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Sample records for human diabetic kidney

  1. Diabetic Kidney Problems

    Science.gov (United States)

    ... too high. Over time, this can damage your kidneys. Your kidneys clean your blood. If they are damaged, waste ... in your blood instead of leaving your body. Kidney damage from diabetes is called diabetic nephropathy. It ...

  2. Diabetes and Kidney Disease

    Science.gov (United States)

    ... et.al. Clinical manifestations of kidney disease among US adults with diabetes. Journal of the American Medical Association. 2016;316( ... of Washington, Associate Director, Kidney Research Institute ... The National Institute of Diabetes and Digestive and Kidney Diseases Health Information Center ...

  3. Diabetic kidney disease.

    Science.gov (United States)

    Thomas, Merlin C; Brownlee, Michael; Susztak, Katalin; Sharma, Kumar; Jandeleit-Dahm, Karin A M; Zoungas, Sophia; Rossing, Peter; Groop, Per-Henrik; Cooper, Mark E

    2015-07-30

    The kidney is arguably the most important target of microvascular damage in diabetes. A substantial proportion of individuals with diabetes will develop kidney disease owing to their disease and/or other co-morbidity, including hypertension and ageing-related nephron loss. The presence and severity of chronic kidney disease (CKD) identify individuals who are at increased risk of adverse health outcomes and premature mortality. Consequently, preventing and managing CKD in patients with diabetes is now a key aim of their overall management. Intensive management of patients with diabetes includes controlling blood glucose levels and blood pressure as well as blockade of the renin-angiotensin-aldosterone system; these approaches will reduce the incidence of diabetic kidney disease and slow its progression. Indeed, the major decline in the incidence of diabetic kidney disease (DKD) over the past 30 years and improved patient prognosis are largely attributable to improved diabetes care. However, there remains an unmet need for innovative treatment strategies to prevent, arrest, treat and reverse DKD. In this Primer, we summarize what is now known about the molecular pathogenesis of CKD in patients with diabetes and the key pathways and targets implicated in its progression. In addition, we discuss the current evidence for the prevention and management of DKD as well as the many controversies. Finally, we explore the opportunities to develop new interventions through urgently needed investment in dedicated and focused research. For an illustrated summary of this Primer, visit: http://go.nature.com/NKHDzg.

  4. Diagnosis of diabetic kidney disease

    DEFF Research Database (Denmark)

    Persson, Frederik; Rossing, Peter

    2018-01-01

    Approximately 20% to 40% of patients with type 1 or type 2 diabetes mellitus develop diabetic kidney disease. This is a clinical syndrome characterized by persistent albuminuria (> 300 mg/24 h, or > 300 mg/g creatinine), a relentless decline in glomerular filtration rate (GFR), raised arterial...... sign of diabetic nephropathy, the first symptom is usually peripheral edema, which occurs at a very late stage. Regular, systematic screening for diabetic kidney disease is needed in order to identify patients at risk of or with presymptomatic diabetic kidney disease. Annual monitoring of urinary...

  5. Effects of SGLT2 inhibition in human kidney proximal tubular cells--renoprotection in diabetic nephropathy?

    Directory of Open Access Journals (Sweden)

    Usha Panchapakesan

    Full Text Available Sodium/glucose cotransporter 2 (SGLT2 inhibitors are oral hypoglycemic agents used to treat patients with diabetes mellitus. SGLT2 inhibitors block reabsorption of filtered glucose by inhibiting SGLT2, the primary glucose transporter in the proximal tubular cell (PTC, leading to glycosuria and lowering of serum glucose. We examined the renoprotective effects of the SGLT2 inhibitor empagliflozin to determine whether blocking glucose entry into the kidney PTCs reduced the inflammatory and fibrotic responses of the cell to high glucose. We used an in vitro model of human PTCs. HK2 cells (human kidney PTC line were exposed to control 5 mM, high glucose (HG 30 mM or the profibrotic cytokine transforming growth factor beta (TGFβ1; 0.5 ng/ml in the presence and absence of empagliflozin for up to 72 h. SGLT1 and 2 expression and various inflammatory/fibrotic markers were assessed. A chromatin immunoprecipitation assay was used to determine the binding of phosphorylated smad3 to the promoter region of the SGLT2 gene. Our data showed that TGFβ1 but not HG increased SGLT2 expression and this occurred via phosphorylated smad3. HG induced expression of Toll-like receptor-4, increased nuclear deoxyribonucleic acid binding for nuclear factor kappa B (NF-κB and activator protein 1, induced collagen IV expression as well as interleukin-6 secretion all of which were attenuated with empagliflozin. Empagliflozin did not reduce high mobility group box protein 1 induced NF-κB suggesting that its effect is specifically related to a reduction in glycotoxicity. SGLT1 and GLUT2 expression was not significantly altered with HG or empagliflozin. In conclusion, empagliflozin reduces HG induced inflammatory and fibrotic markers by blocking glucose transport and did not induce a compensatory increase in SGLT1/GLUT2 expression. Although HG itself does not regulate SGLT2 expression in our model, TGFβ increases SGLT2 expression through phosphorylated smad3.

  6. CKD in diabetes: diabetic kidney disease versus nondiabetic kidney disease.

    Science.gov (United States)

    Anders, Hans-Joachim; Huber, Tobias B; Isermann, Berend; Schiffer, Mario

    2018-06-01

    The increasing global prevalence of type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) has prompted research efforts to tackle the growing epidemic of diabetic kidney disease (DKD; also known as diabetic nephropathy). The limited success of much of this research might in part be due to the fact that not all patients diagnosed with DKD have renal dysfunction as a consequence of their diabetes mellitus. Patients who present with CKD and diabetes mellitus (type 1 or type 2) can have true DKD (wherein CKD is a direct consequence of their diabetes status), nondiabetic kidney disease (NDKD) coincident with diabetes mellitus, or a combination of both DKD and NDKD. Preclinical studies using models that more accurately mimic these three entities might improve the ability of animal models to predict clinical trial outcomes. Moreover, improved insights into the pathomechanisms that are shared by these entities - including sodium-glucose cotransporter 2 (SGLT2) and renin-angiotensin system-driven glomerular hyperfiltration and tubular hyper-reabsorption - as well as those that are unique to individual entities might lead to the identification of new treatment targets. Acknowledging that the clinical entity of CKD plus diabetes mellitus encompasses NDKD as well as DKD could help solve some of the urgent unmet medical needs of patients affected by these conditions.

  7. Cyclodextrin Protects Podocytes in Diabetic Kidney Disease

    Science.gov (United States)

    Merscher-Gomez, Sandra; Guzman, Johanna; Pedigo, Christopher E.; Lehto, Markku; Aguillon-Prada, Robier; Mendez, Armando; Lassenius, Mariann I.; Forsblom, Carol; Yoo, TaeHyun; Villarreal, Rodrigo; Maiguel, Dony; Johnson, Kevin; Goldberg, Ronald; Nair, Viji; Randolph, Ann; Kretzler, Matthias; Nelson, Robert G.; Burke, George W.; Groop, Per-Henrik; Fornoni, Alessia

    2013-01-01

    Diabetic kidney disease (DKD) remains the most common cause of end-stage kidney disease despite multifactorial intervention. We demonstrated that increased cholesterol in association with downregulation of ATP-binding cassette transporter ABCA1 occurs in normal human podocytes exposed to the sera of patients with type 1 diabetes and albuminuria (DKD+) when compared with diabetic patients with normoalbuminuria (DKD−) and similar duration of diabetes and lipid profile. Glomerular downregulation of ABCA1 was confirmed in biopsies from patients with early DKD (n = 70) when compared with normal living donors (n = 32). Induction of cholesterol efflux with cyclodextrin (CD) but not inhibition of cholesterol synthesis with simvastatin prevented podocyte injury observed in vitro after exposure to patient sera. Subcutaneous administration of CD to diabetic BTBR (black and tan, brachiuric) ob/ob mice was safe and reduced albuminuria, mesangial expansion, kidney weight, and cortical cholesterol content. This was followed by an improvement of fasting insulin, blood glucose, body weight, and glucose tolerance in vivo and improved glucose-stimulated insulin release in human islets in vitro. Our data suggest that impaired reverse cholesterol transport characterizes clinical and experimental DKD and negatively influences podocyte function. Treatment with CD is safe and effective in preserving podocyte function in vitro and in vivo and may improve the metabolic control of diabetes. PMID:23835338

  8. Cadmium, diabetes and chronic kidney disease

    International Nuclear Information System (INIS)

    Edwards, Joshua R.; Prozialeck, Walter C.

    2009-01-01

    Recent epidemiological studies suggest a positive association between exposure to the environmental pollutant cadmium (Cd) and the incidence and severity of diabetes. In this review, we examine the literature suggesting a relationship between Cd exposure, elevated blood glucose levels, and the development of diabetes. In addition we review human and animal studies indicating that Cd potentiates or exacerbates diabetic nephropathy. We also review the various possible cellular mechanisms by which Cd may alter blood glucose levels. In addition, we present some novel findings from our own laboratories showing that Cd elevates fasting blood glucose levels in an animal model of subchronic Cd exposure before overt signs of renal dysfunction are evident. These studies also show that Cd reduces insulin levels and has direct cytotoxic effects on the pancreas. Together, these findings indicate that Cd may be a factor in the development of some types of diabetes and they raise the possibility that Cd and diabetes-related hyperglycemia may act synergistically to damage the kidney.

  9. Increased podocyte Sirtuin-1 function attenuates diabetic kidney injury.

    Science.gov (United States)

    Hong, Quan; Zhang, Lu; Das, Bhaskar; Li, Zhengzhe; Liu, Bohan; Cai, Guangyan; Chen, Xiangmei; Chuang, Peter Y; He, John Cijiang; Lee, Kyung

    2018-06-01

    Podocyte injury and loss contribute to the progression of glomerular diseases, including diabetic kidney disease. We previously found that the glomerular expression of Sirtuin-1 (SIRT1) is reduced in human diabetic glomeruli and that the podocyte-specific loss of SIRT1 aggravated albuminuria and worsened kidney disease progression in diabetic mice. SIRT1 encodes an NAD-dependent deacetylase that modifies the activity of key transcriptional regulators affected in diabetic kidneys, including NF-κB, STAT3, p53, FOXO4, and PGC1-α. However, whether the increased glomerular SIRT1 activity is sufficient to ameliorate the pathogenesis of diabetic kidney disease has not been explored. We addressed this by inducible podocyte-specific SIRT1 overexpression in diabetic OVE26 mice. The induction of SIRT1 overexpression in podocytes for six weeks in OVE26 mice with established albuminuria attenuated the progression of diabetic glomerulopathy. To further validate the therapeutic potential of increased SIRT1 activity against diabetic kidney disease, we developed a new, potent and selective SIRT1 agonist, BF175. In cultured podocytes BF175 increased SIRT1-mediated activation of PGC1-α and protected against high glucose-mediated mitochondrial injury. In vivo, administration of BF175 for six weeks in OVE26 mice resulted in a marked reduction in albuminuria and in glomerular injury in a manner similar to podocyte-specific SIRT1 overexpression. Both podocyte-specific SIRT1 overexpression and BT175 treatment attenuated diabetes-induced podocyte loss and reduced oxidative stress in glomeruli of OVE26 mice. Thus, increased SIRT1 activity protects against diabetes-induced podocyte injury and effectively mitigates the progression of diabetic kidney disease. Published by Elsevier Inc.

  10. Estrogens and progression of diabetic kidney damage.

    Science.gov (United States)

    Doublier, Sophie; Lupia, Enrico; Catanuto, Paola; Elliot, Sharon J

    2011-01-01

    It is generally accepted that estrogens affect and modulate the development and progression of chronic kidney diseases (CKD) not related to diabetes. Clinical studies have indeed demonstrated that the severity and rate of progression of renal damage tends to be greater among men, compared with women. Experimental studies also support the notion that female sex is protective and male sex permissive, for the development of CKD in non-diabetics, through the opposing actions of estrogens and testosterone. However, when we consider diabetes-induced kidney damage, in the setting of either type 1 or type 2 diabetes, the contribution of gender to the progression of renal disease is somewhat uncertain. Previous studies on the effects of estrogens in the pathogenesis of progressive kidney damage have primarily focused on mesangial cells. More recently, data on the effects of estrogens on podocytes, the cell type whose role may include initiation of progressive diabetic renal disease, became available. The aim of this review will be to summarize the main clinical and experimental data on the effects of estrogens on the progression of diabetes-induced kidney injury. In particular, we will highlight the possible biological effects of estrogens on podocytes, especially considering those critical for the pathogenesis of diabetic kidney damage.

  11. Hypoglycemia, chronic kidney disease, and diabetes mellitus.

    Science.gov (United States)

    Alsahli, Mazen; Gerich, John E

    2014-11-01

    Hypoglycemia is a major problem associated with substantial morbidity and mortality in patients with diabetes and is often a major barrier to achieving optimal glycemic control. Chronic kidney disease not only is an independent risk factor for hypoglycemia but also augments the risk of hypoglycemia that is already present in people with diabetes. This article summarizes our current knowledge of the epidemiology, pathogenesis, and morbidity of hypoglycemia in patients with diabetes and chronic kidney disease and reviews therapeutic considerations in this situation. PubMed and MEDLINE were searched for literature published in English from January 1989 to May 2014 for diabetes mellitus, hypoglycemia, chronic kidney disease, and chronic renal insufficiency. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  12. Diabetic kidney disease: a report from an ADA Consensus Conference.

    Science.gov (United States)

    Tuttle, Katherine R; Bakris, George L; Bilous, Rudolf W; Chiang, Jane L; de Boer, Ian H; Goldstein-Fuchs, Jordi; Hirsch, Irl B; Kalantar-Zadeh, Kamyar; Narva, Andrew S; Navaneethan, Sankar D; Neumiller, Joshua J; Patel, Uptal D; Ratner, Robert E; Whaley-Connell, Adam T; Molitch, Mark E

    2014-10-01

    The incidence and prevalence of diabetes mellitus have grown significantly throughout the world, due primarily to the increase in type 2 diabetes. This overall increase in the number of people with diabetes has had a major impact on development of diabetic kidney disease (DKD), one of the most frequent complications of both types of diabetes. DKD is the leading cause of end-stage renal disease (ESRD), accounting for approximately 50% of cases in the developed world. Although incidence rates for ESRD attributable to DKD have recently stabilized, these rates continue to rise in high-risk groups such as middle-aged African Americans, Native Americans, and Hispanics. The costs of care for people with DKD are extraordinarily high. In the Medicare population alone, DKD-related expenditures among this mostly older group were nearly $25 billion in 2011. Due to the high human and societal costs, the Consensus Conference on Chronic Kidney Disease and Diabetes was convened by the American Diabetes Association in collaboration with the American Society of Nephrology and the National Kidney Foundation to appraise issues regarding patient management, highlighting current practices and new directions. Major topic areas in DKD included (1) identification and monitoring, (2) cardiovascular disease and management of dyslipidemia, (3) hypertension and use of renin-angiotensin-aldosterone system blockade and mineralocorticoid receptor blockade, (4) glycemia measurement, hypoglycemia, and drug therapies, (5) nutrition and general care in advanced-stage chronic kidney disease, (6) children and adolescents, and (7) multidisciplinary approaches and medical home models for health care delivery. This current state summary and research recommendations are designed to guide advances in care and the generation of new knowledge that will meaningfully improve life for people with DKD. Copyright © 2014 American Diabetes Association and the National Kidney Foundation. Published by Elsevier Inc

  13. National Institute of Diabetes and Digestive and Kidney Diseases

    Science.gov (United States)

    ... Events Follow Us National Institute of Diabetes and Digestive and Kidney Diseases NIDDK conducts and supports research ... to improve health. Learn more Health Topics Diabetes Digestive Diseases Kidney Disease Weight Management Liver Disease Urologic ...

  14. Circulating CXCL16 in Diabetic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Usama Elewa

    2016-09-01

    Full Text Available Background/Aims: Chronic kidney disease and, specifically, diabetic kidney disease, is among the fastest increasing causes of death worldwide. A better understanding of the factors contributing to the high mortality may help design novel monitoring and therapeutic approaches. CXCL16 is both a cholesterol receptor and a chemokine with a potential role in vascular injury and inflammation. We aimed at identifying predictors of circulating CXCL16 levels in diabetic patients with chronic kidney disease. Methods: We have now studied plasma CXCL16 in 134 European patients with diabetic kidney disease with estimated glomerular filtration rate (eGFR categories G1-G4 and albuminuria categories A1-A3, in order to identify factors influencing plasma CXCL16 in this population. Results: Plasma CXCL16 levels were 4.0±0.9 ng/ml. Plasma CXCL16 increased with increasing eGFR category from G1 to G4 (that is, with decreasing eGFR values and with increasing albuminuria category. Plasma CXCL16 was higher in patients with prior cardiovascular disease (4.33±1.03 vs 3.88±0.86 ng/ml; p=0.013. In multivariate analysis, eGFR and serum albumin had an independent and significant negative correlation with plasma CXCL16. Conclusion: In diabetic kidney disease patients, GFR and serum albumin independently predicted plasma CXCL16 levels.

  15. 76 FR 11501 - National Institute of Diabetes and Digestive and Kidney Diseases

    Science.gov (United States)

    2011-03-02

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases Amended Notice of Meeting Notice is hereby given of a change in the meeting of the National Institute of Diabetes and Digestive and Kidney Diseases Special Emphasis...

  16. Diabetes and chronic kidney disease

    African Journals Online (AJOL)

    2007-08-16

    Aug 16, 2007 ... chronic dialysis or transplantation due to significant extrarenal disease, mainly .... including coronary heart disease, silent myocardial ischaemia and left ... diabetics and should be kept in mind: • renal papillary necrosis.

  17. Epidemiology of diabetic kidney disease.

    Science.gov (United States)

    Reutens, Anne T

    2013-01-01

    The increasing prevalence of diabetes has led to DKD becoming the leading cause of ESRD in many regions. The economic cost of DKD will grow to prohibitive amounts unless strategies to prevent its onset or progression are urgently implemented. In type 1 and type 2 diabetes, the presence of microalbuminuria and macroalbuminuria confers increased risk of developing ESRD and of death. Comparison of recent studies with earlier historical studies shows that the incidence of ESRD and death has decreased in DKD. Increased risk of albuminuria has been identified in certain non-European ethnic groups. However, the initial concept of progression of DKD as an albuminuric phenotype involving development of microalbuminuria, macroalbuminuria, and then ESRD has had to be modified. Albumin excretion frequently regresses, and GFR can decline without abnormality in albumin excretion. There is emerging evidence that changes in renal function occurring early in the course of diabetes predict future outcomes. The major challenges are to prevent DKD onset, to detect it early, and to improve DKD outcomes globally. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Kidney Disease and Diabetes - What You Need to Know

    Science.gov (United States)

    ... Bar Home Current Issue Past Issues Special Section Kidney Disease and Diabetes: What You Need to Know ... page please turn Javascript on. March is National Kidney Month , a good time to check if you ...

  19. The role of SIRT1 in diabetic kidney disease

    Directory of Open Access Journals (Sweden)

    Rabi eYacoub

    2014-10-01

    Full Text Available Sirtuins (SIRTs are members of the silent information regulator 2 (Sir2 family. In mammals, of the seven known SIRTs, SIRT1 function is most studied and has been shown to regulate wide range of cellular functions that affect metabolic homeostasis and aging. SIRT1 exerts anti-apoptotic, anti-oxidative, and anti-inflammatory effects against cellular injury, and protects the cells through the regulation of mitochondrial biogenesis, autophagy, and metabolism in response to the cellular energy and redox status. SIRT1 also promotes vasodilation and protects vascular tissues. In humans and animal models with diabetic kidney disease, its expression tends to be decreased in renal cells, and increased expression of SIRT1 was found to play a renal protective role in animal models with diabetic kidney disease. In this review we discuss the role and potential mechanisms by which SIRT1 protects against DKD.

  20. Clinico-pathological features of kidney disease in diabetic cases.

    Science.gov (United States)

    Furuichi, Kengo; Shimizu, Miho; Okada, Hirokazu; Narita, Ichiei; Wada, Takashi

    2018-03-21

    Diabetic kidney disease is the major cause of end-stage kidney disease in developed countries. However, the onset of kidney disorder and the progression pattern of kidney dysfunction and proteinuria greatly vary cases by cases. Therefore, risk classification with clinical data and pathological findings is important. Recent clinico-pathological study with kidney biopsy samples from diabetic patients revealed that pathological changes of diabetic nephropathy are characteristic and have special impacts on prognosis in each clinical stage. Moreover, comparison of the clinico-pathological findings of diabetic nephropathy with hypertensive nephrosclerosis revealed that there are few differences in their pathological findings in cases with low albuminuria and preserved estimated glomerular filtration rate (eGFR). Because it is so difficult to clearly distinguish pure kidney lesions caused by diabetes and kidney lesions due to effects other than diabetes, it is vital that these overlapped pathological findings be confirmed on kidney biopsy in cases of early stage diabetes. Further research is warranted regarding the pathogenesis of diabetic nephropathy and indication of kidney biopsy in diabetic cases.

  1. New Onset Diabetes: A Guide for Kidney Transplant Recipients

    Science.gov (United States)

    ... American Diabetes Association + Kidney Disease Outcomes Quality Initiative ** Fasting Blood Sugar ++ Post Prandial Glucose 11 Weight Control ➤ Obesity increases the risk of PTDM • Increased risk of ...

  2. Metformin in Patients With Type 2 Diabetes and Kidney Disease

    Science.gov (United States)

    Inzucchi, Silvio E.; Lipska, Kasia J.; Mayo, Helen; Bailey, Clifford J.; McGuire, Darren K.

    2015-01-01

    IMPORTANCE Metformin is widely viewed as the best initial pharmacological option to lower glucose concentrations in patients with type 2 diabetes mellitus. However, the drug is contraindicated in many individuals with impaired kidney function because of concerns of lactic acidosis. OBJECTIVE To assess the risk of lactic acidosis associated with metformin use in individuals with impaired kidney function. EVIDENCE ACQUISITION In July 2014, we searched the MEDLINE and Cochrane databases for English-language articles pertaining to metformin, kidney disease, and lactic acidosis in humans between 1950 and June 2014. We excluded reviews, letters, editorials, case reports, small case series, and manuscripts that did not directly pertain to the topic area or that met other exclusion criteria. Of an original 818 articles, 65 were included in this review, including pharmacokinetic/metabolic studies, large case series, retrospective studies, meta-analyses, and a clinical trial. RESULTS Although metformin is renally cleared, drug levels generally remain within the therapeutic range and lactate concentrations are not substantially increased when used in patients with mild to moderate chronic kidney disease (estimated glomerular filtration rates, 30-60 mL/min per 1.73 m2). The overall incidence of lactic acidosis in metformin users varies across studies from approximately 3 per 100 000 person-years to 10 per 100 000 person-years and is generally indistinguishable from the background rate in the overall population with diabetes. Data suggesting an increased risk of lactic acidosis in metformin-treated patients with chronic kidney disease are limited, and no randomized controlled trials have been conducted to test the safety of metformin in patients with significantly impaired kidney function. Population-based studies demonstrate that metformin may be prescribed counter to prevailing guidelines suggesting a renal risk in up to 1 in 4 patients with type 2 diabetes mellitus

  3. Diabetic Kidney Disease: A Syndrome Rather Than a Single Disease

    Science.gov (United States)

    Piccoli, Giorgina B.; Grassi, Giorgio; Cabiddu, Gianfranca; Nazha, Marta; Roggero, Simona; Capizzi, Irene; De Pascale, Agostino; Priola, Adriano M.; Di Vico, Cristina; Maxia, Stefania; Loi, Valentina; Asunis, Anna M.; Pani, Antonello; Veltri, Andrea

    2015-01-01

    The term "diabetic kidney" has recently been proposed to encompass the various lesions, involving all kidney structures that characterize protean kidney damage in patients with diabetes. While glomerular diseases may follow the stepwise progression that was described several decades ago, the tenet that proteinuria identifies diabetic nephropathy is disputed today and should be limited to glomerular lesions. Improvements in glycemic control may have contributed to a decrease in the prevalence of glomerular lesions, initially described as hallmarks of diabetic nephropathy, and revealed other types of renal damage, mainly related to vasculature and interstitium, and these types usually present with little or no proteinuria. Whilst glomerular damage is the hallmark of microvascular lesions, ischemic nephropathies, renal infarction, and cholesterol emboli syndrome are the result of macrovascular involvement, and the presence of underlying renal damage sets the stage for acute infections and drug-induced kidney injuries. Impairment of the phagocytic response can cause severe and unusual forms of acute and chronic pyelonephritis. It is thus concluded that screening for albuminuria, which is useful for detecting "glomerular diabetic nephropathy", does not identify all potential nephropathies in diabetes patients. As diabetes is a risk factor for all forms of kidney disease, diagnosis in diabetic patients should include the same combination of biochemical, clinical, and imaging tests as employed in non-diabetic subjects, but with the specific consideration that chronic kidney disease (CKD) may develop more rapidly and severely in diabetic patients. PMID:26676663

  4. Kidney transplant in diabetic patients: modalities, indications and results

    Directory of Open Access Journals (Sweden)

    Rangel Érika B

    2009-08-01

    Full Text Available Abstract Background Diabetes is a disease of increasing worldwide prevalence and is the main cause of chronic renal failure. Type 1 diabetic patients with chronic renal failure have the following therapy options: kidney transplant from a living donor, pancreas after kidney transplant, simultaneous pancreas-kidney transplant, or awaiting a deceased donor kidney transplant. For type 2 diabetic patients, only kidney transplant from deceased or living donors are recommended. Patient survival after kidney transplant has been improving for all age ranges in comparison to the dialysis therapy. The main causes of mortality after transplant are cardiovascular and cerebrovascular events, infections and neoplasias. Five-year patient survival for type 2 diabetic patients is lower than the non-diabetics' because they are older and have higher body mass index on the occasion of the transplant and both pre- and posttransplant cardiovascular diseases prevalences. The increased postransplant cardiovascular mortality in these patients is attributed to the presence of well-known risk factors, such as insulin resistance, higher triglycerides values, lower HDL-cholesterol values, abnormalities in fibrinolysis and coagulation and endothelial dysfunction. In type 1 diabetic patients, simultaneous pancreas-kidney transplant is associated with lower prevalence of vascular diseases, including acute myocardial infarction, stroke and amputation in comparison to isolated kidney transplant and dialysis therapy. Conclusion Type 1 and 2 diabetic patients present higher survival rates after transplant in comparison to the dialysis therapy, although the prevalence of cardiovascular events and infectious complications remain higher than in the general population.

  5. SGLT2 inhibition in the diabetic kidney – an update

    Science.gov (United States)

    Novikov, Aleksandra; Vallon, Volker

    2016-01-01

    Purpose of review The sodium glucose cotransporter SGLT2 reabsorbs most of the glucose filtered by the kidneys. SGLT2 inhibitors reduce glucose reabsorption thereby lowering blood glucose levels and have been approved as new anti-hyperglycemic drugs. While the therapeutic strategy is very promising, many questions remain. Recent findings Using validated antibodies SGLT2 expression was localized to the brush border of the early proximal tubule in human kidney and was found upregulated in genetic murine models of type 1 and 2 diabetes. SGLT2 may functionally interact with the Na/H exchanger NHE3 in the proximal tubule. SGLT1-mediated reabsorption explains the fractional glucose reabsorption of 40–50% during SGLT2 inhibition. SGLT2 is expressed on pancreatic alpha cells where its inhibition induces glucagon secretion. SGLT2 inhibition lowers GFR in hyperfiltering diabetic patients consistent with the tubular hypothesis of diabetic hyperfiltration. New data indicate a potential of SGLT2 inhibition for renal medullary hypoxia and ketoacidosis, but also for blood glucose effect-dependent and independent nephroprotective actions, renal gluconeogenesis inhibition, reduction in cardiovascular mortality, and cancer therapy. Summary The findings expand and refine our understanding of SGLT2 and its inhibition, have relevance for clinical practice, and will help interpret ongoing clinical trials on the long-term safety and cardiovascular effects of SGLT2 inhibitors. PMID:26575393

  6. [Type 2 diabetes mellitus and chronic kidney disease].

    Science.gov (United States)

    Ponťuch, Peter

    The number of type 2 diabetic patients is increasing world-wide and a prediction of prevalence of chronic kidney disease up to 2025 in European diabetic population is alarming. Albuminuria and estimated glomerular filtration rate are cardinal biochemical parameters in diagnostics of diabetic nephropathy. Following diagnostic methods are also used: renal ultrasonography, ophthalmoscopy and in not clarified cases renal biopsy. Long-term optimal glycemic control, efficient antihypertensive treatment by angiotensin converting enzyme inhibitor, or angiotensin receptor blocker and recommended protein intake is a cornerstone of therapy. The research is presently focused on new pathophysiological mechanisms, as analysis of genome, microRNA, kidney injury biomarkers and proteomes.Key words: chronic kidney disease - type 2 diabetes mellitus.

  7. 78 FR 50428 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2013-08-19

    ... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; NIDDK Ancillary R01 Studies on Liver... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Diabetic Ketoacidosis. Date: September...

  8. Biomarker for early renal microvascular and diabetic kidney diseases.

    Science.gov (United States)

    Futrakul, Narisa; Futrakul, Prasit

    2017-11-01

    Recognition of early stage of diabetic kidney disease, under common practice using biomarkers, namely microalbuminuria, serum creatinine level above 1 mg/dL and accepted definition of diabetic kidney disease associated with creatinine clearance value below 60 mL/min/1.73 m 2 , is unlikely. This would lead to delay treatment associated with therapeutic resistance to vasodilator due to a defective vascular homoeostasis. Other alternative biomarkers related to the state of microalbuminuria is not sensitive to screen for early diabetic kidney disease (stages I, II). In this regard, a better diagnostic markers to serve for this purpose are creatinine clearance, fractional excretion of magnesium (FE Mg), cystatin C. Recently, renal microvascular disease and renal ischemia have been demonstrated to correlate indirectly with the development of diabetic kidney disease and its function. Among these are angiogenic and anti-angiogenic factors, namely VEGF, VEGF receptors, angiopoietins and endostatin. With respect to therapeutic prevention, implementation of treatment at early stage of diabetic and nondiabetic kidney disease is able to restore renal perfusion and function.

  9. Glycosylation patterns of kidney proteins differ in rat diabetic nephropathy.

    Science.gov (United States)

    Ravidà, Alessandra; Musante, Luca; Kreivi, Marjut; Miinalainen, Ilkka; Byrne, Barry; Saraswat, Mayank; Henry, Michael; Meleady, Paula; Clynes, Martin; Holthofer, Harry

    2015-05-01

    Diabetic nephropathy often progresses to end-stage kidney disease and, ultimately, to renal replacement therapy. Hyperglycemia per se is expected to have a direct impact on the biosynthesis of N- and O-linked glycoproteins. This study aims to establish the link between protein glycosylation and progression of experimental diabetic kidney disease using orthogonal methods. Kidneys of streptozotocin-diabetic and control rats were harvested at three different time points post streptozotocin injection. A panel of 12 plant lectins was used in the screening of lectin blots. The lectins UEAI, PHA-E, GSI, PNA, and RCA identified remarkable disease-associated differences in glycoprotein expression. Lectin affinity chromatography followed by mass spectrometric analyses led to the identification of several glycoproteins involved in salt-handling, angiogenesis, and extracellular matrix degradation. Our data confirm a substantial link between glycosylation signature and diabetes progression. Furthermore, as suggested by our findings on dipeptidyl peptidase-IV, altered protein glycosylation may reflect changes in biochemical properties such as enzymatic activity. Thus, our study demonstrates the unexplored potential of protein glycosylation analysis in the discovery of molecules linked to diabetic kidney disease.

  10. Systematic kidney disease management in a population with diabetes mellitus: turning the tide of kidney failure.

    Science.gov (United States)

    Rayner, Hugh C; Hollingworth, Lee; Higgins, Robert; Dodds, Simon

    2011-10-01

    A significant proportion of patients with diabetes mellitus do not get the benefit of treatment that would reduce their risk of progressive kidney disease and reach a nephrologist once significant loss of kidney function has already occurred. Systematic disease management of patients with diabetes and kidney disease. Diverse population (approximately 800,000) in and around Birmingham, West Midlands, UK. Number of outpatient appointments, estimated glomerular filtration rate (eGFR) at first contact with nephrologist, number of patients starting kidney replacement therapy (KRT) and mode of KRT at start. Identification of patients with low or deteriorating trend in eGFR from weekly database review, specialist diabetes-kidney clinic, self-management of blood pressure and transfer to multidisciplinary clinic >12 months before end-stage kidney disease. New patients increased from 62 in 2003 to 132 in 2010; follow-ups fell from 251 to 174. Median eGFR at first clinic visit increased from 28.8 ml/min/1.73 m(2) (range 6.1-67.0) in 2000/2001 to 35.0 (11.1-147.5) in 2010 (pmanagement across a large population significantly improves patient outcomes, increases the productivity of a specialist service and could reduce healthcare costs compared with the current model of care.

  11. Monitoring kidney function in diabetic nephropathy

    DEFF Research Database (Denmark)

    Rossing, P; Astrup, A S; Smidt, U M

    1994-01-01

    (SD))(p kidney function ml.min-1.year-1 was 4.7 (3.3) measured and 4.8 (3.5) estimated (mean(SD)) (NS), but the 95% limits...... of decline in glomerular filtration rate are comparable, but the limits of agreement are wide, which make the Cockroft-Gault method unacceptable for clinical purposes, i.e. monitoring progression in kidney function in the individual patient.(ABSTRACT TRUNCATED AT 250 WORDS)...

  12. 75 FR 61766 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2010-10-06

    ... Institute of Diabetes and Digestive and Kidney Diseases Special Emphasis Panel, Liver PPG Application. Date... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the...: National Institute of Diabetes and Digestive and Kidney Diseases Special Emphasis Panel, Nutrition Obesity...

  13. 76 FR 36931 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2011-06-23

    ... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Liver Disease and Transplantation... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the... of Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Urinary Tract Dysfunction P01...

  14. 75 FR 69685 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2010-11-15

    ... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Liver Ancillary Studies. Date: December... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Special Emphasis Panel for R01...

  15. 78 FR 9401 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2013-02-08

    ... Institute of Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Liver Related Ancillary... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Beta-Cell Function and Cognition. Date...

  16. Role of the Immune System in Diabetic Kidney Disease.

    Science.gov (United States)

    Hickey, Fionnuala B; Martin, Finian

    2018-03-12

    The purpose of this review is to examine the proposed role of immune modulation in the development and progression of diabetic kidney disease (DKD). Diabetic kidney disease has not historically been considered an immune-mediated disease; however, increasing evidence is emerging in support of an immune role in its pathophysiology. Both systemic and local renal inflammation have been associated with DKD. Infiltration of immune cells, predominantly macrophages, into the kidney has been reported in a number of both experimental and clinical studies. In addition, increased levels of circulating pro-inflammatory cytokines have been linked to disease progression. Consequently, a variety of therapeutic strategies involving modulation of the immune response are currently being investigated in diabetic kidney disease. Although no current therapies for DKD are directly based on immune modulation many of the therapies in clinical use have anti-inflammatory effects along with their primary actions. Macrophages emerge as the most likely beneficial immune cell target and compounds which reduce macrophage infiltration to the kidney have shown potential in both animal models and clinical trials.

  17. Optimal conditions of LDR to protect the kidney from diabetes

    Science.gov (United States)

    Cheng, Jie; Li, Fengsheng; Cui, Jiuwei; Guo, Weiying; Li, Cai; Li, Wei; Wang, Guixia; Xing, Xiao; Gao, Ying; Ge, Yuanyuan; Wang, Guanjun; Cai, Lu

    2014-01-01

    Aims We reported the attenuation of diabetes-induced renal dysfunction by exposure to multiple low-dose radiation (LDR) at 25 mGy every other day via suppressing renal oxidative damage. We here explored the optimal conditions of LDR to protect the kidney from diabetes. Main methods Type 1 diabetic mice were induced with multiple injections of low-dose streptozotocin in male C57BL/6J mice. Diabetic mice received whole body X-irradiation at dose of 12.5, 25 or 50 mGy every other day for either 4 or 8 weeks. Age-matched normal mice were similarly irradiated at the dose of 25 mGy for 4 or 8 weeks. The renal function and histopathological changes were examined at the 4th and 8th week of the study. Key findings Diabetes induced renal dysfunction, shown by the decreased creatinine and increased microalbumin in urinary. Renal oxidative damage, detected by protein nitration and lipid oxidation, and remodeling, reflected by increased expression of connective tissue growth factor, collagen IV and fibronectin, were significantly increased in diabetic mice. All these renal pathological and function changes in diabetic mice were significantly attenuated by exposure to LDR at all regimens, among which, however, exposure to LDR at 12.5 mGy for 8 weeks provided the best preventive effect on the kidney of diabetic mice. Significance Our results suggest that whole-body LDR at 12.5 mGy every other day for 8 weeks is the optimal condition of LDR to protect the kidney from diabetes. PMID:24631139

  18. New Onset Diabetes Mellitus after Kidney Transplantation in Denmark

    DEFF Research Database (Denmark)

    Hornum, Mette; Jørgensen, Kaj Anker; Hansen, Jesper Melchior

    2010-01-01

    patients remaining on the waiting list for kidney transplantation (uremic controls, age 47 11 years). All were examined at baseline before possible transplantation and after 12 months. The prevalence of diabetes, prediabetes, insulin sensitivity index (ISI), and insulin secretion index (Isecr) were...

  19. Theobromine increases NAD⁺/Sirt-1 activity and protects the kidney under diabetic conditions.

    Science.gov (United States)

    Papadimitriou, Alexandros; Silva, Kamila C; Peixoto, Elisa B M I; Borges, Cynthia M; Lopes de Faria, Jacqueline M; Lopes de Faria, José B

    2015-02-01

    Reduction in sirtuin 1 (Sirt-1) is associated with extracellular matrix (ECM) accumulation in the diabetic kidney. Theobromine may reduce kidney ECM accumulation in diabetic rats. In the current study, we aimed to unravel, under diabetic conditions, the mechanism of kidney ECM accumulation induced by a reduction in Sirt-1 and the effect of theobromine in these events. In vitro, we used immortalized human mesangial cells (iHMCs) exposed to high glucose (HG; 30 mM), with or without small interfering RNA for NOX4 and Sirt-1. In vivo, spontaneously hypertensive rats (SHR) were rendered diabetic by means of streptozotocin and studied after 12 wk. The effects of treatment with theobromine were investigated under both conditions. HG leads to a decrease in Sirt-1 activity and NAD(+) levels in iHMCs. Sirt-1 activity could be reestablished by treatment with NAD(+), silencing NOX4, and poly (ADP-ribose) polymerase-1 (PARP-1) blockade, or with theobromine. HG also leads to a low AMP/ATP ratio, acetylation of SMAD3, and increased collagen IV, which is prevented by theobromine. Sirt-1 or AMPK blockade abolished these effects of theobromine. In diabetic SHR, theobromine prevented increases in albuminuria and kidney collagen IV, reduced AMPK, elevated NADPH oxidase activity and PARP-1, and reduced NAD(+) levels and Sirt-1 activity. These results suggest that in diabetes mellitus, Sirt-1 activity is reduced by PARP-1 activation and NAD(+) depletion due to low AMPK, which increases NOX4 expression, leading to ECM accumulation mediated by transforming growth factor (TGF)-β1 signaling. It is suggested that Sirt-1 activation by theobromine may have therapeutic potential for diabetic nephropathy. Copyright © 2015 the American Physiological Society.

  20. The risk factors for diabetes mellitus after kidney transplantation

    International Nuclear Information System (INIS)

    Effat Razeghi; Monireh Amerian; Peimaneh Heydarian

    2010-01-01

    Post-transplant diabetes mellitus (PTDM) is an adverse complication of kidney transplantation, associated with decreased graft and patient survival. We investigated the risk factors for PTDM and their relation to graft rejection in our kidney transplant recipients. We prospectively included 109 consecutive first kidney transplant recipients transplanted at the Sina Hospital in Tehran from June 2003 to May 2004. Patients were excluded if they had diabetes at the time of transplantation either as the cause of kidney failure or as a comorbidity. PTDM was defined by fasting blood sugar =126 mg/dL or random blood sugar =200 mg/dL on two occasions and the need for insulin therapy and/or oral hypoglycemic drugs for at least two weeks. Thirty non-diabetic transplant recipients were diagnosed as having PTDM during the six month followup period after transplantation. Sixty non-PTDM controls, matched for age, sex and immun suppressive regimen, and transplanted as closely as possible to the PTDM cases, were randomly selected. The risk factors for PTDM were investigated in these 90 transplant recipients. Age older than 50 years (P = 0.04), history of hypertension (P = 0.02), polycystic kidney disease (P = 0.015), duration on dialysis more than one year (P < 0.0001), family history of diabetes mellitus (P < 0.0001), mean daily dose of prednisolone =15 mg/day (P < 0.0001) and cyclosporine =240 mg/day (P < 0.0001) were all more in the PTDM group. Also, the mean serum triglycerides was higher (P = 0.019) and there was an increased risk of graft rejection (P < 0.0001) in the PTDM group (Author).

  1. SGLT2 Inhibitors and the Diabetic Kidney.

    Science.gov (United States)

    Fioretto, Paola; Zambon, Alberto; Rossato, Marco; Busetto, Luca; Vettor, Roberto

    2016-08-01

    Diabetic nephropathy (DN) is the most common cause of end-stage renal disease worldwide. Blood glucose and blood pressure control reduce the risk of developing this complication; however, once DN is established, it is only possible to slow progression. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, the most recent glucose-lowering oral agents, may have the potential to exert nephroprotection not only through improving glycemic control but also through glucose-independent effects, such as blood pressure-lowering and direct renal effects. It is important to consider, however, that in patients with impaired renal function, given their mode of action, SGLT2 inhibitors are less effective in lowering blood glucose. In patients with high cardiovascular risk, the SGLT2 inhibitor empagliflozin lowered the rate of cardiovascular events, especially cardiovascular death, and substantially reduced important renal outcomes. Such benefits on DN could derive from effects beyond glycemia. Glomerular hyperfiltration is a potential risk factor for DN. In addition to the activation of the renin-angiotensin-aldosterone system, renal tubular factors, including SGLT2, contribute to glomerular hyperfiltration in diabetes. SGLT2 inhibitors reduce sodium reabsorption in the proximal tubule, causing, through tubuloglomerular feedback, afferent arteriole vasoconstriction and reduction in hyperfiltration. Experimental studies showed that SGLT2 inhibitors reduced hyperfiltration and decreased inflammatory and fibrotic responses of proximal tubular cells. SGLT2 inhibitors reduced glomerular hyperfiltration in patients with type 1 diabetes, and in patients with type 2 diabetes, they caused transient acute reductions in glomerular filtration rate, followed by a progressive recovery and stabilization of renal function. Interestingly, recent studies consistently demonstrated a reduction in albuminuria. Although these data are promising, only dedicated renal outcome trials will clarify whether

  2. 77 FR 29676 - National Institute of Diabetes and Digestive and Kidney Disorders; Notice of Closed Meetings

    Science.gov (United States)

    2012-05-18

    ... Diabetes and Digestive and Kidney Disorders; Notice of Closed Meetings Pursuant to section 10(d) of the... Digestive and Kidney Diseases. Date: June 21, 2012. Time: 3:00 p.m.-5:00 p.m. Agenda: To evaluate requests... Diabetes and Digestive and Kidney Diseases, Building 2DEM, Room 788B, 6707 Democracy Boulevard, Bethesda...

  3. 75 FR 57971 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2010-09-23

    ... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel, Central Repositories Non-Renewable Sample Access (PAR-10-90)--Liver, Kidney, Urological Sciences. Date: October 12, 2010. Time: 2 p.m. to 4...

  4. 75 FR 4830 - National Institute of Diabetes and Digestive and Kidney Diseases;

    Science.gov (United States)

    2010-01-29

    ... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel. Predictors of Genitourinary Disorders... Digestive and Kidney Diseases Special Emphasis Panel; Small Grant Program. Date: March 12, 2010. Time: 2 p.m...

  5. Collagen Type III Degradation Is Associated with Deterioration of Kidney Function in Patients with Type 2 Diabetes with Microalbuminuria

    DEFF Research Database (Denmark)

    Genovese, Federica; Hansen, Tine Wilum; Guldager, Daniel Kring Rasmussen

    Background In diabetes one of the main features of the progression to diabetic kidney disease is a pathological deposition of extracellular matrix components triggering renal fibrosis. The main structural component of the fibrotic core is collagen. One of the most prominent collagens is collagen...... type III (COL III), which is excessively synthesized and incorporated into the fibrotic extracellular matrix. Multiple studies in both humans and mice have suggested that MMP-9 activity is increased in diabetic kidney disease. We investigated whether a neo-epitope fragment of COL III generated by MMP-9...... (C3M) was associated with deterioration of kidney function in a well-characterised type 2 diabetic population with microalbuminuria and without symptoms of coronary artery disease. Methods The cohort included 200 participants, followed for 6.1 years. We measured C3M levels in serum (S-C3M) and urine...

  6. Reconstruction and Analysis of Human Kidney-Specific Metabolic Network Based on Omics Data

    Directory of Open Access Journals (Sweden)

    Ai-Di Zhang

    2013-01-01

    Full Text Available With the advent of the high-throughput data production, recent studies of tissue-specific metabolic networks have largely advanced our understanding of the metabolic basis of various physiological and pathological processes. However, for kidney, which plays an essential role in the body, the available kidney-specific model remains incomplete. This paper reports the reconstruction and characterization of the human kidney metabolic network based on transcriptome and proteome data. In silico simulations revealed that house-keeping genes were more essential than kidney-specific genes in maintaining kidney metabolism. Importantly, a total of 267 potential metabolic biomarkers for kidney-related diseases were successfully explored using this model. Furthermore, we found that the discrepancies in metabolic processes of different tissues are directly corresponding to tissue's functions. Finally, the phenotypes of the differentially expressed genes in diabetic kidney disease were characterized, suggesting that these genes may affect disease development through altering kidney metabolism. Thus, the human kidney-specific model constructed in this study may provide valuable information for the metabolism of kidney and offer excellent insights into complex kidney diseases.

  7. 75 FR 11188 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2010-03-10

    ... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel, Liver Disease Ancillary Studies. Date... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the.... (301) 594-8895. [email protected] . Name of Committee: National Institute of Diabetes and...

  8. 76 FR 64358 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2011-10-18

    ... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel, PAR09-247: Ancillary Studies in Liver... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the... Assistance Program Nos. 93.847, Diabetes, [[Page 64359

  9. 76 FR 63313 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2011-10-12

    ... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel, Liver Cell Membrane Proteins. Date... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the..., Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and Nutrition Research; 93.849...

  10. 77 FR 9671 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2012-02-17

    ... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Liver Tissue and Cell Distribution... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the... Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases...

  11. 75 FR 38817 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2010-07-06

    ... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel, Acute Liver Failure Study. Date: July 22... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the... Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive...

  12. 77 FR 36564 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2012-06-19

    ... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Clinical Trial Planning Grants in Type 1 Diabetes. Date: July 12, 2012. Time: 4:00 p.m. to 5:30 p.m. Agenda: To review and evaluate grant... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the...

  13. 78 FR 36554 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2013-06-18

    ... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Clinical Trials in Type 1 Diabetes (UC4) Meeting A. Date: July 17, 2013. Time: 1:30 p.m. to 2:30 p.m. Agenda: To review and evaluate grant... Institute of Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Clinical Trials in Type 1...

  14. 76 FR 30370 - National Institute of Diabetes and Digestive and Kidney Diseases; Meetings

    Science.gov (United States)

    2011-05-25

    ... Emphasis Panel; RFA-DK-10-012 Type 1 Diabetes Impact Award (DP3). Date: July 11, 2011. Time: 8 a.m. to 6 p... Institute of Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; NIDDK KUH-Fellowship Review... Diabetes and Digestive and Kidney Diseases; Meetings Notice of Closed Meetings Pursuant to section 10(d) of...

  15. 77 FR 28396 - National Institute of Diabetes and Digestive and Kidney Diseases Notice of Closed Meetings

    Science.gov (United States)

    2012-05-14

    ... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel, Training in Behavioral Research in Type 1 Diabetes. Date: June 11, 2012. Time: 9:00 a.m. to 11:30 a.m. Agenda: To review and evaluate grant... of Diabetes and Digestive and Kidney Diseases Special Emphasis Panel, Improving Adherence in Type 1...

  16. 77 FR 38075 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2012-06-26

    ... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Type 1 Diabetes Mouse Resource. Date: July 23, 2012. Time: 1 p.m. to 3 p.m. Agenda: To review and evaluate grant applications. Place... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the...

  17. 78 FR 18358 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2013-03-26

    ... Emphasis Panel; Biomarkers in Type 1 Diabetes. Date: April 10, 2013. Time: 4:30 p.m. to 5:30 p.m. Agenda... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Review of U34 Clinical Trial Planning... of Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Review of U34 Clinical Trial...

  18. 78 FR 3903 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Meetings

    Science.gov (United States)

    2013-01-17

    ... Diseases Advisory Council, Diabetes, Endocrine and Metabolic Diseases Subcommittee. Date: February 13, 2013... Diabetes and Digestive and Kidney Diseases; Notice of Meetings Pursuant to section 10(d) of the Federal... Diabetes and Digestive and Kidney Diseases Advisory Council. The meetings will be open to the public as...

  19. Use of Readily Accessible Inflammatory Markers to Predict Diabetic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Lauren Winter

    2018-05-01

    Full Text Available Diabetic kidney disease is a common complication of type 1 and type 2 diabetes and is the primary cause of end-stage renal disease in developed countries. Early detection of diabetic kidney disease will facilitate early intervention aimed at reducing the rate of progression to end-stage renal disease. Diabetic kidney disease has been traditionally classified based on the presence of albuminuria. More recently estimated glomerular filtration rate has also been incorporated into the staging of diabetic kidney disease. While albuminuric diabetic kidney disease is well described, the phenotype of non-albuminuric diabetic kidney disease is now widely accepted. An association between markers of inflammation and diabetic kidney disease has previously been demonstrated. Effector molecules of the innate immune system including C-reactive protein, interleukin-6, and tumor necrosis factor-α are increased in patients with diabetic kidney disease. Furthermore, renal infiltration of neutrophils, macrophages, and lymphocytes are observed in renal biopsies of patients with diabetic kidney disease. Similarly high serum neutrophil and low serum lymphocyte counts have been shown to be associated with diabetic kidney disease. The neutrophil–lymphocyte ratio is considered a robust measure of systemic inflammation and is associated with the presence of inflammatory conditions including the metabolic syndrome and insulin resistance. Cross-sectional studies have demonstrated a link between high levels of the above inflammatory biomarkers and diabetic kidney disease. Further longitudinal studies will be required to determine if these readily available inflammatory biomarkers can accurately predict the presence and prognosis of diabetic kidney disease, above and beyond albuminuria, and estimated glomerular filtration rate.

  20. Concise Review: Kidney Generation with Human Pluripotent Stem Cells.

    Science.gov (United States)

    Morizane, Ryuji; Miyoshi, Tomoya; Bonventre, Joseph V

    2017-11-01

    Chronic kidney disease (CKD) is a worldwide health care problem, resulting in increased cardiovascular mortality and often leading to end-stage kidney disease, where patients require kidney replacement therapies such as hemodialysis or kidney transplantation. Loss of functional nephrons contributes to the progression of CKD, which can be attenuated but not reversed due to inability to generate new nephrons in human adult kidneys. Human pluripotent stem cells (hPSCs), by virtue of their unlimited self-renewal and ability to differentiate into cells of all three embryonic germ layers, are attractive sources for kidney regenerative therapies. Recent advances in stem cell biology have identified key signals necessary to maintain stemness of human nephron progenitor cells (NPCs) in vitro, and led to establishment of protocols to generate NPCs and nephron epithelial cells from human fetal kidneys and hPSCs. Effective production of large amounts of human NPCs and kidney organoids will facilitate elucidation of developmental and pathobiological pathways, kidney disease modeling and drug screening as well as kidney regenerative therapies. We summarize the recent studies to induce NPCs and kidney cells from hPSCs, studies of NPC expansion from mouse and human embryonic kidneys, and discuss possible approaches in vivo to regenerate kidneys with cell therapies and the development of bioengineered kidneys. Stem Cells 2017;35:2209-2217. © 2017 AlphaMed Press.

  1. Diabetic Kidney Disease: From Epidemiology to Clinical Perspectives

    Directory of Open Access Journals (Sweden)

    Cheol Whee Park

    2014-08-01

    Full Text Available With worldwide epidemic of diabetes mellitus, diabetic nephropathy which is one of the major causes of microvascular complication has become a serious concern in Korea as well as the rest of the world. In view of its significance, there is an urgent and paramount need for proper managements that could either deter or slow the progression of diabetic nephropathy. Despite advances in care, ever increasing number of patients suffering from diabetic kidney disease and from end-stage renal disease implies that the current management is not adequate in many aspects. The reasons for these inadequacies compromise lack of early diagnosis, failure to intervene with timely and aggressive manner, and lack of understanding on the kind of interventions required. Another issue equally important for the adequate care of patients with diabetic nephropathy is an understanding of past, present and future epidemiology of diabetic nephropathy which serves, especially in Korea, as a material determining standard diagnosis and treatment and a national health-policy decision.

  2. The beneficial effects of zinc on diabetes-induced kidney damage in murine rodent model of type 1 diabetes mellitus.

    Science.gov (United States)

    Yang, Fan; Li, Bing; Dong, Xiaoming; Cui, Wenpeng; Luo, Ping

    2017-07-01

    Diabetes mellitus is a chronic multi-factorial metabolic disorder resulting from impaired glucose homeostasis. Zinc is a key co-factor for the correct functioning of anti-oxidant enzymes. Zinc deficiency therefore, impairs their synthesis, leading to increased oxidative stress within cells. Zinc deficiency occurs commonly in diabetic patients. The aim of this study is to investigate the effects of varying concentrations of zinc on diabetic nephropathy (DN) and the underlying mechanisms involved. FVB male mice aged 8 weeks were injected intraperitoneally with multiple low-dose streptozotocin at a concentration of 50mg/kg body weight daily for 5 days. Diabetic and age-matched control mice were treated with special diets supplemented with zinc at varying concentrations (0.85mg/kg, 30mg/kg, 150mg/kg) for 3 months. The mice were fed with zinc diets to mimic the process of oral administration of zinc in human. Zinc deficiency to some extent aggravated the damage of diabetic kidney. Feeding with normal (30mg/kg zinc/kg diet) and especially high (150mg/kg zinc/kg diet) concentration zinc could protect the kidney against diabetes-induced damage. The beneficial effects of zinc on DN are achieved most likely due to the upregulation of Nrf2 and its downstream factors NQO1, SOD1, SOD2. Zinc upregulated the expression of Akt phosphorylation and GSK-3β phosphorylation, resulting in a reduction in Fyn nuclear translocation and export of Nrf2 to the cytosol. Thus, regular monitoring and maintaining of adequate levels of zinc are recommended in diabetic individuals in order to delay the development of DN. Copyright © 2017 Elsevier GmbH. All rights reserved.

  3. 76 FR 80955 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2011-12-27

    ... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel, Vitamin D and Diabetes. Date: January 25... Democracy Boulevard, Bethesda, MD 20817. Contact Person: Michele L. Barnard, Ph.D., Scientific Review...

  4. Serum and Urinary Progranulin in Diabetic Kidney Disease.

    Science.gov (United States)

    Nicoletto, Bruna Bellincanta; Krolikowski, Thaiana Cirino; Crispim, Daisy; Canani, Luis Henrique

    2016-01-01

    Progranulin has been recognized as an adipokine related to obesity, insulin resistance and type 2 diabetes mellitus (T2DM). There are scarce data regarding progranulin and kidney disease, but there are some data linking diabetic kidney disease (DKD) and increased progranulin levels. We aimed to better describe the relationship between serum and urinary progranulin levels and DKD in T2DM. This is a case-control study including four groups of subjects: 1) Advanced DKD cases: T2DM patients with estimated glomerular filtration rate (eGFR) Progranulin was determined by enzyme-linked immunosorbent assay. One hundred and fourteen patients were included (23 advanced DKD cases, 25 albuminuric DKD cases, 40 diabetic controls and 26 non-diabetic controls). Serum progranulin was increased in advanced DKD compared to other groups [70.84 (59.04-83.16) vs. albuminuric cases 57.16 (42.24-67.38), diabetic controls 57.28 (42.08-70.47) and non-diabetic controls 44.54 (41.44-53.32) ng/mL; pprogranulin was decreased in advanced DKD cases compared to albuminuric cases [10.62 (6.30-16.08) vs. 20.94 (12.35-30.22); diabetic controls 14.06 (9.88-20.82) and non-diabetic controls 13.51 (7.94-24.36) ng/mL; p = 0.017]. There was a positive correlation between serum progranulin and body mass index (r = 0.27; p = 0.004), waist circumference (r = 0.25; p = 0.007); body fat percentage (r = 0.20; p = 0.042), high-sensitive C reactive protein (r = 0.35; pprogranulin was positively associated with albuminuria (r = 0.25; p = 0.010). In conclusion, progranulin is affected by a decrease in eGFR, being at a higher concentration in serum and lower in urine of DKD patients with T2DM and eGFR <60 mL/min/1.73m2. It is also associated with markers of obesity and inflammation.

  5. Type 2 Diabetes Mellitus and Kidney Cancer Risk: A Retrospective Cohort Analysis of the National Health Insurance.

    Science.gov (United States)

    Tseng, Chin-Hsiao

    2015-01-01

    To evaluate the association between incidence of any kidney cancer and type 2 diabetes mellitus. A random sample of 1,000,000 subjects covered by the National Health Insurance was recruited. A total of 998728 people (115655 diabetes and 883073 non-diabetes) without kidney cancer at recruitment were followed from 2003 to 2005. The cumulative incidence of kidney cancer from 2003 to 2005 in diabetic patients and non-diabetic people in all ages and in age kidney cancer with regards to diabetes status and diabetes duration (as a continuous variable or categorized into subgroups of non-diabetes, diabetes duration kidney cancer in the diabetic patients and the non-diabetic people was 166.9 and 33.1 per 100,000 person-years, respectively. The incidence increased with regards to increasing age in both the diabetic patients and the non-diabetic people, but a higher risk of kidney cancer for the diabetic patients compared to the non-diabetic people was consistently observed in different age groups. After multivariable adjustment, the odds ratio for diabetic patients versus non-diabetic people was 1.7 (95% confidence interval: 1.3-2.1, Pkidney cancer. Additionally, living in metropolitan Taipei region might also be associated with a higher risk of kidney cancer in the non-diabetic people, indicating a potential link between kidney cancer and some factors related to urbanization. Patients with type 2 diabetes mellitus have a significantly higher risk of kidney cancer.

  6. Potential new treatments for diabetic kidney disease.

    Science.gov (United States)

    Kania, Deanna S; Smith, Cory T; Nash, Christy L; Gonzalvo, Jasmine D; Bittner, Andrea; Shepler, Brian M

    2013-01-01

    Antifibrotic agents, antioxidant agents, ET-a receptor antagonists, and a few other agents with nonspecific or multifaceted mechanisms of action have been evaluated and progressed to small clinical studies in human subjects. Although there are limited data at the present time, these early evaluations have produced some favorable results that at least warrant further investigation. There is certainly not enough compelling evidence to justify the routine use of any of these products specifically for DKD at the moment; however, more well-controlled and adequately powered studies in several hundred patients will help determine which of these may have a place in the DKD treatment armamentarium of the future. Published by Elsevier Inc.

  7. Glucose Transporters in Diabetic Kidney Disease-Friends or Foes?

    Science.gov (United States)

    Wasik, Anita A; Lehtonen, Sanna

    2018-01-01

    Diabetic kidney disease (DKD) is a major microvascular complication of diabetes and a common cause of end-stage renal disease worldwide. DKD manifests as an increased urinary protein excretion (albuminuria). Multiple studies have shown that insulin resistance correlates with the development of albuminuria in non-diabetic and diabetic patients. There is also accumulating evidence that glomerular epithelial cells or podocytes are insulin sensitive and that insulin signaling in podocytes is essential for maintaining normal kidney function. At the cellular level, the mechanisms leading to the development of insulin resistance include mutations in the insulin receptor gene, impairments in the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway, or perturbations in the trafficking of glucose transporters (GLUTs), which mediate the uptake of glucose into cells. Podocytes express several GLUTs, including GLUT1, GLUT2, GLUT3, GLUT4, and GLUT8. Of these, the most studied ones are GLUT1 and GLUT4, both shown to be insulin responsive in podocytes. In the basal state, GLUT4 is preferentially located in perinuclear and cytosolic vesicular structures and to a lesser extent at the plasma membrane. After insulin stimulation, GLUT4 is sorted into GLUT4-containing vesicles (GCVs) that translocate to the plasma membrane. GCV trafficking consists of several steps, including approaching of the GCVs to the plasma membrane, tethering, and docking, after which the lipid bilayers of the GCVs and the plasma membrane fuse, delivering GLUT4 to the cell surface for glucose uptake into the cell. Studies have revealed novel molecular regulators of the GLUT trafficking in podocytes and unraveled unexpected roles for GLUT1 and GLUT4 in the development of DKD, summarized in this review. These findings pave the way for better understanding of the mechanistic pathways associated with the development and progression of DKD and aid in the development of new treatments for this devastating disease.

  8. 78 FR 34663 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2013-06-10

    ... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel, PAR-12-265 Ancillary Studies: The Microbiome in Child Health, Development and Obesity. Date: June 21, 2013. Time: 1:30 p.m. to 3:00 p.m. Agenda...

  9. 76 FR 12125 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2011-03-04

    ... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; GenitoUrinary Development Molecular Anatomy Project (GUDMAP) Date: March 23, 2011. Time: 12 p.m. to 1 p.m. Agenda: To review and evaluate...

  10. KIDNEY SIZE IN INFANTS OF TIGHTLY CONTROLLED INSULIN-DEPENDENT DIABETIC MOTHERS

    NARCIS (Netherlands)

    BOS, AF; AALDERS, AL; VANDOORMAAL, JJ; MARTIJN, A; OKKEN, A

    The aim of this study was to evaluate the influence of insulin-dependent diabetes mellitus in pregnant women on the kidney size of their infants. We measured kidney length in the first week of life using ultrasonography in 20 infants of tightly controlled insulin-dependent diabetic mothers and 20

  11. 76 FR 80954 - National Institute of Diabetes and Digestive and Kidney Disorders; Notice of Closed Meeting

    Science.gov (United States)

    2011-12-27

    ... Diabetes and Digestive and Kidney Disorders; Notice of Closed Meeting Pursuant to section 10(d) of the... Digestive and Kidney Diseases. Date: January 26, 2012. Time: 3 p.m.-5 p.m. Agenda: To evaluate requests for...; 93.848, Digestive Diseases and Nutrition Research; 98.849, Kidney Diseases, Urology and Hematology...

  12. Oxidative Stress in Diabetic Nephropathy with Early Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Alejandra Guillermina Miranda-Díaz

    2016-01-01

    Full Text Available The increase in the prevalence of diabetes mellitus (DM and the secondary kidney damage produces diabetic nephropathy (DN. Early nephropathy is defined as the presence of microalbuminuria (30–300 mg/day, including normal glomerular filtration rate (GFR or a mildly decreased GFR (60–89 mL/min/1.73 m2, with or without overt nephropathy. The earliest change caused by DN is hyperfiltration with proteinuria. The acceptable excretion rate of albumin in urine is 300 mg/day. Chronic kidney disease (CKD is characterized by abnormalities in renal function that persist for >3 months with health implications. Alterations in the redox state in DN are caused by the persistent state of hyperglycemia and the increase in advanced glycation end products (AGEs with ability to affect the renin-angiotensin system and the transforming growth factor-beta (TGF-β, producing chronic inflammation and glomerular and tubular hypertrophy and favoring the appearance of oxidative stress. In DN imbalance between prooxidant/antioxidant processes exists with an increase in reactive oxygen species (ROS. The overproduction of ROS diminishes expression of the antioxidant enzymes (manganese superoxide dismutase, glutathione peroxidase, and catalase. The early detection of CKD secondary to DN and the timely identification of patients would permit decreasing its impact on health.

  13. Effects of total glucosides of paeony on oxidative stress in the kidney from diabetic rats.

    Science.gov (United States)

    Su, Jing; Zhang, Pei; Zhang, Jing-Jing; Qi, Xiang-Ming; Wu, Yong-Gui; Shen, Ji-Jia

    2010-03-01

    TGP, extracted from the traditional Chinese herb root of Paeonia lactiflora pall, has been shown to have therapeutic effect in experimental diabetic nephropathy. However, its mechanism is not fully understood. In this study, the effects of TGP on oxidative stress were investigated in the kidney of diabetic rats induced by streptozotocin. TGP (50, 100, 200mg/kg) was orally administered once a day for 8 weeks. TGP treatment in all three doses significantly lowered 24 h urinary albumin excretion rate in diabetic rats and attenuated glomerular volume. TGP treatment with 100 and 200mg/kg significantly reduced indices for tubulointerstitial injury in diabetic rats. The level of MDA was significantly increased in the kidney of diabetic rats and attenuated by TGP treatment at the dose of 200mg/kg. TGP treatment in a dose-dependent manner decreased the level of 3-NT protein of the kidney which increased under diabetes. T-AOC was significantly reduced in diabetic rat kidney and remarkably increased by TGP treatment at the dose of 100 and 200mg/kg. Activity of antioxidant enzyme such as SOD, CAT was markedly elevated by TGP treatment with 200mg/kg. Western blot analysis showed that p-p38 MAPK and NF-kappaB p65 protein expression increased in diabetic rat kidney, which were significantly decreased by TGP treatment. It seems likely that oxidative stress is increased in the diabetic rat kidneys, while TGP can prevent diabetes-associated renal damage against oxidative stress.

  14. Comparison of the Ovary and Kidney as Sites for Islet Transplantation in Diabetic Rats.

    Science.gov (United States)

    Karakose, M; Pinarli, F A; Arslan, M S; Boyuk, G; Boztok, B; Albayrak, A; Ulus, A T; Cakal, E; Delibasi, T

    2016-01-01

    Currently, the most commonly used site for clinical islet transplantation is the liver although it is far from being an ideal site. Low oxygen tension and the induction of an inflammatory response impair islet implantation and lead to significant early loss of islet. The present study aimed to investigate and compare the efficacy of islet transplantation to the ovary and kidney subcapsule in diabetic rats. The study was performed with 3 groups of rats (control, ovary, and kidney subcapsule) including 6 Sprague female rats each. Diabetes model was created with the use of streptozotocin, and blood glucose levels of the rats were measured after 72 hours. Thirty days after the transplantation, blood samples were obtained from the rats, and then pancreas, kidney, and ovary specimens were fixed in 10% formaldehyde and the experiment completed. After staining with hematoxylin and eosin, the tissue samples were morphologically evaluated by a specialist histopathologist. Changes in mean blood glucose and C-peptide levels were statistically significant in the ovary and kidney subcapsule groups. Histologic examination revealed that granulosus insulin-bearing cells were detected in the islet grafts of both ovary and kidney subcapsule groups. The renal subcapsule group had inflammation signs on histologic examination. The islet cells of both ovary and renal subcapsule groups had no vacuolization. We showed that the ovary might be a new site for islet transplantation. Further research should be done on whether the initial results of this study can be reproduced in larger numbers of animal models and eventually in humans. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Selective Activation of AMPK β1-Containing Isoforms Improves Kidney Function in a Rat Model of Diabetic Nephropathy.

    Science.gov (United States)

    Salatto, Christopher T; Miller, Russell A; Cameron, Kimberly O; Cokorinos, Emily; Reyes, Allan; Ward, Jessica; Calabrese, Matthew F; Kurumbail, Ravi G; Rajamohan, Francis; Kalgutkar, Amit S; Tess, David A; Shavnya, Andre; Genung, Nathan E; Edmonds, David J; Jatkar, Aditi; Maciejewski, Benjamin S; Amaro, Marina; Gandhok, Harmeet; Monetti, Mara; Cialdea, Katherine; Bollinger, Eliza; Kreeger, John M; Coskran, Timothy M; Opsahl, Alan C; Boucher, Germaine G; Birnbaum, Morris J; DaSilva-Jardine, Paul; Rolph, Tim

    2017-05-01

    Diabetic nephropathy remains an area of high unmet medical need, with current therapies that slow down, but do not prevent, the progression of disease. A reduced phosphorylation state of adenosine monophosphate-activated protein kinase (AMPK) has been correlated with diminished kidney function in both humans and animal models of renal disease. Here, we describe the identification of novel, potent, small molecule activators of AMPK that selectively activate AMPK heterotrimers containing the β 1 subunit. After confirming that human and rodent kidney predominately express AMPK β 1, we explore the effects of pharmacological activation of AMPK in the ZSF1 rat model of diabetic nephropathy. Chronic administration of these direct activators elevates the phosphorylation of AMPK in the kidney, without impacting blood glucose levels, and reduces the progression of proteinuria to a greater degree than the current standard of care, angiotensin-converting enzyme inhibitor ramipril. Further analyses of urine biomarkers and kidney tissue gene expression reveal AMPK activation leads to the modulation of multiple pathways implicated in kidney injury, including cellular hypertrophy, fibrosis, and oxidative stress. These results support the need for further investigation into the potential beneficial effects of AMPK activation in kidney disease. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  16. Kidney Injury Molecule Levels in Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Aslan, Ozgur; Demir, Metin; Koseoglu, Mehmet

    2016-11-01

    This study was designed to determine the diagnostic role of urinary kidney injury molecule (KIM)-1 levels in renal damage in patients with type 2 diabetes mellitus according to the urinary albumin/creatinine ratio. Patients with type 2 diabetes mellitus admitted to different polyclinics in our hospital enrolled in the study and were subdivided into three groups according to albumin/creatinine ratio - normalbuminuric (n: 20); microalbuminuric (n: 20); albuminuric (n: 18) - and compared with the control group. Urine albumin was analyzed using the immunoturbidimetric method (Architect C16000, Abbott Diagnostics). uKIM-1 was determined using a commercially available enzyme-linked immunosorbent assay test kit (USCN Life Science, Hankou, Wuhan, China). One-sample Kolmogorov-Smirnov test, Spearman correlation and Kruskal-Wallis non-parametric tests were performed. Post hoc comparisons were made using Bonferroni-corrected Mann-Whitney U tests. The differences between the controls and normalbuminuric, microalbuminuric and albuminuric groups were highly significant for KIM-1. Positive correlation was found between KIM-1 and urine microalbumin-urine microalbumin/creatinine (r = 0.479 P diabetic nephropathy. J. Clin. Lab. Anal. 00:1-6, 2016. © 2016 Wiley Periodicals, Inc.

  17. L-citrulline protects from kidney damage in type 1 diabetic mice.

    Directory of Open Access Journals (Sweden)

    Maritza J Romero

    2013-12-01

    Full Text Available Rationale. Diabetic nephropathy is a major cause of end-stage renal disease, associated with endothelial dysfunction. Chronic supplementation of L-arginine (L-arg, the substrate for endothelial nitric oxide synthase (eNOS, failed to improve vascular function. L-citrulline (L-cit supplementation not only increases L-arg synthesis, but also inhibits cytosolic arginase I (Arg I, a competitor of eNOS for the use of L-arg, in the vasculature. Aims. To investigate whether L-cit treatment reduces diabetic nephropathy in streptozotocin (STZ-induced type 1 diabetes in mice and rats and to study its effects on arginase II (ArgII function, the main renal isoform. Methods. STZ-C57BL6 mice received L-cit or vehicle supplemented in the drinking water. For comparative analysis, diabetic ArgII knock out mice and L-cit-treated STZ-rats were evaluated. Results. L-cit exerted protective effects in kidneys of STZ-rats, and markedly reduced urinary albumin excretion, tubulo-interstitial fibrosis and kidney hypertrophy, observed in untreated diabetic mice. Intriguingly, L-cit treatment was accompanied by a sustained elevation of tubular ArgII at 16 wks and significantly enhanced plasma levels of the anti-inflammatory cytokine IL-10. Diabetic ArgII knock out mice showed greater BUN levels, hypertrophy, and dilated tubules than diabetic wild type mice. Despite a marked reduction in collagen deposition in ArgII knock out mice, their albuminuria was not significantly different from diabetic wild type animals. L-cit also restored NO/ROS balance and barrier function in high glucose-treated monolayers of human glomerular endothelial cells. Moreover, L-cit also has the ability to establish an anti-inflammatory profile, characterized by increased IL-10 and reduced IL-1beta and IL-12(p70 generation in the human proximal tubular cells. Conclusions. L-cit supplementation established an anti-inflammatory profile and significantly preserved the nephron function during type 1

  18. Successful Dual Kidney Transplantation After Hypothermic Oxygenated Perfusion of Discarded Human Kidneys

    Science.gov (United States)

    Ravaioli, Matteo; De Pace, Vanessa; Comai, Giorgia; Busutti, Marco; Gaudio, Massimo Del; Amaduzzi, Annalisa; Cucchetti, Alessandro; Siniscalchi, Antonio; La Manna, Gaetano; D’Errico, Antonietta A.D.; Pinna, Antonio Daniele

    2017-01-01

    Patient: Female, 58 Final Diagnosis: Nephroangiosclerosis Symptoms: Renal failure Medication: — Clinical Procedure: Resuscitation of grafts by hypothermic oxygenated perfusion Specialty: Transplantology Objective: Challenging differential diagnosis Background: The recovery of discarded human kidneys has increased in recent years and impels to use of unconventional organ preservation strategies that improve graft function. We report the first case of human kidneys histologically discarded and transplanted after hypothermic oxygenated perfusion (HOPE). Case Report: Marginal kidneys from a 78-year-old woman with brain death were declined by Italian transplant centers due to biopsy score (right kidney: 6; left kidney: 7). We recovered and preserved both kidneys through HOPE and we revaluated their use for transplantation by means of perfusion parameters. The right kidney was perfused for 1 h 20 min and the left kidney for 2 h 30 min. During organ perfusion, the renal flow increased progressively. We observed an increase of 34% for the left kidney (median flow 52 ml/min) and 50% for the right kidney (median flow 24 ml/min). Both kidneys had low perfusate’s lactate levels. We used perfusion parameters as important determinants of the organ discard. Based on our previous organ perfusion experience, the increase of renal flow and the low level of lactate following 1 h of HOPE lead us to declare both kidneys as appropriate for dual kidney transplantation (DKT). No complications were reported during the transplant and in the post-transplant hospital stay. The recipient had immediate graft function and serum creatinine value of 0.95 mg/dL at 3 months post-transplant. Conclusions: HOPE provides added information in the organ selection process and may improve graft quality of marginal kidneys. PMID:28928357

  19. Kidney allograft tolerance in diabetic patients after total lymphoid irradiation (TLI)

    Energy Technology Data Exchange (ETDEWEB)

    Ang, K.K.; Vanrenterighem, Y.; Waer, M.; Michielsen, P.; Schueren, E. van der (University Hospital St. Rafael, Leuven (Belgium)); Vandeputte, M. (Louvain Univ. (Belgium). Rega Institute for Medical Research)

    1985-04-01

    The value of total lymphoid irradiation (TLI) combined with low dose prednisone as sole immunosuppressive regimen in renal allograft transplantation in humans has been investigated. Seventeen patients with end-stage diabetic nephropathy received TLI to a cumulative dose of 20-30 Gy in fractions of 1 Gy. Cadaver kidneys were grafted as soon as they were available after completion of TLI. Profound and long-term immunosuppression has been achieved in 17 patients. Six patients live already more than one year and 7 for less than one year with a functioning kidney graft. One patient returned to chronic hemodialysis 11 months after transplantation and died of pericardial tamponade one month later. One patient had severe acute rejection for which cyclosporine A was administered; he died of septic shock as a consequence of immune deficiency a month later. The other two patients succumbed to other causes (myocardial infarction and hyperglycemia).

  20. 75 FR 78717 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2010-12-16

    ... Sample Access (PAR-10-90)-Type 1 Diabetes. Date: January 24, 2011. Time: 2 p.m. to 4 p.m. Agenda: To... in Diabetes. Date: January 25, 2011. Time: 2 p.m. to 5 p.m. Agenda: To review and evaluate grant... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the...

  1. 76 FR 20359 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2011-04-12

    ... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; PA10-067: Stem Cells and Diabetic Skin... Major Ongoing Clinical Research Studies in CKD (R01). Date: May 17, 2011. Time: 2 p.m. to 3:30 p.m... . (Catalogue of Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research...

  2. Conserved and Divergent Features of Human and Mouse Kidney Organogenesis.

    Science.gov (United States)

    Lindström, Nils O; McMahon, Jill A; Guo, Jinjin; Tran, Tracy; Guo, Qiuyu; Rutledge, Elisabeth; Parvez, Riana K; Saribekyan, Gohar; Schuler, Robert E; Liao, Christopher; Kim, Albert D; Abdelhalim, Ahmed; Ruffins, Seth W; Thornton, Matthew E; Basking, Laurence; Grubbs, Brendan; Kesselman, Carl; McMahon, Andrew P

    2018-03-01

    Human kidney function is underpinned by approximately 1,000,000 nephrons, although the number varies substantially, and low nephron number is linked to disease. Human kidney development initiates around 4 weeks of gestation and ends around 34-37 weeks of gestation. Over this period, a reiterative inductive process establishes the nephron complement. Studies have provided insightful anatomic descriptions of human kidney development, but the limited histologic views are not readily accessible to a broad audience. In this first paper in a series providing comprehensive insight into human kidney formation, we examined human kidney development in 135 anonymously donated human kidney specimens. We documented kidney development at a macroscopic and cellular level through histologic analysis, RNA in situ hybridization, immunofluorescence studies, and transcriptional profiling, contrasting human development (4-23 weeks) with mouse development at selected stages (embryonic day 15.5 and postnatal day 2). The high-resolution histologic interactive atlas of human kidney organogenesis generated can be viewed at the GUDMAP database (www.gudmap.org) together with three-dimensional reconstructions of key components of the data herein. At the anatomic level, human and mouse kidney development differ in timing, scale, and global features such as lobe formation and progenitor niche organization. The data also highlight differences in molecular and cellular features, including the expression and cellular distribution of anchor gene markers used to identify key cell types in mouse kidney studies. These data will facilitate and inform in vitro efforts to generate human kidney structures and comparative functional analyses across mammalian species. Copyright © 2018 by the American Society of Nephrology.

  3. An Assessment of Urinary Biomarkers in a Series of Declined Human Kidneys Measured During ex-vivo Normothermic Kidney Perfusion

    OpenAIRE

    Hosgood, Sarah Anne; Nicholson, Michael Lennard

    2016-01-01

    BACKGROUND: The measurement of urinary biomarkers during ex-vivo normothermic kidney perfusion (EVKP) may aid in the assessment of a kidney prior to transplantation. This study measured levels of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and endothelin-1 (ET-1) during EVKP in a series of discarded human kidneys. METHODS: Fifty six kidneys from deceased donors were recruited into the study. Each kidney underwent 60 minutes of EVKP and was scored based ...

  4. Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease

    DEFF Research Database (Denmark)

    de Zeeuw, Dick; Akizawa, Tadao; Audhya, Paul

    2013-01-01

    Although inhibitors of the renin-angiotensin-aldosterone system can slow the progression of diabetic kidney disease, the residual risk is high. Whether nuclear 1 factor (erythroid-derived 2)-related factor 2 activators further reduce this risk is unknown....

  5. 75 FR 33817 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2010-06-15

    ... Institute of Diabetes and Digestive and Kidney Diseases Special Emphasis Panel, Pathogenic Mechanisms in UTI... Diseases Special Emphasis Panel, Planning Grant for Ulcerative Colitis Trial in Children. Date: July 14...

  6. Kidney Measures with Diabetes and Hypertension on Cardiovascular Disease : The Atherosclerosis Risk in Communities Study

    NARCIS (Netherlands)

    Alexander, Nadine; Matsushita, Kunihiro; Sang, Yingying; Ballew, Shoshana; Mahmoodi, Bakhtawar K.; Astor, Brad C.; Coresh, Josef

    2015-01-01

    Background: Whether the association of chronic kidney disease (CKD) with cardiovascular risk differs based on diabetes mellitus (DM) and hypertension (HTN) status remains unanswered. Methods: We investigated 11,050 participants from the Atherosclerosis Risk in Communities Study (fourth examination

  7. 77 FR 27238 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2012-05-09

    ... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel, Tracking Adolescents after Bariatric Surgery. Date: May 25, 2012. Time: 11:00 a.m. to 12:00 p.m. Agenda: To review and evaluate grant...

  8. 76 FR 34717 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2011-06-14

    ... Digestive and Kidney Diseases Special Emphasis Panel, Teen-LABS. Date: July 15, 2011. Time: 2 p.m. to 2 p.m... Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and Nutrition...

  9. Vitamin D analogue therapy, cardiovascular risk and kidney function in people with Type 1 diabetes mellitus and diabetic nephropathy

    DEFF Research Database (Denmark)

    Joergensen, C; Tarnow, L; Goetze, J P

    2015-01-01

    AIM: To evaluate the effects of therapy with the vitamin D analogue paricalcitol on markers of cardiovascular risk and kidney function in people with Type 1 diabetes mellitus and diabetic nephropathy. METHODS: In a double-blind, randomized placebo-controlled, crossover trial, 48 participants on s...

  10. Skin tags associated with obesity and diabetes mellitus in patients with chronic kidney disease

    OpenAIRE

    Sari Funda; Inci Ayca; Dolu Suleyman; Sari Ramazan

    2017-01-01

    Introduction/Objective. Both chronic kidney disease and skin tags are associated with similar cardiovascular risk factors such as obesity, diabetes mellitus, dyslipidemia, hypertension, etc. The aim of this study was to determine the prevalence of skin tags in patients with chronic kidney disease, and to assess the relationship between skin tags and cardiovascular risk factors such as diabetes, hypertension, dyslipidemia, obesity, and metabolic syndrome. Methods. We evaluated 358 patients [14...

  11. High mortality in diabetic recipients of high KDPI deceased donor kidneys.

    Science.gov (United States)

    Pelletier, Ronald P; Pesavento, Todd E; Rajab, Amer; Henry, Mitchell L

    2016-08-01

    Deceased donor (DD) kidney quality is determined by calculating the Kidney Donor Profile Index (KDPI). Optimizing high KDPI (≥85%) DD transplant outcome is challenging. This retrospective study was performed to review our high KDPI DD transplant results to identify clinical practices that can improve future outcomes. We retrospectively calculated the KDPI for 895 DD kidney recipients transplanted between 1/2002 and 11/2013. Age, race, body mass index (BMI), retransplantation, gender, diabetes (DM), dialysis time, and preexisting coronary artery disease (CAD) (previous myocardial infarction (MI), coronary artery bypass (CABG), or stenting) were determined for all recipients. About 29.7% (266/895) of transplants were from donors with a KDPI ≥85%. By Cox regression older age, diabetes, female gender, and dialysis time >4 years correlated with shorter patient survival time. Diabetics with CAD who received a high KDPI donor kidney had a significantly increased risk of death (HR 4.33 (CI 1.82-10.30), P=.001) compared to low KDPI kidney recipients. The Kaplan-Meier survival curve for diabetic recipients of high KDPI kidneys was significantly worse if they had preexisting CAD (P<.001 by log-rank test). Patient survival using high KDPI donor kidneys may be improved by avoiding diabetic candidates with preexisting CAD. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. 78 FR 59945 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2013-09-30

    ... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Small Grants to Promote Diversity. Date... Diseases Special Emphasis Panel; Mechanisms of Upper Gut and Airway Interaction-Program Project Grant. Date..., Endocrinology and Metabolic Research; 93.848, Digestive Diseases and Nutrition Research; 93.849, Kidney Diseases...

  13. Diabetes mellitus and chronic kidney disease in the Eastern Mediterranean Region

    DEFF Research Database (Denmark)

    Mokdad, Ali H

    2017-01-01

    OBJECTIVES: We used findings from the Global Burden of Disease 2015 study to update our previous publication on the burden of diabetes and chronic kidney disease due to diabetes (CKD-DM) during 1990-2015. METHODS: We extracted GBD 2015 estimates for prevalence, mortality, and disability-adjusted ......OBJECTIVES: We used findings from the Global Burden of Disease 2015 study to update our previous publication on the burden of diabetes and chronic kidney disease due to diabetes (CKD-DM) during 1990-2015. METHODS: We extracted GBD 2015 estimates for prevalence, mortality, and disability......-adjusted life years (DALYs) of diabetes (including burden of low vision due to diabetes, neuropathy, and amputations and CKD-DM for 22 countries of the EMR from the GBD visualization tools. RESULTS: In 2015, 135,230 (95% UI 123,034-148,184) individuals died from diabetes and 16,470 (95% UI 13,977-18,961) from...

  14. Effect of spent turmeric on kidney glycoconjugates in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Kumar, Gurusiddaiah Suresh; Salimath, Paramahans Veerayya

    2014-01-01

    Curcumin known to have number of medicinal use and masked the fiber containing ukonan like active polysaccharide in turmeric and its pharmacological effect will be addressed on diabetic nephropathy particularly the glycoconjugates of extracellular components viz., glycoproteins and glycosaminoglycans - heparan sulfate (HS). Male Wistar rats were maintained on AIN-76 diet containing 10% spent turmeric and were grouped into control and STZ induced diabetes SFC/TFC and SFD/TFD, respectively. Diabetic status was monitored using blood and urine, and at the end, harvested kidneys were used to study the amelioration of glycoprotiens (collagen) and HS by enzymatic digestion, spectrophotometric, hydroxyproline and agarose electrophoretic methods. In the present study spent turmeric (10%) fed diabetic rats showed improved glomerular filtration rate (50%), kidney enlargement (60%) and other glycoconjugate metabolism in kidney. Increased collagen content in diabetic group was observed by hydroxyproline estimation (24%) and periodic acid-Schiff's (PAS) staining. Furthermore, elevated activities of enzymes involved in the synthesis and degradation of glycosaminoglycans (GAGs) were significantly lowered in spent turmeric fed diabetic group. Improvement in total GAGs (43%) and sulfate content (18%) followed by fractionation of GAGs using specific enzymes led to HS (28%) in the spent turmeric fed diabetic group, when compared to starch fed diabetic group and was further confirmed by electrophoresis of GAG. These results clearly indicate beneficial role of spent turmeric in controlling glycoconjugates such as glycoproteins and heparan sulfate related kidney complications during diabetes.

  15. Proteases in Plasma and Kidney of db/db Mice as Markers of Diabetes-Induced Nephropathy

    Science.gov (United States)

    Hadler-Olsen, E.; Winberg, J.-O.; Reinholt, F. P.; Larsen, T.; Uhlin-Hansen, L.; Jenssen, T.; Berg, E.; Kolset, S. O.

    2011-01-01

    Db/db mice are overweight, dyslipidemic and develop diabetic complications, relevant for similar complications in human type 2 diabetes. We have used db/db and db/+ control mice to investigate alterations in proteinase expression and activity in circulation and kidneys by SDS-PAGE zymography, electron microscopy, immunohistochemistry, Western blotting, and in situ zymography. Plasma from db/db mice contained larger amounts of serine proteinases compared to db/+ mice. Kidneys from the db/db mice had a significantly larger glomerular surface area and somewhat thicker glomerular basement membranes compared to the db/+ mice. Furthermore, kidney extracts from db/+ mice contained metalloproteinases with M r of approximately 92000, compatible with MMP-9, not observed in db/db mice. These results indicate that higher levels of serine proteinases in plasma may serve as potential markers for kidney changes in db/db mice, whereas a decrease in MMP-9 in the kidney may be related to the glomerular changes. PMID:22363890

  16. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease

    DEFF Research Database (Denmark)

    Pfeffer, Marc A; Burdmann, Emmanuel A; Chen, Chao-Yin

    2009-01-01

    BACKGROUND: Anemia is associated with an increased risk of cardiovascular and renal events among patients with type 2 diabetes and chronic kidney disease. Although darbepoetin alfa can effectively increase hemoglobin levels, its effect on clinical outcomes in these patients has not been adequately...... tested. METHODS: In this study involving 4038 patients with diabetes, chronic kidney disease, and anemia, we randomly assigned 2012 patients to darbepoetin alfa to achieve a hemoglobin level of approximately 13 g per deciliter and 2026 patients to placebo, with rescue darbepoetin alfa when the hemoglobin...... assigned to darbepoetin alfa and 496 patients assigned to placebo (Pchronic kidney disease...

  17. Diabetic kidney lesions of GIPRdn transgenic mice: podocyte hypertrophy and thickening of the GBM precede glomerular hypertrophy and glomerulosclerosis.

    Science.gov (United States)

    Herbach, Nadja; Schairer, Irene; Blutke, Andreas; Kautz, Sabine; Siebert, Angela; Göke, Burkhard; Wolf, Eckhard; Wanke, Ruediger

    2009-04-01

    Diabetic nephropathy is the leading cause of end-stage renal disease and the largest contributor to the total cost of diabetes care. Rodent models are excellent tools to gain more insight into the pathogenesis of diabetic nephropathy. In the present study, we characterize the age-related sequence of diabetes-associated kidney lesions in GIPR(dn) transgenic mice, a novel mouse model of early-onset diabetes mellitus. Clinical-chemical analyses as well as qualitative and quantitative morphological analyses of the kidneys of GIPR(dn) transgenic animals and nontransgenic littermate controls were performed at 3, 8, 20, and 28 wk of age. Early renal changes of transgenic mice consisted of podocyte hypertrophy, reduced numerical volume density of podocytes in glomeruli, and homogenous thickening of the glomerular basement membrane, followed by renal and glomerular hypertrophy as well as mesangial expansion and matrix accumulation. At 28 wk of age, glomerular damage was most prominent, including advanced glomerulosclerosis, tubulointerstitial lesions, and proteinuria. Real-time PCR demonstrated increased glomerular expression of Col4a1, Fn1, and Tgfb1. Immunohistochemistry revealed increased mesangial deposition of collagen type IV, fibronectin, and laminin. The present study shows that GIPR(dn) transgenic mice exhibit renal changes that closely resemble diabetes-associated kidney alterations in humans. Data particularly from male transgenic mice indicate that podocyte hypertrophy is directly linked to hyperglycemia, without the influence of mechanical stress. GIPR(dn) transgenic mice are considered an excellent new tool to study the mechanisms involved in onset and progression of diabetic nephropathy.

  18. Optical coherence tomography of the living human kidney

    Directory of Open Access Journals (Sweden)

    Peter M. Andrews

    2014-03-01

    Full Text Available Acute tubular necrosis (ATN induced by ischemia is the most common insult to donor kidneys destined for transplantation. ATN results from swelling and subsequent damage to cells lining the kidney tubules. In this study, we demonstrate the capability of optical coherence tomography (OCT to image the renal microstructures of living human donor kidneys and potentially provide a measure to determine the extent of ATN. We also found that Doppler-based OCT (i.e., DOCT reveals renal blood flow dynamics that is another major factor which could relate to post-transplant renal function. All OCT/DOCT observations were performed in a noninvasive, sterile and timely manner on intact human kidneys both prior to (ex vivo and following (in vivo their transplantation. Our results indicate that this imaging model provides transplant surgeons with an objective visualization of the transplant kidneys prior and immediately post transplantation.

  19. 76 FR 36554 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2011-06-22

    ... Special Emphasis Panel, Feasibility Studies for Clinical Trials in Type 1 Diabetes. Date: July 18, 2011..., 2011. Time: 1 to 5 p.m. Agenda: To review and evaluate grant applications. Place: National Institutes... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the...

  20. 77 FR 40368 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2012-07-09

    ... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel, Ancillary Studies to the Intestinal Stem Cells Consortium. Date: July 30, 2012. Time: 12 p.m. to 2 p.m. Agenda: To review and evaluate grant... Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases...

  1. Incidence of chronic kidney disease among people with diabetes: a systematic review of observational studies.

    Science.gov (United States)

    Koye, D N; Shaw, J E; Reid, C M; Atkins, R C; Reutens, A T; Magliano, D J

    2017-07-01

    The aim was to systematically review published articles that reported the incidence of chronic kidney disease among people with diabetes. A systematic literature search was performed using MEDLINE, Embase and CINAHL databases. The titles and abstracts of all publications identified by the search were reviewed and 10 047 studies were retrieved. A total of 71 studies from 30 different countries with sample sizes ranging from 505 to 211 132 met the inclusion criteria. The annual incidence of microalbuminuria and albuminuria ranged from 1.3% to 3.8% for Type 1 diabetes. For Type 2 diabetes and studies combining both diabetes types, the range was from 3.8% to 12.7%, with four of six studies reporting annual rates between 7.4% and 8.6%. In studies reporting the incidence of eGFR Disease (MDRD) equation, apart from one study which reported an annual incidence of 8.9%, the annual incidence ranged from 1.9% to 4.3%. The annual incidence of end-stage renal disease ranged from 0.04% to 1.8%. The annual incidence of microalbuminuria and albuminuria is ~ 2-3% in Type 1 diabetes, and ~ 8% in Type 2 diabetes or mixed diabetes type. The incidence of developing eGFR kidney disease, there was only modest variation in incidence rates. These findings may be useful in clinical settings to help understand the risk of developing kidney disease among those with diabetes. © 2017 Diabetes UK.

  2. A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

    DEFF Research Database (Denmark)

    van Zuydam, Natalie R; Ahlqvist, Emma; Sandholm, Niina

    2018-01-01

    complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined (T1D+T2D) GWAS was performed using complementary data available......Identification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight...... for subjects with T1D, which, with replication samples, involved up to 40,340 diabetic subjects (and 18,582 DKD cases).Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, p=4.5×10-8) associated with 'microalbuminuria' in European T2D cases. However, no replication...

  3. Use of intravoxel incoherent motion diffusion-weighted imaging to detect early changes in diabetic kidneys.

    Science.gov (United States)

    Deng, Yi; Yang, Biran; Peng, Yan; Liu, Zhiqiang; Luo, Jinwen; Du, Guoxin

    2018-03-14

    The purpose of the study was to examine differences in kidney intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) parameters in early-stage diabetic patients versus healthy controls. Nineteen type 2 diabetic patients (group A) with a urinary albumin-to-creatinine ratio (ACR) diabetic kidney changes was determined by receiver operating characteristic analysis. Three radiologists independently measured the parameters derived from IVIM-DWI in the two groups by free-hand placing regions of interest, and the interclass coefficients (ICCs) were analyzed by SPSS.16.0 software. The f values of the kidneys were significantly higher in diabetic patients than in healthy volunteers. The D value of the kidneys was significantly lower in diabetic patients than in healthy volunteers. No significant differences in the D* values of the kidneys were observed between diabetic patients and healthy volunteers. The D values of the right kidneys were significantly higher than those of the left kidneys in both groups. The results of the receiver operating characteristic analysis were as follows: left kidney-f value AUC = 0.650 (cutoff point ≥ 27.49%) and D value AUC = 0.752 (cutoff point ≤ 1.68 × 10 -3  mm 2 /s); and right kidney-f value AUC = 0.650 (cutoff point ≥ 28.24%) and D value AUC = 0.752 (cutoff point ≤ 1.81 × 10 -3 mm 2 /s). The diagnostic performance of the D* value was very low (AUC  0.05). The ICCs of the f value and D value were between 0.637 and 0.827. The ICC of the D* value was less than 0.3. The results of our study suggest that changes in kidneys detected by IVIM-DWI may serve as indicators of early diabetic kidney disease.

  4. Vitamin B and its derivatives for diabetic kidney disease.

    Science.gov (United States)

    Raval, Amit D; Thakker, Divyesh; Rangoonwala, Arohi N; Gor, Deval; Walia, Rama

    2015-01-12

    Diabetes is a leading cause of end-stage kidney disease (ESKD) mainly due to development and progression of diabetic kidney disease (DKD). In absence of definitive treatments of DKD, small studies showed that vitamin B may help in delaying progression of DKD by inhibiting vascular inflammation and endothelial cell damage. Hence, it could be beneficial as a treatment option for DKD. To assess the benefits and harms of vitamin B and its derivatives in patients with DKD. We searched the Cochrane Renal Group's Specialised Register to 29 October 2012 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. We included randomised controlled trials comparing vitamin B or its derivatives, or both with placebo, no treatment or active treatment in patients with DKD. We excluded studies comparing vitamin B or its derivatives, or both among patients with pre-existing ESKD. Two authors independently assessed study eligibility, risk of bias and extracted data. Results were reported as risk ratio (RR) or risk differences (RD) with 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) with 95% CI for continuous outcomes. Statistical analyses were performed using the random-effects model. Nine studies compared 1354 participants randomised to either vitamin B or its derivatives with placebo or active control were identified. A total of 1102 participants were randomised to single vitamin B derivatives, placebo or active control in eight studies, and 252 participants randomised to multiple vitamin B derivatives or placebo. Monotherapy included different dose of pyridoxamine (four studies), benfotiamine (1), folic acid (1), thiamine (1), and vitamin B12 (1) while combination therapy included folic acid, vitamin B6, and vitamin B12 in one study. Treatment duration ranged from two to 36 months. Selection bias was unclear in three studies and low in the remaining six studies. Two studies reported blinding of patient

  5. APOPTOSIS DURING HUMAN FETAL KIDNEY DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Rade Čukuranović

    2005-01-01

    Full Text Available Kidney morphogenesis is a complex and stepwise process. The formation of mature kidney in mammals is preceded by two primitive embryonic kidneys known as pronephros and mesonephros. Metanephros develops as a result of reciprocal inductive interactions between two primordial mesodermal derivates: ureteric bud, an epithelial outgrowth of the Wolffian duct, and metanephric blastema, a group of mesenchymal cells. The ureteric bud induces the metanephric mesenchyme to differentiate and form nephrons, whilst the metanephric mesenchyme induces the ureteric bud to grow and branch to form collecting ducts. The nephron goes through four developmental stages, which are described as: 1 vesicle, 2 comma-shaped and S-shaped stages, 3 developing capillary loop, and finally 4 maturing glomerulus. Apoptosis (programmed cell death is a predominant form of physiological cell death, by which organism eliminate unwanted or damaged cells. It is the major component of normal development and disease. Apoptosis is the result of series of biochemical processes happening in certain order in a dying cell, among which the most important is activation of enzyme families called caspases which influence different cell components. Apoptosis is characterized by membrane blebbing, shrinkage of the cell, nuclear fragmentation and chromatin condensation. Organelles are preserved almost intact. Cell surface molecules change. A variety of physiological and pathological stimuli can initiate apoptosis. They act via receptor mechanisms, through biochemical agents, or cause DNA and cell membrane damage. Apoptosis is an important component of fetal development. It is thought that apoptosis is the one of the main regulatory events involved in kidney morphogenesis, considering that among great number of developed cells, only a few of them are involved in the developing program by escaping apoptosis. In any period during kidney development about 3 to 5%of cells are apoptotic. Thorough

  6. Cadmium, type 2 diabetes, and kidney damage in a cohort of middle-aged women

    International Nuclear Information System (INIS)

    Barregard, Lars; Bergström, Göran; Fagerberg, Björn

    2014-01-01

    Background: It has been proposed that diabetic patients are more sensitive to the nephrotoxicity of cadmium (Cd) compared to non-diabetics, but few studies have examined this in humans, and results are inconsistent. Aim: To test the hypothesis that women with type 2 diabetes mellitus (DM) or impaired glucose tolerance (IGT) have higher risk of kidney damage from cadmium compared to women with normal glucose tolerance (NGT). Methods: All 64-year-old women in Gothenburg, Sweden, were invited to a screening examination including repeated oral glucose tolerance tests. Random samples of women with DM, IGT, and NGT were recruited for further clinical examinations. Serum creatinine was measured and used to calculate estimated glomerular filtration rate (eGFR). Albumin (Alb) and retinol-binding protein (RBP) were analyzed in a 12 h urine sample. Cadmium in blood (B-Cd) and urine (U-Cd) was determined using inductively coupled plasma mass spectrometry. Associations between markers of kidney function (eGFR, Alb, and RBP) and quartiles of B-Cd and U-Cd were evaluated in models, including also blood pressure and smoking habits. Results: The mean B-Cd (n=590) was 0.53 µg/L (median 0.34 µg/L). In multivariable models, a significant interaction was seen between high B-Cd (upper quartile, >0.56 µg/L) and DM (point estimate +0.40 mg Alb/12 h, P=0.04). In stratified analyzes, the effect of high B-Cd on Alb excretion was significant in women with DM (53% higher Alb/12 h, P=0.03), but not in women with IGT or NGT. Models with urinary albumin adjusted for creatinine showed similar results. In women with DM, the multivariable odds ratio (OR) for microalbuminuria (>15 mg/12 h) was increased in the highest quartile of B-Cd vs. B-Cd quartiles 1–3 in women with DM (OR 4.2, 95% confidence interval 1.1–12). No such effect was found in women with IGT or NGT. There were no associations between B-Cd and eGFR or excretion of RBP, and no differences between women with DM, IGT, or NGT

  7. Cadmium, type 2 diabetes, and kidney damage in a cohort of middle-aged women

    Energy Technology Data Exchange (ETDEWEB)

    Barregard, Lars, E-mail: lars.barregard@amm.gu.se [Occupational and Environmental Medicine, Sahlgrenska University Hospital and University of Gothenburg P.O. Box 414, SE-405 30 Gothenburg (Sweden); Bergström, Göran, E-mail: goran.bergstrom@wlab.gu.se [Sahlgrenska Center for Cardiovascular and Metabolic Research, Wallenberg Laboratory, Sahlgrenska University Hospital, SE-405 30 Gothenburg (Sweden); Department of Molecular and Clinical Medicine, University of Gothenburg, SE-405 30 Gothenburg (Sweden); Fagerberg, Björn, E-mail: bjorn.fagerberg@wlab.gu.se [Sahlgrenska Center for Cardiovascular and Metabolic Research, Wallenberg Laboratory, Sahlgrenska University Hospital, SE-405 30 Gothenburg (Sweden); Department of Molecular and Clinical Medicine, University of Gothenburg, SE-405 30 Gothenburg (Sweden)

    2014-11-15

    Background: It has been proposed that diabetic patients are more sensitive to the nephrotoxicity of cadmium (Cd) compared to non-diabetics, but few studies have examined this in humans, and results are inconsistent. Aim: To test the hypothesis that women with type 2 diabetes mellitus (DM) or impaired glucose tolerance (IGT) have higher risk of kidney damage from cadmium compared to women with normal glucose tolerance (NGT). Methods: All 64-year-old women in Gothenburg, Sweden, were invited to a screening examination including repeated oral glucose tolerance tests. Random samples of women with DM, IGT, and NGT were recruited for further clinical examinations. Serum creatinine was measured and used to calculate estimated glomerular filtration rate (eGFR). Albumin (Alb) and retinol-binding protein (RBP) were analyzed in a 12 h urine sample. Cadmium in blood (B-Cd) and urine (U-Cd) was determined using inductively coupled plasma mass spectrometry. Associations between markers of kidney function (eGFR, Alb, and RBP) and quartiles of B-Cd and U-Cd were evaluated in models, including also blood pressure and smoking habits. Results: The mean B-Cd (n=590) was 0.53 µg/L (median 0.34 µg/L). In multivariable models, a significant interaction was seen between high B-Cd (upper quartile, >0.56 µg/L) and DM (point estimate +0.40 mg Alb/12 h, P=0.04). In stratified analyzes, the effect of high B-Cd on Alb excretion was significant in women with DM (53% higher Alb/12 h, P=0.03), but not in women with IGT or NGT. Models with urinary albumin adjusted for creatinine showed similar results. In women with DM, the multivariable odds ratio (OR) for microalbuminuria (>15 mg/12 h) was increased in the highest quartile of B-Cd vs. B-Cd quartiles 1–3 in women with DM (OR 4.2, 95% confidence interval 1.1–12). No such effect was found in women with IGT or NGT. There were no associations between B-Cd and eGFR or excretion of RBP, and no differences between women with DM, IGT, or NGT

  8. Endoplasmic Reticulum Stress in the Diabetic Kidney, the Good, the Bad and the Ugly.

    Science.gov (United States)

    Cunard, Robyn

    2015-04-20

    Diabetic kidney disease is the leading worldwide cause of end stage kidney disease and a growing public health challenge. The diabetic kidney is exposed to many environmental stressors and each cell type has developed intricate signaling systems designed to restore optimal cellular function. The unfolded protein response (UPR) is a homeostatic pathway that regulates endoplasmic reticulum (ER) membrane structure and secretory function. Studies suggest that the UPR is activated in the diabetic kidney to restore normal ER function and viability. However, when the cell is continuously stressed in an environment that lies outside of its normal physiological range, then the UPR is known as the ER stress response. The UPR reduces protein synthesis, augments the ER folding capacity and downregulates mRNA expression of genes by multiple pathways. Aberrant activation of ER stress can also induce inflammation and cellular apoptosis, and modify signaling of protective processes such as autophagy and mTORC activation. The following review will discuss our current understanding of ER stress in the diabetic kidney and explore novel means of modulating ER stress and its interacting signaling cascades with the overall goal of identifying therapeutic strategies that will improve outcomes in diabetic nephropathy.

  9. Sodium-glucose co-transporter (SGLT) and glucose transporter (GLUT) expression in the kidney of type 2 diabetic subjects.

    Science.gov (United States)

    Norton, Luke; Shannon, Christopher E; Fourcaudot, Marcel; Hu, Cheng; Wang, Niansong; Ren, Wei; Song, Jun; Abdul-Ghani, Muhammad; DeFronzo, Ralph A; Ren, Jimmy; Jia, Weiping

    2017-09-01

    The sodium-glucose co-transporters (SGLTs) are responsible for the tubular reabsorption of filtered glucose from the kidney into the bloodstream. The inhibition of SGLT2-mediated glucose reabsorption is a novel and highly effective strategy to alleviate hyperglycaemia in patients with type 2 diabetes mellitus (T2DM). However, the effectiveness of SGLT2 inhibitor therapy is diminished due, in part, to a compensatory increase in the maximum reabsorptive capacity (Tm) for glucose in patients with T2DM. We hypothesized that this increase in Tm could be explained by an increase in the tubular expression of SGLT and glucose transporters (GLUT) in these patients. To examine this, we obtained human kidney biopsy specimens from patients with or without T2DM and examined the mRNA expression of SGLTs and GLUTs. The expression of SGLT1 is markedly increased in the kidney of patients with T2DM, and SGLT1 mRNA is highly and significantly correlated with fasting and postprandial plasma glucose and HbA1c. In contrast, our data demonstrate that the levels of SGLT2 and GLUT2 mRNA are downregulated in diabetic patients, but not to a statistically significant level. These important findings are clinically significant and may have implications for the treatment of T2DM using strategies that target SGLT transporters in the kidney. © 2017 John Wiley & Sons Ltd.

  10. Mitochondrial Reactive Oxygen Species and Kidney Hypoxia in the Development of Diabetic Nephropathy.

    Science.gov (United States)

    Schiffer, Tomas A; Friederich-Persson, Malou

    2017-01-01

    The underlying mechanisms in the development of diabetic nephropathy are currently unclear and likely consist of a series of dynamic events from the early to late stages of the disease. Diabetic nephropathy is currently without curative treatments and it is acknowledged that even the earliest clinical manifestation of nephropathy is preceded by an established morphological renal injury that is in turn preceded by functional and metabolic alterations. An early manifestation of the diabetic kidney is the development of kidney hypoxia that has been acknowledged as a common pathway to nephropathy. There have been reports of altered mitochondrial function in the diabetic kidney such as altered mitophagy, mitochondrial dynamics, uncoupling, and cellular signaling through hypoxia inducible factors and AMP-kinase. These factors are also likely to be intertwined in a complex manner. In this review, we discuss how these pathways are connected to mitochondrial production of reactive oxygen species (ROS) and how they may relate to the development of kidney hypoxia in diabetic nephropathy. From available literature, it is evident that early correction and/or prevention of mitochondrial dysfunction may be pivotal in the prevention and treatment of diabetic nephropathy.

  11. Diabetes mellitus, a complex and heterogeneous disease, and the role of insulin resistance as a determinant of diabetic kidney disease.

    Science.gov (United States)

    Karalliedde, Janaka; Gnudi, Luigi

    2016-02-01

    Diabetes mellitus (DM) is increasingly recognized as a heterogeneous condition. The individualization of care and treatment necessitates an understanding of the individual patient's pathophysiology of DM that underpins their DM classification and clinical presentation. Classical type-2 diabetes mellitus is due to a combination of insulin resistance and an insulin secretory defect. Type-1 diabetes is characterized by a near-absolute deficiency of insulin secretion. More recently, advances in genetics and a better appreciation of the atypical features of DM has resulted in more categories of diabetes. In the context of kidney disease, patients with DM and microalbuminuria are more insulin resistant, and insulin resistance may be a pathway that results in accelerated progression of diabetic kidney disease. This review summarizes the updated classification of DM, including more rarer categories and their associated renal manifestations that need to be considered in patients who present with atypical features. The benefits and limitations of the tests utilized to make a diagnosis of DM are discussed. We also review the putative pathways and mechanisms by which insulin resistance drives the progression of diabetic kidney disease. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  12. Triglycerides in the Human Kidney Cortex: Relationship with Body Size

    Science.gov (United States)

    Bobulescu, Ion Alexandru; Lotan, Yair; Zhang, Jianning; Rosenthal, Tara R.; Rogers, John T.; Adams-Huet, Beverley; Sakhaee, Khashayar; Moe, Orson W.

    2014-01-01

    Obesity is associated with increased risk for kidney disease and uric acid nephrolithiasis, but the pathophysiological mechanisms underpinning these associations are incompletely understood. Animal experiments have suggested that renal lipid accumulation and lipotoxicity may play a role, but whether lipid accumulation occurs in humans with increasing body mass index (BMI) is unknown. The association between obesity and abnormal triglyceride accumulation in non-adipose tissues (steatosis) has been described in the liver, heart, skeletal muscle and pancreas, but not in the human kidney. We used a quantitative biochemical assay to quantify triglyceride in normal kidney cortex samples from 54 patients undergoing nephrectomy for localized renal cell carcinoma. In subsets of the study population we evaluated the localization of lipid droplets by Oil Red O staining and measured 16 common ceramide species by mass spectrometry. There was a positive correlation between kidney cortex trigyceride content and BMI (Spearman R = 0.27, P = 0.04). Lipid droplets detectable by optical microscopy had a sporadic distribution but were generally more prevalent in individuals with higher BMI, with predominant localization in proximal tubule cells and to a lesser extent in glomeruli. Total ceramide content was inversely correlated with triglycerides. We postulate that obesity is associated with abnormal triglyceride accumulation (steatosis) in the human kidney. In turn, steatosis and lipotoxicity may contribute to the pathogenesis of obesity-associated kidney disease and nephrolithiasis. PMID:25170827

  13. Extending Metformin Use in Diabetic Kidney Disease: A Pharmacokinetic Study in Stage 4 Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Ajith Munasinghe Dissanayake

    2017-07-01

    Discussion: In our patient cohorts with diabetes and stage 4 chronic kidney disease, treatment with 4 weeks of low-dose metformin was not associated with adverse safety outcomes and revealed stable pharmacokinetics. Our study supports the liberalization of metformin use in this population and supports the use of metformin assays for more individualized dosing.

  14. Effect of alphatocopherol on diameter of proximal convoluted tubules of kidney in diabetic mice

    International Nuclear Information System (INIS)

    Rashid, S.

    2014-01-01

    Objective: To evaluate the effects of alphatocopherol supplement on proximal convoluted tubular diameter of kidney in diabetic mice. Methods: The randomised controlled trials was conducted partly at the National Institute of Health (NIH), Islamabad, and partly in Army Medical College, Rawalpindi, from November 2009 to November 2010. Thirty adult female mice BALB/C were randomly divided into three equal groups. Group A served as the control group. Group B was made diabetic by the intraperitoneal injection of streptozotocin. Group C received injection streptozotocin and was fed with alphatocopherol (vitamin E) supplemented diet. After 12 weeks, the animals were sacrificed and their kidneys were removed for histomorphological study. Results: Diabetes caused significant changes in the diameter of proximal tubule of Experimental Group B (diabetic) compared to the controls in Group A, but these changes were prevented in alphatocopherol treated Group C. Tubular diameter in Group B was significantly reduced compared to the Control Group A (p 0.05). Conclusion: Significant difference in proximal tubular diameter of kidneys between diabetic and alphatocopherol treated diabetic mice confirm that vitamin E does extend a protective role in improving diabetic nephropathy. (author)

  15. Evidence that kidney function but not type 2 diabetes determines retinol-binding protein 4 serum levels

    DEFF Research Database (Denmark)

    Henze, Andrea; Frey, Simone K; Raila, Jens

    2008-01-01

    It has been suggested that retinol-binding protein 4 (RBP4) links adiposity, insulin resistance, and type 2 diabetes. However, circulating RBP4 levels are also affected by kidney function. Therefore, the aim of this study was to test whether RBP4 serum levels are primarily associated with kidney...... function or type 2 diabetes....

  16. Precision Medicine Approaches to Diabetic Kidney Disease: Tissue as an Issue.

    Science.gov (United States)

    Gluck, Caroline; Ko, Yi-An; Susztak, Katalin

    2017-05-01

    Precision medicine approaches, that tailor medications to specific individuals has made paradigm-shifting improvements for patients with certain cancer types. Such approaches, however, have not been implemented for patients with diabetic kidney disease. Precision medicine could offer new avenues for novel diagnostic, prognostic and targeted therapeutics development. Genetic studies associated with multiscalar omics datasets from tissue and cell types of interest of well-characterized cohorts are needed to change the current paradigm. In this review, we will discuss precision medicine approaches that the nephrology community can take to analyze tissue samples to develop new therapeutics for patients with diabetic kidney disease.

  17. Urine RAS components in mice and people with type 1 diabetes and chronic kidney disease.

    Science.gov (United States)

    Wysocki, Jan; Goodling, Anne; Burgaya, Mar; Whitlock, Kathryn; Ruzinski, John; Batlle, Daniel; Afkarian, Maryam

    2017-08-01

    The pathways implicated in diabetic kidney disease (DKD) are largely derived from animal models. To examine if alterations in renin-angiotensin system (RAS) in humans are concordant with those in rodent models, we measured concentration of angiotensinogen (AOG), cathepsin D (CTSD), angiotensin-converting enzyme (ACE), and ACE2 and enzymatic activities of ACE, ACE2, and aminopeptidase-A in FVB mice 13-20 wk after treatment with streptozotocin ( n = 9) or vehicle ( n = 15) and people with long-standing type 1 diabetes, with ( n = 37) or without ( n = 81) DKD. In streptozotocin-treated mice, urine AOG and CTSD were 10.4- and 3.0-fold higher than in controls, respectively ( P animals ( P animals ( P = 0.017). Compared with people without DKD, those with DKD had higher urine AOG (170 vs. 15 μg/g) and CTSD (147 vs. 31 μg/g). In people with DKD, urine ACE concentration was 1.8-fold higher (1.4 vs. 0.8 μg/g in those without DKD), while its enzymatic activity was 0.6-fold lower (1.0 vs. 1.6 × 10 9 RFU/g in those without DKD). Lower ACE activity, but not ACE protein concentration, was associated with ACE inhibitor (ACEI) treatment. After adjustment for clinical covariates, AOG, CTSD, ACE concentration, and ACE activity remained associated with DKD. In conclusion, in mice with streptozotocin-induced diabetes and in humans with DKD, urine concentrations and enzymatic activities of several RAS components are concordantly increased, consistent with enhanced RAS activity and greater angiotensin II formation. ACEI use was associated with a specific reduction in urine ACE activity, not ACE protein concentration, suggesting that it may be a marker of exposure to this widely-used therapy. Copyright © 2017 the American Physiological Society.

  18. Synergistic Interaction of Hypertension and Diabetes in Promoting Kidney Injury and the Role of Endoplasmic Reticulum Stress.

    Science.gov (United States)

    Wang, Zhen; do Carmo, Jussara M; Aberdein, Nicola; Zhou, Xinchun; Williams, Jan M; da Silva, Alexandre A; Hall, John E

    2017-05-01

    Diabetes mellitus and hypertension are major risk factors for chronic kidney injury, together accounting for >70% of end-stage renal disease. In this study, we assessed interactions of hypertension and diabetes mellitus in causing kidney dysfunction and injury and the role of endoplasmic reticulum (ER) stress. Hypertension was induced by aorta constriction (AC) between the renal arteries in 6-month-old male Goto-Kakizaki (GK) type 2 diabetic and control Wistar rats. Fasting plasma glucose averaged 162±11 and 87±2 mg/dL in GK and Wistar rats, respectively. AC produced hypertension in the right kidney (above AC) and near normal blood pressure in the left kidney (below AC), with both kidneys exposed to the same levels of glucose, circulating hormones, and neural influences. After 8 weeks of AC, blood pressure above the AC (and in the right kidney) increased from 109±1 to 152±5 mm Hg in GK rats and from 106±4 to 141±5 mm Hg in Wistar rats. The diabetic-hypertensive right kidneys in GK-AC rats had much greater increases in albumin excretion and histological injury compared with left kidneys (diabetes mellitus only) of GK rats or right kidneys (hypertension only) of Wistar-AC rats. Marked increases in ER stress and oxidative stress indicators were observed in diabetic-hypertensive kidneys of GK-AC rats. Inhibition of ER stress with tauroursodeoxycholic acid for 6 weeks reduced blood pressure (135±4 versus 151±4 mm Hg), albumin excretion, ER and oxidative stress, and glomerular injury, while increasing glomerular filtration rate in hypertensive-diabetic kidneys. These results suggest that diabetes mellitus and hypertension interact synergistically to promote kidney dysfunction and injury via ER stress. © 2017 American Heart Association, Inc.

  19. Does Altered Uric Acid Metabolism Contribute to Diabetic Kidney Disease Pathophysiology?

    Science.gov (United States)

    Gul, Ambreen; Zager, Philip

    2018-03-01

    Multiple experimental and clinical studies have identified pathways by which uric acid may facilitate the development and progression of chronic kidney disease (CKD) in people with diabetes. However, it remains uncertain if the association of uric acid with CKD represents a pathogenic effect or merely reflects renal impairment. In contrast to many published reports, a recent Mendelian randomization study did not identify a causal link between uric acid and CKD in people with type 1 diabetes. Two recent multicenter randomized control trials, Preventing Early Renal Function Loss in Diabetes (PERL) and FEbuxostat versus placebo rAndomized controlled Trial regarding reduced renal function in patients with Hyperuricemia complicated by chRonic kidney disease stage 3 (FEATHER), were recently designed to assess if uric acid lowering slows progression of CKD. We review the evidence supporting a role for uric acid in the pathogenesis of CKD in people with diabetes and the putative benefits of uric acid lowering.

  20. New susceptibility loci associated with kidney disease in type 1 diabetes

    DEFF Research Database (Denmark)

    Sandholm, Niina; Salem, Rany M; McKnight, Amy Jayne

    2012-01-01

    Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion...... mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS) of T1D DN comprising ~2...... SNP in the ERBB4 gene (rs7588550, P = 2.1 × 10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN....

  1. Novel systems biology insights using antifibrotic approaches for diabetic kidney disease

    KAUST Repository

    RamachandraRao, Satish Posettihalli; Talwar, Priti; Ravasi, Timothy; Sharma, Kumar

    2010-01-01

    Although several interventions slow the progression of diabetic nephropathy, current therapies do not halt progression completely. Recent preclinical studies suggested that pirfenidone (PFD) prevents fibrosis in various diseases, but the mechanisms underlying its antifibrotic action are incompletely understood. To explore the therapeutic potential of PFD, we studied the PFD-treated db/db diabetic mouse kidney by liquid chromatography-tandem mass spectrometry proteomics. A total of 21 proteins unique to PFD-treated diabetic kidneys were identified. Analysis of gene ontology and protein-protein interactions of these proteins suggested that PFD may regulate RNA translation. Two key proteins involved in mRNA translation initiation and elongation were further evaluated and found to be regulated by PFD at the level of phosphorylation. In conclusion, insights from combining proteomics and bioinformatics improve the likelihood of rapid advancement of novel clinical therapies focused on reducing inflammation and fibrosis for diabetic complications. © 2010 Expert Reviews Ltd.

  2. Effect of Urtica dioica on morphometric indices of kidney in streptozotocin diabetic rats--a stereological study.

    Science.gov (United States)

    Golalipour, Mohammad Jafar; Gharravi, Anneh Mohammad; Ghafari, Sorya; Afshar, Mohammad

    2007-11-01

    The aim of the present study was to investigate the effect of Urtica dioica on Morphometric indices of kidney in diabetic rats. Thirty male adult albino wistar rats of 125-175 g divided into control, diabetic and Urtica dioica treatment groups. In treatment Group, diabetic rats received 100 mg kg(-1) daily hydroalcoholic extract of U. dioica intraperitoneally for 4 weeks. After the animals had been sacrified, the kidneys were removed and fixed by formaldehyde, cut horizontally into 1 mm slices and processed, Stained with H and E. Stereological study performed using light microscope and the image projected on a table of olysa software. Cavalieri principle was used to estimate the volume of cortex, medulla and whole kidney. All the grouped data statistically evaluated using Student's t-test, expressed as the Mean +/- SE. Ration of kidney weight/body weight in diabetes (0.51) and diabetes-extract group (0.67) were higher then control group (0.42). Ratio of kidney volume/body weight in diabetes (350) and diabetes-extract group (348) were higher then control group (323). Volume Ratio of cortex/medulla in diabetes-extract group (1.65) was higher then control (1.34) and diabetes group (1.33). Glomerular area and diameter and proximal tubule diameter in diabetes-Extract group was higher than control and diabetes groups. This study revealed that Urtica dioica has no effect on renal morphometric indices in induced diabetic rats.

  3. The kidney and type 2 diabetes mellitus: therapeutic implications of SGLT2 inhibitors.

    Science.gov (United States)

    Weir, Matthew R

    2016-01-01

    Understanding the role of the kidneys in type 2 diabetes mellitus (T2DM) has taken on an increased importance in recent years with the arrival of sodium-glucose co-transporter 2 (SGLT2) inhibitors - antihyperglycemic agents (AHAs) that specifically target the kidneys. This review includes an update on the physiology of the kidneys, their role in the pathophysiology of T2DM, and the mechanisms implicated in the development and progression of diabetic kidney disease, such as glomerular hyperfiltration and inflammation. It also discusses renal issues that could influence the choice of AHA for patients with T2DM, including special populations such as patients with concomitant chronic kidney disease. The most recent data published on the clinical efficacy and safety of the SGLT2 inhibitors canagliflozin, dapagliflozin, and empagliflozin and their effects on renal function are presented, showing how the renally mediated mechanisms of action of these agents translate into clinical benefits, including the potential for renoprotection. The observed positive effects of these agents on measures such as glucose control, estimated glomerular filtration rate, albumin-to-creatinine ratio, blood pressure, and body weight in patients both with and without impaired renal function suggest that SGLT2 inhibitors represent an important extension to the diabetes treatment armamentarium.

  4. Newly developed central diabetes insipidus following kidney transplantation: a case report.

    Science.gov (United States)

    Kim, K M; Kim, S M; Lee, J; Lee, S Y; Kwon, S K; Kim, H-Y

    2013-09-01

    Polyuria after kidney transplantation is a common, usually self-limiting disorder. However, persistent polyuria can cause not only patient discomfort, including polyuria and polydipsia, but also volume depletion that can produce allograft dysfunction. Herein, we have report a case of central diabetes insipidus newly diagnosed after kidney transplantation. A 45-year-old woman with end-stage kidney disease underwent deceased donor kidney transplantation. Two months after the transplantation, she was admitted for persistent polyuria, polydipsia, and nocturia with urine output of more than 4 L/d. Urine osmolarity was 100 mOsm/kg, which implied that the polyuria was due to water rather than solute diuresis. A water deprivation test was compatible with central diabetes insipidus; desmopressin treatment resulted in immediate symptomatic relief. Brain magnetic resonance imaging (MRI) demonstrated diffuse thickening of the pituitary stalk, which was considered to be nonspecific finding. MRI 12 months later showed no change in the pituitary stalk, although the patient has been in good health without polyuria or polydipsia on desmopressin treatment. The possibility of central diabetes insipidus should be considered in patients presenting with persistent polyuria after kidney transplantation. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. 78 FR 70063 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2013-11-22

    ... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; NIDDK Career Awards Review. Date: December 4, 2013. Time: 4:00 p.m. to 6:00 p.m. Agenda: To review and evaluate grant applications. Place..., (Telephone Conference Call). Contact Person: Carol J. Goter-Robinson, Ph.D., Scientific Review Officer...

  6. 76 FR 67749 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2011-11-02

    ... Intestinal Stem Cell Consortium (ISCC). Date: December 1, 2011. Time: 1 p.m. to 2:30 p.m. Agenda: To review... Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and Nutrition Research; 93.849, Kidney Diseases, Urology and Hematology Research, National Institutes...

  7. Azilsartan Improves Glycemic Status and Reduces Kidney Damage in Zucker Diabetic Fatty Rats

    Czech Academy of Sciences Publication Activity Database

    Khan, M. A. H.; Neckář, Jan; Haines, J.; Imig, J. D.

    2014-01-01

    Roč. 27, č. 8 (2014), s. 1087-1095 ISSN 0895-7061 R&D Projects: GA ČR(CZ) GA13-10267S Institutional support: RVO:67985823 Keywords : azilsartan medoxomil * blood pressure * hypertension * inflammation * kidney injury * oxidative stress * type 2 diabetes Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.852, year: 2014

  8. Hospital Readmissions in Diabetic Kidney Transplant Recipients with Peripheral Vascular Disease.

    Science.gov (United States)

    Lubetzky, Michelle; Kamal, Layla; Ajaimy, Maria; Akalin, Enver; Kayler, Liise

    2018-04-28

    The benefits of kidney transplantation in diabetic patients with peripheral vascular disease (PVD) are unclear. While patients may have improved survival compared to dialysis, the burden of care after transplant has not been assessed. We performed a retrospective review of adult diabetic kidney-only transplant recipients with and without PVD transplanted from January 2012 until June 30, 2015. Of 203 diabetic kidney transplant recipients, 56 (27.6%) had PVD and 147 (72.4%) had no PVD. At a median of 3.14 years follow up there were no significant differences in 30-, 90-, or 1-year readmission rates. At 1 year after transplant, PVD patients were significantly more likely to have a greater sum of unplanned inpatient days (44.6% versus 27.9% with ≥10 inpatient days, p=0.03) and at least one reoperation (28.6% vs. 8.7%, pPVD had significantly increased rates of non-graft related operations of which 31.2% were PVD related. Diabetic patients with PVD utilize more resources after kidney transplant, spending more time in the hospital and undergoing more post-transplant operations. The causes of readmission are predominantly related to progression of PVD rather than allograft complications. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  9. 77 FR 52042 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2012-08-28

    ... Racial and Ethnic Minority-PA10-236. Date: October 9, 2012. Time: 2 p.m. to 3 p.m. Agenda: To review and... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; DDK-C Conflicts. Date: October 18, 2012...

  10. Annual all-cause mortality rate for patients with diabetic kidney disease in Singapore

    Directory of Open Access Journals (Sweden)

    Yee Gary Ang

    2016-06-01

    Conclusion: Our study estimated the annual all-cause mortality rate for Singaporean patients with diabetic kidney disease by CKD stages and identified predictors of all-cause mortality. This study has affirmed the poor prognosis of these patients and an urgency to intervene early so as to retard the progression to later stages of CKD.

  11. Late Diabetic Complications in Patients with Type 1 Diabetes who Received Simultaneous Pancreas-Kidney Transplantation

    Directory of Open Access Journals (Sweden)

    Aleksandra Mikhaylovna Glazunova

    2015-03-01

    Full Text Available Aim. The aim of this study was to investigate late diabetic complications in patients with Type 1 diabetes mellitus (T1DM who received simultaneous pancreas-kidney transplantation (SPK.Materials and Methods. The study included 16 patients with T1DM who received SPK. All patients underwent clinical examination and diagnostic investigation.Results. After SPK, 93.75% of the patients had a functioning pancreas transplant, and 100% had a functioning kidney transplant within 4–48 months [mean 21 months (10 is revealed; 36. All patients had euglycaemia according to daily monitoring. The mean level of glycated haemoglobin (HbA1c before surgery was 9.1% (range 8.7%–11% and was 5.7% after surgery (5.55%–5.9%; p < 0.0001. The baseline level of insulin was 12.5 μIU/ml (11.4–15.3 μIU/ml and the baseline level of C-peptide was 2.02 ng/ml (1.07–2.77 ng/ml. Normal renal function was observed (glomerular filtration rate 76 ml/min/1.73 m2 (68–90 ml/min/1.73 m2. Other laboratory findings included haemoglobin 127 g/l (120–130 g/l, serum parathyroid hormone 77.5 pg/ml (61–85 pg/ml, serum phosphate 1.2 mmol/l (1.07–1.3 mmol/l and blood pressure 110(100–120/70(64–80 mmHg. In 37.5% of the patients, vitrectomy and additional laser panretinal photocoagulation were performed for proliferative diabetic retinopathy. Other ophthalmological disorders included newly diagnosed cataract (81.25%, secondary cataract (25% that required YAG discission in three patients, glaucoma (25% and macular oedema (12.5%. Ulcers of the lower extremities were observed in 31.25% of the patients, and chronic osteoarthropathy was observed in four. One patient underwent amputation of index and ring fingers and resection of the first and third metatarsal heads to treat osteomyelitis. One patient underwent balloon angioplasty and stenting for advanced atherosclerotic stenosis of blood vessels of the lower extremities.Conclusions. Euglycaemia and recovery of renal function

  12. Human renin biosynthesis and secretion in normal and ischemic kidneys

    International Nuclear Information System (INIS)

    Pratt, R.E.; Carleton, J.E.; Richie, J.P.; Heusser, C.; Dzau, V.J.

    1987-01-01

    The pathway of renin biosynthesis and secretion in normal and ischemic human kidneys has been investigated by pulse-labeling experiments. The results indicate that in normal human kidney, preprorenin is rapidly processed to 47-kDa prorenin. Microradiosequencing showed that this molecule was generated by cleavage between Gly-23 and Leu-24, yielding a 43-amino acid proregion. Analysis of prorenin secreted by the kidney tissue yielded an identical sequence, indicating that prorenin is secreted without any further proteolysis. An examination of the kinetics of processing and secretion suggested that a majority of the newly synthesized prorenin is quickly secreted, while only a small fraction is processed intracellularly to the mature renin. The differences in secretion kinetics between prorenin and mature renin and the selective inhibition of prorenin secretion by monensin suggest that they are secreted independently via two pathways: a constitutive pathway probably from the Golgi or protogranules that rapidly release prorenin and a regulated pathway that secretes mature renin from the mature granules. A comparison of the kinetics of processing between normal and ischemic tissues suggests that renal ischemia leads to an overall increase in the rate of processing or prorenin to mature renin. In addition, prolonged biosynthetic labeling of renin in the ischemic kidney yielded two smaller molecular weight immunoreactive forms suggestive of renin fragments that may be degradative products. These fragments were not detected in normal kidney tissue labeled for similar lengths of time

  13. Lactate levels and risk of lactic acidosis with metformin in diabetic kidney disease patients

    Directory of Open Access Journals (Sweden)

    P K Bipi

    2017-01-01

    Full Text Available Metformin as an oral antidiabetic drug (OAD is not recommended in renal failure due to the presumed risk of lactic acidosis though it has advantages in cardiovascular protection with a low risk of hypoglycemia. Few studies have measured lactic acid blood levels in patients with diabetic kidney disease on metformin and demonstrated lactic acidosis. The aim of our study is to see if patients with diabetic kidney disease are at risk of elevated lactate blood levels and lactic acidosis. Lactate levels and blood pH were estimated in patients with type 2 diabetes mellitus receiving metformin in different stages of chronic kidney disease (CKD and were compared with a similar group not receiving metformin. Patients with diabetic kidney disease, with estimated glomerular filtration rate <60 mL/min who were previously receiving metformin started in centers elsewhere and referred here were studied and compared with a similar group taking other OADs or insulin. Independent sample t-test or ANOVA were used to compare quantitative variables between groups. Pearson correlation was used to analyze association between quantitative variables and linear regression analysis and was employed to note the relationship between quantitative variables. Of 57 patients who received a mean dose of 1.134 grams of metformin, 33 (55.9% were in stage 3, 16 (28.1% in stage 4, and 8 (14% in stage 5 CKD. Mean serum pH (P = 0.572, bicarbonate (P = 0.978, and plasma lactate (P = 0.449 levels in those taking and not taking metformin were comparable. There was no difference in the plasma lactate levels in different stages of CKD in the metformin group (P = 0.498 although there was significant correlation with metformin dose (P <0.05. Blood lactate levels were not elevated in patients with diabetic kidney disease at a daily dose of metformin <1 g.

  14. Chronic Kidney Disease and Associated Cardiovascular Risk Factors in Chinese with Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Qing-Lin Lou

    2012-12-01

    Full Text Available BackgroundTo determine the frequency of chronic kidney disease (CKD and its associated risk factors in Chinese type 2 diabetic patients, we conducted a cross-sectional study in Nanjing, China, in the period between January 2008 and December 2009.MethodsPatients with type 2 diabetes under the care by Jiangsu Province Official Hospital, Nanjing, China were invited for assessment. CKD was defined as the presence of albuminuria or estimated glomerular filtration rate <60 mL/min/1.73 m2. Albuminuria was defined as urinary albumin-to-creatinine ratio ≥30 mg/g.ResultsWe recruited 1,521 urban Chinese patients with type 2 diabetes (mean age, 63.9±12.0 years. The frequency of CKD and albuminuria was 31.0% and 28.9%, respectively. After adjusted by age and sex, hypertension, anemia and duration of diabetes were significantly associated with CKD with odds ratio (95% confidence interval being 1.93 (1.28 to 2.93, 1.70 (1.09 to 2.64, and 1.03 (1.00 to 1.06, respectively.ConclusionIn conclusion, CKD was common in the urban Nanjing Chinese with type 2 diabetes. Strategies to prevent or delay progression of kidney disease in diabetes should be carried out at the early disease course of type 2 diabetes.

  15. Simultaneous pancreas and kidney transplantation as the standard surgical treatment for diabetes mellitus patients with end-stage renal disease.

    Science.gov (United States)

    Chan, C M; Chim, Thomas M Y; Leung, K C; Tong, C H; Wong, T F; Leung, Gilberto K K

    2016-02-01

    To review the outcome following simultaneous pancreas and kidney transplantation in patients with type 1 diabetes mellitus and end-stage renal disease, as well as those with type 2 diabetes mellitus, and to discuss the applicability of this treatment in this locality. A systematic literature review was performed by searching the PubMed and Elsevier databases. The search terms used were "simultaneous pancreas and kidney transplantation", "diabetes", "pancreas transplant" and "SPK". Original and major review articles related to simultaneous pancreas and kidney transplantation were reviewed. Papers published in English after 1985 were included. Clinical outcomes following transplantation were extracted for comparison between different treatment methods. Outcomes of simultaneous pancreas and kidney transplant and other transplantation methods were identified and categorised into patient survival, graft survival, diabetic complications, and quality of life. Patient survivals and graft survivals were also compared. Currently available clinical evidence shows good outcomes for type 1 diabetes mellitus in terms of patient survival, graft survival, diabetic complications, and quality of life. For type 2 diabetes mellitus, the efficacy and application of the procedure remain controversial but the outcomes are possibly comparable with those in type 1 diabetes mellitus. Simultaneous pancreas and kidney transplantation is a technically demanding procedure that is associated with significant complications, and it should be regarded as a 'last resort' treatment in patients whose diabetic complications have become life-threatening or severely burdensome despite best efforts in maintaining good diabetic control through lifestyle modifications and medications.

  16. [Rhein promotes the expression of SIRT1 in kidney tissues of type 2 diabetic rat].

    Science.gov (United States)

    Chen, Weidong; Chang, Baochao; Zhang, Yan; Yang, Ping; Liu, Lei

    2015-05-01

    To observe the effect of rhein on the expression of SIRT1(Sirtuin 1) in kidney of diabetic rats, and to explore the role of rhein in protecting rat kidney against diabetic nephropathy and possible mechanism. The type 2 diabetic rats were induced by high-glucose and high-fat diet combined with streptozotocin (35 mg/kg body mass). Seventy-five eight-week-old male SD rats were randomly divided into 6 groups: normal group, diabetic group, low-, medium- and high-dose (50, 100, 150 mg/kg) rhein treatment groups and 10 mg/kg pioglitazone treatment group. The rats were given corresponding substances intragastrically once a day. At the end of the 16th week, the fasting plasma glucose (FPG), fasting insulin (FINS), triglycerides (TG), total cholesterol (TC), serum creatinine (Scr) and 24 hours urine protein (24 h U-PRO) were determined. The renal hypertrophy index (KM/BM), insulin resistance index (HOMA-IR) were calculated. The pathological changes in renal tissues were examined by PAS staining under a light microscopy. The mean glomerular area (MGA) and mean glomerular volume (MGV) were measured by pathological image analysis system. Western blotting and real-time quantitative PCR were used to determine the expression of SIRT1 in renal tissues at protein and mRNA levels, respectively. The expression of SIRT1 was down-regulated in the kidney of diabetic rats. The levels of FPG, FINS, HOMA-IR, TG, TC, Scr, 24 h U-PRO, KM/BM, MGA and MGV significantly decreased and the histopathology of renal tissues were significantly improved in all treatment groups compared with diabetic group. The expression of SIRT1 mRNA and protein markedly increased in rhein treatment groups and pioglitazone treatment group compared with diabetic group. The indicators in high-dose rhein treatment group were improved more significantly than those in the other groups. Correlation analysis showed that the expression of SIRT1 was negatively correlated with 24 h U-PRO and MGV. The expression of SIRT1 was

  17. Urinary acylcarnitines are altered in human kidney cancer.

    Science.gov (United States)

    Ganti, Sheila; Taylor, Sandra L; Kim, Kyoungmi; Hoppel, Charles L; Guo, Lining; Yang, Joy; Evans, Christopher; Weiss, Robert H

    2012-06-15

    Kidney cancer often diagnosed at late stages when treatment options are severely limited. Thus, greater understanding of tumor metabolism leading ultimately to novel approaches to diagnosis is needed. Our laboratory has been utilizing metabolomics to evaluate compounds appearing in kidney cancer patients' biofluids at concentrations different from control patients. Here, we collected urine samples from kidney cancer patients and analyzed them by chromatography coupled to mass spectrometry. Once normalized to control for urinary concentration, samples were analyzed by two independent laboratories. After technical validation, we now show differential urinary concentrations of several acylcarnitines as a function of both cancer status and kidney cancer grade, with most acylcarnitines being increased in the urine of cancer patients and in those patients with high cancer grades. This finding was validated in a mouse xenograft model of human kidney cancer. Biological validation shows carbon chain length-dependent effects of the acylcarnitines on cytotoxicity in vitro, and higher chain length acylcarnitines demonstrated inhibitory effects on NF-κB activation, suggesting an immune modulatory effect of these compounds. Thus, acylcarnitines in the kidney cancer urine may reflect alterations in metabolism, cell component synthesis and/or immune surveillance, and may help explain the profound chemotherapy resistance seen with this cancer. This study shows for the first time the value of a novel class of metabolites which may lead to new therapeutic approaches for cancer and may prove useful in cancer biomarker studies. Furthermore, these findings open up a new area of investigation into the metabolic basis of kidney cancer. Copyright © 2011 UICC.

  18. Kidney in diabetes: from organ damage target to therapeutic target.

    Science.gov (United States)

    Salvatore, Teresa; Carbonara, Ornella; Cozzolino, Domenico; Torella, Roberto; Nasti, Rodolfo; Lascar, Nadia; Sasso, Ferdinando Carlo

    2011-09-01

    Despite the growing of pharmacological options for the treatment of diabetes, epidemiological studies suggest that a substantial proportion of patients does not achieve glycemic goals and so suffers from the risk of chronic complications. This review explores the inhibition of renal glucose reabsorption as a novel approach to treat hyperglycemia. Sodium-glucose cotransporter 2 (SGLT2), a low-affinity high-capacity transporter located in the brush-border membrane of the early segment (S1) of the proximal renal tubule, accounts for about 90% of the reabsorption of glucose from tubular fluid. Competitive inhibitors of SGLT2 that are responsible for renal excretion of glucose provide a unique mechanism to potentially lower the elevated blood glucose levels in patients with diabetes. They act independently of insulin secretion, thereby minimizing the risk of hypoglycemia and weight gain, to control energy balance in a negative direction, a distinctive advantage of this class of drugs over existing oral hypoglycemic agents. Although this group of medications is still under investigation, it appears to be safe and generally well tolerated and it would be expected to improve the treatment of type 2 diabetes as monotherapy or in combination with other oral or parenteral agents. Dapagliflozin is the first agent within this class, which induces clinically meaningful reductions in FPG, PPG, HbA1c, and body weight in type 2 diabetes.

  19. MicroRNAs in Kidney Fibrosis and Diabetic Nephropathy: Roles on EMT and EndMT

    Directory of Open Access Journals (Sweden)

    Swayam Prakash Srivastava

    2013-01-01

    Full Text Available MicroRNAs (miRNAs are a family of small, noncoding RNAs that regulate gene expression in diverse biological and pathological processes, including cell proliferation, differentiation, apoptosis, and carcinogenesis. As a result, miRNAs emerged as major area of biomedical research with relevance to kidney fibrosis. Fibrosis is characterized by the excess deposition of extracellular matrix (ECM components, which is the end result of an imbalance of metabolism of the ECM molecule. Recent evidence suggests that miRNAs participate in the fibrotic process in a number of organs including the heart, kidney, liver, and lung. Epithelial mesenchymal transition (EMT and endothelial mesenchymal transition (EndMT programs play vital roles in the development of fibrosis in the kidney. A growing number of the extracellular and intracellular molecules that control EMT and EndMT have been identified and could be exploited in developing therapeutics for fibrosis. This review highlights recent advances on the role of miRNAs in the kidney diseases; diabetic nephropathy especially focused on EMT and EndMT program responsible for the development of kidney fibrosis. These miRNAs can be utilized as a potential novel drug target for the studying of underlying mechanism and treatment of kidney fibrosis.

  20. Serum Cystatin C as an Early Diagnostic Biomarker of Diabetic Kidney Disease in Type 2 Diabetic Patients.

    Science.gov (United States)

    Qamar, Ayesha; Hayat, Asma; Ahmad, Tariq Mahmood; Khan, Alamgir; Hasnat, Mohammad Najam Ul; Tahir, Sufyan

    2018-04-01

    To determine the diagnostic accuracy and cut-off values of serum cystatin C as early diagnostic biomarker of diabetic kidney disease. Cross-sectional analytical study. Department of Pathology, Army Medical College, Rawalpindi in collaboration with Endocrinology Department, Military Hospital (MH), Rawalpindi from November 2015 to November 2016. One hundred and nineteen diagnosed patients of type 2 diabetes mellitus were enrolled in the study from the outpatient Endocrinology Department of the MH Rawalpindi. Fifty disease-free controls were also included. Fasting blood samples of the patients and controls were analysed for creatinine by Jaffé's kinetic method and estimated GFR was calculated using MDRD-based equation for GFR. Serum cystatin C was estimated by quantitative turbidimetric method. Serum cystatin C was higher in the diabetic group (mean = 1.022 ±0.33 mg/dl) as compared to the control group (mean = 0.63 ±0.14 mg/dl). ROC curve analysis, keeping less than 60 ml/min/1.73 m2 GFR (CKD-MDRD based) as reference value of the stat variable/gold standard; revealed an area under the curve of 0.914 (95% CI 0.85-0.98) and at optimal sensitivity of 88.2% and specificity of 84.8% the established cut-off of serum cystatin C was 1.26 mg/L. Cystatin C is an accurate biomarker of diabetic kidney disease with good sensitivity and specificity.

  1. Effects of Short Term Exposure of Atrazine on the Liver and Kidney of Normal and Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Dinesh Babu Jestadi

    2014-01-01

    Full Text Available The present study evaluates the effects of short term (15 days exposure of low dose (300 μg kg−1 of atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine on antioxidant status and markers of liver and kidney damage in normal (nondiabetic and diabetic male Wistar rats. Rats were divided into four groups: Group I as normal control, Group II as atrazine treated, Group III as diabetic control, and Group IV as atrazine treated diabetic rats. Atrazine administration resulted in increased MDA concentration as well as increased activities of SOD, CAT, and GPx in both liver and kidney of atrazine treated and atrazine treated diabetic rats. However, GSH level was decreased in both liver and kidney of atrazine treated and atrazine treated diabetic rats. Atrazine administration led to significant increase in liver damage biomarkers such as AST, ALT, and ALP as well as kidney damage biomarkers such as creatinine and urea in both normal and diabetic rats, but this increase was more pronounced in diabetic rats when compared to normal rats. In conclusion, the results of the present study demonstrate that short term exposure of atrazine at a dose of 300 μg kg−1 could potentially induce oxidative damage in liver and kidney of both normal and diabetic rats.

  2. Evidence of chronic kidney disease in veterans with incident diabetes mellitus.

    Science.gov (United States)

    Gatwood, Justin; Chisholm-Burns, Marie; Davis, Robert; Thomas, Fridtjof; Potukuchi, Praveen; Hung, Adriana; Kovesdy, Csaba P

    2018-01-01

    While chronic kidney disease (CKD) is regularly evaluated among patients with diabetes, kidney function may be significantly impaired before diabetes is diagnosed. Moreover, disparities in the severity of CKD in such a population are likely. This study evaluated the extent of CKD in a national cohort of 36,764 US veterans first diagnosed with diabetes between 2003 and 2013 and prior to initiating oral antidiabetic therapy. Evidence of CKD (any stage) at the time of diabetes diagnosis was determined using eGFR and urine-albumin-creatinine ratios, the odds of which were assessed using logistic regression controlling for patient characteristics. CKD was evident in 31.6% of veterans prior to being diagnosed with diabetes (age and gender standardized rates: 241.8 per 1,000 adults [overall] and 247.7 per 1,000 adult males), over half of whom had at least moderate kidney disease (stage 3 or higher). The odds of CKD tended to increase with age (OR: 1.88; 95% CI: 1.82-1.93), hemoglobin A1C (OR: 1.05; 95% CI: 1.04-1.06), systolic blood pressure (OR: 1.04; 95% CI: 1.027-1.043), and BMI (OR: 1.016; 95% CI: 1.011-1.020). Both Asian Americans (OR: 1.53; 95% CI: 1.15-2.04) and African Americans (OR: 1.11; 95% CI: 1.03-1.20) had higher adjusted odds of CKD compared to whites, and prevalence was highest in the Upper Midwest and parts of the Mid-South. Results suggest that evidence of CKD is common among veterans before a diabetes diagnosis, and certain populations throughout the country, such as minorities, may be afflicted at higher rates.

  3. Human genetics of diabetic vascular complications

    Indian Academy of Sciences (India)

    Abstract. Diabetic vascular complications (DVC) affecting several important organ systems of human body such as the ..... cohort with nominal significance, and a recent meta-analysis ..... Whereas it is generally thought that lysine acetylation is.

  4. [Prerenal kidney failure in type 1 diabetes mellitus].

    Science.gov (United States)

    Schloot, N C; Hübinger, A; Scherbaum, W A

    2003-12-05

    A 22-year-old man was admitted in a severely reduced condition. Type 1 diabetes mellitus had been diagnosed when he was 13 years old, hypothyroidism was treated with L-thyroxine for 2 years. For the past 3 years he suffered from repetitive hypoglycemia, combined with vertigo, weakness and low blood pressure. He presented with hypotension and hyperpigmentation of the skin. Pathological laboratory results were: serum creatinine 2.5 mg/dl; urea 145 mg/dl; sodium 124 mmol/l; potassium 8.3 mmol/l, HbA (1c) 9.1%. The ECG showed large T waves. Additionally, plasma aldosterone was decreased (diabetes mellitus type 1 and hypothyroidism (Schmidt-Carpenter-Syndrome) were diagnosed. Initially, the patient was treated with sodium chloride 0.9% i. v. and oral sodium 5 g 4 times/day. In addition, he was given hydrocortisone 100 mg i. v., and then switched to 40 mg per day (20-10-10 mg), fludrocortisone 0.05 mg/ day and L-thyroxine 75 microg/ day orally the clinical condition improved dramatically within 24 hours. Intensified conventional insulin therapy was continued. In patients with type 1 diabetes, especially in combination with associated organ-specific autoimmune diseases, autoimmune polyglandular syndrome should be considered and adequately treated with those hormones that are reduced.

  5. Family clustering of secondary chronic kidney disease with hypertension or diabetes mellitus. A case-control study.

    Science.gov (United States)

    de Almeida, Fernando Antonio; Ciambelli, Giuliano Serafino; Bertoco, André Luz; Jurado, Marcelo Mai; Siqueira, Guilherme Vasconcelos; Bernardo, Eder Augusto; Pavan, Maria Valeria; Gianini, Reinaldo José

    2015-02-01

    In Brazil hypertension and type 2 diabetes mellitus are responsible for 60% of cases of end-stage renal disease in renal replacement therapy. In the United States studies have identified family clustering of chronic kidney disease, predominantly in African-Americans. A single Brazilian study observed family clustering among patients with chronic kidney disease when compared with hospitalized patients with normal renal function. This article aims to assess whether there is family clustering of chronic kidney disease in relatives of individuals in renal replacement therapy caused by hypertension and/or diabetes mellitus. A case-control study with 336 patients in renal replacement therapy with diabetes mellitus or hypertension for at least 5 years (cases) and a control matched sample group of individuals with hypertension or diabetes mellitus and normal renal function (n = 389). Individuals in renal replacement therapy (cases) had a ratio of 2.35 (95% CI 1.42-3.89, p hypertension or diabetes mellitus).

  6. The role of irrational thought in medicine adherence: people with diabetic kidney disease.

    Science.gov (United States)

    Williams, Allison F; Manias, Elizabeth; Walker, Rowan

    2009-10-01

    This paper is a report of a study conducted to examine how irrational thinking affects people's adherence to multiple medicines prescribed to manage their diabetic kidney disease. Approximately 50% of people are non-adherent to their prescribed medicines and the risk of non-adherence escalates as the number of prescribed medicines increases. Adherence to prescribed medicines can slow disease progression in diabetic kidney disease. A descriptive exploratory design was used. In-depth interviews were conducted with 23 participants recruited from a nephrology outpatient clinic in Australia in 2007. Data were analysed using a 'framework' method. Participants' mean age was 59 years, they had approximately six chronic conditions in addition to their diabetic kidney disease and were prescribed a median of ten medicines daily. Two major themes of irrational thinking--heuristics and denial--and subthemes were identified. Heuristics contributed to inaccurate risk assessment and biases affecting rational judgement concerning medicines, whereas denial was used to enhance coping necessary to manage this complex health condition. Participants underestimated their health risks because they had been taking medicines for many years and preferred not to dwell on their ill health. A large amount of irrational thinking was related to maintaining the emotional strength necessary to manage their comorbid conditions as best they could. Regular assessment and support of medicine adherence throughout the disease course is necessary to avert the development of counterproductive heuristics and denial affecting medicine adherence.

  7. Hemoglobin A1c Levels Predicts Acute Kidney Injury after Coronary Artery Bypass Surgery in Non-Diabetic Patients

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    Cevdet Ugur Kocogulları

    Full Text Available Abstract INTRODUCTION: Elevated hemoglobin A1c levels in patients with diabetes mellitus have been known as a risk factor for acute kidney injury after coronary artery bypass grafting. However, the relationship between hemoglobin A1c levels in non-diabetics and acute kidney injury is under debate. We aimed to investigate the association of preoperative hemoglobin A1c levels with acute kidney injury in non-diabetic patients undergoing isolated coronary artery bypass grafting. METHODS: 202 non-diabetic patients with normal renal function (serum creatinine <1.4 mg/dl who underwent isolated coronary bypass were analyzed. Hemoglobin A1c level was measured at the baseline examination. Patients were separated into two groups according to preoperative Hemoglobin A1c level. Group 1 consisted of patients with preoperative HbA1c levels of < 5.6% and Group 2 consisted of patients with preoperative HbA1c levels of ≥ 5.6%. Acute kidney injury diagnosis was made by comparing baseline and postoperative serum creatinine to determine the presence of predefined significant change based on the Kidney Disease Improving Global Outcomes (KDIGO definition. RESULTS: Acute kidney injury occurred in 19 (10.5% patients after surgery. The incidence of acute kidney injury was 3.6% in Group 1 and 16.7% in Group 2. Elevated baseline hemoglobin A1c level was found to be associated with acute kidney injury (P=0.0001. None of the patients became hemodialysis dependent. The cut off value for acute kidney injury in our group of patients was 5.75%. CONCLUSION: Our findings suggest that, in non-diabetics, elevated preoperative hemoglobin A1c level may be associated with acute kidney injury in patients undergoing coronary artery bypass grafting. Prospective randomized studies in larger groups are needed to confirm these results.

  8. Dietary Approaches in the Management of Diabetic Patients with Kidney Disease.

    Science.gov (United States)

    Ko, Gang Jee; Kalantar-Zadeh, Kamyar; Goldstein-Fuchs, Jordi; Rhee, Connie M

    2017-07-31

    Chronic kidney disease (CKD) is one of the most prevalent complications of diabetes, and patients with diabetic kidney disease (DKD) have a substantially higher risk of cardiovascular disease and death compared to their non-diabetic CKD counterparts. In addition to pharmacologic management strategies, nutritional and dietary interventions in DKD are an essential aspect of management with the potential for ameliorating kidney function decline and preventing the development of other end-organ complications. Among DKD patients with non-dialysis dependent CKD, expert panels recommend lower dietary protein intake of 0.8 g/kg of body weight/day, while higher dietary protein intake (>1.2 g/kg of body weight/day) is advised among diabetic end-stage renal disease patients receiving maintenance dialysis to counteract protein catabolism, dialysate amino acid and protein losses, and protein-energy wasting. Carbohydrates from sugars should be limited to less than 10% of energy intake, and it is also suggested that higher polyunsaturated and monounsaturated fat consumption in lieu of saturated fatty acids, trans-fat, and cholesterol are associated with more favorable outcomes. While guidelines recommend dietary sodium restriction to less than 1.5-2.3 g/day, excessively low sodium intake may be associated with hyponatremia as well as impaired glucose metabolism and insulin sensitivity. As patients with advanced DKD progressing to end-stage renal disease may be prone to the "burnt-out diabetes" phenomenon (i.e., spontaneous resolution of hypoglycemia and frequent hypoglycemic episodes), further studies in this population are particularly needed to determine the safety and efficacy of dietary restrictions in this population.

  9. Lycopene Protects the Diabetic Rat Kidney Against Oxidative Stress-mediated Oxidative Damage Induced by Furan

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    Dilek Pandir

    2016-01-01

    Full Text Available Furan is a food and environmental contaminant and a potent carcinogen in animals. Lycopene is one dietary carotenoid found in fruits such as tomato, watermelon and grapefruit. The present study was designed to explore the protective effect of lycopene against furan-induced oxidative damage in streptozotocin (STZ-induced diabetic rat kidney. At the end of the experimental period (28 days, we found that lycopene markedly decreased the malondialdehide (MDA levels in the kidney, urea, uric acid and creatinine levels in the serum of furan-treated rats. The increase of histopathology in the kidney of furan-treated rats were effectively suppressed by lycopene. Furthermore, lycopene markedly restored superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPx and glutathione-S-transferase (GST activities in the kidney of furan-treated rats. In conclusion, these results suggested that lycopene could protect the rat kidney against furan-induced injury by improving renal function, attenuating histopathologic changes, reducing MDA production and renewing the activities of antioxidant enzymes.

  10. Challenging the dogma of mitochondrial reactive oxygen species overproduction in diabetic kidney disease.

    Science.gov (United States)

    Coughlan, Melinda T; Sharma, Kumar

    2016-08-01

    The paradigm that high glucose drives overproduction of superoxide from mitochondria as a unifying theory to explain end organ damage in diabetes complications has been tightly held for more than a decade. With the recent development of techniques and probes to measure the production of distinct reactive oxygen species (ROS) in vivo, this widely held dogma is now being challenged with the emerging view that specific ROS moieties are essential for the function of specific intracellular signaling pathways and represent normal mitochondrial function. This review will provide a balanced overview of the dual nature of ROS, detailing current evidence for ROS overproduction in diabetic kidney disease, with a focus on cell types and sources of ROS. The technical aspects of measurement of mitochondrial ROS, both in isolated mitochondria and emerging in vivo methods will be discussed. The counterargument, that mitochondrial ROS production is reduced in diabetic complications, is consistent with a growing recognition that stimulation of mitochondrial biogenesis and oxidative phosphorylation activity reduces inflammation and fibrosis. It is clear that there is an urgent need to fully characterize ROS production paying particular attention to spatiotemporal aspects and to factor in the relevance of ROS in the regulation of cellular signaling in the pathogenesis of diabetic kidney disease. With improved tools and real-time imaging capacity, a greater understanding of the complex role of ROS will be able to guide novel therapeutic regimens. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  11. Pharmacist managed diabetes and cardiovascular risk reduction clinic in kidney transplant recipients: bridging the gap in care transition.

    Science.gov (United States)

    Pinelli, Nicole R; Clark, Lindsey M; Carrington, Anne C; Carrington, Julia L; Malinzak, Lauren; Patel, Anita

    2014-12-01

    The purpose was to assess the feasibility of a care transition intervention for kidney transplant recipients (KTRs) with diabetes. Results document improved quality indicators and reduced resource utilization. These findings imply that a care transition intervention for KTRs with diabetes is feasible and associated with improved patient outcomes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Discovery of early-stage biomarkers for diabetic kidney disease using ms-based metabolomics (FinnDiane study)

    NARCIS (Netherlands)

    Kloet, F.M. van der; Tempels, F.W.A.; Ismail, N.; Heijden, R. van der; Kasper, P.T.; Rojas-Cherto, M.; Doorn, R. van; Spijksma, G.; Koek, M.; Greef, J. van der; Mäkinen, V.P.; Forsblom, C.; Holthöfer, H.; Groop, P.H.; Reijmers, T.H.; Hankemeier, T.

    2012-01-01

    Diabetic kidney disease (DKD) is a devastating complication that affects an estimated third of patients with type 1 diabetes mellitus (DM). There is no cure once the disease is diagnosed, but early treatment at a sub-clinical stage can prevent or at least halt the progression. DKD is clinically

  13. Daily Intake of Grape Powder Prevents the Progression of Kidney Disease in Obese Type 2 Diabetic ZSF1 Rats

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    Salwa M. K. Almomen

    2017-03-01

    Full Text Available Individuals living with metabolic syndrome (MetS such as diabetes and obesity are at high risk for developing chronic kidney disease (CKD. This study investigated the beneficial effect of whole grape powder (WGP diet on MetS-associated CKD. Obese diabetic ZSF1 rats, a kidney disease model with MetS, were fed WGP (5%, w/w diet for six months. Kidney disease was determined using blood and urine chemical analyses, and histology. When compared to Vehicle controls, WGP intake did not change the rat bodyweight, but lowered their kidney, liver and spleen weight, which were in parallel with the lower serum glucose and the higher albumin or albumin/globin ratio. More importantly, WGP intake improved the renal function as urination and proteinuria decreased, or it prevented kidney tissue damage in these diabetic rats. The renal protection of WGP diet was associated with up-regulation of antioxidants (Dhcr24, Gstk1, Prdx2, Sod2, Gpx1 and Gpx4 and downregulation of Txnip (for ROS production in the kidneys. Furthermore, addition of grape extract reduced H2O2-induced cell death of cultured podocytes. In conclusion, daily intake of WGP reduces the progression of kidney disease in obese diabetic rats, suggesting a protective function of antioxidant-rich grape diet against CKD in the setting of MetS.

  14. Reduced sulfation of chondroitin sulfate but not heparan sulfate in kidneys of diabetic db/db mice.

    Science.gov (United States)

    Reine, Trine M; Grøndahl, Frøy; Jenssen, Trond G; Hadler-Olsen, Elin; Prydz, Kristian; Kolset, Svein O

    2013-08-01

    Heparan sulfate proteoglycans are hypothesized to contribute to the filtration barrier in kidney glomeruli and the glycocalyx of endothelial cells. To investigate potential changes in proteoglycans in diabetic kidney, we isolated glycosaminoglycans from kidney cortex from healthy db/+ and diabetic db/db mice. Disaccharide analysis of chondroitin sulfate revealed a significant decrease in the 4-O-sulfated disaccharides (D0a4) from 65% to 40%, whereas 6-O-sulfated disaccharides (D0a6) were reduced from 11% to 6%, with a corresponding increase in unsulfated disaccharides. In contrast, no structural differences were observed in heparan sulfate. Furthermore, no difference was found in the molar amount of glycosaminoglycans, or in the ratio of hyaluronan/heparan sulfate/chondroitin sulfate. Immunohistochemical staining for the heparan sulfate proteoglycan perlecan was similar in both types of material but reduced staining of 4-O-sulfated chondroitin and dermatan was observed in kidney sections from diabetic mice. In support of this, using qRT-PCR, a 53.5% decrease in the expression level of Chst-11 (chondroitin 4-O sulfotransferase) was demonstrated in diabetic kidney. These results suggest that changes in the sulfation of chondroitin need to be addressed in future studies on proteoglycans and kidney function in diabetes.

  15. Novel combined management approaches to patients with diabetes, chronic kidney disease and cardiovascular disease.

    Science.gov (United States)

    Spaak, J

    2017-03-01

    Most patients we care for today suffer from more than one chronic disease, and multimorbidity is a rapidly growing challenge. Concomitant cardiovascular disease, renal dysfunction and diabetes represent a large proportion of all patients in cardiology, nephrology and diabetology. These entities commonly overlap due to their negative effects on vascular function and an accelerated atherosclerosis progression. At the same time, a progressive subspecialisation has caused the cardiologist to treat 'only' the heart, nephrologists 'only' the kidneys and endocrinologists' 'only' diabetes. Studies and guidelines follow the same pattern. This often requires patients to visit specialists for each field, with a risk of both under-diagnosis and under-treatment. From the patient's perspective, there is a great need for coordination and facilitation of the care, not only to reduce disease progression but also to improve quality of life. Person-centred integrated clinics for patients with cardiovascular disease, renal dysfunction and diabetes are a promising approach for complex chronic disease management.

  16. PGE2, Kidney Disease, and Cardiovascular Risk: Beyond Hypertension and Diabetes

    Science.gov (United States)

    Nasrallah, Rania; Hassouneh, Ramzi

    2016-01-01

    An important measure of cardiovascular health is obtained by evaluating the global cardiovascular risk, which comprises a number of factors, including hypertension and type 2 diabetes, the leading causes of illness and death in the world, as well as the metabolic syndrome. Altered immunity, inflammation, and oxidative stress underlie many of the changes associated with cardiovascular disease, diabetes, and the metabolic syndrome, and recent efforts have begun to elucidate the contribution of PGE2 in these events. This review summarizes the role of PGE2 in kidney disease outcomes that accelerate cardiovascular disease, highlights the role of cyclooxygenase-2/microsomal PGE synthase 1/PGE2 signaling in hypertension and diabetes, and outlines the contribution of PGE2 to other aspects of the metabolic syndrome, particularly abdominal adiposity, dyslipidemia, and atherogenesis. A clearer understanding of the role of PGE2 could lead to new avenues to improve therapeutic options and disease management strategies. PMID:26319242

  17. Bardoxolone Methyl Improves Kidney Function in Patients with Chronic Kidney Disease Stage 4 and Type 2 Diabetes: Post-Hoc Analyses from Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Study

    Science.gov (United States)

    Chin, Melanie P.; Bakris, George L.; Block, Geoffrey A.; Chertow, Glenn M.; Goldsberry, Angie; Inker, Lesley A.; Heerspink, Hiddo J.L.; O'Grady, Megan; Pergola, Pablo E.; Wanner, Christoph; Warnock, David G.; Meyer, Colin J.

    2018-01-01

    Background Increases in measured inulin clearance, measured creatinine clearance, and estimated glomerular filtration rate (eGFR) have been observed with bardoxolone methyl in 7 studies enrolling approximately 2,600 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The largest of these studies was Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), a multinational, randomized, double-blind, placebo-controlled phase 3 trial which enrolled patients with T2D and CKD stage 4. The BEACON trial was terminated after preliminary analyses showed that patients randomized to bardoxolone methyl experienced significantly higher rates of heart failure events. We performed post-hoc analyses to characterize changes in kidney function induced by bardoxolone methyl. Methods Patients in ­BEACON (n = 2,185) were randomized 1: 1 to receive once-daily bardoxolone methyl (20 mg) or placebo. We compared the effects of bardoxolone methyl and placebo on a post-hoc composite renal endpoint consisting of ≥30% decline from baseline in eGFR, eGFR <15 mL/min/1.73 m2, and end-stage renal disease (ESRD) events (provision of dialysis or kidney transplantation). Results Consistent with prior studies, patients randomized to bardoxolone methyl experienced mean increases in eGFR that were sustained through study week 48. Moreover, increases in eGFR from baseline were sustained 4 weeks after cessation of treatment. Patients randomized to bardoxolone methyl were significantly less likely to experience the composite renal endpoint (hazards ratio 0.48 [95% CI 0.36–0.64]; p < 0.0001). Conclusions Bardoxolone methyl preserves kidney function and may delay the onset of ESRD in patients with T2D and stage 4 CKD. PMID:29402767

  18. Associations of recipient illness history with hypertension and diabetes after living kidney donation.

    Science.gov (United States)

    Lentine, Krista L; Schnitzler, Mark A; Xiao, Huiling; Davis, Connie L; Axelrod, David; Abbott, Kevin C; Salvalaggio, Paolo R; Burroughs, Thomas E; Saab, Georges; Brennan, Daniel C

    2011-06-15

    Little is known about associations of family health history with outcomes after kidney donation. Using a database wherein Organ Procurement and Transplantation Network identifiers for 4650 living kidney donors in 1987 to 2007 were linked to administrative data of a US private health insurer (2000-2007 claims), we examined associations of recipient illness history as a measure of family history with postdonation diagnoses and drug-treatment for hypertension and diabetes. Cox regression with left and right censoring was applied to estimate associations (adjusted hazards ratios, aHR) of recipient illness history with postnephrectomy donor diagnoses, stratified by donor-recipient relationship. Recipient end-stage renal disease from hypertension, as compared with other recipient end-stage renal disease causes, was associated with modest, significant increases in the age- and gender-adjusted relative risks of hypertension diagnosis (aHR, 1.37%; 95% confidence interval [CI], 1.08-1.74) after donor nephrectomy among related donors. After adjustment for age, gender, and race, recipient type 2 diabetes compared with non-diabetic recipient status was associated with twice the relative risk of postdonation diabetes (aHR, 2.14; 95% CI, 1.28-3.55; P=0.003) among related donors. These patterns were significant among white but not among non-white related donors. Recipient type 1 diabetes was associated with postdonation diabetes only in black related donors (aHR, 3.22; 95% CI, 1.04-9.98; P=0.04). Recipient illness did not correlate significantly with outcomes in unrelated donors. These data support a need for further study of family health history as a potential sociodemographic correlate of donor outcomes, including examination of potential mediating factors and variation in risk discrimination among donors of different racial groups.

  19. Review: An Australian model of care for co-morbid diabetes and chronic kidney disease.

    Science.gov (United States)

    Lo, Clement; Zimbudzi, Edward; Teede, Helena; Cass, Alan; Fulcher, Greg; Gallagher, Martin; Kerr, Peter G; Jan, Stephen; Johnson, Greg; Mathew, Tim; Polkinghorne, Kevan; Russell, Grant; Usherwood, Tim; Walker, Rowan; Zoungas, Sophia

    2018-02-05

    Diabetes and chronic kidney disease (CKD) are two of the most prevalent co-morbid chronic diseases in Australia. The increasing complexity of multi-morbidity, and current gaps in health-care delivery for people with co-morbid diabetes and CKD, emphasise the need for better models of care for this population. Previously, proposed published models of care for co-morbid diabetes and CKD have not been co-designed with stake-holders or formally evaluated. Particular components of health-care shown to be effective in this population are interventions that: are structured, intensive and multifaceted (treating diabetes and multiple cardiovascular risk factors); involve multiple medical disciplines; improve self-management by the patient; and upskill primary health-care. Here we present an integrated patient-centred model of health-care delivery incorporating these components and co-designed with key stake-holders including specialist health professionals, general practitioners and Diabetes and Kidney Health Australia. The development of the model of care was informed by focus groups of patients and health-professionals; and semi-structured interviews of care-givers and health professionals. Other distinctives of this model of care are routine screening for psychological morbidity; patient-support through a phone advice line; and focused primary health-care support in the management of diabetes and CKD. Additionally, the model of care integrates with the patient-centred health-care home currently being rolled out by the Australian Department of Health. This model of care will be evaluated after implementation across two tertiary health services and their primary care catchment areas. Copyright © 2018 John Wiley & Sons, Ltd. This article is protected by copyright. All rights reserved.

  20. Netrin-1, a urinary proximal tubular injury marker, is elevated early in the time course of human diabetes

    NARCIS (Netherlands)

    Jayakumar, Calpurnia; Nauta, Ferdau L.; Bakker, Stephan J. L.; Bilo, Henk; Gansevoort, Ron T.; Johnson, Maribeth H.; Ramesh, Ganesan

    Netrin-1 was recently identified as an early diagnostic biomarker of chronic kidney disease (CKD) in an experimental animal model. However, its usefulness for early diagnosis of CKD in humans is unknown. The current study evaluated whether netrin-1 is increased in urine from human diabetic patients.

  1. From "Kidneys Govern Bones" to Chronic Kidney Disease, Diabetes Mellitus, and Metabolic Bone Disorder: A Crosstalk between Traditional Chinese Medicine and Modern Science.

    Science.gov (United States)

    Wang, Xiao-Qin; Zou, Xin-Rong; Zhang, Yuan Clare

    2016-01-01

    Although traditional Chinese medicine (TCM) and Western medicine have evolved on distinct philosophical foundations and reasoning methods, an increasing body of scientific data has begun to reveal commonalities. Emerging scientific evidence has confirmed the validity and identified the molecular mechanisms of many ancient TCM theories. One example is the concept of "Kidneys Govern Bones." Here we discuss the molecular mechanisms supporting this theory and its potential significance in treating complications of chronic kidney disease (CKD) and diabetes mellitus. Two signaling pathways essential for calcium-phosphate metabolism can mediate the effect of kidneys in bone homeostasis, one requiring renal production of bioactive vitamin D and the other involving an endocrine axis based on kidney-expressed Klotho and bone-secreted fibroblast growth factor 23. Disruption of either pathway can lead to calcium-phosphate imbalance and vascular calcification, accelerating metabolic bone disorder. Chinese herbal medicine is an adjunct therapy widely used for treating CKD and diabetes. Our results demonstrate the therapeutic effects and underlying mechanisms of a Chinese herbal formulation, Shen-An extracts, in diabetic nephropathy and renal osteodystrophy. We believe that the smart combination of Eastern and Western concepts holds great promise for inspiring new ideas and therapies for preventing and treating complications of CKD and diabetes.

  2. From “Kidneys Govern Bones” to Chronic Kidney Disease, Diabetes Mellitus, and Metabolic Bone Disorder: A Crosstalk between Traditional Chinese Medicine and Modern Science

    Directory of Open Access Journals (Sweden)

    Xiao-Qin Wang

    2016-01-01

    Full Text Available Although traditional Chinese medicine (TCM and Western medicine have evolved on distinct philosophical foundations and reasoning methods, an increasing body of scientific data has begun to reveal commonalities. Emerging scientific evidence has confirmed the validity and identified the molecular mechanisms of many ancient TCM theories. One example is the concept of “Kidneys Govern Bones.” Here we discuss the molecular mechanisms supporting this theory and its potential significance in treating complications of chronic kidney disease (CKD and diabetes mellitus. Two signaling pathways essential for calcium-phosphate metabolism can mediate the effect of kidneys in bone homeostasis, one requiring renal production of bioactive vitamin D and the other involving an endocrine axis based on kidney-expressed Klotho and bone-secreted fibroblast growth factor 23. Disruption of either pathway can lead to calcium-phosphate imbalance and vascular calcification, accelerating metabolic bone disorder. Chinese herbal medicine is an adjunct therapy widely used for treating CKD and diabetes. Our results demonstrate the therapeutic effects and underlying mechanisms of a Chinese herbal formulation, Shen-An extracts, in diabetic nephropathy and renal osteodystrophy. We believe that the smart combination of Eastern and Western concepts holds great promise for inspiring new ideas and therapies for preventing and treating complications of CKD and diabetes.

  3. Drugs to foster kidney regeneration in experimental animals and humans.

    Science.gov (United States)

    Gagliardini, Elena; Benigni, Ariela

    2014-01-01

    The incidence of kidney diseases is increasing worldwide and they are emerging as a major public health problem. Once mostly considered inexorable, renal disease progression can now be halted and lesions can even regress with drugs such as angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II type I receptor blockers, indicating the possibility of kidney repair. The discovery of renal progenitor cells lining the Bowman capsule of adult rat and human kidneys has shed light on the mechanism of repair by ACEi. Parietal progenitors are a reservoir of cells that contribute to podocyte turnover in physiological conditions. In the early phases of renal disease these progenitors migrate chaotically and subsequently proliferate, accumulating in Bowman's space. The abnormal behavior of parietal progenitors is sustained by the activation of CXCR4 receptors in response to an increased production of the chemokine SDF-1 by podocytes activated by the inflammatory environment. Ang II, via the AT1 receptor, also contributes to progenitor cell proliferation. The CXCR4/SDF-1 and Ang II/AT1 receptor pathogenic pathways both pave the way for lesion formation and subsequent sclerosis. ACEi normalize the CXCR4 and AT1 receptor expression on progenitors, limiting their proliferation, concomitant with the regression of hyperplastic lesions in animals, and in a patient with crescentic glomerulopathy. Understanding the molecular and cellular determinants of regeneration triggered by renoprotective drugs will reveal novel pathways that might be challenged or targeted by pharmacological therapy. © 2014 S. Karger AG, Basel.

  4. Dual Blockade of the Renin-angiotensin-aldosterone System in Type 2 Diabetic Kidney Disease

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    Yan-Huan Feng

    2016-01-01

    Full Text Available Objective: To examine the efficacy and safety of dual blockade of the renin-angiotensin-aldosterone system (RAAS among patients with type 2 diabetic kidney disease. Data Sources: We searched the major literature repositories, including the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE, for randomized clinical trials published between January 1990 and October 2015 that compared the efficacy and safety of the use of dual blockade of the RAAS versus the use of monotherapy, without applying any language restrictions. Keywords for the searches included "diabetic nephropathy," "chronic kidney disease," "chronic renal insufficiency," "diabetes mellitus," "dual therapy," "combined therapy," "dual blockade," "renin-angiotensin system," "angiotensin-converting enzyme inhibitor," "angiotensin-receptor blocker," "aldosterone blockade," "selective aldosterone blockade," "renin inhibitor," "direct renin inhibitor," "mineralocorticoid receptor blocker," etc. Study Selection: The selected articles were carefully reviewed. We excluded randomized clinical trials in which the kidney damage of patients was related to diseases other than diabetes mellitus. Results: Combination treatment with an angiotensin-converting enzyme inhibitor supplemented by an angiotensin II receptor blocking agent is expected to provide a more complete blockade of the RAAS and a better control of hypertension. However, existing literature has presented mixed results, in particular, related to patient safety. In view of this, we conducted a comprehensive literature review in order to explain the rationale for dual blockade of the RAAS, and to discuss the pros and cons. Conclusions: Despite the negative results of some recent large-scale studies, it may be immature to declare that the dual blockade is a failure because of the complex nature of the RAAS surrounding its diversified functions and utility. Further trials are warranted to study the combination therapy as an

  5. Serum uric acid to creatinine ratio: A predictor of incident chronic kidney disease in type 2 diabetes mellitus patients with preserved kidney function.

    Science.gov (United States)

    Gu, Liubao; Huang, Liji; Wu, Haidi; Lou, Qinglin; Bian, Rongwen

    2017-05-01

    Serum uric acid has shown to be a predictor of renal disease progression in most but not all studies. This study aims to test whether renal function-normalized serum uric acid is superior to serum uric acid as the predictor of incident chronic kidney disease in type 2 diabetes mellitus patients. In this study, 1339 type 2 diabetes mellitus patients with estimated glomerular filtration rate ⩾60 mL/min/1.73 m 2 and normouricemia were included. Renal function-normalized serum uric acid was calculated using serum uric acid/creatinine. Cox regression analysis was used to estimate the association between serum uric acid, renal function-normalized serum uric acid and incident chronic kidney disease. In total, 74 (5.53%) patients developed to chronic kidney disease 3 or greater during a median follow-up of 4 years, with older ages, longer diabetes duration and lower estimated glomerular filtration rate at baseline. The decline rate of estimated glomerular filtration rate was positively correlated with serum uric acid/creatinine ( r = 0.219, p uric acid ( r = 0.005, p = 0.858). Moreover, multivariate analysis revealed that serum uric acid was not an independent risk factor for incident chronic kidney disease ( p = 0.055), whereas serum uric acid to creatinine ratio was significantly associated with incident chronic kidney disease independently of potential confounders including baseline estimated glomerular filtration rate. serum uric acid to creatinine ratio might be a better predictor of incident chronic kidney disease in type 2 diabetes mellitus patients.

  6. Use of metformin and risk of kidney cancer in patients with type 2 diabetes.

    Science.gov (United States)

    Tseng, Chin-Hsiao

    2016-01-01

    The anticancer effect of metformin has been reported in the literature but requires additional confirmation in epidemiologic studies. With respect to kidney cancer scarce data are available. This study investigates whether metformin use in patients with type 2 diabetes mellitus (T2DM) might affect kidney cancer risk. The reimbursement database of the National Health Insurance in Taiwan was used. T2DM patients aged ≥ 40 years and newly treated with either metformin (n=171,753, "ever users of metformin") or other antidiabetic drugs (n=75,499, "never users of metformin") within 1998-2002 were followed for at least 6 months for kidney cancer until 31 December 2009. The treatment effect was estimated by Cox regression using propensity score weighting by inverse probability of treatment weighting approach. Hazard ratios were estimated for ever versus never users, and for tertiles of cumulative duration of metformin therapy. During follow-up, 917 ever users and 824 never users developed kidney cancer, with respective incidence of 80.09 and 190.30 per 100,000 person-years. The hazard ratio (95% confidence intervals) for ever versus never users is 0.279 (0.254-0.307); and is 0.598 (0.535-0.668), 0.279 (0.243-0.321) and 0.104 (0.088-0.124), respectively, for the first, second, and third tertile of cumulative duration of 45.8 months. In subgroup analyses, the lower risk of kidney cancer associated with metformin use is consistently observed in both sexes, and in patients with or without concomitant use of other antidiabetic drugs. Metformin use is associated with a decreased risk of kidney cancer in patients with T2DM. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Hospital-based prevalence of chronic kidney disease among the newly registered patients with diabetes

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    P A Khanam

    2016-01-01

    Full Text Available Chronic kidney disease (CKD is proved to be a major public health issue worldwide and an important contributor to the overall non-communicable disease burden. It increases risk of mortality, end-stage renal disease and accelerated cardiovascular disease (CVD. Diabetes is the biggest contributor to CKD and end stage renal disease (ESRD. In Bangladesh, very few data on CKD is available. This study aimed to estimate the prevalence of CKD among the newly registered diabetic patients at BIRDEM (Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders, a referral center for diabetes in Bangladesh. Methods: The study included all diabetic patients aged 18 - 80 years and were registered in the year 2012. Socio-demographic (age, sex, residence, income, literacy, clinical (obesity, blood pressure and biochemical (blood glucose, lipids, eGFR information were collected from the BIRDEM registry. CKD was defined according to the K/ DOQI guidelines. Results: A total of 1317 type 2 diabetic patients of age 18 to 80 years were studied. Of them, men and women were 54.7% and 45.3%, respectively. The overall prevalence of CKD (eGFR ≤60 (ml/min/m2 was 13.9%. The prevalence was significantly higher in women than men (21.3 v. 7.8%, p50y, higher sBP (≥140mmHg and taking oral hypoglycemic agent (OHA were significant. Conclusions: Thus, the study concludes that the prevalence of CKD among the newly registered diabetic patients is quite high in Bangladesh. The female diabetic patients with older age and with higher SBP bear the brunt of CKD. Considering high prevalence of CKD with severe lifelong complications it is of utmost importance for early detection and intervention at the primary health care (PHC level.

  8. Human Alpha Defensin 5 Expression in the Human Kidney and Urinary Tract

    Science.gov (United States)

    Porter, Edith; Bevins, Charles L.; DiRosario, Julianne; Becknell, Brian; Wang, Huanyu

    2012-01-01

    Background The mechanisms that maintain sterility in the urinary tract are incompletely understood. Recent studies have implicated the importance of antimicrobial peptides (AMP) in protecting the urinary tract from infection. Here, we characterize the expression and relevance of the AMP human alpha-defensin 5 (HD5) in the human kidney and urinary tract in normal and infected subjects. Methodology/Principal Findings Using RNA isolated from human kidney, ureter, and bladder tissue, we performed quantitative real-time PCR to show that DEFA5, the gene encoding HD5, is constitutively expressed throughout the urinary tract. With pyelonephritis, DEFA5 expression significantly increased in the kidney. Using immunoblot analysis, HD5 production also increased with pyelonephritis. Immunostaining localized HD5 to the urothelium of the bladder and ureter. In the kidney, HD5 was primarily produced in the distal nephron and collecting tubules. Using immunoblot and ELISA assays, HD5 was not routinely detected in non-infected human urine samples while mean urinary HD5 production increased with E.coli urinary tract infection. Conclusions/Significance DEFA5 is expressed throughout the urinary tract in non-infected subjects. Specifically, HD5 is expressed throughout the urothelium of the lower urinary tract and in the collecting tubules of the kidney. With infection, HD5 expression increases in the kidney and levels become detectable in the urine. To our knowledge, our findings represent the first to quantitate HD5 expression and production in the human kidney. Moreover, this is the first report to detect the presence of HD5 in infected urine samples. Our results suggest that HD5 may have an important role in maintaining urinary tract sterility. PMID:22359618

  9. A Selection of Constitutional Perspectives on Human Kidney Sales ...

    African Journals Online (AJOL)

    There are thousands of desperate people globally who need a kidney for transplantation. The number of people who require a kidney transplant continues to escalate faster than the number of kidneys available for a transplant. The specific focus of this article is to determine whether the payment of kidney donors could be ...

  10. Role of Epigenetic Histone Modifications in Diabetic Kidney Disease Involving Renal Fibrosis

    Directory of Open Access Journals (Sweden)

    Jing Sun

    2017-01-01

    Full Text Available One of the commonest causes of end-stage renal disease is diabetic kidney disease (DKD. Renal fibrosis, characterized by the accumulation of extracellular matrix (ECM proteins in glomerular basement membranes and the tubulointerstitium, is the final manifestation of DKD. The TGF-β pathway triggers epithelial-to-mesenchymal transition (EMT, which plays a key role in the accumulation of ECM proteins in DKD. DCCT/EDIC studies have shown that DKD often persists and progresses despite glycemic control in diabetes once DKD sets in due to prior exposure to hyperglycemia called “metabolic memory.” These imply that epigenetic factors modulate kidney gene expression. There is evidence to suggest that in diabetes and hyperglycemia, epigenetic histone modifications have a significant effect in modulating renal fibrotic and ECM gene expression induced by TGF-β1, as well as its downstream profibrotic genes. Histone modifications are also implicated in renal fibrosis through its ability to regulate the EMT process triggered by TGF-β signaling. In view of this, efforts are being made to develop HAT, HDAC, and HMT inhibitors to delay, stop, or even reverse DKD. In this review, we outline the latest advances that are being made to regulate histone modifications involved in DKD.

  11. New susceptibility loci associated with kidney disease in type 1 diabetes.

    Directory of Open Access Journals (Sweden)

    Niina Sandholm

    2012-09-01

    Full Text Available Diabetic kidney disease, or diabetic nephropathy (DN, is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D. Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS of T1D DN comprising ~2.4 million single nucleotide polymorphisms (SNPs imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2 × 10(-8 and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0 × 10(-9. Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-β1 pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1 × 10(-7, a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.

  12. Optimal medication dosing in patients with diabetes mellitus and chronic kidney disease.

    Science.gov (United States)

    MacCallum, Lori

    2014-10-01

    Diabetes mellitus is the leading cause of chronic kidney disease (CKD) in Canada. As rates of diabetes rise, so does the prevalence of CKD. Diabetes and CKD are chronic diseases that require multiple medications for their management. Many of the anticipated effects of these medications are altered by the physiologic changes that occur in CKD. Failure to individualize drug dosing in this population may lead to toxicity or decreased therapeutic response, leading to treatment failure. At times this can be challenging for a multitude of reasons, including the limitations of available calculations for estimating renal function, inconsistent dosing recommendations and the lack of dosing recommendations for some medications. Clinicians caring for these patients need to consider an approach of individualized drug therapy that will ensure optimal outcomes. The better understanding that clinicians have of these challenges, the more effective they will be at using the available information as a guide together with their own professional judgement to make appropriate dosing changes. This article discusses the following: 1) physiologic changes that occur in CKD and its impact on drug dosing; 2) advantages and disadvantages of various calculations used for estimating renal function; 3) pharmacokinetic and pharmacodynamic changes of some commonly used medications in diabetes, and finally, 4) an approach to individualized drug dosing for this patient population. Copyright © 2014 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  13. Direct costs associated with chronic kidney disease among type 2 diabetic patients in India

    Directory of Open Access Journals (Sweden)

    K Satyavani

    2014-01-01

    Full Text Available The aim of this study was to estimate the direct costs of medical care among hospitalized type 2 diabetic patients with chronic kidney disease (CKD. A total of 209 (M:F, 133:76 patients were divided into groups based on the severity of kidney disease. Group 1 subjects had undergone renal transplantation (n = 12, group 2 was CKD patients on hemodialysis (n = 45, group 3 was patients with CKD, prior to end-stage renal disease (ESRD (n = 66, and group 4 (n = 86 consisted of subjects without any complications. Details about expenditure per hospitalization, length of stay during admission, direct medical and nonmedical cost, expenditure for the previous two years, and source of bearing the expenditure were recorded in a questionnaire. Diabetic patients with CKD prior to ESRD spend more per hospitalization than patients without any complications. [Median ₹ 12,664 vs. 3,214]. The total median cost of CKD patients on hemodialysis was significantly higher than other CKD patients (INR 61,170 vs. 12,664. The median cost involved in kidney transplantation was ₹ 392,920. The total expenditure for hospital admissions in two years was significantly higher for dialysis than transplantation. Patients on hemodialysis or kidney transplantation tend to stay longer as inpatient admissions. The source of funds for the expenditure was mainly personal savings (46%. The expenditure on hospital admissions for CKD was considerably higher, and so, there is a need to develop a protocol on a cost-effective strategy for the treatment of CKD.

  14. MDM2 controls NRF2 antioxidant activity in prevention of diabetic kidney disease.

    Science.gov (United States)

    Guo, Weiying; Tian, Dan; Jia, Ye; Huang, Wenlin; Jiang, Mengnan; Wang, Junnan; Sun, Weixia; Wu, Hao

    2018-04-26

    Oxidative stress and P53 contribute to the pathogenesis of diabetic kidney disease (DKD). Nuclear factor erythroid 2-related factor 2 (NRF2) is a master regulator of cellular antioxidant defense system, is negatively regulated by P53 and prevents DKD. Recent findings revealed an important role of mouse double minute 2 (MDM2) in protection against DKD. However, the mechanism remained unclear. We hypothesized that MDM2 enhances NRF2 antioxidant signaling in DKD given that MDM2 is a key negative regulator of P53. The MDM2 inhibitor nutlin3a elevated renal P53, inhibited NRF2 signaling and induced oxidative stress, inflammation, fibrosis, DKD-like renal pathology and albuminuria in the wild-type (WT) non-diabetic mice. These effects exhibited more prominently in nutlin3a-treated WT diabetic mice. Interestingly, nutlin3a failed to induce greater renal injuries in the Nrf2 knockout (KO) mice under both the diabetic and non-diabetic conditions, indicating that NRF2 predominantly mediates MDM2's action. On the contrary, P53 inhibition by pifithrin-α activated renal NRF2 signaling and the expression of Mdm2, and attenuated DKD in the WT diabetic mice, but not in the Nrf2 KO diabetic mice. In high glucose-treated mouse mesangial cells, P53 gene silencing completely abolished nutlin3a's inhibitory effect on NRF2 signaling. The present study demonstrates for the first time that MDM2 controls renal NRF2 antioxidant activity in DKD via inhibition of P53, providing MDM2 activation and P53 inhibition as novel strategies in the management of DKD. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Oral health in diabetic and nondiabetic patients with chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Lingam Amara Swapna

    2017-01-01

    Full Text Available The objective of our study is to assess the subjective and objective oral manifestations and salivary pH in diabetic and nondiabetic uremic patients at a nephrology clinic. A total of 194 diabetic and nondiabetic patients with chronic kidney disease (CKD, who were divided into four groups, Group A, B, C, D, and who were attending a nephrology clinic were included in the study. Predialytic unstimulated whole salivary pH was recorded using pH- measuring strips. Subjective and objective findings were evaluated and recorded in the specially designed pro forma. Dental health assessment consisted of decayed, missing, and filled teeth index and community periodontal index (CPI. Dysgeusia was found to be significantly more prevalent in nondiabetic patients on dialysis. Uremic odor showed high significance (P <0.05 with 75% patients being positive in diabetic dialysis. There was no significant difference in the incidence of tongue coating between the four groups. A statistically high significance was observed with the objective oral manifestation of mucosal petechiae, with P = 0.01. There was an increased periodontal pocket depth among diabetic CKD patients as compared to that in nondiabetic patients. A moderate significance was found, with a CPI score showing P <0.05. Increased prevalence of caries was noticed among the diabetic CKD patients (Groups A, B. Recorded salivary pH showed no significant difference among diabetic and nondiabetic CKD patients. Findings suggest that these patients are at risk of developing complications, related to systemic health causing morbidity and mortality. Hence, these patients are to be motivated for comprehensive professional oral care and self oral hygiene instructions. Additional research is necessary to elucidate and correlate the combined influence of diabetes, CKD, and dialysis on oral health.

  16. Effect of GLP-1 on the expression of NADPH oxidase subunits in the kidney of type 1 diabetic rats

    Directory of Open Access Journals (Sweden)

    Jin-jin LIU

    2013-09-01

    Full Text Available Objective To observe the effect of exenatide, a glucagon-like peptide-1 (GLP-1 receptor agonist, on the expression of NADPH oxidase subunits NOX4 and p22phox and connective tissue growth factor (CTGF in the kidney of streptozotocin (STZ-induced type 1 diabetic rats, and explore the protective effects and mechanisms of exenatide on the kidney of diabetic rats. Methods Thirty male Sprague-Dawley (SD rats were divided into control group (group A, n=7 and diabetic model group (n=23. Type 1 diabetic model was reproduced by intraperitoneal injection of streptozotocin. It was successful in 19 rats. Diabetic rats were randomly divided into diabetic control group (group B, n=10 and diabetic with treatment of exenatide group (group C, n=9. Rats in group C were injected subcutaneously with exenatide in dose of 5μg/kg twice daily. Rats in group A and B were given equivalent volume of normal saline by subcutaneous injection. All rats were sacrificed after eight weeks. The mRNA expression of renal p22phox and NOX4 were detected by real-time fluorescence quantitative PCR. The protein expression of CTGF was detected by immunohistochemical staining. Results The levels of blood glucose, lipids, creatinine, and urea nitrogen, the albumin excretion rate, kidney index, the mRNA expressions of renal NOX4 and p22phox, and the protein expression of renal CTGF were significantly increased in group B compared with that in group A (P0.05. Conclusion Exenatide can decrease the expressions of renal NOX4, p22phox and CTGF, decline the index of urinary protein, and alleviate the kidney hypertrophy in type 1 diabetic rats, implying that exenatide exerted a protective effect on the kidney.

  17. Insufficient insulin administration to diabetic rats increases substrate utilization and maintains lactate production in the kidney

    DEFF Research Database (Denmark)

    Laustsen, Christoffer; Lipsø, Hans Kasper Wigh; Østergaard, Jakob Appel

    2014-01-01

    with insulin, resulting in poor glycemic control, has an additional effect on progression of late diabetic complications, than poor glycemic control on its own. We therefore compared renal metabolic alterations during conditions of poor glycemic control with and without suboptimal insulin administration, which...... administration increased pyruvate utilization and metabolic flux via both anaerobic and aerobic pathways in diabetic rats even though insulin did not affect kidney oxygen availability, HbA1c, or oxidative stress. These results imply direct effects of insulin in the regulation of cellular substrate utilization...... and metabolic fluxes during conditions of poor glycemic control. The study demonstrates that poor glycemic control in combination with suboptimal insulin administration accelerates metabolic alterations by increasing both anaerobic and aerobic metabolism resulting in increased utilization of energy substrates...

  18. Effects of Hyperglycemia and Iron Deficiency on Kidney and Heart Function in Type 2 Diabetes Disease

    Directory of Open Access Journals (Sweden)

    Belma Aščić-Buturović

    2006-02-01

    Full Text Available Untreated anemia can caused significant cardiac and kidney damage. The aim of this study was to investigate the efficiency of anemia and hyperglycemia treatment in type 2 diabetes and their impact on kidney and heart impairment. The study is clinical retrospective and prospective and it was conducted in Clinic of Endocrinology, Diabetes Mellitus and Metabolic Diseases, University Clinical Center of Sarajevo. Prior to the study all patients were taking oral hypoglycemic drugs included sulfonylureas and biguanides. These subjects were put on 2 times daily fix mix insulin and biguanides after lunch. Each day, subjects received Iron tab 1 x 100 mg/ day, and C vitamin 1 x 100 mg/day. The results of our study are showing that effective treatment of glycaemia and anemia in patients with diabetes, reduces blood pressure, urine albumin secretion and pulse rate, diminishing cardiovascular damage and improving kidney function.

  19. Short-term high dose of quercetin and resveratrol alters aging markers in human kidney cells

    Directory of Open Access Journals (Sweden)

    Fatemeh Abharzanjani

    2017-01-01

    Full Text Available Background: Hyperglycemia-mediated oxidative stress implicates in etiology of kidney cell aging and diabetic nephropathy. We evaluated the effects of different doses of resveratrol and quercetin and their combination therapy on aging marker in human kidney cell culture under hyperglycemia condition. Methods: Human embryonic kidney cell (HEK-293 was cultured in Dulbecco's Modified Eagle Medium (DMEM containing 100 mM (18 mg/L for 24 h. The cells were treated with resveratrol (2.5, 5, 10 μm, quercetin (3, 6, 12 μm, and combination of these (R 2.5 μm, Q 3 μm and (R 5 μm, Q 6 μm and (R 10 μm, Q 12 μm for 48 h, and then, cells were lysed to access RNA and lysate. Results: The analysis of data showed that beta-galactosidase enzyme gene expression as an aging marker in all treatment groups has reduced in a dose-dependent manner. Gene expression of Sirtuin1 and thioredoxin (Trx in all treated groups in comparison to control group increased in a dose-dependent fashion. Trx interacting protein (TXNIP gene expression decreased in a dose-dependent manner in all treated groups, especially in resveratrol and combination therapy. Conclusions: According to the results of this research, quercetin, resveratrol, and especially combination treatments with increased expression levels of antioxidants, can reduce aging markers in HEK cell line in hyperglycemia conditions. These results lead us to use flavonoids such as resveratrol for anti-aging potential.

  20. Knowledge regarding the prevention of chronic kidney disease in hypertensive and diabetic patients: a cross-sectional study

    OpenAIRE

    Moura, Elaine Cristina Santa Cruz de; Barbosa, Jefferson Belarmino Nunes; Marinho, Patrícia Érika de Melo

    2017-01-01

    Abstract Introduction: Hypertension (HT) and diabetes mellitus (DM) lead to functional and structural changes in target organs such as the kidneys, characterizing the need for preventive actions to avoid Chronic Kidney Disease (CKD). Objective: To verify cardiologists’ and endocrinologists’ knowledge, indications and practices regarding prevention of CKD in patients with HT and DM. Methods: A cross-sectional study with 14 cardiologists and 5 endocrinologists applying a questionnaire about ...

  1. Human genetics of diabetic vascular complications

    Indian Academy of Sciences (India)

    Diabetic vascular complications (DVC) affecting several important organ systems of human body such as the cardiovascular system constitute a major public health problem. There is evidence demonstrating that genetic factors contribute to the risk of DVC genetic variants, structural variants, and epigenetic changes play ...

  2. Interactive effects of diabetes and impaired kidney function on cognitive performance in old age: a population-based study.

    Science.gov (United States)

    Yin, Zhaoxue; Yan, Zhongrui; Liang, Yajun; Jiang, Hui; Cai, Chuanzhu; Song, Aiqin; Feng, Lei; Qiu, Chengxuan

    2016-01-12

    The interactive effect between diabetes and impaired kidney function on cognitive impairment in older adults has not yet been reported. The aim of this study was to investigate the association of diabetes and impaired kidney function with cognitive impairment among Chinese older people living in a rural area. This cross-sectional study included 1,358 participants (age ≥60 years; 60.5% women) in the population-based Confucius Hometown Aging Project in Shandong, China. Data on demographics, lifestyle factors, health history, use of medications, global cognitive function, and kidney function were collected through structured interviews, clinical examinations, and blood tests. We defined diabetes as a fasting plasma glucose level ≥7.0 mmol/l or use of hypoglycemic agents, impaired kidney function as glomerular filtration rate estimated from cystatin C (eGFRcys) Cognitive impairment was defined using the education-based cut-off scores of Mini-Mental State Examination (MMSE). Data were analyzed using multiple general linear and logistic regression models. Cognitive impairment was defined in 197 (14.5%) persons. The multi-adjusted β coefficient of MMSE score associated with diabetes was -0.06 (95% confidence interval [CI], -0.16, 0.03); the corresponding figures associated with eGFRcys function showed an interactive effect on cognitive impairment ( interaction = 0.02). Compared with individuals having neither diabetes nor impaired kidney function, those with both conditions had a multi-adjusted odds ratio of 4.23 (95% CI, 2.10-8.49) for cognitive impairment. The relative excess risk due to interaction was 2.74. This study suggests that concurrent presence of diabetes and impaired kidney function is associated with a substantial likelihood for cognitive impairment in older adults.

  3. Aerobic exercise in obese diabetic patients with chronic kidney disease: a randomized and controlled pilot study

    Directory of Open Access Journals (Sweden)

    Cooper Cheryl

    2009-12-01

    Full Text Available Abstract Background Patients with obesity, diabetes, and chronic kidney disease (CKD are generally physically inactive, have a high mortality rate, and may benefit from an exercise program. Methods We performed a 24-week randomized controlled feasibility study comparing aerobic exercise plus optimal medical management to medical management alone in patients with type 2 diabetes, obesity (body mass index [BMI] > 30 kg/m2, and stage 2-4 CKD (estimated glomerular filtration rate [eGFR] 15-90 mL/min/1.73 m2 with persistent proteinuria. Subjects randomized to exercise underwent thrice weekly aerobic training for 6 followed by 18 weeks of supervised home exercise. The primary outcome variable was change in proteinuria. Results Seven subjects randomized to exercise and 4 control subjects completed the study. Exercise training resulted in an increase in exercise duration during treadmill testing, which was accompanied by slight but insignificant decreases in resting systolic blood pressure and 24-hour proteinuria. Exercise did not alter GFR, hemoglobin, glycated hemoglobin, serum lipids, or C-reactive protein (CRP. Caloric intake and body weight and composition also did not change with exercise training. Conclusion Exercise training in obese diabetic patients with CKD is feasible and may have clinical benefits. A large-scale randomized controlled trial to determine the effects of exercise on renal functions, cardiovascular fitness, inflammation, and oxidative stress in diabetic patients with CKD is planned.

  4. CYP24A1 exacerbated activity during diabetes contributes to kidney tubular apoptosis via caspase-3 increased expression and activation.

    Directory of Open Access Journals (Sweden)

    Alexandre Tourigny

    Full Text Available Decreases in circulating 25,hydroxyl-vitamin D3 (25 OH D3 and 1,25,dihydroxyl-vitamin D3 (1,25 (OH2 D3 have been extensively documented in patients with type 2 diabetes. Nevertheless, the molecular reasons behind this drop, and whether it is a cause or an effect of disease progression is still poorly understood. With the skin and the liver, the kidney is one of the most important sites for vitamin D metabolism. Previous studies have also shown that CYP24A1 (an enzyme implicated in vitamin D metabolism, might play an important role in furthering the progression of kidney lesions during diabetic nephropathy. In this study we show a link between CYP24A1 increase and senescence followed by apoptosis induction in the renal proximal tubules of diabetic kidneys. We show that CYP24A1 expression was increased during diabetic nephropathy progression. This increase derived from protein kinase C activation and increased H(2O(2 cellular production. CYP24A1 increase had a major impact on cellular phenotype, by pushing cells into senescence, and later into apoptosis. Our data suggest that control of CYP24A1 increase during diabetes has a beneficial effect on senescence induction and caspase-3 increased expression. We concluded that diabetes induces an increase in CYP24A1 expression, destabilizing vitamin D metabolism in the renal proximal tubules, leading to cellular instability and apoptosis, and thereby accelerating tubular injury progression during diabetic nephropathy.

  5. Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardiometabolic risk factors from 1980 to 2010: a comparative risk assessment

    NARCIS (Netherlands)

    Danaei, Goodarz; Lu, Yuan; Singh, Gitanjali M.; Carnahan, Emily; Stevens, Gretchen A.; Cowan, Melanie J.; Farzadfar, Farshad; Lin, John K.; Finucane, Mariel M.; Rao, Mayuree; Khang, Young-Ho; Riley, Leanne M.; Mozaffarian, Dariush; Lim, Stephen S.; Ezzati, Majid; Aamodt, Geir; Abdeen, Ziad; Abdella, Nabila A.; Rahim, Hanan F. Abdul; Addo, Juliet; Aekplakorn, Wichai; Afifi, Mustafa M.; Agabiti-Rosei, Enrico; Salinas, Carlos A. Aguilar; Agyemang, Charles; Ali, Mohammed K.; Ali, Mohamed M.; Al-Nsour, Mohannad; Al-Nuaim, Abdul R.; Ambady, Ramachandran; Di Angelantonio, Emanuele; Aro, Pertti; Azizi, Fereidoun; Babu, Bontha V.; Bahalim, Adil N.; Barbagallo, Carlo M.; Barbieri, Marco A.; Barceló, Alberto; Barreto, Sandhi M.; Barros, Henrique; Bautista, Leonelo E.; Benetos, Athanase; Bjerregaard, Peter; Björkelund, Cecilia; Bo, Simona; Bobak, Martin; Bonora, Enzo; Botana, Manuel A.; Bovet, Pascal; Breckenkamp, Juergen

    2014-01-01

    Background High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes

  6. The self-management experience of patients with type 2 diabetes and chronic kidney disease: A qualitative study.

    Science.gov (United States)

    Shirazian, Shayan; Crnosija, Natalie; Weinger, Katie; Jacobson, Alan M; Park, Joonho; Tanenbaum, Molly L; Gonzalez, Jeffrey S; Mattana, Joseph; Hammock, Amy C

    2016-03-01

    The purpose of this study was to explore views related to the self-management of type 2 diabetes and chronic kidney disease. We conducted three semi-structured focus groups in participants with type 2 diabetes and chronic kidney disease. Interviews were transcribed, coded, and analyzed using thematic analysis. Credibility was supported through triangulation of data sources and the use of multiple investigators from different disciplines. Twenty-three adults participated. Three major themes were identified: emotional reactions to health state, the impact of family dynamics on self-management, and the burden of self-management regimens. Family dynamics were found to be a barrier and support to self-management, while complicated self-management regimens were found to be a barrier. Additionally, participants expressed several emotional reactions related to their CKD status, including regret related to having developed CKD and distress related both to their treatment regimens and the future possibility of dialysis. This exploratory study of patients with type 2 diabetes and chronic kidney disease describes barriers and supports to self-management and emotional reactions to chronic kidney disease status. Future research should confirm these findings in a larger population and should include family members and/or health care providers to help further define problems with self-management in patients with type 2 diabetes and chronic kidney disease. © The Author(s) 2015.

  7. Acoustic Radiation Force Impulse Elastography in Determining the Effects of Type 1 Diabetes on Pancreas and Kidney Elasticity in Children.

    Science.gov (United States)

    Sağlam, Dilek; Bilgici, Meltem Ceyhan; Kara, Cengiz; Yılmaz, Gülay Can; Çamlıdağ, İlkay

    2017-11-01

    The aim of this study is to determine the effects of type 1 diabetes on pancreas and kidney elasticity in children, using acoustic radiation force impulse ultrasound elastography. Sixty autoantibody-positive patients with type 1 diabetes (45% girls; mean [± SD] age, 11.7 ± 4.4 years; range, 1.9-19.3 years) admitted to the pediatric endocrinology outpatient clinic and 32 healthy children (50% girls; mean age, 10.2 ± 3.8 years; range, 2.1-17.3 years) were included in the study. Acoustic radiation force impulse elastography measurements were performed of the kidneys and pancreas in both groups. Body mass index, duration of diabetes, HbA1c levels, and insulin dosage of patients with type 1 diabetes were recorded. The mean shear-wave velocities of the pancreas were 0.99 ± 0.25 m/s in patients with type 1 diabetes and 1.09 ± 0.22 m/s in healthy control subjects; the difference was not significant (p = 0.08). The median shear-wave velocities of the right and left kidneys in patients with type 1 diabetes were 2.43 ± 0.29 and 2.47 ± 0.25 m/s, respectively. There were no significant differences in the shear-wave velocities of the right and left kidneys between the patients with type 1 diabetes and the healthy control subjects (p = 0.91 and p = 0.73, respectively). Correlation analysis showed no correlation between the shear-wave velocities of the pancreas and kidney versus HbA1c level, duration of diabetes, insulin dosage, height, weight, and body mass index of the patients with type 1 diabetes. The current study showed no significant difference in the shear-wave velocity of kidneys in children with type 1 diabetes with normoalbuminuria compared with the healthy control subjects. We also observed that the shear-wave velocity of the pancreas in children with type 1 diabetes and healthy control subjects did not differ significantly.

  8. Hyperactivation of Akt/mTOR and deficiency in tuberin increased the oxidative DNA damage in kidney cancer patients with diabetes.

    Science.gov (United States)

    Habib, Samy L; Liang, Sitai

    2014-05-15

    Recent study from our laboratory showed that patients with diabetes are at a higher risk of developing kidney cancer. In the current study, we have explored one of the mechanisms by which diabetes accelerates tumorigenesis in the kidney. Kidney cancer tissue from patients with diabetes showed a higher activity of Akt and decreased in total protein of tuberin compared to kidney cancer patient without diabetes or diabetes alone. In addition, a significant increase in phospho-Akt/tuberin expression was associated with an increase in Ki67 expression and activation of mTOR in kidney tumor with or without diabetes compared to diabetes alone. In addition, decrease in tuberin expression resulted in a significant decrease in protein expression of OGG1 and increased in oxidative DNA damage, 8-oxodG in kidney tissues from patients with cancer or cancer+diabetes. Importantly, these data showed that the majority of the staining of Akt/tuberin/p70S6K phosphorylation was more prominently in the tubular cells. In addition, accumulation of oxidative DNA damage is localized only in the nucleus of tubular cells within the cortex region. These data suggest that Akt/tuberin/mTOR pathway plays an important role in the regulation DNA damage and repair pathways that may predispose diabetic kidneys to pathogenesis of renal cell carcinoma.

  9. SGLT2 Protein Expression Is Increased in Human Diabetic Nephropathy

    Science.gov (United States)

    Wang, Xiaoxin X.; Levi, Jonathan; Luo, Yuhuan; Myakala, Komuraiah; Herman-Edelstein, Michal; Qiu, Liru; Wang, Dong; Peng, Yingqiong; Grenz, Almut; Lucia, Scott; Dobrinskikh, Evgenia; D'Agati, Vivette D.; Koepsell, Hermann; Kopp, Jeffrey B.; Rosenberg, Avi Z.; Levi, Moshe

    2017-01-01

    There is very limited human renal sodium gradient-dependent glucose transporter protein (SGLT2) mRNA and protein expression data reported in the literature. The first aim of this study was to determine SGLT2 mRNA and protein levels in human and animal models of diabetic nephropathy. We have found that the expression of SGLT2 mRNA and protein is increased in renal biopsies from human subjects with diabetic nephropathy. This is in contrast to db-db mice that had no changes in renal SGLT2 protein expression. Furthermore, the effect of SGLT2 inhibition on renal lipid content and inflammation is not known. The second aim of this study was to determine the potential mechanisms of beneficial effects of SGLT2 inhibition in the progression of diabetic renal disease. We treated db/db mice with a selective SGLT2 inhibitor JNJ 39933673. We found that SGLT2 inhibition caused marked decreases in systolic blood pressure, kidney weight/body weight ratio, urinary albumin, and urinary thiobarbituric acid-reacting substances. SGLT2 inhibition prevented renal lipid accumulation via inhibition of carbohydrate-responsive element-binding protein-β, pyruvate kinase L, SCD-1, and DGAT1, key transcriptional factors and enzymes that mediate fatty acid and triglyceride synthesis. SGLT2 inhibition also prevented inflammation via inhibition of CD68 macrophage accumulation and expression of p65, TLR4, MCP-1, and osteopontin. These effects were associated with reduced mesangial expansion, accumulation of the extracellular matrix proteins fibronectin and type IV collagen, and loss of podocyte markers WT1 and synaptopodin, as determined by immunofluorescence microscopy. In summary, our study showed that SGLT2 inhibition modulates renal lipid metabolism and inflammation and prevents the development of nephropathy in db/db mice. PMID:28196866

  10. In vivo imaging of oxidative stress in the kidney of diabetic mice and its normalization by angiotensin II type 1 receptor blocker

    International Nuclear Information System (INIS)

    Sonta, Toshiyo; Inoguchi, Toyoshi; Matsumoto, Shingo; Yasukawa, Keiji; Inuo, Mieko; Tsubouchi, Hirotaka; Sonoda, Noriyuki; Kobayashi, Kunihisa; Utsumi, Hideo; Nawata, Hajime

    2005-01-01

    This study was undertaken to evaluate oxidative stress in the kidney of diabetic mice by electron spin resonance (ESR) imaging technique. Oxidative stress in the kidney was evaluated as organ-specific reducing activity with the signal decay rates of carbamoyl-PROXYL probe using ESR imaging. The signal decay rates were significantly faster in corresponding image pixels of the kidneys of streptozotocin-induced diabetic mice than in those of controls. This technique further demonstrated that administration of angiotensin II type 1 receptor blocker (ARB), olmesartan (5 mg/kg), completely restored the signal decay rates in the diabetic kidneys to control values. In conclusion, this study provided for the first time the in vivo evidence for increased oxidative stress in the kidneys of diabetic mice and its normalization by ARB as evaluated by ESR imaging. This technique would be useful as a means of further elucidating the role of oxidative stress in diabetic nephropathy

  11. Agonist-induced desensitization of human β3-adrenoceptors expressed in human embryonic kidney cells

    NARCIS (Netherlands)

    Michel-Reher, Martina B.; Michel, Martin C.

    2013-01-01

    β3-Adrenoceptors are resistant to agonist-induced desensitization in some cell types but susceptible in others including transfected human embryonic kidney (HEK) cells. Therefore, we have studied cellular and molecular changes involved in agonist-induced β3-adrenoceptor desensitization in HEK cells.

  12. Effects of low dose radiation on kidney function and morphology of diabetic mice

    International Nuclear Information System (INIS)

    Zhang Chi; Li Xiaokun; Gong Shouliang; Meng Tao; Li Cai; Cai Lu

    2010-01-01

    Objective: To study the effect of low dose radiation (LDR) on the kidney function and morphology in C57BL/6J mice with diabetic nephropathy (DN) induced by streptozotocin (STZ) and illuminate the protective function of LDR on kidney damage caused by diabetes mellitus (DM). Methods: The healthy and right age C57BL/6J mice were divided into 4 groups including control, DM, LDR and DM/LDR. The mice in DM and DM/LDR groups were injected intraperitoneally with STZ to set up DM models. The mice in DM/LDR and LDR groups were irradiated with 25 mGy X-rays every other day for 4 weeks. The changes of blood glucose level, urine index level and the morphology of glomerular were detected at 2, 4, 8, 12, 16 weeks after radiation. Results: The blood glucose levels of mice in DM and DM/LDR groups after STZ-induced DM model preparation were higher than those in LDR and control groups (P<0.05). After treated with LDR for 2 weeks, the blood glucose level in DM/LDR group was supressed and significantly lower than that in DM group (P<0.05). Moreover the the change had been kept to 16 weeks. In addition, compared with DM group, the level of urine micro albumin(MALB) in DM/LDR group was decreased and the urine creatinine (Cre) level was increased. Compared with DM group, the morphological results showed that the glomerular mesangial expansion and mesangial cell proliferation were significantly supressed in DM/LDR group (P<0.05). Conclusion: LDR can promote the decease of blood glucose level efficiently, relief the change of kidney function, supress and delay the pathological changes of DN. (authors)

  13. Impact of dietary fiber intake on glycemic control, cardiovascular risk factors and chronic kidney disease in Japanese patients with type 2 diabetes mellitus: the Fukuoka Diabetes Registry

    OpenAIRE

    Fujii, Hiroki; Iwase, Masanori; Ohkuma, Toshiaki; Ogata-Kaizu, Shinako; Ide, Hitoshi; Kikuchi, Yohei; Idewaki, Yasuhiro; Joudai, Tamaki; Hirakawa, Yoichiro; Uchida, Kazuhiro; Sasaki, Satoshi; Nakamura, Udai; Kitazono, Takanari

    2013-01-01

    Background Dietary fiber is beneficial for the treatment of type 2 diabetes mellitus, although it is consumed differently in ethnic foods around the world. We investigated the association between dietary fiber intake and obesity, glycemic control, cardiovascular risk factors and chronic kidney disease in Japanese type 2 diabetic patients. Methods A total of 4,399 patients were assessed for dietary fiber intake using a brief self-administered diet history questionnaire. The associations betwee...

  14. Effect of total glucosides of paeony on the expression of nephrin in the kidneys from diabetic rats.

    Science.gov (United States)

    Zhang, Pei; Zhang, Jing-Jing; Su, Jing; Qi, Xiang-Ming; Wu, Yong-Gui; Shen, Ji-Jia

    2009-01-01

    Total glucosides of paeony (TGP), extracted from the traditional Chinese herb root of Paeonia lactiflora pall, have been shown to have a therapeutic role in experimental diabetic nephropathy including albuminuria. Recent investigation has identified nephrin, a podocyte-specific transmembrane protein, as a key regulator in the pathogenesis of diabetic albuminuria. The aim of this study was to investigate whether TGP can attenuate albuminuria through prevention of nephrin loss in the experimental diabetic nephropathy. Fifty male Munich-Wistar rats were obtained from the Experimental Animal Center of Anhui Medical University. These rats were divided into 5 groups (n = 10); normal group, control diabetic group, and 3 TGP treated diabetic groups at different concentrations. Diabetes was induced by streptozotocin, and TGP (50, 100, 200 mg/kg) was orally administered to the 3 TGP treated diabetic groups once a day for 8 weeks, respectively. Blood glucose and 24 hour urinary albumin excretion rate (AER) were measured. The expressions of nephrin, tumor necrosis factor-alpha (TNF-alpha), NF-kappaB p65 and 3-nitrotyrosine (3-NT) protein were determined by immunoinfluorescence or Western blot analysis in the kidneys. Elevated AER was markedly attenuated by TGP treatment in diabetic rats. There was a finely dotted linear epithelial staining of nephrin in normal group glomeruli. In contrast, the staining of glomeruli from untreated diabetic rats was attenuated, more diapersed, and clustered. This diabetic-induced loss of glomerular nephrin expression was prevented in a large degree in TGP-treated diabetic rats. Western blot analysis showed that the expression of nephrin protein was reduced in the kidneys of diabetic rats, but significantly increased in the TGP treatment groups. The expressions of TNF-alpha, NF-kappaB p65 and 3-NT protein were significantly increased in the kidneys of diabetic rats, which were all significantly inhibited by TGP treatment. Our results showed that

  15. Ketone body metabolism in normal and diabetic human skeletal muscle

    International Nuclear Information System (INIS)

    Nosadini, R.; Avogaro, A.; Sacca, L.

    1985-01-01

    Although the liver is considered the major source of ketone bodies (KB) in humans, these compounds may also be formed by nonhepatic tissues. To study this aspect further, 3-[ 14 C]hydroxybutyrate (BOH) or [3- 14 C]acetoacetate (AcAc) were constantly infused after a priming dose and contemporaneous arterial and venous samples were taken at splanchnic, heart, kidney, and leg sites in eight normal subjects (N) undergoing diagnostic catheterization and at the forearm site in five normal and six ketotic diabetic (D) subjects. After 70 min of infusion, tracer and tracee levels of AcAc and BOH reached a steady state in the artery and vein in both normal and diabetic subjects. The venous-arterial (V-A) difference at the forearm step for cold KB was negligible both in normal and diabetic subjects, whereas for labeled KB it was approximately 10-fold higher in diabetic subjects (V-A AcAc, -31 +/- 7 and -270 +/- 34 dpm/ml in N and D, respectively; V-A BOH, -38 +/- 6 and -344 +/- 126 dpm/ml in N and D, respectively). The authors assumed that the V-A difference in tracer concentration was consistent with dilution of the tracer by newly synthesized tracee inside the muscle and calculated that the forearm muscle produces KB at a rate of 16.2 +/- 3.3 mumol/min in D and 0.9 +/- 0.9 mumol/min in N. These findings can be accounted for by the hypothesis that the disappearance flux of KB from circulation was replaced by an equivalent flux of KB entering the vein at the muscle step in D but not in N. Moreover, in N KB were not only produced but also utilized by the splanchnic area (39 +/- 9 mumol/min)

  16. Biochemical and Clinical Variables of Normal Parathyroid and Hyperparathyroid Diabetic Chronic Kidney Disease Patients

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    Syed Abdul Kader

    2016-09-01

    Full Text Available Background: In chronic kidney disease (CKD intact parathyroid hormone (iPTH level is often increased before clinical hyperphosphatemia occurs. Despite its importance very few studies evaluated parathyroid status in CKD. Objective: The study was undertaken to estimate level of parathormone in diabetic CKD patients at a tertiary level hospital and assessing its relationship with different parameters like hemoglobin, calcium etc. and comparing biochemical and clinical variables between normal parathyroid and hyperparathyroid groups. Materials and Methods: It was a hospital based cross-sectional study involving purposively selected chronic kidney disease patients attending nephrology and endocrinology outdoor and indoor services of BIRDEM hospital, Dhaka, Bangladesh. Study was conducted during the period of April to October 2010. All the subjects were divided into two groups based on serum parathormone level and different parameters were compared between groups. Results: The mean duration of chronic kidney disease was significantly higher in hyperparathyroid group than that in the normal group (<0.001. Retinopathy and hypertension were more common in hyperparathyroid group than that in patients with normal serum parathormone (p<0.001 and p=0.012. Neuropathy was solely present in hyperparathyroid group (p<0.001. Mean fasting blood glucose, serum creatinine and serum phosphate were significantly higher in the hyperparathyroid group compared to normal group (p<0.001 in all cases while the mean serum calcium and haemoglobin were lower in hyperparathyroid group than those in the normal group (p<0.001 in both cases. Serum creatinine and serum parathormone bears a significantly linear relationship (r=0.986, p<0.001, while serum parathormone and serum calcium bears a significantly negative relationship (r=−0.892 and p<0.001. Conclusion: Earlier intervention on the basis of iPTH in addition to other biochemical parameters of chronic kidney disease is

  17. Optimal conditions of LDR to protect the kidney from diabetes: exposure to 12.5 mGy X-rays for 8 weeks efficiently protects the kidney from diabetes.

    Science.gov (United States)

    Cheng, Jie; Li, Fengsheng; Cui, Jiuwei; Guo, Weiying; Li, Cai; Li, Wei; Wang, Guixia; Xing, Xiao; Gao, Ying; Ge, Yuanyuan; Wang, Guanjun; Cai, Lu

    2014-05-08

    We reported the attenuation of diabetes-induced renal dysfunction by exposure to multiple low-dose radiation (LDR) at 25 mGy every other day by suppressing renal oxidative damage. We here explored the optimal conditions of LDR to protect the kidney from diabetes. Male C57BL/6J mice with type 1 diabetes were induced with multiple injections of low-dose streptozotocin. Diabetic mice received whole body X-irradiation at a dose of 12.5, 25 or 50 mGy every other day for either 4 or 8 weeks. Age-matched normal mice were similarly irradiated at the dose of 25 mGy for 4 or 8 weeks. The renal function and histopathological changes were examined at the 4th and 8th weeks of the study. Diabetes induced renal dysfunction is shown by the decreased creatinine and increased microalbumin in the urine. Renal oxidative damage, detected by protein nitration and lipid oxidation, and remodeling, reflected by increased expression of connective tissue growth factor, collagen IV and fibronectin, were significantly increased in diabetic mice. All these renal pathological and function changes in diabetic mice were significantly attenuated by exposure to LDR at all regimens, among which, however, exposure to LDR at 12.5 mGy for 8 weeks provided the best protective effect on the kidney of diabetic mice. Our results suggest that whole-body LDR at 12.5 mGy every other day for 8 weeks is the optimal condition of LDR to protect the kidney from diabetes. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Kidney Dysfunction in Adult Offspring Exposed In Utero to Type 1 Diabetes Is Associated with Alterations in Genome-Wide DNA Methylation.

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    Jean-François Gautier

    Full Text Available Fetal exposure to hyperglycemia impacts negatively kidney development and function.Our objective was to determine whether fetal exposure to moderate hyperglycemia is associated with epigenetic alterations in DNA methylation in peripheral blood cells and whether those alterations are related to impaired kidney function in adult offspring.Twenty nine adult, non-diabetic offspring of mothers with type 1 diabetes (T1D (case group were matched with 28 offspring of T1D fathers (control group for the study of their leukocyte genome-wide DNA methylation profile (27,578 CpG sites, Human Methylation 27 BeadChip, Illumina Infinium. In a subset of 19 cases and 18 controls, we assessed renal vascular development by measuring Glomerular Filtration Rate (GFR and Effective Renal Plasma Flow (ERPF at baseline and during vasodilatation produced by amino acid infusion.Globally, DNA was under-methylated in cases vs. controls. Among the 87 CpG sites differently methylated, 74 sites were less methylated and 13 sites more methylated in cases vs. controls. None of these CpG sites were located on a gene known to be directly involved in kidney development and/or function. However, the gene encoding DNA methyltransferase 1 (DNMT1--a key enzyme involved in gene expression during early development--was under-methylated in cases. The average methylation of the 74 under-methylated sites differently correlated with GFR in cases and controls.Alterations in methylation profile imprinted by the hyperglycemic milieu of T1D mothers during fetal development may impact kidney function in adult offspring. The involved pathways seem to be a nonspecific imprinting process rather than specific to kidney development or function.

  19. Diet and kidney disease in high-risk individuals with type 2 diabetes mellitus.

    Science.gov (United States)

    Dunkler, Daniela; Dehghan, Mahshid; Teo, Koon K; Heinze, Georg; Gao, Peggy; Kohl, Maria; Clase, Catherine M; Mann, Johannes F E; Yusuf, Salim; Oberbauer, Rainer

    2013-10-14

    Type 2 diabetes mellitus and associated chronic kidney disease (CKD) have become major public health problems. Little is known about the influence of diet on the incidence or progression of CKD among individuals with type 2 diabetes. To examine the association between (healthy) diet, alcohol, protein, and sodium intake, and incidence or progression of CKD among individuals with type 2 diabetes. All 6213 individuals with type 2 diabetes without macroalbuminuria from the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET) were included in this observational study. Recruitment spanned from January 2002 to July 2003, with prospective follow-up through January 2008. Chronic kidney disease was defined as new microalbuminuria or macroalbuminuria or glomerular filtration rate decline of more than 5% per year at 5.5 years of follow-up. We assessed diet using the modified Alternate Healthy Eating Index (mAHEI). The analyses were adjusted for known risk factors, and competing risk of death was considered. After 5.5 years of follow-up, 31.7% of participants had developed CKD and 8.3% had died. Compared with participants in the least healthy tertile of mAHEI score, participants in the healthiest tertile had a lower risk of CKD (adjusted odds ratio [OR], 0.74; 95% CI, 0.64-0.84) and lower risk of mortality (OR, 0.61; 95% CI, 0.48-0.78). Participants consuming more than 3 servings of fruits per week had a lower risk of CKD compared with participants consuming these food items less frequently. Participants in the lowest tertile of total and animal protein intake had an increased risk of CKD compared with participants in the highest tertile (total protein OR, 1.16; 95% CI, 1.05-1.30). Sodium intake was not associated with CKD. Moderate alcohol intake reduced the risk of CKD (OR, 0.75; 95% CI, 0.65-0.87) and mortality (OR, 0.69; 95% CI, 0.53-0.89). A healthy diet and moderate intake of alcohol may decrease the incidence or progression of CKD

  20. Computed Tomography of the diabetic kidney; La Tomografia Computerizzata nello studio del rene diabetico

    Energy Technology Data Exchange (ETDEWEB)

    Angelelli, G.; Stabile Ianora, A.A.; Scardapane, A.; Rotondo, A. [Bari Univ., Bari (Italy). Ist. di Radiologia

    2000-02-01

    The purpose of this work is to investigate whether any morphometric or densitometric are detectable in the kidneys of type 2 diabetic patients. 40 diabetic patients were examined and of 20 non-diabetics (the control group) were submitted to triphasic helical CT for different abdominal conditions. The type 2 diabetic patients were 23 men and 17 women, mean age 62 years, while the nondiabetic controls were 12 men and 8 women, mean age 58 years. All the CT images were analyzed using the Multiplanar Reconstruction (MPR) software. It was evaluated morphometric features, such as the presence of parenchymal or vascular calcifications, axial and coronal renal diameters, coronal renal area, and cortico medullary ratio, and densitometric and functional features, such as unenhanced renal density, cortical and medullary density in the arterial phase, parenchymal density in the nephrographic phase, and contrast elimination. It was also compared the results in the subgroups of patients with those in the controls. Both renal diameters on axial sections and cortical density in the arterial phase were significantly lower in the nephropathic group (p<0.05) than in non-nephropathic patients and control. The patients with shorter duration of their diabetes had significantly greater axial diameters (p<0.05); a longer-standing disease correlated significantly (p<0.05) with smaller axial diameters of kidneys and lower cortical density in the arterial phase. Renal diameters on axial and coronal sections and cortical density in the arterial phase can be useful indices of early nephropathy in diabetic patients. Further studies are warranted to make these findings suitable for use in clinical practice. [Italian] In questo articolo sono presentate le eventuali alterazioni tomodensitometriche a livello renale di pazienti affetti da diabete mellito di tipo 2. Si sono valutate retrospettivamente le immagini TC di 40 soggetti affetti da diabete di tipo 2 (23 maschi, 17 femmine, eta' media 62

  1. Increased kidney size, glomerular filtration rate and renal plasma flow in short-term insulin-dependent diabetics

    DEFF Research Database (Denmark)

    Christiansen, JS; Gammelgaard, J; Frandsen, M

    1981-01-01

    Glomerular filtration rate (GFR), renal plasma flow (RPF) and kidney volume were measured in thirteen male subjects (mean age 30 years) with short-term insulin-dependent diabetes (mean duration of disease 2.4 years) and fourteen normal male subjects (mean age 29 years). GFR and RPF were measured...

  2. A Meta-analysis of the Association of Estimated GFR, Albuminuria, Diabetes Mellitus, and Hypertension With Acute Kidney Injury

    NARCIS (Netherlands)

    James, Matthew T.; Grams, Morgan E.; Woodward, Mark; Elley, C. Raina; Green, Jamie A.; Wheeler, David C.; de Jong, Paul; Gansevoort, Ron T.; Levey, Andrew S.; Warnock, David G.; Sarnak, Mark J.; de Zeeuw, Dick; Bakker, Stephan J. L.; van der Harst, Pim; Heerspink, Hiddo J.

    2015-01-01

    Background: Diabetes mellitus and hypertension are risk factors for acute kidney injury (AKI). Whether estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (ACR) remain risk factors for AKI in the presence and absence of these conditions is uncertain. Study Design:

  3. Predictors of fatal and nonfatal cardiovascular events in patients with type 2 diabetes mellitus, chronic kidney disease, and anemia

    DEFF Research Database (Denmark)

    McMurray, John J V; Uno, Hajime; Jarolim, Petr

    2011-01-01

    This study aims to examine predictors of cardiovascular mortality and morbidity in patients with chronic kidney disease (CKD). Individuals with the triad of diabetes, CKD, and anemia represent a significant proportion of patients with cardiovascular disease and are at particularly high risk...

  4. Incidence and mortality of kidney cancers, and human development index in Asia; a matter of concern

    OpenAIRE

    Arabsalmani, Masoumeh; Mohammadian-Hafshejani, Abdollah; Ghoncheh, Mahshid; Hadadian, Fatemeh; Towhidi, Farhad; Vafaee, Kamran; Salehiniya, Hamid

    2016-01-01

    Background The incidence and mortality of kidney cancer have steadily increased by 2%- 3% per decade worldwide, and an increased risk of kidney cancer has been observed in many Asian countries. The information on the incidence and mortality of a disease and its distribution is essential for better planning for prevention and further studies. Objectives This study aimed to assess the incidence and mortality of kidney cancer and their correlation with the human development index (HDI) in Asia. ...

  5. Diabetes-Resistant NOR Mice Are More Severely Affected by Streptozotocin Compared to the Diabetes-Prone NOD Mice: Correlations with Liver and Kidney GLUT2 Expressions

    Directory of Open Access Journals (Sweden)

    S. Kahraman

    2015-01-01

    Full Text Available Nonobese Diabetic (NOD mice are susceptible strains for Type 1 diabetes development, and Nonobese Diabetes-Resistant (NOR mice are defined as suitable controls for NOD mice in non-MHC-related research. Diabetes is often accelerated in NOD mice via Streptozotocin (STZ. STZ is taken inside cells via GLUT2 transmembrane carrier proteins, the major glucose transporter isoforms in pancreatic beta cells, liver, kidneys, and the small intestine. We observed severe adverse effects in NOR mice treated with STZ compared to NOD mice that were made diabetic with a similar dose. We suggested that the underlying mechanism could be differential GLUT2 expressions in pancreatic beta cells, yet immunofluorescent and immunohistochemical studies revealed similar GLUT2 expression levels. We also detected GLUT2 expression profiles in NOD and NOR hepatic and renal tissues by western blot analysis and observed considerably higher GLUT2 expression levels in liver and kidney tissues of NOR mice. Although beta cell GLUT2 expression levels are frequently evaluated as a marker predicting STZ sensitivity in animal models, we report here very different diabetic responses to STZ in two different animal strains, in spite of similar initial GLUT2 expressions in beta cells. Furthermore, use of NOR mice in STZ-mediated experimental diabetes settings should be considered accordingly.

  6. Dipeptidyl peptidase-4 inhibition in chronic kidney disease and potential for protection against diabetes-related renal injury.

    Science.gov (United States)

    Penno, G; Garofolo, M; Del Prato, S

    2016-05-01

    Type 2 diabetes mellitus (T2DM) is associated with a high risk of chronic kidney disease (CKD). About 20% of patients with T2DM have CKD of stage ≥ 3; up to 40% have some degree of CKD. Beyond targeting all renal risk factors together, renin-angiotensin-aldosterone system blockers are to date the only effective mainstay for the treatment of diabetic kidney disease (DKD). Indeed, several potentially nephroprotective agents have been in use, which have been unsuccessful. Some glucose-lowering agents, including dipeptidyl peptidase-4 inhibitors (DPP-4i), have shown promising results. Here, we discuss the evidence that glucose lowering with DPP-4i may be an option for protecting against diabetes-related renal injury. A comprehensive search was performed of the literature using the terms "alogliptin," "linagliptin," "saxagliptin," "sitagliptin," and "vildagliptin" for original articles and reviews addressing this topic. DPP-4i are an effective, well-tolerated treatment option for T2DM with any degree of renal impairment. Preclinical observations and clinical studies suggest that DPP-4i might also be a promising strategy for the treatment of DKD. The available data are in favor of saxagliptin and linagliptin, but the consistency of results points to the possible nephroprotective effect of DPP-4i. This property appears to be independent of glucose lowering and can potentially complement other therapies that preserve renal function. Larger prospective clinical trials are ongoing, which might strengthen these hypothesis-generating findings. The improvement in albuminuria associated with DPP-4i suggests that these agents may provide renal benefits beyond their glucose-lowering effects, thus offering direct protection from DKD. These promising results must be interpreted with caution and need to be confirmed in forthcoming studies. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human

  7. Association Between Inflammatory Markers and Progression to Kidney Dysfunction: Examining Different Assessment Windows in Patients With Type 1 Diabetes.

    Science.gov (United States)

    Baker, Nathaniel L; Hunt, Kelly J; Stevens, Danielle R; Jarai, Gabor; Rosen, Glenn D; Klein, Richard L; Virella, Gabriel; Lopes-Virella, Maria F

    2018-01-01

    To determine whether biomarkers of inflammation and endothelial dysfunction are associated with the development of kidney dysfunction and the time frame of their association. Biomarkers were measured at four time points during 28 years of treatment and follow-up in patients with type 1 diabetes in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort. In addition to traditional biomarkers of inflammation (C-reactive protein and fibrinogen), we measured interleukin-6 (IL-6) and soluble tumor necrosis factor receptors 1 and 2 (sTNFR-1/2), markers of endothelial dysfunction (soluble intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin [sE-selectin]), and fibrinolysis (total and active plasminogen activator inhibitor-1 [PAI-1]). Renal outcomes were defined as progression to incident chronic kidney disease (stage 3 or more severe) or macroalbuminuria (albumin excretion rate ≥300 mg/24 h). Prospective multivariate event-time analyses were used to determine the association of each biomarker with each subsequent event within prespecified intervals (3-year and 10-year windows). Multivariate event-time models indicated that several markers of inflammation (sTNFR-1/2), endothelial dysfunction (sE-selectin), and clotting/fibrinolysis (fibrinogen and PAI-1) are significantly associated with subsequent development of kidney dysfunction. Although some markers showed variations in the associations between the follow-up windows examined, the results indicate that biomarkers (sTNFR-1/2, sE-selectin, PAI-1, and fibrinogen) are associated with progression to chronic kidney disease in both the 3-year and the 10-year windows. Plasma markers of inflammation, endothelial dysfunction, and clotting/fibrinolysis are associated with progression to kidney dysfunction in type 1 diabetes during both short-term and long-term follow-up. © 2017 by the American Diabetes Association.

  8. Curcumin restores mitochondrial functions and decreases lipid peroxidation in liver and kidneys of diabetic db/db mice

    Directory of Open Access Journals (Sweden)

    María G Soto-Urquieta

    2014-01-01

    Full Text Available BACKGROUND: Nitrosative and oxidative stress play a key role in obesity and diabetes-related mitochondrial dysfunction. The objective was to investigate the effect of curcumin treatment on state 3 and 4 oxygen consumption, nitric oxide (NO synthesis, ATPase activity and lipid oxidation in mitochondria isolated from liver and kidneys of diabetic db/db mice. RESULTS: Hyperglycaemia increased oxygen consumption and decreased NO synthesis in liver mitochondria isolated from diabetic mice relative to the control mice. In kidney mitochondria, hyperglycaemia increased state 3 oxygen consumption and thiobarbituric acid-reactive substances (TBARS levels in diabetic mice relative to control mice. Interestingly, treating db/db mice with curcumin improved or restored these parameters to normal levels; also curcumin increased liver mitochondrial ATPase activity in db/db mice relative to untreated db/db mice. CONCLUSIONS: These findings suggest that hyperglycaemia modifies oxygen consumption rate, NO synthesis and increases TBARS levels in mitochondria from the liver and kidneys of diabetic mice, whereas curcumin may have a protective role against these alterations.

  9. Natural course of kidney function in Type 2 diabetic patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Christensen, P K; Rossing, P; Nielsen, F S

    1999-01-01

    normotensive to borderline hypertensive Type 2 DM patients with diabetic nephropathy. Glomerular filtration rate (GFR) was measured approximately every year (51Cr-EDTA plasma clearance technique). Albuminuria, blood pressure (BP) and haemoglobin A1c (HbA1c) was determined 2-4 times per year and serum...... cholesterol every second year. RESULTS: The patients (12 males/one female), age 56+/-9 (mean +/- SD) years, with a known duration of diabetes of 10+/-6 years, were followed for 55 (24-105) (median (range)) months. GFR decreased from 104 (50-126) to 80 (39-112) ml x min(-1) x 1.73 m(-2) (P = 0.......002) with a median rate of decline of 4.5 (-0.4 to 12) ml x min(-1) x year(-1). During follow-up, albuminuria rose from 494 (301-1868) to 908 (108-2169) mg/24 h (P = 0.25), while BP, HbA1c and serum cholesterol remained essentially unchanged. In univariate analysis the rate of decline in GFR did not correlate...

  10. Antioxidant agents for delaying diabetic kidney disease progression: A systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Davide Bolignano

    Full Text Available Oxidative stress is a key player in the genesis and worsening of diabetic kidney disease (DKD. We aimed at collecting all available information on possible benefits of chronic antioxidant supplementations on DKD progression.Systematic review and meta-analysis.Adults with DKD (either secondary to type 1 or 2 diabetes mellitus.Cochrane CENTRAL, Ovid-MEDLINE and PubMed were searched for randomized controlled trials (RCTs or quasi-RCTs without language or follow-up restriction.Any antioxidant supplementation (including but not limited to vitamin A, vitamin C, vitamin E, selenium, zinc, methionine or ubiquinone alone or in combination.Primary outcome was progression to end-stage kidney disease (ESKD. Secondary outcomes were change in albuminuria, proteinuria, serum creatinine and renal function.From 13519 potentially relevant citations retrieved, 15 articles referring to 14 full studies (4345 participants met the inclusion criteria. Antioxidant treatment significantly decreased albuminuria as compared to control (8 studies, 327 participants; SMD: -0.47; 95% CI -0.78, -0.16 but had apparently no tangible effects on renal function (GFR (3 studies, 85 participants; MD -0.12 ml/min/1.73m2; 95% CI -0.06, 0.01. Evidence of benefits on the other outcomes of interest was inconclusive or lacking.Small sample size and limited number of studies. Scarce information available on hard endpoints (ESKD. High heterogeneity among studies with respect to DKD severity, type and duration of antioxidant therapy.In DKD patients, antioxidants may improve early renal damage. Future studies targeting hard endpoints and with longer follow-up and larger sample size are needed to confirm the usefulness of these agents for retarding DKD progression.

  11. Using optical coherence tomography (OCT) to evaluate the status of human donor kidneys (Conference Presentation)

    Science.gov (United States)

    Andrews, Peter M.; Konkel, Brandon; Anderson, Erik; Stein, Matthew; Cooper, Matthew; Verbesey, Jennifer E.; Ghasemian, Seyed; Chen, Yu

    2016-02-01

    The main cause of delayed renal function following the transplant of donor kidneys is ischemic induced acute tubular necrosis (ATN). The ability to determine the degree of ATN suffered by donor kidneys prior to their transplant would enable transplant surgeons to use kidneys that might otherwise be discarded and better predict post-transplant renal function. Currently, there are no reliable tests to determine the extent of ATN of donor kidneys prior to their transplant. In ongoing clinical trials, we have been using optical coherence tomography (OCT) to non-invasively image the superficial proximal tubules of human donor kidneys prior to and following transplant, and correlate these observations with post-transplant renal function. Thus far we have studied over 40 living donor kidneys and 10 cadaver donor kidneys, and demonstrated that this imaging can be performed in a sterile and expeditious fashion in the operating room (OR). Because of many variables associated with a diverse population of donors/recipients and transplant operation parameters, more transplant data must be collected prior to drawing definite conclusions. Nevertheless, our observations have thus far mirrored our previously published laboratory results indicating that damage to the kidney proximal tubules as indicated by tubule swelling is a good measure of post-transplant ATN and delayed graft function. We conclude that OCT is a useful procedure for analyzing human donor kidneys.

  12. Experimental diabetes increases insulin-like growth factor I and II receptor concentration and gene expression in kidney

    International Nuclear Information System (INIS)

    Werner, H.; Shen-Orr, Z.; Stannard, B.; Burguera, B.; Roberts, C.T. Jr.; LeRoith, D.

    1990-01-01

    Insulinlike growth factor I (IGF-I) is a mitogenic hormone with important regulatory roles in growth and development. One of the target organs for IGF-I action is the kidney, which synthesizes abundant IGF-I receptors and IGF-I itself. To study the involvement of IGF-I and the IGF-I receptor in the development of nephropathy, one of the major complications of diabetes mellitus, we measured the expression of these genes in the kidney and in other tissues of the streptozocin-induced diabetic rat. The binding of 125I-labeled IGF-I to crude membranes was measured in the same tissues. We observed a 2.5-fold increase in the steady-state level of IGF-I-receptor mRNA in the diabetic kidney, which was accompanied by a 2.3-fold increase in IGF-I binding. In addition to this increase in IGF-I binding to the IGF-I receptor, there was also binding to a lower-molecular-weight material that may represent an IGF-binding protein. No change was detected in the level of IGF-I-peptide mRNA. Similarly, IGF-II-receptor mRNA levels and IGF-II binding were significantly increased in the diabetic kidney. IGF-I- and IGF-II-receptor mRNA levels and IGF-I and IGF-II binding returned to control values after insulin treatment. Because the IGF-I receptor is able to transduce mitogenic signals on activation of its tyrosine kinase domain, we hypothesize that, among other factors, high levels of receptor in the diabetic kidney may also be involved in the development of diabetic nephropathy. Increased IGF-II-receptor expression in the diabetic kidney may be important for the intracellular transport and packaging of lysosomal enzymes, although a role for this receptor in signal transduction cannot be excluded. Finally, the possible role of IGF-binding proteins requires further study

  13. Human Genetics of Diabetic Retinopathy: Current Perspectives

    Directory of Open Access Journals (Sweden)

    Daniel P. K. Ng

    2010-01-01

    Full Text Available Diabetic retinopathy (DR is a most severe microvascular complication which, if left unchecked, can be sight-threatening. With the global prevalence of diabetes being relentlessly projected to rise to 438 million subjects by 2030, DR will undoubtedly pose a major public health concern. Efforts to unravel the human genetics of DR have been undertaken using the candidate gene and linkage approaches, while GWAS efforts are still lacking. Aside from evidence for a few genes including aldose reductase and vascular endothelial growth factor, the genetics of DR remain poorly elucidated. Nevertheless, the promise of impactful scientific discoveries may be realized if concerted and collaborative efforts are mounted to identify the genes for DR. Harnessing new genetic technologies and resources such as the upcoming 1000 Genomes Project will help advance this field of research, and potentially lead to a rich harvest of insights into the biological mechanisms underlying this debilitating complication.

  14. At Risk for Kidney Disease?

    Science.gov (United States)

    ... Heart Disease Mineral & Bone Disorder Causes of Chronic Kidney Disease Diabetes and high blood pressure are the most ... blood vessels in your kidneys. Other causes of kidney disease Other causes of kidney disease include a genetic ...

  15. Evaluation of the Zucker diabetic fatty (ZDF rat as a model for human disease based on urinary peptidomic profiles.

    Directory of Open Access Journals (Sweden)

    Justyna Siwy

    Full Text Available Representative animal models for diabetes-associated vascular complications are extremely relevant in assessing potential therapeutic drugs. While several rodent models for type 2 diabetes (T2D are available, their relevance in recapitulating renal and cardiovascular features of diabetes in man is not entirely clear. Here we evaluate at the molecular level the similarity between Zucker diabetic fatty (ZDF rats, as a model of T2D-associated vascular complications, and human disease by urinary proteome analysis. Urine analysis of ZDF rats at early and late stages of disease compared to age- matched LEAN rats identified 180 peptides as potentially associated with diabetes complications. Overlaps with human chronic kidney disease (CKD and cardiovascular disease (CVD biomarkers were observed, corresponding to proteins marking kidney damage (eg albumin, alpha-1 antitrypsin or related to disease development (collagen. Concordance in regulation of these peptides in rats versus humans was more pronounced in the CVD compared to the CKD panels. In addition, disease-associated predicted protease activities in ZDF rats showed higher similarities to the predicted activities in human CVD. Based on urinary peptidomic analysis, the ZDF rat model displays similarity to human CVD but might not be the most appropriate model to display human CKD on a molecular level.

  16. The association of ACE gene polymorphism with diabetic kidney disease and renoprotective efficacy of valsartan

    Directory of Open Access Journals (Sweden)

    Yuying Wang

    2016-09-01

    Full Text Available Introduction: To investigate the associations between the insertion/deletion (I/D polymorphisms in the angiotensin converting enzyme (ACE gene and susceptibility to diabetic kidney disease (DKD; and the efficacy of valsartan in reducing the urine protein in Type 2 diabetes mellitus (T2DM patients. Materials and methods: We enrolled 128 T2DM patients in this study, including 54 cases with DKD (DKD+ and 74 controls (DKD–. The ACE polymorphism was assayed by polymerase chain reaction (PCR, and the genotype distribution and allele frequency were analyzed. The DKD+ group was subdivided into the DD, ID and II subgroups, based on their genotypes. In addition, patients with DKD received valsartan treatment for 12 weeks. We determined changes in the urinary albumin to creatinine ratio (ACR and serum creatinine (SCr. Results: The frequencies of the genotypes DD and ID were higher in the DKD+ than in the DKD– group. The frequency of allele D was higher, and of allele I was lower, in the DKD+ than in DKD– group (p < 0.05. Following valsartan treatment, albuminuria was significantly decreased in subgroups DD and ID (p < 0.05. Conclusions: In T2DM patients, the ACE I/D polymorphism was associated with onset of DKD. Furthermore, the ACE I/D polymorphism influenced the renoprotective response to valsartan: Patients with the DD genotype benefitted the most from this treatment.

  17. The association of ACE gene polymorphism with diabetic kidney disease and renoprotective efficacy of valsartan.

    Science.gov (United States)

    Wang, Yuying; Peng, Wen; Zhang, Xiaoxue; Qiao, Huibo; Wang, Li; Xu, Zhigang; Wu, Chenguang

    2016-07-01

    To investigate the associations between the insertion/deletion (I/D) polymorphisms in the angiotensin converting enzyme (ACE) gene and susceptibility to diabetic kidney disease (DKD); and the efficacy of valsartan in reducing the urine protein in Type 2 diabetes mellitus (T2DM) patients. We enrolled 128 T2DM patients in this study, including 54 cases with DKD (DKD+) and 74 controls (DKD-). The ACE polymorphism was assayed by polymerase chain reaction (PCR), and the genotype distribution and allele frequency were analyzed. The DKD+ group was subdivided into the DD, ID and II subgroups, based on their genotypes. In addition, patients with DKD received valsartan treatment for 12 weeks. We determined changes in the urinary albumin to creatinine ratio (ACR) and serum creatinine (SCr). The frequencies of the genotypes DD and ID were higher in the DKD+ than in the DKD- group. The frequency of allele D was higher, and of allele I was lower, in the DKD+ than in DKD- group (p ACE I/D polymorphism was associated with onset of DKD. Furthermore, the ACE I/D polymorphism influenced the renoprotective response to valsartan: Patients with the DD genotype benefitted the most from this treatment. © The Author(s) 2016.

  18. [Study on prevention and treatment of middle and aged women diabetes with kidney deficiency and bone metabolic disturbance].

    Science.gov (United States)

    Zhu, L; Li, H; Liu, Y

    1999-04-01

    To Study the therapeutic effect of Chinese herbal medicine (CHM) for supplementing Qi, activating blood circulation and tonifying Kidney on prevention and treatment of middle and aged women diabetes with Kidney Deficiency and bone metabolic disturbance. Clinical observation was taken in 52 patients, who were divided into two groups, the control group (treated with hypoglycemic agent alone) and the treated group (treated with hypoglycemic agent and CHM). Before treatment, patients of both groups showed obvious higher blood alkaline phosphatase, beta 2-microglobulin (beta 2-MG) level, urinary beta 2-MG, calcium and phosphorus level, but lower serum estradiol level than those in normal subjects. After 3 months' treatment, no apparent change on serum estradiol level was observed, but other parameters were all lowered obviously in the two groups, the changes revealed more obvious in the treated group. The symptoms of Kidney Deficiency, such as lumbodorsal pain, general fatigue, palpitation and vertigo, were improved after treatment, and the improvement was also more obvious in the treated group. CHM for supplementing Qi, activating blood circulation and tonifying Kidney was effective in improving Kidney Deficiency and mineral substance loss of bone in middle and aged women diabetes patients. The CHM and western drugs may acted synergistically.

  19. TGP attenuates endoplasmic reticulum stress and regulates the expression of thioredoxin-interacting protein in the kidneys of diabetic rats.

    Science.gov (United States)

    Shao, Yunxia; Qi, Xiangming; Xu, Xinxing; Wang, Kun; Wu, Yonggui; Xia, Lingling

    2017-01-16

    Recent evidence suggests that the endoplasmic reticulum stress (ERS)-thioredoxin-interacting protein (TXNIP)-inflammation chain contributes to diabetic renal injury. The aim of the current study was to investigate whether total glucosides of peony (TGP) could inhibit ERS and attenuate up-regulation of TXNIP in the kidneys of rats with streptozotocin-induced diabetes. TGP was orally administered daily at a dose of 50, 100, or 200 mg/kg for 8 weeks. The expression of glucose-regulated protein 78 (GRP78), phospho-protein kinase RNA-like ER kinase (p-PERK), phosphor- eukaryotic translation initiation factor 2α (p-eIF2α), C/EBP-homologous protein (CHOP), and TXNIP was assessed. Results indicated that TGP significantly decreased diabetes-induced albuminuria and it acted by down-regulating activation of the ERS-TXNIP-inflammation chain in the kidneys of diabetic rats. These findings indicate that renoprotection from TGP in diabetic rats possibly contributed to inhibition of ERS and decreased expression of TXNIP. These findings also offer a new perspective from which to study the molecular mechanisms of diabetic nephropathy and prevent its progression.

  20. Relationships between serum MCP-1 and subclinical kidney disease: African American-Diabetes Heart Study

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    Murea Mariana

    2012-11-01

    Full Text Available Abstract Background Monocyte chemoattractant protein-1 (MCP-1 plays important roles in kidney disease susceptibility and atherogenesis in experimental models. Relationships between serum MCP-1 concentration and early nephropathy and subclinical cardiovascular disease (CVD were assessed in African Americans (AAs with type 2 diabetes (T2D. Methods Serum MCP-1 concentration, urine albumin:creatinine ratio (ACR, estimated glomerular filtration rate (eGFR, and atherosclerotic calcified plaque (CP in the coronary and carotid arteries and infrarenal aorta were measured in 479 unrelated AAs with T2D. Generalized linear models were fitted to test for associations between MCP-1 and urine ACR, eGFR, and CP. Results Participants were 57% female, with mean ± SD (median age 55.6±9.5 (55.0 years, diabetes duration 10.3±8.2 (8.0 years, urine ACR 149.7±566.7 (14.0 mg/g, CKD-EPI eGFR 92.4±23.3 (92.0 ml/min/1.73m2, MCP-1 262.9±239.1 (224.4 pg/ml, coronary artery CP 280.1±633.8 (13.5, carotid artery CP 47.1±132.9 (0, and aorta CP 1616.0±2864.0 (319.0. Adjusting for age, sex, smoking, HbA1c, BMI, and LDL, serum MCP-1 was positively associated with albuminuria (parameter estimate 0.0021, P=0.04 and negatively associated with eGFR (parameter estimate −0.0003, P=0.001. MCP-1 remained associated with eGFR after adjustment for urine ACR. MCP-1 levels did not correlate with the extent of CP in any vascular bed, HbA1c or diabetes duration, but were positively associated with BMI. No interaction between BMI and MCP-1 was detected on nephropathy outcomes. Conclusions Serum MCP-1 levels are associated with eGFR and albuminuria in AAs with T2D. MCP-1 was not associated with subclinical CVD in this population. Inflammation appears to play important roles in development and/or progression of kidney disease in AAs.

  1. A transcriptional profile of aging in the human kidney.

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    Graham E J Rodwell

    2004-12-01

    Full Text Available In this study, we found 985 genes that change expression in the cortex and the medulla of the kidney with age. Some of the genes whose transcripts increase in abundance with age are known to be specifically expressed in immune cells, suggesting that immune surveillance or inflammation increases with age. The age-regulated genes show a similar aging profile in the cortex and the medulla, suggesting a common underlying mechanism for aging. Expression profiles of these age-regulated genes mark not only age, but also the relative health and physiology of the kidney in older individuals. Finally, the set of aging-regulated kidney genes suggests specific mechanisms and pathways that may play a role in kidney degeneration with age.

  2. Human leukocyte antigen (HLA) polymorphism and type 1 diabetes ...

    African Journals Online (AJOL)

    Insulin-dependent diabetes mellitus or type 1 diabetes is an autoimmune multifactorial disease which has a great socio-economic impact. In Morocco, less is known about the contribution of Human leukocyte antigen (HLA) alleles to type 1 diabetes susceptibility. Our study focused on evaluating the distribution of class II ...

  3. Development of the Human Fetal Kidney from Mid to Late Gestation in Male and Female Infants

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    Danica Ryan

    2018-01-01

    Interpretation: These findings highlight spatial and temporal variability in nephrogenesis in the developing human kidney, whereas the relative cellular composition of glomeruli does not appear to be influenced by gestational age.

  4. Can glycated hemoglobin act as a reliable glycemic indicator in patients with diabetic chronic kidney disease? evidence from the Northeast of Thailand

    OpenAIRE

    Sojib Bin Zaman; Naznin Hossain; Ahmed E. Rahman; Sheikh M.S. Islam

    2017-01-01

    Background: Chronic kidney diseases (CKD) is a common microvascular complication in patients with diabetes mellitus (DM) which requires adequate glycemic control. Glycated hemoglobin (HbA1c) is a conventional biomarker to estimate glycemic status, but its role in diabetic CKD patients is unclear. Therefore, this study aimed to determine whether patients with high HbA1c are associated to develop diabetic CKD.Methods: Data were obtained from a clinical registry of diabetic patients who were tre...

  5. Kidney Transplantation: MedlinePlus Health Topic

    Science.gov (United States)

    ... as They Affect Physical Fitness: A Physical Therapist's Point of View (National Kidney Foundation) Solitary Kidney (National Institute of Diabetes and Digestive and Kidney Diseases) Travel Tips: A Guide for Kidney Patients (National Kidney ...

  6. Lipid metabolism and levels of proinflammatory cytokines in patients with type 2 diabetes with diabetic nephropathy depending on the stage of chronic kidney disease

    Directory of Open Access Journals (Sweden)

    2012-06-01

    Full Text Available Aim: to study the role and relationship of lipid metabolism and levels of proinflammatory cytokines in patients with type 2 diabetes mellitus (DM2 with diabetic nephropathy (DN, depending on the stage of chronic kidney disease (CKD. Materials and Methods: a total of 240 patients with type 2 diabetes in the early stages of DN and CKD were studied. Results: in patients with type 2 diabetes development of DN was associated with an increased level of proinflammatory cytokines and lipid abnormalities (hypertriglyceridemia. We found a negative correlation between the level of triglycerides (TG and glomerular filtration rate (GFR (r = -0,43 and a direct correlation between the level of IL-6 and TG (r = 0,48. Conclusions: increased levels of proinflammatory cytokines and triglycerides increase the risk of development and progression of DN and CKD.

  7. Metaplasia of the parietal layer of Bowman's capsule in the human kidney. Incidence in alcoholic liver disease and hypertension

    OpenAIRE

    Haensly, William E.

    1988-01-01

    This report is the second of two surveys to determine the incidence of metaplasia of Bowman's parietal epithelium in the human kidney. Human kidney sections obtained at autopsy at the Department of Pathology, University of Texas Medical Branch, Galveston, Texas, were examined with the light microscope. The kidneys were fixed in neutral formalin, sectioned at 6 pm and stained with hematoxylin and eosin. Autopsy records were consulted after kidney section exa...

  8. Total glucosides of paeony regulates JAK2/STAT3 activation and macrophage proliferation in diabetic rat kidneys.

    Science.gov (United States)

    Wang, Kun; Wu, Yong-Gui; Su, Jing; Zhang, Jing-Jing; Zhang, Pei; Qi, Xiang-Ming

    2012-01-01

    Total glucosides of paeony (TGP) is the major active constituent of Paeonia lactiflora Pall., which has shown renoprotection in experimental diabetic nephropathy. Activation of Janus kinase/signal transducers and activators of transcription (JAK/STAT) is an important mechanism by which hyperglycemia contributes to renal damage. Macrophages also play an essential role in the pathogenesis of diabetic nephropathy. Herein, we investigated the ability of TGP to modulate JAK2/STAT3 activation and macrophage proliferation in rats with streptozotocin (STZ)-induced diabetes. TGP (50, 100, and 200 mg/kg) was administered orally once a day for eight weeks. Levels of p-JAK2 and p-STAT3 were determined by Western blot analysis. Immunohistochemistry and double immunohistochemistry were used to identify p-STAT3, ED-1, PCNA/ED-1, and p-STAT3/ED-1-positive (+) cells. The elevated 24-h urinary albumin excretion rate was markedly attenuated by treatment with 50, 100, and 200 mg/kg TGP. Western blot analysis showed that the significantly increased levels of p-JAK2, p-STAT3 proteins in the kidneys of diabetic rats were significantly inhibited by 50, 100, and 200 mg/kg TGP treatment. The marked accumulation and proliferation of macrophages in diabetic kidneys were significantly inhibited by TGP treatment. ED-1+/p-STAT3+ cells were significantly increased in the kidneys from the model group but were significantly inhibited by TGP treatment. These results show that TGP significantly inhibited diabetic nephropathy progression and suggest that these protective effects are associated with the ability of TGP to inhibit the JAK2/STAT3 pathway and macrophage proliferation and action.

  9. Expression of stem cell markers in the human fetal kidney.

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    Sally Metsuyanim

    Full Text Available In the human fetal kidney (HFK self-renewing stem cells residing in the metanephric mesenchyme (MM/blastema are induced to form all cell types of the nephron till 34(th week of gestation. Definition of useful markers is crucial for the identification of HFK stem cells. Because wilms' tumor, a pediatric renal cancer, initiates from retention of renal stem cells, we hypothesized that surface antigens previously up-regulated in microarrays of both HFK and blastema-enriched stem-like wilms' tumor xenografts (NCAM, ACVRIIB, DLK1/PREF, GPR39, FZD7, FZD2, NTRK2 are likely to be relevant markers. Comprehensive profiling of these putative and of additional stem cell markers (CD34, CD133, c-Kit, CD90, CD105, CD24 in mid-gestation HFK was performed using immunostaining and FACS in conjunction with EpCAM, an epithelial surface marker that is absent from the MM and increases along nephron differentiation and hence can be separated into negative, dim or bright fractions. No marker was specifically localized to the MM. Nevertheless, FZD7 and NTRK2 were preferentially localized to the MM and emerging tubules (50% of HFK cells and predominantly co-express EpCAM(bright, indicating they are mostly markers of differentiation. Furthermore, localization of NCAM exclusively in the MM and in its nephron progenitor derivatives but also in stroma and the expression pattern of significantly elevated renal stem/progenitor genes Six2, Wt1, Cited1, and Sall1 in NCAM(+EpCAM(- and to a lesser extent in NCAM(+EpCAM(+ fractions confirmed regional identity of cells and assisted us in pinpointing the presence of subpopulations that are putative MM-derived progenitor cells (NCAM(+EpCAM(+FZD7(+, MM stem cells (NCAM(+EpCAM(-FZD7(+ or both (NCAM(+FZD7(+. These results and concepts provide a framework for developing cell selection strategies for human renal cell-based therapies.

  10. [Effect of total glucosides of paeony on Wnt/β-catenin signal transduction pathway expression in kidney of diabetic rats].

    Science.gov (United States)

    Chang, Bao-Chao; Chen, Wei-Dong; Zhang, Yan; Yang, Ping; Liu, Lei; Wang, Jing

    2014-10-01

    The study is to explore the effect of total glucosides of paeony (TGP)on Wnt/β-catenin signal transduction pathway expression in kidney of diabetic rats, and discuss the protection of TGP in diabetic nephropathy and possible mechanism. Ninety male SD rats of 8 weeks age were randomly divided into normal control group (n = 10) and model group (n = 80). Rats of the normal control group were fed with regular diet, while rats of the model group were fed with high-fat high-sugar diet and 4 weeks later were given an intraperitoneal injection of 35 mg x kg(-1) streptozotocin (STZ). The successfully induced type 2 diabetic rat models were then randomly divided into DM group, three TGP (50, 100, 200 mg x kg(-1) x d(-1)) treatment group and tripterygium wilfordii glycosides (8 mg x kg(-1) x d(-1)) control group. Rats of DM group and each treatment group were given high-fat high-sugar diet. At week 14, the levels of blood sugar, 24 hour urine protein, serum creatinine and blood urea nitrogen were tested. The rats were then sacrificed. Renal pathological changes were examined. Renal tissue Wnt-1 and β-catenin expressions were detected by immunohistochemical assay. Wnt-1 mRNA and β-catenin mRNA expression was semi-quantified by RT-PCR. Wnt-1 protein and β-catenin protein expression was semi-quantified by Western blot. The Result show that Wnt-1 and β-catenin expression increased in kidney of high-fat high-sugar induced type 2 diabetic rats. Compared with diabetic group, the level of serum creatinine, blood urea nitrogen, 24 h urine protein, mean glomerular area and mean glomerular volume were decreased, renal histopathology were improved, expression of Wnt-1 and β-catenin mRNA and protein was reduced in TGP group. Tripterygium wilfordii glycosides had the similar effect. In conclusion, these results showed that Wnt/β-catenin abnormal activation in kidney of type 2 diabetic rats, TGP can improve kidney damage in diabetic rats and delay the development of diabetic

  11. Rationale and trial design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes

    DEFF Research Database (Denmark)

    de Zeeuw, Dick; Akizawa, Tadao; Agarwal, Rajiv

    2013-01-01

    Chronic kidney disease (CKD) associated with type 2 diabetes mellitus constitutes a global epidemic complicated by considerable renal and cardiovascular morbidity and mortality, despite the provision of inhibitors of the renin-angiotensin-aldosterone system (RAAS). Bardoxolone methyl, a synthetic...... triterpenoid that reduces oxidative stress and inflammation through Nrf2 activation and inhibition of NF-κB was previously shown to increase estimated glomerular filtration rate (eGFR) in patients with CKD associated with type 2 diabetes mellitus. To date, no antioxidant or anti-inflammatory therapy has proved...

  12. Renoprotective effects of thiazides combined with loop diuretics in patients with type 2 diabetic kidney disease.

    Science.gov (United States)

    Hoshino, Taro; Ookawara, Susumu; Miyazawa, Haruhisa; Ito, Kiyonori; Ueda, Yuichiro; Kaku, Yoshio; Hirai, Keiji; Mori, Honami; Yoshida, Izumi; Tabei, Kaoru

    2015-04-01

    Type 2 diabetic kidney disease (DKD) is frequently accompanied by uncontrollable hypertension due to the sodium sensitivity inherent in DKD and to diuretic-resistant edema. In general, diuretics are effective in treating this condition, but thiazide diuretics are thought to be innocuous in advanced chronic kidney disease (CKD). We examined the renoprotective effects of combination therapy with thiazides and loop diuretics in type 2 DKD patients with CKD stage G4 or G5. This study included 11 patients with type 2 DKD and an estimated glomerular filtration rate (eGFR) diuretics. Each patient received additional hydrochlorothiazide (HCTZ) therapy, which was continued for more than 12 months. We examined clinical parameters including blood pressure (BP), proteinuria, and eGFR before and after the addition of HCTZ. Patients received a 13.6 ± 3.8 mg/day dose of HCTZ in addition to loop diuretics (azosemide: 120 mg/day in 6 cases, 60 mg/day in 3 cases and furosemide: 80 mg/day in 1 case, 120 mg/day in 1 case). Side effects of HCTZ were not observed in all patients. After the addition of HCTZ therapy, systolic and diastolic blood pressures (S-BP, D-BP) as well as proteinuria significantly decreased (S-BP: at 6 months, p diuretics improves BP levels, and decreases proteinuria even in advanced stage type 2 DKD patients with severe edema. The addition of HCTZ therapy was not found to negatively affect the change in eGFR in the present study.

  13. Diabetes-associated dry eye syndrome in a new humanized transgenic model of type 1 diabetes.

    Science.gov (United States)

    Imam, Shahnawaz; Elagin, Raya B; Jaume, Juan Carlos

    2013-01-01

    Patients with Type 1 Diabetes (T1D) are at high risk of developing lacrimal gland dysfunction. We have developed a new model of human T1D using double-transgenic mice carrying HLA-DQ8 diabetes-susceptibility haplotype instead of mouse MHC-class II and expressing the human beta cell autoantigen Glutamic Acid Decarboxylase in pancreatic beta cells. We report here the development of dry eye syndrome (DES) after diabetes induction in our humanized transgenic model. Double-transgenic mice were immunized with DNA encoding human GAD65, either naked or in adenoviral vectors, to induce T1D. Mice monitored for development of diabetes developed lacrimal gland dysfunction. Animals developed lacrimal gland disease (classically associated with diabetes in Non Obese Diabetic [NOD] mice and with T1D in humans) as they developed glucose intolerance and diabetes. Animals manifested obvious clinical signs of dry eye syndrome (DES), from corneal erosions to severe keratitis. Histological studies of peri-bulbar areas revealed lymphocytic infiltration of glandular structures. Indeed, infiltrative lesions were observed in lacrimal/Harderian glands within weeks following development of glucose intolerance. Lesions ranged from focal lymphocytic infiltration to complete acinar destruction. We observed a correlation between the severity of the pancreatic infiltration and the severity of the ocular disease. Our results demonstrate development of DES in association with antigen-specific insulitis and diabetes following immunization with clinically relevant human autoantigen concomitantly expressed in pancreatic beta cells of diabetes-susceptible mice. As in the NOD mouse model and as in human T1D, our animals developed diabetes-associated DES. This specific finding stresses the relevance of our model for studying these human diseases. We believe our model will facilitate studies to prevent/treat diabetes-associated DES as well as human diabetes.

  14. Effects of Averrhoa carambola L. (Oxalidaceae) juice mediated on hyperglycemia, hyperlipidemia, and its influence on regulatory protein expression in the injured kidneys of streptozotocin-induced diabetic mice.

    Science.gov (United States)

    Pham, Hoa Thi Thai; Huang, Wansu; Han, Chuangye; Li, Juman; Xie, Qiuqiao; Wei, Jinbin; Xu, Xiaohui; Lai, Zefeng; Huang, Xiang; Huang, Renbin; Wen, Qingwei

    2017-01-01

    Recently, many reports have shown that Averrhoa carambola L. (Oxalidaceae) juice (EACJ) could reduce blood glucose in humans. However, its mechanisms have not been well explored; therefore, our study aimed to investigate the beneficial effects of EACJ on hyperglycemia, hyperlipidemia and renal injury in streptozotocin (STZ)-induced diabetic mice. Those mice were injected with STZ via the tail vein (120 mg/kg body weight) and were identified as diabetic mice when the level of blood glucose was ≥ 11.1 mmol/L. Those mice were intragastriced gavage with saline, EACJ (25, 50, 100 g/kg body weight/d) and metformin (320 mg/kg body weight/d) for 21 days. The fasting blood glucose (FBG), free fatty acids (FFA), total cholesterol (TC), triglycerides (TG), Scr (CREA) and blood urea nitrogen (BUN) were significantly decreased, while the sorbitol dehydrogenase (SDH), Cyclic Adenosine monophosphate (cAMP), malondialdehyde (MDA), superoxide dismutase (SOD), and insulin were elevated. Diabetes-dependent alterations in the kidney, such as glomerular hypertrophy, thicken and tubular basement membrane, were improved after 21 days of EACJ treatment. Hyperglycemia, renal formation and the expressions of related proteins such as connective tissue growth factor (CTGF) and transforming growth factor beta 1 (TGF-β1) were markedly decreased by EACJ. These results indicate that EACJ treatment decrease hyperglycemia, hyperlipidemia and inhibit the progression of diabetic nephropathy (DN), which may be linked to regulating several pharmacological targets for treating or preventing DN.

  15. Effect of alogliptin on hypertensive chronic kidney disease patients with type 2 diabetes mellitus

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    Amira Said

    2018-02-01

    Full Text Available Background Diabetes mellitus (DM is a leading cause of chronic kidney disease (CKD. The antihyperglycemic treatment options for patients with Type 2 DM are limited because of safety and tolerability concerns. Aims To retrospectively assess the effect of using Alogliptin; a dipeptidyl peptidase-4 inhibitor (DPP-4i along with conventional gliclazide: a sulphonylurea (SU on renal outcomes and glycaemic control in T2DM patients with mild CKD and hypertension. Methods A total of 76 patient records (38 males and 38 females of patient ages 40–60 were analysed from the kidney unit at Punjab Care hospital, Lahore, Pakistan. All patients had a confirmed history of T2DM with mild CKD and established hypertension. Eligible patients were divided into two groups of 38 individuals each. Group SU received gliclazide monotherapy (SU or Alogliptin (DPP-4i+gliclazide (SU add on therapy. All patients were followed up for 12 months. Results The alogliptin (DPP-4i plus gliclazide (SU add on therapy group, in comparison to the group only receiving gliclazide (SU, showed a significant difference in eGFR values. The mean±SD GFR values post 12 months were 74.8±0.31 (95%CI:74.8±0.09;74.7–74.9 and 76.1±0.25 (95%CI: 76.1±0.08;76.0-76.2 for SU vs. SU+DPP-4i, respectively, with mean calculated effect size of 1.6,. HbA1c, 1,5 AG and ipid profile values have significantly changed (p<0.05 while blood pressure values showed no change. The mean±SD systolic blood pressure readings post 12 months for for SU vs. SU+DPP-4i were 131.4±10.4 (95% CI 131.4±3.3;128.1– 134.7, and 131.8±9.9 (95%CI 131.8±3; 128.8–134.8, respectively. Conclusion In the present study, patients using alogliptin in addition to sulfonyl urea showed improved glycaemic control and lipid profile without increased occurrence of hypoglycaemia. We concluded that, DPP-4i inhibitors are safe treatment options for patients with type 2 diabetes and mild degree of renal impairment.

  16. Pulse pressure is not an independent predictor of outcome in type 2 diabetes patients with chronic kidney disease and anemia

    DEFF Research Database (Denmark)

    Theilade, S; Claggett, B; Hansen, T W

    2015-01-01

    Pulse pressure (PP) remains an elusive cardiovascular risk factor with inconsistent findings. We clarified the prognostic value in patients with type 2 diabetes, chronic kidney disease (CKD) and anemia in the Trial to Reduce cardiovascular Events with Aranesp (darbepoetin alfa) Therapy. In 4038......, CKD and anemia, PP did not independently predict cardiovascular events or ESRD. This may reflect confounding by aggressive antihypertensive treatment, or PP may be too rough a risk marker in these high-risk patients....

  17. Relationship between chronic kidney disease with diabetes or hypertension and frailty in community-dwelling Japanese older adults.

    Science.gov (United States)

    Lee, Sungchul; Lee, Sangyoon; Harada, Kazuhiro; Bae, Seongryu; Makizako, Hyuma; Doi, Takehiko; Tsutsumimoto, Kota; Hotta, Ryo; Nakakubo, Sho; Park, Hyuntae; Suzuki, Takao; Shimada, Hiroyuki

    2017-10-01

    The aim of the present study was to evaluate the relationship between kidney function with concomitant diabetes or hypertension and frailty in community-dwelling Japanese older adults. The participants were 9606 residents (community-dwelling Japanese older adults) who completed baseline assessments. The estimated glomerular filtration rate (mL/min/1.73 m 2 ) was determined according to the serum creatinine level, and participants were classified into four mutually exclusive categories: ≥60.0 (normal range), 45.0-59.9, 30.0-44.9 and who met three, four or five criteria satisfied the definition of having frailty. Multivariate logistic regression was used to examine the relationships between estimated glomerular filtration rate and frailty. After multivariate adjustment, participants with lower kidney function (estimated glomerular filtration rate hypertension (OR 2.53, 95% CI 1.45-5.12) showed a significantly increased risk of frailty in the lower kidney function group, regardless of multivariate controls. Furthermore, the analyses showed an even greater increase in the risk of frailty in patients with a history of both diabetes and hypertension (OR 3.67, 95% CI 1.13-14.1) CONCLUSIONS: A lower level of kidney function was associated with a higher risk of frailty in community-dwelling Japanese older adults. Geriatr Gerontol Int 2017; 17: 1527-1533. © 2016 Japan Geriatrics Society.

  18. Magnesium modifies the association between serum phosphate and the risk of progression to end-stage kidney disease in patients with non-diabetic chronic kidney disease.

    Science.gov (United States)

    Sakaguchi, Yusuke; Iwatani, Hirotsugu; Hamano, Takayuki; Tomida, Kodo; Kawabata, Hiroaki; Kusunoki, Yasuo; Shimomura, Akihiro; Matsui, Isao; Hayashi, Terumasa; Tsubakihara, Yoshiharu; Isaka, Yoshitaka; Rakugi, Hiromi

    2015-10-01

    It is known that magnesium antagonizes phosphate-induced apoptosis of vascular smooth muscle cells and prevents vascular calcification. Here we tested whether magnesium can also counteract other pathological conditions where phosphate toxicity is involved, such as progression of chronic kidney disease (CKD). We explored how the link between the risk of CKD progression and hyperphosphatemia is modified by magnesium status. A post hoc analysis was run in 311 non-diabetic CKD patients who were divided into four groups according to the median values of serum magnesium and phosphate. During a median follow-up of 44 months, 135 patients developed end-stage kidney disease (ESKD). After adjustment for relevant clinical factors, patients in the lower magnesium-higher phosphate group were at a 2.07-fold (95% CI: 1.23-3.48) risk for incident ESKD and had a significantly faster decline in estimated glomerular filtration rate compared with those in the higher magnesium-higher phosphate group. There were no significant differences in the risk of these renal outcomes among the higher magnesium-higher phosphate group and both lower phosphate groups. Incubation of tubular epithelial cells in high phosphate and low magnesium medium in vitro increased apoptosis and the expression levels of profibrotic and proinflammatory cytokine; these changes were significantly suppressed by increasing magnesium concentration. Thus, magnesium may act protectively against phosphate-induced kidney injury.

  19. Chronic kidney disease and diabetes mellitus predict resistance to vitamin D replacement therapy.

    Science.gov (United States)

    Alshayeb, Hala M; Wall, Barry M; Showkat, Arif; Mangold, Therese; Quarles, L Darryl

    2013-04-01

    25-Hydroxyvitamin D [25(OH)D] is a marker of nutritional status; however, chronic kidney disease (CKD) results in alterations in vitamin D metabolism, including the loss of vitamin D-binding proteins and alterations in CYP27B1 and CYP24 enzymes that metabolize 25(OH)D. This study was designed to determine the predictors of responsiveness to correction of vitamin D deficiency with oral vitamin D2 (ergocalciferol) in adults. A retrospective study of 183 veterans with 25(OH)D level vitamin D2, was performed. Logistic regression models were developed to determine the factors predicting the response to treatment, defined as either the change in serum 25(OH)D level/1000 IU of vitamin D2 or the number of vitamin D2 doses (50,000 IU per dose) administered. The mean age of the patients was 63 ± 12 years. About 87% were men and 51% diabetic, and 29% had an estimated glomerular filtration rate of vitamin D2 doses was 10.91 ± 5.95; the average increase in 25(OH)D level was 18 ± 10.80 ng/mL. 25(OH)D levels remained vitamin D2 treatment in logistic regression models. Patients with CKD required greater amounts of vitamin D2 to achieve similar increases in 25(OH)D levels, versus non-CKD patients. The presence of CKD and diabetes mellitus is associated with resistance to correction of 25(OH)D deficiency with vitamin D2 therapy. The underlying mechanism needs to be evaluated in prospective studies.

  20. Drugs meeting the molecular basis of diabetic kidney disease: bridging from molecular mechanism to personalized medicine.

    Science.gov (United States)

    Lambers Heerspink, Hiddo J; Oberbauer, Rainer; Perco, Paul; Heinzel, Andreas; Heinze, Georg; Mayer, Gert; Mayer, Bernd

    2015-08-01

    Diabetic kidney disease (DKD) is a complex, multifactorial disease and is associated with a high risk of renal and cardiovascular morbidity and mortality. Clinical practice guidelines for diabetes recommend essentially identical treatments for all patients without taking into account how the individual responds to the instituted therapy. Yet, individuals vary widely in how they respond to medications and therefore optimal therapy differs between individuals. Understanding the underlying molecular mechanisms of variability in drug response will help tailor optimal therapy. Polymorphisms in genes related to drug pharmacokinetics have been used to explore mechanisms of response variability in DKD, but with limited success. The complex interaction between genetic make-up and environmental factors on the abundance of proteins and metabolites renders pharmacogenomics alone insufficient to fully capture response variability. A complementary approach is to attribute drug response variability to individual variability in underlying molecular mechanisms involved in the progression of disease. The interplay of different processes (e.g. inflammation, fibrosis, angiogenesis, oxidative stress) appears to drive disease progression, but the individual contribution of each process varies. Drugs at the other hand address specific targets and thereby interfere in certain disease-associated processes. At this level, biomarkers may help to gain insight into which specific pathophysiological processes are involved in an individual followed by a rational assessment whether a specific drug's mode of action indeed targets the relevant process at hand. This article describes the conceptual background and data-driven workflow developed by the SysKid consortium aimed at improving characterization of the molecular mechanisms underlying DKD at the interference of the molecular impact of individual drugs in order to tailor optimal therapy to individual patients. © The Author 2015. Published by

  1. Low-Dose Radiation Activates Akt and Nrf2 in the Kidney of Diabetic Mice: A Potential Mechanism to Prevent Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Xiao Xing

    2012-01-01

    Full Text Available Repetitive exposure of diabetic mice to low-dose radiation (LDR at 25 mGy could significantly attenuate diabetes-induced renal inflammation, oxidative damage, remodeling, and dysfunction, for which, however, the underlying mechanism remained unknown. The present study explored the effects of LDR on the expression and function of Akt and Nrf2 in the kidney of diabetic mice. C57BL/6J mice were used to induce type 1 diabetes with multiple low-dose streptozotocin. Diabetic and age-matched control mice were irradiated with whole body X-rays at either single 25 mGy and 75 mGy or accumulated 75 mGy (25 mGy daily for 3 days and then sacrificed at 1–12 h for examining renal Akt phosphorylation and Nrf2 expression and function. We found that 75 mGy of X-rays can stimulate Akt signaling pathway and upregulate Nrf2 expression and function in diabetic kidneys; single exposure of 25 mGy did not, but three exposures to 25 mGy of X-rays could offer a similar effect as single exposure to 75 mGy on the stimulation of Akt phosphorylation and the upregulation of Nrf2 expression and transcription function. These results suggest that single 75 mGy or multiple 25 mGy of X-rays can stimulate Akt phosphorylation and upregulate Nrf2 expression and function, which may explain the prevention of LDR against the diabetic nephropathy mentioned above.

  2. Impact of dietary fiber intake on glycemic control, cardiovascular risk factors and chronic kidney disease in Japanese patients with type 2 diabetes mellitus: the Fukuoka Diabetes Registry.

    Science.gov (United States)

    Fujii, Hiroki; Iwase, Masanori; Ohkuma, Toshiaki; Ogata-Kaizu, Shinako; Ide, Hitoshi; Kikuchi, Yohei; Idewaki, Yasuhiro; Joudai, Tamaki; Hirakawa, Yoichiro; Uchida, Kazuhiro; Sasaki, Satoshi; Nakamura, Udai; Kitazono, Takanari

    2013-12-11

    Dietary fiber is beneficial for the treatment of type 2 diabetes mellitus, although it is consumed differently in ethnic foods around the world. We investigated the association between dietary fiber intake and obesity, glycemic control, cardiovascular risk factors and chronic kidney disease in Japanese type 2 diabetic patients. A total of 4,399 patients were assessed for dietary fiber intake using a brief self-administered diet history questionnaire. The associations between dietary fiber intake and various cardiovascular risk factors were investigated cross-sectionally. Body mass index, fasting plasma glucose, HbA1c, triglyceride and high-sensitivity C-reactive protein negatively associated with dietary fiber intake after adjusting for age, sex, duration of diabetes, current smoking, current drinking, total energy intake, fat intake, saturated fatty acid intake, leisure-time physical activity and use of oral hypoglycemic agents or insulin. The homeostasis model assessment insulin sensitivity and HDL cholesterol positively associated with dietary fiber intake. Dietary fiber intake was associated with reduced prevalence of abdominal obesity, hypertension and metabolic syndrome after multivariate adjustments including obesity. Furthermore, dietary fiber intake was associated with lower prevalence of albuminuria, low estimated glomerular filtration rate and chronic kidney disease after multivariate adjustments including protein intake. Additional adjustments for obesity, hypertension or metabolic syndrome did not change these associations. We demonstrated that increased dietary fiber intake was associated with better glycemic control and more favorable cardiovascular disease risk factors including chronic kidney disease in Japanese type 2 diabetic patients. Diabetic patients should be encouraged to consume more dietary fiber in daily life.

  3. A Meta-analysis of the Association of Estimated GFR, Albuminuria, Diabetes Mellitus, and Hypertension With Acute Kidney Injury.

    Science.gov (United States)

    James, Matthew T; Grams, Morgan E; Woodward, Mark; Elley, C Raina; Green, Jamie A; Wheeler, David C; de Jong, Paul; Gansevoort, Ron T; Levey, Andrew S; Warnock, David G; Sarnak, Mark J

    2015-10-01

    Diabetes mellitus and hypertension are risk factors for acute kidney injury (AKI). Whether estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (ACR) remain risk factors for AKI in the presence and absence of these conditions is uncertain. Meta-analysis of cohort studies. 8 general-population (1,285,045 participants) and 5 chronic kidney disease (CKD; 79,519 participants) cohorts. Cohorts participating in the CKD Prognosis Consortium. Diabetes and hypertension status, eGFR by the 2009 CKD Epidemiology Collaboration creatinine equation, urine ACR, and interactions. Hospitalization with AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results. During a mean follow-up of 4 years, there were 16,480 episodes of AKI in the general-population and 2,087 episodes in the CKD cohorts. Low eGFRs and high ACRs were associated with higher risks of AKI in individuals with or without diabetes and with or without hypertension. When compared to a common reference of eGFR of 80mL/min/1.73m(2) in nondiabetic patients, HRs for AKI were generally higher in diabetic patients at any level of eGFR. The same was true for diabetic patients at all levels of ACR compared with nondiabetic patients. The risk gradient for AKI with lower eGFRs was greater in those without diabetes than with diabetes, but similar with higher ACRs in those without versus with diabetes. Those with hypertension had a higher risk of AKI at eGFRs>60mL/min/1.73m(2) than those without hypertension. However, risk gradients for AKI with both lower eGFRs and higher ACRs were greater for those without than with hypertension. AKI identified by diagnostic code. Lower eGFRs and higher ACRs are associated with higher risks of AKI among individuals with or without either diabetes or hypertension. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  4. Self-management in patients with diabetes and chronic kidney disease is associated with incremental benefit in HRQOL.

    Science.gov (United States)

    Zimbudzi, Edward; Lo, Clement; Ranasinha, Sanjeeva; Kerr, Peter G; Usherwood, Timothy; Cass, Alan; Fulcher, Gregory R; Zoungas, Sophia

    2017-02-01

    There is insufficient and inconsistent data regarding the association between diabetes self-management, the process of facilitating the knowledge, skill, and ability necessary for diabetes self-care, and health-related quality of life (HRQOL) in people with diabetes and moderate to severe chronic kidney disease (CKD). In a cross sectional study, participation in diabetes self-management assessed by the Summary of Diabetes Self-Care Activities (SDSCA) questionnaire and HRQOL was examined in 308 patients with diabetes and CKD (stages 3 to 5) recruited from outpatient diabetes and renal clinics of 4 public tertiary hospitals. Associations were examined by Pearson correlation coefficients and hierarchical multiple regression after controlling for potential confounders. An examination of trend across the levels of patient participation in self-management was assessed using a non-parametric test for trend. The median age and interquartile range (IQR) of patients were 68 and 14.8years, respectively with 59% of the population being over 65years old and 69.5% male. The median durations of diabetes and CKD were 18years (IQR-17) and 5years (IQR-8) respectively. General diet, exercise and medication taking were positively associated with at least one HRQOL subscale (all pdiabetes specific diet, blood sugar testing and foot checking were not. As levels of participation in self-management activities increased there was a graded increase in mean HRQOL scores across all subscales (p for trend diabetes and moderate to severe CKD, participation in diabetes self-management activities, particularly those focused on general diet, exercise and medication taking, was associated with higher HRQOL. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Morphometrical study of the human kidney. Radiodiagnosis and patological anatomy applications

    International Nuclear Information System (INIS)

    Sampaio, J.B.; Lacerda, C.A.M. de

    1987-01-01

    A morphometrical estimate was made on 100 human kidneys obtained by necropsies. The results of the renal measurements showed the averages of 11.06cm long, 6.24cm wide for the superior pole, 5.42cm wide for the inferior pole, 3.26cm thickness, and 119.48g weight. The left kidney presented a greater lenght, greater width, greater thickness and greater weight than the kidney. The statistical analysis of the correlation between several indices is presented. (author) [pt

  6. Measurement of uranium in human teeth and kidney stones with the fission track technique

    International Nuclear Information System (INIS)

    Vartanian, R.

    1986-01-01

    The measurement of uranium in human teeth and in kidney stones was carried out using the fission track activation technique. In this determination 2759 and 2205 absolute counts of tracks for teeth samples and 1689 tracks for kidney stone samples were performed, respectively. The results are as follows: xsub(tooth) (1)=(0.227+-0.006) ppm, xsub(tooth) (2)=(0.143+-0.007) ppm and xsub(kidney)=(0.568+-0.020) ppm. The experimental method is described and the results are discussed. (author)

  7. SGLT2 inhibitors: a novel choice for the combination therapy in diabetic kidney disease.

    Science.gov (United States)

    Zou, Honghong; Zhou, Baoqin; Xu, Gaosi

    2017-05-16

    Diabetic kidney disease (DKD) is the most common cause of end stage renal disease. The comprehensive management of DKD depends on combined target-therapies for hyperglycemia, hypertension, albuminuria, and hyperlipaemia, etc. Sodium-glucose co-transporter 2 (SGLT2) inhibitors, the most recently developed oral hypoglycemic agents acted on renal proximal tubules, suppress glucose reabsorption and increase urinary glucose excretion. Besides improvements in glycemic control, they presented excellent performances in direct renoprotective effects and the cardiovascular (CV) safety by decreasing albuminuria and the independent CV risk factors such as body weight and blood pressure, etc. Simultaneous use of SGLT-2 inhibitors and renin-angiotensin-aldosterone system (RAAS) blockers are novel strategies to slow the progression of DKD via reducing inflammatory and fibrotic markers induced by hyperglycaemia more than either drug alone. The available population and animal based studies have described SGLT2 inhibitors plus RAAS blockers. The present review was to systematically review the potential renal benefits of SGLT2 inhibitors combined with dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, mineralocorticoid receptor antagonists, and especially the angiotensin-converting enzyme inhibitors/angiotensin receptor blockers.

  8. Reducing VEGF-B Signaling Ameliorates Renal Lipotoxicity and Protects against Diabetic Kidney Disease.

    Science.gov (United States)

    Falkevall, Annelie; Mehlem, Annika; Palombo, Isolde; Heller Sahlgren, Benjamin; Ebarasi, Lwaki; He, Liqun; Ytterberg, A Jimmy; Olauson, Hannes; Axelsson, Jonas; Sundelin, Birgitta; Patrakka, Jaakko; Scotney, Pierre; Nash, Andrew; Eriksson, Ulf

    2017-03-07

    Diabetic kidney disease (DKD) is the most common cause of severe renal disease, and few treatment options are available today that prevent the progressive loss of renal function. DKD is characterized by altered glomerular filtration and proteinuria. A common observation in DKD is the presence of renal steatosis, but the mechanism(s) underlying this observation and to what extent they contribute to disease progression are unknown. Vascular endothelial growth factor B (VEGF-B) controls muscle lipid accumulation through regulation of endothelial fatty acid transport. Here, we demonstrate in experimental mouse models of DKD that renal VEGF-B expression correlates with the severity of disease. Inhibiting VEGF-B signaling in DKD mouse models reduces renal lipotoxicity, re-sensitizes podocytes to insulin signaling, inhibits the development of DKD-associated pathologies, and prevents renal dysfunction. Further, we show that elevated VEGF-B levels are found in patients with DKD, suggesting that VEGF-B antagonism represents a novel approach to treat DKD. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Higher protein intake is not associated with decreased kidney function in pre-diabetic older adults following a one-year intervention

    DEFF Research Database (Denmark)

    Møller, Grith; Andersen, Jens Rikardt; Ritz, Christian

    2018-01-01

    Concerns about detrimental renal effects of a high-protein intake have been raised due to an induced glomerular hyperfiltration, since this may accelerate the progression of kidney disease. The aim of this sub-study was to assess the effect of a higher intake of protein on kidney function in pre-diabetic...... intake and creatinine clearance, eGFR, ACR, or serum creatinine. We found no indication of impaired kidney function after one year with a higher protein intake in pre-diabetic older adults....

  10. 78 FR 6123 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2013-01-29

    ... Digestive and Kidney Diseases Special Emphasis Panel; Host Innate Immune Microbial Interactions in... Kidney Diseases Special Emphasis Panel; DDK-D Members Conflict SEP. Date: March 13, 2013. Time: 10:10 a.m...

  11. The impact of metformin use on survival in kidney cancer patients with diabetes: a meta-analysis.

    Science.gov (United States)

    Li, Yang; Hu, Liyi; Xia, Qinghong; Yuan, Yongqiang; Mi, Yonghua

    2017-06-01

    The effects of metformin on the prognosis of kidney cancer patients with diabetes are in controversial. The present study is conducted to classify the association of metformin use with the survival of patients with kidney cancer. Electronic databases, namely PubMed and Web of Science, were used to search the eligible studies up to December, 2016. Pooled hazard ratio (HR) and its corresponding 95% confidence interval (95% CI) were calculated. It was considered as statistically significant when P value was kidney cancer patients. The combined HR suggested that the use of metformin could improve the overall survival (OS) (HR 0.643, 95% CI 0.520-0.795, P cancer-specific survival (CSS) (HR 0.618, 95% CI 0.446-0.858, P = 0.004) in kidney cancer patients. In subgroup analysis, positive associations were found between metformin use and OS/CSS of localized renal cell carcinoma patients (OS: HR 0.634, 95% CI 0.440-0.913, P = 0.014; CSS: HR 0.476, 95% CI 0.295-0.768, P = 0.002). Moreover, we also found that the use of metformin could reduce the risk of death in kidney cancer patients (HR 0.711, 95% CI 0.562-0.899, P = 0.004). Our findings suggest that the use of metformin is in favor of the prognosis of patients with kidney cancers. Further investigations are needed to evaluate the prognostic value of metformin on kidney cancer patients.

  12. Model experiment of in vivo synchrotron X-ray diffraction of human kidney stones

    Energy Technology Data Exchange (ETDEWEB)

    Ancharov, A.I. [Institute of Solid State Chemistry and Mechanochemistry SB RAS, Novosibirsk (Russian Federation)]. E-mail: ancharov@mail.ru; Potapov, S.S. [Institute of Mineralogy UB RAS, Miass (Russian Federation); Moiseenko, T.N. [The State Regional Clinical Hospital, Novosibirsk (Russian Federation); Feofilov, I.V. [The State Regional Clinical Hospital, Novosibirsk (Russian Federation); Nizovskii, A.I. [Boreskov Institute of Catalysis SB RAS, Novosibirsk (Russian Federation)

    2007-05-21

    The diffraction of synchrotron radiation (SR) was used to explore the phase composition of kidney stones placed into a specific object phantom, which imitated the human body. As an imitation of the patient breath, the kidney stone was moved vertically and rotated to an angle of 15{sup o} during the recording of the X-ray pattern. It was shown that rotation and displacement did not distort the X-ray pattern.

  13. Model experiment of in vivo synchrotron X-ray diffraction of human kidney stones

    International Nuclear Information System (INIS)

    Ancharov, A.I.; Potapov, S.S.; Moiseenko, T.N.; Feofilov, I.V.; Nizovskii, A.I.

    2007-01-01

    The diffraction of synchrotron radiation (SR) was used to explore the phase composition of kidney stones placed into a specific object phantom, which imitated the human body. As an imitation of the patient breath, the kidney stone was moved vertically and rotated to an angle of 15 o during the recording of the X-ray pattern. It was shown that rotation and displacement did not distort the X-ray pattern

  14. Glutathione peroxidase-1 gene (GPX1) variants, oxidative stress and risk of kidney complications in people with type 1 diabetes.

    Science.gov (United States)

    Mohammedi, Kamel; Patente, Thiago A; Bellili-Muñoz, Naima; Driss, Fathi; Le Nagard, Hervé; Fumeron, Frédéric; Roussel, Ronan; Hadjadj, Samy; Corrêa-Giannella, Maria Lúcia; Marre, Michel; Velho, Gilberto

    2016-02-01

    Glutathione peroxidase (GPX) is a class of antioxidant enzymes that catalyze the reduction of hydrogen peroxide to water. GPX1 is the most abundant isoform and is expressed in all kidney cells. Isoprostane and advanced oxidation protein products (AOPP) were identified as markers of oxidative stress in patients with kidney disease. We investigated associations of GPX1 genotypes with kidney complications, and with plasma concentrations of isoprostane and AOPP in type 1 diabetic patients. Four SNPs in the GPX1 gene region were genotyped in SURGENE (n=340; 10-year follow-up); GENEDIAB (n=461) and GENESIS (n=584) cohorts of type 1 diabetic patients. Subsets of GENEDIAB (n=237) and GENESIS (n=466) participants were followed up for 9 and 5years, respectively. Plasma concentrations of isoprostane and AOPP were measured at baseline in GENEDIAB. Hazard ratios (HR) were estimated for incidence of kidney complications. In SURGENE, 98 renal events (new cases of microalbuminuria or progression to more severe stage of diabetic nephropathy) occurred during follow-up. The minor T-allele of rs3448 was associated with the incidence of renal events (HR 1.81, 95% CI 1.16-2.84, p=0.008). In GENESIS/GENEDIAB pooled study, end stage renal disease (ESRD) occurred during follow-up in 52 individuals. The same variant was associated with the incidence of ESRD (HR 3.34, 95% CI, 1.69-6.98, p=0.0004). The variant was also associated with higher plasma isoprostane concentration in GENEDIAB cohort: 2.02±0.12 (TT+CT) vs 1.75±0.13 (CC) ng/mL (p=0.009), and with higher plasma AOPP in the subset of participants with the baseline history of ESRD (TT+CT 67±6 vs CC 48±6μmol/L, p=0.006). The minor T-allele of rs3448 was associated with kidney complications (incidences of microalbuminuria, renal events and ESRD) in patients with type 1 diabetes. The risk allele was associated with higher plasma concentrations of isoprostane and AOPP. Our results are consistent with the implication of GPX1 in the

  15. Modifiable lifestyle and social factors affect chronic kidney disease in high-risk individuals with type 2 diabetes mellitus.

    Science.gov (United States)

    Dunkler, Daniela; Kohl, Maria; Heinze, Georg; Teo, Koon K; Rosengren, Annika; Pogue, Janice; Gao, Peggy; Gerstein, Hertzel; Yusuf, Salim; Oberbauer, Rainer; Mann, Johannes F E

    2015-04-01

    This observational study examined the association between modifiable lifestyle and social factors on the incidence and progression of early chronic kidney disease (CKD) among those with type 2 diabetes. All 6972 people from the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) with diabetes but without macroalbuminuria were studied. CKD progression was defined as decline in GFR of more than 5% per year, progression to end-stage renal disease, microalbuminuria, or macroalbuminuria at 5.5 years. Lifestyle/social factors included tobacco and alcohol use, physical activity, stress, financial worries, the size of the social network and education. Adjustments were made for known risks such as age, diabetes duration, GFR, albuminuria, gender, body mass index, blood pressure, fasting plasma glucose, and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers use. Competing risk of death was considered. At study end, 31% developed CKD and 15% had died. The social network score (SNS) was a significant independent risk factor of CKD and death, reducing the risk by 11 and 22% when comparing the third to the first tertile of the SNS (odds ratios of CKD 0.89 and death 0.78). Education showed a significant association with CKD but stress and financial worries did not. Those with moderate alcohol consumption had a significantly decreased CKD risk compared with nonusers. Regular physical activity significantly decreased the risk of CKD. Thus, lifestyle is a determinant of kidney health in people at high cardiovascular risk with diabetes.

  16. Tumor necrosis factor (TNF-alpha) and C-reactive protein (CRP) are positively associated with the risk of chronic kidney disease in patients with type 2 diabetes.

    Science.gov (United States)

    Yeo, Eun-Sil; Hwang, Ji-Yun; Park, Ji Eun; Choi, Young Ju; Huh, Kap Bum; Kim, Wha Young

    2010-07-01

    Chronic low-grade inflammation may induce chronic kidney disease in patients with type 2 diabetes. This study investigated the relation between inflammatory biomarkers and chronic kidney disease in patients with type 2 diabetes, which has not yet been reported in Asian populations. A cross-sectional study was performed in 543 patients recruited from diabetic clinics for an ongoing, prospective study. Multivariate logistic regression was used to evaluate the association between inflammatory biomarkers and the presence of chronic kidney disease (estimated glomerular filtration rate Disease equation using plasma creatinine). The risk of chronic kidney disease increased in the highest quartiles of C-reactive protein (CRP) [multivariate odds ratio (OR) = 3.73; 95% CI = 1.19-1.70] and tumor necrosis factor-alpha (multivariate OR = 4.45; 95% CI = 1.63-12.11) compared to the lowest quartiles after adjustments for age, sex, zinc intake, and other putative risk factors for chronic kidney disease. Our results suggest that CRP and tumor necrosis factor-alpha may be independent risk factors for chronic kidney disease in patients with type 2 diabetes. A causal mechanism of this association should be evaluated in a followup study of Korean patients with type 2 diabetes.

  17. Correlation of chronic kidney disease, diabetes and peripheral artery disease with cardiovascular events in patients using stress myocardial perfusion imaging

    International Nuclear Information System (INIS)

    Furuhashi, Tatsuhiko; Masai, Hirofumi; Kunimasa, Taeko; Nakazato, Ryo; Fukuda, Hiroshi; Sugi, Kaoru; Moroi, Masao

    2011-01-01

    Normal stress myocardial perfusion imaging (MPI) studies generally suggest an excellent prognosis for cardiovascular events. Chronic kidney disease (CKD), diabetes and peripheral artery disease (PAD) have been established as the risk factors for cardiovascular events. However, whether these risk factors significantly predict cardiovascular events in patients with normal stress MPI is unclear. The purpose of this study was to evaluate the prognostic value of these risk factors in patients with normal stress MPI. Patients with normal stress MPI (n=372, male=215 and female=157, age=69 years, CKD without hemodialysis=95, diabetes=99, PAD=19, previous coronary artery disease=116) were followed up for 14 months. Normal stress MPI was defined as a summed stress score of 2 and/or persistent proteinuria. Cardiovascular events included cardiac death, non-fatal myocardial infarction and congestive heart failure requiring hospitalization. Cardiovascular events occurred in 20 of 372 patients (5.4%). In univariate Cox regression analysis, PAD, diabetes, diabetic retinopathy, insulin use, anemia, hypoalbuminemia, CKD, left ventricular ejection fraction and pharmacological stress tests were significant predictors of cardiovascular events. In multivariate Cox regression analysis, PAD, diabetes and CKD were independent and significant predictors for cardiovascular events, and their number was the strongest predictor for cardiovascular events (hazard ratio=21.7, P<0.001). PAD, diabetes and CKD are coexisting, independent and significant risk factors for cardiovascular events, CKD being the strongest predictor. The number of coexisting risk factors is important in predicting cardiovascular events in patients with normal stress MPI. (author)

  18. Genome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND).

    Science.gov (United States)

    Iyengar, Sudha K; Sedor, John R; Freedman, Barry I; Kao, W H Linda; Kretzler, Matthias; Keller, Benjamin J; Abboud, Hanna E; Adler, Sharon G; Best, Lyle G; Bowden, Donald W; Burlock, Allison; Chen, Yii-Der Ida; Cole, Shelley A; Comeau, Mary E; Curtis, Jeffrey M; Divers, Jasmin; Drechsler, Christiane; Duggirala, Ravi; Elston, Robert C; Guo, Xiuqing; Huang, Huateng; Hoffmann, Michael Marcus; Howard, Barbara V; Ipp, Eli; Kimmel, Paul L; Klag, Michael J; Knowler, William C; Kohn, Orly F; Leak, Tennille S; Leehey, David J; Li, Man; Malhotra, Alka; März, Winfried; Nair, Viji; Nelson, Robert G; Nicholas, Susanne B; O'Brien, Stephen J; Pahl, Madeleine V; Parekh, Rulan S; Pezzolesi, Marcus G; Rasooly, Rebekah S; Rotimi, Charles N; Rotter, Jerome I; Schelling, Jeffrey R; Seldin, Michael F; Shah, Vallabh O; Smiles, Adam M; Smith, Michael W; Taylor, Kent D; Thameem, Farook; Thornley-Brown, Denyse P; Truitt, Barbara J; Wanner, Christoph; Weil, E Jennifer; Winkler, Cheryl A; Zager, Philip G; Igo, Robert P; Hanson, Robert L; Langefeld, Carl D

    2015-08-01

    Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10-9). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10-8), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD.

  19. Genome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND.

    Directory of Open Access Journals (Sweden)

    Sudha K Iyengar

    2015-08-01

    Full Text Available Diabetic kidney disease (DKD is the most common etiology of chronic kidney disease (CKD in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND performed a genome-wide association study (GWAS contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10-9. The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10-8, with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD.

  20. Structural and Functional Changes in Human Kidneys with Healthy Aging.

    Science.gov (United States)

    Hommos, Musab S; Glassock, Richard J; Rule, Andrew D

    2017-10-01

    Aging is associated with significant changes in structure and function of the kidney, even in the absence of age-related comorbidities. On the macrostructural level, kidney cortical volume decreases, surface roughness increases, and the number and size of simple renal cysts increase with age. On the microstructural level, the histologic signs of nephrosclerosis (arteriosclerosis/arteriolosclerosis, global glomerulosclerosis, interstitial fibrosis, and tubular atrophy) all increase with age. The decline of nephron number is accompanied by a comparable reduction in measured whole-kidney GFR. However, single-nephron GFR remains relatively constant with healthy aging as does glomerular volume. Only when glomerulosclerosis and arteriosclerosis exceed that expected for age is there an increase in single-nephron GFR. In the absence of albuminuria, age-related reduction in GFR with the corresponding increase in CKD (defined by an eGFRage-standardized mortality risk or ESRD. These findings raise the question of whether disease labeling of an age-related decline in GFR is appropriate. These findings also emphasize the need for a different management approach for many elderly individuals considered to have CKD by current criteria. Copyright © 2017 by the American Society of Nephrology.

  1. Cardiac stress test as a risk-stratification tool for posttransplant cardiac outcomes in diabetic kidney transplant recipients.

    Science.gov (United States)

    Singh, Neeraj; Parikh, Samir; Bhatt, Udayan; Vonvisger, Jon; Nori, Uday; Hasan, Ayesha; Samavedi, Srinivas; Andreoni, Kenneth; Henry, Mitchell; Pelletier, Ronald; Rajab, Amer; Elkhammas, Elmahdi; Pesavento, Todd

    2012-12-27

    The utility of cardiac stress testing as a risk-stratification tool before kidney transplantation remains debatable owing to discordance with coronary angiography and outcome yields at different centers. We conducted a retrospective study of 273 diabetic kidney transplant recipients from 2006 to 2010. By protocol, all diabetic patients underwent pharmacological radionucleotide stress test or dobutamine stress echocardiography before transplant. We compared the 1-year cardiac outcomes between those with negative stress test results and those with positive stress test results. Patients with a positive stress test result (n=67) underwent coronary angiogram, and significant coronary artery disease (≥70% coronary stenosis) was found in 35 (52.2%) patients. Of the latter, 32 (91.4%) underwent cardiac revascularization (24 underwent cardiac stenting and 8 underwent coronary artery bypass grafting). The rest (n=35) were treated medically. Within 1 year after transplant, the group with positive stress test results experienced more cardiac events (34.3% vs. 3.9%, P<0.001) including acute myocardial infarction (22.4% vs. 3.4%, P<0.001) and ventricular arrhythmias (8.9% vs. 0.05%, P=0.001), higher all-cause mortality (19.4% vs. 4.8%, P<0.001), and cardiac mortality (17.9% vs. 0.9%, P<0.001) compared with the group with negative stress test results. In this diabetic population, stress testing showed positive and negative predictive values of 34.3% and 96.1%, respectively. Pharmacological cardiac stress testing provided excellent risk stratification in diabetic kidney transplant recipients.

  2. Regenerative Medicine, Disease Modelling, and Drug Discovery in Human Pluripotent Stem Cell-Derived Kidney Tissue

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    Navin Gupta

    2017-08-01

    Full Text Available The multitude of research clarifying critical factors in embryonic organ development has been instrumental in human stem cell research. Mammalian organogenesis serves as the archetype for directed differentiation protocols, subdividing the process into a series of distinct intermediate stages that can be chemically induced and monitored for the expression of stage-specific markers. Significant advances over the past few years include established directed differentiation protocols of human embryonic stem cells and human induced pluripotent stem cells (hiPSC into human kidney organoids in vitro. Human kidney tissue in vitro simulates the in vivo response when subjected to nephrotoxins, providing a novel screening platform during drug discovery to facilitate identification of lead candidates, reduce developmental expenditures, and reduce future rates of drug-induced acute kidney injury. Patient-derived hiPSC, which bear naturally occurring DNA mutations, may allow for modelling of human genetic diseases to enable determination of pathological mechanisms and screening for novel therapeutics. In addition, recent advances in genome editing with clustered regularly interspaced short palindromic repeats (CRISPR/Cas9 enable the generation of specific mutations to study genetic disease, with non-mutated lines serving as an ideal isogenic control. The growing population of patients with end-stage kidney disease is a worldwide healthcare problem, with high morbidity and mortality rates, that warrants the discovery of novel forms of renal replacement therapy. Coupling the outlined advances in hiPSC research with innovative bioengineering techniques, such as decellularised kidney and three-dimensional printed scaffolds, may contribute to the development of bioengineered transplantable human kidney tissue as a means of renal replacement therapy.

  3. Gain-of-function variants in NLRP1 protect against the development of diabetic kidney disease: NLRP1 inflammasome role in metabolic stress sensing?

    Science.gov (United States)

    Soares, Jaine L S; Fernandes, Fernanda Pereira; Patente, Thiago Andrade; Monteiro, Maria B; Parisi, Maria C; Giannella-Neto, Daniel; Corrêa-Giannella, Maria L; Pontillo, Alessandra

    2018-02-01

    Although inflammasome plays a well-known role in animal models of renal injury, limited studies in humans are available, and its participation in diabetic kidney disease (DKD) remains unknown. Aim of this study was to elucidate the contribution of inflammasome genetics in the development of DKD in type-1 diabetes (T1D). The association of functional variants in inflammasome genes with DKD was assessed by multivariate analysis in a retrospective and in a prospective cohort. NLRP1 rs2670660 and rs11651270 polymorphisms were significantly associated with a decrease risk to develop DKD (p adj <0.01), and rs11651270 also with a lower risk of new renal events during follow-up (p adj =0.01). Supporting these findings, diabetes metabolites (glycated albumin and high glucose) were able to modulate NLRP1 expression. This study is the first to suggest a protective role of NLRP1 in DKD, highlighting an emerging role of NLRP1 as a homeostatic factor against metabolic stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Allelic variations in the CYBA gene of NADPH oxidase and risk of kidney complications in patients with type 1 diabetes.

    Science.gov (United States)

    Patente, Thiago A; Mohammedi, Kamel; Bellili-Muñoz, Naïma; Driss, Fathi; Sanchez, Manuel; Fumeron, Frédéric; Roussel, Ronan; Hadjadj, Samy; Corrêa-Giannella, Maria Lúcia; Marre, Michel; Velho, Gilberto

    2015-09-01

    Oxidative stress plays a pivotal role in the pathophysiology of diabetic nephropathy, and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system is an important source of reactive oxygen species in hyperglycemic conditions in the kidney. Plasma concentration of advanced oxidation protein products (AOPP), a marker of oxidative stress, is increased in patients with diabetic nephropathy. We investigated associations of variants in the CYBA gene, encoding the regulatory subunit p22(phox) of NADPH oxidase, with diabetic nephropathy and plasma AOPP and myeloperoxidase (MPO) concentrations in type 1 diabetic patients. Seven SNPs in the CYBA region were analyzed in 1357 Caucasian subjects with type 1 diabetes from the SURGENE (n=340), GENEDIAB (n=444), and GENESIS (n=573) cohorts. Duration of follow-up was 10, 9, and 6 years, respectively. Cox proportional hazards and logistic regression analyses were used to estimate hazard ratios (HR) or odds ratios (OR) for incidence and prevalence of diabetic nephropathy. The major G-allele of rs9932581 was associated with the incidence of renal events defined as new cases of microalbuminuria or the progression to a more severe stage of nephropathy during follow-up (HR 1.59, 95% CI 1.17-2.18, P=0.003) in SURGENE. The same allele was associated with established/advanced nephropathy (OR 1.52, 95% CI 1.22-1.92, P=0.0001) and with the incidence of end-stage renal disease (ESRD) (HR 2.01, 95% CI 1.30-3.24, P=0.001) in GENEDIAB/GENESIS pooled studies. The risk allele was also associated with higher plasma AOPP concentration in subsets of SURGENE and GENEDIAB, with higher plasma MPO concentration in a subset of GENEDIAB, and with lower estimated glomerular filtration rate (eGFR) in the three cohorts. In conclusion, a functional variant in the promoter of the CYBA gene was associated with lower eGFR and with prevalence and incidence of diabetic nephropathy and ESRD in type 1 diabetic patients. These results are consistent with

  5. Value of adding the renal pathological score to the kidney failure risk equation in advanced diabetic nephropathy.

    Directory of Open Access Journals (Sweden)

    Masayuki Yamanouchi

    Full Text Available There have been a limited number of biopsy-based studies on diabetic nephropathy, and therefore the clinical importance of renal biopsy in patients with diabetes in late-stage chronic kidney disease (CKD is still debated. We aimed to clarify the renal prognostic value of pathological information to clinical information in patients with diabetes and advanced CKD.We retrospectively assessed 493 type 2 diabetics with biopsy-proven diabetic nephropathy in four centers in Japan. 296 patients with stage 3-5 CKD at the time of biopsy were identified and assigned two risk prediction scores for end-stage renal disease (ESRD: the Kidney Failure Risk Equation (KFRE, a score composed of clinical parameters and the Diabetic Nephropathy Score (D-score, a score integrated pathological parameters of the Diabetic Nephropathy Classification by the Renal Pathology Society (RPS DN Classification. They were randomized 2:1 to development and validation cohort. Hazard Ratios (HR of incident ESRD were reported with 95% confidence interval (CI of the KFRE, D-score and KFRE+D-score in Cox regression model. Improvement of risk prediction with the addition of D-score to the KFRE was assessed using c-statistics, continuous net reclassification improvement (NRI, and integrated discrimination improvement (IDI.During median follow-up of 1.9 years, 194 patients developed ESRD. The cox regression analysis showed that the KFRE,D-score and KFRE+D-score were significant predictors of ESRD both in the development cohort and in the validation cohort. The c-statistics of the D-score was 0.67. The c-statistics of the KFRE was good, but its predictive value was weaker than that in the miscellaneous CKD cohort originally reported (c-statistics, 0.78 vs. 0.90 and was not significantly improved by adding the D-score (0.78 vs. 0.79, p = 0.83. Only continuous NRI was positive after adding the D-score to the KFRE (0.4%; CI: 0.0-0.8%.We found that the predict values of the KFRE and the D

  6. Value of adding the renal pathological score to the kidney failure risk equation in advanced diabetic nephropathy.

    Science.gov (United States)

    Yamanouchi, Masayuki; Hoshino, Junichi; Ubara, Yoshifumi; Takaichi, Kenmei; Kinowaki, Keiichi; Fujii, Takeshi; Ohashi, Kenichi; Mise, Koki; Toyama, Tadashi; Hara, Akinori; Kitagawa, Kiyoki; Shimizu, Miho; Furuichi, Kengo; Wada, Takashi

    2018-01-01

    There have been a limited number of biopsy-based studies on diabetic nephropathy, and therefore the clinical importance of renal biopsy in patients with diabetes in late-stage chronic kidney disease (CKD) is still debated. We aimed to clarify the renal prognostic value of pathological information to clinical information in patients with diabetes and advanced CKD. We retrospectively assessed 493 type 2 diabetics with biopsy-proven diabetic nephropathy in four centers in Japan. 296 patients with stage 3-5 CKD at the time of biopsy were identified and assigned two risk prediction scores for end-stage renal disease (ESRD): the Kidney Failure Risk Equation (KFRE, a score composed of clinical parameters) and the Diabetic Nephropathy Score (D-score, a score integrated pathological parameters of the Diabetic Nephropathy Classification by the Renal Pathology Society (RPS DN Classification)). They were randomized 2:1 to development and validation cohort. Hazard Ratios (HR) of incident ESRD were reported with 95% confidence interval (CI) of the KFRE, D-score and KFRE+D-score in Cox regression model. Improvement of risk prediction with the addition of D-score to the KFRE was assessed using c-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). During median follow-up of 1.9 years, 194 patients developed ESRD. The cox regression analysis showed that the KFRE,D-score and KFRE+D-score were significant predictors of ESRD both in the development cohort and in the validation cohort. The c-statistics of the D-score was 0.67. The c-statistics of the KFRE was good, but its predictive value was weaker than that in the miscellaneous CKD cohort originally reported (c-statistics, 0.78 vs. 0.90) and was not significantly improved by adding the D-score (0.78 vs. 0.79, p = 0.83). Only continuous NRI was positive after adding the D-score to the KFRE (0.4%; CI: 0.0-0.8%). We found that the predict values of the KFRE and the D-score were

  7. Pharmacist Intervention for Blood Pressure Control in Patients with Diabetes and/or Chronic Kidney Disease.

    Science.gov (United States)

    Anderegg, Maxwell D; Gums, Tyler H; Uribe, Liz; MacLaughlin, Eric J; Hoehns, James; Bazaldua, Oralia V; Ives, Timothy J; Hahn, David L; Coffey, Christopher S; Carter, Barry L

    2018-03-01

    The objectives of this study were to determine if hypertensive patients with comorbid diabetes mellitus (DM) and/or chronic kidney disease (CKD) receiving a pharmacist intervention had a greater reduction in mean blood pressure (BP) and improved BP control at 9 months compared with those receiving usual care; and compare Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guideline and 2014 guideline (JNC 8) BP control rates in patients with DM and/or CKD. This cluster randomized trial included 32 medical offices in 15 states. Clinical pharmacists made treatment recommendations to physicians at intervention sites. This post hoc analysis evaluated mean BP and BP control rates in the intervention and control groups. The study included 335 patients (227 intervention, 108 control) when mean BP and control rates were evaluated by JNC 7 inclusion and control criteria. When JNC 8 inclusion and control criteria were applied, 241 patients (165 intervention, 76 control) remained and were included in the analysis. The pharmacist-intervention group had significantly greater mean systolic blood pressure reduction compared with usual care at 9 months (8.64 mm Hg; 95% confidence interval [CI] -12.8 to -4.49, pcontrol at 9 months than usual care by either the JNC 7 or JNC 8 inclusion and control groups (adjusted odds ratio [OR] 1.97, 95% CI 1.01-3.86, p=0.0470 and OR 2.16, 95% CI 1.21-3.85, p=0.0102, respectively). This study demonstrated that a physician-pharmacist collaborative intervention was effective in reducing mean systolic BP and improving BP control in patients with uncontrolled hypertension with DM and/or CKD, regardless of which BP guidelines were used. © 2018 Pharmacotherapy Publications, Inc.

  8. Immunological and clinical observations in diabetic kidney graft recipients pretreated with total-lymphoid irradiation

    International Nuclear Information System (INIS)

    Waer, M.; Vanrenterghem, Y.; Roels, L.

    1987-01-01

    In a feasibility study, twenty patients with end-stage diabetic nephropathy were treated with fractionated total-lymphoid irradiation (TLI, mean dose 25 Gy), before transplantation of a first cadaveric kidney. During radiotherapy, only one patient had a serious side effect (bone marrow depression). After transplantation four patients died (one of a myocardial infarction, one of ketoacidosis, and two of infections occurring during treatment of rejection crises). One graft was lost because of chronic rejection. The other 15 patients have a functioning graft (mean follow-up 24 months) and receive low-dose prednisone alone (less than 10 mg/day, n = 11) or in conjunction with cyclosporine (n = 4) as maintenance immunosuppressive therapy. A favorable clinical outcome after TLI (no, or only one, steroid-sensitive rejection crisis) was significantly correlated with a high pre-TLI helper/suppressor lymphocyte ratio, a short interval between TLI and the time of transplantation, and the occurrence of functional suppressor cells early after TLI. The most striking immunological changes provoked by TLI consisted of a long-term depression of the mixed lymphocyte reaction and of the phytohemagglutinin, and Concanavalin A or pokeweed-mitogen-induced blastogenesis. A rapid and complete recovery of the natural killer cell activity was observed after TLI. A permanent inversion of the OKT4+ (T helper/inducer) over OKT8+ (T suppressor/cytotoxic) lymphocyte ratio was provoked by a decrease of the OTK4+ subpopulation, together with a supranormal recovery of the OKT8+ lymphocytes. A majority of the latter lymphocytes did also express the Leu 7 and the Leu 15 phenotype

  9. The association of pioglitazone and urinary tract disease in type 2 diabetic Taiwanese: bladder cancer and chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Mei-Yueh Lee

    Full Text Available OBJECTIVE: Although studies have shown an association between pioglitazone and bladder cancer, the associated factors have not been identified. The aim of this study was to investigate the factors that may link pioglitazone to bladder cancer. MATERIALS AND METHODS: In total, 34,970 study subjects were identified from the National Health Insurance Research Database in 2003 with follow-up from 2005 to 2009. The demographic characteristics of patients who had used and had never used pioglitazone, including age, sex, diabetes duration, urinary tract disease, nephropathy, bladder cancer, and cumulative dose and duration of pioglitazone therapy, were analyzed using the χ2 test. Cox proportional hazard regression models were used to determine the independent effects of pioglitazone on bladder cancer and newly developed chronic kidney disease. RESULTS: Among 3,497 ever users and 31,473 never users of pioglitazone, the respective incident cases of bladder cancer were 12 (0.4% and 72 (0.2%, and for newly developed chronic kidney disease 245 (8.1% and 663 (2.3%, respectively. Ever use of pioglitazone [1.59(1.32-1.91], cumulative dose of pioglitazone 10,500 mg [1.34 (1.04-1.73], and duration of therapy 12 months [1.39 (1.09-1.76] were associated with the development of chronic kidney disease. CONCLUSIONS: There was no association of pioglitazone use with bladder cancer development, however, there was an association with an increased risk of newly developed chronic kidney disease.

  10. The crosstalk of gut microbiota and chronic kidney disease: role of inflammation, proteinuria, hypertension, and diabetes mellitus.

    Science.gov (United States)

    Kanbay, Mehmet; Onal, Emine M; Afsar, Baris; Dagel, Tuncay; Yerlikaya, Aslihan; Covic, Adrian; Vaziri, Nosratola D

    2018-05-04

    Chronic kidney disease (CKD) has been shown to result in profound changes in the composition and functions of the gut microbial flora which by disrupting intestinal epithelial barrier and generating toxic by-products contributes to systemic inflammation and the associated complications. On the other hand, emerging evidence points to the role of the gut microbiota in the development and progression of CKD by provoking inflammation, proteinuria, hypertension, and diabetes. These observations demonstrate the causal interconnection between the gut microbial dysbiosis and CKD. The gut microbiota closely interacts with the inflammatory, renal, cardiovascular, and endocrine systems via metabolic, humoral, and neural signaling pathways, events which can lead to chronic systemic inflammation, proteinuria, hypertension, diabetes, and kidney disease. Given the established role of the gut microbiota in the development and progression of CKD and its complications, favorable modification of the composition and function of the gut microbiome represents an appealing therapeutic target for prevention and treatment of CKD. This review provides an overview of the role of the gut microbial dysbiosis in the pathogenesis of the common causes of CKD including hypertension, diabetes, and proteinuria as well as progression of CKD.

  11. Kidneys and Urinary Tract

    Science.gov (United States)

    ... Videos for Educators Search English Español Kidneys and Urinary Tract KidsHealth / For Teens / Kidneys and Urinary Tract What's ... a sign of diabetes . What the Kidneys and Urinary Tract Do Although the two kidneys work together to ...

  12. Tryptophan Metabolism in Patients With Chronic Kidney Disease Secondary to Type 2 Diabetes: Relationship to Inflammatory Markers

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    Subrata Debnath

    2017-03-01

    Full Text Available Objective: Type 2 diabetes (T2D is the primary case of chronic kidney disease (CKD. Inflammation is associated with metabolic dysregulation in patients with T2D and CKD. Tryptophan (TRP metabolism may have relevance to the CKD outcomes and associated symptoms. We investigated the relationships of TRP metabolism with inflammatory markers in patients with T2D and CKD. Methods: Data were collected from a well-characterized cohort of type 2 diabetic individuals with all stages of CKD, including patients on hemodialysis. Key TRP metabolites (kynurenine [KYN], kynurenic acid [KYNA], and quinolinic acid [QA], proinflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin-6 [IL-6], and C-reactive protein were measured in plasma. The KYN/TRP ratio was utilized as a surrogate marker for indoleamine 2,3-dioxygenase 1 (IDO1 enzyme activity. Results: There was a significant inverse association between circulating TRP level and stages of CKD ( P  < 0.0001. Downstream bioactive TRP metabolites KYN, KYNA, and QA were positively and robustly correlated with the severity of kidney disease ( P  < 0.0001. In multiple linear regression, neither TNF-α nor IL-6 was independently related to KYN/TRP ratio after adjusting for estimated glomerular filtration rate (eGFR. Only TNF-α was independently related to KYN after taking into account the effect of eGFR. Conclusions: Chronic kidney disease secondary to T2D may be associated with accumulation of toxic TRP metabolites due to both inflammation and impaired kidney function. Future longitudinal studies to determine whether the accumulation of KYN directly contributes to CKD progression and associated symptoms in patients with T2D are warranted.

  13. Effects of exercise on kidney function among non-diabetic patients with hypertension and renal disease: randomized controlled trial

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    Barcellos Franklin C

    2012-08-01

    Full Text Available Abstract Background Chronic kidney disease is an important public health threat. Such patients present high morbidity and mortality due to cardiovascular disease, with low quality of life and survival, and also high expenditure resulting from the treatment. Arterial hypertension is both a cause and a complication of kidney disease; also, arterial hypertension is a risk factor for cardiovascular disease among patients with kidney diseases. There is some evidence that exercise interventions may be beneficial to chronic kidney disease patients, but previous studies included only end-stage patients, i.e. those undergoing dialysis. This study aims to evaluate the effect of exercise on kidney function, quality of life and other risk factors for cardiovascular disease among non-diabetic chronic hypertensive kidney disease patients who are not undergoing dialysis. Methods The participants will be located through screening hypertensive patients attended within the public healthcare network in Pelotas, a city in south of Brazil. Eligible individuals will be those with glomerular filtration rate between 15 and 59 ml/min x 1.73 m2. The randomization will be done in fixed-size blocks of six individuals such that 75 participants will be allocated to each group. At baseline, information on demographic, socioeconomic, behavioral, anthropometric, blood pressure and quality-of-life variables will be collected, and laboratory tests will be performed. The intervention will consist of three weekly physical exercise sessions lasting 60–75 minutes each, with a total duration of 16 weeks. The outcomes will be the kidney function progression rate, quality of life, blood pressure, lipid profile, hemoglobin level, ultrasensitive C-reactive protein level, and ankle-arm index. The patients in both groups (intervention and control will be reassessed and compared partway through the study (8th week, at the end of the intervention (16th week and in the 8th week after

  14. Basement membrane abnormalities in human eyes with diabetic retinopathy

    DEFF Research Database (Denmark)

    Ljubimov, A V; Burgeson, R E; Butkowski, R J

    1996-01-01

    Vascular and parenchymal basement membranes (BMs) are thickened in diabetes, but alterations in individual BM components in diabetic eyes, especially in diabetic retinopathy (DR), are obscure. To identify abnormalities in the distribution of specific constituents, we analyzed cryostat sections...... of human eyes obtained at autopsy (seven normal, five diabetic without DR, and 13 diabetic with DR) by immunofluorescence with antibodies to 30 BM and extracellular matrix components. In non-DR eyes, no qualitative changes of ocular BM components were seen. In some DR corneas, epithelial BM was stained...... discontinuously for laminin-1, entactin/nidogen, and alpha3-alpha4 Type IV collagen, in contrast to non-DR corneas. Major BM alterations were found in DR retinas compared to normals and non-DR diabetics. The inner limiting membrane (retinal BM) of DR eyes had accumulations of fibronectin (including cellular...

  15. Prediction of prevalence of chronic kidney disease in diabetic patients in countries of the European Union up to 2025.

    Science.gov (United States)

    Kainz, Alexander; Hronsky, Milan; Stel, Vianda S; Jager, Kitty J; Geroldinger, Angelika; Dunkler, Daniela; Heinze, Georg; Tripepi, Giovanni; Oberbauer, Rainer

    2015-08-01

    Diabetes and chronic kidney disease (CKD) are a growing burden for health-care systems. The prevalence of diabetes has increased constantly during the last decade, although a slight flattening of end-stage renal disease as a result of diabetes has been observed recently in some European countries. In this study, we project the prevalence of CKD in patients with diabetes in European countries up to the year 2025. We analysed the population with diabetes and development of nephropathy in 12 European countries, which we computed from models published previously and on data from the annual reports of the European Renal Association (1998-2011). The prevalence of CKD stage 5 in patients with diabetes up to the year 2025 was projected by the Lee-Carter algorithm. Those for stage 3 and 4 were then estimated by applying the same ratios of CKD prevalences as estimated in the Austrian population with diabetic nephropathy. The estimated prevalence of CKD in patients with diabetes is expected to increase in all 12 countries up to the year 2025. For CKD stage 3, we estimate for Austria in 2025 a prevalence of 215 000 per million diabetic population (p.m.p.) (95% confidence interval 169 000, 275 000), for CKD4 18 600 p.m.p. (14 500, 23 700) and for CKD5 6900 p.m.p. (5400, 8900). The median prevalence in the considered countries is 132 900 p.m.p. (IQR: 118 500, 195 800), 11 500 (10 200, 16 900) and 4300 (3800, 6300) for CKD stages 3, 4 and 5, respectively. Altogether, these data predict in the years 2012-25 an annual increase of 3.2% in the prevalence of diabetic CKD stage 5. Due to the increase in prevalence of diabetes and CKD5, the costs of renal therapy are expected to rise. We believe that these data may help health-care policy makers to make informed decisions. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  16. Diabetes technology and the human factor.

    Science.gov (United States)

    Liberman, A; Buckingham, B; Phillip, M

    2011-02-01

    When developing new technologies for human use the developer should take into consideration not only the efficacy and safety of the technology but also the desire and capabilities of the potential user. Any chronic disease is a challenge for both the patient and his/her caregivers. This statement is especially true in the case of patients with type 1 diabetes mellitus (T1DM) where adherence to therapy is crucial 24 hours a day 365 days a year. No vacation days are possible for the T1DM patient. It is therefore obvious why any new technology which is developed for helping patients cope with the disease should take into consideration the 'human factor' before, during and after the production process starts. There is no doubt that technology has changed the life of patients with T1DM in the last few decades, but despite the availability of new meters, new syringes, new sophisticated insulin pumps and continuous glucose sensors and communication tools, these technologies have not been well utilised by many patients. It is therefore important to understand why the technology is not always utilised and to find new ways to maximise use and benefits from the technology to as many patients as possible. The present chapter will review papers published in the last year where the patient's ability or willingness was an important factor in the success of the technology. We will try to understand why insulin pumps, glucose sensors and self-monitoring of blood glucose (SMBG) are not used enough or appropriately, whether there is a specific group that finds it more difficult than others to adopt new technologies and what can be done to overcome that issue. For this chapter we chose articles from a Public Medicine review of the literature related to human factors affecting the outcome of studies and of user acceptance of continuous glucose monitoring, insulin infusion pump therapy. We also searched the literature in the field of psychology in order to accurately define the problems

  17. Human kidney anion exchanger 1 interacts with kinesin family member 3B (KIF3B)

    Energy Technology Data Exchange (ETDEWEB)

    Duangtum, Natapol [Medical Molecular Biology Unit, Office for Research and Development Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Junking, Mutita; Sawasdee, Nunghathai [Medical Molecular Biology Unit, Office for Research and Development Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Cheunsuchon, Boonyarit [Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Limjindaporn, Thawornchai, E-mail: limjindaporn@yahoo.com [Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Yenchitsomanus, Pa-thai, E-mail: grpye@mahidol.ac.th [Medical Molecular Biology Unit, Office for Research and Development Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand)

    2011-09-16

    Highlights: {yields} Impaired trafficking of kAE1 causes distal renal tubular acidosis (dRTA). {yields} The interaction between kAE1 and kinesin family member 3B (KIF3B) is reported. {yields} The co-localization between kAE and KIF3B was detected in human kidney tissues. {yields} A marked reduction of kAE1 on the cell membrane was observed when KIF3B was knockdown. {yields} KFI3B plays an important role in trafficking of kAE1 to the plasma membrane. -- Abstract: Impaired trafficking of human kidney anion exchanger 1 (kAE1) to the basolateral membrane of {alpha}-intercalated cells of the kidney collecting duct leads to the defect of the Cl{sup -}/HCO{sub 3}{sup -} exchange and the failure of proton (H{sup +}) secretion at the apical membrane of these cells, causing distal renal tubular acidosis (dRTA). In the sorting process, kAE1 interacts with AP-1 mu1A, a subunit of AP-1A adaptor complex. However, it is not known whether kAE1 interacts with motor proteins in its trafficking process to the plasma membrane or not. We report here that kAE1 interacts with kinesin family member 3B (KIF3B) in kidney cells and a dileucine motif at the carboxyl terminus of kAE1 contributes to this interaction. We have also demonstrated that kAE1 co-localizes with KIF3B in human kidney tissues and the suppression of endogenous KIF3B in HEK293T cells by small interfering RNA (siRNA) decreases membrane localization of kAE1 but increases its intracellular accumulation. All results suggest that KIF3B is involved in the trafficking of kAE1 to the plasma membrane of human kidney {alpha}-intercalated cells.

  18. Human kidney anion exchanger 1 interacts with kinesin family member 3B (KIF3B)

    International Nuclear Information System (INIS)

    Duangtum, Natapol; Junking, Mutita; Sawasdee, Nunghathai; Cheunsuchon, Boonyarit; Limjindaporn, Thawornchai; Yenchitsomanus, Pa-thai

    2011-01-01

    Highlights: → Impaired trafficking of kAE1 causes distal renal tubular acidosis (dRTA). → The interaction between kAE1 and kinesin family member 3B (KIF3B) is reported. → The co-localization between kAE and KIF3B was detected in human kidney tissues. → A marked reduction of kAE1 on the cell membrane was observed when KIF3B was knockdown. → KFI3B plays an important role in trafficking of kAE1 to the plasma membrane. -- Abstract: Impaired trafficking of human kidney anion exchanger 1 (kAE1) to the basolateral membrane of α-intercalated cells of the kidney collecting duct leads to the defect of the Cl - /HCO 3 - exchange and the failure of proton (H + ) secretion at the apical membrane of these cells, causing distal renal tubular acidosis (dRTA). In the sorting process, kAE1 interacts with AP-1 mu1A, a subunit of AP-1A adaptor complex. However, it is not known whether kAE1 interacts with motor proteins in its trafficking process to the plasma membrane or not. We report here that kAE1 interacts with kinesin family member 3B (KIF3B) in kidney cells and a dileucine motif at the carboxyl terminus of kAE1 contributes to this interaction. We have also demonstrated that kAE1 co-localizes with KIF3B in human kidney tissues and the suppression of endogenous KIF3B in HEK293T cells by small interfering RNA (siRNA) decreases membrane localization of kAE1 but increases its intracellular accumulation. All results suggest that KIF3B is involved in the trafficking of kAE1 to the plasma membrane of human kidney α-intercalated cells.

  19. Mapping of Carboxypeptidase M in Normal Human Kidney and Renal Cell Carcinoma

    Science.gov (United States)

    Denis, Catherine J.; Van Acker, Nathalie; De Schepper, Stefanie; De Bie, Martine; Andries, Luc; Fransen, Erik; Hendriks, Dirk; Kockx, Mark M.

    2013-01-01

    Although the kidney generally has been regarded as an excellent source of carboxypeptidase M (CPM), little is known about its renal-specific expression level and distribution. This study provides a detailed localization of CPM in healthy and diseased human kidneys. The results indicate a broad distribution of CPM along the renal tubular structures in the healthy kidney. CPM was identified at the parietal epithelium beneath the Bowman’s basement membrane and in glomerular mesangial cells. Capillaries, podocytes, and most interstitial cells were CPM negative. Tumor cells of renal cell carcinoma subtypes lose CPM expression upon dedifferentiation. Tissue microarray analysis demonstrated a correlation between low CPM expression and tumor cell type. CPM staining was intense on phagocytotic tumor-associated macrophages. Immunoreactive CPM was also detected in the tumor-associated vasculature. The absence of CPM in normal renal blood vessels points toward a role for CPM in angiogenesis. Coexistence of CPM and the epidermal growth factor receptor (EGFR) was detected in papillary renal cell carcinoma. However, the different subcellular localization of CPM and EGFR argues against an interaction between these h proteins. The description of the distribution of CPM in human kidney forms the foundation for further study of the (patho)physiological activities of CPM in the kidney. PMID:23172796

  20. The renin–angiotensin–aldosterone system blockade in patients with advanced diabetic kidney disease

    Directory of Open Access Journals (Sweden)

    Sheila Bermejo

    2018-03-01

    Full Text Available Background and objectives: Diabetic kidney disease is the leading cause of end-stage chronic kidney disease (CKD. The renin–angiotensin–aldosterone system (RAAS blockade has been shown to slow the progression of diabetic kidney disease. Our objectives were: to study the percentage of patients with diabetic kidney disease treated with RAAS blockade, to determine its renal function, safety profile and assess whether its administration is associated with increased progression of CKD after 3 years of follow-up. Materials and methods: Retrospective study. 197 diabetic kidney disease patients were included and divided into three groups according to the treatment: patients who had never received RAAS blockade (non-RAAS blockade, patients who at some point had received RAAS blockade (inconstant-RAAS blockade and patients who received RAAS blockade (constant-RAAS blockade. Clinical characteristics and analytical variables such as renal function, electrolytes, glycosylated hemoglobin and glomerular filtration rate according to CKD-EPI and MDRD formulas were assessed. We also studied their clinical course (baseline, 1 and 3 years follow-up in terms of treatment group, survival, risk factors and renal prognosis. Results: Non-RAAS blockade patients had worse renal function and older age (p < 0.05 at baseline compared to RAAS blockade patients. Patients who received RAAS blockade were not found to have greater toxicity or chronic kidney disease progression and no differences in renal prognosis were identified. Mortality was higher in non-RAAS blockade patients, older patients and patients with worse renal function (p < 0.05. In the multivariate analysis, older age and worse renal function were risk factors for mortality. Conclusions: Treatment with RAAS blockade is more common in diabetic kidney disease patients with eGFR ≥ 30 ml/min/1.73 m2. In our study, there were no differences in the evolution of renal function

  1. The Effects of Rumex patientia L. and Urtica dioica L. on Some Blood and Urine Parameters, and Liver and Kidney Histology in Diabetic Rats

    OpenAIRE

    GÜNEŞ, Hasan V.

    2014-01-01

    The effects of Rumex patientia and Urtica dioica on levels of blood glucose, plasma amino acids and other parameters, urine excreta, and liver and kidney histology were examined in diabetic rats induced by streptozotocin. Streptozotocin increased blood glucose and changed the levels of amino acids and other parameters, and caused degenerative changes in the liver and kidney. Rumex patientia had some protective effect on these parameters changed by streptozotocin, while Urtica dioci...

  2. Association of Chronic Kidney Disease and Cerebral Small Vessel Disease with Cognitive Impairment in Elderly Patients with Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Toshitaka Umemura

    2013-07-01

    Full Text Available Background/Aims: In recent years, the relationship between chronic kidney disease (CKD and cognitive impairment has been attracting attention. Cerebral small vessel disease (SVD is also associated with an increased risk of cognitive impairment. However, it is still unknown whether CKD markers are associated with cognitive impairment independently of SVD in elderly diabetic patients. Methods: Seventy-nine type 2 diabetic patients (mean age, 76.0 years were enrolled in the present study. CKD was defined as the presence of albuminuria and/or a low estimated glomerular filtration rate (eGFR 2. SVD was evaluated by the presence and severity of silent brain infarcts (SBIs and white matter lesions (WMLs on brain magnetic resonance imaging. Neuropsychological tests were assessed using four validated cognitive instruments. Results: In multiple linear regression analyses, albuminuria was associated with worse modified Stroop Color Word scores (β = 0.284, p = 0.017 and low eGFR was associated with reduced Digit Symbol Substitution scores (β = -0.224, p = 0.026 after adjustment for age, sex, education years, diabetes duration, hypertension, multiple SBIs, and advanced WMLs. In contrast, there were no significant associations between CKD markers and Mini-Mental State Examination or Word Recall scores. Conclusion: Our findings suggest that albuminuria and low eGFR are associated with frontal lobe dysfunction independently of SVD in elderly type 2 diabetic patients.

  3. Kidney volume in type 1 (insulin-dependent) diabetic patients with normal or increased urinary albumin excretion

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, B; Hegedüs, L; Mathiesen, E R

    1991-01-01

    Forty-seven patients with type 1 (insulin-dependent) diabetes mellitus and 14 normal subjects had renal volume determined by an ultrasonic technique. Renal volume of 299 +/- 49 ml/1.73 m2 (mean +/- SD) in type 1 diabetic patients with normal urinary albumin excretion exceeded that in the normal...... subjects (245 +/- 53 ml/1.73 m2, p less than 0.05). Compared with diabetic patients with normal urinary albumin excretion, renal volume was significantly higher in patients with microalbuminuria (372 +/- 24 ml/1.73 m2, p less than 0.05) and patients with clinical nephropathy (352 +/- 48 ml/1.73 m2, p less...... than 0.05). In a multiple linear regression with HbA1c, urinary albumin excretion, age, diabetes duration and mean blood pressure as independent variables, variations in HbA1c could account for 33% of the variations in kidney volume (n = 47, r = 0.57, p less than 0.01). The other variables played...

  4. Effects of total glucosides of paeony on immune regulatory toll-like receptors TLR2 and 4 in the kidney from diabetic rats.

    Science.gov (United States)

    Xu, Xing-xin; Qi, Xiang-Ming; Zhang, Wei; Zhang, Chao-Qun; Wu, Xiao-Xu; Wu, Yong-Gui; Wang, Kun; Shen, Ji-Jia

    2014-05-15

    TLRs are a family of receptors that play a critical role in the pathogenesis of diabetic nephropathy. TGP have been shown to have anti-inflammatory and immuno-regulatory activities. However, the relation between TGP and TLRs on diabetic nephropathy remains unknown. In this study, we examined effects of TGP on immune regulatory TLR2 and 4 in the kidney from streptozotocin-induced diabetic rats. TGP decreased the levels of 24h urinary albumin excretion rate significantly in diabetic rats. Western blot analysis showed that TGP significantly inhibited the expression of TLR2 and 4, MyD88, p-IRAK1, NF-κB p65, p-IRF3, TNF-α and IL-1β. Quantitative real-time PCR analysis showed that the significantly increased levels of TLR2 and 4, and MyD88mRNA in the kidneys of diabetic rats were significantly suppressed by TGP treatment. Macrophages infiltration were also markedly increased in the kidneys of the diabetic rats, but were significantly inhibited by TGP in a dose-dependent manner. These results suggest that TGP has protective effects on several pharmacological targets in the progress of diabetic nephropathy by selectively blocking TLRs activation in vivo. Copyright © 2013 Elsevier GmbH. All rights reserved.

  5. The Antidiabetic Activity of Curry Leaves “Murraya Koenigii” on the Glucose Levels, Kidneys, and Islets of Langerhans of Rats with Streptozotocin Induced Diabetes

    Directory of Open Access Journals (Sweden)

    Imad M Al-Ani

    2017-08-01

    Full Text Available Background: The aims of this study were to explore the antihyperglycemic effect of curry leaves, Murraya koenigii "MK" aqueous extract, and to examine its possible protective effects on the islets of Langerhans and kidneys of streptozotocin (STZ diabetic rats. Methods: Thirty healthy adult male Sprague Dawley rats were randomized into five groups (n=6; normal control, normal treated with "MK" control, diabetic control (non-treated with "MK", diabetic treated with 200 mg/kg MK aqueous leaf extract and diabetic treated with 400 mg/kg MK aqueous leaf extract. Blood glucose levels and body weight were monitored gravimetrically. The animals were sacrificed on the 30th day; the kidney and pancreatic tissues were processed for histological studies. Results: The diabetic group showed considerable loss of body weight and increase in blood glucose levels and degeneration of the glomeruli and renal convoluted tubules and atrophied islets with disintegration of β-cells. Treatment of diabetic rats with MK extract showed significant (p < 0.001 improvement in blood glucose levels and body weight gain. The MK extract also caused an improvement in tissue injury induced by STZ injection in the kidney and islets of Langerhans. Conclusions: These findings highlighted the beneficial effects of MK aqueous extract against cellular oxidative damage in STZ-induced diabetic rats.

  6. Effect of the Diabetic State on Islet Engraftment and Function in a Large Animal Model of Islet-Kidney Transplantation.

    Science.gov (United States)

    Vallabhajosyula, Prashanth; Hirakata, Atsushi; Weiss, Matthew; Griesemer, Adam; Shimizu, Akira; Hong, Hanzhou; Habertheuer, Andreas; Tchipashvili, Vaja; Yamada, Kazuhiko; Sachs, David H

    2017-11-01

    In islet transplantation, in addition to immunologic and ischemic factors, the diabetic/hyperglycemic state of the recipient has been proposed, although not yet validated, as a possible cause of islet toxicity, contributing to islet loss during the engraftment period. Using a miniature swine model of islet transplantation, we have now assessed the effect of a persistent state of hyperglycemia on islet engraftment and subsequent function. An islet-kidney (IK) model previously described by our laboratory was utilized. Three experimental donor animals underwent total pancreatectomy and autologous islet transplantation underneath the renal capsule to prepare an IK at a load of ≤1,000 islet equivalents (IE)/kg donor weight, leading to a chronic diabetic state during the engraftment period (fasting blood glucose >250 mg/dL). Three control donor animals underwent partial pancreatectomy (sufficient to maintain normoglycemia during islet engraftment period) and IK preparation. As in vivo functional readout for islet engraftment, the IKs were transplanted across an immunologic minor or class I mismatch barrier into diabetic, nephrectomized recipients at an islet load of ∼4,500 IE/kg recipient weight. A 12-d course of cyclosporine was administered for tolerance induction. All experimental donors became diabetic and showed signs of end organ injury, while control donors maintained normoglycemia. All recipients of IK from both experimental and control donors achieved glycemic control over long-term follow-up, with reversal of diabetic nephropathy and with similar glucose tolerance tests. In this preclinical, large animal model, neither islet engraftment nor subsequent long-term islet function after transplantation appear to be affected by the diabetic state.

  7. Effect of the Diabetic State on Islet Engraftment and Function in a Large Animal Model of Islet–Kidney Transplantation

    Science.gov (United States)

    Hirakata, Atsushi; Weiss, Matthew; Griesemer, Adam; Shimizu, Akira; Hong, Hanzhou; Habertheuer, Andreas; Tchipashvili, Vaja; Yamada, Kazuhiko; Sachs, David H.

    2018-01-01

    In islet transplantation, in addition to immunologic and ischemic factors, the diabetic/hyperglycemic state of the recipient has been proposed, although not yet validated, as a possible cause of islet toxicity, contributing to islet loss during the engraftment period. Using a miniature swine model of islet transplantation, we have now assessed the effect of a persistent state of hyperglycemia on islet engraftment and subsequent function. An islet–kidney (IK) model previously described by our laboratory was utilized. Three experimental donor animals underwent total pancreatectomy and autologous islet transplantation underneath the renal capsule to prepare an IK at a load of ≤1,000 islet equivalents (IE)/kg donor weight, leading to a chronic diabetic state during the engraftment period (fasting blood glucose >250 mg/dL). Three control donor animals underwent partial pancreatectomy (sufficient to maintain normoglycemia during islet engraftment period) and IK preparation. As in vivo functional readout for islet engraftment, the IKs were transplanted across an immunologic minor or class I mismatch barrier into diabetic, nephrectomized recipients at an islet load of ∼4,500 IE/kg recipient weight. A 12-d course of cyclosporine was administered for tolerance induction. All experimental donors became diabetic and showed signs of end organ injury, while control donors maintained normoglycemia. All recipients of IK from both experimental and control donors achieved glycemic control over long-term follow-up, with reversal of diabetic nephropathy and with similar glucose tolerance tests. In this preclinical, large animal model, neither islet engraftment nor subsequent long-term islet function after transplantation appear to be affected by the diabetic state. PMID:29338381

  8. The epithelial sodium channel γ-subunit is processed proteolytically in human kidney

    DEFF Research Database (Denmark)

    Langkilde, Rikke Zachar; Skjødt, Karsten; Marcussen, Niels

    2015-01-01

    The epithelial sodium channel (ENaC) of the kidney is necessary for extracellular volume homeostasis and normal arterial BP. Activity of ENaC is enhanced by proteolytic cleavage of the gamma-subunit and putative release of a 43-amino acid inhibitory tract from the gamma-subunit ectodomain. We......ENaC was detected consistently only in tissue from patients with proteinuria and observed in collecting ducts. In conclusion, human kidney gammaENaC is subject to proteolytic cleavage, yielding fragments compatible with furin cleavage, and proteinuria is associated with cleavage at the putative prostasin...

  9. The National Institute of Diabetes and Digestive and Kidney Diseases Central Repositories: A Valuable Resource for Nephrology Research

    Science.gov (United States)

    Akolkar, Beena; Spain, Lisa M.; Guill, Michael H.; Del Vecchio, Corey T.; Carroll, Leslie E.

    2015-01-01

    The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Central Repositories, part of the National Institutes of Health (NIH), are an important resource available to researchers and the general public. The Central Repositories house samples, genetic data, phenotypic data, and study documentation from >100 NIDDK-funded clinical studies, in areas such as diabetes, digestive disease, and liver disease research. The Central Repositories also have an exceptionally rich collection of studies related to kidney disease, including the Modification of Diet in Renal Disease landmark study and recent data from the Chronic Renal Insufficiency Cohort and CKD in Children Cohort studies. The data are carefully curated and linked to the samples from the study. The NIDDK is working to make the materials and data accessible to researchers. The Data Repositories continue to improve flexible online searching tools that help researchers identify the samples or data of interest, and NIDDK has created several different paths to access the data and samples, including some funding initiatives. Over the past several years, the Central Repositories have seen steadily increasing interest and use of the stored materials. NIDDK plans to make more collections available and do more outreach and education about use of the datasets to the nephrology research community in the future to enhance the value of this resource. PMID:25376765

  10. The National Institute of Diabetes and Digestive and Kidney Diseases Central Repositories: a valuable resource for nephrology research.

    Science.gov (United States)

    Rasooly, Rebekah S; Akolkar, Beena; Spain, Lisa M; Guill, Michael H; Del Vecchio, Corey T; Carroll, Leslie E

    2015-04-07

    The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Central Repositories, part of the National Institutes of Health (NIH), are an important resource available to researchers and the general public. The Central Repositories house samples, genetic data, phenotypic data, and study documentation from >100 NIDDK-funded clinical studies, in areas such as diabetes, digestive disease, and liver disease research. The Central Repositories also have an exceptionally rich collection of studies related to kidney disease, including the Modification of Diet in Renal Disease landmark study and recent data from the Chronic Renal Insufficiency Cohort and CKD in Children Cohort studies. The data are carefully curated and linked to the samples from the study. The NIDDK is working to make the materials and data accessible to researchers. The Data Repositories continue to improve flexible online searching tools that help researchers identify the samples or data of interest, and NIDDK has created several different paths to access the data and samples, including some funding initiatives. Over the past several years, the Central Repositories have seen steadily increasing interest and use of the stored materials. NIDDK plans to make more collections available and do more outreach and education about use of the datasets to the nephrology research community in the future to enhance the value of this resource. Copyright © 2015 by the American Society of Nephrology.

  11. Effects of low dose radiation on expressions of ICAM-1 mRNA and protein in kidney of diabetic mice

    International Nuclear Information System (INIS)

    Zhang Chi; Li Xiaokun; Gong Shouliang; Liu Xiaoju; Zhao Xue; Liu Xiaoju; Zhao Xue; Shen Wenjie; Li Cai; Cai Lu

    2010-01-01

    Objective: To study the effects of low dose radiation (LDR) on the expressions of intercellular adhesion molecule-1 (ICAM-1) mRNA and protein in kidney of diabetes mellitus (DM) mice and illuminate that anti-inflammation of LDR is a main mechanism for diabetic therapy. Methods: The healthy and right age C57BL/6J mice were divided into 4 groups including control, DM, LDR and DM/LDR. The mice in DM and DM/LDR groups were injected intraperitoneally with streptozocin (STZ) to set up DM models. The mice in DM/LDR and LDR groups were irradiated with 25 mGy every other day for 4 weeks. The expressions of ICAM-1 mRNA and protein in kidney were detected with RT-PCR and Western blotting 2, 4, 8, 12 and 16 weeks after irradiation. Results: The expressions of ICAM-1 mRNA and protein in kidney had no significant difference among 4 groups before LDR (P>0.05). The expressions of ICAM-1 mRNA and protein 2 weeks after irradiation with LDR were higher than those in the other 3 groups (P<0.05). The expressions of ICAM-1 mRNA and protein in the DM/LDR group 4 weeks after irradiation were also significantly higher than those in non-DM groups (P<0.05), but still significantly lower than those in DM group (P<0.05), and the significant differences were kept to 16 weeks after irradiation. But the expressions of ICAM-1 mRNA and protein in LDR group were significantly higher than those in control group (P<0.05). IHC assay showed that the glomerular and tubular in DM and DM/LDR groups were abnormal and the quantities of the positive staining cells were significantly increased compared with non-DM groups. However the damage of glomerular and tubular in DM/LDR was significantly supressed compared with DM group and the positive staining cells were also decreased. Conclusion: Under the circumstance of DM, LDR can significantly decrease the expressions of ICAM-1 mRNA and protein in mouse kidney to relief the inflammation reaction in kidney; but in normal condition, LDR can improve the immunity and

  12. Human kidney proximal tubule cells are vulnerable to the effects of Rauwolfia serpentina.

    Science.gov (United States)

    Mossoba, Miriam E; Flynn, Thomas J; Vohra, Sanah; Wiesenfeld, Paddy L; Sprando, Robert L

    2015-12-01

    Rauwolfia serpentina (or Snake root plant) is a botanical dietary supplement marketed in the USA for maintaining blood pressure. Very few studies have addressed the safety of this herb, despite its wide availability to consumers. Its reported pleiotropic effects underscore the necessity for evaluating its safety. We used a human kidney cell line to investigate the possible negative effects of R. serpentina on the renal system in vitro, with a specific focus on the renal proximal tubules. We evaluated cellular and mitochondrial toxicity, along with a variety of other kidney-specific toxicology biomarkers. We found that R. serpentina was capable of producing highly detrimental effects in our in vitro renal cell system. These results suggest more studies are needed to investigate the safety of this dietary supplement in both kidney and other target organ systems.

  13. Profile of chronic kidney disease related-mineral bone disorders in newly diagnosed advanced predialysis diabetic kidney disease patients: A hospital based cross-sectional study.

    Science.gov (United States)

    Ray, S; Beatrice, A M; Ghosh, A; Pramanik, S; Bhattacharjee, R; Ghosh, S; Raychaudhury, A; Mukhopadhyay, S; Chowdhury, S

    2017-12-01

    Chronic kidney disease related-mineral bone disorder (CKD-MBD) has been poorly studied in pre-dialysis Indian CKD population. There are limited data on the pattern of these disturbances in diabetic CKD patients. Therefore, a study was conducted to find out the profile of mineral bone disorders in T2DM patients with pre-dialysis CKD. In this cross-sectional design, diabetic patients with newly-diagnosed stage 4 and 5 CKD were evaluated. Serum levels of calcium, phosphorus, intact parathyroid hormone (iPTH), 25 hydroxy vitamin D and total alkaline phosphatase (ALP) were measured in all patients. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA). A total of 72 eligible patients participated (44 males, 28 females; age 54.2±11.7). Patients with CKD Stage 5 had a lower level of corrected serum calcium and significantly higher level of inorganic phosphorus, total ALP and iPTH as compared to stage 4 patients. Overall, 38.5% were hypocalcemic, 31.43% were hyperphosphatemic. 24.2% of CKD subjects were vitamin D deficient (110pg/ml) was detected in nearly 43% of patients. In stage 5, only 32% patients was found to have hyperparathyroidism (iPTH>300pg/ml). There was a good correlation between iPTH and total ALP (r=0.5, p=0.0001) in this cohort. 25 (OH) vitamin D was inversely correlated with ALP (r=-0.39, P=0.001) and showed negative correlation with urine ACR (r=-0.37, P=0.002). As a group, the osteoporotic CKD subjects exhibited higher iPTH (220.1±153.8 vs. 119±108pg/ml, p<0.05) as compared to those who were osteopenic or had normal bone density. There was significant correlation between BMD and iPTH (adjusted r=-0.436; P=0.001). In the multivariate regression model, we found intact PTH to predict BMD even after adjustment of all the confounders. The current study showed that adynamic bone disease is prevalent even in pre-dialysis CKD population. High bone turnover disease may not be the most prevalent type in diabetic CKD. However, it

  14. Strong human leukocyte antigen matching effect in nonsensitized kidney recipients with high pretransplant soluble CD30.

    Science.gov (United States)

    Süsal, Caner; Pelzl, Steffen; Opelz, Gerhard

    2003-10-27

    The influence of human leukocyte antigen (HLA) matching on graft survival is greater in patients with preformed lymphocytotoxic antibodies than in nonsensitized patients. Pretransplant serum soluble CD30 (sCD30) affects graft outcome independently of presensitization status. The impact of HLA compatibility on kidney transplant survival was analyzed in 3980 nonsensitized first cadaveric kidney recipients in relation to the pretransplant serum sCD30 content. Although HLA compatibility influenced graft outcome only marginally in nonsensitized recipients with low sCD30 (at 3 years: P=0.0095; at 5 years: P=0.1033), a strong HLA matching effect was observed in nonsensitized recipients with high sCD30 (at 3 years: PsCD30 benefit from an HLA well-matched kidney. Patients should be tested for sCD30 while on the waiting list for a kidney transplant, and HLA well-matched kidneys should be allocated to patients with high sCD30.

  15. Infestation of the human kidney with Dioctophyma renale.

    Science.gov (United States)

    Ignjatovic, Ivan; Stojkovic, Ivica; Kutlesic, Cedo; Tasic, Suzana

    2003-01-01

    Human infestation with Dioctophyma renale is presented. Clinical signs and diagnostic findings are unspecific. They are discussed and a conservative therapeutic approach is suggested. Copyright 2003 S. Karger AG, Basel

  16. Pharmacokinetics, Pharmacodynamics and Clinical Use of SGLT2 Inhibitors in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease.

    Science.gov (United States)

    Scheen, André J

    2015-07-01

    Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) are proposed as a novel approach for the management of type 2 diabetes mellitus. SGLT2 cotransporters are responsible for reabsorption of 90 % of the glucose filtered by the kidney. The glucuretic effect resulting from SGLT2 inhibition contributes to reduce hyperglycaemia and also assists weight loss and blood pressure reduction. Several SGLT2 inhibitors are already available in many countries (dapagliflozin, canagliflozin, empagliflozin) and in Japan (ipragliflozin, tofogliflozin). These SGLT2 inhibitors share similar pharmacokinetic characteristics with a rapid oral absorption, a long elimination half-life allowing once-daily administration, an extensive hepatic metabolism mainly via glucuronidation to inactive metabolites and a low renal elimination as a parent drug. Pharmacokinetic parameters are slightly altered in the case of chronic kidney disease (CKD). While no dose adjustment is required in the case of mild CKD, SGLT2 inhibitors may not be used or only at a lower daily dose in patients with moderate CKD. Furthermore, the pharmacodynamic response to SGLT2 inhibitors as assessed by urinary glucose excretion declines with increasing severity of renal impairment as assessed by a reduction in the estimated glomerular filtration rate. Nevertheless, the glucose-lowering efficacy and safety of SGLT2 inhibitors are almost comparable in patients with mild CKD as in patients with normal kidney function. In patients with moderate CKD, the efficacy tends to be dampened and safety concerns may occur. In patients with severe CKD, the use of SGLT2 inhibitors is contraindicated. Thus, prescribing information should be consulted regarding dosage adjustments or restrictions in the case of renal dysfunction for each SGLT2 inhibitor. The clinical impact of SGLT2 inhibitors on renal function and their potential to influence the course of diabetic nephropathy deserve attention because of preliminary favourable results

  17. Human Urine-Derived Renal Progenitors for Personalized Modeling of Genetic Kidney Disorders.

    Science.gov (United States)

    Lazzeri, Elena; Ronconi, Elisa; Angelotti, Maria Lucia; Peired, Anna; Mazzinghi, Benedetta; Becherucci, Francesca; Conti, Sara; Sansavini, Giulia; Sisti, Alessandro; Ravaglia, Fiammetta; Lombardi, Duccio; Provenzano, Aldesia; Manonelles, Anna; Cruzado, Josep M; Giglio, Sabrina; Roperto, Rosa Maria; Materassi, Marco; Lasagni, Laura; Romagnani, Paola

    2015-08-01

    The critical role of genetic and epigenetic factors in the pathogenesis of kidney disorders is gradually becoming clear, and the need for disease models that recapitulate human kidney disorders in a personalized manner is paramount. In this study, we describe a method to select and amplify renal progenitor cultures from the urine of patients with kidney disorders. Urine-derived human renal progenitors exhibited phenotype and functional properties identical to those purified from kidney tissue, including the capacity to differentiate into tubular cells and podocytes, as demonstrated by confocal microscopy, Western blot analysis of podocyte-specific proteins, and scanning electron microscopy. Lineage tracing studies performed with conditional transgenic mice, in which podocytes are irreversibly tagged upon tamoxifen treatment (NPHS2.iCreER;mT/mG), that were subjected to doxorubicin nephropathy demonstrated that renal progenitors are the only urinary cell population that can be amplified in long-term culture. To validate the use of these cells for personalized modeling of kidney disorders, renal progenitors were obtained from (1) the urine of children with nephrotic syndrome and carrying potentially pathogenic mutations in genes encoding for podocyte proteins and (2) the urine of children without genetic alterations, as validated by next-generation sequencing. Renal progenitors obtained from patients carrying pathogenic mutations generated podocytes that exhibited an abnormal cytoskeleton structure and functional abnormalities compared with those obtained from patients with proteinuria but without genetic mutations. The results of this study demonstrate that urine-derived patient-specific renal progenitor cultures may be an innovative research tool for modeling of genetic kidney disorders. Copyright © 2015 by the American Society of Nephrology.

  18. Hepcidin-25 in diabetic chronic kidney disease is predictive for mortality and progression to end stage renal disease.

    Directory of Open Access Journals (Sweden)

    Martin Wagner

    Full Text Available Anemia is common and is associated with impaired clinical outcomes in diabetic chronic kidney disease (CKD. It may be explained by reduced erythropoietin (EPO synthesis, but recent data suggest that EPO-resistance and diminished iron availability due to inflammation contribute significantly. In this cohort study, we evaluated the impact of hepcidin-25--the key hormone of iron-metabolism--on clinical outcomes in diabetic patients with CKD along with endogenous EPO levels.249 diabetic patients with CKD of any stage, excluding end-stage renal disease (ESRD, were enrolled (2003-2005, if they were not on EPO-stimulating agent and iron therapy. Hepcidin-25 levels were measured by radioimmunoassay. The association of hepcidin-25 at baseline with clinical variables was investigated using linear regression models. All-cause mortality and a composite endpoint of CKD progression (ESRD or doubling of serum creatinine were analyzed by Cox proportional hazards models.Patients (age 67 yrs, 53% male, GFR 51 ml/min, hemoglobin 131 g/L, EPO 13.5 U/L, hepcidin-25 62.0 ng/ml were followed for a median time of 4.2 yrs. Forty-nine patients died (19.7% and forty (16.1% patients reached the composite endpoint. Elevated hepcidin levels were independently associated with higher ferritin-levels, lower EPO-levels and impaired kidney function (all p<0.05. Hepcidin was related to mortality, along with its interaction with EPO, older age, greater proteinuria and elevated CRP (all p<0.05. Hepcidin was also predictive for progression of CKD, aside from baseline GFR, proteinuria, low albumin- and hemoglobin-levels and a history of CVD (all p<0.05.We found hepcidin-25 to be associated with EPO and impaired kidney function in diabetic CKD. Elevated hepcidin-25 and EPO-levels were independent predictors of mortality, while hepcidin-25 was also predictive for progression of CKD. Both hepcidin-25 and EPO may represent important prognostic factors of clinical outcome and have the

  19. The Antioxidant Capacity and Anti-diabetic Effect of Boswellia serrata Triana and Planch Aqueous Extract in Fertile Female Diabetic Rats and the Possible Effects on Reproduction and Histological Changes in the Liver and Kidneys.

    Science.gov (United States)

    Azemi, Mohamad Ebrahim; Namjoyan, Foroogh; Khodayar, Mohammad Javad; Ahmadpour, Forouzan; Darvish Padok, Azam; Panahi, Marziyeh

    2012-01-01

    Boswellia serrata has been used in a wide variety of diseases, including diabetes mellitus and inflammatory diseases. This study focused on the effects of Boswellia serrata aqueous extract on blood glucose and the complications of diabetes in the liver and kidneys and examined the impact of plant on reproduction in diabetic rats. The antioxidant capacity of plant extract was performed using FRAP assay. Diabetic and control rats were administered 200, 400, and 600 mg/kg Boswellia serrata extract. Vaginal plaque was mentioned as a positive sign of pregnancy ;and treatment started with extract or vehicle from 1th to 17th day of gestation by gastric gavage. Blood glucose was measured during 17 days. The Administration of Boswellia serrata in diabetic rats significantly decreased the level of blood glucose and HbA1c after 17th days (P ≤ 0.01). In diabetic group that received no treatment, the abortion of fetus spontaneous was 19.14%. The percentage of absorptions significantly was elevated in vehicle-treated diabetic rats, in comparison with vehicle- treated healthy rats. In the diabetic group, separated necrosis of hepatocytes, anarchism of liver plates, and lymphocytic inflammation were improved. Diabetic complications were not seen and the severity of damage was reduced. These damages include: lymphocytic inflammation in the port areas, irregularities, apoptosis of liver cells, and dilatation of the sinusoids. The results suggest that Boswellia serrata extract has the antidiabetic effects and can prevent the complications of diabetes in the kidneys and liver.

  20. Comparison of human and automatic segmentations of kidneys from CT images

    International Nuclear Information System (INIS)

    Rao, Manjori; Stough, Joshua; Chi, Y.-Y.; Muller, Keith; Tracton, Gregg; Pizer, Stephen M.; Chaney, Edward L.

    2005-01-01

    Purpose: A controlled observer study was conducted to compare a method for automatic image segmentation with conventional user-guided segmentation of right and left kidneys from planning computerized tomographic (CT) images. Methods and materials: Deformable shape models called m-reps were used to automatically segment right and left kidneys from 12 target CT images, and the results were compared with careful manual segmentations performed by two human experts. M-rep models were trained based on manual segmentations from a collection of images that did not include the targets. Segmentation using m-reps began with interactive initialization to position the kidney model over the target kidney in the image data. Fully automatic segmentation proceeded through two stages at successively smaller spatial scales. At the first stage, a global similarity transformation of the kidney model was computed to position the model closer to the target kidney. The similarity transformation was followed by large-scale deformations based on principal geodesic analysis (PGA). During the second stage, the medial atoms comprising the m-rep model were deformed one by one. This procedure was iterated until no changes were observed. The transformations and deformations at both stages were driven by optimizing an objective function with two terms. One term penalized the currently deformed m-rep by an amount proportional to its deviation from the mean m-rep derived from PGA of the training segmentations. The second term computed a model-to-image match term based on the goodness of match of the trained intensity template for the currently deformed m-rep with the corresponding intensity data in the target image. Human and m-rep segmentations were compared using quantitative metrics provided in a toolset called Valmet. Metrics reported in this article include (1) percent volume overlap; (2) mean surface distance between two segmentations; and (3) maximum surface separation (Hausdorff distance

  1. Erythropoetin receptor expression in the human diabetic retina

    Directory of Open Access Journals (Sweden)

    Tsang Stephen H

    2009-11-01

    Full Text Available Abstract Background Recent evidence suggests erythropoietin (EPO and the erythropoietin receptor (EPOR may play a direct role in the pathogenesis of diabetic retinopathy. Better characterization of the EPO-EPOR signaling system in the ischemic retina may offer a new therapeutic modality for ischemic ophthalmic diseases. This study was performed to identify EPOR mRNA expression in the human diabetic eye. Findings EPOR antisense RNA probes were validated on human pancreas tissue. In the normal eye, EPOR was expressed in the retinal ganglion cell layer. Minimal expression was observed in the inner and outer nuclear layer. Under conditions of diabetic retinopathy, EPOR expression shifted to photoreceptor cells. Increased expression was also observed in the peripheral retina. Conclusion EPOR expression may be a biomarker or contribute to disease mechanisms in diabetic retinopathy.

  2. Ultrastructure of neurovascular changes in human diabetic retinopathy.

    Science.gov (United States)

    Fehér, János; Taurone, Samanta; Spoletini, Marialuisa; Biró, Zsolt; Varsányi, Balázs; Scuderi, Gianluca; Orlando, Maria Patrizia; Turchetta, Rosaria; Micera, Alessandra; Artico, Marco

    2018-01-01

    The previous concept regarding diabetic retinopathy assigned a primary role to hyperglycemia-induced microvascular alterations, while neuronal and glial abnormalities were considered to be secondary to either ischemia or exudation. The aim of this study was to reveal the potential role of neuronal and glial cells in initial and advanced alterations of the retinopathy in human type 2 diabetes. Electron microscopy and histochemical studies were performed on 38 surgically removed human eyes (28 obtained from diabetic patients and 10 from non-diabetic patients). Morphometric analysis of basement membrane material and lipids was performed. An accumulation of metabolic by-products was found in the capillary wall with aging: this aspect was significantly more pronounced in diabetics. Müller glial cells were found to contribute to alterations of the capillary wall and to occlusion, as well as to the development of proliferative retinopathy and cystoid degeneration of the retina. Our results showed morphological evidence regarding the role of neuronal and glial cells in the pathology of diabetic retinopathy, prior and in addition to microangiopathy. These morphological findings support a neurovascular pathogenesis at the origin of diabetic retinopathy, thus the current treatment approach should be completed by neuroprotective measures.

  3. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults

    DEFF Research Database (Denmark)

    Larsen, Nadja; Vogensen, Finn Kvist; van der Berg, Franciscus Winfried J

    2010-01-01

    . Methods and Findings The study included 36 male adults with a broad range of age and body-mass indices (BMIs), among which 18 subjects were diagnosed with diabetes type 2. The fecal bacterial composition was investigated by real-time quantitative PCR (qPCR) and in a subgroup of subjects (N = 20) by tag...... = 0.04). Conclusions The results of this study indicate that type 2 diabetes in humans is associated with compositional changes in intestinal microbiota. The level of glucose tolerance should be considered when linking microbiota with metabolic diseases such as obesity and developing strategies......Background Recent evidence suggests that there is a link between metabolic diseases and bacterial populations in the gut. The aim of this study was to assess the differences between the composition of the intestinal microbiota in humans with type 2 diabetes and non-diabetic persons as control...

  4. Correlations of dietary energy and protein intakes with renal function impairment in chronic kidney disease patients with or without diabetes.

    Science.gov (United States)

    Chen, Mei-En; Hwang, Shang-Jyh; Chen, Hung-Chun; Hung, Chi-Chih; Hung, Hsin-Chia; Liu, Shao-Chun; Wu, Tsai-Jiin; Huang, Meng-Chuan

    2017-05-01

    Dietary energy and protein intake can affect progression of chronic kidney disease (CKD). CKD complicated with diabetes is often associated with a decline in renal function. We investigated the relative importance of dietary energy intake (DEI) and dietary protein intake (DPI) to renal function indicators in nondiabetic and diabetic CKD patients. A total of 539 Stage 3-5 CKD patients [estimated glomerular filtration rate (eGFR)Disease equation] with or without diabetes were recruited from outpatient clinics of Nephrology and Nutrition in a medical center in Taiwan. Appropriateness of DEI and DPI was used to subcategorize CKD patients into four groups:(1) kidney diet (KD) A (KD-A), the most appropriate diet, was characterized by low DPI and adequate DEI; (2) KD-B, low DPI and inadequate DEI; (3) KD-C, excess DPI and adequate DEI; and (4) KD-D, the least appropriate diet, excess DPI and inadequate DEI. Inadequate DEI was defined as a ratio of actual intake/recommended intake less than 90% and adequate DEI as over 90%. Low DPI was defined as less than 110% of recommended intake and excessive when over 110%. Outcome measured was eGFR. In both groups of CKD patients, DEI was significantly lower (ppatients were KD-C and KD-D significantly correlated with reduced eGFR compared with KD-A at increments of -5.63 mL/min/1.73 m 2 (p = 0.029) and -7.72 mL/min/1.73 m 2 (p=0.015). In conclusion, inadequate energy and excessive protein intakes appear to correlate with poorer renal function in nondiabetic CKD patients. Patients with advanced CKD are in need of counseling by dietitians to improve adherence to diets. Copyright © 2017. Published by Elsevier Taiwan.

  5. The breast cancer resistance protein transporter ABCG2 is expressed in the human kidney proximal tubule apical membrane.

    NARCIS (Netherlands)

    Huls, M.; Brown, C.D.; Windass, A.S.; Sayer, R.; Heuvel, J.J.M.W. van den; Heemskerk, S.; Russel, F.G.M.; Masereeuw, R.

    2008-01-01

    The Breast Cancer Resistance Protein (BCRP/ABCG2) is a transporter restricting absorption and enhancing excretion of many compounds including anticancer drugs. This transporter is highly expressed in many tissues; however, in human kidney, only the mRNA was found in contrast to the mouse kidney,

  6. Incidence and mortality of kidney cancers, and human development index in Asia; a matter of concern.

    Science.gov (United States)

    Arabsalmani, Masoumeh; Mohammadian-Hafshejani, Abdollah; Ghoncheh, Mahshid; Hadadian, Fatemeh; Towhidi, Farhad; Vafaee, Kamran; Salehiniya, Hamid

    2017-01-01

    The incidence and mortality of kidney cancer have steadily increased by 2%- 3% per decade worldwide, and an increased risk of kidney cancer has been observed in many Asian countries. The information on the incidence and mortality of a disease and its distribution is essential for better planning for prevention and further studies. This study aimed to assess the incidence and mortality of kidney cancer and their correlation with the human development index (HDI) in Asia. This ecological study was based on GLOBOCAN data Asia for assessment the correlation between age-specific incidence rate (ASIR) and age-specific mortality rate (ASMR) with HDI and its details that include life expectancy at birth, mean years of schooling and gross national income (GNI) per capita. We use of correlation bivariate method for assessment the correlation between ASIR and ASMR with HDI and its components. A total of 121 099 kidney cancer cases were recorded in Asian countries in 2012.Overall, 80 080 cases (66.12%) were males. Sex ratio was 1.95. The three countries with the highest number of new patients were china (66 466 cases), Japan (16 830 cases), India(9658 cases), respectively. Positive correlation were seen between HDI and ASIR of kidney cancer 0.655 ( P = 0.001), and HDI and ASMR of kidney cancer 0.285 ( P = 0.055). A positive relationship between ASIR and the HDI was seen. The relationship is due to risk factors in countries with high development such as older age, smoking, hypertension, obesity, and diet. However, ASMR showed no significant relationship with HDI.

  7. Usefulness of Estimation of Glycated Albumin and Glycosylated Haemoglobin in Indian Diabetic Chronic Kidney Disease Patients

    Directory of Open Access Journals (Sweden)

    Kumaresan Ramanathan

    2014-09-01

    CONCLUSION: GA estimation is a useful marker in assessment of short term glycemic control in stage III & IV (< 30 ml/min/1.73m2 diabetic CKD patients. GA: HbA1c ratio if routinely done may also become a useful marker in Diabetic CKD population in future.

  8. Native Americans with Diabetes

    Science.gov (United States)

    ... Read the MMWR Science Clips Native Americans with Diabetes Better diabetes care can decrease kidney failure Language: ... between 1996 and 2013. Problem Kidney failure from diabetes was highest among Native Americans. Native Americans are ...

  9. Harmonization of Glutamic Acid Decarboxylase and Islet Antigen-2 Autoantibody Assays for National Institute of Diabetes and Digestive and Kidney Diseases Consortia

    OpenAIRE

    Bonifacio, Ezio; Yu, Liping; Williams, Alastair K.; Eisenbarth, George S.; Bingley, Polly J.; Marcovina, Santica M.; Adler, Kerstin; Ziegler, Anette G.; Mueller, Patricia W.; Schatz, Desmond A.; Krischer, Jeffrey P.; Steffes, Michael W.; Akolkar, Beena

    2010-01-01

    Background/Rationale: Autoantibodies to islet antigen-2 (IA-2A) and glutamic acid decarboxylase (GADA) are markers for diagnosis, screening, and measuring outcomes in National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) consortia studies. A harmonization program was established to increase comparability of results within and among these studies.

  10. Aqueous Extract of Phyllanthus niruri Leaves Displays In Vitro Antioxidant Activity and Prevents the Elevation of Oxidative Stress in the Kidney of Streptozotocin-Induced Diabetic Male Rats

    Directory of Open Access Journals (Sweden)

    Nelli Giribabu

    2014-01-01

    Full Text Available P. niruri has been reported to possess antidiabetic and kidney protective effects. In the present study, the phytochemical constituents and in vitro antioxidant activity of P. niruri leaf aqueous extract were investigated together with its effect on oxidative stress and antioxidant enzymes levels in diabetic rat kidney. Results. Treatment of diabetic male rats with P. niruri leaf aqueous extract (200 and 400 mg/kg for 28 consecutive days prevents the increase in the amount of lipid peroxidation (LPO product, malondialdehyde (MDA, and the diminution of superoxide dismutase (SOD, catalase (CAT, and glutathione peroxidase (GPx activity levels in the kidney of diabetic rats. The amount of LPO showed strong negative correlation with SOD, CAT, and GPx activity levels. P. niruri leaf aqueous extract exhibits in vitro antioxidant activity with IC50 slightly lower than ascorbic acid. Phytochemical screening of plant extract indicates the presence of polyphenols. Conclusion. P. niruri leaf extract protects the kidney from oxidative stress induced by diabetes.

  11. Biomarker discovery in biological specimens (plasma, hair, liver and kidney) of diabetic mice based upon metabolite profiling using ultra-performance liquid chromatography with electrospray ionization time-of-flight mass spectrometry.

    Science.gov (United States)

    Tsutsui, Haruhito; Maeda, Toshio; Min, Jun Zhe; Inagaki, Shinsuke; Higashi, Tatsuya; Kagawa, Yoshiyuki; Toyo'oka, Toshimasa

    2011-05-12

    The number of diabetic patients has recently been increasing worldwide. Diabetes is a multifactorial disorder based on environmental factors and genetic background. In many cases, diabetes is asymptomatic for a long period and the patient is not aware of the disease. Therefore, the potential biomarker(s), leading to the early detection and/or prevention of diabetes mellitus, are strongly required. However, the diagnosis of the prediabetic state in humans is a very difficult issue, because the lifestyle is variable in each person. Although the development of a diagnosis method in humans is the goal of our research, the extraction and structural identification of biomarker candidates in several biological specimens (i.e., plasma, hair, liver and kidney) of ddY strain mice, which undergo naturally occurring diabetes along with aging, were carried out based upon a metabolite profiling study. The low-molecular-mass compounds including metabolites in the biological specimens of diabetic mice (ddY-H) and normal mice (ddY-L) were globally separated by ultra-performance liquid chromatography (UPLC) using different reversed-phase columns (i.e., T3-C18 and HS-F5) and detected by electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS). The biomarker candidates related to diabetes mellitus were extracted from a multivariate statistical analysis, such as an orthogonal partial least-squares-discriminant analysis (OPLS-DA), followed by a database search, such as ChemSpider, KEGG and HMDB. Many metabolites and unknown compounds in each biological specimen were detected as the biomarker candidates related to diabetic mellitus. Among them, the elucidation of the chemical structures of several possible metabolites, including more than two biological specimens, was carried out along with the comparison of the tandem MS/MS analyses using authentic compounds. One metabolite was clearly identified as N-acetyl-L-leucine based upon the MS/MS spectra and the retention time on

  12. Kidney transplant

    Science.gov (United States)

    ... always take your medicine as directed. Alternative Names Renal transplant; Transplant - kidney Patient Instructions Kidney removal - discharge Images Kidney anatomy Kidney - blood and urine flow Kidneys Kidney transplant - ...

  13. A low molecular weight urinary proteome profile of human kidney aging

    OpenAIRE

    Zürbig, Petra; Decramer, Stéphane; Dakna, Mohammed; Jantos, Justyna; Good, David M.; Coon, Joshua J.; Bandin, Flavio; Mischak, Harald; Bascands, Jean-Loup; Schanstra, Joost P

    2009-01-01

    Aging induces morphological changes of the kidney and reduces renal function. We analyzed the low molecular weight urinary proteome of 324 healthy individuals from 2-73 years of age to gain insight on renal aging in humans. We observed age-related modification of secretion of 325 out of 5000 urinary peptides. The majority of these changes was associated with renal development before and during puberty, while 49 peptides were related to aging in adults. Of these 49 peptides, the majority were ...

  14. Metaplasia of the parietal layer of Bowman's capsule. A histopathological survey of the human kidney

    OpenAIRE

    Haensly, William E.; Lee, J.C.

    1986-01-01

    Human kidney sections taken at autopsy were examined to determine the incidence of metaplasia of the Bowman's parietal epithelium. Autopsy records were consulted to determine if there was any correlation between clinical disease, histopathological changes in organ systems and metaplasia of Bowman's capsule. The sections represented both sexes in 9 age groups from 2 to 87 years. The sections were fixed in neutral formalin, embedded in paraffin, sectioned at 6 pm...

  15. Blood cleaner on-chip design for artificial human kidney manipulation

    Directory of Open Access Journals (Sweden)

    Suwanpayak N

    2011-05-01

    Full Text Available N Suwanpayak1, MA Jalil2, MS Aziz3, FD Ismail3, J Ali3, PP Yupapin11Nanoscale Science and Engineering Research Alliance (N'SERA, Advanced Research Center for Photonics, Faculty of Science, King Mongkut's Institute of Technology, Ladkrabang, Bangkok, Thailand; 2Ibnu Sina Institute of Fundamental Science Studies (IIS, 3Institute of Advanced Photonics Science, Nanotechnology Research Alliance, Universiti Teknologi Malaysia, Johor Bahru, MalaysiaAbstract: A novel design of a blood cleaner on-chip using an optical waveguide known as a PANDA ring resonator is proposed. By controlling some suitable parameters, the optical vortices (gradient optical fields/wells can be generated and used to form the trapping tools in the same way as optical tweezers. In operation, the trapping force is formed by the combination between the gradient field and scattering photons by using the intense optical vortices generated within the PANDA ring resonator. This can be used for blood waste trapping and moves dynamically within the blood cleaner on-chip system (artificial kidney, and is performed within the wavelength routers. Finally, the blood quality test is exploited by the external probe before sending to the destination. The advantage of the proposed kidney on-chip system is that the unwanted substances can be trapped and filtered from the artificial kidney, which can be available for blood cleaning applications.Keywords: optical trapping, blood dialysis, blood cleaner, human kidney manipulation

  16. Effects of gallic acid on delta - aminolevulinic dehydratase activity and in the biochemical, histological and oxidative stress parameters in the liver and kidney of diabetic rats.

    Science.gov (United States)

    de Oliveira, Lizielle Souza; Thomé, Gustavo Roberto; Lopes, Thauan Faccin; Reichert, Karine Paula; de Oliveira, Juliana Sorraila; da Silva Pereira, Aline; Baldissareli, Jucimara; da Costa Krewer, Cristina; Morsch, Vera Maria; Chitolina Schetinger, Maria Rosa; Spanevello, Roselia Maria

    2016-12-01

    Diabetes mellitus (DM) is characterised by hyperglycaemia associated with the increase of oxidative stress. Gallic acid has potent antioxidant properties. The aim of this study was to evaluate the effect of gallic acid on the biochemical, histological and oxidative stress parameters in the liver and kidney of diabetic rats. Male rats were divided in groups: control, gallic acid, diabetic and diabetic plus gallic acid. DM was induced in the animals by intraperitoneal injection of streptozotocin (65mg/kg). Gallic acid (30mg/kg) was administered orally for 21days. Our results showed an increase in reactive species levels and lipid peroxidation, and a decrease in activity of the enzymes superoxide dismutase and delta-aminolevulinic acid dehydratase in the liver and kidney of the diabetic animals (PGallic acid treatment showed protective effects in these parameters evaluated, and also prevented a decrease in the activity of catalase and glutathione S-transferase, and vitamin C levels in the liver of diabetic rats. In addition, gallic acid reduced the number of nuclei and increased the area of the core in hepatic tissue, and increased the glomerular area in renal tissue. These results indicate that gallic acid can protect against oxidative stress-induced damage in the diabetic state. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  17. Association between MYH9 and APOL1 Gene Polymorphisms and the Risk of Diabetic Kidney Disease in Patients with Type 2 Diabetes in a Chinese Han Population

    Directory of Open Access Journals (Sweden)

    Hailing Zhao

    2018-01-01

    Full Text Available Single-nucleotide polymorphisms (SNPs in MYH9-APOL1 gene regions have been reported to be associated with diabetic kidney disease (DKD in the American population. We examined the association between polymorphisms in MYH9-APOL1 and DKD susceptibility in a Chinese Han population. MYH9 rs3752462 (T>C and APOL1 rs136161 (C>G were genotyped in 303 DKD patients and 364 type 2 diabetes mellitus (T2DM patients without kidney disease using the TaqMan SNP genotyping assay. Chi-squared test and multivariate logistic regression were used to evaluate the association. We observed that only MYH9 rs3752462 was associated with DKD (genotype, P=0.004; allele, P=0.002. Genetic model analysis revealed that rs3752462 was associated with increased risk of DKD under a dominant model adjusted by age and sex (adjusted odds ratio (aOR, 1.675; 95% CI 1.225–2.289; P=0.001 and an additive model (TC versus TT: aOR, 1.649; 95% CI 1.187–2.290; CC versus TT: aOR, 1.817; 95% CI 0.980–3.367; P=0.005. The combined effect of rs3752462 TC + rs136161 CC genotype showed an association of DKD adjusted by age and sex (aOR, 1.732; 95% CI 1.128–2.660; P=0.012. After a Holm-Bonferroni correction for multiple tests, the C allele frequencies of the rs3752462 and the TC + CC genotype in the dominant model were considered statistically significant with a markedly increased risk of DKD (P<0.00208; P<0.002. Our results suggest that MYH9 rs3752462 is significantly associated with an increased risk of DKD in Chinese Han individuals.

  18. The effect of glucagon infusion on kidney function in short-term insulin-dependent juvenile diabetics

    DEFF Research Database (Denmark)

    Parving, H H; Christiansen, J S; Noer, I

    1980-01-01

    Kidney function was studied in nine, metabolically well controlled, short-term insulin-dependent male diabetics before and during glucagon infusion of 4 to 5 and 8 to 10 ng/kg/min. Glomerular filtration rate, effective renal plasma flow (steady-state infusion technique, with urinary collections......, using 125I-iothalamate and 131I-iodohippurate), and urinary albumin and beta 2-microglobulin excretion rates were measured. The mean plasma glucagon concentration increased during infusion from 254 +/- 19 pg/ml to 440 +/- 31 pg/ml (low dose) and 730 +/- 52 pg/ml (high dose). Glomerular filtration rate...... increased in all subjects from 133 +/- 5 before the glucagon infusion to 141 +/- 4 with the low dose, and 148 +/- 7 ml/min/1.73 m2 with the high dose (p

  19. P2X(7 receptor in the kidneys of diabetic rats submitted to aerobic training or to N-acetylcysteine supplementation [corrected].

    Directory of Open Access Journals (Sweden)

    Adelson M Rodrigues

    Full Text Available Previous studies in our laboratory showed that N-acetylcysteine supplementation or aerobic training reduced oxidative stress and the progression of diabetic nephropathy in rats. The P2X(7 receptor is up-regulated in pathological conditions, such as diabetes mellitus. This up-regulation is related to oxidative stress and induces tissue apoptosis or necrosis. The aim of the present study is to assess the role of P2X(7 receptor in the kidneys of diabetic rats submitted to aerobic training or N-acetylcysteine supplementation. Diabetes was induced in male Wistar rats by streptozotocin (60 mg/kg, i.v. and the training was done on a treadmill; N-acetylcysteine was given in the drinking water (600 mg/L. By confocal microscopy, as compared to control, the kidneys of diabetic rats showed increased P2 × 7 receptor expression and a higher activation in response to 2'(3'-O-(4-benzoylbenzoyl adenosine5'-triphosphate (specific agonist and adenosine triphosphate (nonspecific agonist (all p<0.05. All these alterations were reduced in diabetic rats treated with N-acetylcysteine, exercise or both. We also observed measured proteinuria and albuminuria (early marker of diabetic nephropathy in DM groups. Lipoperoxidation was strongly correlated with P2X(7 receptor expression, which was also correlated to NO•, thus associating this receptor to oxidative stress and kidney lesion. We suggest that P2X(7 receptor inhibition associated with the maintenance of redox homeostasis could be useful as coadjuvant treatment to delay the progression of diabetic nephropathy.

  20. P2X(7) receptor in the kidneys of diabetic rats submitted to aerobic training or to N-acetylcysteine supplementation [corrected].

    Science.gov (United States)

    Rodrigues, Adelson M; Bergamaschi, Cassia T; Fernandes, Maria Jose S; Paredes-Gamero, Edgar J; Buri, Marcus V; Curi, Marcus V; Ferreira, Alice T; Araujo, Sergio R R; Punaro, Giovana R; Maciel, Fabiane R; Nogueira, Guilherme B; Higa, Elisa M S

    2014-01-01

    Previous studies in our laboratory showed that N-acetylcysteine supplementation or aerobic training reduced oxidative stress and the progression of diabetic nephropathy in rats. The P2X(7 receptor is up-regulated in pathological conditions, such as diabetes mellitus. This up-regulation is related to oxidative stress and induces tissue apoptosis or necrosis. The aim of the present study is to assess the role of P2X(7) receptor in the kidneys of diabetic rats submitted to aerobic training or N-acetylcysteine supplementation. Diabetes was induced in male Wistar rats by streptozotocin (60 mg/kg, i.v.) and the training was done on a treadmill; N-acetylcysteine was given in the drinking water (600 mg/L). By confocal microscopy, as compared to control, the kidneys of diabetic rats showed increased P2 × 7 receptor expression and a higher activation in response to 2'(3')-O-(4-benzoylbenzoyl) adenosine5'-triphosphate (specific agonist) and adenosine triphosphate (nonspecific agonist) (all p<0.05). All these alterations were reduced in diabetic rats treated with N-acetylcysteine, exercise or both. We also observed measured proteinuria and albuminuria (early marker of diabetic nephropathy) in DM groups. Lipoperoxidation was strongly correlated with P2X(7) receptor expression, which was also correlated to NO•, thus associating this receptor to oxidative stress and kidney lesion. We suggest that P2X(7) receptor inhibition associated with the maintenance of redox homeostasis could be useful as coadjuvant treatment to delay the progression of diabetic nephropathy.

  1. 75 FR 28029 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2010-05-19

    ... Panel; Type 2 Diabetes Mellitus. Date: July 9, 2010. Time: 1 p.m. to 2 p.m. Agenda: To review and... Diabetes. Date: July 6, 2010. Time: 1 p.m. to 2:30 p.m. Agenda: To review and evaluate grant applications...: July 7, 2010. Time: 1 p.m. to 5 p.m. Agenda: To review and evaluate grant applications, Place: National...

  2. Effect of spent turmeric on kidney glycoconjugates in streptozotocin-induced diabetic rats

    OpenAIRE

    Kumar, Gurusiddaiah Suresh; Salimath, Paramahans Veerayya

    2014-01-01

    Background Curcumin known to have number of medicinal use and masked the fiber containing ukonan like active polysaccharide in turmeric and its pharmacological effect will be addressed on diabetic nephropathy particularly the glycoconjugates of extracellular components viz., glycoproteins and glycosaminoglycans - heparan sulfate (HS). Methods Male Wistar rats were maintained on AIN-76 diet containing 10% spent turmeric and were grouped into control and STZ induced diabetes SFC/TFC and SFD/TFD...

  3. The Endoplasmic Reticulum Stress Protein Calreticulin in Diabetic Chronic Kidney Disease

    Science.gov (United States)

    2016-07-01

    persisted over 5 months. Downregulation of CRT expression in diabetic CRT floxed mice showed a significant reduction in the urinary albumin /creatinine...responses to glucose and TGF-beta; publication of 1-2 peer reviewed papers Specific Aim 2: To determine the role of CRT in mouse models of diabetic...monitor animals over 22 weeks (66 mice) 7-12 0% Subtask 5: animal model analysis (histology, ECM, serum creatinine, urinary albumin /creatinine, IHC

  4. Prevention of contrast-induced nephropathy with single bolus erythropoietin in patients with diabetic kidney disease: A randomized controlled trial.

    Science.gov (United States)

    Shema-Didi, Lilach; Kristal, Batya; Eizenberg, Sarit; Marzuq, Nabil; Sussan, Majdy; Feldman-Idov, Yulie; Ofir, Pnina; Atar, Shaul

    2016-04-01

    Contrast-induced-nephropathy (CIN) is associated with poor outcomes, thus prevention of CIN may be of clinical value. Erythropoietin (EPO) has been shown to elicit tissue-protective effects in experimental models and in clinical studies of acute kidney injury. We therefore evaluated its effectiveness for prevention of CIN after coronary angiography (CA) ± percutaneous coronary intervention (PCI) in diabetic patients with chronic kidney disease. A prospective, randomized, controlled trial was carried out in 138 diabetic patients with eGFR <60 mL/min who underwent non-urgent CA ± PCI. Patients received normal saline and n-acetyl cysteine before CA, with or without 50,000 U of EPO administered 30 min prior to CA. CIN was defined as an increase in serum creatinine of at least 0.5 mg/dL during the first 2 days after exposure to contrast media. Primary outcome was the incidence of CIN. Secondary outcomes were the sensitivity and positive predictive value (PPV) of Cystatin C (CC) and Neutrophil-gelatinase-associated-lipocalin (NGAL) for diagnosis of CIN. The observed incidence of CIN was 8.7%, significantly lower than the expected for such high-risk population. The administration of EPO prior to CA did not reduce the incidence of CIN (9.7% vs. 7.6%, P = 0.65). CC and NGAL demonstrated a low sensitivity (16.6%) and low PPV (6.7 and 33.3%, respectively) for detecting CIN. The administration of EPO prior to CA did not reduce the incidence of CIN. Additional prospective research with a larger sample size and in other patient categories is essential to further define the potential protective effect of EPO on prevention of CIN. © 2015 Asian Pacific Society of Nephrology.

  5. Protection against death and renal failure by renin-angiotensin system blockers in patients with diabetes and kidney disease.

    Science.gov (United States)

    Shen, Jian; Huang, Yan-Mei; Song, Xin-Nan; Hong, Xue-Zhi; Wang, Min; Ling, Wei; Zhang, Xiao-Xi; Zhao, Hai-Lu

    2016-07-01

    Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are widely used to block the renin-angiotensin system (RAS). Yet it remains uncertain whether these drugs are equally effective and safe. Systematic reviews and meta-analyses of ACEis/ARBs in diabetes and kidney disease published in PubMed, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases were searched for clinical outcomes including all-cause mortality, end-stage renal disease (ESRD), hyperkalemia and cough. Eight meta-analyses included 2177-61,264 patients with follow-up of 6-108 months. RAS blockers reduced mortality (relative risk ratio (RR), 0.90, 95% confidence interval (CI), 0.86-0.95) without heterogeneity. The death protection was significant specifically with ACEis (RR, 0.85, 95% CI, 0.79-0.91), but not with ARBs. Protection against ESRD was homogenously evident by ARBs (RR, 0.79, 95% CI, 0.73-0.87), ACEis (RR, 0.79, 95% , 0.64-0.94), and both (RR, 0.79, 95% CI, 0.73-0.87). Significant side effects were hyperkalemia by ARBs (RR, 2.44, 95% CI, 1.13-5.26), and cough by ACEis (RR, 2.38, 95% CI, 1.75-3.22) CONCLUSIONS: In patients with diabetes and kidney disease, ACEis and ARBs are consistently protective for the development of ESRD. Use of ACEis alone additionally reduces deaths and increases the risk for cough. Use of ARBs alone increases the risk for hyperkalemia without additional benefit of death protection. © The Author(s) 2016.

  6. Human papilloma virus infection in female kidney transplant recipients

    Directory of Open Access Journals (Sweden)

    Shirin Ghazizadeh

    2011-01-01

    Full Text Available The objective of this study was to evaluate the incidence of genital human papilloma virus (HPV infection and cervical intra-epithelial lesions in transplanted patients. Cervical Papanicolaou (Pap smear/HPV test and colposcopic examinations were performed in 58 patients who were candidates for renal transplant surgery; these tests were repeated one year later. Their age range was 26-53 years (mean, 37.2 years. Hypertension was the most common cause of renal insufficiency (34.4%, while in 41.4% of the patients, the causative pathology was unknown. In 24.1% of the patients, there was no history of dialysis, i.e. they had pre-emptive transplantation. The mean duration of marriage (years since first intercourse was 16.2 years (range, 1-35. Coitus interruptus was the most common contraceptive method used (37.9%, followed by tubal ligation and condom (10.3% and 6.9%, respectively. All patients had negative Pap tests and normal gynecologic exam before undergoing transplantation. The Pap test remained normal after transplant surgery, although the HPV test became positive in four patients (6.9%. There were five cases of white epithelium on colposcopy, but biopsy showed normal metaplasia. Two cases of extensive anogenital warts were treated by CO 2 laser, and one patient had recurrent warts, which responded well to second laser surgery. None of the study patients had squamous intra-epithelial lesions (SIL or vulvar intra-epithelial neoplasia. Our study suggests that screening with HPV and Pap test should be performed before transplant surgery and should be repeated at regular intervals in order to avoid irreversible situations such as high-grade SILs, which are difficult to treat. Avoiding high-risk sexual relations in this group of patients is highly recommended.

  7. Uptake and release of glucose by the human kidney. Postabsorptive rates and responses to epinephrine.

    Science.gov (United States)

    Stumvoll, M; Chintalapudi, U; Perriello, G; Welle, S; Gutierrez, O; Gerich, J

    1995-11-01

    Despite ample evidence that the kidney can both produce and use appreciable amounts of glucose, the human kidney is generally regarded as playing a minor role in glucose homeostasis. This view is based on measurements of arteriorenal vein glucose concentrations indicating little or no net release of glucose. However, inferences from net balance measurements do not take into consideration the simultaneous release and uptake of glucose by the kidney. Therefore, to assess the contribution of release and uptake of glucose by the human kidney to overall entry and removal of plasma glucose, we used a combination of balance and isotope techniques to measure renal glucose net balance, fractional extraction, uptake and release as well as overall plasma glucose appearance and disposal in 10 normal volunteers under basal postabsorptive conditions and during a 3-h epinephrine infusion. In the basal postabsorptive state, there was small but significant net output of glucose by the kidney (66 +/- 22 mumol.min-1, P = 0.016). However, since renal glucose fractional extraction averaged 2.9 +/- 0.3%, there was considerable renal glucose uptake (2.3 +/- 0.2 mumol.kg-1.min-1) which accounted for 20.2 +/- 1.7% of systemic glucose disposal (11.4 +/- 0.5 mumol.kg-1.min-1). Renal glucose release (3.2 +/- 0.2 mumol.kg-1.min-1) accounted for 27.8 +/- 2.1% of systemic glucose appearance (11.4 +/- 0.5 mumol.kg-1.min-1). Epinephrine infusion, which increased plasma epinephrine to levels observed during hypoglycemia (3722 +/- 453 pmol/liter) increased renal glucose release nearly twofold (5.2 +/- 0.5 vs 2.8 +/- 0.1 mol.kg-1.min-1, P = 0.01) so that at the end of the infusion, renal glucose release accounted for 40.3 +/- 5.5% of systemic glucose appearance and essentially all of the increase in systemic glucose appearance. These observations suggest an important role for the human kidney in glucose homeostasis.

  8. Characterization of human myotubes from type 2 diabetic and non-diabetic subjects using complementary quantitative mass spectrometric methods

    DEFF Research Database (Denmark)

    Thingholm, Tine E; Bak, Steffen; Beck-Nielsen, Henning

    2011-01-01

    2 diabetes. Several abnormalities have been identified in skeletal muscle from type 2 diabetic subjects, however, the exact molecular mechanisms leading to the diabetic phenotype has still not been found. Here we present a large-scale study in which we combine a quantitative proteomic discovery...... strategy using iTRAQ and a label-free study with a targeted quantitative proteomic approach using selected reaction monitoring (SRM) to identify, quantify and validate changes in protein abundance between human myotubes obtained from non-diabetic lean, non-diabetic obese and type 2 diabetic subjects...

  9. THE EFFECT OF L- ARGININE ON OXIDATIVE STRESS AND MICROALBUMINURIA IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND CHRONIC KIDNEY DISEASE

    Directory of Open Access Journals (Sweden)

    L. P. Martynyuk

    2017-07-01

    Full Text Available Background. One of the severest complications of diabetes is diabetic kidney disease (DKD. Microalbuminuria (MAU is one of the first signals of DKD and an important pathogenetic mechanism of disease progression. With diabetes dramatically antioxidant properties worsen. Objective. The aim was to investigate the effect of L-arginine on oxidative stress parameters and microalbuminuria in type 2 diabetes mellitus and chronic kidney disease patients. Methods. Total of 57 patients with type 2 diabetes mellitus and chronic kidney disease and 30 healthy subjects (control group were included in the study. The patients were divided into 2 congruent groups. The 1-st group of patients (n=33, in addition to standard therapy, received L-arginine 4.2 g intravenously for 5 days, after that they took it 1,0 g orally three times a day during meals for 1 month. The second group of patients (n=24 received a standard therapy. The concentration of lipid peroxidation products was measured by a spectrophotometric method. The determination of MAU was carried out in morning portion of urine immunological semiquantitative using test strips. Results. Significant improvement in indexes of lipid peroxidation was observed in both groups after therapy (p˂0.01, but in patients treated with L-arginine it was more expressed (p˂0,01. The standard therapy did not significantly affect the level of MAU (p˃0,05. The patients treated with L-Arginine, showed a significant reduction in MAU (p˂0.01. Conclusions. The usage of L-arginine facilitates the correction of lipid peroxidation processes and reduces the severity of microalbuminuria in patients with diabetic kidney disease that slowing its progression.

  10. Critical concentrations of cadmium in human liver and kidney measured by prompt-gamma neutron activation

    International Nuclear Information System (INIS)

    Cohn, S.H.; Vartsky, D.; Yasumura, S.; Zanzi, I.; Ellis, K.J.

    1979-01-01

    Few data exist on Cd metabolism in human beings. In particular, data are needed on the role of parameters such as age, sex, weight, diet, smoking habits, and state of health. Prompt-gamma neutron activation analysis (PGNAA) provides the only currently available means for measuring in vivo levels of liver and kidney Cd. The method employs an 85 Ci, 235 Pu,Be neutron source and a gamma ray detection system consisting of two Ge(Li) detector. The dose delivered to the liver and left kidney is 666 mrem (detection limit is 1.4 μg/g Cd in the liver and 2.0 mg Cd for one kidney). Absolute levels of Cd in the kidney and concentrations of Cd in the liver were measured in vivo in twenty healthy adult males using 238 Pu,Be neutron sources. Organ Cd levels of smokers were significantly elevated above those of nonsmokers. Biological half-time for Cd in the body was estimated to be 15.7 yr. Cigarette smoking was estimated to result in the absorption of 1.9 μg of Cd per pack. No relationship was bound between body stores of Cd (liver and kidney) and Cd or β-microglobulin levels in urine and blood. Currently the above neutron activation facility is being mounted on a 34-ft mobile trailer unit. This unit will be used to monitor levels of Cd in industrial workers. It is anticipated that critically important data, particularly on industrially exposed workers, will provide a better basis for determining critical concentrations and for the setting or revision of standards for industrial and environmental Cd pollution

  11. Applied Developmental Biology: Making Human Pancreatic Beta Cells for Diabetics.

    Science.gov (United States)

    Melton, Douglas A

    2016-01-01

    Understanding the genes and signaling pathways that determine the differentiation and fate of a cell is a central goal of developmental biology. Using that information to gain mastery over the fates of cells presents new approaches to cell transplantation and drug discovery for human diseases including diabetes. © 2016 Elsevier Inc. All rights reserved.

  12. The Use of Starfish in the Regenaration of Human Kidney. Fact or Fiction?

    Directory of Open Access Journals (Sweden)

    Mehdi Mahmudpour

    2016-11-01

    Full Text Available With performing the first kidney transplantations in 1950s and 1960s, medical science hopes were raised to find out proper ways for treatment of End Stage Renal Disease or dialysis patients. But regarding to immunologic bases of transplantation and the use of immunosuppressant medicines and their side effects, patients may encounter to severe and inevitable side effects that sometimes may even lead to death. Therefore, in recent years, medical sciences in convergence with technology, pursue a new kind of approach so called "regenerative medicine"; however this method has its own challenges and complexities. But regarding to potential regenerative abilities of aquatic animals such as starfish, it may be possible to overcome on some of these challenges. The results of recent studies on evolutionary processes of human kidney and development and regeneration in starfish and, and presence of path and common cytokines among these processes proves this claim. This article presents some evidences that imply on practical usage of starfish in human kidney regeneration.

  13. Dual roles for coactivator activator and its counterbalancing isoform coactivator modulator in human kidney cell tumorigenesis.

    Science.gov (United States)

    Kang, Yun Kyoung; Schiff, Rachel; Ko, Lan; Wang, Tao; Tsai, Sophia Y; Tsai, Ming-Jer; O'Malley, Bert W

    2008-10-01

    Coactivator activator (CoAA) has been reported to be a coactivator that regulates steroid receptor-mediated transcription and alternative RNA splicing. Herein, we show that CoAA is a dual-function coregulator that inhibits G(1)-S transition in human kidney cells and suppresses anchorage-independent growth and xenograft tumor formation. Suppression occurs in part by down-regulating c-myc and its downstream effectors ccnd1 and skp2 and causing accumulation of p27/Kip1 protein. In this cellular setting, CoAA directly represses the proto-oncogene c-myc by recruiting HDAC3 protein and decreasing both the acetylation of histone H3 and the presence of RNA polymerase II on the c-myc promoter. Interestingly, a splicing isoform of CoAA, coactivator modulator (CoAM), antagonizes CoAA-induced G(1)-S transition and growth inhibition by negatively regulating the mRNA levels of the endogenous CoAA isoform. In addition, we found that expression of CoAA protein is significantly decreased in human renal cell carcinoma compared with normal kidney. Our study presents evidence that CoAA is a potential tumor suppressor in renal carcinoma and that CoAM is a counterbalancing splice isoform. This is, thus far, the only example of a nuclear receptor coregulator involved in suppression of kidney cancer and suggests potentially significant new roles for coregulators in renal cancer biology.

  14. Higher Protein Intake Is Not Associated with Decreased Kidney Function in Pre-Diabetic Older Adults Following a One-Year Intervention—A Preview Sub-Study

    Directory of Open Access Journals (Sweden)

    Grith Møller

    2018-01-01

    Full Text Available Concerns about detrimental renal effects of a high-protein intake have been raised due to an induced glomerular hyperfiltration, since this may accelerate the progression of kidney disease. The aim of this sub-study was to assess the effect of a higher intake of protein on kidney function in pre-diabetic men and women, aged 55 years and older. Analyses were based on baseline and one-year data in a sub-group of 310 participants included in the PREVIEW project (PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World. Protein intake was estimated from four-day dietary records and 24-hour urinary urea excretion. We used linear regression to assess the association between protein intake after one year of intervention and kidney function markers: creatinine clearance, estimated glomerular filtration rate (eGFR, urinary albumin/creatinine ratio (ACR, urinary urea/creatinine ratio (UCR, serum creatinine, and serum urea before and after adjustments for potential confounders. A higher protein intake was associated with a significant increase in UCR (p = 0.03 and serum urea (p = 0.05 after one year. There were no associations between increased protein intake and creatinine clearance, eGFR, ACR, or serum creatinine. We found no indication of impaired kidney function after one year with a higher protein intake in pre-diabetic older adults.

  15. Gastrointestinal transit in nonobese diabetic mouse: an animal model of human diabetes type 1.

    Science.gov (United States)

    El-Salhy, M

    2001-01-01

    Gastrointestinal transit (GI) in the nonobese diabetic (NOD) mouse, an animal model of human diabetes type 1, was examined in animals with short- (duration 1-5 days) and long-term (duration 28-35 days) diabetes. Blood glucose level, serum insulin concentration, and gut neuroendocrine peptide content were also measured. GI was significantly rapid in NOD mice with long-term diabetes (LTD), but was not correlated with blood glucose level, serum insulin concentration, or pancreatic insulin content. GI was correlated with duodenal secretin content, but not with the content of other neuroendocrine peptides in the different segments investigated. Whereas antral vasoactive intestinal peptide (VIP) content in NOD mice with LTD was significantly higher, colonic VIP was lower in NOD mice with short-term diabetes (STD). In the duodenum, whereas the concentration of secretin in NOD mice with both STD and LTD was lower, the gastrin content was higher. Duodenal somatostatin content in NOD mice with LTD was lower. In colon, the content of galanin in NOD mice with LTD was higher than in controls. The decreased content of secretin may be among the factors that cause rapid GI in NOD mice with LTD. Changes in the antral content of VIP, duodenal somatostatin, and colonic galanin in NOD mice with LTD may cause low intestinal secretion and, together with rapid GI, give rise to diarrhoea, which is a common symptom in diabetes.

  16. The Role of the Kidney and SGLT2 Inhibitors in Type 2 Diabetes.

    Science.gov (United States)

    Katz, Pamela M; Leiter, Lawrence A

    2015-12-01

    Effective glycemic control reduces the risk for diabetes-related complications. However, the majority of patients with type 2 diabetes still do not achieve glycemic targets. Beyond metformin therapy, current practice guidelines for the management of type 2 diabetes recommend individualized treatment based on patient and agent characteristics. The sodium glucose cotransporter type 2 (SGLT2) inhibitors represent a novel treatment strategy, independent of impaired beta-cell function and insulin resistance. SGLT2 inhibitors decrease renal glucose reabsorption, thereby increasing urinary glucose excretion with subsequent reduction in plasma glucose levels and glycosylated hemoglobin concentrations. Current evidence suggests that they are effective as monotherapy or as add-ons to metformin either alone, or in combination with other oral glucose-lowering agents or insulin. They are generally well tolerated, though rates of lower urinary tract and genital mycotic infections are slightly increased. The advantages of this class include modest reductions in body weight and blood pressure, and low risk for hypoglycemia. Long-term safety data and results of ongoing cardiovascular outcome studies are awaited so we can fully understand the role that SGLT2 inhibitors will play in the comprehensive management of type 2 diabetes. Copyright © 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  17. Differing manifestations of hepatitis C and tacrolimus on hospitalized diabetes mellitus occurring after kidney transplantation.

    Science.gov (United States)

    Abbott, Kevin C; Bernet, Victor J; Agodoa, Lawrence Y; Yuan, Christina M

    2005-09-01

    Previous studies suggest the association of recipient hepatitis C seropositivity (HCV+) and use of tacrolimus (TAC) with post-transplant diabetes mellitus (PTDM) may differ by manifestations of type I or type II diabetes, but this has not been assessed in the era of current immunosuppression. We performed a retrospective cohort study of 10,342 Medicare primary renal transplantation recipients without evidence of diabetes at the time of listing in the United States Renal Data System between January 1, 1998 and July 31, 2000, followed until December 31, 2000. Outcomes were hospitalizations for a primary diagnosis of diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar syndrome (HHS). Cox regression analysis was used to calculate adjusted hazard ratios (AHR) for time to DKA or HHS, stratified by diabetes status at the time of transplant. In Cox regression analysis, use of TAC at discharge was independently associated with shorter time to DKA (AHR, 1.88; 95% CI, 1.05-3.37, p=0.034) but not HHS. In contrast, recipient HCV+ was independently associated with shorter time to HHS (AHR, 3.90; 1.59-9.60, p=.003), but not DKA. There was no interaction between TAC and HCV+ for either outcome. These results confirm earlier findings that TAC and HCV+ may mediate the risk of PTDM through different mechanisms, even in the modern era.

  18. Identification of differential gene expression patterns in human arteries from patients with chronic kidney disease

    DEFF Research Database (Denmark)

    Stubbe, Jane; Skov, Vibe; Thiesson, Helle Charlotte

    2018-01-01

    BACKGROUND: Uremia accelerates atherosclerosis but little is known about affected pathways in human vasculature. This study aimed to identify differentially expressed arterial transcripts in patients with chronic kidney disease (CKD) Methods: Global mRNA expression was estimated by microarray...... hybridization in iliac arteries (n=14) from renal transplant recipients and compared with renal arteries from healthy living kidney donors (n=19) in study 1. Study 2 compared non-atherosclerotic internal mammary arteries (IMA) from five patients with elevated plasma creatinine levels and age and gender matched...... controls with normal levels. Western blotting and immunohistochemistry for selected proteins was performed on a subset of study 1 samples. RESULTS: 15 gene transcripts with fold changes (FC)>1.05 were significantly different between the two groups in study 1, with false discovery rates (FDR) of

  19. Heterogeneous Downregulation of Angiotensin II AT1-A and AT1-B Receptors in Arterioles in STZ-Induced Diabetic Rat Kidneys

    Directory of Open Access Journals (Sweden)

    Zsolt Razga

    2014-01-01

    Full Text Available Introduction. The renin granulation of kidney arterioles is enhanced in diabetes despite the fact that the level of angiotensin II in the diabetic kidney is elevated. Therefore, the number of angiotensin II AT1-A and AT1-B receptors in afferent and efferent arteriole’s renin-positive and renin-negative smooth muscle cells (SMC was estimated. Method. Immunohistochemistry at the electron microscopic level was combined with 3D stereological sampling techniques. Results. In diabetes the enhanced downregulation of AT1-B receptors in the renin-positive than in the renin-negative SMCs in both arterioles was resulted: the significant difference in the number of AT1 (AT1-A + AT1-B receptors between the two types of SMCs in the normal rats was further increased in diabetes and in contrast with the significant difference observed between the afferent and efferent arterioles in the normal animals, there was no such difference in diabetes. Conclusions. The enhanced downregulation of the AT1-B receptors in the renin-negative SMCs in the efferent arterioles demonstrates that the regulation of the glomerular filtration rate by the pre- and postglomerular arterioles is changed in diabetes. The enhanced downregulation of the AT1-B receptors in the renin-positive SMCs in the arterioles may result in an enhanced level of renin granulation in the arterioles.

  20. Na+-H+ exchange and Na+-dependent transport systems in streptozotocin diabetic rat kidneys

    International Nuclear Information System (INIS)

    El-Seifi, S.; Freiberg, J.M.; Kinsella, F.J.; Cheng, L.; Sacktor, B.

    1987-01-01

    The streptozotocin-induced diabetic rat was used to test the hypothesis that Na + -H + exchange activity in the proximal tubule luminal membrane would be increased in association with renal hypertrophy, altered glomerular hemodynamics, enhanced filtered load and tubular reabsorption of 22 Na + , and stimulated 22 Na= pump activity in the basolateral membrane, previously reported characteristics of this experimental animal model. Amiloride-sensitive H + gradient-dependent Na + uptake and Na + gradient-dependent H + flux were increased in brush-border membrane vesicles from the streptozotocin-treated animals. Na + gradient-dependent uptakes of phosphate, D-glucose, L-proline, and myoinositol were decreased in the drug-induced diabetic animals. These membrane transport alterations were not found when the streptozotocin-diabetic animals were treated with insulin

  1. Risk of development of chronic kidney disease in patients with type 2 diabetes having metabolic syndrome

    International Nuclear Information System (INIS)

    Moin, S.; Gondal, G.M.G.

    2008-01-01

    To measure the relation of creatinine clearance in type-2 diabetic patients with different components of metabolic syndrome and to quantify the relationship of frequency of incident CKD with increasing number of metabolic syndrome components while controlling for age, gender and duration of diabetes. Cross-sectional descriptive study. Patients having type-2 Diabetes for more than 5 years were enrolled. Information regarding age, gender, duration of diabetes, type of diabetes, treatment taking, complete fasting lipid profile, fasting blood glucose, Body Mass Index (BMI), 24 hours urinary proteins and creatinine clearance, co-existent risk factors like hypertension and ischemic heart disease was taken. Patients were divided into groups having one to all five metabolic syndrome traits. Progressive increase in the metabolic syndrome traits was compared with decline in creatinine clearance. Pearson correlation test and multiple logistic regression were applied to determine correlation with significance at r and p <0.05. Out of 104 evaluated female and male patients, 70% had hypertension, ischemic heart disease and a family history of diabetes. While 20% had normal creatinine clearance, 37% had a creatinine clearance between 60-90 ml/min, 19% had a creatinine clearance of 30-59 ml/min, 18% had a creatinine clearance of less than 30 ml/min and 10% were already in stage 5 CKD. The decline in renal function was more severe in subjects evaluated who had a higher number of features of the metabolic syndrome. Age was the only significant determinant of development of CKD (p=0.05). The renal function progressively declined with 3 or more features of the metabolic syndrome. (author)

  2. Effect of low-protein diet on kidney function in diabetic nephropathy: meta-analysis of randomised controlled trials.

    Science.gov (United States)

    Nezu, Uru; Kamiyama, Hiroshi; Kondo, Yoshinobu; Sakuma, Mio; Morimoto, Takeshi; Ueda, Shinichiro

    2013-05-28

    To evaluate the effect of low-protein diet on kidney function in patients with diabetic nephropathy. A systematic review and a meta-analysis of randomised controlled trials. MEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov, International Standard Randomised Controlled Trial Number (ISRCTN) Register and University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) from inception to 10 December 2012. Internet searches were also carried out with general search engines (Google and Google Scholar). Randomised controlled trials that compared low-protein diet versus control diet and assessed the effects on kidney function, proteinuria, glycaemic control or nutritional status. The primary outcome was a change in the glomerular filtration rate (GFR). The secondary outcomes were changes in proteinuria, post-treatment value of glycated haemoglobin A1C (HbA1c) and post-treatment value of serum albumin. The results were summarised as the mean difference for continuous outcomes and pooled by the random effects model. Subgroup analyses and sensitivity analyses were conducted regarding patient characteristics, intervention period, methodological quality and assessment of diet compliance. The assessment of diet compliance was performed based on the actual protein intake ratio (APIR) of the low-protein diet group to the control group. We identified 13 randomised controlled trials enrolling 779 patients. A low-protein diet was associated with a significant improvement in GFR (5.82 ml/min/1.73 m(2), 95% CI 2.30 to 9.33, I(2)=92%; n=624). This effect was consistent across the subgroups of type of diabetes, stages of nephropathy and intervention period. However, GFR was improved only when diet compliance was fair (8.92, 95% CI 2.75 to 15.09, I(2)=92% for APIR <0.9 and 0.03, 95% CI -1.49 to 1.56, I(2)=90% for APIR ≥0.9). Proteinuria and serum albumin were not differed between the groups. HbA1c was slightly but significantly decreased in the low-protein diet

  3. Correlations of dietary energy and protein intakes with renal function impairment in chronic kidney disease patients with or without diabetes

    Directory of Open Access Journals (Sweden)

    Mei-En Chen

    2017-05-01

    Full Text Available Dietary energy and protein intake can affect progression of chronic kidney disease (CKD. CKD complicated with diabetes is often associated with a decline in renal function. We investigated the relative importance of dietary energy intake (DEI and dietary protein intake (DPI to renal function indicators in nondiabetic and diabetic CKD patients. A total of 539 Stage 3–5 CKD patients [estimated glomerular filtration rate (eGFR<60 mL/min/1.73 m2 using the Modification of Diet in Renal Disease equation] with or without diabetes were recruited from outpatient clinics of Nephrology and Nutrition in a medical center in Taiwan. Appropriateness of DEI and DPI was used to subcategorize CKD patients into four groups:(1 kidney diet (KD A (KD-A, the most appropriate diet, was characterized by low DPI and adequate DEI; (2 KD-B, low DPI and inadequate DEI; (3 KD-C, excess DPI and adequate DEI; and (4 KD-D, the least appropriate diet, excess DPI and inadequate DEI. Inadequate DEI was defined as a ratio of actual intake/recommended intake less than 90% and adequate DEI as over 90%. Low DPI was defined as less than 110% of recommended intake and excessive when over 110%. Outcome measured was eGFR. In both groups of CKD patients, DEI was significantly lower (p<0.001 and DPI higher (p=0.002 than recommended levels. However, only in the nondiabetic CKD patients were KD-C and KD-D significantly correlated with reduced eGFR compared with KD-A at increments of −5.63 mL/min/1.73 m2 (p = 0.029 and −7.72 mL/min/1.73 m2 (p=0.015. In conclusion, inadequate energy and excessive protein intakes appear to correlate with poorer renal function in nondiabetic CKD patients. Patients with advanced CKD are in need of counseling by dietitians to improve adherence to diets.

  4. Dose-dependent effects of dihydrotestosterone in the streptozotocin-induced diabetic rat kidney

    OpenAIRE

    Xu, Qin; Prabhu, Anjali; Xu, Shujing; Manigrasso, Michaele B.; Maric, Christine

    2009-01-01

    We recently reported that castration exacerbates albuminuria, glomerulosclerosis, and tubulointerstitial fibrosis associated with diabetic renal disease. The aim of the present study was to examine whether these effects of castration can be attenuated with dihydrotestosterone (DHT) supplementation. The study was performed in castrated male Sprague-Dawley, streptozotocin-induced diabetic rats treated with 0 mg/day DHT (DHT0), 0.75 mg/day DHT (DHT0.75), or 2.0 mg/day DHT (DHT2.0) for 14 wk. Tre...

  5. Both ERK/MAPK and TGF-Beta/Smad Signaling Pathways Play a Role in the Kidney Fibrosis of Diabetic Mice Accelerated by Blood Glucose Fluctuation

    Directory of Open Access Journals (Sweden)

    Xiaoyun Cheng

    2013-01-01

    Full Text Available Background. The notion that diabetic nephropathy is the leading cause of renal fibrosis prompted us to investigate the effects of blood glucose fluctuation (BGF under high glucose condition on kidney in the mice. Methods. The diabetic and BGF animal models were established in this study. Immunohistochemistry, Western blot, and RT-PCR analysis were applied to detect the expression of type I collagen, matrix metalloproteinase-1 (MMP1, metalloproteinase inhibitor 1 (TIMP1, transforming growth factor beta 1 (TGF-β1, phosphorylated-ERK, p38, smad2/3, and Akt. Results. BGF treatment increased type I collagen synthesis by two times compared with the control. The expression of MMP1 was reduced markedly while TIMP1 synthesis was enhanced after BGF treatment. ERK phosphorylation exhibits a significant increase in the mice treated with BGF. Furthermore, BGF can markedly upregulate TGF-β1 expression. The p-smad2 showed 2-fold increases compared with the only diabetic mice. However, p-AKT levels were unchanged after BGF treatment. Conclusions. These data demonstrate that BGF can accelerate the trend of kidney fibrosis in diabetic mice by increasing collagen production and inhibiting collagen degradation. Both ERK/MAPK and TGF-β/smad signaling pathways seem to play a role in the development of kidney fibrosis accelerated by blood glucose fluctuation.

  6. Cycloxygenase-2 is expressed in vasculature of normal and ischemic adult human kidney and is colocalized with vascular prostaglandin E2 EP4 receptors

    DEFF Research Database (Denmark)

    Therland, Karina L; Stubbe, Jane; Thiesson, Helle C

    2004-01-01

    The study was performed to elucidate the distribution and cellular localization of cyclooxygenase (COX)-2 in human kidney and to address localization of downstream targets for COX-derived prostanoids. Cortex and outer and inner medulla tissue were obtained from control kidneys (cancer specimens),...... feature encountered in human kidneys at all ages, whereas COX-2 was seen in macula densa only in fetal kidney. Vascular COX-2 activity in human kidney and extrarenal tissues may support blood flow and affect vascular wall-blood interaction....

  7. 76 FR 30733 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Meeting

    Science.gov (United States)

    2011-05-26

    ... meeting will be open to the public as indicated below, with attendance limited to space available... confidential trade secrets or commercial property such as patentable material, and personal information... Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive...

  8. 78 FR 58322 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Meeting

    Science.gov (United States)

    2013-09-23

    ... meeting will be open to the public as indicated below, with attendance limited to space available... confidential trade secrets or commercial property such as patentable material, and personal information... . (Catalogue of Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research...

  9. 77 FR 3479 - National Institute of Diabetes and Digestive and Kidney Diseases Notice of Meeting

    Science.gov (United States)

    2012-01-24

    ... meeting will be open to the public as indicated below, with attendance limited to space available... confidential trade secrets or commercial property such as patentable material, and personal information... Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and...

  10. Short-term effects of liraglutide on kidney function and vasoactive hormones in type 2 diabetes

    DEFF Research Database (Denmark)

    Skov, J.; Pedersen, M.; Holst, Jens Juul

    2016-01-01

    AIMS: To investigate the effects of a single dose of 1.2 mg liraglutide, a once-daily glucagon-like peptide-1 (GLP-1) receptor agonist, on key renal parameters in patients with type 2 diabetes. METHODS: The study was a placebo-controlled, double-blind, cross-over in 11 male patients with type 2 d...

  11. 78 FR 79706 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2013-12-31

    ... Nutrition. Date: February 13, 2014. Time: 8:00 a.m. to 4:00 p.m. Agenda: To review and evaluate grant... Special Emphasis Panel; PAR-13-305: Collaborative Interdisciplinary Team Science in NIDDK Research Areas....847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and Nutrition Research...

  12. Early and late scanning electron microscopy findings in diabetic kidney disease.

    Science.gov (United States)

    Conti, Sara; Perico, Norberto; Novelli, Rubina; Carrara, Camillo; Benigni, Ariela; Remuzzi, Giuseppe

    2018-03-20

    Diabetic nephropathy (DN), the single strongest predictor of mortality in patients with type 2 diabetes, is characterized by initial glomerular hyperfiltration with subsequent progressive renal function loss with or without albuminuria, greatly accelerated with the onset of overt proteinuria. Experimental and clinical studies have convincingly shown that early interventions retard disease progression, while treatment if started late in the disease course seldom modifies the slope of GFR decline. Here we assessed whether the negligible renoprotection afforded by drugs in patients with proteinuric DN could be due to loss of glomerular structural integrity, explored by scanning electron microscopy (SEM). In diabetic patients with early renal disease, glomerular structural integrity was largely preserved. At variance SEM documented that in the late stage of proteinuric DN, glomerular structure was subverted with nearly complete loss of podocytes and lobular transformation of the glomerular basement membrane. In these circumstances one can reasonably imply that any form of treatment, albeit personalized, is unlikely to reach a given cellular or molecular target. These findings should persuade physicians to start the putative renoprotective therapy soon after the diagnosis of diabetes or in an early phase of the disease before structural integrity of the glomerular filter is irreversibly compromised.

  13. Effects of long-term antihypertensive treatment on kidney function in diabetic nephropathy

    DEFF Research Database (Denmark)

    Parving, H H; Andersen, A R; Hommel, Eva

    1985-01-01

    Hg. Eight patients received treatment with metoprolol (200-400 mg/day), hydralazine (100-200 mg/day), and furosemide (80-500 mg/day). The untreated control group consisted of eight patients matched for age (mean 32 years), diabetes duration (mean 17 years), and sex (two female and six male patients...

  14. Validation of an LC-MS/MS method to measure tacrolimus in rat kidney and liver tissue and its application to human kidney biopsies.

    Science.gov (United States)

    Noll, Benjamin D; Coller, Janet K; Somogyi, Andrew A; Morris, Raymond G; Russ, Graeme R; Hesselink, Dennis A; Van Gelder, Teun; Sallustio, Benedetta C

    2013-10-01

    Tacrolimus (TAC) has a narrow therapeutic index and high interindividual and intraindividual pharmacokinetic variability, necessitating therapeutic drug monitoring to individualize dosage. Recent evidence suggests that intragraft TAC concentrations may better predict transplant outcomes. This study aimed to develop a method for the quantification of TAC in small biopsy-sized samples of rat kidney and liver tissue, which could be applied to clinical biopsy samples from kidney transplant recipients. Kidneys and livers were harvested from Mrp2-deficient TR- Wistar rats administered TAC (4 mg·kg·d for 14 days, n = 8) or vehicle (n = 10). Tissue samples (0.20-1.00 mg of dry weight) were solubilized enzymatically and underwent liquid-liquid extraction before analysis by liquid chromatography tandem mass spectrometry method. TAC-free tissue was used in the calibrator and quality control samples. Analyte detection was accomplished using positive electrospray ionization (TAC: m/z 821.5 → 768.6; internal standard ascomycin m/z 809.3 → 756.4). Calibration curves (0.04-2.6 μg/L) were linear (R > 0.99, n = 10), with interday and intraday calibrator coefficients of variation and bias <17% at the lower limit of quantification and <15% at all other concentrations (n = 6-10). Extraction efficiencies for TAC and ascomycin were approximately 70%, and matrix effects were minimal. Rat kidney TAC concentrations were higher (range 109-190 pg/mg tissue) than those in the liver (range 22-53 pg/mg of tissue), with median tissue/blood concentrations ratios of 72.0 and 17.6, respectively. In 2 transplant patients, kidney TAC concentrations ranged from 119 to 285 pg/mg of tissue and were approximately 20 times higher than whole blood trough TAC concentrations. The method displayed precision and accuracy suitable for application to TAC measurement in human kidney biopsy tissue.

  15. Humanized in vivo Model for Autoimmune Diabetes

    National Research Council Canada - National Science Library

    Nepom, Gerald T; Gebe, John A

    2008-01-01

    The CD4+ T cell response is critical for cellular autoimmunity in human T1D, but incomplete understanding of issues of specific cell frequency, avidity, function, and correlation with disease status presents...

  16. Kidney Transplantation: The Challenge of Human Leukocyte Antigen and Its Therapeutic Strategies

    Directory of Open Access Journals (Sweden)

    Tilahun Alelign

    2018-01-01

    Full Text Available Kidney transplantation remains the treatment of choice for end-stage renal failure. When the immune system of the recipient recognizes the transplanted kidney as a foreign object, graft rejection occurs. As part of the host immune defense mechanism, human leukocyte antigen (HLA is a major challenge for graft rejection in transplantation therapy. The impact of HLA mismatches between the donor and the potential recipient prolongs the time for renal transplantation therapy, tethered to dialysis, latter reduces graft survival, and increases mortality. The formation of pretransplant alloantibodies against HLA class I and II molecules can be sensitized through exposures to blood transfusions, prior transplants, and pregnancy. These preformed HLA antibodies are associated with rejection in kidney transplantation. On the other hand, the development of de novo antibodies may increase the risk for acute and chronic rejections. Allograft rejection results from a complex interplay involving both the innate and the adaptive immune systems. Thus, further insights into the mechanisms of tissue rejection and the risk of HLA sensitization is crucial in developing new therapies that may blunt the immune system against transplanted organs. Therefore, the purpose of this review is to highlight facts about HLA and its sensitization, various mechanisms of allograft rejection, the current immunosuppressive approaches, and the directions for future therapy.

  17. Kidney Transplantation: The Challenge of Human Leukocyte Antigen and Its Therapeutic Strategies

    Science.gov (United States)

    Ahmed, Momina M.; Bobosha, Kidist; Tadesse, Yewondwossen; Howe, Rawleigh; Petros, Beyene

    2018-01-01

    Kidney transplantation remains the treatment of choice for end-stage renal failure. When the immune system of the recipient recognizes the transplanted kidney as a foreign object, graft rejection occurs. As part of the host immune defense mechanism, human leukocyte antigen (HLA) is a major challenge for graft rejection in transplantation therapy. The impact of HLA mismatches between the donor and the potential recipient prolongs the time for renal transplantation therapy, tethered to dialysis, latter reduces graft survival, and increases mortality. The formation of pretransplant alloantibodies against HLA class I and II molecules can be sensitized through exposures to blood transfusions, prior transplants, and pregnancy. These preformed HLA antibodies are associated with rejection in kidney transplantation. On the other hand, the development of de novo antibodies may increase the risk for acute and chronic rejections. Allograft rejection results from a complex interplay involving both the innate and the adaptive immune systems. Thus, further insights into the mechanisms of tissue rejection and the risk of HLA sensitization is crucial in developing new therapies that may blunt the immune system against transplanted organs. Therefore, the purpose of this review is to highlight facts about HLA and its sensitization, various mechanisms of allograft rejection, the current immunosuppressive approaches, and the directions for future therapy. PMID:29693023

  18. Creating computer aided 3D model of spleen and kidney based based on Visible Human Project

    International Nuclear Information System (INIS)

    Aldur, Muhammad M.

    2005-01-01

    To investigate the efficacy of computer aided 3-dimensional (3D) reconstruction technique on visualization and modeling of gross anatomical structures with an affordable methodology applied on the spleen and kidney. From The Visible Human Project Dataset cryosection images, developed by the National Library of Medicine, the spleen and kidney sections were preferred to be used due to their highly distinct contours. The software used for the reconstruction were Surf Driver 3.5.3 for Mac and Cinema 4D X L version 7.1 for Mac OS X. This study was carried out in May 2004 at the Department of Anatomy, Hacettepe University, Ankara, Turkey. As a result of this study, it is determined that these 2 programs could be effectively used both for 3D modeling of the mentioned organs and volumetric analyses on these models. It is also seen that it is possible to hold the physical models of these gross anatomical digital ones with stereolithography technique by means of the data exchange file format provided by the program and present such images as anaglyph. Surf Driver 3.5.3 for Mac OS and Cinema 4 DXL version 7.1 for Mac OS X can be used effectively for reconstruction of gross anatomical structures from serial parallel sections with distinct contours such as spleen and kidney and the animation of models. These software constitute a highly effective way of getting volumetric calculations, spatial relations and morphometrical measurements of reconstructed structures. (author)

  19. NETosis Delays Diabetic Wound Healing in Mice and Humans.

    Science.gov (United States)

    Fadini, Gian Paolo; Menegazzo, Lisa; Rigato, Mauro; Scattolini, Valentina; Poncina, Nicol; Bruttocao, Andrea; Ciciliot, Stefano; Mammano, Fabio; Ciubotaru, Catalin Dacian; Brocco, Enrico; Marescotti, Maria Cristina; Cappellari, Roberta; Arrigoni, Giorgio; Millioni, Renato; Vigili de Kreutzenberg, Saula; Albiero, Mattia; Avogaro, Angelo

    2016-04-01

    Upon activation, neutrophils undergo histone citrullination by protein arginine deiminase (PAD)4, exocytosis of chromatin and enzymes as neutrophil extracellular traps (NETs), and death. In diabetes, neutrophils are primed to release NETs and die by NETosis. Although this process is a defense against infection, NETosis can damage tissue. Therefore, we examined the effect of NETosis on the healing of diabetic foot ulcers (DFUs). Using proteomics, we found that NET components were enriched in nonhealing human DFUs. In an independent validation cohort, a high concentration of neutrophil elastase in the wound was associated with infection and a subsequent worsening of the ulcer. NET components (elastase, histones, neutrophil gelatinase-associated lipocalin, and proteinase-3) were elevated in the blood of patients with DFUs. Circulating elastase and proteinase-3 were associated with infection, and serum elastase predicted delayed healing. Neutrophils isolated from the blood of DFU patients showed an increased spontaneous NETosis but an impaired inducible NETosis. In mice, skin PAD4 activity was increased by diabetes, and FACS detection of histone citrullination, together with intravital microscopy, showed that NETosis occurred in the bed of excisional wounds. PAD4 inhibition by Cl-amidine reduced NETting neutrophils and rescued wound healing in diabetic mice. Cumulatively, these data suggest that NETosis delays DFU healing. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  20. Hypoxis hemerocallidea Significantly Reduced Hyperglycaemia and Hyperglycaemic-Induced Oxidative Stress in the Liver and Kidney Tissues of Streptozotocin-Induced Diabetic Male Wistar Rats

    Directory of Open Access Journals (Sweden)

    Oluwafemi O. Oguntibeju

    2016-01-01

    Full Text Available Background. Hypoxis hemerocallidea is a native plant that grows in the Southern African regions and is well known for its beneficial medicinal effects in the treatment of diabetes, cancer, and high blood pressure. Aim. This study evaluated the effects of Hypoxis hemerocallidea on oxidative stress biomarkers, hepatic injury, and other selected biomarkers in the liver and kidneys of healthy nondiabetic and streptozotocin- (STZ- induced diabetic male Wistar rats. Materials and Methods. Rats were injected intraperitoneally with 50 mg/kg of STZ to induce diabetes. The plant extract-Hypoxis hemerocallidea (200 mg/kg or 800 mg/kg aqueous solution was administered (daily orally for 6 weeks. Antioxidant activities were analysed using a Multiskan Spectrum plate reader while other serum biomarkers were measured using the RANDOX chemistry analyser. Results. Both dosages (200 mg/kg and 800 mg/kg of Hypoxis hemerocallidea significantly reduced the blood glucose levels in STZ-induced diabetic groups. Activities of liver enzymes were increased in the diabetic control and in the diabetic group treated with 800 mg/kg, whereas the 200 mg/kg dosage ameliorated hepatic injury. In the hepatic tissue, the oxygen radical absorbance capacity (ORAC, ferric reducing antioxidant power (FRAP, catalase, and total glutathione were reduced in the diabetic control group. However treatment with both doses improved the antioxidant status. The FRAP and the catalase activities in the kidney were elevated in the STZ-induced diabetic group treated with 800 mg/kg of the extract possibly due to compensatory responses. Conclusion. Hypoxis hemerocallidea demonstrated antihyperglycemic and antioxidant effects especially in the liver tissue.

  1. Shift of galectin-3 expression in the human kidney during development

    Directory of Open Access Journals (Sweden)

    Clara Gerosa

    2013-06-01

    Full Text Available Galectin-3 (Gal-3 is a member of the lectin family, including 14 mammalian galectins, and has been shown to be involved in the many biological processes. In fact it has been reported to be expressed during human nephrogenesis, in the ureteric bud tips and in the medullary regions. In 11 developing human kidney the immunoexpression of Gal-3 was studied. Previously observations on Gal-3 expression in collecting ducts were confirmed and a wild variable reactivity was detected among the range from 20 to 36 weeks of gestational age considered. Between the early and late phases of gestation two phases have been identified: the first, from 20 up to 26 weeks of gestation, with a strong reactivity and the second, from 30 to 36 weeks, with a decrease in Gal-3 expression. This finding clearly indicates a major role for Gal-3 in early human nephrogenesis ending around the 30th week of gestation. In conclusion, Gal-3 apparently plays a role in kidney development at different check points, participating both to ureteric bud proliferation and to differentiation of structures originating from the metanephric mesenchyme. Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research

  2. Sulodexide for kidney protection in type 2 diabetes patients with microalbuminuria

    DEFF Research Database (Denmark)

    Lewis, Edmund J; Lewis, Julia B; Greene, Tom

    2011-01-01

    Sulodexide, a heterogenous group of sulfated glycosaminoglycans, includes low-molecular-weight heparin (~80% ± 8%), high-molecular-weight heparin (~5% ± 3%), and dermatan (~20% ± 8%), with a mean molecular weight of ~9 kDa. The drug is absorbed orally and has no anticoagulant effect in the doses ...... used. Small preliminary studies consistently showed sulodexide to be associated with decreased albuminuria in patients with diabetes....

  3. Detection of Chronic Kidney Disease by Using Different Equations of Glomerular Filtration Rate in Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Analysis

    OpenAIRE

    Zaman, Sojib Bin

    2017-01-01

    Introduction Chronic kidney disease (CKD) is a global threat due to its high mortality. It is essential to know the actual magnitude of diabetic CKD to design a specific management program. However, there is limited knowledge regarding the most suitable equation to measure CKD in patients with Type 2 diabetes mellitus (T2DM). This paper aimed to analyze estimated glomerular filtration rate (eGFR) based on different equations to detect the CKD among T2DM.? Methods A hospital-based cross-sectio...

  4. Biomarkers of chronic kidney disease in the urine of diabetic/hypertensive patients by means of Raman spectroscopy

    Science.gov (United States)

    Vieira, Elzo Everton de Sousa; Bispo, Jeyse Aliana Martis; Fernandes, Adriana Barrinha; Silveira, Landulfo

    2016-03-01

    Diabetes mellitus (DM) and arterial hypertension (AH) are common diseases that, if untreated, predispose the patient to renal failure. This study aimed to evaluate possible biomarkers in the urine of patients with DM and AH capable to predict the chronic renal disease, by means of Raman spectroscopy. Urines were obtained from patients with DM and AH, and separated into four groups: no symptoms of diseases related to DM and AH (G1), with low clinical complications (G2), with severe clinical complications (G3), and with chronic kidney disease (G4) arised from DM and AH. It has been used a dispersive Raman spectrometer (830nm, 250mW, 20s accumulation). In the spectra of urine it was identified Raman peaks at 680cm-1 (creatinine), 1004cm-1 (urea) and 1128cm-1 (glucose). The results revealed that G2, G3 and G4 presented the creatinine peak with lower intensity than G1 (p < 0.05). It was observed that G2, G3 and G4 showed lower intensity of the urea peak compared to G1 (p < 0.05) and G4 showed lower intensity compared to G2 and G3 (p < 0.05). Despite not significant, the glucose peak showed lower intensity in G1 when compared to the other groups. A model for classification of groups according to clinical criteria, using Sparse Multinomial Logistic Regression, taking as inputs the intensities of creatine, urea and glucose peaks allowed correct classification of 88.9% for G1, 36.8% for G2, 43.8% for G3 and 84.2% for G4. These results demonstrated the possibility of obtaining diagnostic information for complications of kidney disease associated to DM and AH, particularly the renal failure.

  5. Tranilast prevents renal interstitial fibrosis by blocking mast cell infiltration in a rat model of diabetic kidney disease.

    Science.gov (United States)

    Yin, Dan-Dan; Luo, Jun-Hui; Zhao, Zhu-Ye; Liao, Ying-Jun; Li, Ying

    2018-05-01

    Renal interstitial fibrosis is a final pathway that is observed in various types of kidney diseases, including diabetic kidney disease (DKD). The present study investigated the effect of tranilast on renal interstitial fibrosis and the association between its role and mast cell infiltration in a rat model of DKD. A total of 30 healthy 6‑week‑old male Sprague‑Dawley rats were randomly divided into the following four groups: Normal control group; DKD model group; low‑dose tranilast group (200 mg/kg/day); and high‑dose tranilast group (400 mg/kg/day). The morphological alterations of tubulointerstitial fibrosis were evaluated by Masson's trichrome staining, while mast cell infiltration into the renal tubular interstitium was measured by toluidine blue staining and complement C3a receptor 1 (C3aR) immunohistochemical staining (IHC). The expression of fibronectin (FN), collagen I (Col‑I), stem cell factor (SCF) and proto‑oncogene c‑kit (c‑kit) was detected by IHC, western blotting and reverse transcription‑quantitative‑polymerase chain reaction. The results demonstrated that tubulointerstitial fibrosis and mast cell infiltration were observed in DKD model rats, and this was improved dose‑dependently in the tranilast treatment groups. The expression of FN, Col‑I, SCF and c‑kit mRNA and protein was upregulated in the tubulointerstitium of DKD model rats compared with the normal control rats, and tranilast inhibited the upregulated expression of these markers. Furthermore, the degree of SCF and c‑kit expression demonstrated a significant positive correlation with C3aR‑positive mast cells and the markers of renal interstitial fibrosis. The results of the present study indicate that mast cell infiltration may promote renal interstitial fibrosis via the SCF/c‑kit signaling pathway. Tranilast may prevent renal interstitial fibrosis through inhibition of mast cell infiltration mediated through the SCF/c-kit signaling pathway.

  6. Visit-to-Visit Variability in Blood Pressure and Kidney and Cardiovascular Outcomes in Patients With Type 2 Diabetes and Nephropathy

    DEFF Research Database (Denmark)

    McMullan, Ciaran J; Lambers Heerspink, Hiddo J; Parving, Hans-Henrik

    2014-01-01

    -to-visit variability was calculated from the SD of the systolic blood pressure from 4 visits occurring 3-12 months postrandomization. OUTCOMES: The kidney disease outcome was defined as time to confirmed doubling of serum creatinine level, end-stage renal disease, or death; the cardiovascular outcome was defined......BACKGROUND: Increased systolic blood pressure variability between outpatient visits is associated with increased incidence of cardiovascular end points. However, few studies have examined the association of visit-to-visit variability in systolic blood pressure with clinically relevant kidney...... disease outcomes. We analyzed the association of systolic blood pressure visit-to-visit variability with renal and cardiovascular morbidity and mortality among individuals with diabetes and nephropathy. STUDY DESIGN: Observational analysis of IDNT (Irbesartan Diabetic Nephropathy Trial) and the RENAAL...

  7. Effects of garlic extract on TNF-α expression and oxidative stress status in the kidneys of rats with STZ + nicotinamide-induced diabetes.

    Science.gov (United States)

    Ziamajidi, Nasrin; Nasiri, Abolfazl; Abbasalipourkabir, Roghayeh; Sadeghi Moheb, Somayeh

    2017-12-01

    Allium sativum L. (Liliaceae) (garlic) is a medicinal plant that is widely used in herbal medicine. Nephropathy is a complication of diabetes that is induced by long-term hyperglycaemia. The effects of aqueous extract of garlic (AGE) on the expression of tumour necrosis factor-alpha (TNF-α) and oxidative stress status were studied in the kidneys of rats with streptozotocin (STZ) + nicotinamide-induced diabetes. Twenty-four Wistar rats were divided into four groups: control rats, rats with STZ + nicotinamide-induced diabetes that received a single dose of STZ (65 mg/kg) and nicotinamide (110 mg/kg) intraperitoneally, diabetic rats that were treated with garlic (2 g/kg/d, gavage), and normal rats that received garlic (2 g/kg/d, gavage). The glucose level was determined in the start of study, 7 d after induction of diabetes and 33 d after treatment with garlic. At the end of the treatment period, urea, uric acid and creatinine levels were estimated in sera. Malondialdehyde (MDA), total oxidant status (TOS), nitric oxide (NO) levels and TNF-α gene and protein expression were measured in the renal tissues of the rats. The glucose, uric acid, and urea levels increased in the serum of diabetic rats compared with control rats, and decreased in garlic-treated diabetic rats compared with diabetic rats (p garlic-treated diabetic rats compared with diabetic rats (p garlic, it was close to the normal level (p garlic extract has hypoglycaemic, antioxidant and anti-inflammatory properties; therefore, it can be useful for the alleviation of diabetic complications.

  8. Effects of short-term rosuvastatin therapy on heart and kidney function in patients with acute coronary syndrome combining diabetes mellitus and concomitant chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Heng WU

    2014-08-01

    Full Text Available Objective To observe the effects and safety of rosuvastatin therapy on protecting the renal and heart function in patients with acute coronary syndrome (ACS combining diabetes mellitus (DM and concomitant chronic kidney disease (CKD undergoing contrast media injection. Methods Concurrent parallel control and before-after self-control method were employed in present study. From Dec. 2008 to Oct. 2011, 2998 patients from 53 central hospitals in China were enrolled in a TRACK-D project. Out of 2998, 2309 patients with ACS combining DM and concomitant CKD were randomly assigned to rosuvastatin group (n=1183 or control group (n=1126. Patients in rosuvastatin group were given rosuvastatin 10mg/d for five days (two days before and three days post-procedure, while those in control group received no treatment. Isotonic non-ionic contrast medium (iodixanol was used in both groups when angiography, left ventriculography and percutaneous vascular intervention were started. Serum creatinine (Scr, estimated glomerular filtration rate (eGFR and urinary albumin/creatinine ratio (ACR were measured before and 48h, 72h after exposure to contrast medium. A 30-day clinical follow-up was conducted including the evaluation of aggravated heart failure, acute renal failure, dialysis/hemofiltration and all-cause mortality. Results No significant difference existed between the two groups at the preoperative levels of Scr (95.11±23.79μmol/L vs 94.88±20.31μmol/L, P=0.80 and eGFR [73.98±14.52ml/(min.1.73m2 vs 74.10±13.80ml/(min.1.73m2, P=0.85]. The postoperative Scr level showed no significant difference between the two groups (94.87±25.15μmol/L vs 95.74±30.50μmol/L, P=0.45, however, the postoperative Scr value presented a decline tendency in rosuvastatin group, while an upward trend in control group. The 30-day clinical follow-up found that the incidence of aggravated heart failure was significantly lower in rosuvastatin group than in control group (2.4% vs

  9. Diabetes and kidney disease: the role of sodium-glucose cotransporter-2 (SGLT-2) and SGLT-2 inhibitors in modifying disease outcomes.

    Science.gov (United States)

    Mende, Christian W

    2017-03-01

    Patients with type 2 diabetes (T2D) often have coexisting chronic kidney disease (CKD). However, healthy renal function is crucial in maintaining glucose homeostasis, assuring that almost all of the filtered glucose is reabsorbed by the sodium glucose cotransporters (SGLTs) SGLT-1 and SGLT-2. In diabetes, an increased amount of glucose is filtered by the kidneys and SGLT-2 is upregulated, leading to increased glucose absorption and worsening hyperglycemia. Prolonged hyperglycemia contributes to the development of CKD by inducing metabolic and hemodynamic changes in the kidneys. Due to the importance of SGLT-2 in regulating glucose levels, investigation into SGLT-2 inhibitors was initiated as a glucose-dependent mechanism to control hyperglycemia, and there are three agents currently approved for use in the United States: dapagliflozin, canagliflozin, and empagliflozin. SGLT-2 inhibitors have been shown to reduce glycated hemoglobin (A1C), weight, and blood pressure, which not only affects glycemic control, but may also help slow the progression of renal disease by impacting the underlying mechanisms of kidney injury. In addition, SGLT-2 inhibitors have shown reductions in albuminuria, uric acid, and an increase in magnesium. Caution is advised when prescribing SGLT-2 inhibitors to patients with moderately impaired renal function and those at risk for volume depletion and hypotension. Published data on slowing of the development, as well as progression of CKD, is a hopeful indicator for the possible renal protection potential of this drug class. This narrative review provides an in-depth discussion of the interplay between diabetes, SGLT-2 inhibitors, and factors that affect kidney function.

  10. Laser Capture Microdissection and Multiplex-Tandem PCR Analysis of Proximal Tubular Epithelial Cell Signaling in Human Kidney Disease

    Science.gov (United States)

    Wilkinson, Ray; Wang, Xiangju; Kassianos, Andrew J.; Zuryn, Steven; Roper, Kathrein E.; Osborne, Andrew; Sampangi, Sandeep; Francis, Leo; Raghunath, Vishwas; Healy, Helen

    2014-01-01

    Interstitial fibrosis, a histological process common to many kidney diseases, is the precursor state to end stage kidney disease, a devastating and costly outcome for the patient and the health system. Fibrosis is historically associated with chronic kidney disease (CKD) but emerging evidence is now linking many forms of acute kidney disease (AKD) with the development of CKD. Indeed, we and others have observed at least some degree of fibrosis in up to 50% of clinically defined cases of AKD. Epithelial cells of the proximal tubule (PTEC) are central in the development of kidney interstitial fibrosis. We combine the novel techniques of laser capture microdissection and multiplex-tandem PCR to identify and quantitate “real time” gene transcription profiles of purified PTEC isolated from human kidney biopsies that describe signaling pathways associated with this pathological fibrotic process. Our results: (i) confirm previous in-vitro and animal model studies; kidney injury molecule-1 is up-regulated in patients with acute tubular injury, inflammation, neutrophil infiltration and a range of chronic disease diagnoses, (ii) provide data to inform treatment; complement component 3 expression correlates with inflammation and acute tubular injury, (iii) identify potential new biomarkers; proline 4-hydroxylase transcription is down-regulated and vimentin is up-regulated across kidney diseases, (iv) describe previously unrecognized feedback mechanisms within PTEC; Smad-3 is down-regulated in many kidney diseases suggesting a possible negative feedback loop for TGF-β in the disease state, whilst tight junction protein-1 is up-regulated in many kidney diseases, suggesting feedback interactions with vimentin expression. These data demonstrate that the combined techniques of laser capture microdissection and multiplex-tandem PCR have the power to study molecular signaling within single cell populations derived from clinically sourced tissue. PMID:24475278

  11. Anti-liver-kidney microsome antibody type 1 recognizes human cytochrome P450 db1.

    Science.gov (United States)

    Gueguen, M; Yamamoto, A M; Bernard, O; Alvarez, F

    1989-03-15

    Anti-liver-kidney microsome antibody type 1 (LKM1), present in the sera of a group of children with autoimmune hepatitis, was recently shown to recognize a 50 kDa protein identified as rat liver cytochromes P450 db1 and db2. High homology between these two members of the rat P450 IID subfamily and human P450 db1 suggested that anti-LKM1 antibody is directed against this human protein. To test this hypothesis, a human liver cDNA expression library in phage lambda GT-11 was screened using rat P450 db1 cDNA as a probe. Two human cDNA clones were found to be identical to human P450 db1 by restriction mapping. Immunoblot analysis using as antigen, the purified fusion protein from one of the human cDNA clones showed that only anti-LKM1 with anti-50 kDa reactivity recognized the fusion protein. This fusion protein was further used to develop an ELISA test that was shown to be specific for sera of children with this disease. These results: 1) identify the human liver antigen recognized by anti-LKM1 auto-antibodies as cytochrome P450 db1, 2) allow to speculate that mutation on the human P450 db1 gene could alter its expression in the hepatocyte and make it auto-antigenic, 3) provide a simple and specific diagnostic test for this disease.

  12. Single Cell Dissection of Human Pancreatic Islet Dysfunction in Diabetes

    Science.gov (United States)

    2017-06-01

    of memory T cells , innate cells and the differentiation potential of naive T cells during ME/CFS; and 3) To determine the T cell and innate cell ...apoptosis and the innate immune response in human pancreatic β- cells . Diabetes 64: 3808–3817. Marselli L, Thorne J, Dahiya S, Sgroi DC, Sharma A, Bonner-Weir...interactive nature of CellView aids in cell doublet identification. In the PBMC data, ‘Subcluster-analysis’ reveals a mixture of lymphoid and myeloid

  13. Changes of the glomerular size during the human fetal kidney development

    Directory of Open Access Journals (Sweden)

    Daković-Bjelaković Marija

    2006-01-01

    Full Text Available Introduction. Newborns adaptation on postnatal conditions includes significant morphological and functional renal changes. Every kidney contains a constant number of nephrons, at the end of the nephrogenesis period, which extends from week 8 to 34 of gestation. Mature juxtamedullary nephrons possess higher filtration capacity than primitive superficial nephrons, which have insufficient vascularization. Objective. The objective of the study was to calculate an average glomerular diameter in cortical zones of the kidney during development, to define periods of their most intensive growth, and to record differences of glomerular size between different cortical zones. METHOD A total of 30 human fetal kidneys aged from IV to X lunar months were analyzed. Stereological methods were used for calculating the average glomerular diameter in superficial, intermediate and juxtamedullary zone of the kidney cortex. Results. Glomeruli in the superficial cortical zone had the lowest average diameter. The average glomerular diameter continually increased from IV lunar month (0.057±0.004 mm to X lunar month (0.082±0.004 mm, with highly significant correlation with gestational age (r=0.755; p<0.01. The average glomerular diameter in the intermediate zone increased from 0.081±0.004 mm (IV lunar month to 0.096±0.004 mm (X lunar month with low linear correlation with gestational age (r=0.161. Juxtamedullary glomeruli were the biggest ones. Their average diameter, during the IV LM ranged from 0.093±0.006 mm to 0.101±0.004 mm. In the newborns (X lunar month, juxtamedullary glomeruli had spherical structures with an average diameter of 0.103±0.004 mm, and low negative correlation (r=-0.032 with gestational age. In the IV and V lunar months of gestation, there was significant difference (p<0.01; p<0.05 between the average glomerular diameter in the different zones of the kidney cortex. Conclusion. Superficial glomeruli had the smallest diameter, while

  14. Adaptive regulation of taurine and beta-alanine uptake in a human kidney cell line from the proximal tubule

    DEFF Research Database (Denmark)

    Jessen, H; Jacobsen, Christian

    1997-01-01

    1. The underlying mechanisms involved in the adaptive regulation of beta-amino acid uptake in the human proximal tubule were examined by use of an immortalized human embryonic kidney epithelial cell line (IHKE). 2. The results indicated that the adaptive response to maintain whole-body taurine...

  15. PGE2 receptor EP3 inhibits water reabsorption and contributes to polyuria and kidney injury in a streptozotocin-induced mouse model of diabetes.

    Science.gov (United States)

    Hassouneh, Ramzi; Nasrallah, Rania; Zimpelmann, Joe; Gutsol, Alex; Eckert, David; Ghossein, Jamie; Burns, Kevin D; Hébert, Richard L

    2016-06-01

    The first clinical manifestation of diabetes is polyuria. The prostaglandin E2 (PGE2) receptor EP3 antagonises arginine vasopressin (AVP)-mediated water reabsorption and its expression is increased in the diabetic kidney. The purpose of this work was to study the contribution of EP3 to diabetic polyuria and renal injury. Male Ep 3 (-/-) (also known as Ptger3 (-/-)) mice were treated with streptozotocin (STZ) to generate a mouse model of diabetes and renal function was evaluated after 12 weeks. Isolated collecting ducts (CDs) were microperfused to study the contribution of EP3 to AVP-mediated fluid reabsorption. Ep 3 (-/-)-STZ mice exhibited attenuated polyuria and increased urine osmolality compared with wild-type STZ (WT-STZ) mice, suggesting enhanced water reabsorption. Compared with WT-STZ mice, Ep 3 (-/-)-STZ mice also had increased protein expression of aquaporin-1, aquaporin-2, and urea transporter A1, and reduced urinary AVP excretion, but increased medullary V2 receptors. In vitro microperfusion studies indicated that Ep 3 (-/-) and WT-STZ CDs responded to AVP stimulation similarly to those of wild-type mice, with a 60% increase in fluid reabsorption. In WT non-injected and WT-STZ mice, EP3 activation with sulprostone (PGE2 analogue) abrogated AVP-mediated water reabsorption; this effect was absent in mice lacking EP3. A major finding of this work is that Ep 3 (-/-)-STZ mice showed blunted renal cyclooxygenase-2 protein expression, reduced renal hypertrophy, reduced hyperfiltration and reduced albuminuria, as well as diminished tubular dilation and nuclear cysts. Taken together, the data suggest that EP3 contributes to diabetic polyuria by inhibiting expression of aquaporins and that it promotes renal injury during diabetes. EP3 may prove to be a promising target for more selective management of diabetic kidney disease.

  16. Reading First Coordinates from the Nephrogenic Zone in Human Fetal Kidney.

    Science.gov (United States)

    Minuth, Will W

    2018-01-01

    While substantial information is available on organ anlage and the primary formation of nephrons, molecular mechanisms acting during the late development of the human kidney have received an astonishing lack of attention. In healthy newborn babies, nephrogenesis takes place unnoticed until birth. Upon delivery, morphogenetic activity in the nephrogenic zone decreases, and the stem cell niches aligned beyond the organ capsule vanish by an unknown signal. However, this signal also plays a key role in preterm and low birth weight babies. Although they are born in a phase of active nephrogenesis, pathological findings illustrate that they evolve to a high incidence oligonephropathy and prematurity of renal parenchyma. Different extra- and intrauterine influences seem to be responsible, but independent from chemical nature, all of them culminate in the nephrogenic zone. One assumes that the marred development is caused either by an overshoot of metabolites, misleading signaling of morphogens, unbalanced synthesis of extracellular matrix or restricted contact between mesenchymal and epithelial stem cells. Even more surprising is that there is only a few vague morphological information of the nephrogenic zone in the human fetal kidney available and ultrastructural data is severely lacking. On this account, the first coordinates were determined by optical microscopy and morphometry. Without claiming to be complete, generated results made it possible to create schematic illustrations true to scale for orientation. It will help graduating students, young pediatricians, pathologists, and scientists working in the field of biomedicine to interpret professionally the nephrogenic zone and contained niches. © 2017 S. Karger AG, Basel.

  17. Organoid cystogenesis reveals a critical role of microenvironment in human polycystic kidney disease

    Science.gov (United States)

    Cruz, Nelly M.; Song, Xuewen; Czerniecki, Stefan M.; Gulieva, Ramila E.; Churchill, Angela J.; Kim, Yong Kyun; Winston, Kosuke; Tran, Linh M.; Diaz, Marco A.; Fu, Hongxia; Finn, Laura S.; Pei, York; Himmelfarb, Jonathan; Freedman, Benjamin S.

    2017-11-01

    Polycystic kidney disease (PKD) is a life-threatening disorder, commonly caused by defects in polycystin-1 (PC1) or polycystin-2 (PC2), in which tubular epithelia form fluid-filled cysts. A major barrier to understanding PKD is the absence of human cellular models that accurately and efficiently recapitulate cystogenesis. Previously, we have generated a genetic model of PKD using human pluripotent stem cells and derived kidney organoids. Here we show that systematic substitution of physical components can dramatically increase or decrease cyst formation, unveiling a critical role for microenvironment in PKD. Removal of adherent cues increases cystogenesis 10-fold, producing cysts phenotypically resembling PKD that expand massively to 1-centimetre diameters. Removal of stroma enables outgrowth of PKD cell lines, which exhibit defects in PC1 expression and collagen compaction. Cyclic adenosine monophosphate (cAMP), when added, induces cysts in both PKD organoids and controls. These biomaterials establish a highly efficient model of PKD cystogenesis that directly implicates the microenvironment at the earliest stages of the disease.

  18. Isolation and characterization of multipotent progenitor cells from the Bowman's capsule of adult human kidneys.

    Science.gov (United States)

    Sagrinati, Costanza; Netti, Giuseppe Stefano; Mazzinghi, Benedetta; Lazzeri, Elena; Liotta, Francesco; Frosali, Francesca; Ronconi, Elisa; Meini, Claudia; Gacci, Mauro; Squecco, Roberta; Carini, Marco; Gesualdo, Loreto; Francini, Fabio; Maggi, Enrico; Annunziato, Francesco; Lasagni, Laura; Serio, Mario; Romagnani, Sergio; Romagnani, Paola

    2006-09-01

    Regenerative medicine represents a critical clinical goal for patients with ESRD, but the identification of renal adult multipotent progenitor cells has remained elusive. It is demonstrated that in human adult kidneys, a subset of parietal epithelial cells (PEC) in the Bowman's capsule exhibit coexpression of the stem cell markers CD24 and CD133 and of the stem cell-specific transcription factors Oct-4 and BmI-1, in the absence of lineage-specific markers. This CD24+CD133+ PEC population, which could be purified from cultured capsulated glomeruli, revealed self-renewal potential and a high cloning efficiency. Under appropriate culture conditions, individual clones of CD24+CD133+ PEC could be induced to generate mature, functional, tubular cells with phenotypic features of proximal and/or distal tubules, osteogenic cells, adipocytes, and cells that exhibited phenotypic and functional features of neuronal cells. The injection of CD24+CD133+ PEC but not of CD24-CD133- renal cells into SCID mice that had acute renal failure resulted in the regeneration of tubular structures of different portions of the nephron. More important, treatment of acute renal failure with CD24+CD133+ PEC significantly ameliorated the morphologic and functional kidney damage. This study demonstrates the existence and provides the characterization of a population of resident multipotent progenitor cells in adult human glomeruli, potentially opening new avenues for the development of regenerative medicine in patients who have renal diseases.

  19. Can glycated hemoglobin act as a reliable glycemic indicator in patients with diabetic chronic kidney disease? evidence from the Northeast of Thailand

    Directory of Open Access Journals (Sweden)

    Sojib Bin Zaman

    2017-08-01

    Full Text Available Background: Chronic kidney diseases (CKD is a common microvascular complication in patients with diabetes mellitus (DM which requires adequate glycemic control. Glycated hemoglobin (HbA1c is a conventional biomarker to estimate glycemic status, but its role in diabetic CKD patients is unclear. Therefore, this study aimed to determine whether patients with high HbA1c are associated to develop diabetic CKD.Methods: Data were obtained from a clinical registry of diabetic patients who were treated in a district hospital in the Northeast of Thailand. CKD was defined according to the estimated glomerular filtration rate (eGFR<60mL/min/1.73m2. Anthropometric and biochemical measurements of the patient were taken by review of medical records. Multiple logistic regression analysis was used to determine the likelihood of the association between HbA1c and CKD.Results: Among 4,050 participants, 1,027 (25.3% developed diabetic CKD. Older age (adjusted odds ratio (AOR: 4.88, 95% confidence interval (CI: 3.71–6.42, p<0.05, female (AOR: 1.38, 95% CI: 1.05–1.73, p<0.05, and hypertension (AOR: 1.52, 95% CI: 1.21–1.91, p<0.05 were found as the risk factors of diabetic CKD. However, patients with high HbA1c (>6.5% were negatively associated with diabetic CKD (AOR: 0.66, 95% CI: 0.51–0.86, p<0.05.Conclusion: This study found patients with higher HbA1c level were not associated with diabetic CKD. Therefore, using the conventional cut-off values of HbA1c in diabetic CKD patients may be problematic in the clinical settings. Enhanced detection of glycemic status in patients with diabetic CKD is warranted to improve the outcome.

  20. Study of rat kidney transamidinase structure and regulation with monoclonal antibodies and the purification and characterization of human kidney transamidinase

    International Nuclear Information System (INIS)

    Gross, M.D.

    1985-01-01

    The isolation of monoclonal antibodies to transamidinase made possible the development of an immunosorbent inhibition assay for transamidinase protein using a 125 I-labeled monoclonal antibody. This assay is a more direct measurement of transamidinase protein than the determination of the amount of polyclonal antibody required to precipitate the transamidinase activities. Rats were fed diets supplemented with creatine and/or glycine, and the amounts of transamidinase protein were determined with the assay using the monoclonal antibody. The transamidinase activities of kidneys from the rats fed the various supplemented diets ranged from 10 to 40% of the control values, whereas, the amounts of transamidinase protein were, in all instances no lower than 66% of the control values. Purified homogeneous rat kidney transamidinase and rat kidney supernatants were subjected to isoelectric focussing and four to five fractions of the enzyme were obtained. Polyclonal antibodies, but not the monoclonal antibodies were found by Western blotting experiments to recognize all the forms of the enzyme obtained by the isoelectric focussing. The author concluded that the monoclonal antibodies recognized forms of the enzyme that changed very little in amount, relative to the alterations in enzyme activities, when rats were fed a diet containing creatine

  1. Comparison of results of integrated nuclear medical kidney examinations in different stages of Diabetes mellitus

    International Nuclear Information System (INIS)

    Krieger, E.

    1979-01-01

    In 67 diabetics and 33 hypertonics the author carried out the following tests: 1. Serial renal function scintiscanning with 131 J-oJH; 2. Simultaneous assessment of global sup(99m)Tc-dtpa and 131 J-oJH clearance using a partly screened-off whole-body count 3. Unilateral assessment of 131 J-oJH clearance; 4. Assessment of sup(99m)Tc-dtpa and 131 J-oJH excretion. From the integral gamma-camera time-activity curves established by ROI technique as a part of serial functional scintiscanning, the nephrogram parameters secretion value, secretion maximum and elimination half-time were ascertained. The values thus obtained were compared with the global and unilateral 131 J-oJH clearance. Moreover the excretion of the radiopharmaceuticals in the urine was compared with whole-body clearance determined simultaneously. At normal renal function, the biological half-life for 131 J-oJH and sup(99m)Tc-dtpa was calculated and the distribute volumes were assessed from the elimination constant and from renal clearance. The results of the nuclear-medical renal-function parameters in varying stages of diabetic renal disease indicate that the elimination half-time is the only RIN criterion to permit a differentiation of collectives. (orig./MG) [de

  2. The Relationship between Maternal Nutrition during Pregnancy and Offspring Kidney Structure and Function in Humans: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Yu Qi Lee

    2018-02-01

    Full Text Available The intrauterine environment is critical for fetal growth and organ development. Evidence from animal models indicates that the developing kidney is vulnerable to suboptimal maternal nutrition and changes in health status. However, evidence from human studies are yet to be synthesised. Therefore, the aim of the current study was to systematically review current research on the relationship between maternal nutrition during pregnancy and offspring kidney structure and function in humans. A search of five databases identified 9501 articles, of which three experimental and seven observational studies met the inclusion criteria. Nutrients reviewed to date included vitamin A (n = 3, folate and vitamin B12 (n = 2, iron (n = 1, vitamin D (n = 1, total energy (n = 2 and protein (n = 1. Seven studies were assessed as being of “positive” and three of “neutral” quality. A variety of populations were studied, with limited studies investigating maternal nutrition during pregnancy, while measurements of offspring kidney outcomes were diverse across studies. There was a lack of consistency in the timing of follow-up for offspring kidney structure and/or function assessments, thus limiting comparability between studies. Deficiencies in maternal folate, vitamin A, and total energy during pregnancy were associated with detrimental impacts on kidney structure and function, measured by kidney volume, proteinuria, eGFRcystC and mean creatinine clearance in the offspring. Additional experimental and longitudinal prospective studies are warranted to confirm this relationship, especially in Indigenous populations where the risk of renal disease is greater.

  3. The Relationship between Maternal Nutrition during Pregnancy and Offspring Kidney Structure and Function in Humans: A Systematic Review

    Science.gov (United States)

    Lee, Yu Qi; Collins, Clare E.; Gordon, Adrienne; Rae, Kym M.; Pringle, Kirsty G.

    2018-01-01

    The intrauterine environment is critical for fetal growth and organ development. Evidence from animal models indicates that the developing kidney is vulnerable to suboptimal maternal nutrition and changes in health status. However, evidence from human studies are yet to be synthesised. Therefore, the aim of the current study was to systematically review current research on the relationship between maternal nutrition during pregnancy and offspring kidney structure and function in humans. A search of five databases identified 9501 articles, of which three experimental and seven observational studies met the inclusion criteria. Nutrients reviewed to date included vitamin A (n = 3), folate and vitamin B12 (n = 2), iron (n = 1), vitamin D (n = 1), total energy (n = 2) and protein (n = 1). Seven studies were assessed as being of “positive” and three of “neutral” quality. A variety of populations were studied, with limited studies investigating maternal nutrition during pregnancy, while measurements of offspring kidney outcomes were diverse across studies. There was a lack of consistency in the timing of follow-up for offspring kidney structure and/or function assessments, thus limiting comparability between studies. Deficiencies in maternal folate, vitamin A, and total energy during pregnancy were associated with detrimental impacts on kidney structure and function, measured by kidney volume, proteinuria, eGFRcystC and mean creatinine clearance in the offspring. Additional experimental and longitudinal prospective studies are warranted to confirm this relationship, especially in Indigenous populations where the risk of renal disease is greater. PMID:29466283

  4. Secondary hyperparathyroidism prevalence and profile, between diabetic and non-diabetic patients with stage 3 to 4 chronic kidney disease attended in internal medicine wards. MiPTH study.

    Science.gov (United States)

    Arévalo-Lorido, José Carlos; Carretero-Gómez, Juana; García-Sánchez, Francisco; Maciá-Botejara, Enrique; Ramiro-Lozano, José Manuel; Masero-Carretero, Antonio; Robles, Nicolás Roberto; Bureo-Dacal, Juan Carlos

    2016-01-01

    Secondary hyperparathyroidism (SHPTH) is a leading cause of renal osteodystrophy, and an independent risk factor for all-cause and cardiovascular mortality. Our aim is to establish differences in prevalence and profile of SHPTH, regarding diabetics or non-diabetics with chronic kidney disease (CKD). Cross-sectional multicenter study which included patients with stages 3 to 4 CKD. SHPTH was considered when the intact PTH levels (iPTH) were equal or higher than 70pg/ml. We divided the sample into two groups (diabetics and non-diabetics). We used robust statistical methods. 409 patients (214 diabetics) were studied. HPTH was found in 60.4% of diabetics vs 65% of non-diabetics (P=0.42). Diabetics with HPTH were younger (79.5 vs 82.3 years-old, P=0.005), and had more hypertension (P=0.0014), dyslipidemia (P=0.0001) and comorbidities. In multivariate analysis, we found a significant relationship in case of diabetics, with age (OR: 1.04, 95%CI 1.005-1.09 P=0.02 ), and with statins treatment (OR 2.3, 95%CI 1.17-4.54, P=0.01). The prevalence of SHPTH between the groups was similar, however, diabetics had more presence of hypertension and dyslipidemia, and SHPTH in this case was also related with moderate microalbuminuria and lower levels of vitamin D. An association with statins was also found in this group. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  5. Kidney function after withdrawal of long-term antihypertensive treatment in diabetic nephropathy

    DEFF Research Database (Denmark)

    Hansen, H P; Nielsen, F S; Rossing, P

    1997-01-01

    ) [median (range)] with diabetic nephropathy receiving antihypertensive treatment (angiotensin converting enzyme inhibition, N = 30) for 5 years (1 to 20 years). The following variables were measured the last day on antihypertensive treatment and one month after withdrawal of treatment; GFR (51Cr-EDTA), 24......-hour arterial blood pressure (24 hr MABP, Takeda TM2420) and albuminuria (ELISA); the mean 24-hour MABP rose from 102 +/- 11 to 111 +/- 10 (P ... +/- 25 to 70 +/- 26 ml.min-1.1.73 m-2, P = 0.21), after withdrawal of antihypertensive treatment. A significant correlation between the relative change in the 24 hour MABP measurement and the relative change in GFR (r = 0.44, P

  6. Human leukocyte antigen in the allocation of kidneys from cadaveric donors in the United States.

    Science.gov (United States)

    Ting, Alan; Edwards, Leah Bennett

    2004-02-27

    Minorities wait longer for a cadaveric donor kidney transplant than whites. For example, the median waiting time to transplant for candidates listed from 1997 to 1998 was 874 days for whites, 1,493 days for blacks, 1,281 days for Hispanics, 1,491 days for Asians, and 1,466 days for others. The current allocation algorithm has been criticized as contributing to decreased access to transplants for racial minorities. There are two levels in the current algorithm: The first is mandatory national sharing between donors and patients with zero human leukocyte antigen (HLA)-A, B, and DR mismatches. The second occurs if there are no candidates and local placement is accomplished based on an algorithm with an HLA component that assigns seven, five, and two points to zero, one, and two HLA-B and DR mismatches, respectively. An analysis of the data shows that a higher percentage of white recipients (21%) received zero antigen mismatched kidneys compared with other races: blacks (7%), Hispanics (14%), and Asians (7%). Whites also received the highest percentage of kidneys with zero B and DR mismatches and one B and DR mismatch compared with the other races. These data indicate that the current algorithm favors whites over minorities, and it is most likely that giving points for HLA-B matching is a strong contributory factor. To address this inequity, the Organ Procurement and Transplantation Network and United Network for Organ Sharing Board of Directors approved a recommendation in November 2002 to change the HLA points to award two points for zero DR mismatches and one point for one DR mismatch. Obviously it will take some time to gather sufficient data to allow meaningful analysis of the effect of the policy change.

  7. Association of Human Development Index with global bladder, kidney, prostate and testis cancer incidence and mortality.

    Science.gov (United States)

    Greiman, Alyssa K; Rosoff, James S; Prasad, Sandip M

    2017-12-01

    To describe contemporary worldwide age-standardized incidence and mortality rates for bladder, kidney, prostate and testis cancer and their association with development. We obtained gender-specific, age-standardized incidence and mortality rates for 184 countries and 16 major world regions from the GLOBOCAN 2012 database. We compared the mortality-to-incidence ratios (MIRs) at national and regional levels in males and females, and assessed the association with socio-economic development using the 2014 United Nations Human Development Index (HDI). Age-standardized incidence rates were 2.9 (bladder) to 7.4 (testis) times higher for genitourinary malignancies in more developed countries compared with less developed countries. Age-standardized mortality rates were 1.5-2.2 times higher in more vs less developed countries for prostate, bladder and kidney cancer, with no variation in mortality rates observed in testis cancer. There was a strong inverse relationship between HDI and MIR in testis (regression coefficient 1.65, R 2 = 0.78), prostate (regression coefficient -1.56, R 2 = 0.85), kidney (regression coefficient -1.34, R 2 = 0.74), and bladder cancer (regression coefficient -1.01, R 2 = 0.80). While incidence and mortality rates for genitourinary cancers vary widely throughout the world, the MIR is highest in less developed countries for all four major genitourinary malignancies. Further research is needed to understand whether differences in comorbidities, exposures, time to diagnosis, access to healthcare, diagnostic techniques or treatment options explain the observed inequalities in genitourinary cancer outcomes. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

  8. Ultrasound-targeted stromal cell-derived factor-1-loaded microbubble destruction promotes mesenchymal stem cell homing to kidneys in diabetic nephropathy rats

    Directory of Open Access Journals (Sweden)

    Wu S

    2014-12-01

    Full Text Available Shengzheng Wu,1 Lu Li,1 Gong Wang,1 Weiwei Shen,2 Yali Xu,1 Zheng Liu,1 Zhongxiong Zhuo,1 Hongmei Xia,1 Yunhua Gao,1 Kaibin Tan1 1Department of Ultrasound, 2Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing, People’s Republic of China Abstract: Mesenchymal stem cell (MSC therapy has been considered a promising strategy to cure diabetic nephropathy (DN. However, insufficient MSCs can settle in injured kidneys, which constitute one of the major barriers to the effective implementation of MSC therapy. Stromal cell-derived factor-1 (SDF-1 plays a vital role in MSC migration and involves activation, mobilization, homing, and retention, which are presumably related to the poor homing in DN therapy. Ultrasound-targeted microbubble destruction has become one of the most promising strategies for the targeted delivery of drugs and genes. To improve MSC homing to DN kidneys, we present a strategy to increase SDF-1 via ultrasound-targeted microbubble destruction. In this study, we developed SDF-1-loaded microbubbles (MBSDF-1 via covalent conjugation. The characterization and bioactivity of MBSDF-1 were assessed in vitro. Target release in the targeted kidneys was triggered with diagnostic ultrasound in combination with MBSDF-1. The related bioeffects were also elucidated. Early DN was induced in rats with streptozotocin. Green fluorescent protein-labeled MSCs were transplanted intravenously following the target release of SDF-1 in the kidneys of normal and DN rats. The homing efficacy was assessed by detecting the implanted exogenous MSCs at 24 hours. The in vitro results showed an impressive SDF-1 loading efficacy of 79% and a loading content of 15.8 µg/mL. MBSDF-1 remained bioactive as a chemoattractant. In the in vivo study, SDF-1 was successfully released in the targeted kidneys. The homing efficacy of MSCs to DN kidneys after the target release of SDF-1 was remarkably ameliorated at 24 hours compared with

  9. Diabetes Complications

    Science.gov (United States)

    If you have diabetes, your blood glucose, or blood sugar, levels are too high. Over time, this can cause problems with other body ... as your kidneys, nerves, feet, and eyes. Having diabetes can also put you at a higher risk ...

  10. Associations of Early Kidney Disease With Brain Magnetic Resonance Imaging and Cognitive Function in African Americans With Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Freedman, Barry I; Sink, Kaycee M; Hugenschmidt, Christina E; Hughes, Timothy M; Williamson, Jeff D; Whitlow, Christopher T; Palmer, Nicholette D; Miller, Michael E; Lovato, Laura C; Xu, Jianzhao; Smith, S Carrie; Launer, Lenore J; Barzilay, Joshua I; Cohen, Robert M; Sullivan, Mark D; Bryan, R Nick; Wagner, Benjamin C; Bowden, Donald W; Maldjian, Joseph A; Divers, Jasmin

    2017-11-01

    Relationships between early kidney disease, neurocognitive function, and brain anatomy are poorly defined in African Americans with type 2 diabetes mellitus (T2DM). Cross-sectional associations were assessed between cerebral anatomy and cognitive performance with estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) in African Americans with T2DM. African Americans with cognitive testing and cerebral magnetic resonance imaging (MRI) in the African American-Diabetes Heart Study Memory in Diabetes (AA-DHS MIND; n=512; 480 with MRI) and Action to Control Cardiovascular Risk in Diabetes (ACCORD) MIND (n=484; 104 with MRI) studies. eGFR (CKD-EPI creatinine equation), spot UACR. MRI-based cerebral white matter volume (WMV), gray matter volume (GMV), and white matter lesion volume; cognitive performance (Mini-Mental State Examination, Digit Symbol Coding, Stroop Test, and Rey Auditory Verbal Learning Test). Multivariable models adjusted for age, sex, body mass index, scanner, intracranial volume, education, diabetes duration, hemoglobin A 1c concentration, low-density lipoprotein cholesterol concentration, smoking, hypertension, and cardiovascular disease were used to test for associations between kidney phenotypes and the brain in each study; a meta-analysis was performed. Mean participant age was 60.1±7.9 (SD) years; diabetes duration, 12.1±7.7 years; hemoglobin A 1c concentration, 8.3%±1.7%; eGFR, 88.7±21.6mL/min/1.73m 2 ; and UACR, 119.2±336.4mg/g. In the fully adjusted meta-analysis, higher GMV associated with lower UACR (Passociation with higher eGFR. Higher white matter lesion volume was associated with higher UACR (Passociated with either kidney parameter. Higher UACR was associated with lower Digit Symbol Coding performance (Passociation with higher Stroop interference; eGFR was not associated with cognitive tests. Cross-sectional; single UACR measurement. In African Americans with T2DM, mildly high UACR and mildly low e

  11. Sodium-Glucose Cotransporter 2 Inhibitor and a Low Carbohydrate Diet Affect Gluconeogenesis and Glycogen Content Differently in the Kidney and the Liver of Non-Diabetic Mice.

    Science.gov (United States)

    Atageldiyeva, Kuralay; Fujita, Yukihiro; Yanagimachi, Tsuyoshi; Mizumoto, Katsutoshi; Takeda, Yasutaka; Honjo, Jun; Takiyama, Yumi; Abiko, Atsuko; Makino, Yuichi; Haneda, Masakazu

    2016-01-01

    A low carbohydrate diet (LCHD) as well as sodium glucose cotransporter 2 inhibitors (SGLT2i) may reduce glucose utilization and improve metabolic disorders. However, it is not clear how different or similar the effects of LCHD and SGLT2i are on metabolic parameters such as insulin sensitivity, fat accumulation, and especially gluconeogenesis in the kidney and the liver. We conducted an 8-week study using non-diabetic mice, which were fed ad-libitum with LCHD or a normal carbohydrate diet (NCHD) and treated with/without the SGLT-2 inhibitor, ipragliflozin. We compared metabolic parameters, gene expression for transcripts related to glucose and fat metabolism, and glycogen content in the kidney and the liver among the groups. SGLT2i but not LCHD improved glucose excursion after an oral glucose load compared to NCHD, although all groups presented comparable non-fasted glycemia. Both the LCHD and SGLT2i treatments increased calorie-intake, whereas only the LCHD increased body weight compared to the NCHD, epididimal fat mass and developed insulin resistance. Gene expression of certain gluconeogenic enzymes was simultaneously upregulated in the kidney of SGLT2i treated group, as well as in the liver of the LCHD treated group. The SGLT2i treated groups showed markedly lower glycogen content in the liver, but induced glycogen accumulation in the kidney. We conclude that LCHD induces deleterious metabolic changes in the non-diabetic mice. Our results suggest that SGLT2i induced gluconeogenesis mainly in the kidney, whereas for LCHD it was predominantly in the liver.

  12. Gene Expression in the Normal Adult Human Kidney Assessed by Complementary DNA Microarray

    OpenAIRE

    Higgins, John P.T.; Wang, Lingli; Kambham, Neeraja; Montgomery, Kelli; Mason, Veronica; Vogelmann, Stefanie U.; Lemley, Kevin V.; Brown, Patrick O.; Brooks, James D.; van de Rijn, Matt

    2004-01-01

    The kidney is a highly specialized organ with a complex, stereotyped architecture and a great diversity of functions and cell types. Because the microscopic organization of the nephron, the functional unit of the kidney, has a consistent relationship to the macroscopic anatomy of the kidney, knowledge of the characteristic patterns of gene expression in different compartments of the kidney could provide insight into the functions and functional organization of the normal nephron. We studied g...

  13. Human embryonic mesenchymal stem cell-derived conditioned medium rescues kidney function in rats with established chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Arianne van Koppen

    Full Text Available Chronic kidney disease (CKD is a major health care problem, affecting more than 35% of the elderly population worldwide. New interventions to slow or prevent disease progression are urgently needed. Beneficial effects of mesenchymal stem cells (MSC have been described, however it is unclear whether the MSCs themselves or their secretome is required. We hypothesized that MSC-derived conditioned medium (CM reduces progression of CKD and studied functional and structural effects in a rat model of established CKD. CKD was induced by 5/6 nephrectomy (SNX combined with L-NNA and 6% NaCl diet in Lewis rats. Six weeks after SNX, CKD rats received either 50 µg CM or 50 µg non-CM (NCM twice daily intravenously for four consecutive days. Six weeks after treatment CM administration was functionally effective: glomerular filtration rate (inulin clearance and effective renal plasma flow (PAH clearance were significantly higher in CM vs. NCM-treatment. Systolic blood pressure was lower in CM compared to NCM. Proteinuria tended to be lower after CM. Tubular and glomerular damage were reduced and more glomerular endothelial cells were found after CM. DNA damage repair was increased after CM. MSC-CM derived exosomes, tested in the same experimental setting, showed no protective effect on the kidney. In a rat model of established CKD, we demonstrated that administration of MSC-CM has a long-lasting therapeutic rescue function shown by decreased progression of CKD and reduced hypertension and glomerular injury.

  14. About Chronic Kidney Disease

    Science.gov (United States)

    ... detect CKD: blood pressure, urine albumin and serum creatinine. What causes CKD? The two main causes of chronic kidney disease are diabetes and high blood pressure , which are responsible for up to ...

  15. Acquired Cystic Kidney Disease

    Science.gov (United States)

    ... including diabetes, high blood pressure, glomerulonephritis, and cys tic kidney diseases. Participants in clinical trials can play ... Life Options Rehabilitation Resource Center c/o Medical Education Institute, Inc. 414 D’Onofrio Drive, Suite 200 ...

  16. Low vascularization of the nephrogenic zone of the fetal kidney suggests a major role for hypoxia in human nephrogenesis.

    Science.gov (United States)

    Gerosa, C; Fanni, D; Faa, A; Van Eyken, P; Ravarino, A; Fanos, V; Faa, G

    2017-09-01

    CD31 reactivity is generally utilized as a marker of endothelial cells. CD31 immunoreactivity in the developing human kidney revealed that fetal glomerular capillary endothelial cells change their immunohistochemical phenotype during maturation. The aim of this study was to analyze CD31 reactivity in the fetal human kidney in the different stages of intrauterine development: We observed different distribution of CD31-reactive vascular progenitors in the different areas of the developing kidney. In particular, the nephrogenic zone and the renal capsule were characterized by a scarcity of CD31-reactive cells at all gestational ages. These data suggest the hypothesis that nephrogenesis does not need high oxygen levels and confirms a major role of hypoxia in nephrogenesis.

  17. Diabetes increases the susceptibility to acute kidney injury after myocardial infarction through augmented activation of renal Toll-like receptors in rats.

    Science.gov (United States)

    Ohno, Kouhei; Kuno, Atsushi; Murase, Hiromichi; Muratsubaki, Shingo; Miki, Takayuki; Tanno, Masaya; Yano, Toshiyuki; Ishikawa, Satoko; Yamashita, Tomohisa; Miura, Tetsuji

    2017-12-01

    Acute kidney injury (AKI) after acute myocardial infarction (MI) worsens the prognosis of MI patients. Although type 2 diabetes mellitus (DM) is a major risk factor of AKI after MI, the underlying mechanism remains unclear. Here, we examined the roles of renal Toll-like receptors (TLRs) in the impact of DM on AKI after MI. MI was induced by coronary artery ligation in Otsuka-Long-Evans-Tokushima fatty (OLETF) rats, a rat DM model, and Long-Evans-Tokushima-Otsuka (LETO) rats, nondiabetic controls. Sham-operated rats served as no-MI controls. Renal mRNA levels of TLR2 and myeloid differentiation factor 88 (MyD88) were significantly higher in sham-operated OLETF rats than in sham-operated LETO rats, although levels of TLR1, TLR3, and TLR4 were similar. At 12 h after MI, protein levels of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in the kidney were elevated by 5.3- and 4.0-fold, respectively, and their mRNA levels were increased in OLETF but not LETO rats. The increased KIM-1 and NGAL expression levels after MI in the OLETF kidney were associated with upregulated expression of TLR1, TLR2, TLR4, MyD88, IL-6, TNF-α, chemokine (C-C motif) ligand 2, and transforming growth factor-β 1 and also with activation of p38 MAPK, JNK, and NF-κB. Cu-CPT22, a TLR1/TLR2 antagonist, administered before MI significantly suppressed MI-induced upregulation of KIM-1, TLR2, TLR4, MyD88, and chemokine (C-C motif) ligand 2 levels and activation of NF-κB, whereas NGAL levels and IL-6 and TNF-α expression levels were unchanged. The results suggest that DM increases the susceptibility to AKI after acute MI by augmented activation of renal TLRs and that TLR1/TLR2-mediated signaling mediates KIM-1 upregulation after MI. NEW & NOTEWORTHY This is the first report to demonstrate the involvement of Toll-like recpetors (TLRs) in diabetes-induced susceptibility to acute kidney injury after acute myocardial infarction. We propose that the TLR1/TLR2

  18. 78 FR 55266 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2013-09-10

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of...., Scientific Review Officer, Review Branch, DEA, NIDDK, National Institutes Of Health, Room 759, 6707 Democracy... grant applications. Place: Hotel Kabuki, 1625 Post Street, San Francisco, CA 94115. Contact Person...

  19. [Early human transplants: 60th anniversary of the first successful kidney transplants].

    Science.gov (United States)

    Gentili, Marc E

    2015-11-01

    First kidney transplant attempts begin with the 20th century: improving vascular sutures, understanding the phenomena of rejection or tolerance, then progress in HLA groups enable early success in the second half of the century. Definition of brain death, use of corticosteroids, radiotherapy and prime immunosuppressors promote the development of transplants. Discover of cyclosporine in the 1980s, and legislative developments augur a new era. Many advances are arising: use of stem cells from the donor, enhancement of Maastricht 3 donor or living donation. Finally organ transplantation remains an immense human adventure, but also scientific and ethic. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  20. Effect of Qufengtongluo Decoction on PI3K/Akt Signaling Pathway in the Kidney of Type 2 Diabetes Mellitus Rat (GK Rat with Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Wei-Jun Huang

    2018-01-01

    Full Text Available Qufengtongluo (QFTL decoction is an effective treatment for diabetic nephropathy (DN. However, the underlying molecular mechanism is still unclear. In this study, we try to investigate whether QFTL decoction acts via inhibiting PI3K/Akt signaling pathway. Twenty-four GK rats were randomly divided into 3 groups: blank group, sham-operated group, and QFTL group. After model establishment, rats in QFTL group were given QFTL decoction by gavage, while the rest were given pure water. During the 8-week intervention, 24 hr urinal protein was measured every 2-3 weeks. After intervention, kidneys were removed for pathological smear, quantitative real-time PCR, and western blotting to detect expression levels of p-PI3K, p-Akt, PTEN, TGF-β, PI3K mRNA, Akt mRNA, PTEN mRNA, and TGF-β mRNA. QFTL group showed a slighter degree of renal fibrosis in Masson and PASM staining and a greater reduction of 24 hr urinal protein than blank group. Compared to blank group, expression levels of p-PI3K, p-Akt, PI3K mRNA, and Akt mRNA were lower in QFTL group, while expression levels of PTEN and PTEN mRNA were higher. Besides, TGF-β was downregulated by QFTL decoction. In conclusion, this study suggests that QFTL decoction might inhibit PI3K/Akt signaling pathway via activating PTEN and inhibiting TGF-β.

  1. Minireview: Epigenetics of obesity and diabetes in humans.

    Science.gov (United States)

    Slomko, Howard; Heo, Hye J; Einstein, Francine H

    2012-03-01

    Understanding the determinants of human health and disease is overwhelmingly complex, particularly for common, late-onset, chronic disorders, such as obesity and diabetes. Elucidating the genetic and environmental factors that influence susceptibility to disruptions in energy homeostasis and metabolic regulation remain a challenge, and progress will entail the integration of multiple assessments of temporally dynamic environmental exposures in the context of each individual's genotype. To meet this challenge, researchers are increasingly exploring the epigenome, which is the malleable interface of gene-environment interactions. Epigenetic variation, whether innate or induced, contributes to variation in gene expression, the range of potential individual responses to internal and external cues, and risk for metabolic disease. Ultimately, advancement in our understanding of chronic disease susceptibility in humans will depend on refinement of exposure assessment tools and systems biology approaches to interpretation. In this review, we present recent progress in epigenetics of human obesity and diabetes, existing challenges, and the potential for new approaches to unravel the complex biology of metabolic dysregulation.

  2. In vivo sodium ({sup 23}Na) imaging of the human kidneys at 7 T: Preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Haneder, Stefan [University Medical Center Mannheim, Heidelberg University, Institute of Clinical Radiology and Nuclear Medicine, Mannheim (Germany); Medical University of Vienna/Vienna General Hospital, Department of Biomedical Imaging and Image-guided Therapy, Department of Radiology, Vienna (Austria); Juras, Vladimir; Trattnig, Siegfried; Zbyn, Stefan [Medical University of Vienna/Vienna General Hospital, Department of Biomedical Imaging and Image-guided Therapy, Department of Radiology, Vienna (Austria); Michaely, Henrik J.; Schoenberg, Stefan O. [University Medical Center Mannheim, Heidelberg University, Institute of Clinical Radiology and Nuclear Medicine, Mannheim (Germany); Deligianni, Xeni; Bieri, Oliver [University of Basel Hospital, Department of Radiology, Division of Radiological Physics, Basel (Switzerland)

    2014-02-15

    To evaluate the feasibility of in vivo {sup 23}Na imaging of the corticomedullary {sup 23}Na gradient and to measure {sup 23}Na transverse relaxation times (T2*) in human kidneys. In this prospective, IRB-approved study, eight healthy volunteers (4 female, 4 male; mean age 29.4 ± 3.6 years) were examined on a 7-T whole-body MR system using a {sup 23}Na-only spine-array coil. For morphological {sup 23}Na-MRI, a 3D gradient echo (GRE) sequence with a variable echo time scheme (vTE) was used. T2* times were calculated using a multiecho 3D vTE-GRE approach. {sup 23}Na signal-to-noise ratios (SNR) were given on a pixel-by-pixel basis for a 20-mm section from the cortex in the direction of the medulla. T2* maps were calculated by fitting the {sup 23}Na signal decay monoexponentially on a pixel-by-pixel basis, using least squares fit. Mean corticomedullary {sup 23}Na-SNR increased from the cortex (32.2 ± 5.6) towards the medulla (85.7 ± 16.0). The SNR increase ranged interindividually from 57.2 % to 66.3 %. Mean {sup 23}Na-T2* relaxation times differed statistically significantly (P < 0.001) between the cortex (17.9 ± 0.8 ms) and medulla (20.6 ± 1.0 ms). The aim of this study was to evaluate the feasibility of in vivo {sup 23}Na MRI of the corticomedullary {sup 23}Na gradient and to measure the {sup 23}Na T2* relaxation times of human kidneys at 7 T. (orig.)

  3. Recombinant human GLP-1(rhGLP-1) alleviating renal tubulointestitial injury in diabetic STZ-induced rats.

    Science.gov (United States)

    Yin, Weiqin; Xu, Shiqing; Wang, Zai; Liu, Honglin; Peng, Liang; Fang, Qing; Deng, Tingting; Zhang, Wenjian; Lou, Jinning

    2018-01-01

    GLP-1-based treatment improves glycemia through stimulation of insulin secretion and inhibition of glucagon secretion. Recently, more and more findings showed that GLP-1 could also protect kidney from diabetic nephropathy. Most of these studies focused on glomeruli, but the effect of GLP-1 on tubulointerstitial and tubule is not clear yet. In this study, we examined the renoprotective effect of recombinant human GLP-1 (rhGLP-1), and investigated the influence of GLP-1 on inflammation and tubulointerstitial injury using diabetic nephropathy rats model of STZ-induced. The results showed that rhGLP-1 reduced urinary albumin without influencing the body weight and food intake. rhGLP-1 could increased the serum C-peptide slightly but not lower fasting blood glucose significantly. In diabetic nephropathy rats, beside glomerular sclerosis, tubulointerstitial fibrosis was very serious. These lesions could be alleviated by rhGLP-1. rhGLP-1 decreased the expression of profibrotic factors collagen I, α-SMA, fibronectin, and inflammation factors MCP-1 and TNFα in tubular tissue and human proximal tubular cells (HK-2 cells). Furthermore, rhGLP-1 significantly inhibited the phosphorylation of NF-κB, MAPK in both diabetic tubular tissue and HK-2 cells. The inhibition of the expression of TNFα, MCP-1, collagen I and α-SMA in HK-2 cells by GLP-1 could be mimicked by blocking NF-κB or MAPK. These results indicate that rhGLP-1 exhibit renoprotective effect by alleviation of tubulointerstitial injury via inhibiting phosphorylation of MAPK and NF-κB. Therefore, rhGLP-1 may be a potential drug for treatment of diabetic nephropathy. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Non-invasive determination of metabolite concentrations in human transplanted kidney in vivo by 31P MR spectroscopy

    International Nuclear Information System (INIS)

    Kugel, H.; Wittsack, H.J.; Wenzel, F.; Heindel, W.; Lackner, K.; Stippel, D.

    2000-01-01

    To investigate concentrations of phosphorus-containing metabolites in human transplanted kidney in vivo by quantitative 31 P MR spectroscopy (MRS) using surface coils and to compare the obtained values with previous data. Material and Methods: In 5 patients with well-functioning transplanted kidneys, 31 P spectra were obtained with the three-dimensional localization image-selected in vivo spectroscopy technique applying a protocol for quantitative spectroscopy using surface coils. Relaxation corrected signal intensities determined by time domain fitting were used to derive absolute molar concentrations for phosphate-containing metabolites. Results: Little or no phosphocreatine in all spectra verified the absence of muscle contamination, confirming proper volume localization. The mean concentrations in the transplanted kidneys were as follows: ATP 1.60±0.26 mmol/l, PDE 2.14±0.91 mmol/l, Pi 0.66±0.25 mmol/l, PME 2.32±0.50 mmol/l. These values are consistent with previously reported values determined by other techniques. Conclusion: The non-invasive determination of absolute metabolite concentrations in human kidney using MRS supplements the use of signal intensity ratios to detect pathologic changes in the energy metabolism of transplanted kidneys

  5. Organ slices as an in vitro test system for drug metabolism in human liver, lung and kidney

    NARCIS (Netherlands)

    Olinga, Peter; de Jager, M.H; Meijer, D.K F; Groothuis, Geny; Merema, M.T.

    1999-01-01

    Metabolism of xenobiotics occurs mainly in the liver, but in addition, the lungs and kidneys may contribute considerably. The choice of the animal species during drug development as a predictive model for the human condition is often inadequate due to large interspecies differences. Therefore, a

  6. Human mesenchymal stem cells alter macrophage phenotype and promote regeneration via homing to the kidney following ischemia-reperfusion injury

    NARCIS (Netherlands)

    Wise, Andrea F; Williams, Timothy M; Kiewiet, Mensiena B G; Payne, Natalie L; Siatskas, Christopher; Samuel, Chrishan S; Ricardo, Sharon D

    2014-01-01

    Mesenchymal stem cells (MSCs) ameliorate injury and accelerate repair in many organs, including the kidney, although the reparative mechanisms and interaction with macrophages have not been elucidated. This study investigated the reparative potential of human bone marrow-derived MSCs and traced

  7. Ectopic expression of PTTG1/securin promotes tumorigenesis in human embryonic kidney cells

    Directory of Open Access Journals (Sweden)

    Malik Mohammed T

    2005-01-01

    Full Text Available Abstract Background Pituitary tumor transforming gene1 (PTTG1 is a novel oncogene that is expressed in most tumors. It encodes a protein that is primarily involved in the regulation of sister chromatid separation during cell division. The oncogenic potential of PTTG1 has been well characterized in the mouse, particularly mouse fibroblast (NIH3T3 cells, in which it induces cell proliferation, promotes tumor formation and angiogenesis. Human tumorigenesis is a complex and a multistep process often requiring concordant expression of a number of genes. Also due to differences between rodent and human cell biology it is difficult to extrapolate results from mouse models to humans. To determine if PTTG1 functions similarly as an oncogene in humans, we have characterized its effects on human embryonic kidney (HEK293 cells. Results We report that introduction of human PTTG1 into HEK293 cells through transfection with PTTG1 cDNA resulted in increased cell proliferation, anchorage-independent growth in soft agar, and formation of tumors after subcutaneous injection of nu/nu mice. Pathologic analysis revealed that these tumors were poorly differentiated. Both analysis of HEK293 cells transiently transfected with PTTG1 cDNA and analysis of tumors developed on injection of HEK293 cells that had been stably transfected with PTTG1 cDNA indicated significantly higher levels of secretion and expression of bFGF, VEGF and IL-8 compared to HEK293 cells transfected with pcDNA3.1 vector or uninvolved tissues collected from the mice. Mutation of the proline-rich motifs at the C-terminal of PTTG1 abolished its oncogenic properties. Mice injected with this mutated PTTG1 either did not form tumors or formed very small tumors. Taken together our results suggest that PTTG1 is a human oncogene that possesses the ability to promote tumorigenesis in human cells at least in part through the regulation of expression or secretion of bFGF, VEGF and IL-8. Conclusions Our results

  8. The archetype enhancer of simian virus 40 DNA is duplicated during virus growth in human cells and rhesus monkey kidney cells but not in green monkey kidney cells

    International Nuclear Information System (INIS)

    O'Neill, Frank J.; Greenlee, John E.; Carney, Helen

    2003-01-01

    Archetype SV40, obtained directly from its natural host, is characterized by a single 72-bp enhancer element. In contrast, SV40 grown in cell culture almost invariably exhibits partial or complete duplication of the enhancer region. This distinction has been considered important in studies of human tumor material, since SV40-associated tumor isolates have been described having a single enhancer region, suggesting natural infection as opposed to possible contamination by laboratory strains of virus. However, the behavior of archetypal SV40 in cultured cells has never been methodically studied. In this study we reengineered nonarchetypal 776-SV40 to contain a single 72-bp enhancer region and used this reengineered archetypal DNA to transfect a number of simian and human cell lines. SV40 DNA recovered from these cells was analyzed by restriction endonuclease analysis, PCR, and DNA sequencing. Reengineered archetype SV40 propagated in green monkey TC-7 or BSC-1 kidney cells remained without enhancer region duplication even after extensive serial virus passage. Archetype SV40 grown in all but one of the rhesus or human cell lines initially appeared exclusively archetypal. However, when virus from these cell types was transferred to green monkey cells, variants with partial enhancer duplication appeared after as little as a single passage. These findings suggest (1) that virus with a single 72-bp enhancer may persist in cultured cells of simian and human origin; (2) that variants with partially duplicated enhancer regions may arise within cell lines in quantities below limits of detection; (3) that these variants may enjoy a selective advantage in cell types other than those from which they arose (e.g., green monkey kidney cells); and (4) that certain cell lines may support a selective growth advantage for the variants without supporting their formation. Our data indicate that enhancer duplication may also occur in human as well as rhesus kidney cells. Thus, detection of

  9. Carboxylated nanodiamonds are neither cytotoxic nor genotoxic on liver, kidney, intestine and lung human cell lines.

    Science.gov (United States)

    Paget, V; Sergent, J A; Grall, R; Altmeyer-Morel, S; Girard, H A; Petit, T; Gesset, C; Mermoux, M; Bergonzo, P; Arnault, J C; Chevillard, S

    2014-08-01

    Although nanodiamonds (NDs) appear as one of the most promising nanocarbon materials available so far for biomedical applications, their risk for human health remains unknown. Our work was aimed at defining the cytotoxicity and genotoxicity of two sets of commercial carboxylated NDs with diameters below 20 and 100 nm, on six human cell lines chosen as representative of potential target organs: HepG2 and Hep3B (liver), Caki-1 and Hek-293 (kidney), HT29 (intestine) and A549 (lung). Cytotoxicity of NDs was assessed by measuring cell impedance (xCELLigence® system) and cell survival/death by flow cytometry while genotoxicity was assessed by γ-H2Ax foci detection, which is considered the most sensitive technique for studying DNA double-strand breaks. To validate and check the sensitivity of the techniques, aminated polystyrene nanobeads were used as positive control in all assays. Cell incorporation of NDs was also studied by flow cytometry and luminescent N-V center photoluminescence (confirmed by Raman microscopy), to ensure that nanoparticles entered the cells. Overall, we show that NDs effectively entered the cells but NDs do not induce any significant cytotoxic or genotoxic effects on the six cell lines up to an exposure dose of 250 µg/mL. Taken together these results strongly support the huge potential of NDs for human nanomedicine but also their potential as negative control in nanotoxicology studies.

  10. Value of urinary trace proteins in evaluating kidney function in the course of diabetes mellitus II rehabilitation%尿微量蛋白检测在 2型糖尿病中评估肾功能的价值

    Institute of Scientific and Technical Information of China (English)

    陈宝平; 宋新瑞

    2001-01-01

    Objective To discuss the value of urinary trace proteins in evaluating kidney function in the course of diabetes mellitus II rehabilitation.Method To assay level of urinary trace proteins in 50 cases of diabetes mellitus II and healthy control subjects. Result Level of trace proteins in 40 cases with diabetes mellitus ranged between normal values.They showed significantly increased urinary trace proteins(80% ).Conclusion Urinary trace proteins is a sensible indicator for evaluating kidney function in diabetes mellitus II.

  11. Knockout of Na-glucose transporter SGLT2 attenuates hyperglycemia and glomerular hyperfiltration but not kidney growth or injury in diabetes mellitus

    Science.gov (United States)

    Rose, Michael; Gerasimova, Maria; Satriano, Joseph; Platt, Kenneth A.; Koepsell, Hermann; Cunard, Robyn; Sharma, Kumar; Thomson, Scott C.; Rieg, Timo

    2013-01-01

    The Na-glucose cotransporter SGLT2 mediates high-capacity glucose uptake in the early proximal tubule and SGLT2 inhibitors are developed as new antidiabetic drugs. We used gene-targeted Sglt2 knockout (Sglt2−/−) mice to elucidate the contribution of SGLT2 to blood glucose control, glomerular hyperfiltration, kidney growth, and markers of renal growth and injury at 5 wk and 4.5 mo after induction of low-dose streptozotocin (STZ) diabetes. The absence of SGLT2 did not affect renal mRNA expression of glucose transporters SGLT1, NaGLT1, GLUT1, or GLUT2 in response to STZ. Application of STZ increased blood glucose levels to a lesser extent in Sglt2−/− vs. wild-type (WT) mice (∼300 vs. 470 mg/dl) but increased glucosuria and food and fluid intake to similar levels in both genotypes. Lack of SGLT2 prevented STZ-induced glomerular hyperfiltration but not the increase in kidney weight. Knockout of SGLT2 attenuated the STZ-induced renal accumulation of p62/sequestosome, an indicator of impaired autophagy, but did not attenuate the rise in renal expression of markers of kidney growth (p27 and proliferating cell nuclear antigen), oxidative stress (NADPH oxidases 2 and 4 and heme oxygenase-1), inflammation (interleukin-6 and monocyte chemoattractant protein-1), fibrosis (fibronectin and Sirius red-sensitive tubulointerstitial collagen accumulation), or injury (renal/urinary neutrophil gelatinase-associated lipocalin). SGLT2 deficiency did not induce ascending urinary tract infection in nondiabetic or diabetic mice. The results indicate that SGLT2 is a determinant of hyperglycemia and glomerular hyperfiltration in STZ-induced diabetes mellitus but is not critical for the induction of renal growth and markers of renal injury, inflammation, and fibrosis. PMID:23152292

  12. Effects of Intensive Control of Glycemia on Clinical Kidney Outcomes in Type 2 Diabetes Patients Compared with Standard Control: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Francisco Herrera-Gómez

    2017-11-01

    Full Text Available Background: Association between poor control of glycemia and the onset of microvascular complications in type 2 diabetes mellitus (T2DM patients is a hard issue. However, it seems that the impact of pharmacological treatment is important only in early stages of diabetic nephropathy. We sought to examine whether intensive glycemic control is associated with improvement of clinical Chronic Kidney Disease (CKD outcomes compared to standard glycemic control.Methods: Meta-analysis of published and unpublished randomized controlled trials (RCT and post-hoc analysis of RCTs comparing anti-diabetic drugs and/or insulin (intensive control vs. dietary measures (standard control for relevant outcomes related to progression of CKD clinically manifest was undertaken. Summary estimates obtained by random effects model and funnel plots for assessing reporting bias are presented.Results: Our analysis was based on four RCTs representing 27,391 adult T2DM patients with CKD from around the world. The pooled OR for the outcomes of doubling of serum creatinine and need of dialysis were, respectively, of 0.98 with 95% confidence interval (95% CI 0.81–1.19, and 0.84 with 95% CI 0.69–1.02. The pooled OR for the outcome of death from kidney failure was 0.62 with 95% CI 0.39–0.98. Clinical differences between studies were not translated in statistical heterogeneity. Reporting bias may be present.Conclusions: Intensive glycemic control has an effect on death from kidney failure compared to standard glycemic control. Better comprehension of glycemic control effects on both T2DM patients with and without CKD is important for individualization of these two treatment modalities.

  13. Attenuation of inflammatory response by a novel chalcone protects kidney and heart from hyperglycemia-induced injuries in type 1 diabetic mice

    International Nuclear Information System (INIS)

    Fang, Qilu; Wang, Jingying; Wang, Lintao; Zhang, Yali; Yin, Haimin; Li, Yunzhou; Tong, Chao; Liang, Guang; Zheng, Chao

    2015-01-01

    High glucose-induced inflammatory response in diabetic complications plays an important role in disease occurrence and development. With inflammatory cytokines and signaling pathways as important mediators, targeting inflammation may be a new avenue for treating diabetic complications. Chalcones are a class of natural products with various pharmacological activities. Previously, we identified L2H17 as a chalcone with good anti-inflammatory activity, inhibiting LPS-induced inflammatory response in macrophages. In this study, we examined L2H17's effect on hyperglycemia-induced inflammation both in mouse peritoneal macrophages and a streptozotocin-induced T1D mouse model. Our results indicate that L2H17 exhibits a strong inhibitory effect on the expression of pro-inflammatory cytokines, cell adhesion molecules, chemokines and macrophage adhesion via modulation of the MAPK/NF-κB pathway. Furthermore, in vivo oral administration of L2H17 resulted in a significant decrease in the expression of pro-inflammatory cytokines and cell adhesion molecules, contributing to a reduction of key markers for renal and cardiac dysfunction and improvements in fibrosis and pathological changes in both renal and cardiac tissues of diabetic mice. These findings provide the evidence supporting targeting MAPK/NF-κB pathway may be effective therapeutic strategy for diabetic complications, and suggest that L2H17 may be a promising anti-inflammatory agent with potential as a therapeutic agent in the treatment of renal and cardiac diabetic complications. - Highlights: • Chalcones are a class of natural products with various pharmacological activities. • We identified L2H17 a chalcone with good anti-inflammatory activity. • L2H17 improved histological abnormalities both in diabetic heart and kidney. • L2H17 reduced inflammatory responses in HG-stimulated mouse peritoneal macrophages. • MAPKs/NF-κB pathway may be a promising therapeutic target for diabetic complications.

  14. Attenuation of inflammatory response by a novel chalcone protects kidney and heart from hyperglycemia-induced injuries in type 1 diabetic mice

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Qilu [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Diabetes Center and Department of Endocrinology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang (China); Wang, Jingying; Wang, Lintao; Zhang, Yali [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Yin, Haimin [Diabetes Center and Department of Endocrinology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang (China); Li, Yunzhou [Hunter Holmes McGuire VA Medical Center, Richmond, VA 23249 (United States); Tong, Chao [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Liang, Guang, E-mail: wzmcliangguang@163.com [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Zheng, Chao, E-mail: wallbb_1022@163.com [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Diabetes Center and Department of Endocrinology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang (China)

    2015-10-15

    High glucose-induced inflammatory response in diabetic complications plays an important role in disease occurrence and development. With inflammatory cytokines and signaling pathways as important mediators, targeting inflammation may be a new avenue for treating diabetic complications. Chalcones are a class of natural products with various pharmacological activities. Previously, we identified L2H17 as a chalcone with good anti-inflammatory activity, inhibiting LPS-induced inflammatory response in macrophages. In this study, we examined L2H17's effect on hyperglycemia-induced inflammation both in mouse peritoneal macrophages and a streptozotocin-induced T1D mouse model. Our results indicate that L2H17 exhibits a strong inhibitory effect on the expression of pro-inflammatory cytokines, cell adhesion molecules, chemokines and macrophage adhesion via modulation of the MAPK/NF-κB pathway. Furthermore, in vivo oral administration of L2H17 resulted in a significant decrease in the expression of pro-inflammatory cytokines and cell adhesion molecules, contributing to a reduction of key markers for renal and cardiac dysfunction and improvements in fibrosis and pathological changes in both renal and cardiac tissues of diabetic mice. These findings provide the evidence supporting targeting MAPK/NF-κB pathway may be effective therapeutic strategy for diabetic complications, and suggest that L2H17 may be a promising anti-inflammatory agent with potential as a therapeutic agent in the treatment of renal and cardiac diabetic complications. - Highlights: • Chalcones are a class of natural products with various pharmacological activities. • We identified L2H17 a chalcone with good anti-inflammatory activity. • L2H17 improved histological abnormalities both in diabetic heart and kidney. • L2H17 reduced inflammatory responses in HG-stimulated mouse peritoneal macrophages. • MAPKs/NF-κB pathway may be a promising therapeutic target for diabetic complications.

  15. Doubling of serum creatinine and the risk of cardiovascular outcomes in patients with chronic kidney disease and type 2 diabetes mellitus: a cohort study

    Directory of Open Access Journals (Sweden)

    Schneider C

    2016-06-01

    Full Text Available Cornelia Schneider,1,2 Blai Coll,3 Susan S Jick,4 Christoph R Meier1,2,4 1Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland; 2Hospital Pharmacy, University Hospital Basel, Basel, Switzerland; 3Renal Development, AbbVie, North Chicago, IL, USA; 4Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, MA, USA Background: Doubling of serum creatinine is often used as a marker for worsening kidney function in nephrology trials. Most people with chronic kidney disease die of other causes before reaching end-stage renal disease. We were interested in the association between doubling of serum creatinine and the risk of a first-time diagnosis of angina pectoris, congestive heart failure (CHF, myocardial infarction (MI, stroke, or transient ischemic attack in patients with chronic kidney disease and with diagnosed type 2 diabetes mellitus. Methods: We identified all adult patients registered in the “Clinical Practice Research Datalink” between 2002 and 2011 with incident chronic kidney disease and type 2 diabetes mellitus and did a cohort study with a Cox proportional hazard analysis. Results: We identified in total 27,811 patients, 693 developed angina pectoris, 1,069 CHF, 508 MI, 970 stroke, and 578 transient ischemic attacks. Patients whose serum creatinine doubled during follow-up had increased risks of CHF (hazard ratio [HR] 2.98, 95% confidence interval [CI] 2.27–3.89, MI (HR 2.53, 95% CI 1.62–3.96, and stroke (HR 1.93, 95% CI 1.38–2.69, as compared with patients whose serum creatinine did not double. The relative risks of angina pectoris (HR 1.18, 95% CI 0.66–2.10 or a transient ischemic attack (HR 1.32, 95% CI 0.78–2.22 were similar in both groups. Conclusion: Diabetic patients with a doubling of serum creatinine were at an increased risk of CHF, MI, or stroke, compared with diabetic

  16. A randomized controlled study of finerenone vs. eplerenone in patients with worsening chronic heart failure and diabetes mellitus and/or chronic kidney disease

    DEFF Research Database (Denmark)

    Filippatos, Gerasimos; Anker, Stefan D; Böhm, Michael

    2016-01-01

    Aims To evaluate oral doses of the non-steroidal mineralocorticoid receptor antagonist finerenone given for 90 days in patients with worsening heart failure and reduced ejection fraction and chronic kidney disease and/or diabetes mellitus. Methods and results Miner Alocorticoid Receptor antagonist...... Tolerability Study-Heart Failure (ARTS-HF) was a randomized, double-blind, phase 2b multicentre study (ClinicalTrials.gov: NCT01807221). Of 1286 screened patients, 1066 were randomized. Patients received oral, once-daily finerenone (2.5, 5, 7.5, 10, or 15 mg, uptitrated to 5, 10, 15, 20, or 20 mg, respectively...

  17. [Gene transfer-induced human heme oxygenase-1 over-expression protects kidney from ischemia-reperfusion injury in rats].

    Science.gov (United States)

    Lü, Jin-xing; Yan, Chun-yin; Pu, Jin-xian; Hou, Jian-quan; Yuan, He-xing; Ping, Ji-gen

    2010-12-14

    To study the protection of gene transfer-induced human heme oxygenase-1 over-expression against renal ischemia reperfusion injury in rats. The model of kidney ischemia-reperfusion injury was established with Sprague-Dawley rats. In the therapy group (n=18), the left kidney was perfused and preserved with Ad-hHO-1 at 2.5×10(9) pfu/1.0 ml after flushed with 0-4°C HC-A organ storage solution via donor renal aorta. The rats in control groups were perfused with 0.9% saline solution (n=12) or the vector carrying no interest gene Ad-EGFP 2.5×10(9) pfu/1.0 ml (n=18) instead of Ad-hHO-1. BUN and Cr in serum were measured by slide chemical methods. The kidney samples of rats were harvested for assay of histology, immunohistochemistry and quantification of HO enzymatic activity. Apoptosis cells in the kidney were measured by TUNEL. Ad-hHO-1 via donor renal aorta could transfect renal cells of rats effectively, enzymatic activity of HO in treated group [(1.62±0.07) nmol×mg(-1)×min(-1)] is higher than in control groups treated with saline solution team [(1.27±0.07) nmol×mg(-1)×min(-1)] and vector EGFP team [(1.22±0.06) nmol×mg(-1)×min(-1)] (PhHO-1 expressed hHO-1 in kidneys at a high level. Corresponding to this, the level of BUN and Cr, as well as the number of apoptosis cells, were decreased, and the damage in histology by HE staining was ameliorated. Over-expression of human HO-1 can protect the kidney from ischemia/reperfusion injury in rats.

  18. Human Embryonic Kidney 293 Cells: A Vehicle for Biopharmaceutical Manufacturing, Structural Biology, and Electrophysiology.

    Science.gov (United States)

    Hu, Jianwen; Han, Jizhong; Li, Haoran; Zhang, Xian; Liu, Lan Lan; Chen, Fei; Zeng, Bin

    2018-01-01

    Mammalian cells, e.g., CHO, BHK, HEK293, HT-1080, and NS0 cells, represent important manufacturing platforms in bioengineering. They are widely used for the production of recombinant therapeutic proteins, vaccines, anticancer agents, and other clinically relevant drugs. HEK293 (human embryonic kidney 293) cells and their derived cell lines provide an attractive heterologous system for the development of recombinant proteins or adenovirus productions, not least due to their human-like posttranslational modification of protein molecules to provide the desired biological activity. Secondly, they also exhibit high transfection efficiency yielding high-quality recombinant proteins. They are easy to maintain and express with high fidelity membrane proteins, such as ion channels and transporters, and thus are attractive for structural biology and electrophysiology studies. In this article, we review the literature on HEK293 cells regarding their origins but also stress their advancements into the different cell lines engineered and discuss some significant aspects which make them versatile systems for biopharmaceutical manufacturing, drug screening, structural biology research, and electrophysiology applications. © 2018 S. Karger AG, Basel.

  19. Antihyperglycaemic and organic protective effects on pancreas, liver and kidney by polysaccharides from Hericium erinaceus SG-02 in streptozotocin-induced diabetic mice.

    Science.gov (United States)

    Zhang, Chen; Li, Juan; Hu, Chunlong; Wang, Jing; Zhang, Jianjun; Ren, Zhenzhen; Song, Xinling; Jia, Le

    2017-09-07

    The present work was designed to investigate the antihyperglycaemic and protective effects of two Hericium erinaceus intracellular polysaccharide (HIPS) purified fractions (HIPS1 and HIPS2) from mycelia of H. erinaceus SG-02 on pancreas, liver and kidney in streptozotocin (STZ)-induced diabetic mice. The supplementation of HIPS1 and HIPS2 significantly decreased the blood glucose (GLU) levels; suppressed the abnormal elevations of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen (BUN) and creatinine (CRE) levels in serum; improved the antioxidant enzymatic (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)) activities; and attenuated the pathological damage to these organs. The HIPS1 showed superior effects in antihyperglycaemia and organic protection than HIPS2 possible owing to the abundant functional groups (-NH 2 , -COOH and S=O) in HIPS1, indicating that H. erinaceus SG-02 could be used as a functional food and natural drug for the prevention of diabetes and its complications.

  20. Characterization of human kidney stones using micro-PIXE and RBS: A comparative study between two different populations

    International Nuclear Information System (INIS)

    Pineda-Vargas, C.A.; Eisa, M.E.M.; Rodgers, A.L.

    2009-01-01

    The micro-PIXE and RBS techniques are used to investigate the matrix as well as the trace elemental composition of calcium-rich human tissues on a microscopic scale. This paper deals with the spatial distribution of trace metals in hard human tissues such as kidney stone concretions, undertaken at the nuclear microprobe (NMP) facility. Relevant information about ion beam techniques used for material characterization will be discussed. Mapping correlation between different trace metals to extract information related to micro-regions composition will be illustrated with an application using proton energies of 1.5 and 3.0 MeV and applied to a comparative study for human kidney stone concretions nucleation region analysis from two different population groups (Sudan and South Africa)

  1. Pakistan's kidney trade: an overview of the 2007 'Transplantation of Human Organs and Human Tissue Ordinance.' To what extent will it curb the trade?

    Science.gov (United States)

    Raza, Mohsen; Skordis-Worrall, Jolene

    2012-01-01

    Pakistan has the unenviable reputation for being one of the world's leading 'transplant tourism' destinations, largely the buying and selling of kidneys from its impoverished population to rich international patients. After nearly two decades of pressure to formally prohibit the trade, the Government of Pakistan promulgated the 'Transplantation of Human Organs and Human Tissue Ordinance' (THOTO) in 2007. This was then passed by Senate and enshrined in law in March 2010. This paper gives a brief overview of the organ trade within Pakistan and analyses the criteria of THOTO in banning the widespread practise. It then goes on to answer: 'To what extent will THOTO succeed in curbing Pakistan's kidney trade?' This is aided by the use of a comparative case study looking at India's failed organ trade legislation. This paper concludes THOTO has set a strong basis for curbing Pakistan's kidney trade. However, for this to be successfully achieved, it needs to be implemented with strong and sustained political will, strict and efficient enforcement as well as effective monitoring and evaluation. Efforts are needed to tackle both 'supply' and 'demand' factors of Pakistan's kidney trade, with developed countries also having a responsibility to reduce the flow of citizens travelling to Pakistan to purchase a kidney.

  2. A murine model of type 2 diabetes mellitus developed using a combination of high fat diet and multiple low doses of streptozotocin treatment mimics the metabolic characteristics of type 2 diabetes mellitus in humans.

    Science.gov (United States)

    Nath, Sayantan; Ghosh, Sankar Kumar; Choudhury, Yashmin

    A murine model of type 2 diabetes mellitus was used to compare the antidiabetic effects of the dipeptidyl peptidase-4 (DPP4) inhibitor vildagliptin and biguanide, metformin. Swiss albino mice (n=20 males; n=25 females) were given high fat diet (HFD) ad libitum for 3weeks followed by low dose (40mgkg -1 body weight, bw daily) of streptozotocin (STZ) intraperitoneally five times from the 22nd day of treatment onwards, with HFD continued up to 26th day. Controls (n=15 males; n=15 females) were fed normal balanced diet without administration of STZ. Successful induction of diabetes mellitus was confirmed by testing for fasting blood glucose, intraperitoneal glucose tolerance and intraperitoneal insulin sensitivity. Diabetic mice were administered vildagliptin (10mgkg -1 bw daily) and metformin (50mgkg -1 bw daily) orally for 4weeks. Control, diabetic, vildagliptin and metformin-treated diabetic mice were evaluated for alterations in lipid profile using blood serum and histopathology and oxidative stress using tissues including liver, kidney and heart. Diabetic mice showed significant alterations in lipid profile, tissue histopathology, impaired glucose tolerance, lower insulin sensitivity and elevated lipid peroxidation and protein carbonylation, with depressed catalase activity, when compared to age and gender-matched controls. Metformin and vildagliptin ameliorated the abovementioned diabetic conditions, with vildagliptin found to be more effective. A murine model developed by the combination of HFD and multiple low dose of STZ mimics the metabolic characteristics of type 2 diabetes mellitus in humans, and may be useful for antidiabetic drug screening. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Obesity and kidney disease

    Directory of Open Access Journals (Sweden)

    Geraldo Bezerra da Silva Junior

    Full Text Available Abstract Obesity has been pointed out as an important cause of kidney diseases. Due to its close association with diabetes and hypertension, excess weight and obesity are important risk factors for chronic kidney disease (CKD. Obesity influences CKD development, among other factors, because it predisposes to diabetic nephropathy, hypertensive nephrosclerosis and focal and segmental glomerulosclerosis. Excess weight and obesity are associated with hemodynamic, structural and histological renal changes, in addition to metabolic and biochemical alterations that lead to kidney disease. Adipose tissue is dynamic and it is involved in the production of "adipokines", such as leptin, adiponectin, tumor necrosis factor-α, monocyte chemoattractant protein-1, transforming growth factor-β and angiotensin-II. A series of events is triggered by obesity, including insulin resistance, glucose intolerance, dyslipidemia, atherosclerosis and hypertension. There is evidence that obesity itself can lead to kidney disease development. Further studies are required to better understand the association between obesity and kidney disease.

  4. Calcium isotope signature: new proxy for net change in bone volume for chronic kidney disease and diabetic rats.

    Science.gov (United States)

    Tanaka, Yu-Ki; Yajima, Nobuyuki; Higuchi, Yusuke; Yamato, Hideyuki; Hirata, Takafumi

    2017-12-01

    Herein, we measure the Ca isotope ratios ( 44 Ca/ 42 Ca and 43 Ca/ 42 Ca) in serum and bone samples collected from rats with chronic kidney disease (CKD) or diabetes mellitus (DM). For the serum samples, the isotope ratios are lower for the CKD (δ 44 Ca/ 42 Ca serum = 0.16 ± 0.11‰; 2SD, n = 6) and the DM (δ 44 Ca/ 42 Ca serum = -0.11 ± 0.25‰; 2SD, n = 7) rats than that for the control rats (δ 44 Ca/ 42 Ca serum = 0.25 ± 0.04‰; 2SD, n = 7). Bone samples from two distinct positions of 20 rats in total, namely, the center and proximal parts of the tibial diaphysis, are subject to Ca isotope analysis. The resulting δ 44 Ca/ 42 Ca values for the bone of the proximal part are about 0.3‰ lower than that for the serum samples from the same rats. The larger isotope fractionations between the serum and bone are consistent with previously reported data for vertebrate animals (e.g., Skulan and DePaolo, 1999), which suggests the preferential incorporation of lighter Ca isotopes through bone formation. For the bones from the control and CKD rats, there were no differences in the δ 44 Ca/ 42 Ca values between the positions of the bone. In contrast, the δ 44 Ca/ 42 Ca values of the bone for the DM rats were different between the positions of the bone. Due to the lower bone turnover rate for the DM rats, the δ 44 Ca/ 42 Ca for the middle of the diaphysis can reflect the Ca isotopes in the bone formed prior to the progression of DM states. Thus, the resulting δ 44 Ca/ 42 Ca values show a clear correlation with bone mineral density (BMD). This can be due to the release of isotopically lighter Ca from the bone to the serum. In the present study, our data demonstrate that the δ 44 Ca/ 42 Ca value for serum can be used as a new biomarker for evaluating changes in bone turnover rate, followed by changes in bone volume.

  5. Diabetes HealthSense: Resources for Living Well

    Medline Plus

    Full Text Available ... treatment methods from others living with diabetes. Heart Disease and Diabetes 6 Heart disease is the number ... their diagnoses and support networks. Diabetes and Kidney Disease 12 Diabetes is the leading cause of kidney ...

  6. The association of the human development index with global kidney cancer incidence and mortality.

    Science.gov (United States)

    Patel, Amit R; Prasad, Sandip M; Shih, Ya-Chen Tina; Eggener, Scott E

    2012-06-01

    We describe contemporary worldwide age standardized incidence and mortality rates for kidney cancer, and their association with social and economic development metrics. We obtained gender specific, age standardized incidence and mortality rates for 184 countries and 16 major world regions from the GLOBOCAN 2008 database. We compared the mortality-to-incidence ratio on the national and regional levels in males and females, and assessed the association with the development level of each country using the United Nations Human Development Index. The age standardized incidence rate varied twentyfold worldwide with the highest rate in North America, and the lowest in Africa and South Central Asia (11.8 vs 1.2 and 1.0/100,000 individuals, respectively). The geographic distribution of the age standardized mortality rate was similar to that of the age standardized incidence rate with the highest rates in Europe and North America (3.1 and 2.6/100,000 individuals, respectively) and the lowest rates in Asian and African regions (0.6 to 1.5). Age standardized incidence and mortality rates were 4.5 and 2.8 times higher, respectively, in more developed countries than in developing countries. However, the mortality-to-incidence ratio was highest in Africa and Asia, and lowest in North America (0.6 to 0.8 vs 0.2/100,000 individuals). There was a strong inverse relationship between the Human Development Index and the mortality-to-incidence ratio (regression coefficient -0.79, p<0.0001). Kidney cancer incidence and mortality rates vary widely throughout the world while the mortality-to-incidence ratio is highest in less developed nations. These observations suggest significant health care disparities and may reflect differences in risk factors, health care access, quality of care, diagnostic modalities and treatment options available. Future research should assess whether the mortality-to-incidence ratio decreases with increasing development. Copyright © 2012 American Urological

  7. Dioxins, furans and dioxin-like PCBs in human blood: causes or consequences of diabetic nephropathy?

    Science.gov (United States)

    Everett, Charles J; Thompson, Olivia M

    2014-07-01

    Nephropathy, or kidney disease, is a major, potential complication of diabetes. We assessed the association of 6 chlorinated dibenzo-p-dioxins, 9 chlorinated dibenzofurans and 8 polychlorinated biphenyls (PCBs) in blood with diabetic nephropathy in the 1999-2004 National Health and Nutrition Examination Survey (unweighted N=2588, population estimate=117,658,357). Diabetes was defined as diagnosed or undiagnosed (glycohemoglobin ≥ 6.5%) and nephropathy defined as urinary albumin to creatinine ratio >30 mg/g, representing microalbuminuria or macroalbuminuria. For the 8 chemicals analyzed separately, values above the 75th percentile were considered elevated, whereas for the other 15 compounds values above the maximum limit of detection were considered elevated. Seven of 8 dioxins and dioxin-like compounds, analyzed separately, were found to be associated with diabetic nephropathy. The chemicals associated with diabetic nephropathy were: 1,2,3,6,7,8-Hexachlorodibenzo-p-dioxin; 1,2,3,4,6,7,8,9-Octachlorodibenzo-p-dioxin; 2,3,4,7,8-Pentachlorodibenzofuran; PCB 126; PCB 169; PCB 118; and PCB 156. Three of the 8 dioxins and dioxin-like compounds; 1,2,3,4,6,7,8,9-Octachlorodibenzo-p-dioxin; 2,3,4,7,8-Pentachlorodibenzofuran and PCB 118; expressed as log-transformed continuous variables; were associated with diabetes without nephropathy. When 4 or more of the 23 chemicals were elevated the odds ratios were 7.00 (95% CI=1.80-27.20) for diabetic nephropathy and 2.13 (95% CI=0.95-4.78) for diabetes without nephropathy. Log-transformed toxic equivalency (TEQ) was associated with both diabetic nephropathy, and diabetes without nephropathy, the odds ratios were 2.35 (95% CI=1.57-3.52) for diabetic nephropathy, and 1.44 (95% CI=1.11-1.87) for diabetes without nephropathy. As the kidneys function to remove waste products from the blood, diabetic nephropathy could be either the cause or the consequence (or both) of exposure to dioxins, furans and dioxin-like PCBs. Copyright © 2014

  8. Epigenetics of kidney disease.

    Science.gov (United States)

    Wanner, Nicola; Bechtel-Walz, Wibke

    2017-07-01

    DNA methylation and histone modifications determine renal programming and the development and progression of renal disease. The identification of the way in which the renal cell epigenome is altered by environmental modifiers driving the onset and progression of renal diseases has extended our understanding of the pathophysiology of kidney disease progression. In this review, we focus on current knowledge concerning the implications of epigenetic modifications during renal disease from early development to chronic kidney disease progression including renal fibrosis, diabetic nephropathy and the translational potential of identifying new biomarkers and treatments for the prevention and therapy of chronic kidney disease and end-stage kidney disease.

  9. XYLITOL IMPROVES ANTI-OXIDATIVE DEFENSE SYSTEM IN SERUM, LIVER, HEART, KIDNEY AND PANCREAS OF NORMAL AND TYPE 2 DIABETES MODEL OF RATS.

    Science.gov (United States)

    Chukwuma, Chika Ifeanyi; Islam, Shahidul

    2017-05-01

    The present study investigated the anti-oxidative effects of xylitol both in vitro and in vivo in normal and type 2 diabetes (T2D) rat model. Free radical scavenging and ferric reducing potentials of different concentrations of xylitol were investigated in vitro. For in vivo study, six weeks old male Sprague-Dawley rats were divided into four groups, namely: Normal Control (NC), Diabetic Control (DBC), Normal Xylitol (NXYL) and Diabetic Xylitol (DXYL). T2D was induced in the DBC and DXYL groups. After the confirmation of diabetes, a 10% xylitol solution was supplied instead of drinking water to NXYL and DXYL, while normal drinking water was supplied to NC and DBC ad libitum. After five weeks intervention period, the animals were sacri- ficed and thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) concentrations as well as superoxide dismutase, catalase glutathione reductase and glutathione peroxidase activities were determined in the liver, heart, kidney, pancreatic tissues and serum samples. Xylitol exhibited significant (p foods and food products.

  10. Influence of diabetes mellitus on immunity to human tuberculosis.

    Science.gov (United States)

    Kumar Nathella, Pavan; Babu, Subash

    2017-09-01

    Type 2 diabetes mellitus(DM) is a major risk factor for the development of active pulmonary tuberculosis (TB), with development of DM pandemic in countries where TB is also endemic. Understanding the impact of DM on TB and the determinants of co-morbidity is essential in responding to this growing public health problem with improved therapeutic approaches. Despite the clinical and public health significance posed by the dual burden of TB and DM, little is known about the immunological and biochemical mechanisms of susceptibility. One possible mechanism is that an impaired immune response in patients with DM facilitates either primary infection with Mycobacterium tuberculosis or reactivation of latent TB. Diabetes is associated with immune dysfunction and alterations in the components of the immune system, including altered levels of specific cytokines and chemokines. Some effects of DM on adaptive immunity that are potentially relevant to TB defence have been identified in humans. In this review, we summarize current findings regarding the alterations in the innate and adaptive immune responses and immunological mechanisms of susceptibility of patients with DM to M. tuberculosis infection and disease. © 2017 John Wiley & Sons Ltd.

  11. Avocado oil induces long-term alleviation of oxidative damage in kidney mitochondria from type 2 diabetic rats by improving glutathione status.

    Science.gov (United States)

    Ortiz-Avila, Omar; Figueroa-García, María Del Consuelo; García-Berumen, Claudia Isabel; Calderón-Cortés, Elizabeth; Mejía-Barajas, Jorge A; Rodriguez-Orozco, Alain R; Mejía-Zepeda, Ricardo; Saavedra-Molina, Alfredo; Cortés-Rojo, Christian

    2017-04-01

    Hyperglycemia and mitochondrial ROS overproduction have been identified as key factors involved in the development of diabetic nephropathy. This has encouraged the search for strategies decreasing glucose levels and long-term improvement of redox status of glutathione, the main antioxidant counteracting mitochondrial damage. Previously, we have shown that avocado oil improves redox status of glutathione in liver and brain mitochondria from streptozotocin-induced diabetic rats; however, the long-term effects of avocado oil and its hypoglycemic effect cannot be evaluated because this model displays low survival and insulin depletion. Therefore, we tested during 1 year the effects of avocado oil on glycemia, ROS levels, lipid peroxidation and glutathione status in kidney mitochondria from type 2 diabetic Goto-Kakizaki rats. Diabetic rats exhibited glycemia of 120-186 mg/dL the first 9 months with a further increase to 250-300 mg/dL. Avocado oil decreased hyperglycemia at intermediate levels between diabetic and control rats. Diabetic rats displayed augmented lipid peroxidation and depletion of reduced glutathione throughout the study, while increased ROS generation was observed at the 3rd and 12th months along with diminished content of total glutathione at the 6th and 12th months. Avocado oil ameliorated all these defects and augmented the mitochondrial content of oleic acid. The beneficial effects of avocado oil are discussed in terms of the hypoglycemic effect of oleic acid and the probable dependence of glutathione transport on lipid peroxidation and thiol oxidation of mitochondrial carriers.

  12. Epithelial hyperplasia in human polycystic kidney diseases. Its role in pathogenesis and risk of neoplasia.

    OpenAIRE

    Bernstein, J.; Evan, A. P.; Gardner, K. D.

    1987-01-01

    The importance of tubular epithelial hyperplasia in polycystic kidney diseases has become apparent during the last decade. Micropapillary hyperplasia occurs in autosomal dominant polycystic kidney disease, in localized cystic disease, and in acquired cystic disease. Neoplastic or severely dysplastic epithelial hyperplasia occurs in von Hippel-Lindau disease. A histopathologically distinctive epithelial hyperplasia occurs in tuberous sclerosis. In each of these conditions, epithelial hyperplas...

  13. Type 2 diabetes

    Science.gov (United States)

    ... type 2 diabetes; Oral hypoglycemic - type 2 diabetes; High blood sugar - type 2 diabetes ... your kidneys are working well ( microalbuminuria and serum creatinine ). Visit your eye doctor at least once a ...

  14. Expression of the vitamin D receptor, 25-hydroxylases, 1alpha-hydroxylase and 24-hydroxylase in the human kidney and renal clear cell cancer

    DEFF Research Database (Denmark)

    Blomberg Jensen, Martin; Andersen, Claus B.; Nielsen, John E

    2010-01-01

    The vitamin D receptor (VDR), CYP27B1 and CYP24A1 are expressed in the human kidney, but the segmental expression of the 25-hydroxylases is unknown. A comprehensive analysis of CYP2R1, CYP27A1, CYP27B1, VDR and CYP24A1 expression in normal kidney and renal clear cell cancer (CCc) would reveal...

  15. Evaluation of Porcine Pancreatic Islets Transplanted in the Kidney Capsules of Diabetic Mice Using a Clinically Approved Superparamagnetic Iron Oxide (SPIO) and a 1.5T MR Scanner

    International Nuclear Information System (INIS)

    Kim, Hoe Suk; Kim, Hyoung Su; Park, Kyong Soo; Moon, Woo Kyung

    2010-01-01

    To evaluate transplanted porcine pancreatic islets in the kidney capsules of diabetic mice using a clinically approved superparamagnetic iron oxide (SPIO) and a 1.5T MR scanner. Various numbers of porcine pancreatic islets labeled with Resovist, a carboxydextran-coated SPIO, were transplanted into the kidney capsules of normal mice and imaged with a 3D FIESTA sequence using a 1.5T clinical MR scanner. Labeled (n = 3) and unlabeled (n = 2) islets were transplanted into the kidney capsules of streptozotocin-induced diabetic mice. Blood glucose levels and MR signal intensities were monitored for 30 days post-transplantation. There were no significant differences in viability or insulin secretion between labeled and unlabeled islets. A strong correlation (γ 2 > 0.94) was evident between the number of transplanted islets and T 2 relaxation times quantified by MRI. Transplantation with labeled or unlabeled islets helped restore normal sustained glucose levels in diabetic mice, and nephrectomies induced the recurrence of diabetes. The MR signal intensity of labeled pancreatic islets decreased by 80% over 30 days. The transplantation of SPIO-labeled porcine islets into the kidney capsule of diabetic mice allows to restore normal glucose levels, and these islets can be visualized and quantified using a 1.5T clinical MR scanner

  16. Neuronal human BACE1 knockin induces systemic diabetes in mice.

    Science.gov (United States)

    Plucińska, Kaja; Dekeryte, Ruta; Koss, David; Shearer, Kirsty; Mody, Nimesh; Whitfield, Phillip D; Doherty, Mary K; Mingarelli, Marco; Welch, Andy; Riedel, Gernot; Delibegovic, Mirela; Platt, Bettina

    2016-07-01

    β-Secretase 1 (BACE1) is a key enzyme in Alzheimer's disease pathogenesis that catalyses the amyloidogenic cleavage of amyloid precursor protein (APP). Recently, global Bace1 deletion was shown to protect against diet-induced obesity and diabetes, suggesting that BACE1 is a potential regulator of glucose homeostasis. Here, we investigated whether increased neuronal BACE1 is sufficient to alter systemic glucose metabolism, using a neuron-specific human BACE1 knockin mouse model (PLB4). Glucose homeostasis and adiposity were determined by glucose tolerance tests and EchoMRI, lipid species were measured by quantitative lipidomics, and biochemical and molecular alterations were assessed by western blotting, quantitative PCR and ELISAs. Glucose uptake in the brain and upper body was measured via (18)FDG-PET imaging. Physiological and molecular analyses demonstrated that centrally expressed human BACE1 induced systemic glucose intolerance in mice from 4 months of age onward, alongside a fatty liver phenotype and impaired hepatic glycogen storage. This diabetic phenotype was associated with hypothalamic pathology, i.e. deregulation of the melanocortin system, and advanced endoplasmic reticulum (ER) stress indicated by elevated central C/EBP homologous protein (CHOP) signalling and hyperphosphorylation of its regulator eukaryotic translation initiation factor 2α (eIF2α). In vivo (18)FDG-PET imaging further confirmed brain glucose hypometabolism in these mice; this corresponded with altered neuronal insulin-related signalling, enhanced protein tyrosine phosphatase 1B (PTP1B) and retinol-binding protein 4 (RBP4) levels, along with upregulation of the ribosomal protein and lipid translation machinery. Increased forebrain and plasma lipid accumulation (i.e. ceramides, triacylglycerols, phospholipids) was identified via lipidomics analysis. Our data reveal that neuronal BACE1 is a key regulator of metabolic homeostasis and provide a potential mechanism for the high

  17. Pathway of 3-MCPD-induced apoptosis in human embryonic kidney cells.

    Science.gov (United States)

    Ji, Jian; Zhu, Pei; Sun, Chao; Sun, Jiadi; An, Lu; Zhang, Yinzhi; Sun, Xiulan

    2017-01-01

    3-Chloropropane-1,2-diol (3-MCPD) is a heat-produced contaminant formed during the preparation of soy sauce worldwide. The present investigation was conducted to determine the molecular aspects of 3-MCPD toxicity on human embryonic kidney cells (HEK293). Cell viability and apoptosis were assessed in response to exposure to 3-MCPD using the MTT assay and high-content screening (HCS). DNA damage, intracellular reactive oxygen species (ROS) and apoptosis-related proteins were evaluated. Genes related with apoptosis were detected by qPCR-array for further understanding the 3-MCPD induced cell apoptosis signaling pathway. Our results clearly showed that 3-MCPD treatment inhibits cell proliferation and reactive oxygen species generation. qPCR-array indicated that nine apoptotic genes were up-regulated more than 2-fold and six down-regulated more than 2-fold. Genes associated with the mitochondrial apoptotic pathway, especially BCL2 family genes, changed significantly, indicating that the mitochondrial apoptotic pathway is activated. Death receptor pathway-related genes, TNFRSF11B and TNFRSF1A, changed significantly, indicating that the death receptor pathway is also activated, resulting in the inhibition of cell growth and proliferation as well as induction of apoptosis. To sum up, the experiment results indicated that 3-MCPD induced HEK293 cell toxicity through the death receptor pathway and mitochondrial pathway.

  18. Ultrasonic propulsion of kidney stones: preliminary results of human feasibility study.

    Science.gov (United States)

    Bailey, Michael; Cunitz, Bryan; Dunmire, Barbrina; Paun, Marla; Lee, Franklin; Ross, Susan; Lingeman, James; Coburn, Michael; Wessells, Hunter; Sorensen, Mathew; Harper, Jonathan

    2014-09-03

    One in 11 Americans has experienced kidney stones, with a 50% average recurrence rate within 5-10 years. Ultrasonic propulsion (UP) offers a potential method to expel small stones or residual fragments before they become a recurrent problem. Reported here are preliminary findings from the first investigational use of UP in humans. The device uses a Verasonics ultrasound engine and Philips HDI C5-2 probe to generate real-time B-mode imaging and targeted "push" pulses on demand. There are three arms of the study: de novo stones, post-lithotripsy fragments, and the preoperative setting. A pain questionnaire is completed prior to and following the study. Movement is classified based on extent. Patients are followed for 90 days. Ten subjects have been treated to date: three de novo , five post-lithotripsy, and two preoperative. None of the subjects reported pain associated with the treatment or a treatment related adverse event, beyond the normal discomfort of passing a stone. At least one stone was moved in all subjects. Three of five post-lithotripsy subjects passed a single or multiple stones within 1-2 weeks following treatment; one subject passed two (1-2 mm) fragments before leaving clinic. In the pre-operative studies we successfully moved 7 - 8 mm stones. In four subjects, UP revealed multiple stone fragments where the clinical image and initial ultrasound examination indicated a single large stone.

  19. Diabetes and Kidney Disease

    Science.gov (United States)

    ... Going to the bathroom more often at night High levels of BUN and creatinine in blood Less need for insulin or antidiabetic medications Morning sickness, nausea and vomiting Weakness, paleness and ... high blood pressure Get treatment for urinary tract infections ...

  20. Differential proteome analysis of human embryonic kidney cell line (HEK-293 following mycophenolic acid treatment

    Directory of Open Access Journals (Sweden)

    Rahman Hazir

    2011-09-01

    Full Text Available Abstract Background Mycophenolic acid (MPA is widely used as a post transplantation medicine to prevent acute organ rejection. In the present study we used proteomics approach to identify proteome alterations in human embryonic kidney cells (HEK-293 after treatment with therapeutic dose of MPA. Following 72 hours MPA treatment, total protein lysates were prepared, resolved by two dimensional gel electrophoresis and differentially expressed proteins were identified by QTOF-MS/MS analysis. Expressional regulations of selected proteins were further validated by real time PCR and Western blotting. Results The proliferation assay demonstrated that therapeutic MPA concentration causes a dose dependent inhibition of HEK-293 cell proliferation. A significant apoptosis was observed after MPA treatment, as revealed by caspase 3 activity. Proteome analysis showed a total of 12 protein spots exhibiting differential expression after incubation with MPA, of which 7 proteins (complement component 1 Q subcomponent-binding protein, electron transfer flavoprotein subunit beta, cytochrome b-c1 complex subunit, peroxiredoxin 1, thioredoxin domain-containing protein 12, myosin regulatory light chain 2, and profilin 1 showed significant increase in their expression. The expression of 5 proteins (protein SET, stathmin, 40S ribosomal protein S12, histone H2B type 1 A, and histone H2B type 1-C/E/F/G/I were down-regulated. MPA mainly altered the proteins associated with the cytoskeleton (26%, chromatin structure/dynamics (17% and energy production/conversion (17%. Both real time PCR and Western blotting confirmed the regulation of myosin regulatory light chain 2 and peroxiredoxin 1 by MPA treatment. Furthermore, HT-29 cells treated with MPA and total kidney cell lysate from MMF treated rats showed similar increased expression of myosin regulatory light chain 2. Conclusion The emerging use of MPA in diverse pathophysiological conditions demands in-depth studies to

  1. Chronic kidney disease screening methods and its implication for Malaysia: an in depth review.

    Science.gov (United States)

    Almualm, Yasmin; Zaman Huri, Hasniza

    2015-01-01

    Chronic Kidney Disease has become a public health problem, imposing heath, social and human cost on societies worldwide. Chronic Kidney Disease remains asymptomatic till late stage when intervention cannot stop the progression of the disease. Therefore, there is an urgent need to detect the disease early. Despite the high prevalence of Chronic Kidney Disease in Malaysia, screening is still lacking behind. This review discusses the strengths and limitations of current screening methods for Chronic Kidney Disease from a Malaysian point of view. Diabetic Kidney Disease was chosen as focal point as Diabetes is the leading cause of Chronic Kidney Disease in Malaysia. Screening for Chronic Kidney Disease in Malaysia includes a urine test for albuminuria and a blood test for serum creatinine. Recent literature indicates that albuminuria is not always present in Diabetic Kidney Disease patients and serum creatinine is only raised after substantial kidney damage has occurred.  Recently, cystatin C was proposed as a potential marker for kidney disease but this has not been studied thoroughly in Malaysia.  Glomerular Filtration Rate is the best method for measuring kidney function and is widely estimated using the Modification of Diet for Renal Disease equation. Another equation, the Chronic Kidney Disease Epidemiology Collaboration Creatinine equation was introduced in 2009. The new equation retained the precision and accuracy of the Modification of Diet for Renal Disease equation at GFR 60ml/min/1.73m2. In Asian countries, adding an ethnic coefficient to the equation enhanced its performance. In Malaysia, a multi-ethnic Asian population, the Chronic Kidney Disease Epidemiology Collaboration equation should be validated and the Glomerular Filtration Rate should be reported whenever serum creatinine is ordered. Reporting estimated Glomerular Filtration Rate will help diagnose patients who would have been otherwise missed if only albuminuria and serum creatinine are measured.

  2. Metabolic imaging of human kidney triglyceride content: reproducibility of proton magnetic resonance spectroscopy.

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    Sebastiaan Hammer

    Full Text Available OBJECTIVE: To assess the feasibility of renal proton magnetic resonance spectroscopy for quantification of triglyceride content and to compare spectral quality and reproducibility without and with respiratory motion compensation in vivo. MATERIALS AND METHODS: The Institutional Review Board of our institution approved the study protocol, and written informed consent was obtained. After technical optimization, a total of 20 healthy volunteers underwent renal proton magnetic resonance spectroscopy of the renal cortex both without and with respiratory motion compensation and volume tracking. After the first session the subjects were repositioned and the protocol was repeated to assess reproducibility. Spectral quality (linewidth of the water signal and triglyceride content were quantified. Bland-Altman analyses and a test by Pitman were performed. RESULTS: Linewidth changed from 11.5±0.4 Hz to 10.7±0.4 Hz (all data pooled, p<0.05, without and with respiratory motion compensation respectively. Mean % triglyceride content in the first and second session without respiratory motion compensation were respectively 0.58±0.12% and 0.51±0.14% (P = NS. Mean % triglyceride content in the first and second session with respiratory motion compensation were respectively 0.44±0.10% and 0.43±0.10% (P = NS between sessions and P = NS compared to measurements with respiratory motion compensation. Bland-Altman analyses showed narrower limits of agreement and a significant difference in the correlated variances (correlation of -0.59, P<0.05. CONCLUSION: Metabolic imaging of the human kidney using renal proton magnetic resonance spectroscopy is a feasible tool to assess cortical triglyceride content in humans in vivo and the use of respiratory motion compensation significantly improves spectral quality and reproducibility. Therefore, respiratory motion compensation seems a necessity for metabolic imaging of renal triglyceride content in vivo.

  3. Cytotoxicity and oxidative stress induced by different metallic nanoparticles on human kidney cells

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    Ohayon-Courtès Céline

    2011-03-01

    Full Text Available Abstract Background Some manufactured nanoparticles are metal-based and have a wide variety of applications in electronic, engineering and medicine. Until now, many studies have described the potential toxicity of NPs on pulmonary target, while little attention has been paid to kidney which is considered to be a secondary target organ. The objective of this study, on human renal culture cells, was to assess the toxicity profile of metallic nanoparticles (TiO2, ZnO and CdS usable in industrial production. Comparative studies were conducted, to identify whether particle properties impact cytotoxicity by altering the intracellular oxidative status. Results Nanoparticles were first characterized by size, surface charge, dispersion and solubility. Cytotoxicity of NPs was then evaluated in IP15 (glomerular mesangial and HK-2 (epithelial proximal cell lines. ZnO and CdS NPs significantly increased the cell mortality, in a dose-dependent manner. Cytotoxic effects were correlated with the physicochemical properties of NPs tested and the cell type used. Analysis of reactive oxygen species and intracellular levels of reduced and oxidized glutathione revealed that particles induced stress according to their composition, size and solubility. Protein involved in oxidative stress such as NF-κb was activated with ZnO and CdS nanoparticles. Such effects were not observed with TiO2 nanoparticles. Conclusion On glomerular and tubular human renal cells, ZnO and CdS nanoparticles exerted cytotoxic effects that were correlated with metal composition, particle scale and metal solubility. ROS production and oxidative stress induction clearly indicated their nephrotoxic potential.

  4. Human embryonic stem cell-derived pancreatic endoderm alleviates diabetic pathology and improves reproductive outcome in C57BL/KsJ-Lep(db/+) gestational diabetes mellitus mice.

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    Xing, Baoheng; Wang, Lili; Li, Qin; Cao, Yalei; Dong, Xiujuan; Liang, Jun; Wu, Xiaohua

    2015-07-01

    Gestational diabetes mellitus is a condition commonly encountered during mid to late pregnancy with pathologic manifestations including hyperglycemia, hyperinsulinemia, insulin resistance, and fetal maldevelopment. The cause of gestational diabetes mellitus can be attributed to both genetic and environmental factors, hence complicating its diagnosis and treatment. Pancreatic progenitors derived from human embryonic stem cells were shown to be able to effectively treat diabetes in mice. In this study, we have developed a system of treating diabetes using human embryonic stem cell-derived pancreatic endoderm in a mouse model of gestational diabetes mellitus. Human embryonic stem cells were differentiated in vitro into pancreatic endoderm, which were then transplanted into db/+ mice suffering from gestational diabetes mellitus. The transplant greatly improved glucose metabolism and reproductive outcome of the females compared with the control groups. Our findings support the feasibility of using differentiated human embryonic stem cells for treating gestational diabetes mellitus patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Human Anti-Oxidation Protein A1M—A Potential Kidney Protection Agent in Peptide Receptor Radionuclide Therapy

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    Jonas Ahlstedt

    2015-12-01

    Full Text Available Peptide receptor radionuclide therapy (PRRT has been in clinical use for 15 years to treat metastatic neuroendocrine tumors. PRRT is limited by reabsorption and retention of the administered radiolabeled somatostatin analogues in the proximal tubule. Consequently, it is essential to develop and employ methods to protect the kidneys during PRRT. Today, infusion of positively charged amino acids is the standard method of kidney protection. Other methods, such as administration of amifostine, are still under evaluation and show promising results. α1-microglobulin (A1M is a reductase and radical scavenging protein ubiquitously present in plasma and extravascular tissue. Human A1M has antioxidation properties and has been shown to prevent radiation-induced in vitro cell damage and protect non-irradiated surrounding cells. It has recently been shown in mice that exogenously infused A1M and the somatostatin analogue octreotide are co-localized in proximal tubules of the kidney after intravenous infusion. In this review we describe the current situation of kidney protection during PRRT, discuss the necessity and implications of more precise dosimetry and present A1M as a new, potential candidate for renal protection during PRRT and related targeted radionuclide therapies.

  6. Finite element modeling of the human kidney for probabilistic occupant models: Statistical shape analysis and mesh morphing.

    Science.gov (United States)

    Yates, Keegan M; Untaroiu, Costin D

    2018-04-16

    Statistical shape analysis was conducted on 15 pairs (left and right) of human kidneys. It was shown that the left and right kidney were significantly different in size and shape. In addition, several common modes of kidney variation were identified using statistical shape analysis. Semi-automatic mesh morphing techniques have been developed to efficiently create subject specific meshes from a template mesh with a similar geometry. Subject specific meshes as well as probabilistic kidney meshes were created from a template mesh. Mesh quality remained about the same as the template mesh while only taking a fraction of the time to create the mesh from scratch or morph with manually identified landmarks. This technique can help enhance the quality of information gathered from experimental testing with subject specific meshes as well as help to more efficiently predict injury by creating models with the mean shape as well as models at the extremes for each principal component. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Clearance from the anterior chamber of RBCs from human diabetics

    International Nuclear Information System (INIS)

    Williams, G.A.; Hatchell, D.L.; Collier, B.D.; Knobel, J.

    1984-01-01

    Erythrocytes from diabetic patients manifest decreased deformability and increased adherence. These abnormal membrane properties may diminish the ability of erythrocytes (RBCs) from diabetics to undergo deformation in passage through the trabecular meshwork. Using sodium chromate Cr 51-labeled RBCs from type I diabetic patients with proliferative retinopathy and normal control subjects, we studied RBC clearance from the rabbit anterior chamber. The mean time for 50% clearance (T50) of RBCs from diabetics (76 hours) was significantly longer than that for RBCs from normal subjects (19.5 hours). In this model, RBCs from diabetics have a slower clearance from the anterior chamber than do RBCs from normal subjects

  8. Prognostic significance of stress myocardial ECG-gated perfusion imaging in asymptomatic patients with diabetic chronic kidney disease on initiation of haemodialysis

    Energy Technology Data Exchange (ETDEWEB)

    Momose, Mitsuru; Kondo, Chisato; Kobayashi, Hideki; Kusakabe, Kiyoko [Tokyo Women' s Medical University, School of Medicine, Department of Radiology, Shinjuku-ku, Tokyo (Japan); Babazono, Tetsuya [Tokyo Women' s Medical University, School of Medicine, Diabetes Centre, Shinjuku-ku, Tokyo (Japan); Nakajima, Takatomo [Tokyo Women' s Medical University, School of Medicine, Department of Cardiology, Shinjuku-ku, Tokyo (Japan)

    2009-08-15

    Diabetic patients with chronic kidney disease (CKD) frequently develop cardiac events within several years of the initiation of haemodialysis. The present study assesses the prognostic significance of stress myocardial ECG-gated perfusion imaging (MPI) in patients with diabetic CKD requiring haemodialysis. Fifty-five asymptomatic patients with diabetic stage V CKD and no history of heart disease scheduled to start haemodialysis were enrolled in this study (56{+-}11 years old; 49 with type 2 diabetes mellitus). All patients underwent {sup 201}Tl stress ECG-gated MPI 1 month before or after the initiation of haemodialysis to assess myocardial involvement. We evaluated SPECT images using 17-segment defect scores graded on a 5-point scale, summed stress score (SSS) and summed difference scores (SDS). The patients were followed up for at least 2 years (42{+-}15 months) to determine coronary intervention (CI) and heart failure (HF) as soft events and acute myocardial infarction (AMI) and all causes of deaths as hard events. The frequencies of myocardial ischaemia, resting perfusion defects, low ejection fraction and left ventricular (LV) dilatation were 24,20,29 and 49%, respectively. Ten events (18%) developed during the follow-up period including four CI, one HF, one AMI and four sudden deaths. Multivariate Cox analysis selected SDS (p=0.0011) and haemoglobin A{sub 1c} (HbA{sub 1c}) (p=0.0076) as independent prognostic indicators for all events. Myocardial ischaemia, in addition to glycaemic control, is a strong prognostic marker for asymptomatic patients with diabetic CKD who are scheduled to start haemodialysis. Stress MPI is highly recommended for the management and therapeutic stratification of such patients. (orig.)

  9. DNA damage in hemodialysis patients with chronic kidney disease; a test of the role of diabetes mellitus; a comet assay investigation.

    Science.gov (United States)

    Mamur, Sevcan; Unal, Fatma; Altok, Kadriye; Deger, Serpil Muge; Yuzbasioglu, Deniz

    2016-04-01

    The incidence of chronic kidney disease (CKD) is increasing rapidly. Diabetes mellitus (DM) is the most important cause of CKD. We studied the possible role of DM in CKD patients with respect to DNA damage, as assessed by the comet assay in 60 CKD patients (with or without DM) undergoing hemodialysis and in 26 controls. Effects of other factors, such as age, sex, hypertension, duration of hemodialysis, body mass index (BMI), and levels of hemoglobin (HB), intact parathormone (iPTH), and ferritin (FER), were also examined. Primary DNA damage measured by the comet assay was significantly higher in CKD patients than in controls. Among CKD patients, the following correlations were observed. (1) There was no difference in comet tail length or tail intensity between diabetic and non-diabetic individuals. (2) Age, sex, hemoglobin, hypertension, duration of hemodialysis, and ferritin levels affected neither tail length nor intensity. (3) BMI values above 25kg/m(2) and iPTH levels above 300pg/ml were associated with significantly greater comet tail length. Our results indicate that primary DNA damage is increased in CKD patients undergoing hemodialysis, compared to controls; however, DM had no additional effect. Copyright © 2016. Published by Elsevier B.V.

  10. The Utility of the Mini-Addenbrooke's Cognitive Examination as a Screen for Cognitive Impairment in Elderly Patients with Chronic Kidney Disease and Diabetes.

    Science.gov (United States)

    Hobson, Peter; Rohoma, Kamel H; Wong, Stephen P; Kumwenda, Mick J

    2016-01-01

    We tested the utility of the Mini-Addenbrooke's Cognitive Examination (M-ACE) in a cohort of older adults with chronic kidney disease (CKD) and diabetes. The M-ACE was administered to 112 CKD and diabetes patients attending a nephrology clinic. Cognitive impairment was based upon patient, informant, and case review, neuropsychological assessment, and application of criteria for mild cognitive impairment (MCI) and the Diagnostic and Statistical Manual of Mental Disorders, fifth edition for dementia. The M-ACE was also compared to the Mini-Mental State Examination (MMSE). Upon assessment, 52 patients had normal cognitive function, 33 had MCI, and 27 had dementia. The area under the receiver operating curve for the M-ACE was 0.96 (95% CI 0.95-1.00). The sensitivity and specificity for a dementia diagnosis were 0.96 and 0.84 at the cut point <25 and 0.70 and 1.00 at the cut point <21. Mean M-ACE scores differed significantly between normal, demented, and MCI groups ( p < 0.001), and compared to the MMSE, the M-ACE did not suffer from ceiling effects. The M-ACE is an easily administered test with good sensitivity and specificity to capture and assist in the diagnosis of MCI or dementia in patients with CKD and diabetes.

  11. Kidney Disease

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Kidney Disease KidsHealth / For Teens / Kidney Disease What's in ... Coping With Kidney Conditions Print What Do the Kidneys Do? You might never think much about some ...

  12. Kidney Problems

    Science.gov (United States)

    ... our e-newsletter! Aging & Health A to Z Kidney Problems Basic Facts & Information The kidneys are two ... kidney (renal) diseases are called nephrologists . What are Kidney Diseases? For about one-third of older people, ...

  13. Trabecular bone histomorphometry in humans with Type 1 Diabetes Mellitus.

    Science.gov (United States)

    Armas, Laura A G; Akhter, Mohammed P; Drincic, Andjela; Recker, Robert R

    2012-01-01

    Patients with Type 1 Diabetes Mellitus (DM) have markedly increased risk of fracture, but little is known about abnormalities in bone microarchitecture or remodeling properties that might give insight into the pathogenesis of skeletal fragility in these patients. We report here a case-control study comparing bone histomorphometric and micro-CT results from iliac biopsies in 18 otherwise healthy subjects with Type 1 Diabetes Mellitus with those from healthy age- and sex-matched non-diabetic control subjects. Five of the diabetics had histories of low-trauma fracture. Transilial bone biopsies were obtained after tetracycline labeling. The biopsy specimens were fixed, embedded, and scanned using a desktop μCT at 16 μm resolution. They were then sectioned and quantitative histomorphometry was performed as previously described by Recker et al. [1]. Two sections, >250 μm apart, were read from the central part of each biopsy. Overall there were no significant differences between diabetics and controls in histomorphometric or micro-CT measurements. However, fracturing diabetics had structural and dynamic trends different from nonfracturing diabetics by both methods of analysis. In conclusion, Type 1 Diabetes Mellitus does not result in abnormalities in bone histomorphometric or micro-CT variables in the absence of manifest complications from the diabetes. However, diabetics suffering fractures may have defects in their skeletal microarchitecture that may underlie the presence of excess skeletal fragility. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Prevalence of chronic kidney disease in newly diagnosed patients with Human immunodeficiency virus in Ilorin, Nigeria.

    Science.gov (United States)

    Ayokunle, Dada Samuel; Olusegun, Olanrewaju Timothy; Ademola, Aderibigbe; Adindu, Chijioke; Olaitan, Rafiu Mojeed; Oladimeji, Ajayi Akande

    2015-01-01

    Human immunodeficiency virus (HIV) the causative agent of Acquired immunodeficiency syndrome (AIDS) is an important cause of renal diseases in sub-Saharan Africa. There is paucity of studies on the burden of chronic kidney disease (CKD) among patients with HIV/AIDS in the North-Central zone of Nigeria. This is a cross-sectional study of 227 newly-diagnosed, antiretroviral naïve patients with HIV/AIDS seen at the HIV clinic of the Medical Out-patient Department (MOPD) of University of Ilorin Teaching Hospital (UITH). They were matched with 108 control group. Laboratory investigations were performed for the participants. CKD was defined as estimated glomerular filtration rate (eGFR) 30 mg/g. There were 100 (44%) males among the patients and 47 (43.5%) among the control group. The mean ages of the patients and controls were 40.3 ± 10.3 years and 41.8 ± 9.5 years respectively. CKD was observed in 108 (47.6%) among the patients and 18 (16.7%) of the controls (p = 0.01). The median CD4 T-cell count was significantly lower in patients with CKD. Ninety-three (41.0%) of the patients had dipstick proteinuria of > 2 +. The median albumin creatinine ratio (ACR) was significantly higher among the HIV-positive patients (272.3 mg/g) compared with the HIV-negative controls (27.22 mg/g) p = 0.01. The CD4 T-cell count correlates positively with eGFR (r = 0.463, p = 0.001) and negatively with ACR (r = -0.806, p = 0.001). CKD is very common among patients with HIV/AIDS in Ilorin. Screening and early intervention for CKD should be part of the protocols in the management of these patients.

  15. Src family kinases in chronic kidney disease.

    Science.gov (United States)

    Wang, Jun; Zhuang, Shougang

    2017-09-01

    Src family kinases (SFKs) belong to nonreceptor protein tyrosine kinases and have been implicated in the regulation of numerous cellular processes, including cell proliferation, differentiation, migration and invasion, and angiogenesis. The role and mechanisms of SFKs in tumorgenesis have been extensively investigated, and some SFK inhibitors are currently under clinical trials for tumor treatment. Recent studies have also demonstrated the importance of SFKs in regulating the development of various fibrosis-related chronic diseases (e.g., idiopathic pulmonary fibrosis, liver fibrosis, renal fibrosis, and systemic sclerosis). In this article, we summarize the roles of SFKs in various chronic kidney diseases, including glomerulonephritis, diabetic nephropathy, human immunodeficiency virus-associated nephropathy, autosomal dominant form of polycystic kidney disease, and obesity-associated kidney disease, and discuss the mechanisms involved. Copyright © 2017 the American Physiological Society.

  16. Cardioprotection by controlling hyperamylinemia in a "humanized" diabetic rat model.

    Science.gov (United States)

    Despa, Sanda; Sharma, Savita; Harris, Todd R; Dong, Hua; Li, Ning; Chiamvimonvat, Nipavan; Taegtmeyer, Heinrich; Margulies, Kenneth B; Hammock, Bruce D; Despa, Florin

    2014-08-21

    Chronic hypersecretion of the pancreatic hormone amylin is common in humans with obesity or prediabetic insulin resistance and induces amylin aggregation and proteotoxicity in the pancreas. We recently showed that hyperamylinemia also affects the cardiovascular system. Here, we investigated whether amylin aggregates interact directly with cardiac myocytes and whether controlling hyperamylinemia protects the heart. By Western blot, we found abundant amylin aggregates in lysates of cardiac myocytes from obese patients, but not in controls. Aggregated amylin was elevated in failing hearts, suggesting a role in myocyte injury. Using rats overexpressing human amylin in the pancreas (HIP rats) and control myocytes incubated with human amylin, we show that amylin aggregation at the sarcolemma induces oxidative stress and Ca(2+) dysregulation. In time, HIP rats developed cardiac hypertrophy and left-ventricular dilation. We then tested whether metabolites with antiaggregation properties, such as eicosanoid acids, limit myocardial amylin deposition. Rats were treated with an inhibitor of soluble epoxide hydrolase, the enzyme that degrades endogenous eicosanoids. Treatment doubled the blood concentration of eicosanoids, which drastically reduced incorporation of aggregated amylin in cardiac myocytes and blood cells, without affecting pancreatic amylin secretion. Animals in the treated group showed reduced cardiac hypertrophy and left-ventricular dilation. The cardioprotective mechanisms included the mitigation of amylin-induced cardiac oxidative stress and Ca(2+) dysregulation. The results suggest blood amylin as a novel therapeutic target in diabetic heart disease and elevating blood levels of antiaggregation metabolites as a pharmacological strategy to reduce amylin aggregation and amylin-mediated cardiotoxicity. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  17. Dual roles for CoAA and its counterbalancing isoform CoAM in human kidney cell tumorigenesis

    Science.gov (United States)

    Kang, Yun Kyoung; Schiff, Rachel; Ko, Lan; Wang, Tao; Tsai, Sophia Y.; Tsai, Ming-Jer; W. O’Malley, Bert

    2008-01-01

    Co-Activator Activator (CoAA) has been reported to be a coactivator that regulates steroid receptor-mediated transcription and alternative RNA splicing. Herein we show that CoAA is a dual-function coregulator that inhibits G1/S transition in human kidney cells and suppresses anchorage independent growth and xenograft tumor formation. Suppression occurs in part by downregulating c-myc and its downstream effectors ccnd1 and skp2, and causing accumulation of p27/Kip1 protein. In this cellular setting, CoAA directly represses the proto-oncogene, c-myc by recruiting HDAC3 protein and decreasing both the acetylation of histone H3 and the presence of RNA polymerase II on the c-myc promoter. Interestingly, a splicing isoform of CoAA, Coactivator Modulator (CoAM), antagonizes CoAA-induced G1/S transition and growth inhibition by negatively regulating the mRNA levels of the endogenous CoAA isoform. In addition, we found that expression of CoAA protein is significantly decreased in human renal cell carcinoma as compared to normal kidney. Our study presents evidence that CoAA is a potential tumor suppressor in renal carcinoma and that CoAM is a counterbalancing splice-isoform. This is so far the only example of a nuclear receptor coregulator involved in suppression of kidney cancer, and suggests potentially significant new roles for coregulators in renal cancer biology. PMID:18829545

  18. Surrogate markers of the kidney and liver in the assessment of gestational diabetes mellitus and fetal outcome.

    Science.gov (United States)

    Liu, Hong; Shao-Gang, Ma; Liang, Cheng; Feng, Bai; Wei, Xu

    2015-01-01

    To investigate whether serum levels of butyrylcho-linesterase activity, cystatin C, and pre-albumin has the potential value as γ-glutamyl transferase in reflecting gestational diabetes mellitus and its fetal outcome. Seventy-six gestational diabetes mellitus women and 76 pregnancies with normal glucose tolerance in the second trimester were enrolled. Maternal serum parameters of butyrylcholinesterase activity, γ-glutamyl transferase, cystatin C, and pre-albumin were detected and evaluated. The pregnant complications and fetal outcome were also evaluated. Levels of butyrylcholinesterase activity, γ-glutamyl transferase, cystatin C, pre-albumin and glycemic variables were higher in the gestational diabetes mellitus patients than in the controls. Levels of butyrylcholinesterase activity were significantly correlated to the levels of fasting plasma glucose, cystatin C, and γ- glutamyl transferase (p gestational diabetes mellitus group. There were statistical differences in cases of preterm delivery, preeclampsia and postpartum hemorrhage. Higher levels of γ-glutamyl transferase and pre-albumin were risk markers for gestational diabetes mellitus (p gestational diabetes mellitus status but not with the fetal outcome. Pre-albumin can be equivalent as γ-glutamyl transferase in reflecting the presence of gestational diabetes mellitus.

  19. Concentration of gadolinium-diethylene triamine pentaacetic acid in human kidney

    International Nuclear Information System (INIS)

    Takeda, Masayuki; Katayama, Yasushi; Tsutsui, Toshiki; Komeyama, Takeshi; Mizusawa, Takaki; Tanikawa, Toshiki; Sato, Shotaro

    1993-01-01

    Although gadolinium diethylene triamine pentaacetic acid (Gd-DTPA) has been used as a contrast material in magnetic resonance imaging, it is known that contrast enhancement effect disappears if the concentration of Gd-DTPA increases beyond some levels. In this study, to evaluate the proper pulse sequences for dynamic magnetic resonance imaging (MRI) in the human kidney, the concentration of Gd-DTPA was quantitatively measured by inductively coupled plasma (ICP) emission spectrometry in human biological samples after administration of Gd-DTPA, and the signal intensity of MRI is the solution of several concentrations of Gd-DTPA was measured. In using a low magnetic field apparatus, signal intensity linearly correlated with the concentration of Gd-DTPA between 0 and 2.0 μmol/g under saturation recovery sequences (flip angle was 60deg or 90deg). Using a high magnetic field apparatus, signal intensity linearly correlated with the concentration of Gd-DTPA between 0 and 2.0 or 3.0 μmol/g under spin echo or gradient-echo sequences. Gd-DTPA concentration of the renal cortex ranged from 0.132 to 0.152 μmol/g tissue at 5 min after intravenous injection of Gd-DTPA 0.05 mmol/kg body weight in 7 patients with adrenal tumor or renal cell cancer, and 1 patient with both urinary bladder cancer and prostatic cancer. Seven of them showed normal renal function and the other had renal insufficiency (GFR 25 ml/min/1.48 m 2 ). Gd-DTPA concentrations of renal medulla and renal cell cancer tissue were 0.123 and 0.108 μmol/g tissue, respectively, at 5 min after intravenous injection of Gd-DTPA 0.05 mmol/kg body weight. These results suggest that the signal intensity of renal cortex, renal medulla, and renal cell cancer tissue may linearly correlate with Gd-DTPA concentration of tissues at 5 min after intravenous injection of Gd-DTPA 0.5 mmol/kg body weight. (author)

  20. Progranulin serum levels in human kidney transplant recipients: A longitudinal study.

    Science.gov (United States)

    Nicoletto, Bruna Bellincanta; Pedrollo, Elis Forcellini; Carpes, Larissa Salomoni; Coloretti, Natália Gomes; Krolikowski, Thaiana Cirino; Souza, Gabriela Corrêa; Gonçalves, Luiz Felipe Santos; Manfro, Roberto Ceratti; Canani, Luis Henrique

    2018-01-01

    The adipokine progranulin has metabolic proprieties, playing a role in obesity and insulin resistance. Its levels seems to be dependent of renal function, since higher progranulin concentration is observed in patients with end-stage kidney disease. However, the effect of kidney transplantation on progranulin remains unknown. To assess the serum progranulin levels in kidney transplant recipients before and after kidney transplantation. Forty-six prospective kidney transplant recipients were included in this longitudinal study. They were evaluated before transplantation and at three and twelve months after transplantation. Clinical, anthropometric and laboratorial measurements were assessed. Progranulin was determined with enzyme-linked immunosorbent assays. Serum progranulin significantly decreased in the early period after transplantation (from 72.78 ± 2.86 ng/mL before transplantation to 40.65 ± 1.49 ng/mL at three months; pProgranulin was associated with waist circumference and fasting plasma glucose after adjusted for age, gender, study period, glomerular filtration rate, interleukin-6, high sensitivity C reactive protein and adiponectin. Progranulin serum levels are increased before transplantation and a reduction is observed in the early period after transplantation, possibly attributed to an improvement in renal function. At one year after transplantation, an increment in progranulin is observed, seems to be independent of glomerular filtration, and remained significantly lower than before transplantation.

  1. Age modifies the risk factor profiles for acute kidney injury among recently diagnosed type 2 diabetic patients: a population-based study.

    Science.gov (United States)

    Chao, Chia-Ter; Wang, Jui; Wu, Hon-Yen; Huang, Jenq-Wen; Chien, Kuo-Liong

    2018-04-01

    The incidence of acute kidney injury (AKI) rises with age and is associated with multiple risk factors. Here, we compared the risk factors for AKI between younger and older incident diabetic patients to examine the trends in risk alteration for individual factors across different age groups. Between 2007 and 2013, we selected all incident type 2 diabetic adults from the Taiwan National Health Insurance registry, stratified based on age: young (< 65 years), old (≥ 65 but < 75 years), and older-old (≥ 75 years). All factors with potential renal influence (e.g., comorbidities, medications, and diagnostics/procedures) were recorded during the study period, with a nested case-controlled approach utilized to identify independent risk factors for AKI in each age group. Totally, 930,709 type 2 diabetic patients were categorized as young (68.7%), old (17.7%), or older-old (13.6%). Older-old patients showed a significantly higher incidence of AKI than the old and the young groups. Cardiovascular morbidities (hypertension, atrial fibrillation, acute coronary syndrome, and cerebrovascular disease) were shown to increase the risk of AKI, although the risk declined with increasing age. Chronic obstructive pulmonary disease and receiving cardiac catheterization elevated the risk of AKI preferentially in the older-old/old and older-old group, respectively, while the administration of angiotensin-converting enzyme/α-blocker and angiotensin receptor blocker/calcium channel blocker reduced the risk of AKI preferentially in the older-old and older-old/old group, respectively. In conclusion, our findings highlight the importance of devising age-specific risk factor panels for AKI in patients with recently diagnosed type 2 diabetes.

  2. Treatment choices for the glycaemic management of patients with type 2 diabetes and chronic kidney disease: Analysis of the SAIL patient linked dataset.

    Science.gov (United States)

    Min, Thinzar; Davies, Gareth I; Rice, Sam; Chess, James; Stephens, Jeffrey W

    Chronic kidney disease (CKD) is common in type 2 diabetes and limits the treatment choices for glycaemic control. Our aim was to examine real-world prescribing for managing hyperglycaemia in the presence of CKD. The SAIL (Secure Anonymised Information Linkage) databank was used to examine prescribing during the period from the 1st of January to 30th December 2014. CKD was defined as:- none or mild CKD, eGFR ≥60mL/min/1.73m 2 ; moderate CKD eGFR <60mL/min/1.73m 2 ; and severe CKD eGFR <30mL/min/1.73m 2 or requiring dialysis. We identified 9585 subjects who received any form of glucose lowering therapy (8363 had no/mild CKD; 1137 moderate CKD; 85 severe CKD). There was a linear association between insulin use and CKD severity with approximately 54% of those with severe CKD receiving insulin. Sulphonylureas use did not differ among the CKD groups and was approximately 40%. Metformin showed a linear decrease across the groups, however approximately 21% in the severe CKD group received metformin. The use of dipeptidyl peptidase 4 inhibitors (DPP-4i) was approximately 20% and did not differ among groups. The DPP-4 inhibitor choice was:- 1% vildagliptin, 9% saxagliptin, 58% sitagliptin, and 32% linaglitpin. With respect to sitagliptin and saxagliptin, 72% and 62% received an inappropriately high dose in the setting of CKD. We observed that a considerable proportion of patients with type 2 diabetes and CKD were receiving metformin and non dose-adjusted DPP-4 inhibitors. Careful consideration of medication use and dosaging is required in the setting of CKD and type 2 diabetes. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  3. A randomized, placebo-controlled, double-blind, prospective trial to evaluate the effect of vildagliptin in new-onset diabetes mellitus after kidney transplantation

    Directory of Open Access Journals (Sweden)

    Hörl Walter H

    2010-10-01

    Full Text Available Abstract Background New-onset diabetes mellitus after transplantation (NODAT, a frequent and serious complication after transplantation, is associated with decreased graft and patient survival. Currently, it is diagnosed and treated primarily according to existing guidelines for type II diabetes. To date, only a few trials have studied antidiabetic drugs in patients with NODAT. Vildagliptin is a novel dipeptidyl peptidase-4 (DPP-4 inhibitor that improves pancreatic islet function by enhancing both α- and β-cell responsiveness to increased blood glucose. Experimental data show potential protective effects of DPP-4 inhibitors on islet function after exogenous stress stimuli including immunosuppressants. Therefore, the therapy of NODAT with this class of compounds seems attractive. At present, vildagliptin is used to treat type II diabetes as monotherapy or in combination with other antidiabetic drugs, since that it efficiently decreases glycated hemoglobin (HbA1c values. Additionally, vildagliptin has been shown to be safe in patients with moderately impaired kidney function. This study will evaluate the safety and efficacy of vildagliptin monotherapy in renal transplant recipients with recently diagnosed NODAT. Methods/Design This study is a randomized, placebo-controlled, double-blind, prospective phase II trial. Using the results of routinely performed oral glucose tolerance tests (OGTT in stable renal transplant patients at our center, we will recruit patients without a history of diabetes and a 2 h glucose value surpassing 200 mg/dl (11.1 mmol/l. They are randomized to receive either 50 mg vildagliptin or placebo once daily. A total of 32 patients with newly diagnosed NODAT will be included. The primary endpoint is the difference in the 2 h glucose value between baseline and the repeated OGTT performed 3 months after treatment start, compared between the vildagliptin- and the placebo-group. Secondary endpoints include changes in HbA1c and

  4. Connections between the human gut microbiome and gestational diabetes mellitus.

    Science.gov (United States)

    Kuang, Ya-Shu; Lu, Jin-Hua; Li, Sheng-Hui; Li, Jun-Hua; Yuan, Ming-Yang; He, Jian-Rong; Chen, Nian-Nian; Xiao, Wan-Qing; Shen, Song-Ying; Qiu, Lan; Wu, Ying-Fang; Hu, Cui-Yue; Wu, Yan-Yan; Li, Wei-Dong; Chen, Qiao-Zhu; Deng, Hong-Wen; Papasian, Christopher J; Xia, Hui-Min; Qiu, Xiu

    2017-08-01

    The human gut microbiome can modulate metabolic health and affect insulin resistance, and it may play an important role in the etiology of gestational diabetes mellitus (GDM). Here, we compared the gut microbial composition of 43 GDM patients and 81 healthy pregnant women via whole-metagenome shotgun sequencing of their fecal samples, collected at 21-29 weeks, to explore associations between GDM and the composition of microbial taxonomic units and functional genes. A metagenome-wide association study identified 154 837 genes, which clustered into 129 metagenome linkage groups (MLGs) for species description, with significant relative abundance differences between the 2 cohorts. Parabacteroides distasonis, Klebsiella variicola, etc., were enriched in GDM patients, whereas Methanobrevibacter smithii, Alistipes spp., Bifidobacterium spp., and Eubacterium spp. were enriched in controls. The ratios of the gross abundances of GDM-enriched MLGs to control-enriched MLGs were positively correlated with blood glucose levels. A random forest model shows that fecal MLGs have excellent discriminatory power to predict GDM status. Our study discovered novel relationships between the gut microbiome and GDM status and suggests that changes in microbial composition may potentially be used to identify individuals at risk for GDM. © The Author 2017. Published by Oxford University Press.

  5. Adherence and Outcomes of the Low and Very Low Protein Diets in Chronic Diabetic Kidney Disease – A Debate that Needs Consensus

    Directory of Open Access Journals (Sweden)

    Teodoru Ileana

    2015-03-01

    Full Text Available Since the Brenner`s theory of the „workload” in the remnant nephrons, due to the largely available access to the dialysis facilities, many patients with advanced chronic kidney disease (CKD were given low-protein diets (LPDs apparently with great success. Four main diets are today accepted for achieving a balanced intake of 0.6 g protein/kg/day diet and together with a very low-protein diet of 0.3 g protein/kg/day with keto-analogues and amino-acids supplementation, known as keto-diet, are recommended in specific situations. Still, some questions have debatable answers and are waiting for more conclusive studies: are low and very low-protein diets (VLPDs really effective in diabetic CKD?; which LPD should be given? and what strategy should be used in order to get maximum compliance and best outcomes?

  6. Evaluation of the Prevalence of Chronic Kidney Disease and Rates of Oral Antidiabetic Prescribing in Accordance with Guidelines and Manufacturer Recommendations in Type 2 Diabetic Patients within a Long-Term Care Setting

    Directory of Open Access Journals (Sweden)

    Ning Wu

    2014-01-01

    Full Text Available This retrospective study assessed the prevalence of moderate to severe chronic kidney disease (CKD among nursing home (NH residents with type 2 diabetes. The pattern of oral antidiabetic drug (OAD use and their concordance with the National Kidney Foundation (NKF guideline and prescribing information (PI was also assessed. About half (47% of diabetic residents had moderate to severe CKD. A little over a quarter of the 186 residents using OADs received at least one NKF-discordant OAD prescription. Metformin was the most commonly misused OAD. PI nonconcordance was observed in 58.6% of residents and was highest in glipizide and metformin users. With the high prevalence of moderate to severe CKD in NH residents with diabetes, physicians should consider residents’ renal function when choosing treatment plans and review treatments regularly to check compliance with the NKF guidelines or PIs.

  7. Reduced statherin reactivity of human submandibular gland in diabetes.

    Science.gov (United States)

    Isola, M; Solinas, P; Proto, E; Cossu, M; Lantini, M S

    2011-03-01

     Statherin is a salivary protein involved in the formation of enamel pellicle and in regulation of calcium homeostasis. Diabetes and other pathologies affect both salivary flow and protein secretion by salivary glands, causing increased susceptibility to mucosal infections, tooth demineralization, and caries. The purpose of this study was to compare the statherin expression in submandibular glands of healthy and diabetic subjects.  Fragments of submandibular glands obtained from diabetic and non diabetic patients were fixed, dehydrated, embedded in Epon Resin and processed for the immunogold histochemistry. The results were statistically evaluated.  Specific statherin labeling was demonstrated in secretory granules of acinar cells in both diabetic and normal samples. The staining was much more intense in the latter compared to those of diabetics. The labeling density was quantified by evaluating the number and spatial distribution of gold particles within the granules. The number of gold particles was significantly lower in glands from diabetics than in control glands.  The results obtained suggest that a reduced statherin secretion by salivary glands might be partly responsible for a less effective protection of the oral tissues, resulting in an higher incidence of caries and oral infections associated with diabetes. © 2010 John Wiley & Sons A/S.

  8. Quercetin-Rich Guava (Psidium guajava) Juice in Combination with Trehalose Reduces Autophagy, Apoptosis and Pyroptosis Formation in the Kidney and Pancreas of Type II Diabetic Rats.

    Science.gov (United States)

    Lin, Chia-Fa; Kuo, Yen-Ting; Chen, Tsung-Ying; Chien, Chiang-Ting

    2016-03-10

    We explored whether the combination of anti-oxidant and anti-inflammatory guava (Psidium guajava) and trehalose treatment protects the kidney and pancreas against Type II diabetes (T2DM)-induced injury in rats. We measured the active component of guava juice by HPLC analysis. T2DM was induced in Wistar rats by intraperitoneal administration of nicotinamide and streptozotocin and combination with high fructose diets for 8 weeks. The rats fed with different dosages of guava juice in combination with or without trehalose for 4 weeks were evaluated the parameters including OGTT, plasma insulin, HbA1c, HOMA-IR (insulin resistance) and HOMA-β (β cell function and insulin secretion). We measured oxidative and inflammatory degrees by immunohistochemistry stain, fluorescent stain, and western blot and serum and kidney reactive oxygen species (ROS) by a chemiluminescence analyzer. High content of quercetin in the guava juice scavenged H2O2 and HOCl, whereas trehalose selectively reduced H2O2, not HOCl. T2DM affected the levels in OGTT, plasma insulin, HbA1c, HOMA-IR and HOMA-β, whereas these T2DM-altered parameters, except HbA1c, were significantly improved by guava and trehalose treatment. The levels of T2DM-enhanced renal ROS, 4-hydroxynonenal, caspase-3/apoptosis, LC3-B/autophagy and IL-1β/pyroptosis were significantly decreased by guava juice and trehalose. The combination with trehalose and guava juice protects the pancreas and kidney against T2DM-induced injury.

  9. Arsenic and diabetes and hypertension in human populations: A review

    International Nuclear Information System (INIS)

    Chen, C.-J.; Wang, S.-L.; Chiou, J.-M.; Tseng, C.-H.; Chiou, H.-Y.; Hsueh, Y.-M.; Chen, S.-Y.; Wu, M.-M.; Lai, M.-S.

    2007-01-01

    Long-term exposure to ingested arsenic from drinking water has been well documented to be associated with an increased risk of diabetes mellitus and hypertension in a dose-response relationship among residents of arseniasis-endemic areas in southwestern Taiwan and Bangladesh. An increased risk of self-reported hypertension but not diabetes was reported in a community-based study of residents who consumed drinking water with a low level of arsenic. Increased glycosylated hemoglobin level and systolic blood pressure were observed in workers occupationally exposed to arsenic. Inconsistent findings of arsenic and diabetes in occupational studies may result from the healthy worker effect and the variation in exposure measurement, age composition, number of patients, accuracy in diagnosis and classification of underlying causes of death, competing causes of death, and method to detect diabetes. The dose-response relationship and toxicological mechanisms of arsenic-induced diabetes and hypertension need further elucidation

  10. Renal denervation and hypertension - The need to investigate unintended effects and neural control of the human kidney.

    Science.gov (United States)

    Grisk, Olaf

    2017-05-01

    Increased renal sympathetic nerve activity (RSNA) is present in human and experimental forms of arterial hypertension. Experimental denervation studies showed that renal nerves contribute to the development of hypertension. Clinical trials provided equivocal results on the antihypertensive efficacy of renal denervation in patients spurring discussions on technical aspects of renal denervation and further research on the role of renal nerves for the regulation of kidney function as well as the pathophysiology of hypertension. This review summarizes recent findings on adrenoceptor expression and function in the human kidney, adrenoceptor-dependent regulation of sodium chloride transport in the distal nephron, experimental data on chronic RSNA and the development of high arterial pressure and consequences of renal denervation that may limit its antihypertensive efficacy. Future research needs to reduce the gap between our knowledge on neural control of renal function in animals vs. humans to facilitate translation of experimental animal data to humans. More experimental studies on the temporal relationship between RSNA and arterial pressure in the chronic setting are needed to better define the pathogenetic role of heightened RSNA in different forms of arterial hypertension in order to improve the rational basis for renal denervation in antihypertensive therapy. Finally, research on unintended consequences of renal denervation including but not limited to reinnervation and denervation supersensitivity needs to be intensified to further assess the potential of renal denervation to slow the progression of renal disease and hypertension. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Expression of human oxoguanine glycosylase 1 or formamidopyrimidine glycosylase in human embryonic kidney 293 cells exacerbates methylmercury toxicity in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Ondovcik, Stephanie L.; Preston, Thomas J.; McCallum, Gordon P. [Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario M5S 3M2 (Canada); Wells, Peter G., E-mail: pg.wells@utoronto.ca [Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario M5S 3M2 (Canada); Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario M5S 1A8 (Canada)

    2013-08-15

    Exposure to methylmercury (MeHg) acutely at high levels, or via chronic low-level dietary exposure from daily fish consumption, can lead to adverse neurological effects in both the adult and developing conceptus. To determine the impact of variable DNA repair capacity, and the role of reactive oxygen species (ROS) and oxidatively damaged DNA in the mechanism of toxicity, transgenic human embryonic kidney (HEK) 293 cells that stably express either human oxoguanine glycosylase 1 (hOgg1) or its bacterial homolog, formamidopyrimidine glycosylase (Fpg), which primarily repair the oxidative lesion 8-oxo-2′-deoxyguanosine (8-oxodG), were used to assess the in vitro effects of MeHg. Western blotting confirmed the expression of hOgg1 or Fpg in both the nuclear and mitochondrial compartments of their respective cell lines. Following acute (1–2 h) incubations with 0–10 μM MeHg, concentration-dependent decreases in clonogenic survival and cell growth accompanied concentration-dependent increases in lactate dehydrogenase (LDH) release, ROS formation, 8-oxodG levels and apurinic/apyrimidinic (AP) sites, consistent with the onset of cytotoxicity. Paradoxically, hOgg1- and Fpg-expressing HEK 293 cells were more sensitive than wild-type cells stably transfected with the empty vector control to MeHg across all cellular and biochemical parameters, exhibiting reduced clonogenic survival and cell growth, and increased LDH release and DNA damage. Accordingly, upregulation of specific components of the base excision repair (BER) pathway may prove deleterious potentially due to the absence of compensatory enhancement of downstream processes to repair toxic intermediary abasic sites. Thus, interindividual variability in DNA repair activity may constitute an important risk factor for environmentally-initiated, oxidatively damaged DNA and its pathological consequences. - Highlights: • hOgg1 and Fpg repair oxidatively damaged DNA. • hOgg1- and Fpg-expressing cells are more

  12. Comparative Aspects of Human, Canine, and Feline Obesity and Factors Predicting Progression to Diabetes

    OpenAIRE

    Margarethe Hoenig

    2014-01-01

    Obesity and diabetes mellitus are common diseases in humans, dogs and cats and their prevalence is increasing. Obesity has been clearly identified as a risk factor for type 2 diabetes in humans and cats but recent data are missing in dogs, although there is evidence that the unprecedented rise in canine obesity in the last decade has led to a rise in canine diabetes of similar magnitude. The insulin resistance of obesity has often been portrayed as major culprit in the loss of glucose control...

  13. Comparative Aspects of Human, Canine, and Feline Obesity and Factors Predicting Progression to Diabetes

    Directory of Open Access Journals (Sweden)

    Margarethe Hoenig

    2014-08-01

    Full Text Available Obesity and diabetes mellitus are common diseases in humans, dogs and cats and their prevalence is increasing. Obesity has been clearly identified as a risk factor for type 2 diabetes in humans and cats but recent data are missing in dogs, although there is evidence that the unprecedented rise in canine obesity in the last decade has led to a rise in canine diabetes of similar magnitude. The insulin resistance of obesity has often been portrayed as major culprit in the loss of glucose control; however, insulin resistance alone is not a good indicator of progression to diabetes in people or pets. A loss of beta cell function is necessary to provide the link to impaired fasting and post-prandial plasma glucose. Increased endogenous glucose output by the liver is also a prerequisite for the increase in fasting blood glucose when non-diabetic obese humans and pets develop diabetes. This may be due to decreased hepatic insulin sensitivity, decreased insulin concentrations, or a combination of both. While inflammation is a major link between obesity and diabetes in humans, there is little evidence that a similar phenomenon exists in cats. In dogs, more studies are needed to examine this important issue.

  14. Topically applied connective tissue growth factor/CCN2 improves diabetic preclinical cutaneous wound healing: potential role for CTGF in human diabetic foot ulcer healing.

    Science.gov (United States)

    Henshaw, F R; Boughton, P; Lo, L; McLennan, S V; Twigg, S M

    2015-01-01

    Topical application of CTGF/CCN2 to rodent diabetic and control wounds was examined. In parallel research, correlation of CTGF wound fluid levels with healing rate in human diabetic foot ulcers was undertaken. Full thickness cutaneous wounds in diabetic and nondiabetic control rats were treated topically with 1 μg rhCTGF or vehicle alone, on 2 consecutive days. Wound healing rate was observed on day 14 and wound sites were examined for breaking strength and granulation tissue. In the human study across 32 subjects, serial CTGF regulation was analyzed longitudinally in postdebridement diabetic wound fluid. CTGF treated diabetic wounds had an accelerated closure rate compared with vehicle treated diabetic wounds. Healed skin withstood more strain before breaking in CTGF treated rat wounds. Granulation tissue from CTGF treatment in diabetic wounds showed collagen IV accumulation compared with nondiabetic animals. Wound α-smooth muscle actin was increased in CTGF treated diabetic wounds compared with untreated diabetic wounds, as was macrophage infiltration. Endogenous wound fluid CTGF protein rate of increase in human diabetic foot ulcers correlated positively with foot ulcer healing rate (r = 0.406; P diabetic foot ulcers.

  15. The Inflammatory Transcription Factors NFκB, STAT1 and STAT3 Drive Age-Associated Transcriptional Changes in the Human Kidney

    Science.gov (United States)

    O’Brown, Zach K.; Van Nostrand, Eric L.; Higgins, John P.; Kim, Stuart K.

    2015-01-01

    Human kidney function declines with age, accompanied by stereotyped changes in gene expression and histopathology, but the mechanisms underlying these changes are largely unknown. To identify potential regulators of kidney aging, we compared age-associated transcriptional changes in the human kidney with genome-wide maps of transcription factor occupancy from ChIP-seq datasets in human cells. The strongest candidates were the inflammation-associated transcription factors NFκB, STAT1 and STAT3, the activities of which increase with age in epithelial compartments of the renal cortex. Stimulation of renal tubular epithelial cells with the inflammatory cytokines IL-6 (a STAT3 activator), IFNγ (a STAT1 activator), or TNFα (an NFκB activator) recapitulated age-associated gene expression changes. We show that common DNA variants in RELA and NFKB1, the two genes encoding subunits of the NFκB transcription factor, associate with kidney function and chronic kidney disease in gene association studies, providing the first evidence that genetic variation in NFκB contributes to renal aging phenotypes. Our results suggest that NFκB, STAT1 and STAT3 underlie transcriptional changes and chronic inflammation in the aging human kidney. PMID:26678048

  16. The protolobar structure of the human kidney: Its biologic and clinical significance

    International Nuclear Information System (INIS)

    Inke, G.

    1988-01-01

    This book depicts the uniqueness of each kidney as a result of the interaction of the process of nephronogenesis with the random variability of vascular channels within the bounds of a limited space. The fields of anatomy, developmental biology, comparative morphology, embryology, nephrology, pathology, physiology, radiology, and urologic surgery are treated

  17. Effect of brain death on gene expression and tissue activation in human donor kidneys

    NARCIS (Netherlands)

    Nijboer, WN; Schuurs, TA; van der Hoeven, JAB; Fekken, S; Wiersema-Buist, J; Leuvenink, HGD; Hofker, Hendrik; Homan van der Heide, J; van Son, WJ; Ploeg, RJ

    2004-01-01

    Background. After kidney transplantation, decreased graft survival is seen in grafts from brain dead (BD) donors compared with living donors. This might result partly from a progressive nonspecific inflammation in the graft. In this study, we focused on the effects of BD on inflammatory response

  18. Effect of brain death on gene expression and tissue activation in human donor kidneys

    NARCIS (Netherlands)

    Nijboer, Willemijn N.; Schuurs, Theo A.; van der Hoeven, Joost A. B.; Fekken, Susan; Wiersema-Buist, Janneke; Leuvenink, Henri G. D.; Hofker, Sijbrand; Homan van der Heide, Jaap J.; van Son, Willem J.; Ploeg, Rutger J.

    2004-01-01

    After kidney transplantation, decreased graft survival is seen in grafts from brain dead (BD) donors compared with living donors. This might result partly from a progressive nonspecific inflammation in the graft. In this study, we focused on the effects of BD on inflammatory response (adhesion

  19. Research of human kidney thermal properties for the purpose of cryosurgery

    Science.gov (United States)

    Ponomarev, D. E.; Pushkarev, A. V.

    2017-11-01

    Calculation of the heat transfer is required to correctly predict the results of cryosurgery, cryopreservation, etc. One of the important initial pa