis grave Acute kidney injury in severe sepsis

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    Hernán Trimarchi

    2009-06-01

    Full Text Available La sepsis afecta al 40% de los pacientes críticos, siendo su mortalidad de aproximadamente un 30% en el caso de la sepsis grave, y de 75% con injuria renal aguda, la cual sucede en el 20-51% de los casos. Se realizó un estudio prospectivo, observacional, longitudinal, en 80 pacientes sépticos graves en el lapso de 1 año para determinar el desarrollo de injuria renal aguda y su relación con la mortalidad; correlacionar antecedentes clínicos y variaciones del laboratorio con la mortalidad; determinar la tasa de mortalidad de la sepsis grave; relacionar óbito y foco séptico primario; evaluar la predictibilidad de mortalidad según niveles de creatinina de ingreso y sus variaciones finales. Se definieron dos grupos: Obito (n = 25 y No-óbito (n = 55. Analizados según la creatinina de ingreso, 39 tenían valores normales de creatinina (10 óbitos y 41 la presentaban elevada (15 óbitos; según la creatinina de egreso, 48 presentaron creatinina normal y fallecieron 7, mientras que 32 tenían daño renal agudo, de los cuales 18 fallecieron. De los 25 pacientes fallecidos, el 72% presentaron daño renal. De éstos, 7 pacientes vivos y 2 fallecidos requirieron hemodiálisis. El foco primario más frecuente fue el respiratorio (26.4%. El desarrollo de daño renal es un alto predictor de mortalidad en la sepsis, independientemente de los valores iniciales de creatinina. Edad más avanzada, hipertensión arterial, score APACHE más elevado, anemia más grave, hipoalbuminemia, hiperfosfatemia e hiperkalemia se asociaron a mayor mortalidad. La mortalidad global fue 31.3%. La imposibilidad de identificar el foco séptico primario se asoció a mayor mortalidad. El foco respiratorio se relacionó a mayor riesgo de requerir hemodiálisis.Sepsis affects 40% of critically ill patients, with a reported mortality of approximately 30% in severe sepsis, raising to 75% when acute kidney injury ensues, which occurs in about 20-51% of cases. The present study

  20. Metabolic Acidosis and Strong Ion Gap in Critically Ill Patients with Acute Kidney Injury

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    Cai-Mei Zheng

    2014-01-01

    Full Text Available Purpose. To determine the influence of physicochemical parameters on survival in metabolic acidosis (MA and acute kidney injury (AKI patients. Materials and Methods. Seventy-eight MA patients were collected and assigned to AKI or non-AKI group. We analyzed the physiochemical parameters on survival at 24 h, 72 h, 1 week, 1 month, and 3 months after AKI. Results. Mortality rate was higher in the AKI group. AKI group had higher anion gap (AG, strong ion gap (SIG, and apparent strong ion difference (SIDa values than non-AKI group. SIG value was higher in the AKI survivors than nonsurvivors and this value was correlated serum creatinine, phosphate, albumin, and chloride levels. SIG and serum albumin are negatively correlated with Acute Physiology and Chronic Health Evaluation IV scores. AG was associated with mortality at 1 and 3 months post-AKI, whereas SIG value was associated with mortality at 24 h, 72 h, 1 week, 1 month, and 3 months post-AKI. Conclusions. Whether high or low SIG values correlate with mortality in MA patients with AKI depends on its correlation with serum creatinine, chloride, albumin, and phosphate (P levels. AG predicts short-term mortality and SIG value predicts both short- and long-term mortality among MA patients with AKI.

  1. Acute kidney injury: short-term and long-term effects.

    Science.gov (United States)

    Doyle, James F; Forni, Lui G

    2016-01-01

    Acute kidney injury (AKI) is the most common cause of organ dysfunction in critically ill adults, with a single episode of AKI, regardless of stage, carrying a significant morbidity and mortality risk. Since the consensus on AKI nomenclature has been reached, data reflecting outcomes have become more apparent allowing investigation of both short- and long-term outcomes.Classically the short-term effects of AKI can be thought of as those reflecting an acute deterioration in renal function per se. However, the effects of AKI, especially with regard to distant organ function ("organ cross-talk"), are being elucidated as is the increased susceptibility to other conditions. With regards to the long-term effects, the consideration that outcome is a simple binary endpoint of dialysis or not, or survival or not, is overly simplistic, with the reality being much more complex.Also discussed are currently available treatment strategies to mitigate these adverse effects, as they have the potential to improve patient outcome and provide considerable economic health savings. Moving forward, an agreement for defining renal recovery is warranted if we are to assess and extrapolate the efficacy of novel therapies. Future research should focus on targeted therapies assessed by measure of long-term outcomes. PMID:27373891

  2. Evidence for different mechanisms of ‘unhooking’ for melphalan and cisplatin-induced DNA interstrand cross-links in vitro and in clinical acquired resistant tumour samples

    International Nuclear Information System (INIS)

    DNA interstrand cross-links (ICLs) are critical lesions produced by several cancer chemotherapy agents including platinum drugs and nitrogen mustards. We have previously shown in haematological (multiple myeloma) and solid tumours (ovarian cancer) that clinical sensitivity to such agents can result from a defect in DNA ICL processing leading to their persistence. Conversely, enhanced repair can result in clinical acquired resistance following chemotherapy. The repair of ICLs is complex but it is assumed that the ‘unhooking’ step is common to all ICLs. Using a modification of the single cell gel electrophoresis (Comet) assay we measured the formation and unhooking of melphalan and cisplatin-induced ICLs in cell lines and clinical samples. DNA damage response in the form of γ-H2AX foci formation and the formation of RAD51 foci as a marker of homologous recombination were also determined. Real-time PCR of 84 genes involved in DNA damage signalling pathways was also examined pre- and post-treatment. Plasma cells from multiple myeloma patients known to be clinically resistant to melphalan showed significant unhooking of melphalan-induced ICLs at 48 hours, but did not unhook cisplatin-induced ICLs. In ovarian cancer cells obtained from patients following platinum-based chemotherapy, unhooking of cisplatin-induced ICLs was observed at 48 hours, but no unhooking of melphalan-induced ICLs. In vitro, A549 cells were proficient at unhooking both melphalan and cisplatin-induced ICLs. γ-H2AX foci formation closely followed the formation of ICLs for both drugs, and rapidly declined following the peak of formation. RPMI8226 cells unhooked melphalan, but not cisplatin-induced ICLs. In these cells, although cross-links form with cisplatin, the γ-H2AX response is weak. In A549 cells, addition of 3nM gemcitabine resulted in complete inhibition of cisplatin-induced ICL unhooking but no effect on repair of melphalan ICLs. The RAD51 foci response was both drug and cell line

  3. Outcomes of acute kidney injury in children at Muhammad Husin Hospital, Palembang

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    Hertanti Indah Lestari

    2014-09-01

    Full Text Available Background Acute kidney injury (AKI is a common problem in hospitalized pediatric patients, with effects on morbidity and mortality. Objectives To assess for the incidence and common etiologies of AKI, as well as to review factors that affect patient outcomes at Muhammad Husin Hospital, Palembang. Methods We reviewed data from our nephrology registry from January 2010 to June 2013. Independent variables were age, stage and etiology of AKI, requirement of renal replacement therapy (RRT, and PICU admission. The dependent variable was patient outcomes, categorized as survived or died. Association between clinical data and outcomes were analyzed by Chi-square test. Results The incidence of AKI was 28.3%. Using the pediatric risk, injury, failure, loss, end stage renal disease (pRrIFLEle criteria, 65 (36.7% patients were in the risk stage, 56 (31.6% in the injury stage, and 56 (31.6% in the failure stage. Twelve (6.8% patients required RRT and 29 (16.4% patients were admitted to the PICU. The mortality rate from AKI was 20.9%. The common etiologies of AKI were acute glomerulonephritis (55 subjects; 31.1%, multiple organ dysfunction (24 subjects; 13.6%, dehydration (23 subjects; 13.0%, hypoalbuminemia (20 subjects; 11.3%, heart failure (11 subjects; 6.2% and nephrotoxic agents (12 subjects; 6.8%. The mortality rate was significantly higher in children of younger age (<5 years (P=0.0001, in the failure stage of AKI (P=0.014, with non-renal origin of illness (P=0.0001 and those with an indication for PICU admission (P=0.0001. Conclusion AKI is found in one-third of nephrology patients. The most common etiology of AKI is acute glomerulonephritis. One-fifth of patients with AKI do not survive. Recognition of risk factors and detection of AKI in early stages might improve patient outcomes. [Paediatr Indones. 2014;54:266-72.].

  4. Erythropoiesis-stimulating agents increase the risk of acute stroke in patients with chronic kidney disease

    Science.gov (United States)

    Seliger, Stephen L.; Zhang, Amy D.; Weir, Matthew R.; Walker, Loreen; Hsu, Van Doren; Parsa, Afshin; Diamantidis, Clarissa; Fink, Jeffrey C.

    2013-01-01

    Erythropoiesis-stimulating agents (ESAs) are effective in ameliorating anemia in chronic kidney disease (CKD). However, a recent trial in diabetic CKD patients suggested a greater stroke risk associated with full correction of anemia using ESAs. We performed a case-control study examining the association of incident ESA use with acute stroke in CKD patients, using national Veterans Affairs data. Patients with eGFR<60 cc/min/1.73m2 and outpatient hemoglobin (Hb)<12g/dL were included. Acute hospitalized stroke cases (N=2071) were identified using diagnosis codes and matched 1:5 to controls without stroke. Conditional logistic regression was used to estimate the association of ESA use with stroke, adjusting for potential confounders. After multivariate adjustment, ESA use (N=1026, 8.3%) was associated with 30% greater odds of stroke (odds ratio[OR]=1.30, 95% confidence interval[CI]: 1.06, 1.58). There was significant interaction (p=.015) between ESA use and cancer; ESA use was associated with 85% greater odds of stroke in cancer patients (95% CI: 1.26, 2.65), but not associated with stroke in patients without cancer (OR=1.07, 95% CI: 0.85, 1.35). ESA-treated patients with cancer received a median initial dose 2.5 to 4 times greater than ESA patients without cancer, but pre-ESA Hb and rate of Hb change did not differ between groups. Among a large national sample of anemic CKD patients, ESA treatment is associated with an increased risk of acute stroke, with the greatest effect among patients with cancer. PMID:21389972

  5. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE of urinary protein in acute kidney injury

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    Sufi M Suhail

    2011-01-01

    Full Text Available Recent experimental and clinical studies have shown the importance of urinary proteomics in acute kidney injury (AKI. We analyzed the protein in urine of patients with clinical AKI using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE for its diagnostic value, and followed them up for 40 months to evaluate prognosis. Urine from 31 consecutive cases of AKI was analyzed with SDS-PAGE to determine the low, middle and high molecular weight proteins. Fractional excretion of sodium (FENa was estimated from serum and urine creatinine and sodium (Na. The cases were followed-up for 40 months from the end of the recruitment of study cases. Glomerular protein was higher in the hematuria group when compared with the non-hematuria group (P <0.04 and in the AKI group than in the acute on chronic renal failure (AKI-on-CRF group (P <0.002. Tubular protein was higher in the AKI-on-CRF group (P <0.003 than in the AKI group. Tubular protein correlated with FENa in groups with diabetes mellitus (DM, AKI-on-CRF, and without hematuria (P <0.03, P <0.02 and P <0.004, respectively. Pattern of protein did not differ between groups with and without DM and clinical acute tubular necrosis (ATN. At the end of 40 months follow-up, category with predominantly glomerular protein progressed to chronic renal failure (CRF or end-stage renal failure in higher proportion (P <0.05. In clinical AKI, we observed that glomerular protein dominated in cases with glomerular insult, as indicated by hematuria. Tubular protein was common in the study cases with CRF, DM and cases without hematuria. This indicates tubulo-interstitial injury for AKI in these cases. Patients with predominantly glomerular protein had an adverse outcome.

  6. A Patient with an Unusual Cause Right Lower Quadrant Pain and Vomiting: Pyelonephritis of an Ectopic Right Kidney Masquerading as Acute Appendicitis

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    Michele N. Lossius

    2009-01-01

    Full Text Available An adolescent female presented with one day of abdominal pain and clinical findings of acute appendicitis. CT scan revealed an ectopic right kidney with changes of acute pyelonephritis. This paper underscores the importance of imaging the right pelvis prior to surgical intervention in suspected cases of acute appendicitis in children.

  7. Selectivity analysis of protein kinase CK2 inhibitors DMAT, TBB and resorufin in cisplatin-induced stress responses

    DEFF Research Database (Denmark)

    Fritz, Gerhard; Issinger, Olaf-Georg; Olsen, Birgitte Brinkmann

    2009-01-01

    Targeting protein kinases as a therapeutic approach to treat various diseases, especially cancer is currently a fast growing business. Although many inhibitors are available, exhibiting remarkable potency, the major challenge is their selectivity. Here we show that the protein kinase CK2 inhibitors...... DMAT, TBB and resorufin differ in their selectivity against PI3K family members, since PI3K and DNA-PK are subject to inhibition by DMAT and TBB, however, not by resorufin. TBB and DMAT treatment together with cisplatin lead to an inhibition of cisplatin-induced stress signaling (as detected...... by phosphorylation of JNK and H2AX). In the case of resorufin no interference with the stress-signaling pathway is observed, supporting the notion that TBB and DMAT interfere with upstream molecules involved in genotoxic stress signaling. We have also tested the protein kinase CK2 inhibitors with respect to cell...

  8. An unusual case of acute kidney injury due to vancomycin lessons learnt from reliance on eGFR.

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    Barraclough, Katherine; Harris, Marianne; Montessori, Val; Levin, Adeera

    2007-08-01

    We present a case of renal impairment in an emaciated HIV-infected male that initially went unrecognized because of reliance on serum creatinine and estimated glomerular filtration rate (eGFR). Inaccurate vancomycin dosing led to toxic drug levels (66 mg/l), associated with acute and severe worsening of kidney function. This occurred in the context of escalating doses of vancomycin given in the presence of changing kidney function, albeit kidney function that always remained well within the normal range (serum creatinine 29 - 42 mumol/l). In the absence of other plausible explanations, a presumptive diagnosis of vancomycin nephrotoxicity was made. Given the rarity of this diagnosis in the current era, we discuss the pathophysiology of vancomycin nephrotoxicity. We also explore the potential reasons for inaccuracy of GFR prediction equations in the HIV population, and discuss the potential pitfalls associated with application of eGFR or even serum creatinine without appropriate understanding of their limitations. We believe our case highlights a number of important teaching points: Vancomycin nephrotoxitiy is rare but can occur in the setting of kidney dysfunction. Current assessment of kidney function using creatinine and eGFR requires awareness of the clinical caveats in which these measures may be misleading. Acute changes in kidney function, irrespective of the test used, should be contextualized to the individual situation. Persons with HIV and low muscle mass constitute a specific subgroup in whom assessment of kidney function may be problematic using creatinine. We support ongoing efforts to develop or refine equations for specific unique and easily identifiable populations. PMID:17470454

  9. Prevention of iodinated contrast induced acute kidney injury (ICI--AKI - what have we learnt so far?

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    Asim Muhammad

    2009-01-01

    Full Text Available The use of imaging modalities and endovascular procedures has escalated phenol-menally in the last two decades. In view of increasing number of elderly patients, rising incidence of chronic kidney disease and diabetes along with the complication of nephrogenic systemic fibrosis with gadolinium, a large patient population will be at risk of developing iodinated contrast induced acute kidney injury (ICI-AKI which is associated with significant morbidity and mortality and increased health care costs. Hence a search for more effective ways to prevent ICI-AKI continues to be a focus within the medical community.

  10. Correlation of serum neutrophil gelatinase-associated lipocalin with acute kidney injury in hypertensive disorders of pregnancy

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    Patel ML

    2013-10-01

    Full Text Available ML Patel,1 Rekha Sachan,2 Radheyshyam Gangwar,3 Pushpalata Sachan,4 SM Natu51Department of Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India; 2Department of Obstetrics and Gynaecology, King George's Medical University, Lucknow, Uttar Pradesh, India; 3Department of Critical Care, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India; 4Department of Physiology, King George's Medical University, Lucknow, Uttar Pradesh, India; 5Department of Pathology, King George's Medical University, Lucknow, Uttar Pradesh, IndiaAbstract: Hypertensive disorders of pregnancy (HDP remain one of the largest single causes of maternal and fetal morbidity and mortality, accounting for 16.1% of maternal deaths in developed countries. The aim of the study was to evaluate acute kidney injury (AKI in hypertensive disorders of pregnancy and to examine the correlation of serum neutrophil gelatinase-associated lipocalin (NGAL with acute kidney injury. This prospective case control study was carried out over a period of 1 year. After written, informed consent and ethical clearance, 149 cases of hypertensive disorders of pregnancy were screened, and seven were lost to follow-up. Acute kidney injury was detected in 88 cases and acute renal failure in 30 cases of HDP. Thirty-one healthy pregnant nonhypertensive women were enrolled as controls. Quantitative measurement of serum NGAL levels was done by enzyme linked immunosorbent assay technique using a sandwich enzyme-linked immunosorbent assay kit. As per the Kidney Diseases Improving Global Outcomes International guidelines acute kidney injury network (AKIN, 50 cases (42.37% of AKI stage I, 38 (32.2% cases of AKI stage II, and 30 (25.42% cases of renal failure were detected. Serum NGAL had a positive association with increasing proteinuria. It also had a positive correlation with systolic blood pressure (r~0.36, diastolic blood pressure (r~0.37, and serum creatinine (r~0

  11. Microparticles from kidney-derived mesenchymal stem cells act as carriers of proangiogenic signals and contribute to recovery from acute kidney injury.

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    Hoon Young Choi

    Full Text Available We recently demonstrated the use of in vitro expanded kidney-derived mesenchymal stem cells (KMSC protected peritubular capillary endothelial cells in acute renal ischemia-reperfusion injury. Herein, we isolated and characterized microparticles (MPs from KMSC. We investigated their in vitro biologic effects on human endothelial cells and in vivo renoprotective effects in acute ischemia-reperfusion renal injury. MPs were isolated from the supernatants of KMSC cultured in anoxic conditions in serum-deprived media for 24 hours. KMSC-derived MPs demonstrated the presence of several adhesion molecules normally expressed on KMSC membranes, such as CD29, CD44, CD73, α4, 5, and 6 integrins. Quantitative real time PCR confirmed the presence of 3 splicing variants of VEGF-A (120, 164, 188, bFGF and IGF-1 in isolated MPs. MPs labeled with PKH26 red fluorescence dye were incorporated by cultured human umbilical vein endothelial cells (HUVEC via surface molecules such as CD44, CD29, and α4, 5, and 6 integrins. MP dose dependently improved in vitro HUVEC proliferation and promoted endothelial tube formation on growth factor reduced Matrigel. Moreover, apoptosis of human microvascular endothelial cell was inhibited by MPs. Administration of KMSC-derived MPs into mice with acute renal ischemia was followed by selective engraftment in ischemic kidneys and significant improvement in renal function. This was achieved by improving proliferation, of peritubular capillary endothelial cell and amelioration of peritubular microvascular rarefaction. Our results support the hypothesis that KMSC-derived MPs may act as a source of proangiogenic signals and confer renoprotective effects in ischemic kidneys.

  12. Urinary biomarkers TIMP-2 and IGFBP7 early predict acute kidney injury after major surgery.

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    Ivan Gocze

    Full Text Available To assess the ability of the urinary biomarkers IGFBP7 (insulin-like growth factor-binding protein 7 and TIMP-2 (tissue inhibitor of metalloproteinase 2 to early predict acute kidney injury (AKI in high-risk surgical patients.Postoperative AKI is associated with an increase in short and long-term mortality. Using IGFBP7 and TIMP-2 for early detection of cellular kidney injury, thus allowing the early initiation of renal protection measures, may represent a new concept of evaluating renal function.In this prospective study, urinary [TIMP-2]×[IGFBP7] was measured in surgical patients at high risk for AKI. A predefined cut-off value of [TIMP-2]×[IGFBP7] >0.3 was used for assessing diagnostic accuracy. Perioperative characteristics were evaluated, and ROC analyses as well as logistic regression models of risk assessment were calculated with and without a [TIMP-2]×[IGFBP7] test.107 patients were included in the study, of whom 45 (42% developed AKI. The highest median values of biomarker were detected in septic, transplant and patients after hepatic surgery (1.24 vs 0.45 vs 0.47 ng/l²/1000. The area under receiving operating characteristic curve (AUC for the risk of any AKI was 0.85, for early use of RRT 0.83 and for 28-day mortality 0.77. In a multivariable model with established perioperative risk factors, the [TIMP-2]×[IGFBP7] test was the strongest predictor of AKI and significantly improved the risk assessment (p<0.001.Urinary [TIMP-2]×[IGFBP7] test sufficiently detect patients with risk of AKI after major non-cardiac surgery. Due to its rapid responsiveness it extends the time frame for intervention to prevent development of AKI.

  13. Herbal Medicines for Acute Kidney Injury:Evidence, Gaps and Frontiers

    Institute of Scientific and Technical Information of China (English)

    Vale´ rian Bunel; Fan Qu; Pierre Duez; Qi-he Xu

    2015-01-01

    Acute kidney injury (AKI) is a major health threat worldwide. The literature on herbal intervention in AKI was searched from English and Chinese databases and reports were critically analyzed in terms of preventing AKI, promoting repair and regeneration, enhancing extrarenal clearance of uremic toxins, and preventing progression to chronic kidney disease (CKD). Altogether, 16 herbal formulae and a few extracts derived from individual herbs were reported to prevent or mitigate AKI in animal models induced by renal ischemia/reperfusion, cisplastin, gentamicin, glycerol, adenine, sepsis or physical exhaustion. Four formulae and six individual herbs were reported to accelerate recovery and/or to prevent CKD in established AKI animal models. Intrarectal herbal medicines, with or without simultaneous oral administration, were reported in six clinical trials and in an animal model to increase extrarenal clearance of uremic toxins. Additional 13 clinical trials reported oral or intravenous herbal interventions in AKI of different etiologies. Despite recurring problems, notably poor compliance with good practice guidelines for clinical trials and for authentication, naming and quality control of herbal materials, accumulating experimental data on the preventive effects of herbal medicines in AKI look encouraging and urge for better, definitive trials to guide clinical practice. Herbal enemas promoting extrarenal clearance of uremic toxins seem cost-effective, but better clinical evidence is certainly needed before any affirmative recommendation be made for AKI patients without access to dialysis. New frontiers, however, lie in those herbal remedies that promote repair/regeneration and prevent chronicity after AKI. Recent experimental data suggest that this may be possible.

  14. Maximising Acute Kidney Injury Alerts--A Cross-Sectional Comparison with the Clinical Diagnosis.

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    Simon Sawhney

    Full Text Available Acute kidney injury (AKI is serious and widespread across healthcare (1 in 7 hospital admissions but recognition is often delayed causing avoidable harm. Nationwide automated biochemistry alerts for AKI stages 1-3 have been introduced in England to improve recognition. We explored how these alerts compared with clinical diagnosis in different hospital settings.We used a large population cohort of 4464 patients with renal impairment. Each patient had case-note review by a nephrologist, using RIFLE criteria to diagnose AKI and chronic kidney disease (CKD. We identified and staged AKI alerts using the new national NHS England AKI algorithm and compared this with nephrologist diagnosis across hospital settings.Of 4464 patients, 525 had RIFLE AKI, 449 had mild AKI, 2185 had CKD (without AKI and 1305 were of uncertain chronicity. NHS AKI algorithm criteria alerted for 90.5% of RIFLE AKI, 72.4% of mild AKI, 34.1% of uncertain cases and 14.0% of patients who actually had CKD.The algorithm identified AKI particularly well in intensive care (95.5% and nephrology (94.6%, but less well on surgical wards (86.4%. Restricting the algorithm to stage 2 and 3 alerts reduced the over-diagnosis of AKI in CKD patients from 14.0% to 2.1%, but missed or delayed alerts in two-thirds of RIFLE AKI patients.Automated AKI detection performed well across hospital settings, but was less sensitive on surgical wards. Clinicians should be mindful that restricting alerts to stages 2-3 may identify fewer CKD patients, but including stage 1 provides more sensitive and timely alerting.

  15. The Related Risk Factors Analysis of Snake-Bite Induced Acute Kidney Injury.

    Science.gov (United States)

    Li, Wei; Chen, Fang; Wu, Shukun

    2016-01-01

    BACKGROUND The pathogenic mechanism of snake-bite induced acute kidney injury (AKI) remains unclear. Analyzing the risk factors for snake-bite induced AKI may provide the guidance needed for AKI prevention and early treatment. MATERIAL AND METHODS This retrospective study included 119 snake-bite patients who were hospitalized at the emergency department of Sichuan Provincial People's Hospital from January 2011 to September 2013. The patients were divided into AKI and non-AKI groups according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guideline. Gender, age, and clinical examination data of the patients were recorded. The Mann-Whitney U test and Fisher exact test were performed to analyze the collected data; preliminary analysis of independent risk factors was performed with multivariate logistic regression. RESULTS Among the snake-bite patients, 98.3% were farmers. The mean age of patients was 46±12 years. Of the 119 patients (13.4%), 16 suffered from AKI. There were statistically significant differences between the AKI and non-AKI groups with respect to age, time interval from snake bite to antivenin therapy, creatine kinase, blood myoglobin, advanced age, regional lymphadenopathy, incision drainage, and hemoglobin. Preliminary analysis with multivariate logistic regression showed that advanced age and increased time interval from snake bite to antivenin therapy might be independent risk factors for snake-bite induced AKI. CONCLUSIONS Age, time interval from snake bite to antivenin therapy, creatine kinase, blood myoglobin, advanced age, regional lymphadenopathy, incision drainage, and hemoglobin were risk factors for snake-bite induced AKI. Advanced age and delayed antivenin therapy might be independent risk factors for snake-bite induced AKI. PMID:27377078

  16. Prehospitalization Risk Factors for Acute Kidney Injury during Hospitalization for Serious Infections in the REGARDS Cohort

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    Henry E. Wang

    2015-11-01

    Full Text Available Background/Aims: Acute kidney injury (AKI frequently occurs in hospitalized patients. In this study, we determined prehospitalization characteristics associated with AKI in community-dwelling adults hospitalized for a serious infection. Methods: We used prospective data from 30,239 participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS study, a national cohort of community-dwelling adults ≥45 years old. We identified serious infection hospitalizations between 2003 and 2012. Using the Kidney Disease Improving Global Outcomes (KDIGO criteria, we defined AKI as an increase in serum creatinine (sCr ≥0.3 mg/dl from the first inpatient sCr measurement during the first 7 hospitalization days. We excluded individuals with a history of renal transplant or preexisting end-stage renal disease as well as individuals with Results: Over a median follow-up of 4.5 years (interquartile range 2.4-6.3, we included 2,074 serious infection hospitalizations among 1,543 individuals. AKI occurred in 296 of 2,074 hospitalizations (16.5%. On multivariable analysis, prehospitalization characteristics independently associated with AKI among individuals hospitalized for a serious infection included a history of diabetes [odds ratio (OR 1.38; 95% CI 1.02-1.89], increased cystatin C (OR 1.73 per SD; 95% CI 1.20-2.50, and increased albumin-to-creatinine ratio (OR 1.19 per SD; 95% CI 1.007-1.40. Sex, race, hypertension, myocardial infarction, estimated glomerular filtration rate, high-sensitivity C-reactive protein, and the use of nonsteroidal anti-inflammatory, statin, or antihypertensive medications were not associated with AKI. Conclusions: Community-dwelling adults with a history of diabetes or increased cystatin C or albumin-to-creatinine ratio are at increased risk for AKI after hospitalization for a serious infection. These findings may be used to identify individuals at high risk for AKI.

  17. Urinary L-FABP predicts poor outcomes in critically ill patients with early acute kidney injury.

    Science.gov (United States)

    Parr, Sharidan K; Clark, Amanda J; Bian, Aihua; Shintani, Ayumi K; Wickersham, Nancy E; Ware, Lorraine B; Ikizler, T Alp; Siew, Edward D

    2015-03-01

    Biomarker studies for early detection of acute kidney injury (AKI) have been limited by nonselective testing and uncertainties in using small changes in serum creatinine as a reference standard. Here we examine the ability of urine L-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), and kidney injury molecule-1 (KIM-1) to predict injury progression, dialysis, or death within 7 days in critically ill adults with early AKI. Of 152 patients with known baseline creatinine examined, 36 experienced the composite outcome. Urine L-FABP demonstrated an area under the receiver-operating characteristic curve (AUC-ROC) of 0.79 (95% confidence interval 0.70-0.86), which improved to 0.82 (95% confidence interval 0.75-0.90) when added to the clinical model (AUC-ROC of 0.74). Urine NGAL, IL-18, and KIM-1 had AUC-ROCs of 0.65, 0.64, and 0.62, respectively, but did not significantly improve discrimination of the clinical model. The category-free net reclassification index improved with urine L-FABP (total net reclassification index for nonevents 31.0%) and urine NGAL (total net reclassification index for events 33.3%). However, only urine L-FABP significantly improved the integrated discrimination index. Thus, modest early changes in serum creatinine can help target biomarker measurement for determining prognosis with urine L-FABP, providing independent and additive prognostic information when combined with clinical predictors.

  18. Urinary L-FABP predicts poor outcomes in critically ill patients with early acute kidney injury.

    Science.gov (United States)

    Parr, Sharidan K; Clark, Amanda J; Bian, Aihua; Shintani, Ayumi K; Wickersham, Nancy E; Ware, Lorraine B; Ikizler, T Alp; Siew, Edward D

    2015-03-01

    Biomarker studies for early detection of acute kidney injury (AKI) have been limited by nonselective testing and uncertainties in using small changes in serum creatinine as a reference standard. Here we examine the ability of urine L-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), and kidney injury molecule-1 (KIM-1) to predict injury progression, dialysis, or death within 7 days in critically ill adults with early AKI. Of 152 patients with known baseline creatinine examined, 36 experienced the composite outcome. Urine L-FABP demonstrated an area under the receiver-operating characteristic curve (AUC-ROC) of 0.79 (95% confidence interval 0.70-0.86), which improved to 0.82 (95% confidence interval 0.75-0.90) when added to the clinical model (AUC-ROC of 0.74). Urine NGAL, IL-18, and KIM-1 had AUC-ROCs of 0.65, 0.64, and 0.62, respectively, but did not significantly improve discrimination of the clinical model. The category-free net reclassification index improved with urine L-FABP (total net reclassification index for nonevents 31.0%) and urine NGAL (total net reclassification index for events 33.3%). However, only urine L-FABP significantly improved the integrated discrimination index. Thus, modest early changes in serum creatinine can help target biomarker measurement for determining prognosis with urine L-FABP, providing independent and additive prognostic information when combined with clinical predictors. PMID:25229339

  19. Distinct injury markers for the early detection and prognosis of incident acute kidney injury in critically ill adults with preserved kidney function

    OpenAIRE

    Siew, Edward D.; Ware, Lorraine B.; Bian, Aihua; Shintani, Ayumi; Eden, Svetlana; Wickersham, Nancy; Cripps, Ben; Ikizler, T. Alp

    2013-01-01

    The use of novel biomarkers to detect incident acute kidney injury (AKI) in the critically ill is hindered by heterogeneity of injury and the potentially confounding effects of prevalent AKI. Here we examined the ability of urine NGAL (NGAL), L-type Fatty Acid Binding Protein (L-FABP), and Cystatin C to predict AKI development, death, and dialysis in a nested case-control study of 380 critically ill adults with an eGFR over 60 ml/min/1.73 m2. One-hundred thirty AKI cases were identified follo...

  20. A Case of Mushroom Poisoning with Russula subnigricans: Development of Rhabdomyolysis, Acute Kidney Injury, Cardiogenic Shock, and Death.

    Science.gov (United States)

    Cho, Jong Tae; Han, Jin Hyung

    2016-07-01

    Mushroom exposures are increasing worldwide. The incidence and fatality of mushroom poisoning are reported to be increasing. Several new syndromes in mushroom poisoning have been described. Rhabdomyolytic mushroom poisoning is one of new syndromes. Russula subnigricans mushroom can cause delayed-onset rhabdomyolysis with acute kidney injury in the severely poisoned patient. There are few reports on the toxicity of R. subnigricans. This report represents the first record of R. subnigricans poisoning with rhabdomyolysis in Korea, describing a 51-year-old man who suffered from rhabdomyolysis, acute kidney injury, severe hypocalcemia, respiratory failure, ventricular tachycardia, cardiogenic shock, and death. Mushroom poisoning should be considered in the evaluation of rhabdomyolysis of unknown cause. Furthermore, R. subnigricans should be considered in the mushroom poisoning with rhabdomyolysis. PMID:27366018

  1. Prognostic impact of atrial fibrillation on clinical outcomes of acute coronary syndromes,heart failure and chronic kidney disease

    Institute of Scientific and Technical Information of China (English)

    Nileshkumar; J; Patel; Aashay; Patel; Kanishk; Agnihotri; Dhaval; Pau; Samir; Patel; Badal; Thakkar; Nikhil; Nalluri; Deepak; Asti; Ritesh; Kanotra; Sabeeda; Kadavath; Shilpkumar; Arora; Nilay; Patel; Achint; Patel; Azfar; Sheikh; Neil; Patel; Apurva; O; Badheka; Abhishek; Deshmukh; Hakan; Paydak; Juan; Viles-Gonzalez

    2015-01-01

    Atrial fibrillation(AF) is the most common type of sustained arrhythmia,which is now on course to reach epidemic proportions in the elderly population. AF is a commonly encountered comorbidity in patients with cardiac and major non-cardiac diseases. Morbidity and mortality associated with AF makes it a major healthcare burden. The objective of our article is to determine the prognostic impact of AF on acute coronary syndromes,heart failure and chronic kidney disease. Multiple studies have been conducted to determine if AF has an independent role in the overall mortality of such patients. Our review suggests that AF has an independent adverse prognostic impact on the clinical outcomes of acute coronary syndromes,heart failure and chronic kidney disease.

  2. Role of cystathionine gamma-lyase in immediate renal impairment and inflammatory response in acute ischemic kidney injury

    OpenAIRE

    Lajos Markó; Szijártó, István A.; Filipovic, Milos R.; Mario Kaßmann; András Balogh; Joon-Keun Park; Lukasz Przybyl; Gabriele N’diaye; Stephanie Krämer; Juliane Anders; Isao Ishii; Müller, Dominik N.; Maik Gollasch

    2016-01-01

    Hydrogen sulfide (H2S) is known to act protectively during renal ischemia/reperfusion injury (IRI). However, the role of the endogenous H2S in acute kidney injury (AKI) is largely unclear. Here, we analyzed the role of cystathionine gamma-lyase (CTH) in acute renal IRI using CTH-deficient (Cth(-/-)) mice whose renal H2S levels were approximately 50% of control (wild-type) mice. Although levels of serum creatinine and renal expression of AKI marker proteins were equivalent between Cth(-/-) and...

  3. Mesenchymal stem cells ameliorate rhabdomyolysis-induced acute kidney injury via the activation of M2 macrophages

    OpenAIRE

    Geng, Yanqiu; ZHANG Li; Fu, Bo; Zhang, Jianrong; Hong, Quan; Hu, Jie; Li, Diangeng; Luo, Congjuan; Cui, Shaoyuan; Zhu, Fei; Chen, Xiangmei

    2014-01-01

    Introduction The mortality of rhabdomyolysis-induced acute kidney injury (AKI) is still high, as there is no effective therapy. It has been shown that bone marrow-derived mesenchymal stem cells (MSCs) can induce M2 macrophages, which mediate MSC protection in other experimental inflammation-related organ injury. This study was designed to investigate the protective effects of macrophage activation in MSC therapy of rhabdomyolysis-induced AKI. Methods MSCs were injected into glycerol-induced r...

  4. Acute-on-Chronic Kidney Injury in Thyroid Hormone Withdrawal: A Case with Possible Implications for Radioactive Iodine Planning

    OpenAIRE

    McAninch, Elizabeth A.; Lagari, Violet S.

    2015-01-01

    The association between renal dysfunction and hypothyroidism is of increasing clinical importance as thyroid hormone replacement may attenuate decline in renal function and improve cardiovascular outcomes in patients with chronic kidney disease (CKD). Although multiple mechanisms for the induction of renal insufficiency in hypothyroidism have been described, the renal impact of short-term, acute hypothyroidism is unknown, which has possible implications for thyroid cancer patients preparing t...

  5. Early prediction of acute kidney injury biomarkers after endovascular stent graft repair of aortic aneurysm: a prospective observational study

    OpenAIRE

    Ueta, Kazuyoshi; Watanabe, Michiko; Iguchi, Naoya; Uchiyama, Akinori; Shirakawa, Yukitoshi; Kuratani, Toru; Sawa, Yoshiki; Fujino, Yuji

    2014-01-01

    Background Acute kidney injury (AKI) is a common and serious condition usually detected some time after onset by changes in serum creatinine (sCr). Although stent grafting to repair aortic aneurysms is associated with AKI caused by surgical procedures or the use of contrast agents, early biomarkers for AKI have not been adequately examined in stent graft recipients. We studied biomarkers including urinary neutrophil gelatinase-associated lipocalin (NGAL), blood NGAL, N-acetyl-β-d-glucosaminid...

  6. Levels of Protein C and Soluble Thrombomodulin in Critically Ill Patients with Acute Kidney Injury: A Multicenter Prospective Observational Study

    OpenAIRE

    Josée Bouchard; Rakesh Malhotra; Shamik Shah; Yu-Ting Kao; Florin Vaida; Akanksha Gupta; Berg, David T.; Grinnell, Brian W.; Brenda Stofan; Tolwani, Ashita J.; Mehta, Ravindra L

    2015-01-01

    Endothelial dysfunction contributes to the development of acute kidney injury (AKI) in animal models of ischemia reperfusion injury and sepsis. There are limited data on markers of endothelial dysfunction in human AKI. We hypothesized that Protein C (PC) and soluble thrombomodulin (sTM) levels could predict AKI. We conducted a multicenter prospective study in 80 patients to assess the relationship of PC and sTM levels to AKI, defined by the AKIN creatinine (AKI Scr) and urine output criteria ...

  7. Primary Injuries and Secondary Organ Failures in Trauma Patients with Acute Kidney Injury Treated with Continuous Renal Replacement Therapy

    OpenAIRE

    Sigrid Beitland; Ingrid Os; Kjetil Sunde

    2014-01-01

    Background. Acute kidney injury (AKI) treated with continuous renal replacement therapy (CRRT) is a severe complication in trauma patients. The aim of the study was to assess primary traumatic injuries and secondary organ failures in severe posttraumatic AKI. Methods. Retrospective review of adult trauma patients admitted to the trauma centre at Oslo University Hospital Ullevål. Injury severity score (ISS) was used to assess the severity of primary injuries, and sequential organ failure asses...

  8. Cutaneous and renal glomerular vasculopathy as a cause of acute kidney injury in dogs in the UK

    OpenAIRE

    Holm, L. P.; Hawkins, I.; Robin, C.; Newton, R. J.; Jepson, R.; Stanzani, G.; McMahon, L. A.; Pesavento, P.; Carr, T; Cogan, T.; Couto, C.G.; Cianciolo, R.; Walker, D J

    2015-01-01

    To describe the signalment, clinicopathological findings and outcome in dogs presenting with acute kidney injury (AKI) and skin lesions between November 2012 and March 2014, in whom cutaneous and renal glomerular vasculopathy (CRGV) was suspected and renal thrombotic microangiopathy (TMA) was histopathologically confirmed. The medical records of dogs with skin lesions and AKI, with histopathologically confirmed renal TMA, were retrospectively reviewed. Thirty dogs from across the UK were iden...

  9. A Rare Cause of Acute Kidney Injury in a Female Patient with Breast Cancer Presenting as Renal Colic

    OpenAIRE

    Roxana Jurubita; Bogdan Obrisca; Gener Ismail

    2016-01-01

    Renal infarction is a rare cause of acute kidney injury which could lead to permanent loss of renal function. A prompt diagnosis is necessary in order to achieve a successful revascularization of the occluded artery. Given the rarity of the disease and the paucity of the reported cases in the previous literature a high index of suspicion must be maintained not only in the classical cardiac sources of systemic emboli (atrial fibrillation, dilated cardiomyopathy, or endocarditis), but also in t...

  10. Successful use of combined high cut-off haemodialysis and bortezomib for acute kidney injury associated with myeloma cast nephropathy.

    LENUS (Irish Health Repository)

    Ward, F

    2012-05-01

    We present the case of a 58-year old female with de novo dialysis-dependent acute kidney injury (AKI) secondary to myeloma cast nephropathy. The patient underwent extended high cut-off haemodialysis (HCO-HD), in conjunction with bortezomib-based chemotherapy, and soon became dialysis independent with normal renal function. To our knowledge, this is the first time this treatment strategy has been employed successfully in an Irish centre.

  11. Mannitol increases renal blood flow and maintains filtration fraction and oxygenation in postoperative acute kidney injury: a prospective interventional study

    OpenAIRE

    Bragadottir, Gudrun; Redfors, Bengt; Ricksten, Sven-Erik

    2012-01-01

    Introduction Acute kidney injury (AKI), which is a major complication after cardiovascular surgery, is associated with significant morbidity and mortality. Diuretic agents are frequently used to improve urine output and to facilitate fluid management in these patients. Mannitol, an osmotic diuretic, is used in the perioperative setting in the belief that it exerts reno-protective properties. In a recent study on uncomplicated postcardiac-surgery patients with normal renal function, mannitol i...

  12. Acute Kidney Injury Induced by Systemic Inflammatory Response Syndrome is an Avid and Persistent Sodium-Retaining State

    OpenAIRE

    Daniel Vitorio; Alexandre Toledo Maciel

    2014-01-01

    Acute kidney injury (AKI) is a frequent complication of the systemic inflammatory response syndrome (SIRS), which is triggered by many conditions in the intensive care unit, including different types of circulatory shock. One under-recognized characteristic of the SIRS-induced AKI is its avidity for sodium retention, with progressive decreases in urinary sodium concentration (NaU) and its fractional excretion (FENa). This phenomenon occurs in parallel with increases in serum creatinine, being...

  13. Assessing glomerular filtration rate (GFR) in critically ill patients with acute kidney injury - true GFR versus urinary creatinine clearance and estimating equations

    OpenAIRE

    Bragadottir, Gudrun; Redfors, Bengt; Ricksten, Sven-Erik

    2013-01-01

    Introduction Estimation of kidney function in critically ill patients with acute kidney injury (AKI), is important for appropriate dosing of drugs and adjustment of therapeutic strategies, but challenging due to fluctuations in kidney function, creatinine metabolism and fluid balance. Data on the agreement between estimating and gold standard methods to assess glomerular filtration rate (GFR) in early AKI are lacking. We evaluated the agreement of urinary creatinine clearance (CrCl) and three...

  14. Profile of acute kidney injury after open heart surgeries in a tertiary care hospital.

    Science.gov (United States)

    Rather, Fayaz A; Najar, Saleem M; Malla, Hilal A; Ahangar, A G; Bhat, Hilal M; Wani, Imtiyaz A

    2015-11-01

    Our objective is to determine the incidence, etiology, risk factors and outcome of acute kidney injury (AKI) after open heart surgery. A prospective study was conducted on 62 patients who underwent open heart surgery and were followed-up for the development of AKI and to determine its incidence, etiology and outcome. Post-operative AKI was considered when the post-operative serum creatinine was >1.5 mg/dL or there was doubling of serum creatinine above the baseline (pre-operative) with a prior normal renal function. The incidence of AKI in the post-operative period in our study was 17.7%. The common etiological factors for AKI in our study were sepsis, hypotension, prolonged need for ventilator and inotropic support and drugs given in the post-operative period. The important risk factors for the development of AKI in the post-operative period were hypertension, diabetes mellitus, gout, prolonged total bypass time and prolonged aortic cross-clamp time. The overall mortality in our study subjects was 11.3% (seven of 62 died) and the mortality in the patients who developed post-operative AKI was 71.4%.

  15. Professor Eric G.L. Bywaters, Acute Kidney Injury and the "forgotten" letter.

    Science.gov (United States)

    Almond, Michael

    2016-02-01

    The Bywaters seminal 1941 British Medical Journal paper on the crush syndrome was important both for its written content and for using a photomicrograph demonstrating pigmented casts in the renal tubules. He appeared to be reporting the first cases of renal failure secondary to crushing injuries. Most at this point would have been content yet Bywaters demonstrated both determination and humility by publishing a letter in the BMJ 4 months later. This letter, now almost forgotten and rarely referenced, significantly corrected his original paper. He identified that descriptions of the syndrome had been made before, not least by German pathologists in World War 1. The letter recognised various pathologists and surgeons, Colmers (1909) reporting on casualties from the Messina earthquake suffering from acute pressure necrosis and Frankenthal (1916) describing soldiers who had been buried in the trenches showing oedema, bloody urine and post mortem ischaemic muscle necrosis. Others were credited as describing similar cases in inaccessible journals or in "inaugural dissertations". Hackradt (1917) described injuries from burial with oedema of the leg and bloody urine containing albumin and casts, necropsy showed muscle necrosis and tubular degeneration in the kidneys with blood casts and Lewin (1919) described 3 similar cases. Bywaters subsequently credits Minami (1923) a Japanese dermatologist working in Germany for summarizing the literature and providing a description that tallied exactly with his own. Finally Bywaters puzzles why the standard textbooks on war surgery available in Great Britain and the U.S.A. in 1941 make no mention of this entity. PMID:26913877

  16. Contrast-induced acute kidney injury: how much contrast is safe?

    LENUS (Irish Health Repository)

    Keaney, John J

    2013-02-14

    Iodinated contrast media (CM) are used in many investigations that a patient may undergo during the course of an in-patient stay. For the vast majority of patients, exposure to CM has no sequelae; however, in a small percentage, it can result in a worsening in renal function termed contrast-induced acute kidney injury (CI-AKI). CI-AKI is one of the leading causes of in-hospital renal dysfunction. It is associated with a significant increase in morbidity and mortality as well as an increased length of hospital stay and costs. Unfortunately, the results of extensive research into pharmacological inventions to prevent CI-AKI remain disappointing. In this article, we briefly outline the pathophysiological mechanisms by which iodinated CM may cause CI-AKI and discuss the evidence for reducing CI-AKI by limiting contrast volumes. In particular, we review the data surrounding the use of contrast volume to glomerular filtration rate ratios, which can be used by clinicians to effectively lower the incidence of CI-AKI in their patients.

  17. Recent advances in pathophysiology and biomarkers of sepsis-induced acute kidney injury.

    Science.gov (United States)

    Umbro, Ilaria; Gentile, Giuseppe; Tinti, Francesca; Muiesan, Paolo; Mitterhofer, Anna Paola

    2016-02-01

    Sepsis is a complex clinical syndrome characterized by a systemic inflammatory response to an infective insult. This process often leads to widespread tissue injury and multiple organ dysfunction. In particular, the development of acute kidney injury (AKI) is one of the most frequent complications, which increases the complexity and cost of care, and is an independent risk factor for mortality. Previous suggestions highlighting systemic hypotension, renal vasoconstriction and ischaemia-reperfusion injury as the primary pathophysiological mechanisms involved in sepsis-induced AKI have been challenged. Recently it has been shown that sepsis-induced AKI occurs in the setting of microvascular dysfunction with release of microparticles, inflammation and energetic adaptation of highly metabolic organs to cellular stress. The intolerable high mortality rate associated with sepsis-induced AKI is partially explained by an incomplete understanding of its pathophysiology and a delay in diagnosis. The aim of this review is to focus on advances in understanding the sepsis pathophysiology, with particular attention to the fundamental mechanisms of sepsis-induced AKI and the potential diagnostic and prognostic markers involved.

  18. Professor Eric G.L. Bywaters, Acute Kidney Injury and the "forgotten" letter.

    Science.gov (United States)

    Almond, Michael

    2016-02-01

    The Bywaters seminal 1941 British Medical Journal paper on the crush syndrome was important both for its written content and for using a photomicrograph demonstrating pigmented casts in the renal tubules. He appeared to be reporting the first cases of renal failure secondary to crushing injuries. Most at this point would have been content yet Bywaters demonstrated both determination and humility by publishing a letter in the BMJ 4 months later. This letter, now almost forgotten and rarely referenced, significantly corrected his original paper. He identified that descriptions of the syndrome had been made before, not least by German pathologists in World War 1. The letter recognised various pathologists and surgeons, Colmers (1909) reporting on casualties from the Messina earthquake suffering from acute pressure necrosis and Frankenthal (1916) describing soldiers who had been buried in the trenches showing oedema, bloody urine and post mortem ischaemic muscle necrosis. Others were credited as describing similar cases in inaccessible journals or in "inaugural dissertations". Hackradt (1917) described injuries from burial with oedema of the leg and bloody urine containing albumin and casts, necropsy showed muscle necrosis and tubular degeneration in the kidneys with blood casts and Lewin (1919) described 3 similar cases. Bywaters subsequently credits Minami (1923) a Japanese dermatologist working in Germany for summarizing the literature and providing a description that tallied exactly with his own. Finally Bywaters puzzles why the standard textbooks on war surgery available in Great Britain and the U.S.A. in 1941 make no mention of this entity.

  19. Clofarabine-associated acute kidney injury in patients undergoing hematopoietic stem cell transplant.

    Science.gov (United States)

    Petri, Camille R; O'Donnell, Peter H; Cao, Hongyuan; Artz, Andrew S; Stock, Wendy; Wickrema, Amittha; Hard, Marjie; van Besien, Koen

    2014-12-01

    Abstract We examined clofarabine pharmacokinetics and association with renal toxicity in 62 patients participating in a phase I-II study of clofarabine-melphalan-alemtuzumab conditioning for hematopoietic stem cell transplant (HSCT). Pharmacokinetic parameters, including clofarabine area under the concentration-time curve (AUC), maximum concentration and clearance, were measured, and patients were monitored for renal injury. All patients had normal pretreatment creatinine values, but over half (55%) experienced acute kidney injury (AKI) after clofarabine administration. Age was the strongest predictor of AKI, with older patients at greater risk (p = 0.002). Clofarabine AUC was higher in patients who developed AKI, and patients with the highest dose-normalized AUCs experienced the most severe grades of AKI (p = 0.01). Lower baseline renal function, even when normal, was associated with lower clofarabine clearance (p = 0.008). These data suggest that renal-adjustment of clofarabine dosing should be considered for older and at-risk patients even when renal function is ostensibly normal. PMID:24564572

  20. Role of markers for acute kidney injury in surgical management of patients with renal cancer

    Directory of Open Access Journals (Sweden)

    O. I. Kit

    2015-01-01

    Full Text Available The paper gives the results of studying the urinary levels of markers of acute kidney injury (AKI in 46 patients with renal cancer during separate ureteral catheterization before the surgery and 24 hours after laparoscopic partial nephrectomy performed due to elective indications under warm ischemia. The levels of cystatin C, neutrophil gelatinase-associated lipocalin (NGAL, liver-type fatty acid-binding protein (L-FABP, and interleukin-18 were examined by enzyme immunoassay. It has been established that the risk of early postoperative AKI may be predicted from the baseline urinary levels of cystatin C and LFABP in patients with renal cancer resulting from 15-20-min warm ischemia time during the partial nephrectomy. An approach based on estimation of the baseline urinary levels of cystatin C and L-FABP to be incorporated into a preoperative examination scheme is proposed for surgical treatment policy choosing in patients with renal cancer. A scheme for examining patients with renal cancer is also suggested for the risk of complications and the degree of AKI assessing in the early post-operative period.

  1. Association of oliguria with the development of acute kidney injury in the critically ill.

    Science.gov (United States)

    Vaara, Suvi T; Parviainen, Ilkka; Pettilä, Ville; Nisula, Sara; Inkinen, Outi; Uusaro, Ari

    2016-01-01

    Urine output (UO) criterion may increase the sensitivity of the definition of acute kidney injury (AKI). We determined whether the empirically derived definition for oliguria(<0.5 ml/kg/h) is independently associated with adverse outcome. Data analysis included hourly recorded UO from the prospective, multicenter FINNAKI study conducted in 16 Finnish intensive care units. Confounder-adjusted association of oliguria of different severity and duration primarily with the development of AKI defined by creatinine criterion (Cr-AKI) or renal replacement therapy(RRT) was assessed. Secondarily, we determined the association of oliguria with 90-day mortality. Of the 1966 patients analyzed for the development of AKI, 454 (23.1%) reached this endpoint. Within this AKI cohort, 312 (68.7%)developed Cr-AKI, 21 (4.6%) commenced RRT without Cr-AKI, and 121 (26.7%) commenced RRT with Cr-AKI. Episodes of severe oliguria (<0.1 ml/kg/h) for more than 3 h were independently associated with the development of Cr-AKI or RRT. The shortest periods of consecutive oliguria independently associated with an increased risk for 90-day mortality were 6–12 h of oliguria from 0.3 to <0.5 ml/kg/h, over 6 h of oliguria from 0.1 to <0.3 ml/kg/h, and severe oliguria lasting over 3 h.Thus, our findings underlie the importance of hourly UO measurements.

  2. Increased Risk of Acute Kidney Injury following Pneumococcal Pneumonia: A Nationwide Cohort Study

    Science.gov (United States)

    Lin, Te-Yu; Chen, Yu-Guang; Lin, Cheng-Li; Kao, Chia-Hung

    2016-01-01

    Purpose Pneumococcal disease leads to renal complications ranging from persistent proteinuria to end-stage renal disease. Studies on the association between pneumococcal pneumonia (PP) and acute kidney injury (AKI) are scant. This study assessed the relationship between PP and risk of AKI. Methods This nationwide population-based cohort study examined data from the Taiwan National Health Insurance Research Database for the period 2000–2011. We identified inpatients with newly diagnosed PP according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. In addition, we selected a comparison cohort from inpatient claims without the diagnosis of PP that was randomly frequency-matched with the PP cohort according to age, sex, index year and comorbidities. We analyzed the risks of AKI by using Cox proportional hazards regression models, adjusted for sex, age, and comorbidities. Results A total of 10,069 patients with PP and 10,069 controls were enrolled in this study. After adjustments for age, sex, and comorbidities, patients with PP had a 1.11-fold risk of developing AKI compared with the comparison cohort. Conclusion This study indicates that AKI risks are higher in patients with PP compared with the comparison cohort. Careful follow-up observation and aggressive treatment are necessary for patients with PP to reduce the risk of AKI. PMID:27362355

  3. Efficacy of extracorporeal albumin dialysis for acute kidney injury due to cholestatic jaundice nephrotoxicity.

    Science.gov (United States)

    Sens, Florence; Bacchetta, Justine; Rabeyrin, Maud; Juillard, Laurent

    2016-01-01

    We report a case of a 37-year-old man with Maturity Onset Diabetes of the Youth (MODY) type 5, admitted for an episode of cholestasis and a simultaneous acute kidney injury (AKI). Chronic liver disease was due to a mutation in the transcription factor 2 (TCF2) gene, thus highlighting the need for a close liver follow-up in these patients. AKI was attributed to a cholemic nephropathy based on the following rationale: (1) alternative diagnoses were actively ruled out; (2) the onset of AKI coincided with the onset of severe hyperbilirubinaemia; (3) renal pathology showed large bile tubular casts and a marked tubular necrosis and (4) creatinine serum dramatically decreased when bilirubin levels improved after the first sessions of extracorporeal albumin dialysis (ECAD), thus suggesting its role in renal recovery. Even though cholestasis can precipitate renal injury, the diagnosis of cholemic nephropathy could require a renal biopsy at times. Future studies should confirm the benefits of ECAD in cholemic nephropathy. PMID:27389722

  4. Rosiglitazone Did Not Induce Acute Kidney Injury in Normocholesterolemic Rats Despite Reduction in Glomerular Filtration Rate

    Directory of Open Access Journals (Sweden)

    Cristiano Dias

    2014-04-01

    Full Text Available Background/Aims: Rosiglitazone (RGL has been used to ameliorate lipids homeostasis and also to treat inflammatory diseases. However, RGL may reduce renal blood flow and glomerular filtration rate (GFR predisposing to acute kidney injury (AKI. We investigated whether the treatment with RGL induces AKI in normocholesterolemic (NC and hypercholesterolemic (HC rats. Methods: We measured GFR by inulin clearance technique and we quantified urinary neutrophil gelatinase-associated lipocalin (uNGAL in all groups at baseline and during Ang II-stimulated vasoconstriction. Moreover, we evaluated the presence of renal damaged by histologic examination. Results: At baseline, NC and HC had normal and similar GFR. RGL treatment reduced GFR only in NC+RGL. Unexpectedly, HC+RGL showed high levels of uNGAL although GFR was at normal range. During Ang II-stimulated vasoconstriction, all groups showed reduction in GFR to the same range and we found high levels of uNGAL and high score of renal damage in HC and HC+RGL. Conclusion: RGL acts distinctly in normocholesterolemia and in hypercholesterolemia. Reduction in GFR provoked by RGL treatment did not allow the diagnosis of AKI in NC even in the presence of ANG II-stimulated vasoconstriction. However, AKI was diagnosed in HC+RGL at baseline although GFR was within normal range.

  5. Heterogeneity of epigenetic changes at ischemia/reperfusion- and endotoxin-induced acute kidney injury genes.

    Science.gov (United States)

    Mar, Daniel; Gharib, Sina A; Zager, Richard A; Johnson, Ali; Denisenko, Oleg; Bomsztyk, Karol

    2015-10-01

    Aberrant gene expression is a molecular hallmark of acute kidney injury (AKI). As epigenetic processes control gene expression in a cell- and environment-defined manner, understanding the epigenetic pathways that regulate genes altered by AKI may open vital new insights into the complexities of disease pathogenesis and identify possible therapeutic targets. Here we used matrix chromatin immunoprecipitation and integrative analysis to study 20 key permissive and repressive epigenetic histone marks at transcriptionally induced Tnf, Ngal, Kim-1, and Icam-1 genes in mouse models of AKI; unilateral renal ischemia/reperfusion, lipopolysaccharide (LPS), and their synergistically injurious combination. Results revealed unexpected heterogeneity of transcriptional and epigenetic responses. Tnf and Ngal were transcriptionally upregulated in response to both treatments individually, and to combination treatment. Kim-1 was induced by ischemia/reperfusion and Icam-1 by LPS only. Epigenetic alterations at these genes exhibited distinct time-dependent changes that shared some similarities, such as reduction in repressive histone modifications, and also had major ischemia/reperfusion versus endotoxin differences. Thus, diversity of changes at AKI genes in response to different insults indicates involvement of several epigenetic pathways. This could be exploited pharmacologically through rational-drug design to alter the course and improve clinical outcomes of this syndrome. PMID:26061546

  6. Rhabdomyolysis-Induced Acute Kidney Injury Under Hypoxia and Deprivation of Food and Water

    Directory of Open Access Journals (Sweden)

    Jingwen Wang

    2013-10-01

    Full Text Available Background: To investigate the renal pathophysiologyin rhabdomyolysis-induced acute kidney injury (AKI in rats under hypoxia and deprivation of food and water (HDFW, thus broadening the knowledge about rhabdomyolysis-induced AKI in massive earthquake. Methods: Male Wistar rats weighing 200-230g were randomized into control, rhabdomyolysis (R, HDFW and rhabdomyolysis in combination with HDFW (R/HDFW group. Experimental rhabdomyolysis rat model was established through clamping hind limb muscles, HDFW model rats were kept in 10% hypoxic chamber unavailable to food and water. At 1, 3, 5, 7, 9, 11d after treatment, serum creatinine (Scr level, renal index, renal structural changes and cell apoptosis were analyzed. Results: After R, HDFW, R/HDFW treatment, the animals showed significantly higher Scr levels than the control group. Renal index in R and R/HDFW groups elevated remarkably compared with that in control and HDFW group. The results of histopathology, ultra-structure and apoptosis assay suggested that rhabdomyolysis caused renal tubular injury, HDFW treatment resulted in renal vascular dilation, tissue congestion and tubular cell damage. In addition, more severe renal lesion appeared in R/HDFW. Conclusions: We conclude that the association of experimental rhabdomyolysis with HDFW results in a different functional and histological pattern. The rhabdomyolysis-HDFW combination causes more severe renal injury.

  7. Hydronephrosis of one kidney

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    ... Acute hydronephrosis; Urinary obstruction; Unilateral hydronephrosis; Nephrolithiasis - hydronephrosis; Kidney stone - hydronephrosis; Renal calculi - hydronephrosis; Ureteral calculi - hydronephrosis; ...

  8. A nationwide survey of clinical characteristics, management, and outcomes of acute kidney injury (AKI) - patients with and without preexisting chronic kidney disease have different prognoses.

    Science.gov (United States)

    Pan, Heng-Chih; Wu, Pei-Chen; Wu, Vin-Cent; Yang, Ya-Fei; Huang, Tao-Min; Shiao, Chih-Chung; Chen, Te-Chuan; Tarng, Der-Cherng; Lin, Jui-Hsiang; Yang, Wei-Shun; Sun, Chiao-Yin; Lin, Chan-Yu; Chu, Tzong-Shinn; Wu, Mai-Szu; Wu, Kwan-Dun; Chen, Yung-Chang; Huang, Chiu-Ching

    2016-09-01

    Acute kidney injury (AKI) is a common complication in hospitalized patients. The International Society of Nephrology implemented the "0 by 25" initiative aimed at preventing deaths from treatable AKI worldwide by 2025 and conducted a global snapshot survey in 2014. We joined in the project and conducted this study to compare the epidemiology, risk factors, and prognosis between patients with pure AKI and those with acute-on-chronic kidney disease (ACKD). In this study, we prospectively collected demographic parameters and data on clinical characteristics, baseline comorbidities, management, and outcomes of 201 AKI patients in 18 hospitals in Taiwan from September 2014 to November 2014. The in-hospital mortality rate was 16%. AKI was mostly attributed to sepsis (52%). Multivariate logistic regression indicated that oliguria was a positive independent predictor of in-hospital mortality, whereas preexisting CKD and exposure to nephrotoxic agents were negative independent predictors. The prevalence of vasopressor use, intensive care unit care, and mortality were significantly higher in pure AKI patients than in ACKD patients. Moreover, serum creatinine (SCr) levels significantly increased within 7 days after AKI diagnosis in nonsurvivors but not in survivors in the pure AKI group. By contrast, SCr levels were persistently lower in nonsurvivors than in survivors in the ACKD group during the same period. We thus determined that the prognosis of ACKD patients differed from that of pure AKI patients. Considering the CKD history in the future AKI staging system may improve prognosis prediction. PMID:27684854

  9. Hypomagnesemia is a risk factor for nonrecovery of renal function and mortality in AIDS patients with acute kidney injury.

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    Santos, M S Biagioni; Seguro, A C; Andrade, L

    2010-03-01

    The objective of the present study was to determine the prevalence of electrolyte disturbances in AIDS patients developing acute kidney injury in the hospital setting, as well as to determine whether such disturbances constitute a risk factor for nephrotoxic and ischemic injury. A prospective, observational cohort study was carried out. Hospitalized AIDS patients were evaluated for age; gender; coinfection with hepatitis; diabetes mellitus; hypertension; time since HIV seroconversion; CD4 count; HIV viral load; proteinuria; serum levels of creatinine, urea, sodium, potassium and magnesium; antiretroviral use; nephrotoxic drug use; sepsis; intensive care unit (ICU) admission, and the need for dialysis. Each of these characteristics was correlated with the development of acute kidney injury, with recovery of renal function and with survival. Fifty-four patients developed acute kidney injury: 72% were males, 59% had been HIV-infected for >5 years, 72% had CD4 counts dialysis, sepsis and hypomagnesemia were all significantly associated with nonrecovery of renal function and with mortality. Nonrecovery of renal function was significantly associated with hypomagnesemia, as was mortality in the multivariate analysis. The risks for nonrecovery of renal function and for death were 6.94 and 6.92 times greater, respectively, for patients with hypomagnesemia. In hospitalized AIDS patients, hypomagnesemia is a risk factor for nonrecovery of renal function and for in-hospital mortality. To determine whether hypomagnesemia is a determinant or simply a marker of critical illness, further studies involving magnesium supplementation in AIDS patients are warranted.

  10. Cysteine Metabolism and Oxidative Processes in the Rat Liver and Kidney after Acute and Repeated Cocaine Treatment.

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    Danuta Kowalczyk-Pachel

    Full Text Available The role of cocaine in modulating the metabolism of sulfur-containing compounds in the peripheral tissues is poorly understood. In the present study we addressed the question about the effects of acute and repeated (5 days cocaine (10 mg/kg i.p. administration on the total cysteine (Cys metabolism and on the oxidative processes in the rat liver and kidney. The whole pool of sulfane sulfur, its bound fraction and hydrogen sulfide (H2S were considered as markers of anaerobic Cys metabolism while the sulfate as a measure of its aerobic metabolism. The total-, non-protein- and protein- SH group levels were assayed as indicators of the redox status of thiols. Additionally, the activities of enzymes involved in H2S formation (cystathionine γ-lyase, CSE; 3-mercaptopyruvate sulfurtransferase, 3-MST and GSH metabolism (γ-glutamyl transpeptidase, γ-GT; glutathione S-transferase, GST were determined. Finally, we assayed the concentrations of reactive oxygen species (ROS and malondialdehyde (MDA as markers of oxidative stress and lipid peroxidation, respectively. In the liver, acute cocaine treatment, did not change concentrations of the whole pool of sulfane sulfur, its bound fraction, H2S or sulfate but markedly decreased levels of non-protein SH groups (NPSH, ROS and GST activity while γ-GT was unaffected. In the kidney, acute cocaine significantly increased concentration of the whole pool of sulfane sulfur, reduced the content of its bound fraction but H2S, sulfate and NPSH levels were unchanged while ROS and activities of GST and γ-GT were reduced. Acute cocaine enhanced activity of the CSE and 3-MST in the liver and kidney, respectively. Repeatedly administered cocaine enhanced the whole pool of sulfane sulfur and reduced H2S level simultaneously increasing sulfate content both in the liver and kidney. After repeated cocaine, a significant decrease in ROS was still observed in the liver while in the kidney, despite unchanged ROS content, a marked

  11. Cysteine Metabolism and Oxidative Processes in the Rat Liver and Kidney after Acute and Repeated Cocaine Treatment.

    Science.gov (United States)

    Kowalczyk-Pachel, Danuta; Iciek, Małgorzata; Wydra, Karolina; Nowak, Ewa; Górny, Magdalena; Filip, Małgorzata; Włodek, Lidia; Lorenc-Koci, Elżbieta

    2016-01-01

    The role of cocaine in modulating the metabolism of sulfur-containing compounds in the peripheral tissues is poorly understood. In the present study we addressed the question about the effects of acute and repeated (5 days) cocaine (10 mg/kg i.p.) administration on the total cysteine (Cys) metabolism and on the oxidative processes in the rat liver and kidney. The whole pool of sulfane sulfur, its bound fraction and hydrogen sulfide (H2S) were considered as markers of anaerobic Cys metabolism while the sulfate as a measure of its aerobic metabolism. The total-, non-protein- and protein- SH group levels were assayed as indicators of the redox status of thiols. Additionally, the activities of enzymes involved in H2S formation (cystathionine γ-lyase, CSE; 3-mercaptopyruvate sulfurtransferase, 3-MST) and GSH metabolism (γ-glutamyl transpeptidase, γ-GT; glutathione S-transferase, GST) were determined. Finally, we assayed the concentrations of reactive oxygen species (ROS) and malondialdehyde (MDA) as markers of oxidative stress and lipid peroxidation, respectively. In the liver, acute cocaine treatment, did not change concentrations of the whole pool of sulfane sulfur, its bound fraction, H2S or sulfate but markedly decreased levels of non-protein SH groups (NPSH), ROS and GST activity while γ-GT was unaffected. In the kidney, acute cocaine significantly increased concentration of the whole pool of sulfane sulfur, reduced the content of its bound fraction but H2S, sulfate and NPSH levels were unchanged while ROS and activities of GST and γ-GT were reduced. Acute cocaine enhanced activity of the CSE and 3-MST in the liver and kidney, respectively. Repeatedly administered cocaine enhanced the whole pool of sulfane sulfur and reduced H2S level simultaneously increasing sulfate content both in the liver and kidney. After repeated cocaine, a significant decrease in ROS was still observed in the liver while in the kidney, despite unchanged ROS content, a marked increase

  12. Significance of downregulation of renal organic cation transporter (SLC47A1 in cisplatin-induced proximal tubular injury

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    Mizuno T

    2015-07-01

    Full Text Available Tomohiro Mizuno,1–3 Waichi Sato,2,3 Kazuhiro Ishikawa,4 Yuki Terao,1 Kazuo Takahashi,2 Yukihiro Noda,5 Yukio Yuzawa,2 Tadashi Nagamatsu1 1Department of Analytical Pharmacology, Meijo University Faculty of Pharmacy, Nagoya, 2Department of Nephrology, School of Medicine, Fujita Health University, Toyoake, 3Department of Nephrology, Nagoya University School of Medicine, Nagoya, 4Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, 5Division of Clinical Sciences and Neuropsychopharmacology, Meijo University Faculty of Pharmacy, Nagoya, Japan Background/aim: To elucidate the mechanism responsible for developing acute kidney injury in patients with diabetes mellitus, we also evaluated the issue of whether advanced glycation endproducts (AGEs influence the expressions of multi antimicrobial extrusion protein (MATE1/SLC47A1 in tubular cells. Materials and methods: To detect changing expression of MATE1/SLC47A1 in dose- and time-dependent manners, human proximal tubular epithelial cells were incubated with AGE-aggregated-human serum albumin. As a function assay for MATE1/SLC47A1, human proximal tubular epithelial cells were incubated with cisplatin or carboplatin. Results: On incubation with AGEs, the expressions of MATE1/SLC47A1 were decreased in tubular cells. In addition, the toxicities of cisplatin were increased in tubular cells that had been pretreated with AGEs. However, the toxicities of carboplatin were smaller than that of cisplatin in proximal tubular epithelial cells. Conclusion: The expression of the MATE1/SLC47A1 is decreased by AGEs, which increases the risk for proximal tubular injury. Keywords: advanced glycation endproducts, cisplatin, SLC47A1, diabetes mellitus, acute kidney injury

  13. A mouse model of Townes-Brocks syndrome expressing a truncated mutant Sall1 protein is protected from acute kidney injury.

    Science.gov (United States)

    Hirsch, Sara; El-Achkar, Tarek; Robbins, Lynn; Basta, Jeannine; Heitmeier, Monique; Nishinakamura, Ryuichi; Rauchman, Michael

    2015-11-15

    It has been postulated that developmental pathways are reutilized during repair and regeneration after injury, but functional analysis of many genes required for kidney formation has not been performed in the adult organ. Mutations in SALL1 cause Townes-Brocks syndrome (TBS) and nonsyndromic congenital anomalies of the kidney and urinary tract, both of which lead to childhood kidney failure. Sall1 is a transcriptional regulator that is expressed in renal progenitor cells and developing nephrons in the embryo. However, its role in the adult kidney has not been investigated. Using a mouse model of TBS (Sall1TBS), we investigated the role of Sall1 in response to acute kidney injury. Our studies revealed that Sall1 is expressed in terminally differentiated renal epithelia, including the S3 segment of the proximal tubule, in the mature kidney. Sall1TBS mice exhibited significant protection from ischemia-reperfusion injury and aristolochic acid-induced nephrotoxicity. This protection from acute injury is seen despite the presence of slowly progressive chronic kidney disease in Sall1TBS mice. Mice containing null alleles of Sall1 are not protected from acute kidney injury, indicating that expression of a truncated mutant protein from the Sall1TBS allele, while causative of congenital anomalies, protects the adult kidney from injury. Our studies further revealed that basal levels of the preconditioning factor heme oxygenase-1 are elevated in Sall1TBS kidneys, suggesting a mechanism for the relative resistance to injury in this model. Together, these studies establish a functional role for Sall1 in the response of the adult kidney to acute injury. PMID:26311113

  14. Role of electrolytes disturbances and Na(+)-K(+)-ATPase in cisplatin - induced renal toxicity and effects of ethanolic extract of Cichorium intybus.

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    Noori, Shafaq; Mahboob, Tabassum

    2012-10-01

    Cisplatin is known by its toxicity by disturbing electrolytes homeostasis. Thus we aimed to find out the role of herbal plant Cichorium intybus on Cisplatin - induced toxicity. 24 male Albino Wistar rats were randomly divided into 4 groups: Group I is termed as untreated control; Group II is Cisplatin control and received 3 mg/ kg b.w.; i.p.; Group III received C. intybus ethanolic extract at a dose of 500 mg/kg b.w. orally for 10 consecutive days and Group IV is Cisplatin + C. intybus pretreated group. C. intybus is given 30 minutes prior to Cisplatin. Cisplatin - induced electrolytes disturbances is indicated by increase Intra - erythrocyte sodium content, decreased plasma magnesium, calcium and Intra-erythrocyte Na(+)-K(+)-ATPase which implicates the renal toxicity. At a dose of 500 mg/kg b.w. of C. Intybus pretreatment showed partial counter action on the electrolytes imbalances and Na(+)-K(+)-ATPase activity. PMID:23010005

  15. Sildenafil citrate for prophylaxis of nephropathy in an animal model of contrast-induced acute kidney injury.

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    Lauver, D Adam; Carey, E Grant; Bergin, Ingrid L; Lucchesi, Benedict R; Gurm, Hitinder S

    2014-01-01

    Contrast-induced acute kidney injury (CIAKI) is one of the commonest complications associated with contrast media (CM). Although the exact etiology of CIAKI remains unclear, one hypothesis involves vasoconstriction of afferent arterioles resulting in renal ischemia. Increased renal blood flow, therefore, might represent an attractive target for the treatment of CIAKI. In this study we evaluated the protective effects of the phosphodiesterase type 5 (PDE5) inhibitor, sildenafil citrate, in a rabbit model of CIAKI. New Zealand white rabbits were used due to their susceptibility to CIAKI. To evaluate the effects of sildenafil, the drug was administered before CM infusion and repeatedly throughout the remainder of the experiment (6 mg/kg, p.o.). Animals were sacrificed after 48 hours and kidneys were prepared for histological evaluation. Intravenous administration of CM produced marked kidney injury. Serum creatinine concentrations were elevated within two hours of the infusion and remained elevated for the duration of the experiment. Histological evaluation of the kidneys revealed significant tubular necrosis. The effects of the CM were dose dependent. Treatment with sildenafil was associated with lesser degree of histological injury, attenuation in markers of acute kidney injury (48 hour creatinine 1.54±0.21 versus 4.42±1.31 mg/dl, p<0.05) and reduction in electrolyte derangement (percent change in serum K+ at 48 hours 2.55±3.80% versus 15.53±4.47%, p<0.05; serum Na+ at 48 hours -0.14±0.26% versus -1.97±1.29%, p = 0.20). The results suggest a possible role for PDE5 inhibitors in the treatment of CIAKI and warrant further evaluation to determine the exact mechanism of protection.

  16. C-phycocyanin prevents cisplatin-induced mitochondrial dysfunction and oxidative stress.

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    Fernández-Rojas, Berenice; Rodríguez-Rangel, Daniela Sarai; Granados-Castro, Luis Fernando; Negrette-Guzmán, Mario; León-Contreras, Juan Carlos; Hernández-Pando, Rogelio; Molina-Jijón, Eduardo; Reyes, José L; Zazueta, Cecilia; Pedraza-Chaverri, José

    2015-08-01

    The potential of C-phycocyanin (C-PC) to prevent cisplatin (CP)-induced kidney mitochondrial dysfunction was determined in CD-1 male mice. The CP-induced mitochondrial dysfunction was characterized by ultrastructural abnormalities and by decrease in the following parameters in isolated kidney mitochondria: adenosine diphosphate (ADP)-induced oxygen consumption (state 3), respiratory control ratio, ADP/oxygen (ADP/O) ratio, adenosine triphosphate synthesis, membrane potential, calcium retention, glutathione (GSH) content, and activity of respiratory complex I, aconitase, catalase, and GSH peroxidase. These mitochondria also showed increase in hydrogen peroxide production, malondialdehyde, and 3-nitrotyrosine protein adducts content. The above-described changes, as well as CP-induced nephrotoxicity, were attenuated in mice pretreated with a single injection of C-PC. Our data suggest that the attenuation of mitochondrial abnormalities is involved in the protective effect of C-PC against CP-induced nephrotoxicity. This is the first demonstration that C-PC pretreatment prevents CP-induced mitochondrial dysfunction in mice. PMID:25971372

  17. CCR9 interactions support ovarian cancer cell survival and resistance to cisplatin-induced apoptosis in a PI3K-dependent and FAK-independent fashion

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    Johnson Erica L

    2010-06-01

    Full Text Available Abstract Background Cisplatin is more often used to treat ovarian cancer (OvCa, which provides modest survival advantage primarily due to chemo-resistance and up regulated anti-apoptotic machineries in OvCa cells. Therefore, targeting the mechanisms responsible for cisplatin resistance in OvCa cell may improve therapeutic outcomes. We have shown that ovarian cancer cells express CC chemokine receptor-9 (CCR9. Others have also shown that CCL25, the only natural ligand for CCR9, up regulates anti-apoptotic proteins in immature T lymphocytes. Hence, it is plausible that CCR9-mediated cell signals might be involved in OvCa cell survival and inhibition of cisplatin-induced apoptosis. In this study, we investigated the potential role and molecular mechanisms of CCR9-mediated inhibition of cisplatin-induced apoptosis in OvCa cells. Methods Cell proliferation, vibrant apoptosis, and TUNEL assays were performed with or without cisplatin treatment in presence or absence of CCL25 to determine the role of the CCR9-CCL25 axis in cisplatin resistance. In situ Fast Activated cell-based ELISA (FACE assays were performed to determine anti-apoptotic signaling molecules responsible for CCL25-CCR9 mediated survival. Results Our results show interactions between CCR9 and CCL25 increased anti-apoptotic signaling cascades in OvCa cells, which rescued cells from cisplatin-induced cell death. Specifically, CCL25-CCR9 interactions mediated Akt, activation as well as GSK-3β and FKHR phosphorylation in a PI3K-dependent and FAK-independent fashion. Conclusions Our results suggest the CCR9-CCL25 axis plays an important role in reducing cisplatin-induced apoptosis of OvCa cells.

  18. The relationship between hyperuricemia and the risk of contrast-induced acute kidney injury after percutaneous coronary intervention in patients with relatively normal serum creatinine

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    Yong Liu

    2013-01-01

    Full Text Available OBJECTIVES: Hyperuricemia is a risk factor for contrast-induced acute kidney injury in patients with chronic kidney disease. This study evaluated the value of hyperuricemia for predicting the risk of contrast-induced acute kidney injury in patients with relatively normal serum creatinine who were undergoing percutaneous coronary interventions. METHODS AND RESULTS: A total of 788 patients with relatively normal baseline serum creatinine (7 mg/ dL in males and >6 mg/dL in females. The incidence of contrast-induced acute kidney injury was significantly higher in the hyperuricemic group than in the normouricemic group (8.1% vs. 1.4%, p75 years, emergent percutaneous coronary intervention, diuretic usage and the need for an intra-aortic balloon pump. CONCLUSION: Hyperuricemia was significantly associated with the risk of contrast-induced acute kidney injury in patients with relatively normal serum creatinine after percutaneous coronary interventions. This observation will help to generate hypotheses for further prospective trials examining the effect of uric acid-lowering therapies for preventing contrast-induced acute kidney injury.

  19. Ghrelin Prevents Cisplatin-Induced Testicular Damage by Facilitating Repair of DNA Double Strand Breaks Through Activation of p53 in Mice.

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    Garcia, Jose M; Chen, Ji-an; Guillory, Bobby; Donehower, Lawrence A; Smith, Roy G; Lamb, Dolores J

    2015-07-01

    Cisplatin administration induces DNA damage resulting in germ cell apoptosis and subsequent testicular atrophy. Although 50 percent of male cancer patients receiving cisplatin-based chemotherapy develop long-term secondary infertility, medical treatment to prevent spermatogenic failure after chemotherapy is not available. Under normal conditions, testicular p53 promotes cell cycle arrest, which allows time for DNA repair and reshuffling during meiosis. However, its role in the setting of cisplatin-induced infertility has not been studied. Ghrelin administration ameliorates the spermatogenic failure that follows cisplatin administration in mice, but the mechanisms mediating these effects have not been well established. The aim of the current study was to characterize the mechanisms of ghrelin and p53 action in the testis after cisplatin-induced testicular damage. Here we show that cisplatin induces germ cell damage through inhibition of p53-dependent DNA repair mechanisms involving gamma-H2AX and ataxia telangiectasia mutated protein kinase. As a result, testicular weight and sperm count and motility were decreased with an associated increase in sperm DNA damage. Ghrelin administration prevented these sequelae by restoring the normal expression of gamma-H2AX, ataxia telangiectasia mutated, and p53, which in turn allows repair of DNA double stranded breaks. In conclusion, these findings indicate that ghrelin has the potential to prevent or diminish infertility caused by cisplatin and other chemotherapeutic agents by restoring p53-dependent DNA repair mechanisms. PMID:26019260

  20. Epidemiology of acute kidney injury in Hungarian intensive care units: a multicenter, prospective, observational study

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    Bencsik Gabor

    2011-09-01

    Full Text Available Abstract Background Despite the substantial progress in the quality of critical care, the incidence and mortality of acute kidney injury (AKI continues to rise during hospital admissions. We conducted a national, multicenter, prospective, epidemiological survey to evaluate the importance of AKI in intensive care units (ICUs in Hungary. The objectives of this study were to determine the incidence of AKI in ICU patients; to characterize the differences in aetiology, illness severity and clinical practice; and to determine the influencing factors of the development of AKI and the patients' outcomes. Methods We analysed the demographic, morbidity, treatment modality and outcome data of patients (n = 459 admitted to ICUs between October 1st, 2009 and November 30th, 2009 using a prospectively filled in electronic survey form in 7 representative ICUs. Results The major reason for ICU admission was surgical in 64.3% of patients and medical in the remaining 35.7%. One-hundred-twelve patients (24.4% had AKI. By AKIN criteria 11.5% had Stage 1, 5.4% had Stage 2 and 7.4% had Stage 3. In 44.0% of patients, AKI was associated with septic shock. Vasopressor treatment, SAPS II score, serum creatinine on ICU admission and sepsis were the independent risk factors for development of any stage of AKI. Among the Stage 3 patients (34 50% received renal replacement therapy. The overall utilization of intermittent renal replacement therapy was high (64.8%. The overall in-hospital mortality rate of AKI was 49% (55/112. The ICU mortality rate was 39.3% (44/112. The independent risk factors for ICU mortality were age, mechanical ventilation, SOFA score and AKI Stage 3. Conclusions For the first time we have established the incidence of AKI using the AKIN criteria in Hungarian ICUs. Results of the present study confirm that AKI has a high incidence and is associated with high ICU and in-hospital mortality.

  1. Acute kidney injury in cirrhotic patients undergoing contrast-enhanced computed tomography.

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    Filomia, Roberto; Maimone, Sergio; Caccamo, Gaia; Saitta, Carlo; Visconti, Luca; Alibrandi, Angela; Caloggero, Simona; Bottari, Antonio; Franzè, Maria Stella; Gambino, Carmine Gabriele; Lembo, Tindaro; Oliva, Giovanni; Cacciola, Irene; Raimondo, Giovanni; Squadrito, Giovanni

    2016-09-01

    Contrast medium administration is one of the leading causes of acute kidney injury (AKI) in different clinical settings. The aim of the study was to investigate occurrence and predisposing factors of AKI in cirrhotic patients undergoing contrast-enhanced computed tomography (CECT).Datasets of 1279 consecutively hospitalized cirrhotic patients were retrospectively analyzed. Two hundred forty-nine of 1279 patients (mean age 64 ± 11 years, 165 male) who had undergone CECT were selected on the basis of the availability of serum creatinine (sCr) values evaluated before and after CECT (CECT group). In analogy, 203/1279 cases (mean age 66 ± 10 years, 132 male) who had not undergone CECT and had been tested twice for sCr in 7 days were also included as controls (Control group). AKI network criteria were employed to assess contrast-induced AKI (CI-AKI) development. Apart from lack of narrowed double sCr measurements, additional exclusion criteria were active bacterial infections, nephrotoxic drugs intake, and estimated glomerular filtration rate sCr values (OR: 0.124, 95% CI: 0.016-0.975; P = 0.047). In the CECT group, presence of ascites (OR: 2.796, 95% CI: 1.109-7.052; P = 0.029), female sex (OR: 0.192, 95% CI: 0.073-0.510; P = 0.001), and hyperazotemia (OR: 1.018, 95% CI: 1.001-1.037; P = 0.043) correlated with CI-AKI development at multivariate analysis.CI-AKI is a quite frequent occurrence in cirrhotic patients with female sex, presence of ascites, and hyperazotemia being the predisposing factors. PMID:27661025

  2. Early Trends in Cystatin C and Outcomes in Patients with Cirrhosis and Acute Kidney Injury

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    Justin M. Belcher

    2014-01-01

    Full Text Available Background. Acute kidney injury (AKI is a common and severe complication in patients with cirrhosis. Progression of AKI to a higher stage associates with increased mortality. Intervening early in AKI when renal dysfunction is worsening may improve outcomes. However, serum creatinine correlates poorly with glomerular filtration in patients with cirrhosis and fluctuations may mask progression early in the course of AKI. Cystatin C, a low-molecular-weight cysteine proteinase inhibitor, is a potentially more accurate marker of glomerular filtration. Methods. We conducted a prospective multicenter study in patients with cirrhosis comparing changes in cystatin and creatinine immediately following onset of AKI as predictors of a composite endpoint of dialysis or mortality. Results. Of 106 patients, 37 (35% met the endpoint. Cystatin demonstrated less variability between samples than creatinine. Patients were stratified into four groups reflecting changes in creatinine and cystatin: both unchanged or decreased 38 (36% (Scr−/CysC−; only cystatin increased 25 (24% (Scr−/CysC+; only creatinine increased 15 (14% (Scr+/CysC−; and both increased 28 (26% (Scr+/CysC+. With Scr−/CysC− as the reference, in both instances where cystatin rose, Scr−/CysC+ and Scr+/CysC+, the primary outcome was significantly more frequent in multivariate analysis, P=0.02 and 0.03, respectively. However, when only creatinine rose, outcomes were similar to the reference group. Conclusions. Changes in cystatin levels early in AKI are more closely associated with eventual dialysis or mortality than creatinine and may allow more rapid identification of patients at risk for adverse outcomes.

  3. Acute kidney injury in cirrhotic patients undergoing contrast-enhanced computed tomography

    Science.gov (United States)

    Filomia, Roberto; Maimone, Sergio; Caccamo, Gaia; Saitta, Carlo; Visconti, Luca; Alibrandi, Angela; Caloggero, Simona; Bottari, Antonio; Franzè, Maria Stella; Gambino, Carmine Gabriele; Lembo, Tindaro; Oliva, Giovanni; Cacciola, Irene; Raimondo, Giovanni; Squadrito, Giovanni

    2016-01-01

    Abstract Contrast medium administration is one of the leading causes of acute kidney injury (AKI) in different clinical settings. The aim of the study was to investigate occurrence and predisposing factors of AKI in cirrhotic patients undergoing contrast-enhanced computed tomography (CECT). Datasets of 1279 consecutively hospitalized cirrhotic patients were retrospectively analyzed. Two hundred forty-nine of 1279 patients (mean age 64 ± 11 years, 165 male) who had undergone CECT were selected on the basis of the availability of serum creatinine (sCr) values evaluated before and after CECT (CECT group). In analogy, 203/1279 cases (mean age 66 ± 10 years, 132 male) who had not undergone CECT and had been tested twice for sCr in 7 days were also included as controls (Control group). AKI network criteria were employed to assess contrast-induced AKI (CI-AKI) development. Apart from lack of narrowed double sCr measurements, additional exclusion criteria were active bacterial infections, nephrotoxic drugs intake, and estimated glomerular filtration rate sCr values (OR: 0.124, 95% CI: 0.016–0.975; P = 0.047). In the CECT group, presence of ascites (OR: 2.796, 95% CI: 1.109–7.052; P = 0.029), female sex (OR: 0.192, 95% CI: 0.073–0.510; P = 0.001), and hyperazotemia (OR: 1.018, 95% CI: 1.001–1.037; P = 0.043) correlated with CI-AKI development at multivariate analysis. CI-AKI is a quite frequent occurrence in cirrhotic patients with female sex, presence of ascites, and hyperazotemia being the predisposing factors. PMID:27661025

  4. Impact of hydroxyethyl starch 70/0.5 on acute kidney injury after gastroenterological surgery

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    Uba, Takeo; Sumi, Chisato; Sakamoto, Sachiyo; Jomura, Sachiko; Hirota, Kiichi; Shingu, Koh

    2016-01-01

    Background Previous studies reported a higher mortality risk and a greater need for renal replacement therapy in patients administered hydroxyethyl starch (HES) rather than other fluid resuscitation preparations. In this study, we investigated the association between 6% HES 70/0.5 use and postoperative acute kidney injury (AKI) in gastroenterological surgery patients. Methods We conducted retrospective full-cohort and propensity-score-based analyses of patients who underwent gastroenterological surgery between June 2011 and August 2013 in a Japanese university hospital. The study sample comprised 66 AKI and 2,152 non-AKI patients in the full-cohort analysis and 35 AKI and 1,269 non-AKI patients in the propensity-score-based analysis. Propensity scores were calculated using an ordered logistic regression model in which the dependent variable comprised three groups based on HES infusion volumes (0, 1–999, and ≥ 1,000 ml). The association between HES groups and postoperative AKI incidence was analyzed using multiple logistic regression models. Other candidate independent variables included patient characteristics and intraoperative measures. Results In the full-cohort analysis, 40 (60.6%) AKI patients were diagnosed as "risk", 15 (22.7%) as "injury," and 11 (16.7%) as "failure". In the propensity-score-based analysis, the corresponding values were 22 (62.9%), 8 (22.9%), and 5 (14.3%). There was no significant association between total infused HES and postoperative AKI incidence in either the full-cohort or the propensity-score-based analysis (P = 0.168 and P = 0.42, respectively). Conclusions AKI incidence was not associated with clinical 6% HES 70/0.5 administration in gastroenterological surgery patients treated at a single center.

  5. Degree of Acute Kidney Injury before Dialysis Initiation and Hospital Mortality in Critically Ill Patients

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    Charuhas V. Thakar

    2013-01-01

    Full Text Available In a multicenter observational cohort of patients-admitted to intensive care units (ICU, we assessed whether creatinine elevation prior to dialysis initiation in acute kidney injury (AKI-D further discriminates risk-adjusted mortality. AKI-D was categorized into four groups (Grp based on creatinine elevation after ICU admission but before dialysis initiation: Grp I  > 0.3 mg/dL to <2-fold increase, Grp II ≥2 times but <3 times increase, Grp III ≥3-fold increase in creatinine, and Grp IV none or <0.3 mg/dl increase. Standardized mortality rates (SMR were calculated by using a validated risk-adjusted mortality model and expressed with 95% confidence intervals (CI. 2,744 patients developed AKI-D during ICU stay; 36.7%, 20.9%, 31.2%, and 11.2% belonged to groups I, II, III, and IV, respectively. SMR showed a graded increase in Grp I, II, and III (1.40 (95% CI, 1.29–1.42, 1.84 (1.66–2.04, and 2.25 (2.07–2.45 and was 0.98 (0.78–1.20 in Grp IV. In ICU patients with AKI-D, degree of creatinine elevation prior to dialysis initiation is independently associated with hospital mortality. It is the lowest in those experiencing minor or no elevations in creatinine and may represent reversible fluid-electrolyte disturbances.

  6. Pretreatment with Darbepoetin Attenuates Renal Injury in a Rat Model of Cisplatin-Induced Nephrotoxicity

    OpenAIRE

    Choi, Dae Eun; Jeong, Jin Young; Lim, Beom Jin; Lee, Kang Wook; Shin, Young-Tai; Na, Ki-Ryang

    2009-01-01

    Background/Aims Darbepoetin alfa (DPO) exhibits comparable renoprotective effects to erythropoietin (EPO) in several animal models of acute renal injury. We examined whether DPO also attenuated renal injury in a rat model of cisplatin nephrotoxicity. Methods Male Spague-Dawley rats were divided into four groups: untreated, DPO-treated, cisplatin-injected, and DPO-treated cisplatin-injected. DPO pretreatment was conducted 24 hours after and just before cisplatin administration. Ninety-six hour...

  7. Fas Ligand Has a Greater Impact than TNF-α on Apoptosis and Inflammation in Ischemic Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    Kengo Furuichi

    2012-02-01

    Full Text Available Background/Aim: Fas ligand (FasL and tumor necrosis factor (TNF-α are major pro-apoptotic molecules and also induce inflammation through cytokine and chemokine production. Although precise intracellular mechanisms of action have been reported for each molecule, the differential impact of these molecules on kidney injury in vivo still requires clarification. Methods: We explored the differential impact of FasL and TNF-α upon apoptosis and inflammation in ischemic acute kidney injury using neutralizing anti-FasL antibodies and TNF-α receptor 1 (TNFR1-deficient mice. Results: TNFR1 deficiency was associated with a lesser anti-inflammatory effect upon leukocyte infiltration and tubular necrosis than treatment with anti-FasL antibody. Furthermore, the number of TUNEL-positive cells was significantly reduced in anti-FasL antibody-treated mice, whereas it was only partially diminished in TNFR1-deficient mice. In vitro studies confirmed these findings. FasL administration induced both apoptosis and cytokine/chemokine production from cultured tubular epithelial cells. However, TNF-α had a limited effect upon tubular epithelial cells. Conclusion: In ischemic acute kidney injury, FasL has a greater impact than TNF-α on the apoptosis and inflammatory reaction through cytokine/chemokine production from tubular epithelial cells.

  8. Acute kidney injury in the era of big data: the 15(th) Consensus Conference of the Acute Dialysis Quality Initiative (ADQI).

    Science.gov (United States)

    Bagshaw, Sean M; Goldstein, Stuart L; Ronco, Claudio; Kellum, John A

    2016-01-01

    The world is immersed in "big data". Big data has brought about radical innovations in the methods used to capture, transfer, store and analyze the vast quantities of data generated every minute of every day. At the same time; however, it has also become far easier and relatively inexpensive to do so. Rapidly transforming, integrating and applying this large volume and variety of data are what underlie the future of big data. The application of big data and predictive analytics in healthcare holds great promise to drive innovation, reduce cost and improve patient outcomes, health services operations and value. Acute kidney injury (AKI) may be an ideal syndrome from which various dimensions and applications built within the context of big data may influence the structure of services delivery, care processes and outcomes for patients. The use of innovative forms of "information technology" was originally identified by the Acute Dialysis Quality Initiative (ADQI) in 2002 as a core concept in need of attention to improve the care and outcomes for patients with AKI. For this 15(th) ADQI consensus meeting held on September 6-8, 2015 in Banff, Canada, five topics focused on AKI and acute renal replacement therapy were developed where extensive applications for use of big data were recognized and/or foreseen. In this series of articles in the Canadian Journal of Kidney Health and Disease, we describe the output from these discussions. PMID:26925244

  9. Acute kidney injury in the era of big data: the 15(th) Consensus Conference of the Acute Dialysis Quality Initiative (ADQI).

    Science.gov (United States)

    Bagshaw, Sean M; Goldstein, Stuart L; Ronco, Claudio; Kellum, John A

    2016-01-01

    The world is immersed in "big data". Big data has brought about radical innovations in the methods used to capture, transfer, store and analyze the vast quantities of data generated every minute of every day. At the same time; however, it has also become far easier and relatively inexpensive to do so. Rapidly transforming, integrating and applying this large volume and variety of data are what underlie the future of big data. The application of big data and predictive analytics in healthcare holds great promise to drive innovation, reduce cost and improve patient outcomes, health services operations and value. Acute kidney injury (AKI) may be an ideal syndrome from which various dimensions and applications built within the context of big data may influence the structure of services delivery, care processes and outcomes for patients. The use of innovative forms of "information technology" was originally identified by the Acute Dialysis Quality Initiative (ADQI) in 2002 as a core concept in need of attention to improve the care and outcomes for patients with AKI. For this 15(th) ADQI consensus meeting held on September 6-8, 2015 in Banff, Canada, five topics focused on AKI and acute renal replacement therapy were developed where extensive applications for use of big data were recognized and/or foreseen. In this series of articles in the Canadian Journal of Kidney Health and Disease, we describe the output from these discussions.

  10. Differences in estimates of cisplatin-induced cell kill in vitro between colorimetric and cell count/colony assays.

    Science.gov (United States)

    Henriksson, Eva; Kjellén, Elisabeth; Wahlberg, Peter; Wennerberg, Johan; Kjellström, Johan H

    2006-01-01

    The aim of this study was to evaluate some bioassays that are different in principle: cell counting, colony forming assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT), sulforhodamine B (SRB), crystal violet, and alamarBlue, with respect to their ability to measure cisplatin-induced cell death of in vitro-cultivated squamous cell carcinoma of the head and neck (SCCHN). Cisplatin was applied in concentrations of 1.0, 5.0, 10.0, 50.0, and 100 microM. The cells were incubated for 1 h, and the cell survival was measured 5 d after treatment. We found the colorimetric assays and cell counting to be comparable. The colony forming assay indicated a higher degree of cell kill compared with the other techniques. Measurement of cell survival after treatment with cisplatin can be done by use of any of the above tested assays. However, the majority of SCCHN cell lines available do not form colonies easily, or at all. Therefore, comparing the chemosensitivity between such cell lines is limited to alternative assays. In this respect, any of the tested colorimetric assays can be used. However, they seem to underestimate cell kill. Cell counting is also an alternative. This technique, however, is time consuming and operator dependent, as in the case of manual counting, or relatively expensive when counting is performed electronically, compared with the colorimetric assays. PMID:17316066

  11. High temporal resolution parametric MRI monitoring of the initial ischemia/reperfusion phase in experimental acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Andreas Pohlmann

    Full Text Available Ischemia/reperfusion (I/R injury, a consequence of kidney hypoperfusion or temporary interruption of blood flow is a common cause of acute kidney injury (AKI. There is an unmet need to better understand the mechanisms operative during the initial phase of ischemic AKI. Non-invasive in vivo parametric magnetic resonance imaging (MRI may elucidate spatio-temporal pathophysiological changes in the kidney by monitoring the MR relaxation parameters T2* and T2, which are known to be sensitive to blood oxygenation. The aim of our study was to establish the technical feasibility of fast continuous T2*/T2 mapping throughout renal I/R. MRI was combined with a remotely controlled I/R model and a segmentation model based semi-automated quantitative analysis. This technique enabled the detailed assessment of in vivo changes in all kidney regions during ischemia and early reperfusion. Significant changes in T2* and T2 were observed shortly after induction of renal ischemia and during the initial reperfusion phase. Our study demonstrated for the first time that continuous and high temporal resolution parametric MRI is feasible for in-vivo monitoring and characterization of I/R induced AKI in rats. This technique may help in the identification of the timeline of key events responsible for development of renal damage in hypoperfusion-induced AKI.

  12. Involvement of the Hippo pathway in regeneration and fibrogenesis after ischaemic acute kidney injury: YAP is the key effector.

    Science.gov (United States)

    Xu, Jing; Li, Pei-Xue; Wu, Jun; Gao, Yi-Jun; Yin, Meng-Xin; Lin, Ye; Yang, Ming; Chen, Dong-Ping; Sun, Hai-Peng; Liu, Zeng-Bo; Gu, Xiang-Chen; Huang, Hong-Ling; Fu, Li-Li; Hu, Hui-Min; He, Liang-Liang; Wu, Wen-Qing; Fei, Zhao-Liang; Ji, Hong-Bin; Zhang, Lei; Mei, Chang-Lin

    2016-03-01

    Renal tubule cells can recover after they undergo AKI (acute kidney injury). An incomplete repair of renal tubules can result in progressive fibrotic CKD (chronic kidney disease). Studies have revealed the relationship between tubular epithelial cells and kidney fibrogenesis. However, the underlying mechanism remains unclear. Hippo pathway components were evaluated in complete/incomplete repair of I/R (ischaemia/reperfusion) AKI rat models, HK-2 cells and AKI human renal biopsy samples. We found that the expression levels of the Hippo pathway components changed dynamically during kidney regeneration and fibrogenesis in rat models of I/R-induced AKI and human renal biopsy samples. The transcription cofactor YAP (Yes-associated protein) might be a key effector of renal regeneration and fibrogenesis. Our results showed further that YAP might elicit both beneficial and detrimental effects on I/R AKI. After I/R injury occurred, YAP could promote the repair of the injured epithelia. The constant YAP increase and activation might be related to interstitial fibrosis and abnormal renal tubule differentiation. These results indicate that the proper modulation of the Hippo pathway, specifically the transcription cofactor YAP, during repair might be a potent therapeutic target in AKI-CKD transition after I/R injury.

  13. Forkhead box protein 3 mRNA expression in the peripheral blood of kidney-transplant recipients with acute rejection

    Institute of Scientific and Technical Information of China (English)

    WANG Wei; LI Xiao-bei; YANG Xiao-yong; ZHANG Xiao-dong

    2011-01-01

    Background Regulatory T cells (Tregs) are immunologically and clinically interesting not least because of the important role they play in allograft rejection. Likewise, expression of the transcription factor forkhead box protein 3 (FOXP3), detected in transplant biopsies, is also of interest because of its role in the development of regulatory T cells. In this study, we Investigated the relationship between FoxP3 mRNA expression and acute organ rejection in kidney-transplant recipients.Methods In this prospective study, FoxP3 mRNA expression levels in peripheral blood samples from 10 recipients of living relative-donor kidney transplants were measured before transplantation as well as at the 14th and 90th days post-transplantation. In addition, 46 first-time kidney-transplant recipients participated in a cross-sectional study, with 28 patients classified as having acute organ rejection; whilst the remaining 18 patients had functionally stable allografts. FoxP3 mRNA expression levels in peripheral blood samples were compared between these two different groups.Results Before transplantation mean FoxP3 mRNA levels vs. GADPH mRNA levels (lg(FoxP3 mRNA/GADPH mRNA)) in the 10 recipients were 1.11±0.67. The mean FoxP3 mRNA expression levels measured at 14th and 90th days post-transplantation were significantly higher than before transplantation (1.69±0.38, P=0.03; 1.44±0.21, P=0.04, respectively). Additionally, the mean FoxP3 mRNA levels vs. GADPH mRNA expression levels (lg(FoxP3 mRNA/GADPH mRNA)) were significantly higher in recipients suffering acute rejection compared with those with stable allografts (1.77±0.61 and 1.43±0.27, respectively, P=0.03).Conclusions After kidney transplantation, FoxP3 mRNA levels were found to increase in the peripheral blood of all recipients. Considerably higher FoxP3 mRNA levels were observed in recipients suffering acute rejection. These results suggest that FoxP3 mRNA levels in peripheral blood samples can be used as a diagnostic

  14. Fiber optic probe enabled by surface-enhanced Raman scattering for early diagnosis of potential acute rejection of kidney transplant

    Science.gov (United States)

    Chi, Jingmao; Chen, Hui; Tolias, Peter; Du, Henry

    2014-06-01

    We have explored the use of a fiber-optic probe with surface-enhanced Raman scattering (SERS) sensing modality for early, noninvasive and, rapid diagnosis of potential renal acute rejection (AR) and other renal graft dysfunction of kidney transplant patients. Multimode silica optical fiber immobilized with colloidal Ag nanoparticles at the distal end was used for SERS measurements of as-collected urine samples at 632.8 nm excitation wavelength. All patients with abnormal renal graft function (3 AR episodes and 2 graft failure episodes) who were clinically diagnosed independently show common unique SERS spectral features in the urines collected just one day after transplant. SERS-based fiber-optic probe has excellent potential to be a bedside tool for early diagnosis of kidney transplant patients for timely medical intervention of patients at high risk of transplant dysfunction.

  15. Loss of CD28 on Peripheral T Cells Decreases the Risk for Early Acute Rejection after Kidney Transplantation.

    Directory of Open Access Journals (Sweden)

    Burç Dedeoglu

    Full Text Available End-stage renal disease patients have a dysfunctional, prematurely aged peripheral T-cell system. Here we hypothesized that the degree of premature T-cell ageing before kidney transplantation predicts the risk for early acute allograft rejection (EAR.222 living donor kidney transplant recipients were prospectively analyzed. EAR was defined as biopsy proven acute allograft rejection within 3 months after kidney transplantation. The differentiation status of circulating T cells, the relative telomere length and the number of CD31+ naive T cells were determined as T-cell ageing parameters.Of the 222 patients analyzed, 30 (14% developed an EAR. The donor age and the historical panel reactive antibody score were significantly higher (p = 0.024 and p = 0.039 respectively and the number of related donor kidney transplantation was significantly lower (p = 0.018 in the EAR group. EAR-patients showed lower CD4+CD28null T-cell numbers (p<0.01 and the same trend was observed for CD8+CD28null T-cell numbers (p = 0.08. No differences regarding the other ageing parameters were found. A multivariate Cox regression analysis showed that higher CD4+CD28null T-cell numbers was associated with a lower risk for EAR (HR: 0.65, p = 0.028. In vitro, a significant lower percentage of alloreactive T cells was observed within CD28null T cells (p<0.001.Immunological ageing-related expansion of highly differentiated CD28null T cells is associated with a lower risk for EAR.

  16. Hypomagnesemia is a risk factor for nonrecovery of renal function and mortality in AIDS patients with acute kidney injury

    Directory of Open Access Journals (Sweden)

    M.S. Biagioni Santos

    2010-03-01

    Full Text Available The objective of the present study was to determine the prevalence of electrolyte disturbances in AIDS patients developing acute kidney injury in the hospital setting, as well as to determine whether such disturbances constitute a risk factor for nephrotoxic and ischemic injury. A prospective, observational cohort study was carried out. Hospitalized AIDS patients were evaluated for age; gender; coinfection with hepatitis; diabetes mellitus; hypertension; time since HIV seroconversion; CD4 count; HIV viral load; proteinuria; serum levels of creatinine, urea, sodium, potassium and magnesium; antiretroviral use; nephrotoxic drug use; sepsis; intensive care unit (ICU admission, and the need for dialysis. Each of these characteristics was correlated with the development of acute kidney injury, with recovery of renal function and with survival. Fifty-four patients developed acute kidney injury: 72% were males, 59% had been HIV-infected for >5 years, 72% had CD4 counts <200 cells/mm³, 87% developed electrolyte disturbances, 33% recovered renal function, and 56% survived. ICU admission, dialysis, sepsis and hypomagnesemia were all significantly associated with nonrecovery of renal function and with mortality. Nonrecovery of renal function was significantly associated with hypomagnesemia, as was mortality in the multivariate analysis. The risks for nonrecovery of renal function and for death were 6.94 and 6.92 times greater, respectively, for patients with hypomagnesemia. In hospitalized AIDS patients, hypomagnesemia is a risk factor for nonrecovery of renal function and for in-hospital mortality. To determine whether hypomagnesemia is a determinant or simply a marker of critical illness, further studies involving magnesium supplementation in AIDS patients are warranted.

  17. Monitoring of Urinary L-Type Fatty Acid-Binding Protein Predicts Histological Severity of Acute Kidney Injury

    OpenAIRE

    Negishi, Kousuke; Noiri, Eisei; DOI, Kent; Maeda-Mamiya, Rui; Sugaya, Takeshi; Portilla, Didier; Fujita, Toshiro

    2009-01-01

    The present study aimed to evaluate whether levels of urinary L-type fatty acid-binding protein (L-FABP) could be used to monitor histological injury in acute kidney injury (AKI) induced by cis-platinum (CP) injection and ischemia reperfusion (IR). Different degrees of AKI severity were induced by several renal insults (CP dose and ischemia time) in human L-FABP transgenic mice. Renal histological injury scores increased with both CP dose and ischemic time. In CP-induced AKI, urinary L-FABP l...

  18. Assessments of urine cofilin-1 in patients hospitalized in the intensive care units with acute kidney injury

    Science.gov (United States)

    Lee, Yi-Jang; Chao, Cheng-Han; Chang, Ying-Feng; Chou, Chien

    2013-02-01

    The actin depolymerizing factor (ADF)/cofilin protein family has been reported to be associated with ischemia induced renal disorders. Here we examine if cofilin-1 is associated with acute kidney injury (AKI). We exploited a 96-well based fiber-optic biosensor that uses conjugated gold nanoparticles and a sandwich immunoassay to detect the urine cofilin-1 level of AKI patients. The mean urine cofilin-1 level of the AKI patients was two-fold higher than that of healthy adults. The receiver operating characteristic (ROC) curve showed that cofilin-1 is a potential biomarker for discriminating AKI patients from healthy adults for intensive care patients.

  19. An elderly ‘kawara’ craftsman with acute kidney injury and haemoptysis: a case of silica-induced autoimmunity

    OpenAIRE

    Matsui, Satoshi; Tsuji, Hiroko; Ono, Shinji

    2010-01-01

    A 62-year-old Japanese ‘kawara’ (ceramic roof tile) craftsman presented with acute kidney injury and haemoptysis. This case met the systemic lupus erythematosus and microscopic polyangiitis criteria, with high titres of myeloperoxidase–antineutrophil cytoplasmic antibody (570 EU). Results showed the presence of antinuclear antibody at a high titre (1:2560), but detection of rheumatoid factor, anti-dsDNA, anti-SSA and anti-SSB antibodies was not apparent. This serology was similar to drug-indu...

  20. Reversion by ozone treatment of acute nephrotoxicity induced by cisplatin in rats

    Directory of Open Access Journals (Sweden)

    Ricardo González

    2004-01-01

    Full Text Available BACKGROUND: Ozone therapy has become a useful treatment for pathological processes, in which the damage mediated by reactive oxygen species is involved. Several lines of evidence suggest that cisplatin-induced acute nephrotoxicity is partially mediated by reactive oxygen species.

  1. Asparagus racemosus ameliorates cisplatin induced toxicities and augments its antileishmanial activity by immunomodulation in vivo.

    Science.gov (United States)

    Sachdeva, Heena; Sehgal, Rakesh; Kaur, Sukhbir

    2014-02-01

    Current drugs for the treatment of visceral leishmaniasis are inadequate and their efficacies are also compromised due to suppression of immune function associated during the course of infection. To overcome this problem, efforts are needed to develop therapies with effective immunomodulatory agents where decrease of parasitic burden and simultaneous enhancement of adaptive immunity can be achieved. In this study we have evaluated a new therapeutic approach based on combination of Asparagus racemosus, an immunomodulatory drug, in combination with cisplatin against Leishmania donovani infected BALB/c mice. We demonstrate that A. racemosus (650 mg/kg b.wt./day for 15 days, orally) in combination with cisplatin (5 mg/kg b.wt./day for 5 days, intraperitoneally) enhanced the clearance of parasites as determined by Giemsa-stained liver impression smears. Besides having better killing activity, this combination group achieved increased production of disease resolving Th-1 response (IFN-gamma, IL-2), heightened DTH (delayed type hypersensitivity) response and augmented levels of IgG2a. Moreover, A. racemosus in combination with cisplatin not only provided enhanced protective immune response but also resulted in remarkable improved kidney and liver function tests as manifested by normal levels of SGOT, SGPT, alkaline phosphatase, creatinine and urea in blood plasma with normal histological observations as compared to only cisplatin treated L. donovani infected BALB/c mice. Through this study we have ascertained that A. racemosus in combination with cisplatin in L. donovani infected BALB/c mice boosted as well as restored both cellular and humoral immunity. Thus in view of severe immunosuppression in visceral leishmaniasis, a better and effective strategy for optimum efficacy of future antileishmanial drugs would direct not only killing of parasite by the drug, but also simultaneous generation of immunity against the disease.

  2. Age-related differences in susceptibility to cisplatin-induced renal toxicity.

    Science.gov (United States)

    Espandiari, P; Rosenzweig, B; Zhang, J; Zhou, Y; Schnackenberg, L; Vaidya, V S; Goering, P L; Brown, R P; Bonventre, J V; Mahjoob, K; Holland, R D; Beger, R D; Thompson, K; Hanig, J; Sadrieh, N

    2010-03-01

    Limited experimental models exist to assess drug toxicity in pediatric populations. We recently reported how a multi-age rat model could be used for pre-clinical studies of comparative drug toxicity in pediatric populations. The objective of this study was to expand the utility of this animal model, which previously demonstrated an age-dependent sensitivity to the classic nephrotoxic compound, gentamicin, to another nephrotoxicant, namely cisplatin (Cis). Sprague-Dawley rats (10, 25, 40 and 80 days old) were injected with a single dose of Cis (0, 1, 3 or 6 mg kg(-1) i.p.). Urine samples were collected prior and up to 72 h after treatment in animals that were >or= 25 days old. Several serum, urinary and 'omic' injury biomarkers as well as renal histopathology lesions were evaluated. Statistically significant changes were noted with different injury biomarkers in different age groups. The order of age-related Cis-induced nephrotoxicity was different than our previous study with gentamicin: 80 > 40 > 10 > 25 day-old vs 10 >or= 80 > 40 > 25-day-old rats, respectively. The increased levels of kidney injury molecule-1 (Kim-1: urinary protein/tissue mRNA) provided evidence of early Cis-induced nephrotoxicity in the most sensitive age group (80 days old). Levels of Kim-1 tissue mRNA and urinary protein were significantly correlated to each other and to the severity of renal histopathology lesions. These data indicate that the multi-age rat model can be used to demonstrate different age-related sensitivities to renal injury using mechanistically distinct nephrotoxicants, which is reflected in measurements of a variety of metabolite, gene transcript and protein biomarkers.

  3. Age-related differences in susceptibility to cisplatin-induced renal toxicity†

    Science.gov (United States)

    Espandiari, P.; Rosenzweig, B.; Zhang, J.; Zhou, Y.; Schnackenberg, L.; Vaidya, V. S.; Goering, P. L.; Brown, R. P.; Bonventre, J. V.; Mahjoob, K.; Holland, R. D.; Beger, R. D.; Thompson, K.; Hanig, J.; Sadrieh, N.

    2009-01-01

    Limited experimental models exist to assess drug toxicity in pediatric populations. We recently reported how a multi-age rat model could be used for pre-clinical studies of comparative drug toxicity in pediatric populations. The objective of this study was to expand the utility of this animal model, which previously demonstrated an age-dependent sensitivity to the classic nephrotoxic compound, gentamicin, to another nephrotoxicant, namely cisplatin (Cis). Sprague-Dawley rats (10, 25, 40 and 80 days old) were injected with a single dose of Cis (0, 1, 3 or 6 mg kg−1 i.p.). Urine samples were collected prior and up to 72 h after treatment in animals that were ≥25 days old. Several serum, urinary and `omic' injury biomarkers as well as renal histopathology lesions were evaluated. Statistically significant changes were noted with different injury biomarkers in different age groups. The order of age-related Cis-induced nephrotoxicity was different than our previous study with gentamicin: 80 > 40 > 10 > 25 day-old vs 10 ≥ 80 > 40 > 25-day-old rats, respectively. The increased levels of kidney injury molecule-1 (Kim-1: urinary protein/tissue mRNA) provided evidence of early Cis-induced nephrotoxicity in the most sensitive age group (80 days old). Levels of Kim-1 tissue mRNA and urinary protein were significantly correlated to each other and to the severity of renal histopathology lesions. These data indicate that the multi-age rat model can be used to demonstrate different age-related sensitivities to renal injury using mechanistically distinct nephrotoxicants, which is reflected in measurements of a variety of metabolite, gene transcript and protein biomarkers. PMID:19839026

  4. Renal kallikrein excretion and epigenetics in human acute kidney injury: Expression, mechanisms and consequences

    Directory of Open Access Journals (Sweden)

    Tolwani Ashita

    2011-06-01

    Full Text Available Abstract Background Renal kallikrein (KLK1 synthesis and urinary excretion are reportedly diminished during AKI (acute kidney injury in animal models, and provision of kallikrein abrogates renal injury in this setting, but data in human AKI is limited. Therefore we first examined KLK1 renal excretion in human AKI, and then probed potential endocrine and epigenetic mechanisms for its alterations. Methods KLK1 enzymatic activity excretion was evaluated in urine from patients with established or incipient AKI, versus healthy/non-hospital as well as ICU controls. Endocrine control of KLK1 excretion was then probed by catecholamine and aldosterone measurements in established AKI versus healthy controls. To examine epigenetic control of KLK1 synthesis, we tested blood and urine DNA for changes in promoter CpG methylation of the KLK1 gene, as well as LINE-1 elements, by bisulfite sequencing. Results Patients with early/incipient AKI displayed a modest reduction of KLK1 excretion, but unexpectedly, established AKI displayed substantially elevated urine KLK1 excretion, ~11-fold higher than healthy controls, and ~3-fold greater than ICU controls. We then probed potential mechanisms of the change. Established AKI patients had lower SBP, higher heart rate, and higher epinephrine excretion than healthy controls, though aldosterone excretion was not different. Promoter KLK1 CpG methylation was higher in blood than urine DNA, while KLK1 methylation in blood DNA was significantly higher in established AKI than healthy controls, though KLK1 methylation in urine tended to be higher in AKI, directionally consistent with earlier/incipient but not later/established changes in KLK1 excretion in AKI. On multivariate ANOVA, AKI displayed coordinate changes in KLK1 excretion and promoter methylation, though directionally opposite to expectation. Control (LINE-1 repetitive element methylation in blood and urine DNA was similar between AKI and controls. Conclusions

  5. Combination of biomarkers for diagnosis of acute kidney injury after cardiopulmonary bypass.

    Science.gov (United States)

    Prowle, John Richard; Calzavacca, Paolo; Licari, Elisa; Ligabo, E Valentina; Echeverri, Jorge E; Bagshaw, Sean M; Haase-Fielitz, Anja; Haase, Michael; Ostland, Vaughn; Noiri, Eisei; Westerman, Mark; Devarajan, Prasad; Bellomo, Rinaldo

    2015-04-01

    Novel acute kidney injury (AKI) biomarkers offer promise of earlier diagnosis and risk stratification, but have yet to find widespread clinical application. We measured urinary α and π glutathione S-transferases (α-GST and π-GST), urinary l-type fatty acid-binding protein (l-FABP), urinary neutrophil gelatinase-associated lipocalin (NGAL), urinary hepcidin and serum cystatin c (CysC) before surgery, post-operatively and at 24 h after surgery in 93 high risk patient undergoing cardiopulmonary bypass (CPB) and assessed the ability of these biomarkers alone and in combination to predict RIFLE-R defined AKI in the first 5 post-operative days. Twenty-five patients developed AKI. π-GST (ROCAUC = 0.75), lower urine Hepcidin:Creatine ratio at 24 h (0.77), greater urine NGAL:Cr ratio post-op (0.73) and greater serum CysC at 24 h (0.72) best predicted AKI. Linear combinations with significant improvement in AUC were: Hepcidin:Cr 24 h + post-operative π-GST (AUC = 0.86, p = 0.01), Hepcidin:Cr 24 h + NGAL:Cr post-op (0.84, p = 0.03) and CysC 24 h + post-operative π-GST (0.83, p = 0.03), notably these significant biomarkers combinations all involved a tubular injury and a glomerular filtration biomarker. Despite statistical significance in receiver-operator characteristic (ROC) analysis, when assessed by ability to define patients to two groups at high and low risk of AKI, combinations failed to significantly improve classification of risk compared to the best single biomarkers. In an alternative approach using Classification and Regression Tree (CART) analysis a model involving NGAL:Cr measurement post-op followed by Hepcidin:Cr at 24 h was developed which identified high, intermediate and low risk groups for AKI. Regression tree analysis has the potential produce models with greater clinical utility than single combined scores. PMID:25585949

  6. Contrast-induced acute kidney injury after computed tomography prior to transcatheter aortic valve implantation

    International Nuclear Information System (INIS)

    Aim: To identify independent predictors of contrast medium-induced acute kidney injury (CI-AKI) after enhanced multidetector-row computed tomography (MDCT) prior to transcatheter aortic valve implantation (TAVI) in high-risk patients. Materials and methods: The present single-centre study analysed retrospectively 361 patients who were assessed using MDCT prior to TAVI. CI-AKI was defined as an increase in serum creatinine (SCr) of ≥25% or ≥0.5 mg/dl in at least one sample over baseline (24 h before MDCT) and at 24, 48, and 72 h after MDCT. Results: A total of 38 patients (10.5%) experienced CI-AKI. As compared to patients without CI-AKI, they presented more frequently with estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2, (81.6% versus 64.4%, p = 0.045) and tended to receive higher volumes of iodinated contrast media (ICM; 55.3% versus 39%, p = 0.057). There was a significant interaction between baseline eGFR and the amount of intravenous ICM administered (pfor interaction = <0.001) identifying the amount of ICM >90 ml as independent predictive factor of CI-AKI only in patients with baseline eGFR <60 ml/min/1.73m2 (OR 2.615; 95% CI: 1.21–5.64). Conclusion: One in ten elderly patients with aortic stenosis undergoing MDCT to plan a TAVI procedure experienced CI-AKI after intravenous ICM injection. Intravenous administration of <90 ml of ICM reduces this risk in patients with or without pre-existing impaired renal function. However, in the majority of patients renal function recovers before the TAVI procedure. - Highlights: • We analyzed retrospectively 361 patients who were assessed by MDCT prior to TAVI. • Overall incidence of CI-AKI after intravenous ICM injection was 10.5%. • Interaction between baseline eGFR*amount of ICM injected predicts the risk of CI-AKI. • ICM <90 ml reduces the risk in patients with or without impaired renal function. • In the majority of patients renal function recovers before TAVI procedure

  7. Early segmental changes in ischemic acute tubular necrosis of the rat kidney

    DEFF Research Database (Denmark)

    Faarup, Poul; Nørgaard, Tove; Hegedüs, Viktor;

    2004-01-01

    pentothal-anesthetized Wistar rats (body weight 200-250 g) ischemia of the right kidney was obtained by clamping (clamp diameter 0.15 mm) the ipsilateral renal artery for varying periods of time (10 min to 6 h) followed by removal and instant freezing of the kidney in isopentane at -165 degrees C...... and subsequent freeze-substitution in alcohol. The microscopic slides from the kidneys were silver methenamine-PAS stained. In the segments of the proximal convoluted tubules of the nephrons, presence of nuclear pyknosis, places of denuded basement membranes and presence of exfoliated tubular cells were counted...

  8. Emergency surgical treatment of complicated acute pancreatitis after kidney transplantation with acute rejection: Case report and literature review

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    Dušan Klos

    2016-06-01

    Conclusions: With regard to the patient's comorbidities, early surgical therapy was indicated – drainage and closed lavage and immunosuppressive medication as a suspected tobe ethiological factor was discontinued. This course of treatment led to a complete recovery with preservation of good function of the cadaverous kidney.

  9. Changes in dendritic cells and dendritic cell subpopulations in peripheral blood of recipients during acute rejection after kidney transplantation

    Institute of Scientific and Technical Information of China (English)

    Ma Linlin; Liu Yong; Wu Junjie; Xu Xiuhong; Liu Fen; Feng Lang; Xie Zelin

    2014-01-01

    Background Advances in transplantation immunology show that the balance between dendritic cells (DCs) and their subsets can maintain stable immune status in the induction of tolerance after transplantation.The aim of this study was to investigate if DCs and DC subpopulations in recipient peripheral blood are effective diagnostic indicators of acute rejection following kidney transplantation.Methods Immunofluorescent flow cytometry was used to classify white blood cells (WBCs),the levels of mononuclear cells and DCs (including the dominant subpopulations,plasmacytoid DC (pDC) and myeloid DC (mDC)) in peripheral blood at 0,1,7,and 28 days and 1 year after kidney transplantation in 33 patients.In addition,the blood levels of interleukin-10 (IL-10) and IL-12 were monitored before and after surgery.Fifteen healthy volunteers served as normal controls.Patients were undertaking hemodialysis owing to uremia before surgery.Results The total number of DCs,pDC,and mDC in peripheral blood and the pDC/mDC ratio were significantly lower in patients than controls (P <0.05).Peripheral DCs suddenly decreased at the end of day 1,then gradually increased through day 28 but remained below normal levels.After 1 year,levels were higher than before surgery but lower than normal.The mDC levels were higher in patients with acute rejection before and 1 day after surgery (P <0.005).There was no significant difference in IL-10 and IL-12 levels between patients with and without acute rejection.Conclusion The changes in DCs and DC subpopulations during the acute rejection period may serve as effective markers and referral indices for monitoring the immune state,and predicting rejection and reasonably adjusting immunosuppressants.

  10. PROSPECTIVE STUDY OF ETIOLOGY, CLINICAL PROFILE AND OUTCOME IN PATIENTS WITH FEVER, JAUNDICE AND ACUTE KIDNEY INJURY

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    Pradeep

    2015-09-01

    Full Text Available OBJECTIVE: To study etiology, risk factors, various clinical and lab parameters and outcome of patients presenting with fever, jaundice and acute kidney injury. MATERIALS AND METHODS : An open prospective study was done on 100 patients presented with triad of fever, jaundice and acute kidney injury (AKI in the Depar tment of Medicine of G R Medical College and JA Group of Hospitals, Gwalior, MP from September 2011 to November 2012. Patients having temperature more than >100 0 F, serum creatinine ≥1.3 mg/dL or a 50 % increase from baseline or a reduction in urine output (documented oliguria of 6 hours, serum bilirubin >1.8 mg/dL were included in the study. A detailed history, clinical examination and investigations were done to find the cause of these derangements and all the patients were managed acc ordingly. RESULTS: A total 100 patients were included in study out of which 70% were males. Out of 100 patients, 50% were of septicemia, 34% were having malaria, 12% had acute pancreatitis and 4% patients were of dengue. Out of 50 septicemia patients, 35(7 0% were male, out of which 11(31.42% were of 56 - 65 years of age. Out of 17 deaths, 13(76% were males. Among total death, 11(22% were in septicemia followed by 5(14.70% in malaria patients. CONCLUSION: Many infectious and non - infectious diseases like malaria, septicemia, acute pancreatitis, dengue fever etc. can present with fever, jaundice and deranged renal functions. This triad of presentation is associated wi th high morbidity and mortality and the advanced age, male gender presences of anemia were the risk factors for high mortality. AKI occurs most commonly in association with P. falciparum malaria. Early diagnosis and prompt management including dialysis can reduce mortality and expedite recovery of renal function

  11. Hindbrain GLP-1 receptor mediation of cisplatin-induced anorexia and nausea.

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    De Jonghe, Bart C; Holland, Ruby A; Olivos, Diana R; Rupprecht, Laura E; Kanoski, Scott E; Hayes, Matthew R

    2016-01-01

    While chemotherapy-induced nausea and vomiting are clinically controlled in the acute (anorexia, nausea, fatigue, and other illness-type behaviors during the delayed phase (>24 h) of chemotherapy are largely uncontrolled. As the hindbrain glucagon-like peptide-1 (GLP-1) system contributes to energy balance and mediates aversive and stressful stimuli, here we examine the hypothesis that hindbrain GLP-1 signaling mediates aspects of chemotherapy-induced nausea and reductions in feeding behavior in rats. Specifically, hindbrain GLP-1 receptor (GLP-1R) blockade, via 4th intracerebroventricular (ICV) exendin-(9-39) injections, attenuates the anorexia, body weight reduction, and pica (nausea-induced ingestion of kaolin clay) elicited by cisplatin chemotherapy during the delayed phase (48 h) of chemotherapy-induced nausea. Additionally, the present data provide evidence that the central GLP-1-producing preproglucagon neurons in the nucleus tractus solitarius (NTS) of the caudal brainstem are activated by cisplatin during the delayed phase of chemotherapy-induced nausea, as cisplatin led to a significant increase in c-Fos immunoreactivity in NTS GLP-1-immunoreactive neurons. These data support a growing body of literature suggesting that the central GLP-1 system may be a potential pharmaceutical target for adjunct anti-emetics used to treat the delayed-phase of nausea and emesis, anorexia, and body weight loss that accompany chemotherapy treatments.

  12. Hindbrain GLP-1 receptor mediation of cisplatin-induced anorexia and nausea.

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    De Jonghe, Bart C; Holland, Ruby A; Olivos, Diana R; Rupprecht, Laura E; Kanoski, Scott E; Hayes, Matthew R

    2016-01-01

    While chemotherapy-induced nausea and vomiting are clinically controlled in the acute (24 h) of chemotherapy are largely uncontrolled. As the hindbrain glucagon-like peptide-1 (GLP-1) system contributes to energy balance and mediates aversive and stressful stimuli, here we examine the hypothesis that hindbrain GLP-1 signaling mediates aspects of chemotherapy-induced nausea and reductions in feeding behavior in rats. Specifically, hindbrain GLP-1 receptor (GLP-1R) blockade, via 4th intracerebroventricular (ICV) exendin-(9-39) injections, attenuates the anorexia, body weight reduction, and pica (nausea-induced ingestion of kaolin clay) elicited by cisplatin chemotherapy during the delayed phase (48 h) of chemotherapy-induced nausea. Additionally, the present data provide evidence that the central GLP-1-producing preproglucagon neurons in the nucleus tractus solitarius (NTS) of the caudal brainstem are activated by cisplatin during the delayed phase of chemotherapy-induced nausea, as cisplatin led to a significant increase in c-Fos immunoreactivity in NTS GLP-1-immunoreactive neurons. These data support a growing body of literature suggesting that the central GLP-1 system may be a potential pharmaceutical target for adjunct anti-emetics used to treat the delayed-phase of nausea and emesis, anorexia, and body weight loss that accompany chemotherapy treatments. PMID:26522737

  13. Protective effect of low potassium dextran solution on acute kidney injury following acute lung injury induced by oleic acid in piglets

    Institute of Scientific and Technical Information of China (English)

    WU Rui-ping; LIANG Xiu-bin; GUO Hui; ZHOU Xiao-shuang; ZHAO Li; WANG Chen; LI Rong-shan

    2012-01-01

    Background Low potassium dextran (LPD) solution can attenuate acute lung injury (ALI).However,LPD solution for treating acute kidney injury secondary to ALI has not been reported.The present study was performed to examine the renoprotective effect of LPD solution in ALI induced by oleic acid (OA) in piglets.Methods Twelve animals that suffered an ALI induced by administration of OA into the right atrium were divided into two groups:the placebo group (n=6) pretreated with normal saline and the LPD group (n=6),pretreated with LPD solution.LPD solution was injected intravenously at a dose of 12.5 ml/kg via the auricular vein 1 hour before OA injection.Results All animals survived the experiments with mild histopathological injury to the kidney.There were no significant differences in mean arterial pressure (MAP),creatinin and renal damage scores between the two groups.Compared with the placebo group,the LPD group had better gas exchange parameters at most of the observation points ((347.0±12.6)mmHg vs.(284.3±11.3) mmHg at 6 hours after ALI,P<0.01).After 6 hours of treatment with OA,the plasma concentrations of NGAL and interleukin (IL)-6 in both groups increased dramatically compared to baseline ((6.0±0.6) and (2.50±0.08) folds in placebo group; and (2.5±0.5) and (1.40±0.05) folds in LPD group),but the change of both parameters in the LPD group was significantly lower (P <0.01) than in the placebo group.And 6 hours after ALl the kidney tissue concentration of IL-6 in the LPD group ((165.7 ± 22.5) pg.ml-1.g-1 protein) was significantly lower (P <0.01) than that in placebo group ((67.2± 25.3) pg.ml-1.g-1 protein).Conclusion These findings suggest that pretreatment with LPD solution via systemic administration might attenuate acute kidney injury and the cytokine response of IL-6 in the ALl piglet model induced by OA injection.

  14. Cisplatin-induced caspase activation mediates PTEN cleavage in ovarian cancer cells: a potential mechanism of chemoresistance

    International Nuclear Information System (INIS)

    The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) tumor suppressor protein is a central negative regulator of the PI3K/AKT signaling cascade and suppresses cell survival as well as cell proliferation. PTEN is found to be either inactivated or mutated in various human malignancies. In the present study, we have investigated the regulation of PTEN during cisplatin induced apoptosis in A2780, A270-CP (cisplatin resistant), OVCAR-3 and SKOV3 ovarian cancer cell lines. Cells were treated with 10μM of cisplatin for 24h. Transcript and protein levels were analysed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and western blotting, respectively. Immunofluorescence microscopy was used to assess the intracellular localization of PTEN. Proteasome inhibitor and various caspases inhibitors were used to find the mechanism of PTEN degradation. PTEN protein levels were found to be decreased significantly in A2780 cells; however, there was no change in PTEN protein levels in A2780-CP, OVCAR-3 and SKOV3 cells with cisplatin treatment. The decrease in PTEN protein was accompanied with an increase in the levels of AKT phosphorylation (pAKT) in A2780 cells and a decrease of BCL-2. Cisplatin treatment induced the activation/cleavage of caspase-3, -6, -7, -8, -9 in all cell lines tested in this study except the resistant variant A2780-CP cells. In A2780 cells, restoration of PTEN levels was achieved upon pre-treatment with Z-DEVD-FMK (broad range caspases inhibitor) and not with MG132 (proteasome inhibitor) and by overexpression of BCL-2, suggesting that caspases and BCL-2 are involved in the decrease of PTEN protein levels in A2780 cells. The decrease in pro-apoptotic PTEN protein levels and increase in survival factor pAKT in A2780 ovarian cancer cells suggest that cisplatin treatment could further exacerbate drug resistance in A2780 ovarian cancer cells

  15. Anticancer drug-induced kidney disorders.

    Science.gov (United States)

    Kintzel, P E

    2001-01-01

    Nephrotoxicity is an inherent adverse effect of certain anticancer drugs. Renal dysfunction can be categorised as prerenal uraemia, intrinsic damage or postrenal uraemia according to the underlying pathophysiological process. Renal hypoperfusion promulgates prerenal uraemia. Intrinsic renal damage results from prolonged hypoperfusion, exposure to exogenous or endogenous nephrotoxins, renotubular precipitation of xenobiotics or endogenous compounds, renovascular obstruction, glomerular disease, renal microvascular damage or disease, and tubulointerstitial damage or disease. Postrenal uraemia is a consequence of clinically significant urinary tract obstruction. Clinical signs of nephrotoxicity and methods used to assess renal function are discussed. Mechanisms of chemotherapy-induced renal dysfunction generally include damage to vasculature or structures of the kidneys, haemolytic uraemic syndrome and prerenal perfusion deficits. Patients with cancer are frequently at risk of renal impairment secondary to disease-related and iatrogenic causes. This article reviews the incidence, presentation, prevention and management of anticancer drug-induced renal dysfunction. Dose-related nephrotoxicity subsequent to administration of certain chloroethylnitrosourea compounds (carmustine, semustine and streptozocin) is commonly heralded by increased serum creatinine levels, uraemia and proteinuria. Additional signs of streptozocin-induced nephrotoxicity include hypophosphataemia, hypokalaemia, hypouricaemia, renal tubular acidosis, glucosuria, aceturia and aminoaciduria. Cisplatin and carboplatin cause dose-related renal dysfunction. In addition to increased serum creatinine levels and uraemia, electrolyte abnormalities, such as hypomagnesaemia and hypokalaemia, are commonly reported adverse effects. Rarely, cisplatin has been implicated as the underlying cause of haemolytic uraemic syndrome. Pharmaceutical antidotes to cisplatin-induced nephrotoxicity include amifostine, sodium

  16. Acute kidney injury in patients with newly diagnosed high-grade hematological malignancies: impact on remission and survival.

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    Emmanuel Canet

    Full Text Available BACKGROUND: Optimal chemotherapy with minimal toxicity is the main determinant of complete remission in patients with newly diagnosed hematological malignancies. Acute organ dysfunctions may impair the patient's ability to receive optimal chemotherapy. DESIGN AND METHODS: To compare 6-month complete remission rates in patients with and without acute kidney injury (AKI, we collected prospective data on 200 patients with newly diagnosed high-grade malignancies (non-Hodgkin lymphoma, 53.5%; acute myeloid leukemia, 29%; acute lymphoblastic leukemia, 11.5%; and Hodgkin disease, 6%. RESULTS: According to RIFLE criteria, 137 (68.5% patients had AKI. Five causes of AKI accounted for 91.4% of cases: hypoperfusion, tumor lysis syndrome, tubular necrosis, nephrotoxic agents, and hemophagocytic lymphohistiocytosis. Half of the AKI patients received renal replacement therapy and 14.6% received suboptimal chemotherapy. AKI was associated with a lower 6-month complete remission rate (39.4% vs. 68.3%, P<0.01 and a higher mortality rate (47.4% vs. 30.2%, P<0.01 than patients without AKI. By multivariate analysis, independent determinants of 6-month complete remission were older age, poor performance status, number of organ dysfunctions, and AKI. CONCLUSION: AKI is common in patients with newly diagnosed high-grade malignancies and is associated with lower complete remission rates and higher mortality.

  17. Design of clinical trials in acute kidney injury: a report from an NIDDK workshop--prevention trials.

    Science.gov (United States)

    Okusa, Mark D; Molitoris, Bruce A; Palevsky, Paul M; Chinchilli, Vernon M; Liu, Kathleen D; Cheung, Alfred K; Weisbord, Steven D; Faubel, Sarah; Kellum, John A; Wald, Ron; Chertow, Glenn M; Levin, Adeera; Waikar, Sushrut S; Murray, Patrick T; Parikh, Chirag R; Shaw, Andrew D; Go, Alan S; Chawla, Lakhmir S; Kaufman, James S; Devarajan, Prasad; Toto, Robert M; Hsu, Chi-yuan; Greene, Tom H; Mehta, Ravindra L; Stokes, John B; Thompson, Aliza M; Thompson, B Taylor; Westenfelder, Christof S; Tumlin, James A; Warnock, David G; Shah, Sudhir V; Xie, Yining; Duggan, Emily G; Kimmel, Paul L; Star, Robert A

    2012-05-01

    AKI is an important clinical problem that has become increasingly more common. Mortality rates associated with AKI remain high despite advances in supportive care. Patients surviving AKI have increased long-term mortality and appear to be at increased risk of developing CKD and progressing to ESRD. No proven effective pharmacologic therapies are currently available for the prevention or treatment of AKI. Advances in addressing this unmet need will require the development of novel therapeutic agents based on precise understanding of key pathophysiological events and the implementation of well designed clinical trials. To address this need, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored the "Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers" workshop in December 2010. The event brought together representatives from academia, industry, the National Institutes of Health, and the US Food and Drug Administration. We report the discussions of workgroups that developed outlines of clinical trials for the prevention of AKI in two patient populations: patients undergoing elective surgery who are at risk for or who develop AKI, and patients who are at risk for contrast-induced AKI. In both of these populations, primary prevention or secondary therapy can be delivered at an optimal time relative to kidney injury. The workgroups detailed primary and secondary endpoints for studies in these groups, and explored the use of adaptive clinical trial designs for trials of novel preventive strategies to improve outcomes of patients with AKI.

  18. Health status, renal function, and quality of life after multiorgan failure and acute kidney injury requiring renal replacement therapy

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    Faulhaber-Walter R

    2016-05-01

    Full Text Available Robert Faulhaber-Walter,1,2 Sebastian Scholz,1,3 Herrmann Haller,1 Jan T Kielstein,1,* Carsten Hafer1,4,* 1Department of Renal and Hypertensive Disease, Medical School Hannover, Hannover, Germany; 2Facharztzentrum Aarberg, Waldshut-Tiengen, Germany; 3Sanitaetsversorgungszentrum Wunstorf, Wunstorf, Germany; 4HELIOS Klinikum Erfurt, Erfurt, Germany *These authors contributed equally to this work Background: Critically ill patients with acute kidney injury (AKI in need of renal replacement therapy (RRT may have a protracted and often incomplete rehabilitation. Their long-term outcome has rarely been investigated. Study design: Survivors of the HANnover Dialysis OUTcome (HANDOUT study were evaluated after 5 years for survival, health status, renal function, and quality of life (QoL. The HANDOUT study had examinded mortality and renal recovery of patients with AKI receiving either standard extendend or intensified dialysis after multi organ failure. Results: One hundred fifty-six former HANDOUT participants were analyzed. In-hospital mortality was 56.4%. Five-year survival after AKI/RRT was 40.1% (86.5% if discharged from hospital. Main causes of death were cardiovascular complications and sepsis. A total of 19 survivors presented to the outpatient department of our clinic and had good renal recovery (mean estimated glomerular filtration rate 72.5±30 mL/min/1.73 m2; mean proteinuria 89±84 mg/d. One person required maintenance dialysis. Seventy-nine percent of the patients had a pathological kidney sonomorphology. The Charlson comorbidity score was 2.2±1.4 and adjusted for age 3.3±2.1 years. Numbers of comorbid conditions averaged 2.38±1.72 per patient (heart failure [52%] > chronic kidney disease/myocardial infarction [each 29%]. Median 36-item short form health survey (SF-36™ index was 0.657 (0.69 physical health/0.66 mental health. Quality-adjusted life-years after 5 years were 3.365. Conclusion: Mortality after severe AKI is higher than

  19. Successful Antiviral Triple Therapy in a Longstanding Refractory Hepatitis C Virus Infection with an Acute Kidney Injury

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    David Callau Monje

    2014-01-01

    Full Text Available Introduction. The HCV infection is a common disease with many chronically infected patients worldwide. So far, the standard therapy of a chronic HCV infection consisted of interferon as single therapy or in combination with ribavirin. After approval of the two protease inhibitors, boceprevir and telaprevir, the standard therapy for patients with genotype 1 changed. In patients with acute kidney injury (AKI these therapies are not approved and have so far not been evaluated in studies. Case Report. In April 2012, a 58-year-old female was admitted due to a cryoglobulin-positive chronic HCV infection which had been treated with interferon and ribavirin. Currently, the patient was admitted because of severe complications with an acute kidney injury. We treated our patient successfully with a boceprevir based triple therapy. Conclusion. Limited data suggests that a therapy with ribavirin in patients with AKI seems to be safe under close monitoring. Our patient was treated successfully with a protease inhibitor based triple therapy. Nevertheless, it is necessary to plan an interventional study to evaluate the exact risk-benefit profile of triple therapy regimens in patients with AKI and hepatitis C.

  20. Role of Cystathionine Gamma-Lyase in Immediate Renal Impairment and Inflammatory Response in Acute Ischemic Kidney Injury.

    Science.gov (United States)

    Markó, Lajos; Szijártó, István A; Filipovic, Milos R; Kaßmann, Mario; Balogh, András; Park, Joon-Keun; Przybyl, Lukasz; N'diaye, Gabriele; Krämer, Stephanie; Anders, Juliane; Ishii, Isao; Müller, Dominik N; Gollasch, Maik

    2016-01-01

    Hydrogen sulfide (H2S) is known to act protectively during renal ischemia/reperfusion injury (IRI). However, the role of the endogenous H2S in acute kidney injury (AKI) is largely unclear. Here, we analyzed the role of cystathionine gamma-lyase (CTH) in acute renal IRI using CTH-deficient (Cth(-/-)) mice whose renal H2S levels were approximately 50% of control (wild-type) mice. Although levels of serum creatinine and renal expression of AKI marker proteins were equivalent between Cth(-/-) and control mice, histological analysis revealed that IRI caused less renal tubular damage in Cth(-/-) mice. Flow cytometric analysis revealed that renal population of infiltrated granulocytes/macrophages was equivalent in these mice. However, renal expression levels of certain inflammatory cytokines/adhesion molecules believed to play a role in IRI were found to be lower after IRI only in Cth(-/-) mice. Our results indicate that the systemic CTH loss does not deteriorate but rather ameliorates the immediate AKI outcome probably due to reduced inflammatory responses in the kidney. The renal expression of CTH and other H2S-producing enzymes was markedly suppressed after IRI, which could be an integrated adaptive response for renal cell protection. PMID:27273292