WorldWideScience

Sample records for human diabetic kidney

  1. Microarray profile of human kidney from diabetes, renal cell carcinoma and renal cell carcinoma with diabetes

    OpenAIRE

    Kosti, Adam; Harry Chen, Hung-I; Mohan, Sumathy; Liang, Sitai; Chen, Yidong; Habib, Samy L.

    2015-01-01

    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 screened whole human DNA genome from healthy control, patients with diabetes or renal cell carcinoma (RCC) or RCC+diabetes. We found that 883 genes gain/163 genes loss of copy number in RCC+diabetes group, 669 genes gain/307 genes loss in RCC group and 458 genes gain/38 genes loss of copy number in diabetes group, after removing gain/loss genes ob...

  2. Diabetes and Kidney Disease

    Science.gov (United States)

    ... disease of diabetes, or diabetic nephropathy. How does diabetes cause kidney disease? High blood glucose , also called ... I keep my kidneys healthy if I have diabetes? The best way to slow or prevent diabetes- ...

  3. 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 ...

  4. 76 FR 20358 - National Institute of Diabetes and Digestive and Kidney Diseases Diabetes Mellitus Interagency...

    Science.gov (United States)

    2011-04-12

    ... . Dated: April 4, 2011. Sanford Garfield, Executive Secretary, DMICC, Division of Diabetes, Endocrinology... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases Diabetes Mellitus Interagency Coordinating Committee; Notice of Workshop The Diabetes...

  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. Effects of SGLT2 Inhibition in Human Kidney Proximal Tubular Cells—Renoprotection in Diabetic Nephropathy?

    OpenAIRE

    Usha Panchapakesan; Kate Pegg; Simon Gross; Muralikrishna Gangadharan Komala; Harshini Mudaliar; Josephine Forbes; Carol Pollock; Amanda Mather

    2013-01-01

    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 fib...

  7. Diabetes and kidney disease

    Science.gov (United States)

    Diabetic nephropathy; Nephropathy - diabetic; Diabetic glomerulosclerosis; Kimmelstiel-Wilson disease ... 26696680 . Tong LL, Adler S. Prevention and treatment of diabetic nephropathy. In: Johnson RJ, Feehally J, Floege J, eds. ...

  8. C-peptide and diabetic kidney disease.

    Science.gov (United States)

    Brunskill, N J

    2017-01-01

    Kidney disease is a serious development in diabetes mellitus and poses an increasing clinical problem. Despite increasing incidence and prevalence of diabetic kidney disease, there have been no new therapies for this condition in the last 20 years. Mounting evidence supports a biological role for C-peptide, and findings from multiple studies now suggest that C-peptide may beneficially affect the disturbed metabolic and pathophysiological pathways leading to the development of diabetic nephropathy. Studies of C-peptide in animal models and in humans with type 1 diabetes all suggest a renoprotective effect for this peptide. In diabetic rodents, C-peptide reduces glomerular hyperfiltration and albuminuria. Cohort studies of diabetic patients with combined islet and kidney transplants suggest that maintained C-peptide secretion is protective of renal graft function. Further, in short-term studies of patients with type 1 diabetes, administration of C-peptide is also associated with a lowered hyperfiltration rate and reduced microalbuminuria. Thus, the available information suggests that type 1 diabetes should be regarded as a dual hormone deficiency disease and that clinical trials of C-peptide in diabetic nephropathy are both justified and urgently required.

  9. Histological changes of kidney in diabetic nephropathy.

    Science.gov (United States)

    Pourghasem, Mohsen; Shafi, Hamid; Babazadeh, Zahra

    2015-01-01

    Diabetes mellitus is the most common cause of chronic renal disorders and end-stage kidney disease in developed countries. It is the major cause of dialysis and transplantation. Failure in renal function causes wide disorders in the body. Diabetes results in wide range of alterations in the renal tissue. It is believed that early histological changes in diabetic nephropathy are detectable 2 years after diabetes is diagnosed. The glomerular alterations are the most important lesions in the diabetic nephropathy (DN). The Renal Pathology Society provides a new pathological classification for the detection of histopathology of DN. It divides diabetic nephropathy into four hierarchical glomerular lesions. Alloxan or streptozotocin induced diabetic rat is the one most widely used specie to study DN. Histological changes in the rat DN closely resemble the human disease and the most information of this review was obtained through the study of rat DN. All cell types of the kidney such as mesangial cells, podocytes and tubulointerstitial cells are liable to be affected in the event of DN. Severity of renal lesions is associated to the clinical aspect of renal outcome, but the aim of this article was only to review the histological changes of kidney in diabetes mellitus.

  10. Aldose reductase inhibition counteracts nitrosative stress and poly(ADP-ribose) polymerase activation in diabetic rat kidney and high-glucose-exposed human mesangial cells

    OpenAIRE

    Drel, Viktor R.; Pacher, Pal; Stevens, Martin J; Obrosova, Irina G.

    2006-01-01

    Both increased aldose reductase (AR) activity and oxidative/nitrosative stress have been implicated in the pathogenesis of diabetic nephropathy, but the relation between the two factors remains a subject of debate. This study evaluated the effects of AR inhibition on nitrosative stress and poly(ADP-ribose) polymerase (PARP) activation in diabetic rat kidney and high-glucose-exposed human mesangial cells. In animal experiments, control (C) and streptozotocin-diabetic (D) rats were treated with...

  11. Human iPS cell-derived insulin producing cells form vascularized organoids under the kidney capsules of diabetic mice.

    Directory of Open Access Journals (Sweden)

    Sudhanshu P Raikwar

    Full Text Available Type 1 diabetes (T1D is caused by autoimmune disease that leads to the destruction of pancreatic β-cells. Transplantation of cadaveric pancreatic organs or pancreatic islets can restore normal physiology. However, there is a chronic shortage of cadaveric organs, limiting the treatment of the majority of patients on the pancreas transplantation waiting list. Here, we hypothesized that human iPS cells can be directly differentiated into insulin producing cells (IPCs capable of secreting insulin. Using a series of pancreatic growth factors, we successfully generated iPS cells derived IPCs. Furthermore, to investigate the capability of these cells to secrete insulin in vivo, the differentiated cells were transplanted under the kidney capsules of diabetic immunodeficient mice. Serum glucose levels gradually declined to either normal or near normal levels over 150 days, suggesting that the IPCs were secreting insulin. In addition, using MRI, a 3D organoid appeared as a white patch on the transplanted kidneys but not on the control kidneys. These organoids showed neo-vascularization and stained positive for insulin and glucagon. All together, these data show that a pancreatic organ can be created in vivo providing evidence that iPS cells might be a novel option for the treatment of T1D.

  12. [Diabetic nephropathy/diabetic kidney disease].

    Science.gov (United States)

    Boucek, P

    2013-03-01

    Diabetic kidney disease (DKD), which belongs to the triad of diabetic microvascular complications, is currently the main cause of end-stage renal disease in developed countries. DKD usually simultaneously leads to a deteriorated long-term control of glucose metabolism and blood pressure, and to the development of diabetic retinopathy, neuropathy and atherosclerotic complications, which are the main causes of patients' mortality. Screening of the initial stages of DKD is to be based on the detection of increased albumin leak into the urine, microalbuminuria, and the reduction of renal function by means of estimates of glomerular filtration rate based on the serum creatinine level. The main objective of the prophylactic and treatment measures is to prevent the onset of DKD, or at least to stop its transition into an irreversible, progressive stage characterised by a permanent, often nephrotic proteinuria. The basic procedures in the prevention and treatment of DKD are maintaining the optimal metabolic control of diabetes and intensive hypertension treatment based on the inhibition of the renin-angiotensin system. Reaching the stage of progressive renal insufficiency (serum creatinine level approximately > or = 200 micromol/l) is an indication for further follow-up in the nephrology department, which will then take the necessary preparatory measures for dialysis treatment. The optimal method of kidney function replacement for patients with DKD is kidney transplantation, or combined kidney-pancreas transplantation in patients with type 1 diabetes.

  13. Novel Role of Parathyroid Hormone-Related Protein in the Pathophysiology of the Diabetic Kidney: Evidence from Experimental and Human Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Montserrat Romero

    2013-01-01

    Full Text Available Parathyroid hormone-related protein (PTHrP and its receptor type 1 (PTH1R are extensively expressed in the kidney, where they are able to modulate renal function. Renal PTHrP is known to be overexpressed in acute renal injury. Recently, we hypothesized that PTHrP involvement in the mechanisms of renal injury might not be limited to conditions with predominant damage of the renal tubulointerstitium and might be extended to glomerular diseases, such as diabetic nephropathy (DN. In experimental DN, the overexpression of both PTHrP and the PTH1R contributes to the development of renal hypertrophy as well as proteinuria. More recent data have shown, for the first time, that PTHrP is upregulated in the kidney from patients with DN. Collectively, animal and human studies have shown that PTHrP acts as an important mediator of diabetic renal cell hypertrophy by a mechanism which involves the modulation of cell cycle regulatory proteins and TGF-β1. Furthermore, angiotensin II (Ang II, a critical factor in the progression of renal injury, appears to be responsible for PTHrP upregulation in these conditions. These findings provide novel insights into the well-known protective effects of Ang II antagonists in renal diseases, paving the way for new therapeutic approaches.

  14. Novel role of parathyroid hormone-related protein in the pathophysiology of the diabetic kidney: evidence from experimental and human diabetic nephropathy.

    Science.gov (United States)

    Romero, Montserrat; Ortega, Arantxa; Olea, Nuria; Arenas, María Isabel; Izquierdo, Adriana; Bover, Jordi; Esbrit, Pedro; Bosch, Ricardo J

    2013-01-01

    Parathyroid hormone-related protein (PTHrP) and its receptor type 1 (PTH1R) are extensively expressed in the kidney, where they are able to modulate renal function. Renal PTHrP is known to be overexpressed in acute renal injury. Recently, we hypothesized that PTHrP involvement in the mechanisms of renal injury might not be limited to conditions with predominant damage of the renal tubulointerstitium and might be extended to glomerular diseases, such as diabetic nephropathy (DN). In experimental DN, the overexpression of both PTHrP and the PTH1R contributes to the development of renal hypertrophy as well as proteinuria. More recent data have shown, for the first time, that PTHrP is upregulated in the kidney from patients with DN. Collectively, animal and human studies have shown that PTHrP acts as an important mediator of diabetic renal cell hypertrophy by a mechanism which involves the modulation of cell cycle regulatory proteins and TGF- β 1. Furthermore, angiotensin II (Ang II), a critical factor in the progression of renal injury, appears to be responsible for PTHrP upregulation in these conditions. These findings provide novel insights into the well-known protective effects of Ang II antagonists in renal diseases, paving the way for new therapeutic approaches.

  15. Vitamin D in the Pathophysiology of Hypertension, Kidney Disease, and Diabetes: Examining the Relationship Between Vitamin D and the Renin-Angiotensin System in Human Diseases

    Science.gov (United States)

    Vaidya, Anand; Williams, Jonathan S.

    2011-01-01

    Objective Vitamin D has been implicated in the pathophysiology of extra-skeletal conditions such as hypertension, kidney disease, and diabetes, via its ability to negatively regulate the renin-angiotensin system (RAS). This article reviews the evidence supporting a link between vitamin D and the RAS in these conditions, with specific emphasis on translational observations and their limitations. Methods Literature review of animal and human studies evaluating the role of vitamin D in hypertension, kidney disease, and diabetes. Results Excess activity of the RAS has been implicated in the pathogenesis of hypertension, chronic kidney disease, decreased insulin secretion, and insulin resistance. Animal studies provide strong support for 1,25(OH)2D mediated down-regulation of renin expression and RAS activity via its interaction with the vitamin D receptor. Furthermore, the activity of vitamin D metabolites in animals is associated with reductions in blood pressure, proteinuria and renal injury, and with improved β–cell function. Many observational, and a few interventional, studies in humans have supported these findings; however, there is a lack of well designed prospective human interventional studies to definitively assess clinical outcomes. Conclusion Animal studies implicate vitamin D receptor agonist therapy to lower RAS activity as a potential method to reduce the risk of hypertension, kidney disease, and diabetes. There is a need for more well designed prospective interventional studies to validate this hypothesis in human clinical outcomes. PMID:22075270

  16. 76 FR 20692 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Meeting

    Science.gov (United States)

    2011-04-13

    ... Kidney Diseases Initial Review Group; Diabetes, Endocrinology and Metabolic Diseases B Subcommittee. Date... of Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and...

  17. 76 FR 75553 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2011-12-02

    ... Kidney Diseases Special Emphasis Panel, Diabetes, Endocrinology, and Metabolism Career Awards. Date... cycle. (Catalogue of Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and...

  18. Aberrant heparan sulfate profile in the human diabetic kidney offers new clues for therapeutic glycomimetics.

    NARCIS (Netherlands)

    Wijnhoven, T.J.M.; Lensen, J.F.M.; Rops, A.L.; Vlag, J. van der; Kolset, S.O.; Bangstad, H.J.; Pfeffer, P.; Hoven, M.J.W. van den; Berden, J.H.M.; Heuvel, L.P.W.J. van den; Kuppevelt, A.H.M.S.M. van

    2006-01-01

    BACKGROUND: Diabetic nephropathy poses an increasing health problem in the Western world, and research to new leads for diagnosis and therapy therefore is warranted. In this respect, heparan sulfates (HSs) offer new possibilities because crude mixtures of these polysaccharides are capable of amelior

  19. Kidney Transplantation in the Diabetic Patient

    Directory of Open Access Journals (Sweden)

    María José Pérez-Sáez

    2015-06-01

    Full Text Available Diabetes mellitus is one of the most important causes of chronic kidney disease (CKD. In patients with advanced diabetic kidney disease, kidney transplantation (KT with or without a pancreas transplant is the treatment of choice. We aimed to review current data regarding kidney and pancreas transplant options in patients with both type 1 and 2 diabetes and the outcomes of different treatment modalities. In general, pancreas transplantation is associated with long-term survival advantages despite an increased short-term morbidity and mortality risk. This applies to simultaneous pancreas kidney transplantation or pancreas after KT compared to KT alone (either living donor or deceased. Other factors as living donor availability, comorbidities, and expected waiting time have to be considered whens electing one transplant modality, rather than a clear benefit in survival of one strategy vs. others. In selected type 2 diabetic patients, data support cautious utilization of simultaneous pancreas kidney transplantation when a living kidney donor is not an option. Pancreas and kidney transplantation seems to be the treatment of choice for most type 1 diabetic and selected type 2 diabetic patients.

  20. Aldose reductase inhibition counteracts nitrosative stress and poly(ADP-ribose) polymerase activation in diabetic rat kidney and high-glucose-exposed human mesangial cells.

    Science.gov (United States)

    Drel, Viktor R; Pacher, Pal; Stevens, Martin J; Obrosova, Irina G

    2006-04-15

    Both increased aldose reductase (AR) activity and oxidative/nitrosative stress have been implicated in the pathogenesis of diabetic nephropathy, but the relation between the two factors remains a subject of debate. This study evaluated the effects of AR inhibition on nitrosative stress and poly(ADP-ribose) polymerase (PARP) activation in diabetic rat kidney and high-glucose-exposed human mesangial cells. In animal experiments, control (C) and streptozotocin-diabetic (D) rats were treated with/without the AR inhibitor fidarestat (F, 16 mg kg(-1) day(-1)) for 6 weeks starting from induction of diabetes. Glucose, sorbitol, and fructose concentrations were significantly increased in the renal cortex of D vs C (p diabetes-induced increase in kidney weight as well as nitrotyrosine (NT, a marker of peroxynitrite-induced injury and nitrosative stress), and poly(ADP-ribose) (a marker of PARP activation) accumulation, assessed by both immunohistochemistry and Western blot analysis, in glomerular and tubular compartments of the renal cortex. In vitro studies revealed the presence of both AR and PARP-1 in human mesangial cells, and none of these two variables were affected by high glucose or F treatment. Nitrosylated and poly(ADP-ribosyl)ated proteins (Western blot analysis) accumulated in cells cultured in 30 mM D-glucose (vs 5.55 mM glucose, p diabetic renal cortex and high-glucose-exposed human mesangial cells. These findings reveal new beneficial properties of the AR inhibitor F and provide the rationale for detailed studies of F on diabetic nephropathy.

  1. [Human physiology: kidney].

    Science.gov (United States)

    Natochin, Iu V

    2010-01-01

    The content of human physiology as an independent part of current physiology is discussed. Substantiated is the point that subjects of human physiology are not only special sections of physiology where functions are inherent only in human (physiology of intellectual activity, speech, labor, sport), but also in peculiarities of functions, specificity of regulation of each of physiological systems. By the example of physiology of kidney and water-salt balance there are shown borders of norm, peculiarities of regulation in human, new chapters of renal physiology which have appeared in connection with achievements of molecular physiology.

  2. 77 FR 50518 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Meetings

    Science.gov (United States)

    2012-08-21

    ... Kidney Diseases Advisory Council; Diabetes, Endocrinology and Metabolic Diseases Subcommittee. Date... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... U.S.C. App.), notice is hereby given of meetings of the National Diabetes and Digestive and...

  3. 76 FR 25700 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2011-05-05

    ... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel, Periodontitis and Glycemic Control. Date... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive and...

  4. Diabetes Mellitus in the Transplanted Kidney

    Directory of Open Access Journals (Sweden)

    Vasil ePeev

    2014-08-01

    Full Text Available Diabetes mellitus (DM is the most common cause of chronic kidney disease (CKD and end stage renal disease (ESRD. New onset diabetes mellitus after transplant (NODAT has been described in approximately 30 percent of non-diabetic kidney transplant recipients many years post transplantation. DM in patients with kidney transplantation constitutes a major comorbidity, and has significant impact on the patients and allografts’ outcome. In addition to the major comorbidity and mortality that result from cardiovascular and other DM complications, long standing DM after kidney transplant has significant pathological injury to the allograft, which results in lowering the allografts and the patients’ survivals. In spite of the cumulative body of data on diabetic nephropathy (DN in the native kidney, there has been very limited data on the DN in the transplanted kidney. In this review, we will shed the light on the risk factors that lead to the development of NODAT. We will also describe the impact of DM on the transplanted kidney, and the outcome of kidney transplant recipients with NODAT. Additionally, we will present the most acceptable data on management of NODAT.

  5. Complications of Diabetes: Chronic Kidney Disease (CKD) and Diabetic Nephropathy

    OpenAIRE

    iyabet Dunyagoz Hospitals G

    2014-01-01

    Today, almost half of the patients who are on chronic kidney replacement therapy have diabetes. The enormous worldwide rise in these cases pose potential economic burden for every country and therefore monitoring kidney function should be a practice provided in outpatient settings. Poorly controlled diabetes will not only result in chronic renal failure, but also patients with chronic renal disease will have some metabolic abnormalities that will increase both morbidity and mortality of the p...

  6. 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.

  7. 78 FR 34663 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2013-06-10

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive and Kidney Diseases Special Emphasis Panel, PAR-12-265 Ancillary Studies: The Microbiome in Child...

  8. 76 FR 60849 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2011-09-30

    ... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive and Kidney Diseases Special Emphasis Panel, FGF23 Physiology. Date: November 7, 2011. Time: 12 p.m. to 1...

  9. Diabetic kidney disease:Act now or pay later

    Institute of Scientific and Technical Information of China (English)

    Robert C Atkins; Paul Zimmet

    2009-01-01

    @@ For the 2010 International Society of Nephrology/International Federation of Kidney Foundations World Kidney Day Steering Committee~* ( RA ) and the International Diabetes Federation (PZ) World Kidney Day 11 March 2010: we must act on diabetic kidney disease In 2003, the International Society of Nephrology and the International Diabetes Federation launched a booklet called " Diabetes in the Kidney: Time to act"~([1]) to highlight the global pandemic of type 2 diabetes and diabetic kidney disease. It aimed to alert governments, health organisations, providers, doctors and patients to the increasing health and socio-economic problems due to diabetic kidney disease and its sequelae, end stage kidney disease requiring dialysis and cardiovascular death. Seven years later, the same message has become even more urgent.

  10. Kidney growth in normal and diabetic mice is not affected by human insulin-like growth factor binding protein-1 administration

    NARCIS (Netherlands)

    V. Cingel-Ristic; B.F. Schrijvers; A.K. van Vliet (Arlène); R. Rasch; V.K. Han; S.L.S. Drop (Stenvert); A. Flyvbjerg (Allan)

    2005-01-01

    textabstractInsulin-like growth factor I (IGF-I) accumulates in the kidney following the onset of diabetes, initiating diabetic renal hypertrophy. Increased renal IGF-I protein content, which is not reflected in messenger RNA (mRNA) levels, suggests that renal IGF-I accumulation is

  11. Diabetes and chronic kidney disease

    African Journals Online (AJOL)

    2007-08-16

    Aug 16, 2007 ... to be classified as nephrotic syndrome. In the natural history of ... low-protein diet (which blocks afferent arteriolar dilatation) or .... Rapid decline in renal function without significant proteinuria, particularly in type 2 diabetics ...

  12. 77 FR 34395 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2012-06-11

    ... Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  13. 78 FR 14312 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2013-03-05

    ... Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  14. 75 FR 39548 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2010-07-09

    .... 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and Nutrition... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  15. 76 FR 60507 - National Institute of Diabetes and Digestive and Kidney Diseases Notice of Closed Meeting

    Science.gov (United States)

    2011-09-29

    ... Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  16. 78 FR 15728 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2013-03-12

    ....gov . (Catalogue of Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  17. 77 FR 10540 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2012-02-22

    ... Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  18. 77 FR 8889 - National Institute of Diabetes and Digestive and Kidney Diseases Notice of Closed Meeting

    Science.gov (United States)

    2012-02-15

    ...@niddk.nih.gov . (Catalogue of Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  19. 76 FR 23325 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2011-04-26

    ... . (Catalogue of Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  20. 78 FR 6123 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2013-01-29

    ....nih.gov . (Catalogue of Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  1. 78 FR 5467 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2013-01-25

    ... . (Catalogue of Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  2. 75 FR 4094 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2010-01-26

    ... Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  3. 75 FR 27350 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2010-05-14

    ... Kidney Diseases Special Emphasis Panel; Team Science (R24) in Diabetes, Endocrinology and Metabolic... Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and...

  4. 78 FR 26641 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2013-05-07

    ... Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  5. 77 FR 47082 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2012-08-07

    ... Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  6. 77 FR 33751 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2012-06-07

    ....gov . (Catalogue of Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  7. 76 FR 71986 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2011-11-21

    ....gov . (Catalogue of Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  8. 77 FR 28396 - National Institute of Diabetes and Digestive and Kidney Diseases Notice of Closed Meetings

    Science.gov (United States)

    2012-05-14

    ....gov . (Catalogue of Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  9. 78 FR 11212 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2013-02-15

    ...@niddk.nih.gov . (Catalogue of Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  10. 77 FR 6130 - National Institute of Diabetes and Digestive and Kidney Diseases Notice of Closed Meeting

    Science.gov (United States)

    2012-02-07

    ..., ls38z@nih.gov . (Catalogue of Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  11. 76 FR 56206 - National Institute of Diabetes and Digestive and Kidney Diseases Notice of Closed Meetings

    Science.gov (United States)

    2011-09-12

    ... Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  12. 77 FR 20646 - National Institute of Diabetes and Digestive and Kidney Diseases: Notice of Closed Meeting

    Science.gov (United States)

    2012-04-05

    ..., Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and Nutrition Research; 93.849... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  13. 76 FR 67749 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2011-11-02

    ... Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  14. 76 FR 56207 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2011-09-12

    ....847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and Nutrition Research... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Commitee: National Institute of Diabetes and Digestive...

  15. 77 FR 65698 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2012-10-30

    .... 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and Nutrition... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  16. 76 FR 37133 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2011-06-24

    ... . (Catalogue of Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  17. 78 FR 36554 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2013-06-18

    ... Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  18. 76 FR 78286 - National Institute of Diabetes and Digestive and Kidney Diseases Notice of Closed Meeting

    Science.gov (United States)

    2011-12-16

    ....847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and Nutrition Research... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  19. 76 FR 63933 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2011-10-14

    ....847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and Nutrition Research... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  20. 77 FR 66076 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2012-11-01

    ... Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  1. 75 FR 32485 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2010-06-08

    ....gov . (Catalogue of Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  2. 75 FR 54891 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2010-09-09

    ....847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and Nutrition Research... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  3. 78 FR 11211 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2013-02-15

    .... 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and Nutrition... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  4. 76 FR 20359 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2011-04-12

    ....847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and Nutrition Research... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  5. 78 FR 55266 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2013-09-10

    ... Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  6. 78 FR 19275 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2013-03-29

    ... Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... individual intramural programs and projects conducted by the National Institute of Diabetes and Digestive...

  7. 78 FR 75358 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2013-12-11

    ... Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and Nutrition... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  8. 77 FR 50515 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2012-08-21

    ....gov . (Catalogue of Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  9. 78 FR 13360 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2013-02-27

    ...@mail.nih.gov . (Catalogue of Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  10. 76 FR 45585 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2011-07-29

    ..., Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and Nutrition Research; 93.849... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  11. 77 FR 15784 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2012-03-16

    ... Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  12. 76 FR 4926 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Meeting

    Science.gov (United States)

    2011-01-27

    ... Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  13. 75 FR 57971 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2010-09-23

    ... cycle. (Catalogue of Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  14. 76 FR 57747 - National Institute of Diabetes and Digestive and Kidney Diseases Notice of Meetings

    Science.gov (United States)

    2011-09-16

    ... Review Group; Diabetes, Endocrinology and Metabolic Diseases B Subcommittee. Date: October 26-28, 2011... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  15. 77 FR 12855 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2012-03-02

    ... Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  16. 78 FR 6122 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2013-01-29

    ... Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  17. 78 FR 63994 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2013-10-25

    .... 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and Nutrition... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  18. 75 FR 9911 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2010-03-04

    ... Kidney Diseases Special Emphasis Panel, Seeding Team Science in Diabetes Endocrinology and Metabolic... Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and...

  19. 78 FR 18613 - National Institute of Diabetes and Digestive and Kidney Diseases Notice of Closed Meeting

    Science.gov (United States)

    2013-03-27

    ...@niddk.nih.gov . (Catalogue of Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  20. 76 FR 31618 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2011-06-01

    ....gov . (Catalogue of Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  1. 77 FR 40368 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2012-07-09

    ... Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  2. 76 FR 8752 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2011-02-15

    ....gov .(Catalogue of Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  3. 75 FR 28029 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2010-05-19

    ....gov . (Catalogue of Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  4. 78 FR 17421 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2013-03-21

    ... . (Catalogue of Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  5. 76 FR 64358 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2011-10-18

    ... Program Nos. 93.847, Diabetes, ] Endocrinology and Metabolic Research; 93.848, Digestive Diseases and... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  6. 75 FR 5602 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2010-02-03

    .... 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and Nutrition... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  7. 77 FR 25488 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2012-04-30

    ... Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  8. 77 FR 71430 - National Institute of Diabetes and Digestive and Kidney Diseases Notice of Closed Meeting

    Science.gov (United States)

    2012-11-30

    ... Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  9. 77 FR 34396 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2012-06-11

    ... Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  10. 77 FR 33750 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2012-06-07

    ... Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and Nutrition... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  11. 78 FR 21381 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2013-04-10

    ..., Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and Nutrition Research; 93.849... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  12. Diabetes and the kidney in pregnancy.

    Science.gov (United States)

    Powe, Camille E; Thadhani, Ravi

    2011-01-01

    The prevalence of diabetes in pregnant women is increasing, with 4% of deliveries in the United States occurring in women with pregestational or gestational diabetes. The proteinuria of late pregnancy is exaggerated in women with diabetes. However, diabetic women with preserved renal function before pregnancy appear to have little risk of deterioration of kidney function during pregnancy. Women with impaired renal function before pregnancy may be at risk for permanent decline of renal function during pregnancy, although it is unclear whether this represents the effect of pregnancy or the natural history of their diabetic renal disease. Preeclampsia, which is more common in women with diabetes, may be difficult to diagnose in this group of women. From the currently available literature, there appears to be no negative effect of pregnancy on the long-term progression of diabetic renal disease if renal function is normal and marked proteinuria is absent, but in light of recent findings in which preeclampsia appears to be associated with an increased risk of end-stage renal disease, large cohort studies will be necessary before this question can be definitively answered.

  13. 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 ...

  14. Prevalence of Diabetes Mellitus in Patients with Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Olivera Stojceva-Taneva

    2016-01-01

    CONCLUSION: Our study showed that chronic kidney disease is frequent in the Republic of Macedonia and is associated with older age and diabetes. Diabetes had a significantly stronger association with CKD at younger age.

  15. Anaemia and kidney dysfunction in Caribbean Type 2 diabetic patients

    OpenAIRE

    Seales Dawn; Nwagbara Emeka; Jones-LeCointe Altheia; Ezenwaka Chidum E; Okali Fidelis

    2008-01-01

    Abstract Background Anaemia has been shown in previous studies to be a risk factor for cardiovascular disease in diabetic patients with chronic kidney disorder. This study was aimed to assess the prevalence of anaemia and kidney dysfunction in Caribbean type 2 diabetic patients that have been previously shown to have a high prevalence of the metabolic syndrome. Methods 155 type 2 diabetic patients and 51 non-diabetic subjects of African origin were studied. Anthropometric parameters were meas...

  16. 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

  17. 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.

  18. 75 FR 61765 - National Institute of Diabetes and Digestive and Kidney Diseases; Amended Notice of Meeting

    Science.gov (United States)

    2010-10-06

    ... 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 Diabetes, Endocrinology and Metabolic Diseases B Subcommittee, October 20, 2010, 5 p.m. to October 22, 2010, 5 p.m.,...

  19. 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.

  20. 78 FR 76849 - National Institute of Diabetes and Digestive and Kidney and Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2013-12-19

    ..., Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and Nutrition Research; 93.849... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney and... unwarranted invasion of personal privacy. Name of Committee: National Institute of Diabetes and Digestive...

  1. The human kidney as a regulator of body cytokine homeostasis

    Directory of Open Access Journals (Sweden)

    A. Bonanni

    2011-01-01

    Full Text Available Evidence is accumulating that the human kidney is a major site for the removal of several cytokines and growth factors, which can accumulate in body pools in patients with acute and chronic kidney disease (CKD. In addition, progressive renal failure and the increase in circulating proinflammatory cytokines are associated with mortality, suggesting that altered cytokines handling by the kidney is associated with worse outcome. Also, the kidney itself may be damaged by signals arising by endothelia and peripheral tissues during the course of the metabolic syndrome, type 2 diabetes and obesity. In this paper we provide a review of kidney handling of several adipokines and myokines, with special emphasis to interleukin-6 (IL-6, leptin, resistin and transforming growth factor-beta (TGF-beta.

  2. Ursolic Acid provides kidney protection in diabetic rats.

    Science.gov (United States)

    Ling, Chen; Jinping, Lu; Xia, Li; Renyong, Yang

    2013-12-01

    Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes and the leading cause of end-stage renal failure. However, the treatment of DN is still a problem in the world. Inflammatory process plays a critical role in the development of DN. Therefore, anti-inflammatory treatment of DN is worth exploring now and in the future. The study aimed to evaluate the impact of ursolic acid (UA) on renal function in streptozotocin-induced diabetes. Rats with streptozotocin-induced diabetes were treated with UA for 16 weeks. After 16 weeks, urine albumin excretion, serum creatinine, and blood urea nitrogen were measured. In addition, renal oxidative stress level, nuclear factor kappa-B (NF-κB) activity, P-selectin expression, and kidney histopathologic changes were evaluated. Sixteen weeks following streptozotocin injection, the rats produced significant alteration in renal function and increased oxidative stress, NF-κB activity, and P-selectin expression in the kidneys. Interestingly, UA significantly prevented biochemical and histopathologic changes in the kidneys associated with diabetes. Compared with untreated diabetic rats, UA treatment lowered urine albumin excretion, renal oxidative stress level, NF-κB activity, and P-selectin expression. Moreover, UA treatment also improved renal histopathologic changes in rats with diabetes. UA treatment exhibited a protective effect on kidneys in diabetic rats, implying that UA could be a potential treatment for diabetic nephropathy.

  3. Ursolic Acid Provides Kidney Protection in Diabetic Rats☆

    Science.gov (United States)

    Ling, Chen; Jinping, Lu; Xia, Li; Renyong, Yang

    2013-01-01

    Background Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes and the leading cause of end-stage renal failure. However, the treatment of DN is still a problem in the world. Inflammatory process plays a critical role in the development of DN. Therefore, anti-inflammatory treatment of DN is worth exploring now and in the future. Objective The study aimed to evaluate the impact of ursolic acid (UA) on renal function in streptozotocin-induced diabetes. Methods Rats with streptozotocin-induced diabetes were treated with UA for 16 weeks. After 16 weeks, urine albumin excretion, serum creatinine, and blood urea nitrogen were measured. In addition, renal oxidative stress level, nuclear factor kappa-B (NF-κB) activity, P-selectin expression, and kidney histopathologic changes were evaluated. Results Sixteen weeks following streptozotocin injection, the rats produced significant alteration in renal function and increased oxidative stress, NF-κB activity, and P-selectin expression in the kidneys. Interestingly, UA significantly prevented biochemical and histopathologic changes in the kidneys associated with diabetes. Compared with untreated diabetic rats, UA treatment lowered urine albumin excretion, renal oxidative stress level, NF-κB activity, and P-selectin expression. Moreover, UA treatment also improved renal histopathologic changes in rats with diabetes. Conclusions UA treatment exhibited a protective effect on kidneys in diabetic rats, implying that UA could be a potential treatment for diabetic nephropathy. PMID:24465045

  4. Diabetic ketoacidosis, sodium glucose transporter-2 inhibitors and the kidney.

    Science.gov (United States)

    Palmer, Biff F; Clegg, Deborah J; Taylor, Simeon I; Weir, Matthew R

    2016-08-01

    Diabetic ketoacidosis is a serious metabolic condition that may occur in patients with either Type 1 or Type 2 diabetes. The accumulation of ketoacids in the serum is a consequence of insulin deficiency and glucagon excess. Sodium Glucose Transporter 2 (SGLT2) inhibitors are novel therapeutic treatments for improving glucose homeostasis in patients with diabetes. Through reductions in glucose reabsorption by the kidney, they lower serum glucose in patients with Type 2 diabetes and they improve glucose control whether used alone or in combination with other therapies. Mechanistically, these drugs increase serum ketoacids and increase glucagon production, which in some individuals, can lead to formation of diabetic ketoacidosis. This review will first focus in how the kidney normally handles ketoacids, and second will discuss how the SGLT2 inhibitors affect the kidney in such a way so as to enhance the risk for development of ketoacidosis in susceptible individuals.

  5. Anaemia and kidney dysfunction in Caribbean Type 2 diabetic patients

    Directory of Open Access Journals (Sweden)

    Seales Dawn

    2008-08-01

    Full Text Available Abstract Background Anaemia has been shown in previous studies to be a risk factor for cardiovascular disease in diabetic patients with chronic kidney disorder. This study was aimed to assess the prevalence of anaemia and kidney dysfunction in Caribbean type 2 diabetic patients that have been previously shown to have a high prevalence of the metabolic syndrome. Methods 155 type 2 diabetic patients and 51 non-diabetic subjects of African origin were studied. Anthropometric parameters were measured and fasting blood samples were collected for glucose, creatinine, glycated hemoglobin and complete blood count. Anaemia was defined as haemoglobin 2. Comparisons for within- and between-gender, between diabetic and non-diabetic subjects were performed using Student's t-test while chi-square test was employed for categorical variables. Results The diabetic patients were older than the non-diabetic subjects. While male non-diabetic subjects had significantly higher red blood cell count (RBC, haemoglobin and hematocrit concentrations than non-diabetic female subjects (p 2, p Conclusion A high prevalence of anaemia was identified in this group of type 2 diabetic patients previously shown to have a high prevalence of the metabolic syndrome. It is therefore recommended that diagnostic laboratories in developing countries and elsewhere should include complete blood count in routine laboratory investigations in the management of diabetic patients.

  6. Diabetic kidney disease : a clinical update from Kidney Disease: Improving Global Outcomes

    NARCIS (Netherlands)

    Molitch, Mark E.; Adler, Amanda I.; Flyvbjerg, Allan; Nelson, Robert G.; So, Wing-Yee; Wanner, Christoph; Kasiske, Bertram L.; Wheeler, David C.; de Zeeuw, Dick; Mogensen, Carl E.

    The incidence and prevalence of diabetes mellitus (DM) continue to grow markedly throughout the world, due primarily to the increase in type 2 DM (T2DM). Although improvements in DM and hypertension management have reduced the proportion of diabetic individuals who develop chronic kidney disease

  7. Diabetic nephropathy; principles of diagnosis and treatment of diabetic kidney disease

    OpenAIRE

    Nazar, Chaudhary Muhammad Junaid

    2014-01-01

    Diabetes mellitus is a leading epidemic of the present world. It is considered the leading cause of death among end-stage renal disease (ESRD) patients. The complications associated with diabetes mellitus have boosted the number of deaths in the last years. These complications are the result of long lasting effects of diabetes mellitus on the glomerular microvasculature of the kidney. Diabetic nephropathy (DN) develops in patients with several years’ medical history of diabetes and renal fail...

  8. 78 FR 62639 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2013-10-22

    ... Kidney Diseases Special Emphasis Panel; Diabetic Nephropathy Ancillary Studies. Date: December 6, 2013... and Metabolic Research; 93.848, Digestive Diseases and Nutrition Research; 93.849, Kidney...

  9. 78 FR 55086 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Meeting

    Science.gov (United States)

    2013-09-09

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. App.), notice is hereby given of a...

  10. Large kidneys predict poor renal outcome in subjects with diabetes and chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Vendrely Benoit

    2010-03-01

    Full Text Available Abstract Background Renal hypertrophy occurs early in diabetic nephropathy, its later value is unknown. Do large kidneys still predict poor outcome in patients with diabetes and Chronic Kidney Disease (CKD? Methods Seventy-five patients with diabetes and CKD according to a Glomerular Filtration Rate (GFR, by 51Cr-EDTA clearance below 60 mL/min/1.73 m2 or an Albumin Excretion Rate above 30 mg/24 H, had an ultrasound imaging of the kidneys and were cooperatively followed during five years by the Diabetology and Nephrology departments of the Centre Hospitalier Universitaire de Bordeaux. Results The patients were mainly men (44/75, aged 62 ± 13 yrs, with long-standing diabetes (duration:17 ± 9 yrs, 55/75 type 2, and CKD: initial GFR: 56.5 (8.5-209 mL/min/1.73 m2, AER: 196 (20-2358 mg/24 H. Their mean kidney lenght (108 ± 13 mm, 67-147 was correlated to the GFR (r = 0.23, p Conclusions Large kidneys still predict progression in advanced CKD complicating diabetes. In these patients, ultrasound imaging not only excludes obstructive renal disease, but also provides information on the progression of the renal disease.

  11. Diabetic kidney disease; review of the current knowledge.

    Science.gov (United States)

    Shahbazian, Heshmatollah; Rezaii, Isa

    2013-01-01

    Diabetes is the most common cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in most parts of the world. 20 to 30% of diabetic patient have diabetic nephropathy in type 1 and type 2. Hyperglycemia is the key of nephropathy creation. Hyperglycemia also by production of toxic materials, advanced glycosylated end product (AGE), increased activity of aldose reductase has some role. Some metabolites of arachidonic acid, hemodynamic derangements and genetic factors have also some role. Although diabetic nephropathy is most common cause of nephropathy in these patients, but diabetic patients are also prone to other urinary tract and renal parenchymal disease and should not be confused with renal failure due to diabetic nephropathy. The principle of treatment of diabetic nephropathy is based on tight control of hyperglycemia, tight control of blood pressure and glomerular pressure, control of dyslipidemia, restriction of protein intake and smoking withdrawal.

  12. A novel SGLT is expressed in the human kidney

    OpenAIRE

    Kothinti, Rajendra K.; Blodgett, Amy B.; North, Paula E.; Roman, Richard J.; Tabatabai, Niloofar M.

    2012-01-01

    Selective inhibitors of sodium-glucose cotransporter 2 (SGLT2)-mediated reabsorption of glucose in the proximal tubule of the kidney are being developed for the treatment of diabetes. SGLT2 shares high degree of homology with SGLT3; however, very little is known about the expression and functional role of SGLT3 in the human kidney. Indeed, the SGLT2 inhibitors that are currently in clinical trials might affect the expression and/or the activity of SGLT3. Therefore, the present study examined ...

  13. [Pentosan polysulfate sodium prevents kidney morphological changes and albuminuria in rats with type 1 diabetes].

    Science.gov (United States)

    Mathison Natera, Y; Finol, H J; Quero, Z; González, R; González, J

    2010-01-01

    Decreased levels of glycosaminoglycans (GAGs) have been observed in the kidney and other organs, in human and animal models of diabetes. Long-term administration of heparins and other glycosaminoglycans has demonstrated a beneficial effect on morphological and functional kidney abnormalities in diabetic rats. We assessed the effect of pentosan polysulfate sodium (PPS), a semi-synthetic glycosaminoglycan with low anticoagulant activity, on kidney involvement in streptozotocin diabetic rats. Diabetes was induced in male Sprague-Dawley rats by i.v. administration of streptozotocin (STZ). Animals were randomly allocated to three groups: C = control, STZ and STZ + PPS = pretreated with PPS (15 mg/kg, s.c.). After three months of follow-up, blood and 24 h-urine samples were obtained, the animals were sacrificed and the kidney microdissected for morphometric analysis. Urinary albumin excretion was markedly increased in untreated diabetic rats (C = 0.26 ± 0.03 vs STZ = 7.75 ± 1.8 mg/24 h) and PPS treatment partially prevented the albumin rise (3.7 ± 0.7 mg/24 h), without affecting the metabolic control HbA1c (C = 3.6 ± 1.7; STZ = 8.82 ± 0.47; STZ + PPS = 8.63 ± 0.54). Electron microscope observation revealed typical renal lesions described in experimental diabetes (STZ group). PPS administration prevents the tubular basement membrane thickening and the loss of cytoarchitecture induced by experimental diabetes. Our data demonstrate that long-term administration of PPS has a favourable effect on morphological and functional abnormalities in kidneys of diabetic rats and suggests a potential therapeutic use for this compound.

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

    OpenAIRE

    Miranda-Díaz, Alejandra Guillermina; Pazarín-Villaseñor, Leonardo; Yanowsky-Escatell, Francisco Gerardo; Andrade-Sierra, Jorge

    2016-01-01

    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 disea...

  15. New-onset diabetes mellitus after kidney transplantation in Denmark

    DEFF Research Database (Denmark)

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

    2010-01-01

    Background and objectives: This study aimed to investigate the development of new-onset diabetes mellitus (NODM) in a prospective study of 97 nondiabetic uremic patients. Design, setting, participants, & measurements: Included were 57 kidney recipients (Tx group, age 39 13 years) and 40 uremic...... 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...

  16. For People with Diabetes or High Blood Pressure: Get Checked for Kidney Disease

    Science.gov (United States)

    ... Language URL Español For People with Diabetes or High Blood Pressure: Get Checked for Kidney Disease Page Content Make ... I be checked for kidney disease? Diabetes and high blood pressure can damage the kidneys and lead to kidney ...

  17. Proteomics analysis reveals diabetic kidney as a ketogenic organ in type 2 diabetes

    National Research Council Canada - National Science Library

    Dongjuan Zhang; Hang Yang; Xiaomu Kong; Kang Wang; Xuan Mao; Xianzhong Yan; Yuan Wang; Siqi Liu; Xiaoyan Zhang; Jing Li; Lihong Chen; Jing Wu; Mingfen Wei; Jichun Yang; Youfei Guan

    2011-01-01

    .... Proteomic analysis revealed that 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase 2 (HMGCS2), the key enzyme in ketogenesis, was increased fourfold in the kidneys of type 2 diabetic db/db mice...

  18. 76 FR 30370 - National Institute of Diabetes and Digestive and Kidney Diseases; Meetings

    Science.gov (United States)

    2011-05-25

    ... Institute of Diabetes and Digestive and Kidney Diseases; Meetings Notice of Closed Meetings Pursuant to... Committee: National Institute of Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; NIDDK... and Kidney Diseases Special Emphasis Panel; RFA-DK-10-012 Type 1 Diabetes Impact Award (DP3)....

  19. Diabetes mellitus after kidney transplantation in Japanese patients: The Japan Academic Consortium of Kidney Transplantation study.

    Science.gov (United States)

    Okumi, Masayoshi; Unagami, Kohei; Hirai, Toshihito; Shimizu, Tomokazu; Ishida, Hideki; Tanabe, Kazunari

    2017-03-01

    To clarify the incidence rate of post-transplant diabetes mellitus and associated risk factors in Japanese kidney transplant recipients, and to explore which treatment components are most effective in reducing post-transplant diabetes mellitus. We analyzed 849 Japanese non-diabetic adult recipients who had undergone living kidney transplantation and had received tacrolimus-based immunosuppression from 1996 to 2013 with a median follow-up of 5 years. In all, 127 patients developed post-transplant diabetes mellitus during the follow-up period. The incidence rate of post-transplant diabetes mellitus was 15.1% (95% confidence interval 12.7-17.5) at 5 years. Recipient age (hazard ratio 1.05, 95% confidence interval 1.05-1.06, P level at 2 weeks post-transplantation (hazard ratio 1.06, 95% confidence interval 1.03-1.09, P diabetes mellitus. Estimated 5-year predicted incidence rate after adjusting for age and obesity was 9.4% for recipients with a low tacrolimus trough level, and receiving mycophenolate mofetil and 38.4% for recipients with a high tacrolimus trough level and not receiving mycophenolate mofetil. Post-transplant diabetes mellitus is a common complication in Japan, similar to that in other Western countries. The present results show that an appropriate immunosuppressive regimen with a combination of tacrolimus and mycophenolate mofetil can reduce the likelihood of developing post-transplant diabetes mellitus. Clinical trials are required to confirm these findings. © 2016 The Japanese Urological Association.

  20. 77 FR 3479 - National Institute of Diabetes and Digestive and Kidney Diseases Notice of Meeting

    Science.gov (United States)

    2012-01-24

    ... Diabetes and Digestive and Kidney Diseases Initial Review Group; Diabetes, Endocrinology and Metabolic... Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and... Institute of Diabetes and Digestive and Kidney Diseases Notice of Meeting Pursuant to section 10(d) of...

  1. Diabetes and Kidney Disease: Role of Oxidative Stress

    Science.gov (United States)

    Jha, Jay C.; Banal, Claudine; Chow, Bryna S.M.; Cooper, Mark E.

    2016-01-01

    Abstract Significance: Intrarenal oxidative stress plays a critical role in the initiation and progression of diabetic kidney disease (DKD). Enhanced oxidative stress results from overproduction of reactive oxygen species (ROS) in the context of concomitant, insufficient antioxidant pathways. Renal ROS production in diabetes is predominantly mediated by various NADPH oxidases (NOXs), but a defective antioxidant system as well as mitochondrial dysfunction may also contribute. Recent Advances: Effective agents targeting the source of ROS generation hold the promise to rescue the kidney from oxidative damage and prevent subsequent progression of DKD. Critical Issues and Future Directions: In the present review, we summarize and critically analyze molecular and cellular mechanisms that have been demonstrated to be involved in NOX-induced renal injury in diabetes, with particular focus on the role of increased glomerular injury, the development of albuminuria, and tubulointerstitial fibrosis, as well as mitochondrial dysfunction. Furthermore, novel agents targeting NOX isoforms are discussed. Antioxid. Redox Signal. 25, 657–684. PMID:26906673

  2. [DIABETIC NEPHROPATHY AS A CAUSE OF CHRONIC KIDNEY DISEASE].

    Science.gov (United States)

    Kos, Ivan; Prkačin, Ingrid

    2014-12-01

    Diabetic nephropathy is the leading cause of end-stage chronic kidney disease in most developed countries. Hyperglycemia, hypertension and genetic predisposition are the main risk factors for the development of diabetic nephropathy. Elevated serum lipids, smoking habits, and the amount and origin of dietary protein also seem to play a role as risk factors. Clinical picture includes a progressive increase in albuminuria, decline in glomerular filtration, hypertension, and a high risk of cardiovascular morbidity and mortality. Screening for albuminuria should be performed yearly, starting 5 years after diagnosis in type 1 diabetes or earlier in the presence of adolescence or poor metabolic control. In patients with type 2 diabetes, screening should be performed at diagnosis and yearly thereafter. Patients with albuminuria should undergo evaluation regarding the presence of associated comorbidities, especially retinopathy and macrovascular disease. Achieving the best metabolic control (HbA1c diabetes.

  3. Dyslipidemia, kidney disease, and cardiovascular disease in diabetic patients.

    Science.gov (United States)

    Chen, Szu-chi; Tseng, Chin-Hsiao

    2013-01-01

    This article reviews the relationship between dyslipidemia, chronic kidney disease, and cardiovascular diseases in patients with diabetes. Diabetes mellitus is associated with complications in the cardiovascular and renal system, and is increasing in prevalence worldwide. Modification of the multifactorial risk factors, in particular dyslipidemia, has been suggested to reduce the rates of diabetes-related complications. Dyslipidemia in diabetes is a condition that includes hypertriglyceridemia, low high-density lipoprotein levels, and increased small and dense low-density lipoprotein particles. This condition is associated with higher cardiovascular risk and mortality in diabetic patients. Current treatment guidelines focus on lowering the low-density lipoprotein cholesterol level; multiple trials have confirmed the cardiovascular benefits of treatment with statins. Chronic kidney disease also contributes to dyslipidemia, and dyslipidemia in turn is related to the occurrence and progression of diabetic nephropathy. Different patterns of dyslipidemia are associated with different stages of diabetic nephropathy. Some trials have shown that treatment with statins not only decreased the risk of cardiovascular events, but also delayed the progression of diabetic nephropathy. However, studies using statins as the sole treatment of hyperlipidemia in patients on dialysis have not shown benefits with respect to cardiovascular risk. Diabetic patients with nephropathy have a higher risk of cardiovascular events than those without nephropathy. The degree of albuminuria and the reduction in estimated glomerular filtration rate are also correlated with the risk of cardiovascular events. Treatment with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers to reduce albuminuria in diabetic patients has been shown to decrease the risk of cardiovascular morbidity and mortality.

  4. 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.

  5. A novel SGLT is expressed in the human kidney.

    Science.gov (United States)

    Kothinti, Rajendra K; Blodgett, Amy B; North, Paula E; Roman, Richard J; Tabatabai, Niloofar M

    2012-09-05

    Selective inhibitors of sodium-glucose cotransporter 2 (SGLT2)-mediated reabsorption of glucose in the proximal tubule of the kidney are being developed for the treatment of diabetes. SGLT2 shares high degree of homology with SGLT3; however, very little is known about the expression and functional role of SGLT3 in the human kidney. Indeed, the SGLT2 inhibitors that are currently in clinical trials might affect the expression and/or the activity of SGLT3. Therefore, the present study examined the expression of SGLT3 mRNA and protein in human kidney and in a human proximal tubule HK-2 cell line. The results indicated that human SGLT3 (hSGLT3) message and protein are expressed both in vivo and in vitro. We also studied the activity of hSGLT3 protein following its over-expression in mammalian kidney-derived COS-7 cells and in HK-2 cells treated with the imino sugar deoxynojirimycin (DNJ), a potent agonist of hSGLT3. Over-expression of hSGLT3 in COS-7 cells increased intracellular sodium concentration by 3-fold without affecting glucose transport. Activation of hSGLT3 with DNJ (50μM) increased sodium uptake in HK-2 cells by 5.5 fold and this effect could be completely blocked with SGLT inhibitor phlorizin (50μM). These results suggest that SGLT3 is expressed in human proximal tubular cells where it serves as a novel sodium transporter. Up-regulation of the expression of SGLT3 in the proximal tubule in diabetic patients may contribute to the elevated sodium transport in this segment of the nephron that has been postulated to promote hyperfiltration and renal injury.

  6. The Impact of Method on Kidney Graft and Patient Survival in Kidney-Pancreas Transplantations for Type I Diabetes Mellitus

    OpenAIRE

    Dinckan, Ayhan; Aliosmanoglu, Ibrahim; Kocak, Huseyin; Mesci, Ayhan; Altunbas, Hasan; Gurkan, Alihan

    2015-01-01

    Patients who develop end-stage renal disease (ESRD) associated with Type I Diabetes Mellitus may receive kidney alone (KA) transplantation, simultaneous pancreas-kidney (SPK) transplantation, or a pancreas after kidney (PAK) transplantation. The goal of this study is to examine the long-term impact of pancreas transplantation on kidney graft and patient survival rates. A total of 85 transplantation cases, consisting of 30 that received living donor KA, 21 that received SPK, and 34 that receiv...

  7. Ethnic/Race Diversity and Diabetic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Vasantha Muthu Muthuppalaniappan

    2015-07-01

    Full Text Available Ethnicity and race are often used interchangeably in the literature. However, the traditional definition of race and ethnicity is related to biological (bone structure and skin, hair, or eye color and sociological factors (nationality, regional culture, ancestry, and language respectively. Diabetes mellitus (DM is a huge global public health problem. As the number of individuals with Type 2 DM grows, the prevalence of diabetic kidney disease (DKD, which is one of the most serious complications, is expected to rise sharply. Many ethnic and racial groups have a greater risk of developing DM and its associated macro and micro-vascular complications.

  8. Oral health and kidney disease with emphasis on diabetic nephropathy

    OpenAIRE

    Vesterinen, Maarit

    2011-01-01

    Chronic kidney disease (CKD) is a worldwide health problem, with adverse outcomes of cardiovascular disease and premature death. The ageing of populations along with the growing prevalence of chronic diseases such as diabetes and hypertension is leading to worldwide increase in the number of CKD patients. It has become evident that inflammation plays an important role in the pathogenesis of atherosclerosis complications. CKD patients also have an increased risk of atherosclerosis complication...

  9. Nutrition Intervention for Advanced Stages of Diabetic Kidney Disease.

    Science.gov (United States)

    Goldstein-Fuchs, Jordi; Kalantar-Zadeh, Kamyar

    2015-08-01

    IN BRIEF For the goals of reducing diabetic kidney disease (DKD) onset and progression, approaches to nutritional therapy are a subject of much debate. This article discusses selected nutrients that have a role in affecting DKD outcomes and introduces application of newer, individualized concepts for healthful eating, as supported by clinical evidence relevant to patients with DKD. Selected aspects of management of advanced DKD are also reviewed.

  10. Immunohistochemical distribution of leptin in kidney tissues of melatonin treated diabetic rats.

    Science.gov (United States)

    Elis Yildiz, S; Deprem, T; Karadag Sari, E; Bingol, S A; Koral Tasci, S; Aslan, S; Nur, G; Sozmen, M

    2015-05-01

    We examined using immunohistochemistry the distribution of leptin in kidney tissues of melatonin treated, streptozotocin (STZ) diabetic rats. The animals were divided into five groups: control, sham, melatonin-treated, diabetic and melatonin-treated diabetic. Kidney sections were prepared and stained with hematoxylin and eosin, and Crossman's triple staining for histological examination. The immunohistochemical localization of leptin in the kidney tissue was determined using the streptavidin-biotin-peroxidase method. We determined that on days 7 and 14, the leptin immunoreactivity of the diabetic and melatonin-treated diabetic groups was weaker than for the other groups. Weak immunoreactivity was found in the proximal and distal tubules of the kidney in the diabetic and melatonin-treated diabetic groups on days 7 and 14, and strong immunoreactivity was found in the control, sham and melatonin groups. Melatonin application had no significant effect on leptin production in the kidney tissues of diabetic rats.

  11. Diabetes mellitus and kidney disease in the elderly.

    Science.gov (United States)

    Iglesias, Pedro; Heras, Manuel; Díez, Juan J

    2014-05-21

    Management of diabetic elderly patients with chronic kidney disease involves specific characteristics that affect both metabolic control and therapeutic measures. Blood glucose control targets should be individualised based on life expectancy, renal function, hypoglycaemia risk and comorbidity. Metformin may be used alone or in combination with other oral anti-diabetic drugs but must be discontinued when the glomerular filtration rate is less than 30 mL/min. Gliclazide and glipizide are sulfonylureas that do not require dose adjustment in chronic kidney disease but they should be avoided in cases of advanced kidney disease because of the risk of hypoglycaemia. Repaglinide is the only meglitinide recommended in these patients. Alpha-glucosidase inhibitors must be avoided in patients with a glomerular filtration rate of less than 25 mL/min or those undergoing dialysis. Pioglitazone does not require dose adjustment but it has potentially adverse effects in this population. Dipeptidyl peptidase-4 inhibitors are effective and well tolerated. Of the latter, linagliptin does not require dose adjustment. Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors are not recommended in elderly patients with advanced kidney disease. Lastly, insulin therapy, particularly using the new insulin analogues, allows adequate management of hyperglycaemia in these patients, with different therapeutic regimens that must be individualised in order to avoid hypoglycaemia.

  12. 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 of ...

  13. 78 FR 79706 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2013-12-31

    ... Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases and... Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings Pursuant to section 10(d... Institute of Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Fellowships in...

  14. 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, Nutrition Obesity Research...; 93.848, Digestive Diseases and Nutrition Research; 93.849, Kidney Diseases, Urology and Hematology...

  15. Diabetic kidney disease: from epidemiology to clinical perspectives.

    Science.gov (United States)

    Park, Cheol Whee

    2014-08-01

    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.

  16. 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.

  17. Diabetic nephropathy; principles of diagnosis and treatment of diabetic kidney disease.

    Science.gov (United States)

    Nazar, Chaudhary Muhammad Junaid

    2014-01-01

    Diabetes mellitus is a leading epidemic of the present world. It is considered the leading cause of death among end-stage renal disease (ESRD) patients. The complications associated with diabetes mellitus have boosted the number of deaths in the last years. These complications are the result of long lasting effects of diabetes mellitus on the glomerular microvasculature of the kidney. Diabetic nephropathy (DN) develops in patients with several years' medical history of diabetes and renal failure. However, research shows that patients with type 1 diabetes progress early to ESRD as compared to those with type 2. DN is more prevalent in ethnic minorities as compared to other groups in society. There are new and different treatment options available since medical science has progressed due to increased research efforts. Unfortunately, there is no permanent cure. The aim of this article is to explore the research of therapeutic strategies currently in use by medical practitioners in order to increase understanding of DN.

  18. 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.

  19. The diabetic rat kidney mediates inosituria and selective urinary partitioning of D-chiro-inositol.

    Science.gov (United States)

    Chang, Hao-Han; Choong, Bernard; Phillips, Anthony R J; Loomes, Kerry M

    2015-01-01

    Diabetic nephropathy is a serious complication of diabetes mellitus with a pressing need for effective metabolic markers to detect renal impairment. Of potential significance are the inositol compounds, myo-inositol (MI), and the less abundant stereoisomer, D-chiro-inositol (DCI), which are excreted at increased levels in the urine in diabetes mellitus, a phenomenon known as inosituria. There is also a selective urinary excretion of DCI compared to MI. As the biological origins of altered inositol metabolism in diabetes mellitus are unknown, the aim of this study was to determine whether the diabetic kidney was directly responsible. Kidneys isolated from four-week streptozotocin-induced diabetic rats were characterized by a 3-fold reduction in glomerular filtration rate (GFR) compared to matched non-diabetic kidneys. When perfused with fixed quantities of MI (50 µM) and DCI (5 µM) under normoglycemic conditions (5 mM glucose), GFR-normalized urinary excretion of MI was increased by 1.7-fold in diabetic vs. non-diabetic kidneys. By comparison, GFR-normalized urinary excretion of DCI was increased by 4-fold. Perfusion conditions replicating hyperglycemia (20 mM glucose) potentiated DCI but not MI urinary excretion in both non-diabetic and diabetic kidneys. Overall, there was a 2.4-fold increase in DCI urinary excretion compared to MI in diabetic kidneys that was independent of glucose ambience. This increased urinary excretion of DCI and MI in diabetic kidneys occurred despite increased renal expression of the inositol transporters, sodium myo-inositol transporter subtype 1 and 2 (SMIT1 and SMIT2). These findings show that the diabetic kidney primarily mediates inosituria and altered urinary partitioning of MI and DCI. Urinary inositol levels might therefore serve as an indicator of impaired renal function in diabetes mellitus with wider implications for monitoring chronic kidney disease.

  20. Prevention of cardiovascular diseases, diabetes mellitus and chronic kidney diseases in general practice.

    NARCIS (Netherlands)

    Nielen, M.; Assendelft, P.; Drenthen, T.; Hombergh, P. van den; Dis, I. van; Schellevis, F.

    2009-01-01

    Purpose: To study the attitudes and working methods of general practitioners (GPs) in primary prevention of cardiovascular diseases, diabetes mellitus and chronic kidney diseases. Methods: A questionnaire with questions about primary prevention of cardiovascular diseases, diabetes mellitus and

  1. BMP-7 PROTEIN EXPRESSION IS DOWNREGULATED IN HUMAN DIABETIC NEPHROPATHY.

    Science.gov (United States)

    Ivanac-Janković, Renata; Ćorić, Marijana; Furić-Čunko, Vesna; Lovičić, Vesna; Bašić-Jukić, Nikolina; Kes, Petar

    2015-06-01

    Bone morphogenetic protein-7 (BMP-7) is expressed in all parts of the normal kidney parenchyma, being highest in the epithelium of proximal tubules. It protects kidney against acute and chronic injury, inflammation and fibrosis. Diabetic nephropathy is the leading cause of chronic kidney disease, and is characterized by decreased expression of BMP-7. The aim of our study was to analyze whether the expression of BMP-7 is significantly changed in advanced stages of human diabetic nephropathy. Immunohistochemical analysis of the expression of BMP-7 was performed on archival material of 30 patients that underwent renal biopsy and had confirmed diagnosis of diabetic nephropathy. Results showed that BMP-7 was differently expressed in the cytoplasm of epithelial cells of proximal tubules and podocytes among all stages of diabetic nephropathy. At early stages of diabetic nephropathy, BMP-7 was strongly positive in proximal tubules and podocytes, while low expression was recorded in the majority of samples at advanced stages. In conclusion, increased expression of BMP-7 at initial stages of diabetic nephropathy with subsequent decrease at advanced stage highlights the role of BMP-7 in the protection of kidney structure and function. Further investigations should be focused on disturbances of BMP-7 receptors and signaling pathways in patients with diabetic nephropathy.

  2. Mouse Models of Diabetes, Obesity and Related Kidney Disease

    Science.gov (United States)

    Glastras, Sarah J.; Chen, Hui; Teh, Rachel; McGrath, Rachel T.; Chen, Jason; Pollock, Carol A.; Wong, Muh Geot; Saad, Sonia

    2016-01-01

    Multiple rodent models have been used to study diabetic kidney disease (DKD). The purpose of the present study was to compare models of diabetes and obesity-induced metabolic syndrome and determine differences in renal outcomes. C57BL/6 male mice were fed either normal chow or high fat diet (HFD). At postnatal week 8, chow-fed mice were randomly assigned to low-dose streptozotocin (STZ, 55 mg/kg/day, five consecutive days) or vehicle control, whereas HFD-fed mice were given either one high-dose of STZ (100 mg/kg) or vehicle control. Intraperitoneal glucose tolerance tests were performed at Week 14, 20 and 30. Urinary albumin to creatinine ratio (ACR) and serum creatinine were measured, and renal structure was assessed using Periodic Acid Schiff (PAS) staining at Week 32. Results showed that chow-fed mice exposed to five doses of STZ resembled type 1 diabetes mellitus with a lean phenotype, hyperglycaemia, microalbuminuria and increased serum creatinine levels. Their kidneys demonstrated moderate tubular injury with evidence of tubular dilatation and glycogenated nuclear inclusion bodies. HFD-fed mice resembled metabolic syndrome as they were obese with dyslipidaemia, insulin resistance, and significantly impaired glucose tolerance. One dose STZ, in addition to HFD, did not worsen metabolic features (including fasting glucose, non esterified fatty acid, and triglyceride levels). There were significant increases in urinary ACR and serum creatinine levels, and renal structural changes were predominantly related to interstitial vacuolation and tubular dilatation in HFD-fed mice. PMID:27579698

  3. Metformin and Diabetic Kidney Disease: A Mini-Review on Recent Findings

    OpenAIRE

    Nasri, Hamid; Rafieian-Kopaei, Mahmoud

    2014-01-01

    Metformin, an oral anti-diabetic agent in the biguanide class is a widely prescribed drug to treat high blood glucose in patients with type 2 diabetes mellitus. Metformin has three different roles, including blood glucose regulatory effect, protection of kidney tubular cell by acting as an effective antioxidant and finally ameliorative effect on diabetic kidney disease through saving the podocytes. Therefore, diabetic patients may benefit from all of these three distinct ameliorative effects.

  4. Metformin and diabetic kidney disease: a mini-review on recent findings.

    Science.gov (United States)

    Nasri, Hamid; Rafieian-Kopaei, Mahmoud

    2014-10-01

    Metformin, an oral anti-diabetic agent in the biguanide class is a widely prescribed drug to treat high blood glucose in patients with type 2 diabetes mellitus. Metformin has three different roles, including blood glucose regulatory effect, protection of kidney tubular cell by acting as an effective antioxidant and finally ameliorative effect on diabetic kidney disease through saving the podocytes. Therefore, diabetic patients may benefit from all of these three distinct ameliorative effects.

  5. Altered magnesium transport in slices of kidney cortex from chemically-induced diabetic rats

    Energy Technology Data Exchange (ETDEWEB)

    Hoskins, B.

    1981-10-01

    The uptake of magnesium-28 was measured in slices of kidney cortex from rats with alloxan-diabetes and from rats with streptozotocin-diabetes of increasing durations. In both forms of chemically-induced diabetes, magnesium-28 uptake by kidney cortex slices was significantly increased over uptake measured in kidney cortex slices from control rats. Immediate institution of daily insulin therapy to the diabetic rats prevented the diabetes-induced elevated uptake of magnesium without controlling blood glucose levels. Late institution of daily insulin therapy was ineffective in restoring the magnesium uptake to control values. These alterations in magnesium uptake occurred prior to any evidence of nephropathy (via the classic indices of proteinuria and increased BUN levels). The implications of these findings, together with our earlier demonstrations of altered calcium transport by kidney cortex slices from chemically-induced diabetic rats, are discussed in terms of disordered divalent cation transport being at least part of the basic pathogenesis underlying diabetic nephropathy.

  6. 77 FR 76056 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2012-12-26

    ... Kidney Diseases Special Emphasis Panel; Renal Supportive Care Studies. Date: December 27, 2012. Time: 4... of Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Diverse Studies for Diabetes... Panel; Pilot Studies for CKD. Date: January 29, 2013. Time: 8:00 a.m. to 5:00 p.m. Agenda: To review...

  7. Tubular markers are associated with decline in kidney function in proteinuric type 2 diabetic patients

    DEFF Research Database (Denmark)

    Nielsen, Stine; Reinhard, Henrik; Zdunek, Dietmar

    2012-01-01

    Our aim was to investigate u-NGAL, u-KIM1 and p-FGF23 and prediction of decline in kidney function in type 2 diabetic patients with proteinuria.......Our aim was to investigate u-NGAL, u-KIM1 and p-FGF23 and prediction of decline in kidney function in type 2 diabetic patients with proteinuria....

  8. Mannan-binding lectin in diabetic kidney disease: the impact of mouse genetics in a type 1 diabetes model

    DEFF Research Database (Denmark)

    Østergaard, Jakob; Bjerre, Mette; RamachandraRao, Satish Posettihalli

    2012-01-01

    of diabetic kidney disease is observed in one animal strain. However, this involvement may differ among the animal strains. We thus examined the impact of the genetic background on the role of MBL in diabetic nephropathy. MATERIALS/METHODS: C57BL/6JBomTac and 129S6/SvEvTac mice were compared. In both strains......, experimental type 1 diabetes was induced in wild-type (WT) and MBL-knockout (MBL-KO) mice by streptozotocin. Nondiabetic WT and MBL-KO mice were used as controls. We tested if MBL modified the diabetes-induced kidney changes by two-way ANOVA allowing for interaction. RESULTS: MBL aggravated diabetes....... CONCLUSIONS: Strain-specific MBL effects were found on downstream diabetic kidney changes. This emphasizes the importance of genetic background in this model of diabetic complications....

  9. Insulin signaling: implications for podocyte biology in diabetic kidney disease

    Science.gov (United States)

    Coward, Richard; Fornoni, Alessia

    2015-01-01

    Purpose of review Several key elements of the insulin signaling cascade contribute to podocyte function and survival. While it was initially thought that the consequences of altered insulin signaling to podocyte function was strictly related to altered glucose uptake, it has become clear that upstream signaling events involved in cell survival, lipid metabolism or nutrient sensing and modulated by insulin are strong independent contributors to podocyte function. Recent findings Akt2, the major isoform of Akt activated following cellular insulin stimulation, protects against the progression of renal disease in nephron-deficient mice, and podocyte-specific deletion of Akt2 results in a more rapid progression of experimental glomerular disease. In diabetes, podocyte mammalian target of rapamycin activation clearly contributes to podocyte injury and regulated autophagy. Furthermore, podocyte-specific glucose transporter type 4 (GLUT4) deficiency protects podocytes by preventing mammalian target of rapamycin signaling independently of glucose uptake. Finally, intracellular lipids have been recently recognized as major modulators of podocyte insulin signaling and as a new therapeutic target. Summary The identification of new contributors to podocyte insulin signaling is of extreme translational value as it may lead to new drug development strategies for diabetic kidney disease, as well as for other proteinuric kidney diseases. PMID:25415617

  10. 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.

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

    Science.gov (United States)

    Andrade-Sierra, Jorge

    2016-01-01

    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. PMID:27525285

  12. Withania coagulans fruit extract reduces oxidative stress and inflammation in kidneys of streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Ojha, Shreesh; Alkaabi, Juma; Amir, Naheed; Sheikh, Azimullah; Agil, Ahmad; Fahim, Mohamed Abdelmonem; Adem, Abdu

    2014-01-01

    The present study was carried out to investigate the changes in oxidative and inflammatory status in streptozotocin-induced diabetic rat's kidneys and serum following treatment with Withania coagulans, a popular herb of ethnomedicinal significance. The key markers of oxidative stress and inflammation such as inflammatory cytokines (IL-1β, IL-6, and TNF-α) and immunoregulatory cytokines (IL-4 and IFN-γ) were increased in kidneys along with significant hyperglycemia. However, treatment of four-month diabetic rats with Withania coagulans (10 mg/kg) for 3 weeks significantly attenuated hyperglycemia and reduced the levels of proinflammatory cytokines in kidneys. In addition, Withania coagulans treatment restored the glutathione levels and inhibited lipid peroxidation along with marked reduction in kidney hypertrophy. The present study demonstrates that Withania coagulans corrects hyperglycemia and maintained antioxidant status and reduced the proinflammatory markers in kidneys, which may subsequently reduce the development and progression of renal injury in diabetes. The results of the present study are encouraging for its potential use to delay the onset and progression of diabetic renal complications. However, the translation of therapeutic efficacy in humans requires further studies.

  13. Reversal of Early Diabetic Nephropathy by Islet Transplantation under the Kidney Capsule in a Rat Model

    Directory of Open Access Journals (Sweden)

    Yunqiang He

    2016-01-01

    Full Text Available Objective. Diabetic nephropathy (DN is a common microvascular complication of diabetes mellitus, and insulin therapy has many side effects in the treatment of DN. Islet transplantation has emerged as a promising therapy for diabetic patients. This study was established to investigate its advantageous effects in a rat model of early DN. Methods. Streptozotocin was administered to the rats to induce diabetes. Twelve weeks later, the diabetic rats were divided into 3 groups: the islet-transplanted group (IT group, the insulin-treated group (IN group, and the untreated group (DN group. Renal injury and kidney structure were assessed by urinalysis and transmission electron microscopy (TEM detection. Immunohistochemical staining and western blotting were performed to assess renal fibrosis levels. Results. The early DN features were reversed and the glomerular filtration barrier and basement membrane structures were improved at 4 weeks after islet transplantation. The urine microalbumin-to-creatinine ratio (ACR, protein-to-creatinine ratio, and mean thickness of the glomerular basement membrane (GBM were significantly decreased in the IT group. The expression of renal fibrotic factors was also significantly decreased. Conclusions. These data suggest that early DN can be reversed after islet transplantation, and they may facilitate the development of a clinical therapeutic strategy for human diabetes mellitus.

  14. Glycated albumin in diabetic patients with chronic kidney disease.

    Science.gov (United States)

    Zheng, Cai-Mei; Ma, Wen-Ya; Wu, Chia-Chao; Lu, Kuo-Cheng

    2012-10-09

    Chronic hyperglycemia results in a non-enzymatic glycation of proteins, and produces Amadori products, such as glycated albumin (GA), glycosylated hemoglobin (HbA1c), and fructosamine. In current clinical practice, long-term glycemic control is assessed by quarterly measurements of HbA1c. Since the degree of hemoglobin glycosylation depends not only on the level of glycemic control, but also on the lifespan of red blood cells, patients with hemoglobin disorders or anemia of any cause may have erroneous HbA1c levels, and consequently receive insufficient treatment. Patients with chronic kidney disease (CKD) often suffer from various types of anemia, and consequently, they are frequently treated with iron and/or erythropoietin therapy or frequent blood transfusion. Thus, serum GA is a potentially useful glycemic index in diabetic patients with CKD, since it is not influenced by anemia and associated treatments. GA may also reflect the status of blood glucose more rapidly (2-3 weeks) than HbA1c (2-3 months), and is beneficial in those with wide variations in blood glucose or at higher risk for hypoglycemia. If clinical investigations support its utility, it may be applicable as a screening tool for all patients with diabetes during routine health examinations. Serum GA levels are also associated with AGE-related fluorescence and the number of glycation sites, and it may influence the structural and functional changes inalbumin. Since end-stage renal disease is an extreme microvascular complication of diabetic nephropathy, CKD patients with diabetes should be carefully managed to prevent disease progression. In this review, the clinical aspects of GA were discussed, including a comparison of GA with other glycated proteins, the utility and limitations of GA as a glycemic index, its influence on the therapeutic effects of hypoglycemic agents, its correlations with vascular complications, and its potential role in pathogenesis, specifically in diabetic patients with CKD.

  15. Mannan-Binding Lectin in Diabetic Kidney Disease: The Impact of Mouse Genetics in a Type 1 Diabetes Model

    Directory of Open Access Journals (Sweden)

    Jakob Appel Østergaard

    2012-01-01

    Full Text Available Background. Mannan-binding lectin (MBL is involved in the development of diabetic nephropathy. MBL is a part of the innate immune system where it can activate the complement system. Serum MBL level predicts later renal impairment in diabetes patients. Direct involvement of MBL in the development of diabetic kidney disease is observed in one animal strain. However, this involvement may differ among the animal strains. We thus examined the impact of the genetic background on the role of MBL in diabetic nephropathy. Materials/Methods. C57BL/6JBomTac and 129S6/SvEvTac mice were compared. In both strains, experimental type 1 diabetes was induced in wild-type (WT and MBL-knockout (MBL-KO mice by streptozotocin. Nondiabetic WT and MBL-KO mice were used as controls. We tested if MBL modified the diabetes-induced kidney changes by two-way ANOVA allowing for interaction. Results. MBL aggravated diabetes-induced kidney growth and glomerulus enlargement in C57BL/6JBomTac mice. MBL did not modify diabetes effects on glomerular basement membrane thickness or mesangial volume in any strain. Diabetes-induced changes in renal gene transcription of growth factors and matrix components were unaffected by MBL. Conclusions. Strain-specific MBL effects were found on downstream diabetic kidney changes. This emphasizes the importance of genetic background in this model of diabetic complications.

  16. Decellularized Human Kidney Cortex Hydrogels Enhance Kidney Microvascular Endothelial Cell Maturation and Quiescence.

    Science.gov (United States)

    Nagao, Ryan J; Xu, Jin; Luo, Ping; Xue, Jun; Wang, Yi; Kotha, Surya; Zeng, Wen; Fu, Xiaoyun; Himmelfarb, Jonathan; Zheng, Ying

    2016-10-01

    The kidney peritubular microvasculature is highly susceptible to injury from drugs and toxins, often resulting in acute kidney injury and progressive chronic kidney disease. Little is known about the process of injury and regeneration of human kidney microvasculature, resulting from the lack of appropriate kidney microvascular models that can incorporate the proper cells, extracellular matrices (ECMs), and architectures needed to understand the response and contribution of individual vascular components in these processes. In this study, we present methods to recreate the human kidney ECM (kECM) microenvironment by fabricating kECM hydrogels derived from decellularized human kidney cortex. The majority of native matrix proteins, such as collagen-IV, laminin, and heparan sulfate proteoglycan, and their isoforms were preserved in similar proportions as found in normal kidneys. Human kidney peritubular microvascular endothelial cells (HKMECs) became more quiescent when cultured on this kECM gel compared with culture on collagen-I-assessed using phenotypic, genotypic, and functional assays; whereas human umbilical vein endothelial cells became stimulated on kECM gels. We demonstrate for the first time that human kidney cortex can form a hydrogel suitable for use in flow-directed microphysiological systems. Our findings strongly suggest that selecting the proper ECM is a critical consideration in the development of vascularized organs on a chip and carries important implications for tissue engineering of all vascularized organs.

  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. Kidney injury biomarkers in hypertensive, diabetic, and nephropathy rat models treated with contrast media.

    Science.gov (United States)

    Rouse, Rodney L; Stewart, Sharron R; Thompson, Karol L; Zhang, Jun

    2013-01-01

    Contrast-induced nephropathy (CIN) refers to a decline in renal function following exposure to iodinated contrast media (CM). The present study was initiated to explore the role of known human risk factors (spontaneous hypertension, diabetes, protein-losing nephropathy) on CIN development in rodent models and to determine the effect of CM administration on kidney injury biomarkers in the face of preexisting kidney injury. Spontaneously hypertensive rats (hypertension), streptozotocin-treated Sprague Dawley rats (diabetes), and Dahl salt-sensitive rats (protein-losing nephropathy) were given single intravenous injections of the nonionic, low osmolar contrast medium, iohexol. Blood urea nitrogen (BUN), serum creatinine (sCr), and urinary biomarkers; albumin, lipocalin 2 (Lcn-2), osteopontin (Opn), kidney injury molecule 1 (Kim-1), renal papillary antigen 1 (Rpa-1), α-glutathione S-transferase (α-Gst), µ-glutathione S-transferase (µ-Gst), and beta-2 microglobulin (β2m) were measured in disease models and appropriate controls to determine the response of these biomarkers to CM administration. Each disease model produced elevated biomarkers of kidney injury without CM. Preexisting histopathology was exacerbated by CM but little or no significant increases in biomarkers were observed. When 1.5-fold or greater sCr increases from pre-CM were used to define true positives, receiver-operating characteristic curve analysis of biomarker performance showed sCr was the best predictor of CIN across disease models. β2m, Lcn-2, and BUN were the best predictors of histopathology defined kidney injury.

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

    Science.gov (United States)

    2012-05-18

    ... Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848... Diabetes and Digestive and Kidney Disorders; Notice of Closed Meetings Pursuant to section 10(d) of the... requests for preclinical development resources for potential new therapeutics for type 1 diabetes....

  1. Promoter polymorphism of the erythropoietin gene in severe diabetic eye and kidney complications.

    Science.gov (United States)

    Tong, Zongzhong; Yang, Zhenglin; Patel, Shrena; Chen, Haoyu; Gibbs, Daniel; Yang, Xian; Hau, Vincent S; Kaminoh, Yuuki; Harmon, Jennifer; Pearson, Erik; Buehler, Jeanette; Chen, Yuhong; Yu, Baifeng; Tinkham, Nicholas H; Zabriskie, Norman A; Zeng, Jiexi; Luo, Ling; Sun, Jennifer K; Prakash, Manvi; Hamam, Rola N; Tonna, Stephen; Constantine, Ryan; Ronquillo, Cecinio C; Sadda, SriniVas; Avery, Robert L; Brand, John M; London, Nyall; Anduze, Alfred L; King, George L; Bernstein, Paul S; Watkins, Scott; Jorde, Lynn B; Li, Dean Y; Aiello, Lloyd Paul; Pollak, Martin R; Zhang, Kang

    2008-05-13

    Significant morbidity and mortality among patients with diabetes mellitus result largely from a greatly increased incidence of microvascular complications. Proliferative diabetic retinopathy (PDR) and end stage renal disease (ESRD) are two of the most common and severe microvascular complications of diabetes. A high concordance exists in the development of PDR and ESRD in diabetic patients, as well as strong familial aggregation of these complications, suggesting a common underlying genetic mechanism. However, the precise gene(s) and genetic variant(s) involved remain largely unknown. Erythropoietin (EPO) is a potent angiogenic factor observed in the diabetic human and mouse eye. By a combination of case-control association and functional studies, we demonstrate that the T allele of SNP rs1617640 in the promoter of the EPO gene is significantly associated with PDR and ESRD in three European-American cohorts [Utah: P = 1.91 x 10(-3); Genetics of Kidneys in Diabetes (GoKinD) Study: P = 2.66 x 10(-8); and Boston: P = 2.1 x 10(-2)]. The EPO concentration in human vitreous body was 7.5-fold higher in normal subjects with the TT risk genotype than in those with the GG genotype. Computational analysis suggests that the risk allele (T) of rs1617640 creates a matrix match with the EVI1/MEL1 or AP1 binding site, accounting for an observed 25-fold enhancement of luciferase reporter expression as compared with the G allele. These results suggest that rs1617640 in the EPO promoter is significantly associated with PDR and ESRD. This study identifies a disease risk-associated gene and potential pathway mediating severe diabetic microvascular complications.

  2. Protective effect of pioglitazone on kidney injury in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Xiao-Hui Peng; Pei-Yu Liang; Shan-Ji Ou; Xiong-Bing Zu

    2014-01-01

    Objective:To investigate the protective effect of pioglitazone on kidney injury in diabetic rat model and its mechanisms.Methods:Forty healthySpragueDawley rats were selected and randomly divided into five groups, with8 rats in each group.GroupA served as control group and were administered with sterile citrate buffer(i.p.) as placebo.GroupsB,C,D andE rats were injected(i.p.) with streptozotocin to induce typeⅠdiabetes.Diabetic rats inGroupB were intragastrically administered with sterile saline solution alone.GroupsC,D andE rats were intragastrically given pioglitazone hydrochloride suspension at doses of10,20,30 mg/kg per day, respectively.After eight weeks of treatment, all rats were anesthetized and blood was withdrawn from the abdominal aortic for detection of hemoglobinA1c, serum creatinine(SCr) and blood urea nitrogen(BUN) levels.Rats were then sacrificed and the left kidney was excised for calculation of kidney hypertrophy index(KHI), observation of renal pathological changes using light microscope and electron microscope.Mean glomerular cross-sectional areas(MGA), mean glomerular volume (MGV), glomerular basement membrane thickness and foot process fusion ratio were calculated. RT-PCR was employed for detection of podocalyxin(PCX) protein expression.Results:Results showed that levels of hemoglobinA1c,BUN,SCr inGroupsB,C,D andE rats were significantly higher than those inGroupA(P<0.05), whileBUN andSCr levels in rats ofGroupsC,D andE were significantly lower than those inGroupB(P<0.05).KHI,MGA andMGV levels were significantly higher inGroupsB,C,D andE rats than those inGroupA(P<0.05);KHI andMGA levels inGroup B rats were significantly higher than those inGroupsC,D andE(P<0.05) andMGV inGroups D andE was significantly lower than that inGroupsB andC(P<0.05).Histology study showed normal glomerulus structure, morphology, volume, endothelial cells and mesangial cells as well as clear glomerular capillary inGroupA rats.Renal mesangial matrix proliferation and

  3. Mapping time-course mitochondrial adaptations in the kidney in experimental diabetes.

    Science.gov (United States)

    Coughlan, Melinda T; Nguyen, Tuong-Vi; Penfold, Sally A; Higgins, Gavin C; Thallas-Bonke, Vicki; Tan, Sih Min; Van Bergen, Nicole J; Sourris, Karly C; Harcourt, Brooke E; Thorburn, David R; Trounce, Ian A; Cooper, Mark E; Forbes, Josephine M

    2016-05-01

    Oxidative phosphorylation (OXPHOS) drives ATP production by mitochondria, which are dynamic organelles, constantly fusing and dividing to maintain kidney homoeostasis. In diabetic kidney disease (DKD), mitochondria appear dysfunctional, but the temporal development of diabetes-induced adaptations in mitochondrial structure and bioenergetics have not been previously documented. In the present study, we map the changes in mitochondrial dynamics and function in rat kidney mitochondria at 4, 8, 16 and 32 weeks of diabetes. Our data reveal that changes in mitochondrial bioenergetics and dynamics precede the development of albuminuria and renal histological changes. Specifically, in early diabetes (4 weeks), a decrease in ATP content and mitochondrial fragmentation within proximal tubule epithelial cells (PTECs) of diabetic kidneys were clearly apparent, but no changes in urinary albumin excretion or glomerular morphology were evident at this time. By 8 weeks of diabetes, there was increased capacity for mitochondrial permeability transition (mPT) by pore opening, which persisted over time and correlated with mitochondrial hydrogen peroxide (H2O2) generation and glomerular damage. Late in diabetes, by week 16, tubular damage was evident with increased urinary kidney injury molecule-1 (KIM-1) excretion, where an increase in the Complex I-linked oxygen consumption rate (OCR), in the context of a decrease in kidney ATP, indicated mitochondrial uncoupling. Taken together, these data show that changes in mitochondrial bioenergetics and dynamics may precede the development of the renal lesion in diabetes, and this supports the hypothesis that mitochondrial dysfunction is a primary cause of DKD.

  4. Diabetic nephropathy; principles of diagnosis and treatment of diabetic kidney disease

    Directory of Open Access Journals (Sweden)

    Nazar Chaudhary Muhammad Junaid

    2014-01-01

    Full Text Available Diabetes mellitus is a leading epidemic of the present world. It is considered the leading cause of death among end-stage renal disease (ESRD patients. The complications associated with diabetes mellitus have boosted the number of deaths in the last years. These complications are the result of long lasting effects of diabetes mellitus on the glomerular microvasculature of the kidney. Diabetic nephropathy (DN develops in patients with several years’ medical history of diabetes and renal failure. However, research shows that patients with type 1 diabetes progress early to ESRD as compared to those with type 2. DN is more prevalent in ethnic minorities as compared to other groups in society. There are new and different treatment options available since medical science has progressed due to increased research efforts. Unfortunately, there is no permanent cure. The aim of this article is to explore the research of therapeutic strategies currently in use by medical practitioners in order to increase understanding of DN.

  5. Clinical Guidance on Screening Chronic Kidney Disease in Type 2 Diabetic Patients for Family Physicians

    Directory of Open Access Journals (Sweden)

    Seyed Esmaeil Managheb

    2015-10-01

    Full Text Available Incidence of diabetes is increasing in developing countries as well as Iran. Half of the patients are not aware of their disease so screening of diabetes is necessary. Lifestyle changes in society, high-saturated fat diet and decreased physical activity are the factors that influence the growing rate of diabetes in Iran.1 The need for addressing type 2 diabetes has been clarified for family physicians.2 Diabetes is a common disease that is associated with significant morbidity and mortality. It has an asymptomatic stage that may be present for up to several years before diagnosis.3 Diabetes is the leading cause of kidney disease.4 In a study among patients over 45 years with type 2 diabetes, these results were reported: 22% suffered from retinopathy, 7% had impaired vision, 6% had kidney diseases, 9% had clinical symptoms, and 19.1% were at risk for foot ulcers.5 Early treatment of type 2 diabetes can reduce or delay complications.6 Optimal glycemia and BP are important in the prevention of diabetic chronic kidney disease (CKD.4 Therapeutic goals in patients with complications, such as CKD, include maintaining renal function and stopping the trend of renal deterioration.5 Progression of diabetic nephropathy can be slowed through the use of some medications.4 How to screen and manage chronic kidney disease in patients with type 2 diabetes is shown in Figure 1.

  6. A novel mouse model of advanced diabetic kidney disease.

    Directory of Open Access Journals (Sweden)

    Jean-Francois Thibodeau

    Full Text Available Currently available rodent models exhibit characteristics of early diabetic nephropathy (DN such as hyperfiltration, mesangial expansion, and albuminuria yet features of late DN (hypertension, GFR decline, tubulointerstitial fibrosis are absent or require a significant time investment for full phenotype development. Accordingly, the aim of the present study was to develop a mouse model of advanced DN with hypertension superimposed (HD mice. Mice transgenic for human renin cDNA under the control of the transthyretin promoter (TTRhRen were employed as a model of angiotensin-dependent hypertension. Diabetes was induced in TTRhRen mice through low dose streptozotocin (HD-STZ mice or by intercrossing with OVE26 diabetic mice (HD-OVE mice. Both HD-STZ and HD-OVE mice displayed more pronounced increases in urinary albumin levels as compared with their diabetic littermates. Additionally, HD mice displayed renal hypertrophy, advanced glomerular scarring and evidence of tubulointerstitial fibrosis. Both HD-OVE and HD-STZ mice showed evidence of GFR decline as FITC-inulin clearance was decreased compared to hyperfiltering STZ and OVE mice. Taken together our results suggest that HD mice represent a robust model of type I DN that recapitulates key features of human disease which may be significant in studying the pathogenesis of DN and in the assessment of putative therapeutics.

  7. Identification of urinary proteins potentially associated with diabetic kidney disease

    Directory of Open Access Journals (Sweden)

    R K Marikanty

    2016-01-01

    Full Text Available Diabetic nephropathy (DN is the most common cause of chronic kidney disease. Although several parameters are used to evaluate renal damage, in many instances, there is no pathological change until damage is already advanced. Mass spectrometry-based proteomics is a novel tool to identify newer diagnostic markers. To identify urinary proteins associated with renal complications in diabetes, we collected urine samples from 10 type 2 diabetes patients each with normoalbuminuria, micro- and macro-albuminuria and compared their urinary proteome with that of 10 healthy individuals. Urinary proteins were concentrated, depleted of albumin and five other abundant plasma proteins and in-gel trypsin digested after prefractionation on sodium dodecyl sulfate polyacrylamide gel electrophoresis. The peptides were analyzed using a nanoflow reverse phase liquid chromatography system coupled to linear trap quadrupole-Orbitrap mass spectrometer. We identified large number of proteins in each group, of which many were exclusively present in individual patient groups. A total of 53 proteins were common in all patients but were absent in the controls. The majority of the proteins were functionally binding, biologically involved in metabolic processes, and showed enrichment of alternative complement and blood coagulation pathways. In addition to identifying reported proteins such as α2-HS-glycoprotein and Vitamin D binding protein, we detected novel proteins such as CD59, extracellular matrix protein 1 (ECM1, factor H, and myoglobin in the urine of macroalbuminuria patients. ECM1 and factor H are known to influence mesangial cell proliferation, and CD59 causes microvascular damage by influencing membrane attack complex deposition, suggestive their biological relevance to DN. Thus, we have developed a proteome database where various proteins exclusively present in the patients may be further investigated for their role as stage-specific markers and possible therapeutic

  8. Thioredoxin-Interacting Protein Mediates NLRP3 Inflammasome Activation Involved in the Susceptibility to Ischemic Acute Kidney Injury in Diabetes

    Directory of Open Access Journals (Sweden)

    Ye Da Xiao

    2016-01-01

    Full Text Available Kidney in diabetic state is more sensitive to ischemic acute kidney injury (AKI. However, the underlying mechanisms remain unclear. Herein, we examined the impact of diabetes mellitus on thioredoxin-interacting protein (TXNIP expression and whether mediated NLRP3 activation was associated with renal ischemia/reperfusion- (I/R- induced AKI. In an in vivo model, streptozotocin-induced diabetic rats showed higher susceptibility to I/R injury with increased TXNIP expression, which was significantly attenuated by resveratrol (RES treatment (10 mg/kg intraperitoneal daily injection for 7 consecutive days prior to I/R induction. RES treatment significantly inhibited TXNIP binding to NLRP3 in diabetic rats subjected to renal I/R injury. Furthermore, RES treatment significantly reduced cleaved caspase-1 expression and production of IL-1β and IL-18. In an in vitro study using cultured human kidney proximal tubular cell (HK-2 cells in high glucose condition (HG, 30 mM subjected to hypoxia/reoxygenation (H/R, HG combined H/R (HH/R stimulated TXNIP expression which was accompanied by increased NLRP3 expression, ROS generation, caspase-1 activity and IL-1β levels, and aggravated HK-2 cells apoptosis. All these changes were significantly attenuated by TXNIP RNAi and RES treatment. In conclusion, our results demonstrate that TXNIP-mediated NLRP3 activation through oxidative stress is a key signaling mechanism in the susceptibility to AKI in diabetic models.

  9. Diabetic kidney disease: world wide difference of prevalence and risk factors

    Directory of Open Access Journals (Sweden)

    Gheith Osama

    2016-01-01

    Full Text Available Diabetic kidney disease – which is defined by elevated urine albumin excretion or reduced glomerular filtration rate (GFR or both – is a serious complication that occurs in 20% to 40% of all diabetics. In this review we try to highlight the prevalence of diabetic nephropathy which is not uncommon complication of diabetes all over the world. The prevalence of diabetes worldwide has extended epidemic magnitudes and is expected to affect more than 350 million people by the year 2035. There is marked racial/ethnic besides international difference in the epidemiology of diabetic kidney disease which could be explained by the differences in economic viability and governmental infrastructures. Approximately one-third of diabetic patients showed microalbuminuria after 15 years of disease duration and less than half develop real nephropathy. Diabetic kidney disease (DKD is more frequent in African-Americans, Asian-Americans, and Native Americans. Progressive kidney disease is more frequent in Caucasians patients with type 1 than type 2 diabetes mellitus (DM, although its overall prevalence in the diabetic population is higher in patients with type 2 DM while this type of DM is more prevalent. Hyperglycemia is well known risk factor for in addition to other risk factors like male sex, obesity, hypertension, chronic inflammation, resistance to insulin, hypovitaminosis D, and dyslipidemia and some genetic loci and polymorphisms in specific genes. Management of its modifiable risk factors might help in reducing its incidence in the nearby future.

  10. EP4 inhibition attenuates the development of diabetic and non-diabetic experimental kidney disease.

    Science.gov (United States)

    Thieme, Karina; Majumder, Syamantak; Brijmohan, Angela S; Batchu, Sri N; Bowskill, Bridgit B; Alghamdi, Tamadher A; Advani, Suzanne L; Kabir, M Golam; Liu, Youan; Advani, Andrew

    2017-06-13

    The therapeutic targeting of prostanoid subtype receptors may slow the development of chronic kidney disease (CKD) through mechanisms that are distinct from those of upstream COX inhibition. Here, employing multiple experimental models of CKD, we studied the effects of inhibition of the EP4 receptor, one of four receptor subtypes for the prostanoid prostaglandin E2. In streptozotocin-diabetic endothelial nitric oxide synthase knockout mice, EP4 inhibition attenuated the development of albuminuria, whereas the COX inhibitor indomethacin did not. In Type 2 diabetic db/db mice, EP4 inhibition lowered albuminuria to a level comparable with that of the ACE inhibitor captopril. However, unlike captopril, EP4 inhibition had no effect on blood pressure or hyperfiltration although it did attenuate mesangial matrix accumulation. Indicating a glucose-independent mechanism of action, EP4 inhibition also attenuated proteinuria development and glomerular scarring in non-diabetic rats subjected to surgical renal mass ablation. Finally, in vitro, EP4 inhibition prevented transforming growth factor-ß1 induced dedifferentiation of glomerular podocytes. In rodent models of diabetic and non-diabetic CKD, EP4 inhibition attenuated renal injury through mechanisms that were distinct from either broadspectrum COX inhibition or "standard of care" renin angiotensin system blockade. EP4 inhibition may represent a viable repurposing opportunity for the treatment of CKD.

  11. 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 (

  12. 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

  13. 75 FR 69093 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2010-11-10

    ... Kidney Diseases Special Emphasis Panel, Pediatric Ancillary Study to ASSESS-AKI. Date: December 7, 2010....Gov . (Catalogue of Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology...

  14. 78 FR 78373 - National Institute of Diabetes and Digestive and Kidney Diseases Notice of Closed Meeting

    Science.gov (United States)

    2013-12-26

    ... NIDDK (RO1): CKD and Diabetic Nephropathy. Date: February 20, 2014. Time: 4:00 p.m. to 5:30 p.m. Agenda..., Digestive Diseases and Nutrition Research; 93.849, Kidney Diseases, Urology and Hematology...

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

    Science.gov (United States)

    2011-03-02

    ... 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 Panel, April ] 5, 2011, 1 p.m....

  16. Human Urine as a Noninvasive Source of Kidney Cells

    Directory of Open Access Journals (Sweden)

    Fanny Oliveira Arcolino

    2015-01-01

    Full Text Available Urine represents an unlimited source of patient-specific kidney cells that can be harvested noninvasively. Urine derived podocytes and proximal tubule cells have been used to study disease mechanisms and to screen for novel drug therapies in a variety of human kidney disorders. The urinary kidney stem/progenitor cells and extracellular vesicles, instead, might be promising for therapeutic treatments of kidney injury. The greatest advantages of urine as a source of viable cells are the easy collection and less complicated ethical issues. However, extensive characterization and in vivo studies still have to be performed before the clinical use of urine-derived kidney progenitors.

  17. Angiotensin Converting Enzyme Activity in the Serum, Lung, Liver and Kidney in Streptozotocin -Induced Diabetic Rats and Diabetic Nephropathy

    OpenAIRE

    Üstündağ, Bilal

    2014-01-01

    To clarify the relationship between the alterations of the levels of angiotensin converting enzyme (ACE) and diabetic nephropathy, ACE activity in the lung, liver, kid-ney and serum were investigated in streptozotocin (STZ)-induced diabetic rats. The levels of serum ACE activity unchanged 3 days post STZ treatment but it was significantly an increase 12 and 30 days post STZ treatment in diabetic rats (p

  18. Diabetic kidney disease patients on hemodialysis: a retrospective survival analysis across different socioeconomic groups

    OpenAIRE

    Vijayan, Madhusudan; Radhakrishnan, Saranya; Abraham, Georgi; Mathew, Milly; Sampathkumar, Krishnaswamy; Mancha, Nevin Philip

    2016-01-01

    Background Diabetic kidney disease is the leading cause of stage 5 chronic kidney disease (CKD) in India. Renal replacement therapy (RRT) is accessible to very few patients because of socioeconomic deprivation. We studied the effect of diabetes and socioeconomic status on the outcome of patients on maintenance hemodialysis (MHD). Methods We retrospectively analyzed the outcome of 897 patients (629 males/268 females; mean age ± standard deviation 48.69 ± 14.27 years) initiated on MHD from 2003...

  19. 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.......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....

  20. 77 FR 52042 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2012-08-28

    ... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Nutrition Obesity Research Centers (P30... Special Emphasis Panel; Fellowships of Digestive Diseases and Nutrition. Date: October 18-19, 2012. Time..., Digestive Diseases and Nutrition Research; 93.849, Kidney Diseases, Urology and Hematology Research...

  1. 75 FR 4830 - National Institute of Diabetes and Digestive and Kidney Diseases;

    Science.gov (United States)

    2010-01-29

    ... Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory Committee Act, as... Kidney Diseases Special Emphasis Panel. Predictors of Genitourinary Disorders Studies. Date: February 23..., Ls38z@Nih.Gov . Name of Committee: National Institute of Diabetes and Digestive and Kidney...

  2. Optical cryo-imaging of kidney mitochondrial redox state in diabetic mice models

    Science.gov (United States)

    Maleki, S.; Sepehr, R.; Staniszewski, K.; Sheibani, N.; Sorenson, C. M.; Ranji, M.

    2012-03-01

    Oxidative stress (OS), which increases during diabetes, exacerbates the development and progression of diabetes complications including renal vascular and proximal tubule cell dysfunction. The objective of this study was to investigate the changes in the metabolic state of the tissue in diabetic mice kidneys using fluorescence imaging. Mitochondrial metabolic coenzymes NADH (Nicotinamide Adenine Dinucleotide), and FADH-2 (Flavin Adenine Dinucleotide) are autofluorescent and can be monitored without exogenous labels by optical techniques. The ratio of the fluorescence intensity of these fluorophores, (NADH/FAD), called the NADH redox ratio (RR), is a marker of metabolic state of a tissue. We examined mitochondrial redox states of kidneys from diabetic mice, Akita/+ and its control wild type (WT) for a group of 8- and 12-week-old mice. Average intensity and histogram of maximum projected images of FAD, NADH, and NADH RR were calculated for each kidney. Our results indicated a 17% decrease in the mean NADH RR of the kidney from 8-week-old mice compared with WT mice and, a 30% decrease in the mean NADH RR of kidney from12-week-old mice compared with WT mice. These results indicated an increase in OS in diabetic animals and its progression over time. Thus, NADH RR can be used as a hallmark of OS in diabetic kidney allowing temporal identification of oxidative state.

  3. 78 FR 48455 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Meetings

    Science.gov (United States)

    2013-08-08

    ... Diseases Advisory Council Diabetes, Endocrinology and Metabolic Diseases Subcommittee. Date: September 26... available. (Catalogue of Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and...

  4. Is Bariatric Surgery an Effective Treatment for Type II Diabetic Kidney Disease?

    Science.gov (United States)

    Friedman, Allon N; Wolfe, Bruce

    2016-03-07

    Type II diabetic kidney disease is devastating to patients and society alike. This review will evaluate bariatric surgery as a treatment for diabetic kidney disease primarily through its ability to induce and maintain regression of type II diabetes. The review begins by outlining the global challenge of diabetic kidney disease, its link to obesity, and the comparative benefits of bariatric surgery on weight and type II diabetes. It then surveys comprehensively the relevant literature, which reports that although bariatric surgery is associated with reductions in albuminuria, its effect on harder clinical end points like progression of diabetic kidney disease is not known. The review also includes a critical assessment of the risks and costs of bariatric surgery and concludes by acknowledging the major knowledge gaps in the field and providing research strategies to overcome them. Until these knowledge gaps are filled, clinicians will be forced to rely on their own subjective judgment in determining the benefit-risk ratio of bariatric surgery for patients with diabetic kidney disease.

  5. The Promise of Mesenchymal Stem Cell Therapy for Diabetic Kidney Disease.

    Science.gov (United States)

    Griffin, Tomás P; Martin, William Patrick; Islam, Nahidul; O'Brien, Timothy; Griffin, Matthew D

    2016-05-01

    Diabetes mellitus (DM) commonly leads to progressive chronic kidney disease despite current best medical practice. The pathogenesis of diabetic kidney disease (DKD) involves a complex network of primary and secondary mechanisms with both intra-renal and systemic components. Apart from inhibition of the renin angiotensin aldosterone system, targeting individual pathogenic mediators with drug therapy has not, thus far, been proven to have high clinical value. Stem or progenitor cell therapies offer an alternative strategy for modulating complex disease processes through suppressing multiple pathogenic pathways and promoting pro-regenerative mechanisms. Mesenchymal stem cells (MSCs) have shown particular promise based on their accessibility from adult tissues and their diverse mechanisms of action including secretion of paracrine anti-inflammatory and cyto-protective factors. In this review, the progress toward clinical translation of MSC therapy for DKD is critically evaluated. Results from animal models suggest distinct potential for systemic MSC infusion to favourably modulate DKD progression. However, only a few early phase clinical trials have been initiated and efficacy in humans remains to be proven. Key knowledge gaps and research opportunities exist in this field. These include the need to gain greater understanding of in vivo mechanism of action, to identify quantifiable biomarkers of response to therapy and to define the optimal source, dose and timing of MSC administration. Given the rising prevalence of DM and DKD worldwide, continued progress toward harnessing the inherent regenerative functions of MSCs and other progenitor cells for even a subset of those affected has potential for profound societal benefits.

  6. A SELECTION OF CONSTITUTIONAL PERSPECTIVES ON HUMAN KIDNEY SALES

    Directory of Open Access Journals (Sweden)

    Bonnie Venter

    2013-04-01

    Full Text Available 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 regarded as constitutionally acceptable or not. To establish the constitutional acceptability of the reimbursement of kidney donors the following rights are analysed: the right to life, the right to human dignity, the right to self-determination, the right to privacy, and the right of access to healthcare services. Case law regarding the above is also included. After careful consideration of all of the above it is concluded that it should be regarded as constitutionally acceptable to remunerate a kidney donor for his kidney.

  7. Discarded human kidneys as a source of ECM scaffold for kidney regeneration technologies.

    Science.gov (United States)

    Orlando, Giuseppe; Booth, Christopher; Wang, Zhan; Totonelli, Giorgia; Ross, Christina L; Moran, Emma; Salvatori, Marcus; Maghsoudlou, Panagiotis; Turmaine, Mark; Delario, Ginger; Al-Shraideh, Yousef; Farooq, Umar; Farney, Alan C; Rogers, Jeffrey; Iskandar, Samy S; Burns, Alan; Marini, Frank C; De Coppi, Paolo; Stratta, Robert J; Soker, Shay

    2013-08-01

    In the United States, more than 2600 kidneys are discarded annually, from the total number of kidneys procured for transplant. We hypothesized that this organ pool may be used as a platform for renal bioengineering and regeneration research. We previously showed that decellularization of porcine kidneys yields renal extracellular matrix (ECM) scaffolds that maintain their basic components, support cell growth and welfare in vitro and in vivo, and show an intact vasculature that, when such scaffolds are implanted in vivo, is able to sustain physiological blood pressure. The purpose of the current study was to test if the same strategy can be applied to discarded human kidneys in order to obtain human renal ECM scaffolds. The results show that the sodium dodecylsulfate-based decellularization protocol completely cleared the cellular compartment in these kidneys, while the innate ECM framework retained its architecture and biochemical properties. Samples of human renal ECM scaffolds stimulated angiogenesis in a chick chorioallantoic membrane assay. Importantly, the innate vascular network in the human renal ECM scaffolds retained its compliance. Collectively, these results indicate that discarded human kidneys are a suitable source of renal scaffolds and their use for tissue engineering applications may be more clinically applicable than kidneys derived from animals.

  8. Diabetic Nephropathy: The Role of Inflammation in Fibroblasts Activation and Kidney Fibrosis

    Directory of Open Access Journals (Sweden)

    Keizo eKanasaki

    2013-02-01

    Full Text Available Kidney disease associated with diabetes mellitus is a major health problem worldwide. Although established therapeutic strategies, such as appropriate blood glucose control, blood pressure control with renin-angiotensin system blockade and lipid lowering with statins, are used to treat diabetes, the contribution of diabetic end-stage kidney disease to the total number of cases requiring hemodialysis has increased tremendously in the past two decades. Once renal function starts declining, it can result in a higher frequency of renal and extra-renal events, including cardiovascular events. Therefore, slowing renal function decline is one of the main areas of focus in diabetic nephropathy research, and novel strategies are urgently needed to prevent diabetic kidney disease progression. Regardless of the type of injury and etiology, kidney fibrosis is the commonly the final outcome of progressive kidney diseases, and it results in significant destruction of normal kidney structure and accompanying functional deterioration. Kidney fibrosis is caused by prolonged injury and dysregulation of the normal wound-healing process in association with excess extracellular matrix deposition. Kidney fibroblasts play an important role in the fibrotic process, but the origin of the fibroblasts remains elusive. In addition to the activation of residential fibroblasts, other important sources of fibroblasts have been proposed, such as pericytes, fibrocytes and fibroblasts originating from epithelial and endothelial mesenchymal transition. Inflammatory cells and cytokines play a vital role In the process of fibroblast activation. In this review, we will analyze the contribution of inflammation to the process of tissue fibrosis, the type of fibroblast activation and the therapeutic strategies targeting the inflammatory pathways in an effort to slow the progression of diabetic kidney disease.

  9. Diabetic nephropathy: the role of inflammation in fibroblast activation and kidney fibrosis.

    Science.gov (United States)

    Kanasaki, Keizo; Taduri, Gangadhar; Koya, Daisuke

    2013-01-01

    Kidney disease associated with diabetes mellitus is a major health problem worldwide. Although established therapeutic strategies, such as appropriate blood glucose control, blood pressure control with renin-angiotensin system blockade, and lipid lowering with statins, are used to treat diabetes, the contribution of diabetic end-stage kidney disease to the total number of cases requiring hemodialysis has increased tremendously in the past two decades. Once renal function starts declining, it can result in a higher frequency of renal and extra-renal events, including cardiovascular events. Therefore, slowing renal function decline is one of the main areas of focus in diabetic nephropathy research, and novel strategies are urgently needed to prevent diabetic kidney disease progression. Regardless of the type of injury and etiology, kidney fibrosis is the commonly the final outcome of progressive kidney diseases, and it results in significant destruction of normal kidney structure and accompanying functional deterioration. Kidney fibrosis is caused by prolonged injury and dysregulation of the normal wound-healing process in association with excess extracellular matrix deposition. Kidney fibroblasts play an important role in the fibrotic process, but the origin of the fibroblasts remains elusive. In addition to the activation of residential fibroblasts, other important sources of fibroblasts have been proposed, such as pericytes, fibrocytes, and fibroblasts originating from epithelial-to-mesenchymal and endothelial-to-mesenchymal transition. Inflammatory cells and cytokines play a vital role In the process of fibroblast activation. In this review, we will analyze the contribution of inflammation to the process of tissue fibrosis, the type of fibroblast activation and the therapeutic strategies targeting the inflammatory pathways in an effort to slow the progression of diabetic kidney disease.

  10. Sulodexide ameliorates early but not late kidney disease in models of radiation nephropathy and diabetic nephropathy

    OpenAIRE

    Rossini, Michele; Naito, Takashi; Yang, Haichun; Freeman, Michael; Donnert, Ellen; Ma, Li-Jun; Dunn, Stephen R.; Sharma, Kumar; Fogo, Agnes B.

    2010-01-01

    Background. Sulodexide is a glycosaminoglycan with anticoagulant and antithrombotic activities. Although sulodexide reduced albuminuria in patients with type 1 and type 2 diabetes, long-term effects on chronic renal injury are not established. We investigated sulodexide effects and mechanisms in a rat radiation nephropathy model and in the db/db mouse model of diabetic kidney disease.

  11. Troubleshooting methods for microarray gene expression analysis in the onset of diabetic kidney disease

    NARCIS (Netherlands)

    Mazagova, Magdalena; Henning, Robert H.; Duin, Marry; van Buiten, Azuwerus; Buikema, Hendrik; Deelman, Leo E.

    2013-01-01

    Introduction: Microarrays have become the standard technique for discovering new genes involved in the development of (kidney) disease. Diabetic nephropathy is a frequent complication of diabetes and is characterized by renal fibrosis. As the pathways leading to fibrosis are initiated early in diabe

  12. Diabetes Insipidus

    Science.gov (United States)

    ... Health Information Kidney Disease Diabetes Inspidus Related Topics Section Navigation Kidney Disease Acquired Cystic Kidney Disease Amyloidosis & ... for a Child with Kidney Disease Ectopic Kidney Medullary Sponge Kidney Kidney Dysplasia Kidney Failure Choosing a ...

  13. Dialysis modality choice in diabetic patients with end-stage kidney disease

    DEFF Research Database (Denmark)

    Couchoud, Cecile; Bolignano, Davide; Nistor, Ionut

    2015-01-01

    BACKGROUND: Diabetes is the leading cause of end-stage kidney disease (ESKD). Because of conflicting results in observational studies, it is still subject to debate whether in diabetic patients the dialysis modality selected as first treatment (haemodialysis or peritoneal dialysis) may have a major...... on diabetes, end-stage kidney disease and dialysis modality. Selection of relevant studies, data extraction and analysis were performed by two independent reviewers. RESULTS: Twenty-five observational studies (23 on incident and 2 on prevalent cohorts) were included in this review. Mortality was the only main...

  14. Laparoscopically implanted gastric pacemaker after kidney-pancreas transplantation: treatment of morbid obesity and diabetic gastroparesis.

    Science.gov (United States)

    Bonatti, Hugo; Brandacher, Gerald; Hoeller, Elisabeth; Stelzmueller, Ingrid; Mark, Walter; Margreiter, Raimund; Weiss, Helmut

    2007-01-01

    Combined kidney-pancreas transplantation is the treatment of choice for end-stage diabetic nephropathy. Weight gain post-transplant increases the risk for post-transplant complications and death due to cardiovascular events. Gastric pacemakers have been used for therapy of diabetic gastropathy and for the treatment of moderate morbid obesity. We report a patient who experienced significant weight gain following successful kidney-pancreas transplantation and was thereafter successfully treated for diabetic gastroparesis and morbid obesity by use of a laparoscopically implanted gastric pacemaker.

  15. Tangzhiqing Granules Alleviate Podocyte Epithelial-Mesenchymal Transition in Kidney of Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Haiyan Xu

    2017-01-01

    Full Text Available This study discussed the effect of Tangzhiqing granules on podocyte epithelial-mesenchymal transition in kidney of diabetic rats. The diabetic rats were divided randomly into five groups: DM group treated with vehicle, Tangzhiqing granules low-dose treatment group, Tangzhiqing granules middle-dose treatment group, and Tangzhiqing granules high-dose treatment group. Eight Wistar rats used as control group were given saline solution. The intervention was all intragastric administration for 8 weeks. At the end of the 8 weeks, biochemical parameters and kidney weight/body weight ratio were measured. The kidney tissues were observed under light microscope and transmission electron microscopy. To search for the underlying mechanism, we examined the epithelial-to-mesenchymal transition (EMT related molecular markers and TGF-β/smad signaling pathway key proteins expression. The results showed that Tangzhiqing granules relieved the structural damage and functional changes of diabetic kidneys. Kidney podocyte EMT related molecular markers nephrin and CD2AP expression were increased, when desmin and α-SMA levels were decreased by Tangzhiqing granules in diabetic rats. Further TGF-β/smad signaling pathway key proteins TGF-β1 and p-smad2/3 levels were decreased in diabetic rats after treatment with Tangzhiqing granules. These findings suggest that Tangzhiqing granules may protect the podocytes of diabetic nephropathy rats via alleviating podocyte EMT and likely activating TGFβ/smad signaling pathway.

  16. Effects of Aminoguanidine on Lipid and Protein Oxidation in Diabetic Rat Kidneys

    OpenAIRE

    Yavuz, Dilek Gogas; Küçükkaya, Belgin; Ersöz, H. önder; Yalçin, A. Süha; Emerk, Kaya; Akalin, Sema

    2002-01-01

    Nonenzymatic glycation of tissue and plasma proteins may stimulate the production of oxidant and carbonyl stress in diabetes. The aim of this study was to evaluate the effects of aminoguanidine (AG) on lipid peroxidation, protein oxidation and nitric oxide (NO) release in diabetic rat kidneys. After induction of diabetes with streptozotocin, female Wistar rats were divided into 2 groups. Group DAG (n=9) rats were given AG hydrogen carbonate (1 g/L) in drinking water and group D (n=8) was diab...

  17. Podocyte detachment and reduced glomerular capillary endothelial fenestration promote kidney disease in type 2 diabetic nephropathy

    OpenAIRE

    Weil, E. Jennifer; Lemley, Kevin V; Mason, Clinton C; Yee, Berne; Jones, Lois I.; Blouch, Kristina; Lovato, Tracy; Richardson, Meghan; Myers, Bryan D.; Nelson, Robert G.

    2012-01-01

    Podocyte detachment and reduced endothelial cell fenestration and relationships between these features and the classic structural changes of diabetic nephropathy have not been described in patients with type 2 diabetes. Here we studied these relationships in 37 Pima Indians with type 2 diabetes of whom 11 had normal albuminuria, 16 had microalbuminuria, and 10 had macroalbuminuria. Biopsies from ten kidney donors (not Americans Indians) showed almost undetectable (0.03%) podocyte detachment a...

  18. 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...... filtration rate was reduced by 1.5 ml/min/1.73 m(2) (P = 0.2). CONCLUSIONS: Paricalcitol therapy did not affect plasma N-terminal probrain natriuretic peptide concentration in people with Type 1 diabetes and diabetic nephropathy; however, the urinary albumin excretion rate was significantly lowered....

  19. Update on potential drugs for the treatment of diabetic kidney disease.

    Science.gov (United States)

    Shepler, Brian; Nash, Christy; Smith, Cory; Dimarco, Abbey; Petty, Josie; Szewciw, Stephanie

    2012-06-01

    Although controlling hyperglycemia and proteinuria is currently the main focus of diabetic kidney disease management, some existing drugs and other new compounds are being evaluated for their ability to interrupt the disease process. Specifically, drugs that interfere with the formation and action of advanced glycation end products and reduce or inhibit fibrosis of the glomerular structures in the presence of hyperglycemia are just 2 examples. The aim is to provide an in-depth review of drugs currently being investigated to treat diabetic kidney disease (DKD) through novel mechanisms of action that interrupt the pathologic process. A literature search was performed of the search engines PubMed (www.pubmed.gov) and ClinicalTrials.gov (www.clinicaltrials.gov), initially using the broad search terms diabetic nephropathy, diabetic kidney disease, and advanced glycation end products. Limits were set to include only English-language articles and studies performed in human subjects from January 2000. Previous review articles on this subject captured through the initial search also served as a basis for identifying drugs that had been under evaluation. Once a list of drugs and compounds was established, each agent was used as an independent search term through the same search engines listed to capture any new and/or ongoing studies for inclusion in this review. Any trials in DKD patients collected through this process were evaluated in this review including Phase I, II, and III studies. Fifteen drugs were identified, and 24 studies were reviewed. Ten drugs have evidence of beneficial effects in treating DKD patients as reported by improvements in glomerular filtration rate, albumin-to-creatinine ratio, proteinuria, or serum creatinine concentrations. Five drugs demonstrated no significant benefit or side-effect profiles that would prohibit their routine use. Pirfenidone, doxycycline, bardoxolone, pentoxifylline, ruboxistaurin, pyridoxamine, paricalcitol, FG-3019, AST-120

  20. Urinary Microvesicle-Bound Uromodulin: A Potential Molecular Biomarker in Diabetic Kidney Disease

    Science.gov (United States)

    Lou, Neng-jun; Ni, Yi-hong; Jia, Hong-ying; Deng, Jing-ti; Jiang, Lu; Zheng, Feng-jie

    2017-01-01

    This study was designed to investigate the changes of urinary microvesicle-bound uromodulin and total urinary uromodulin levels in human urine and the correlations with the severity of diabetic kidney disease (DKD). 31 healthy subjects without diabetes and 100 patients with type 2 diabetes mellitus (T2DM) were included in this study. The patients with T2DM were divided into three groups based on the urinary albumin/creatinine ratio (UACR): normoalbuminuria group (DM, n = 46); microalbuminuria group (DN1, n = 32); and macroalbuminuria group (DN2, n = 22). We use a specific monoclonal antibody AD-1 to capture the urinary microvesicles. Urinary microvesicle-bound uromodulin and total urinary uromodulin levels were determined by enzyme-linked immunosorbent assay (ELISA). Our results showed that the levels of urinary microvesicle-bound uromodulin in DN1 and DN2 groups were significantly higher than those in control group and DM group (P < 0.01). Multiple stepwise linear regression analysis showed that UACR was independent determinant for urinary microvesicle-bound uromodulin (P < 0.05) but not for total urinary uromodulin. These findings suggest that the levels of urinary microvesicle-bound uromodulin are associated with the severity of DKD. The uromodulin in urinary microvesicles may be a specific marker of DKD and potentially may be used to predict the onset and/or monitor the progression of DKD. PMID:28182086

  1. Management of diabetes mellitus in individuals with chronic kidney disease: therapeutic perspectives and glycemic control

    Directory of Open Access Journals (Sweden)

    Carolina C.R. Betônico

    2016-01-01

    Full Text Available The purpose of this study was to evaluate the therapeutic options for diabetes treatment and their potential side effects, in addition to analyzing the risks and benefits of tight glycemic control in patients with diabetic kidney disease. For this review, a search was performed using several pre-defined keyword combinations and their equivalents: “diabetes kidney disease” and “renal failure” in combination with “diabetes treatment” and “oral antidiabetic drugs” or “oral hypoglycemic agents.” The search was performed in PubMed, Endocrine Abstracts and the Cochrane Library from January 1980 up to January 2015. Diabetes treatment in patients with diabetic kidney disease is challenging, in part because of progression of renal failure-related changes in insulin signaling, glucose transport and metabolism, favoring both hyperglycemic peaks and hypoglycemia. Additionally, the decline in renal function impairs the clearance and metabolism of antidiabetic agents and insulin, frequently requiring reassessment of prescriptions. The management of hyperglycemia in patients with diabetic kidney disease is even more difficult, requiring adjustment of antidiabetic agents and insulin doses. The health team responsible for the follow-up of these patients should be vigilant and prepared to make such changes; however, unfortunately, there are few guidelines addressing the nuances of the management of this specific population.

  2. Management of diabetes mellitus in individuals with chronic kidney disease: therapeutic perspectives and glycemic control.

    Science.gov (United States)

    Betônico, Carolina C R; Titan, Silvia M O; Correa-Giannella, Maria Lúcia C; Nery, Márcia; Queiroz, Márcia

    2016-01-01

    The purpose of this study was to evaluate the therapeutic options for diabetes treatment and their potential side effects, in addition to analyzing the risks and benefits of tight glycemic control in patients with diabetic kidney disease. For this review, a search was performed using several pre-defined keyword combinations and their equivalents: "diabetes kidney disease" and "renal failure" in combination with "diabetes treatment" and "oral antidiabetic drugs" or "oral hypoglycemic agents." The search was performed in PubMed, Endocrine Abstracts and the Cochrane Library from January 1980 up to January 2015. Diabetes treatment in patients with diabetic kidney disease is challenging, in part because of progression of renal failure-related changes in insulin signaling, glucose transport and metabolism, favoring both hyperglycemic peaks and hypoglycemia. Additionally, the decline in renal function impairs the clearance and metabolism of antidiabetic agents and insulin, frequently requiring reassessment of prescriptions. The management of hyperglycemia in patients with diabetic kidney disease is even more difficult, requiring adjustment of antidiabetic agents and insulin doses. The health team responsible for the follow-up of these patients should be vigilant and prepared to make such changes; however, unfortunately, there are few guidelines addressing the nuances of the management of this specific population.

  3. Management of diabetes mellitus in individuals with chronic kidney disease: therapeutic perspectives and glycemic control

    Science.gov (United States)

    Betônico, Carolina C R; Titan, Silvia M O; Correa-Giannella, Maria Lúcia C; Nery, Márcia; Queiroz, Márcia

    2016-01-01

    The purpose of this study was to evaluate the therapeutic options for diabetes treatment and their potential side effects, in addition to analyzing the risks and benefits of tight glycemic control in patients with diabetic kidney disease. For this review, a search was performed using several pre-defined keyword combinations and their equivalents: “diabetes kidney disease” and “renal failure” in combination with “diabetes treatment” and “oral antidiabetic drugs” or “oral hypoglycemic agents.” The search was performed in PubMed, Endocrine Abstracts and the Cochrane Library from January 1980 up to January 2015. Diabetes treatment in patients with diabetic kidney disease is challenging, in part because of progression of renal failure-related changes in insulin signaling, glucose transport and metabolism, favoring both hyperglycemic peaks and hypoglycemia. Additionally, the decline in renal function impairs the clearance and metabolism of antidiabetic agents and insulin, frequently requiring reassessment of prescriptions. The management of hyperglycemia in patients with diabetic kidney disease is even more difficult, requiring adjustment of antidiabetic agents and insulin doses. The health team responsible for the follow-up of these patients should be vigilant and prepared to make such changes; however, unfortunately, there are few guidelines addressing the nuances of the management of this specific population. PMID:26872083

  4. The relationship between vitamin D and the renin-angiotensin system in the pathophysiology of hypertension, kidney disease, and diabetes.

    Science.gov (United States)

    Vaidya, Anand; Williams, Jonathan S

    2012-04-01

    Vitamin D has been implicated in the pathophysiology of extraskeletal conditions such as hypertension, kidney disease, and diabetes via its ability to negatively regulate the renin-angiotensin system (RAS). This article reviews the evidence supporting a link between vitamin D and the RAS in these conditions, with specific emphasis on translational observations and their limitations. A literature review of animal and human studies evaluating the role of vitamin D in hypertension, kidney disease, and diabetes was performed. Excess activity of the RAS has been implicated in the pathogenesis of hypertension, chronic kidney disease, decreased insulin secretion, and insulin resistance. Animal studies provide strong support for 1,25-dihydroxyvitamin D(3)-mediated downregulation of renin expression and RAS activity via its interaction with the vitamin D receptor. Furthermore, the activity of vitamin D metabolites in animals is associated with reductions in blood pressure, proteinuria and renal injury, and with improved β-cell function. Many observational, and a few interventional, studies in humans have supported these findings; however, there is a lack of well-designed prospective human interventional studies to definitively assess clinical outcomes. There is a need for more well-designed prospective interventional studies to validate this hypothesis in human clinical outcomes. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. 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

  6. 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.

  7. Humanized in vivo Model for Autoimmune Diabetes

    Science.gov (United States)

    2009-02-01

    AWARD NUMBER: W81XWH-07-1-0121 TITLE: Humanized in vivo Model for Autoimmune Diabetes PRINCIPAL INVESTIGATOR: Gerald T Nepom, M.D., Ph.D...4. TITLE AND SUBTITLE Sa. CONTRACT NUMBER Humanized in vivo Model for Autoimmune Diabetes Sb. GRANT NUMBER W81XWH-07-1-0121 Sc. PROGRAM ELEMENT...therapies. This research study entails using humanized mice manifesting type 1 diabetes (T1 D)-associated human HLA molecules to address the fate and

  8. Sitagliptin Prevents Inflammation and Apoptotic Cell Death in the Kidney of Type 2 Diabetic Animals

    Directory of Open Access Journals (Sweden)

    Catarina Marques

    2014-01-01

    Full Text Available This study aimed to evaluate the efficacy of sitagliptin, a dipeptidyl peptidase IV (DPP-IV inhibitor, in preventing the deleterious effects of diabetes on the kidney in an animal model of type 2 diabetes mellitus; the Zucker diabetic fatty (ZDF rat: 20-week-old rats were treated with sitagliptin (10 mg/kg bw/day during 6 weeks. Glycaemia and blood HbA1c levels were monitored, as well as kidney function and lesions. Kidney mRNA and/or protein content/distribution of DPP-IV, GLP-1, GLP-1R, TNF-α, IL-1β, BAX, Bcl-2, and Bid were evaluated by RT-PCR and/or western blotting/immunohistochemistry. Sitagliptin treatment improved glycaemic control, as reflected by the significantly reduced levels of glycaemia and HbA1c (by about 22.5% and 1.2%, resp. and ameliorated tubulointerstitial and glomerular lesions. Sitagliptin prevented the diabetes-induced increase in DPP-IV levels and the decrease in GLP-1 levels in kidney. Sitagliptin increased colocalization of GLP-1 and GLP-1R in the diabetic kidney. Sitagliptin also decreased IL-1β and TNF-α levels, as well as, prevented the increase of BAX/Bcl-2 ratio, Bid protein levels, and TUNEL-positive cells which indicates protective effects against inflammation and proapoptotic state in the kidney of diabetic rats, respectively. In conclusion, sitagliptin might have a major role in preventing diabetic nephropathy evolution due to anti-inflammatory and antiapoptotic properties.

  9. 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.

  10. 76 FR 80954 - National Institute of Diabetes and Digestive and Kidney Disorders; Notice of Closed Meeting

    Science.gov (United States)

    2011-12-27

    ..., Diabetes, Translation Research, Division of Diabetes, Endocrinology and Metabolic Diseases, NIDDK, NIH... Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and...

  11. Magnetic resonance imaging (MRI) and pathophysiology of the rat kidney in streptozotocin-induced diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Lohr, J.; Mazurchuk, R.J.; Acara, M.A.; Nickerson, P.A.; Fiel, R.J. (State Univ. of New York, Buffalo (USA))

    1991-01-01

    Proton magnetic resonance imaging was performed on rats before induction of diabetes with streptozotocin (STZ) and at 2 and 12 days postinduction. Images revealed an increase in maximal longitudinal and axial dimensions of the kidneys at 2 days and a further increase at 12 days. Similarly, an increase in the size of the remaining kidney was seen in a rat which underwent uninephrectomy as a positive control. Two major differences were observed between the kidney undergoing compensatory hypertrophy and those developing diabetic nephropathy: (i) Expansion of the renal vasculature was seen only in images of the diabetic rat; (ii) A loss in conspicuity of the normal corticomedullary junction was seen in the T2-weighted images of the diabetic rat but not in the uninephrectomized rat. Histologic examination revealed that the medulla increased to a size greater than the cortex during diabetic nephropathy whereas the medullary volume was less than that of the cortex during compensatory hypertrophy. In vitro T1 relaxation times in cortex, outer medulla and inner medulla of kidneys from control rats were measured and compared with the same respective regions in diabetic rats. When these values were correlated with tissue water content, a linear increase in relaxation rate versus percent water content from cortex to inner medulla was found in the control kidneys, but this correlation was absent in diabetic nephropathy. These studies demonstrate that MRI is an effective noninvasive tool for studying the course of renal hypertrophy and hydration changes in the development of renal disease in STZ-induced diabetes in the rat.

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

    OpenAIRE

    Dilek Pandir; Betul Unal; Hatice Bas

    2016-01-01

    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 aci...

  13. Regulation of elongation factor-1 expression by vitamin E in diabetic rat kidneys.

    Science.gov (United States)

    Al-Maghrebi, May; Cojocel, Constantin; Thompson, Mary S

    2005-05-01

    Translation elongation factor-1 (EF-1) forms a primary site of regulation of protein synthesis and has been implicated amongst others in tumorigenesis, diabetes and cell death. To investigate whether diabetes-induced oxidative stress affects EF-1 gene expression, we used a free radical scavenger, vitamin E. The following groups of rats (5/group) were studied: control, vitamin E control, diabetic and diabetic treated with vitamin E. Markers of hyperglycemia, kidney function, oxidative stress, and kidney hypertrophy were elevated in diabetic rats. Increased urinary protein excretion indicated early signs of glomerular and tubular dysfunction. The mRNA and protein levels of the three EF-1 subunits (A, Balpha, and Bgamma) were determined in renal cortex extracts using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), northern blot analysis and western blotting. EF-1A mRNA expression in renal cortex extracts was significantly increased by at least 2-fold (p glycemic and oxidative stresses in renal cortex and kidney hypertrophy. EF-1A mRNA and protein levels were also reduced to control levels. In conclusion, EF-1A but not EF-1Balpha and EF-1Bgamma gene expression is significantly enhanced in the renal cortex of diabetic rats. Normalization of enhanced EF-1A expression by vitamin E treatment suggests a role for EF-1A during diabetes-induced oxidative stress.

  14. Study of the risk factors and complications of diabetes mellitus after live kidney donation.

    Science.gov (United States)

    Abuelmagd, Mohammed M; Nagib, Ayman M; Abuelmagd, Megahed M; Refaie, Ayman F; Elhindi, Yasser A; Ahmed, Mohammed F; Ali, Mohammed H; Elmaghrabi, Hanzada M; Bakr, Mohammed A

    2015-04-01

    Kidney donors, similar to the general population, are at risk for development of type 2 diabetes mellitus. The course of donors who develop type 2 diabetes mellitus has not been well studied. This work is aimed at estimating the incidence of diabetes after kidney donation, and study some risk factors and some complications of diabetes mellitus after donation. The material of this record based work comprised the records 2267 donors who donated 1 of their kidneys between 1976 and 2014 in the Urology and Nephrology Center, Mansoura University, Egypt, and regularly followed-up at its outpatient clinic. There were 388 donors included in the study and their medical records were revised. Postdonation weight gain and family history of diabetes mellitus were statistically significant on both the development of diabetes mellitus, high, very high albuminuria, and/or decreased creatinine clearance. Metformin and insulin use seemed to significantly reduce the protein excretion, and creatinine clearance decline in the studied group. There is a significant effect of the family history of diabetes mellitus on the development of high, very high albuminuria, and/or decreased creatinine clearance.

  15. Current management of diabetic patients with kidney disease: a renal‑cardio‑endocrine perspective.

    Science.gov (United States)

    Pecoits-Filho, Roberto; Fortes, José; Volaco, Aléxei; Vencio, Sergio; Sposito, Andrei C

    2017-03-01

    Diabetic kidney disease (DKD) is one of the most frequent and dangerous complications of diabetes mellitus type 2, affecting about one‑third of the patients. DKD results in increased hospitalizations and mortality rates, especially due to cardiovascular complications. This high burden of kidney disease is mainly due to the increasing complexity of in- outpatient care for patients with DM. There is a strikingly complex interaction of kidney dysfunction with many aspects of diabetes care, such as redefinition of targets of treatment, interactions of traditional and non‑traditional risk factors, and pharmacological issues related to pharmacokinetic and side effects of drugs. Particularly when not carefully managed, DKD increases the demand for renal replacement therapies, such as dialysis and kidney transplants. The combined economic and social costs of this disease are high and of concern to the world's health systems. The main objective of this review is to provide insight into the recommendations for the evaluation and stratification of DKD and how the presence of kidney disease changes the optimal management of diabetic patients from an integrated renal‑cardio‑endocrine perspective.

  16. Diabetes and Kidney Disease in American Indians: Potential Role of Sugar-Sweetened Beverages.

    Science.gov (United States)

    Yracheta, Joseph M; Lanaspa, Miguel A; Le, MyPhuong T; Abdelmalak, Manal F; Alfonso, Javier; Sánchez-Lozada, Laura G; Johnson, Richard J

    2015-06-01

    Since the early 20th century, a marked increase in obesity, diabetes, and chronic kidney disease has occurred in the American Indian population, especially the Pima Indians of the Southwest. Here, we review the current epidemic and attempt to identify remediable causes. A search was performed using PubMed and the search terms American Indian and obesity, American Indian and diabetes, American Indian and chronic kidney disease, and American Indian and sugar or fructose, Native American, Alaska Native, First Nations, Aboriginal, Amerind, and Amerindian for American Indian for articles linking American Indians with diabetes, obesity, chronic kidney disease, and sugar; additional references were identified in these publications traced to 1900 and articles were reviewed if they were directly discussing these topics. Multiple factors are involved in the increased risk for diabetes and kidney disease in the American Indian population, including poverty, overnutrition, poor health care, high intake of sugar, and genetic mechanisms. Genetic factors may be especially important in the Pima, as historical records suggest that this group was predisposed to obesity before exposure to Western culture and diet. Exposure to sugar-sweetened beverages may also be involved in the increased risk for chronic kidney disease. In these small populations in severe health crisis, we recommend further studies to investigate the role of excess added sugar, especially sugar-sweetened beverages, as a potentially remediable risk factor.

  17. 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.

  18. Simultaneous pancreas–kidney transplant for type I diabetes with renal failure: Anaesthetic considerations

    Directory of Open Access Journals (Sweden)

    Lakshmi Kumar

    2016-01-01

    Full Text Available Pancreatic grafts have been successfully used in patients with diabetes and are combined with kidney transplantation in patients with renal failure. The propagation of awareness in organ donation in India has increased the donor pool of transplantable organs in the last few years making multi visceral transplants feasible in our country. We present the anaesthetic management of a 32-year-old male with diabetes mellitus and end-stage renal failure who was successfully managed with a combined pancreas and kidney transplantation.

  19. Nutritional approach of the patient with diabetes mellitus and chronic kidney disease. A case report

    Science.gov (United States)

    Torres Torres, Beatriz; Izaola Jáuregu, Olatz; De Luis Román, Daniel A

    2017-05-08

    The prevention and treatment of chronic kidney disease (CKD) in diabetes through diet and lifestyle have been a topic of much interest over the years. Consideration of the type and amount of carbohydrate, protein and fat is required for optimal blood glucose control, for clinical outcomes related to renal function and for consideration of risk reduction for cardiovascular disease. Depending on the CKD stage different dietary changes should be considered protein-calorie malnutrition is common in chronic kidney disease patients and is a powerful predictor of morbidity and mortality. We review the nutritional management of a diabetic patient throughout the progression of their CKD.

  20. Lessons From the KK-Ay Mouse, a Spontaneous Animal Model for the Treatment of Human Type 2 Diabetic Nephropathy

    OpenAIRE

    Tomino, Yasuhiko

    2012-01-01

    Abstract Diabetic nephropathy is a major cause of end-stage kidney disease (ESKD) in patients with type 1 and type 2 diabetes throughout the world. In human glomeruli, expansion of diffuse mesangial matrices, exudative lesions and/or segmental nodular sclerosis are pathological features of diabetic nephropathy. There have been many reports on the pathogenesis and treatment of type 2 diabetes using various animal models. It appears that KK-Ay mice, especially in terms of their immunohistologic...

  1. Clinical questionnaire study of oral health care and symptoms in diabetic vs. non-diabetic predialysis chronic kidney disease patients.

    Science.gov (United States)

    Vesterinen, Maarit; Ruokonen, Hellevi; Furuholm, Jussi; Honkanen, Eero; Meurman, Jukka H

    2012-04-01

    This paper aims to study oral symptoms (burning mouth sensation, xerostomia, dysphagia, and dysgeusia) and background characteristics among chronic kidney disease (CKD) patients. The hypothesis was that patients experience oral discomfort and show interest towards dental care differently depending on the origin of their kidney disease. One hundred thirty-eight CKD patients at predialysis stage (94 men, 44 women, mean age 54 years) at the Helsinki University Central Hospital participated in the study. The patients were divided into a diabetic nephropathy group and a group of patients with other kidney diseases. The patients had a clinical oral examination and filled in a structured questionnaire. The data were analyzed and compared between the groups (SPSS for Windows version 15.0). T test was used for parameters normally distributed while binomial data were analyzed with cross-tabulations and chi-square test. Contrary to our study hypothesis, no statistically significant differences were seen in the questionnaire study between the diabetic vs. non-diabetic CKD patients in any other study parameter except in the use of medication (10 ± 2.3 vs. 8 ± 3.1 drugs daily, p diabetic, 48.2% in non-diabetic patients). No difference was seen in the frequency of oral discomfort among the different groups of predialysis patients investigated. Clinicians should be aware of nephropathy patients who frequently suffer from oral discomfort, particularly xerostomia.

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

    KAUST Repository

    RamachandraRao, Satish Posettihalli

    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.

  3. The Effect of Zofenopril on Pancreas, Kidney and Liver of Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Ayşe ÇARLIOĞLU

    2014-05-01

    Full Text Available OBJECTIVE: Oxidative stress is responsible for some important complications of diabetes mellitus. Zofenopril, which has an antioxidant effect, may decrease the oxidative stress of the diabetic microenvironment. The aim of our study was to evaluate the effect of zofenopril in the liver, pancreas and kidney of alloxan-induced diabetic rats. MATERIAL and METHODS: Rats were divided into five groups: control group (n=6, rats treated with zonenopril (50 mg/kg/day, orally four weeks; n=6, rats exposed to alloxane (120 mg/kg single dose intraperitoneal injection, n=6, rats administered alloxan+zofenopril (n=6 and rats administered insulin plus alloxan. RESULTS: After one month, we observed histological improvement in the kidneys but not in the pancreas and liver. CONCLUSION: In conclusion, zofenopril may be effective on the renal complications of diabetes mellitus.

  4. Application of KDIGO classifcation of chronic kidney disease for analyzing the prevalence of kidney disease and other vascular diseases in 1645 type 2 diabetic patients

    Institute of Scientific and Technical Information of China (English)

    李明

    2014-01-01

    Objective To analyze the prevalence,risk factors of kidney disease in type 2 diabetic patients with KDIGO classification of chronic kidney disease,and to study cardiovascular and cerebrovascular diseases and death in these patients,so as to investigate the significance of the KDIGO classification system.Methods One thousand six hundred and forty-five type 2 diabetic patients who were in

  5. 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.

  6. Analysis of the genetic diversity of Candida isolates obtained from diabetic patients and kidney transplant recipients

    Directory of Open Access Journals (Sweden)

    Volmir Pitt Benedetti

    2016-01-01

    Full Text Available Yeasts of the genus Candida have high genetic variability and are the most common opportunistic pathogenic fungi in humans. In this study, we evaluated the genetic diversity among 120 isolates of Candida spp. obtained from diabetic patients, kidney transplant recipients and patients without any immune deficiencies from Paraná state, Brazil. The analysis was performed using the ITS1-5.8S-ITS2 region and a partial sequence of 28S rDNA. In the phylogenetic analysis, we observed a consistent separation of the species C. albicans, C. dubliniensis, C. glabrata, C. tropicalis, C. parapsilosis, C. metapsilosis and C. orthopsilosis, however with low intraspecific variability. In the analysis of the C. albicans species, two clades were formed. Clade A included the largest number of isolates (91.2% and the majority of isolates from GenBank (71.4%. The phylogenetic analysis showed low intraspecific genetic diversity, and the genetic polymorphisms between C. albicans isolates were similar to genetic divergence found in other studies performed with isolates from Brazil. This low genetic diversity of isolates can be explained by the geographic proximity of the patients evaluated. It was observed that yeast colonisation was highest in renal transplant recipients and diabetic patients and that C. albicans was the species most frequently isolated.

  7. Analysis of the genetic diversity of Candida isolates obtained from diabetic patients and kidney transplant recipients

    Science.gov (United States)

    Benedetti, Volmir Pitt; Savi, Daiani Cristina; Aluizio, Rodrigo; Adamoski, Douglas; Kava-Cordeiro, Vanessa; Galli-Terasawa, Lygia V; Glienke, Chirlei

    2016-01-01

    Yeasts of the genus Candida have high genetic variability and are the most common opportunistic pathogenic fungi in humans. In this study, we evaluated the genetic diversity among 120 isolates of Candida spp. obtained from diabetic patients, kidney transplant recipients and patients without any immune deficiencies from Paraná state, Brazil. The analysis was performed using the ITS1-5.8S-ITS2 region and a partial sequence of 28S rDNA. In the phylogenetic analysis, we observed a consistent separation of the species C. albicans, C. dubliniensis, C. glabrata, C. tropicalis, C. parapsilosis, C. metapsilosis and C. orthopsilosis, however with low intraspecific variability. In the analysis of the C. albicans species, two clades were formed. Clade A included the largest number of isolates (91.2%) and the majority of isolates from GenBank (71.4%). The phylogenetic analysis showed low intraspecific genetic diversity, and the genetic polymorphisms between C. albicans isolates were similar to genetic divergence found in other studies performed with isolates from Brazil. This low genetic diversity of isolates can be explained by the geographic proximity of the patients evaluated. It was observed that yeast colonisation was highest in renal transplant recipients and diabetic patients and that C. albicans was the species most frequently isolated. PMID:27276363

  8. Targeting gut microbiota: a potential promising therapy for diabetic kidney disease

    OpenAIRE

    Chen, Zhonge; Zhu, Shuishan; Xu, Gaosi

    2016-01-01

    Conventional studies reveal a contributory role of gut microbiota in the process of diabetes mellitus (DM) and end-stage renal disease (ESRD). However, the mechanism through which gut microbiota influence diabetic kidney disease (DKD) is ignored. In the present article, we reviewed the changes in gut microbiota of patients with DM, DKD as well as ESRD, and how this may contribute to the progression of DKD. Although further studies are needed to either selectively change the composition of the...

  9. Uric acid as a risk factor for progression of non-diabetic chronic kidney disease? The Mild to Moderate Kidney Disease (MMKD) Study

    OpenAIRE

    Sturm, Gisela; Kollerits, Barbara; Neyer, Ulrich; Ritz, Eberhard; Kronenberg, Florian

    2008-01-01

    Uric acid as a risk factor for progression of non-diabetic chronic kidney disease? The Mild to Moderate Kidney Disease (MMKD) Study correspondence: Corresponding author. Tel.: +43 5129003 70560; fax: +43 5129003 73560or73561. (Kronenberg, Florian) (Kronenberg, Florian) Division of Genetic Epidemiology; Department of Medical Genetics, Molecular and Clinical Pharmacology; Innsbruck Medical University - AUSTRIA (Stur...

  10. Therapeutic miR-21 Silencing Ameliorates Diabetic Kidney Disease in Mice.

    Science.gov (United States)

    Kölling, Malte; Kaucsar, Tamas; Schauerte, Celina; Hübner, Anika; Dettling, Angela; Park, Joon-Keun; Busch, Martin; Wulff, Xaver; Meier, Matthias; Scherf, Kristian; Bukosza, Nóra; Szénási, Gábor; Godó, Mária; Sharma, Amit; Heuser, Michael; Hamar, Peter; Bang, Claudia; Haller, Hermann; Thum, Thomas; Lorenzen, Johan M

    2017-01-04

    Diabetic nephropathy is the main cause of end-stage renal disease. MicroRNAs are powerful regulators of the genome, and global expression profiling revealed miR-21 to be among the most highly regulated microRNAs in kidneys of mice with diabetic nephropathy. In kidney biopsies of diabetic patients, miR-21 correlated with tubulointerstitial injury. In situ PCR analysis showed a specific enrichment of miR-21 in glomerular cells. We identified cell division cycle 25a (Cdc25a) and cyclin-dependent kinase 6 (Cdk6) as novel miR-21 targets in mesangial cells. miR-21-mediated repression of Cdc25a and Cdk6 resulted in impaired cell cycle progression and subsequent mesangial cell hypertrophy. miR-21 increased podocyte motility by regulating phosphatase and tensin homolog (Pten). miR-21 antagonism in vitro and in vivo in streptozotocin-induced diabetic mice decreased mesangial expansion, interstitial fibrosis, macrophage infiltration, podocyte loss, albuminuria, and fibrotic- and inflammatory gene expression. In conclusion, miR-21 antagonism rescued various functional and structural parameters in mice with diabetic nephropathy and, thus, might be a viable option in the treatment of patients with diabetic kidney disease.

  11. Triglycerides in the human kidney cortex: relationship with body size.

    Directory of Open Access Journals (Sweden)

    Ion Alexandru Bobulescu

    Full Text Available 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.

  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. When Should We Start Using Angiotensin Converting Enzyme Inhibitors/Angiotensin Receptor Blockers in Diabetic Kidney Disease?

    Directory of Open Access Journals (Sweden)

    D.D. Ivanov

    2017-03-01

    Full Text Available International guidelines do not recommend angiotensin converting enzyme (ACE inhibitors/angiotensin receptor blockers (ARBs usage in the first stage of diabetic kidney disease. It shows the view, based on a small statistical sample, that olmesartan (or possibly other ACE inhibitors/ARBs should be used to prevent the transition of the first stage of diabetic kidney disease to the second one in type 2 diabetes mellitus.

  14. New-onset diabetes mellitus after kidney transplantation in Denmark

    DEFF Research Database (Denmark)

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

    2010-01-01

    This study aimed to investigate the development of new-onset diabetes mellitus (NODM) in a prospective study of 97 nondiabetic uremic patients.......This study aimed to investigate the development of new-onset diabetes mellitus (NODM) in a prospective study of 97 nondiabetic uremic patients....

  15. 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

  16. Bardoxolone Methyl in Type 2 Diabetes and Stage 4 Chronic Kidney Disease

    NARCIS (Netherlands)

    de Zeeuw, Dick; Akizawa, Tadao; Audhya, Paul; Bakris, George L.; Chin, Melanie; Christ-Schmidt, Heidi; Goldsberry, Angie; Houser, Mark; Krauth, Melissa; Heerspink, Hiddo J. Lambers; McMurray, John J.; Meyer, Colin J.; Parving, Hans-Henrik; Remuzzi, Giuseppe; Toto, Robert D.; Vaziri, Nosratola D.; Wanner, Christoph; Wittes, Janet; Wrolstad, Danielle; Chertow, Glenn M.

    2013-01-01

    Background 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. Methods We randomly assigned 2185

  17. 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.

  18. Retinopathy and clinical outcomes in patients with type 2 diabetes mellitus, chronic kidney disease, and anemia

    NARCIS (Netherlands)

    Bello, Natalie A; Pfeffer, Marc A; Skali, Hicham; McGill, Janet B; Rossert, Jerome; Olson, Kurt A; Weinrauch, Larry; Cooper, Mark E; de Zeeuw, Dick; Rossing, Peter; McMurray, John J V; Solomon, Scott D

    2014-01-01

    OBJECTIVE: Retinopathy is an established microvascular complication of type 2 diabetes mellitus (T2DM), but its independent relationship with macrovascular and other microvascular complications is less well defined across the spectrum of kidney disease in T2DM. We examined the prognostic value of

  19. One risk assessment tool for cardiovascular disease, type 2 diabetes, and chronic kidney disease

    NARCIS (Netherlands)

    M. Alssema (Marjan); R.S. Newson (Rachel); S.J.L. Bakker (Stephan); C.D. Stehouwer (Coen); M.W. Heymans (Martijn); M.G.A.A.M. Nijpels (Giel); H.L. Hillege (Hans); A. Hofman (Albert); J.C.M. Witteman (Jacqueline); R.T. Gansevoort (Ron); J.M. Dekker (Jacqueline)

    2012-01-01

    textabstractOBJECTIVE - Individuals at high risk for chronic cardiometabolic disease (cardiovascular disease [CVD], type 2 diabetes, and chronic kidney disease [CKD]) share many risk factors and would benefit from early intervention. We developed a nonlaboratory-based risk-assessment tool for

  20. A Trial of Darbepoetin Alfa in Type 2 Diabetes and Chronic Kidney Disease

    NARCIS (Netherlands)

    Pfeffer, Marc A.; Burdmann, Emmanuel A.; Chen, Chao-Yin; Cooper, Mark E.; de Zeeuw, Dick; Eckardt, Kai-Uwe; Feyzi, Jan M.; Ivanovich, Peter; Kewalramani, Reshma; Levey, Andrew S.; Lewis, Eldrin F.; McGill, Janet B.; McMurray, John J. V.; Parfrey, Patrick; Parving, Hans-Henrik; Remuzzi, Giuseppe; Singh, Ajay K.; Solomon, Scott D.; Toto, Robert

    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 te

  1. RNA-Seq analysis of glycosylation related gene expression in STZ-induced diabetic rat kidney

    Science.gov (United States)

    The UT-A1 urea transporter is crucial to the kidney’s ability to generate the concentrated urine. Native UT-A1 from kidney inner medulla (IM) is a heavily glycosylated protein with two glycosylation forms of 97 and 117 kDa. In diabetes, protein abundance, particularly the 117 kD isoform, is si...

  2. Proteomics for prediction of disease progression and response to therapy in diabetic kidney disease

    NARCIS (Netherlands)

    Pena, Michelle J.; Mischak, Harald; Heerspink, Hiddo J. L.

    The past decade has resulted in multiple new findings of potential proteomic biomarkers of diabetic kidney disease (DKD). Many of these biomarkers reflect an important role in the (patho)physiology and biological processes of DKD. Situations in which proteomics could be applied in clinical practice

  3. Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease

    OpenAIRE

    Yale, J-F; Bakris, G.; B. Cariou; Yue, D; David-Neto,E.; Xi, L; Figueroa, K; Wajs, E; Usiskin, K; Meininger, G

    2013-01-01

    Aims Canagliflozin is a sodium glucose co-transporter 2 inhibitor in development for treatment of type 2 diabetes mellitus (T2DM). This study evaluated the efficacy and safety of canagliflozin in subjects with T2DM and stage 3 chronic kidney disease [CKD; estimated glomerular filtration rate (eGFR) ≥30 and

  4. 78 FR 23771 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2013-04-22

    ... Kidney Diseases Special Emphasis Panel; Artificial Pancreas. Date: July 10-11, 2013. Time: 5:00 p.m. to 5... Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as... Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive Diseases...

  5. Retinopathy and clinical outcomes in patients with type 2 diabetes mellitus, chronic kidney disease, and anemia

    NARCIS (Netherlands)

    Bello, Natalie A; Pfeffer, Marc A; Skali, Hicham; McGill, Janet B; Rossert, Jerome; Olson, Kurt A; Weinrauch, Larry; Cooper, Mark E; de Zeeuw, Dick; Rossing, Peter; McMurray, John J V; Solomon, Scott D

    2014-01-01

    OBJECTIVE: Retinopathy is an established microvascular complication of type 2 diabetes mellitus (T2DM), but its independent relationship with macrovascular and other microvascular complications is less well defined across the spectrum of kidney disease in T2DM. We examined the prognostic value of re

  6. Effects of pioglitazone on expressions of matrix metalloproteinases 2 and 9 in kidneys of diabetic rats

    Institute of Scientific and Technical Information of China (English)

    董凤芹; 李红; 蔡卫民; 陶君; 李群; 阮昱; 郑芬萍; 张哲

    2004-01-01

    Background The changes in matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expressions were examined in the kidneys of diabetic rats to investigate the degradative pathway of collagen type Ⅳ (C-Ⅳ) and the protective effects of pioglitazone on an experimental model of diabetic nephropathy.Methods In 54 SD rats used in our study, 18 served as normal controls. Diabetes mellitus was induced in 36 age- and weight-matched rats by intraperitoneal injection of streptozotocin (70 mg/kg); 18 of the diabetic rats were allocated at random to receive pioglitazone (20 mg*kg-1*d-1) in their drinking water and 18 served as diabetic controls. Rats were killed after 2, 4, or 8 weeks of treatment. Kidneys were examined pathomorphologically and the expressions of MMP-2, MMP-9, and C-Ⅳ were analyzed by immunohistochemistry, and the results were quantified by image analysis techniques.Results Diabetes mellitus was associated with a decrease in the expression of MMP-2 in the glomeruli (P0.05, vs control). The expression of MMP-9 did not show any change when comparing the three groups (P>0.05, vs control). STZ-diabetic rats were also associated with an increase in the expression of C-Ⅳ in the glomeruli and the interstitium (P<0.05, vs control). All diabetes-associated changes in MMP-2 expression were attenuated by pioglitazone treatment in association with reduced C-Ⅳ accumulation. Conclusions These results indicate that a decrease in MMP-2 expression in the glomeruli of diabetic rats may lead to impairment of C-Ⅳ degradation and contribute to the matrix accumulation in diabetic nephropathy. Pioglitazone treatment, which can attenuate the decrease of glomerular MMP-2 and the increase of C-Ⅳ degradation, has curative effects on diabetic nephropathy.

  7. Kidney Diseases

    Science.gov (United States)

    ... until you go to the bathroom. Most kidney diseases attack the nephrons. This damage may leave kidneys ... medicines. You have a higher risk of kidney disease if you have diabetes, high blood pressure, or ...

  8. Risks of Metformin in Type 2 Diabetes and Chronic Kidney Disease: Lessons Learned from Taiwanese Data.

    Science.gov (United States)

    Rhee, Connie M; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar

    2017-01-01

    Like other biguanide agents, metformin is an anti-hyperglycemic agent with lower tendency towards hypoglycemia compared to other anti-diabetic drugs. Given its favorable effects on serum lipids, obese body habitus, cardiovascular disease, and mortality, metformin is recommended as the first-line pharmacologic agent for type 2 diabetes in the absence of contraindications. However, as metformin accumulation may lead to type B non-hypoxemic lactic acidosis, especially in the setting of kidney injury, chronic kidney disease, and overdose, regulatory agencies such as the United States Food and Drug Administration (FDA) have maintained certain restrictions regarding its use in kidney dysfunction. Case series have demonstrated a high fatality rate with metformin-associated lactic acidosis (MALA), and the real-life incidence of MALA may be underestimated by observational studies and clinical trials that have excluded patients with moderate-to-advanced kidney dysfunction. A recent study of advanced diabetic kidney disease patients in Taiwan in Lancet Endocrinology and Diabetes has provided unique insight into the potential consequences of unrestricted metformin use, including a 35% higher adjusted mortality risk that was dose-dependent. This timely study, as well as historical data documenting the toxicities of other biguanides, phenformin and buformin, suggest that the recent relaxation of FDA recommendations to expand metformin use in patients with kidney dysfunction (i.e., those with estimated glomerular filtration rates ≥30 instead of our recommended ≥45 ml/min/1.73 m2) may be too liberal. In this article, we will review the history of metformin use; its pharmacology, mechanism of action, and potential toxicities; and policy-level changes in its use over time.

  9. Incidence, Development, and Prognosis of Diabetic Kidney Disease in China: Design and Methods

    Science.gov (United States)

    Yang, Yao-Zheng; Wang, Jin-Wei; Wang, Fang; Wu, Yun-Tao; Zhao, Hai-Yan; Chen, Min; Zhang, Lu-Xia; Wu, Shou-Ling; Zhao, Ming-Hui

    2017-01-01

    Background: Although that glomerulonephritis is the major cause of end-stage renal disease in developing countries such as China, the increasing prevalence of diabetes has contributed to the changing spectrum of predialysis chronic kidney disease. Recent studies have revealed an increased proportion of patients with diabetic kidney disease (DKD) in hemodialysis populations in large cities in China. However, studies regarding the clinical phenotype of DKD in China are extremely limited. The incidence, development, and prognosis of diabetic kidney disease (INDEED) study aims to investigate the incidence, progression, and prognosis of DKD, as well as the associated genetic, behavioral, and environmental factors and biomarkers in patients with DKD in China. Methods: INDEED study is a prospective cohort study based on all participants with diabetes in the Kailuan study, which is a general population-based cohort study in northern China. Altogether, over 10,000 participants with diabetes will be followed biennially. Questionnaires documenting general characteristics, behavioral and environmental factors, and medical history will be administrated. Anthropometric measurements and a series of laboratory tests will be performed in one central laboratory. The DNA, plasma, and urine samples of every participant will be stored in a biobank for future research. Conclusions: INDEED study will provide essential information regarding the clinical phenotype and prognosis of patients with DKD in China and will be valuable to identify factors and biomarkers associated with patients with DKD in China. PMID:28091412

  10. Incidence, Development, and Prognosis of Diabetic Kidney Disease in China: Design and Methods.

    Science.gov (United States)

    Yang, Yao-Zheng; Wang, Jin-Wei; Wang, Fang; Wu, Yun-Tao; Zhao, Hai-Yan; Chen, Min; Zhang, Lu-Xia; Wu, Shou-Ling; Zha, Ming-Hui

    2017-01-20

    Although that glomerulonephritis is the major cause of end-stage renal disease in developing countries such as China, the increasing prevalence of diabetes has contributed to the changing spectrum of predialysis chronic kidney disease. Recent studies have revealed an increased proportion of patients with diabetic kidney disease (DKD) in hemodialysis populations in large cities in China. However, studies regarding the clinical phenotype of DKD in China are extremely limited. The incidence, development, and prognosis of diabetic kidney disease (INDEED) study aims to investigate the incidence, progression, and prognosis of DKD, as well as the associated genetic, behavioral, and environmental factors and biomarkers in patients with DKD in China. INDEED study is a prospective cohort study based on all participants with diabetes in the Kailuan study, which is a general population-based cohort study in northern China. Altogether, over 10,000 participants with diabetes will be followed biennially. Questionnaires documenting general characteristics, behavioral and environmental factors, and medical history will be administrated. Anthropometric measurements and a series of laboratory tests will be performed in one central laboratory. The DNA, plasma, and urine samples of every participant will be stored in a biobank for future research. INDEED study will provide essential information regarding the clinical phenotype and prognosis of patients with DKD in China and will be valuable to identify factors and biomarkers associated with patients with DKD in China.

  11. 75 FR 28030 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Meetings

    Science.gov (United States)

    2010-05-19

    ... Initial Review Group, Diabetes, Endocrinology and Metabolic Diseases B Subcommittee. Date: June 16-18... . (Catalogue of Federal Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and...

  12. 75 FR 18215 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Meetings

    Science.gov (United States)

    2010-04-09

    ... Diseases Advisory Council Diabetes, Endocrinology, and Metabolic Diseases Subcommittee. Date: May 12, 2010... Domestic Assistance Program Nos. 93.847, Diabetes, Endocrinology and Metabolic Research; 93.848, Digestive... HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and...

  13. Glucuronidation of thyroxine in human liver, jejunum, and kidney microsomes.

    Science.gov (United States)

    Yamanaka, Hiroyuki; Nakajima, Miki; Katoh, Miki; Yokoi, Tsuyoshi

    2007-09-01

    Glucuronidation of thyroxine is a major metabolic pathway facilitating its excretion. In this study, we characterized the glucuronidation of thyroxine in human liver, jejunum, and kidney microsomes, and identified human UDP-glucuronosyltransferase (UGT) isoforms involved in the activity. Human jejunum microsomes showed a lower K(m) value (24.2 microM) than human liver (85.9 microM) and kidney (53.3 microM) microsomes did. Human kidney microsomes showed a lower V(max) value (22.6 pmol/min/mg) than human liver (133.4 pmol/min/mg) and jejunum (184.6 pmol/min/mg) microsomes did. By scaling-up, the in vivo clearances in liver, intestine, and kidney were estimated to be 1440, 702, and 79 microl/min/kg body weight, respectively. Recombinant human UGT1A8 (108.7 pmol/min/unit), UGT1A3 (91.6 pmol/min/unit), and UGT1A10 (47.3 pmol/min/unit) showed high, and UGT1A1 (26.0 pmol/min/unit) showed moderate thyroxine glucuronosyltransferase activity. The thyroxine glucuronosyltransferase activity in microsomes from 12 human livers was significantly correlated with bilirubin O-glucuronosyltransferase (r = 0.855, p microsomes was mainly catalyzed by UGT1A8 and UGT1A10 and to a lesser extent by UGT1A1, and the activity in human kidney microsomes was mainly catalyzed by UGT1A7, UGT1A9, and UGT1A10. The changes of activities of these UGT1A isoforms via inhibition and induction by administered drugs as well as genetic polymorphisms may be a causal factor of interindividual differences in the plasma thyroxine concentration.

  14. Glycosylation gap in patients with diabetes with chronic kidney disease and healthy participants: A comparative study

    Directory of Open Access Journals (Sweden)

    Km Neelofar

    2017-01-01

    Full Text Available Aim: The aim of this study it to determine the level of glycosylation gap in patients with type 2 diabetes and its relation with kidney dysfunction. Materials and Methods: In this study, 150 individuals were enrolled (aged 20–75 year and divided into three groups. Group 1 included 50 nondiabetic individuals who served as control. Group 2 included 50 patients with type 2 diabetes without chronic kidney disease (CKD, and in Group 3, there were 50 patients with type 2 diabetes with CKD. Glycated hemoglobin (HbA1c and fructosamine (FA were measured in all groups to determine the glycosylation gap (GG, predicted HbA1c, and mean blood glucose (MBG. GG is defined as the difference between measured HbA1c and HbA1c predicted from FA based on the population regression of HbA1c on FA. The variables were compared by correlation analysis. Results: Serum creatinine level was significantly high in patients with CKD (1.93 ± 0.99 as compared to patients with diabetes and control (0.891 ± 0.16; 0.912 ± 0.1, respectively. The study demonstrated a significant elevation in serum FA, measured HbA1c and predicted HbA1c, MBG in patients with diabetes with CKD as compared with those of without CKD, and controls. GG was found in healthy control (0.51 ± 0.78, patients with type 2 diabetes without CKD (0.62 ± 0.45, and patients with diabetes with CKD (1.0 ± 0.91, respectively. Conclusion: It is concluded that GG may be a useful clinical research tool for evaluating pathological source of variation in diabetes complications such as kidney disease.

  15. Glycosylation Gap in Patients with Diabetes with Chronic Kidney Disease and Healthy Participants: A Comparative Study.

    Science.gov (United States)

    Neelofar, Km; Ahmad, Jamal

    2017-01-01

    The aim of this study it to determine the level of glycosylation gap in patients with type 2 diabetes and its relation with kidney dysfunction. In this study, 150 individuals were enrolled (aged 20-75 year) and divided into three groups. Group 1 included 50 nondiabetic individuals who served as control. Group 2 included 50 patients with type 2 diabetes without chronic kidney disease (CKD), and in Group 3, there were 50 patients with type 2 diabetes with CKD. Glycated hemoglobin (HbA1c) and fructosamine (FA) were measured in all groups to determine the glycosylation gap (GG), predicted HbA1c, and mean blood glucose (MBG). GG is defined as the difference between measured HbA1c and HbA1c predicted from FA based on the population regression of HbA1c on FA. The variables were compared by correlation analysis. Serum creatinine level was significantly high in patients with CKD (1.93 ± 0.99) as compared to patients with diabetes and control (0.891 ± 0.16; 0.912 ± 0.1), respectively. The study demonstrated a significant elevation in serum FA, measured HbA1c and predicted HbA1c, MBG in patients with diabetes with CKD as compared with those of without CKD, and controls. GG was found in healthy control (0.51 ± 0.78), patients with type 2 diabetes without CKD (0.62 ± 0.45), and patients with diabetes with CKD (1.0 ± 0.91), respectively. It is concluded that GG may be a useful clinical research tool for evaluating pathological source of variation in diabetes complications such as kidney disease.

  16. Management of patients with diabetes and CKD: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference.

    Science.gov (United States)

    Perkovic, Vlado; Agarwal, Rajiv; Fioretto, Paola; Hemmelgarn, Brenda R; Levin, Adeera; Thomas, Merlin C; Wanner, Christoph; Kasiske, Bertram L; Wheeler, David C; Groop, Per-Henrik

    2016-12-01

    The prevalence of diabetes around the world has reached epidemic proportions and is projected to increase to 642 million people by 2040. Diabetes is already the leading cause of end-stage kidney disease (ESKD) in most developed countries, and the growth in the number of people with ESKD around the world parallels the increase in diabetes. The presence of kidney disease is associated with a markedly elevated risk of cardiovascular disease and death in people with diabetes. Several new therapies and novel investigational agents targeting chronic kidney disease patients with diabetes are now under development. This conference was convened to assess our current state of knowledge regarding optimal glycemic control, current antidiabetic agents and their safety, and new therapies being developed to improve kidney function and cardiovascular outcomes for this vulnerable population.

  17. Clinical outcomes of kidney transplants on patients with end-stage renal disease secondary to lupus nephritis, polycystic kidney disease and diabetic nephropathy

    Science.gov (United States)

    Nieto-Ríos, John Fredy; Builes-Rodriguez, Sheila Alexandra; Restrepo-Correa, Ricardo Cesar; Aristizabal-Alzate, Arbey; Ocampo-Kohn, Catalina; Serna-Campuzano, Angélica; Cardona-Díaz, Natalia; Giraldo-Ramirez, Nelson Darío; Zuluaga-Valencia, Gustavo Adolfo

    2016-01-01

    Background: Patients with lupus nephritis could progress to end-stage renal disease (10-22%); hence, kidney transplants should be considered as the treatment of choice for these patients. Objective: To evaluate the clinical outcomes after kidney transplants in patients with chronic kidney diseases secondary to lupus nephritis, polycystic kidney disease and diabetes nephropathy at Pablo Tobon Uribe Hospital. Methods: A descriptive and retrospective study performed at one kidney transplant center between 2005 and 2013. Results: A total of 136 patients, 27 with lupus nephritis (19.9%), 31 with polycystic kidney disease (22.8%) and 78 with diabetes nephropathy (57.4%), were included in the study. The graft survivals after one, three and five years were 96.3%, 82.5% and 82.5% for lupus nephritis; 90%, 86% and 76.5% for polycystic kidney disease and 91.7%, 80.3% and 67.9% for diabetes nephropathy, respectively, with no significant differences (p= 0.488); the rate of lupus nephritis recurrence was 0.94%/person-year. The etiology of lupus vs diabetes vs polycystic disease was not a risk factor for a decreased time of graft survival (Hazard ratio: 1.43; 95% CI: 0.52-3.93). Conclusion: Kidney transplant patients with end stage renal disease secondary to lupus nephritis has similar graft and patient survival success rates to patients with other kidney diseases. The complication rate and risk of recurrence for lupus nephritis are low. Kidney transplants should be considered as the treatment of choice for patients with end stage renal disease secondary to lupus nephritis. PMID:27226665

  18. Obesity and Diabetic Kidney Disease: Role of Oxidant Stress and Redox Balance.

    Science.gov (United States)

    Sharma, Kumar

    2016-08-01

    Reactive oxygen species (ROS) reactive nitrogen species (RNS) and redox processes are of key importance in obesity- and diabetes-related kidney disease; however, there remains significant controversy in the field. New data from imaging and in vivo models of obesity and diabetic kidney disease have shed new insights into this field. In the setting of obesity- and diabetes-related kidney injury, there is a growing recognition that the major moieties of ROS and RNS are hydrogen peroxide and peroxynitrite with the enzymatic sources being NADPH oxidases and nitric oxide synthase, respectively. However, the role of mitochondrial superoxide as a driver of renal complications remains unclear. Several key issues that are often not discussed are the specific ROS and RNS molecules, the source of generation, the location of production, and downstream targets. Further understanding of the role of ROS/RNS/redox and their relationship with key signaling and metabolic pathways such as AMP-activated protein kinase (AMPK) and hypoxia-inducible factor 1-α (HIF1α) will be critical to a new understanding of kidney complications of caloric challenges and new therapeutic approaches. Antioxid. Redox Signal. 25, 208-216.

  19. Relationship between inpatient hyperglycemia and insulin treatment after kidney transplantation and future new onset diabetes mellitus.

    Science.gov (United States)

    Chakkera, Harini A; Knowler, William C; Devarapalli, Yugandhara; Weil, E Jennifer; Heilman, Raymond L; Dueck, Amylou; Mulligan, David C; Reddy, Kunam S; Moss, Adyr A; Mekeel, Kristin L; Mazur, Marek J; Hamawi, Khaled; Castro, Janna C; Cook, Curtiss B

    2010-09-01

    Approximately two-thirds of kidney transplant recipients with no previous history of diabetes experience inpatient hyperglycemia immediately after kidney transplant surgery; whether inpatient hyperglycemia predicts future new onset diabetes after transplant (NODAT) is not established. A retrospective study was conducted to determine the risk conferred by inpatient hyperglycemia on development of NODAT within 1 year posttransplant. All adult nondiabetic kidney transplant recipients between June 1999 and January 2008 were included. Posttransplant inpatient hyperglycemia was defined as any bedside capillary blood glucose > or = 200 mg/dl or insulin therapy during hospitalization. NODAT was defined as HbA1C > or = 6.5%, fasting venous serum glucose > or = 126 mg/dl, or prescribed diet or medical therapy for diabetes mellitus. The study cohort included 377 patients. NODAT developed in 1 (4%) of the 28 patients without inpatient hyperglycemia, 4 (18%) of the 22 patients with inpatient hyperglycemia but not treated with insulin, and in 98 (30%) of the 327 of the patients who were diagnosed with inpatient hyperglycemia and were treated with insulin. In adjusted analyses, requirement of insulin therapy during hospitalization posttransplant was associated with a 4-fold increase in NODAT (relative risk 4.01; confidence interval, 1.49 to 10.7; P = 0.006). Development of inpatient hyperglycemia after kidney transplantation in nondiabetic patients significantly increased the risk of NODAT. Additionally, we observed a significantly increased risk of cardiovascular events in patients who developed NODAT.

  20. Effect of alcohol on blood glucose and antioxidant enzymes in the liver and kidney of diabetic rats

    Directory of Open Access Journals (Sweden)

    K R Shanmugam

    2011-01-01

    Full Text Available Objective: Diabetes mellitus affects every organ in the man including eyes, kidney, heart, and nervous system. Alcohol consumption is a widespread practice. As the effects of chronic alcohol consumption on diabetic state have been little studied, this study was conducted with the objective of evaluating the effect of alcohol in diabetic rats. Materials and Methods: For this study, the rats were divided into five groups (n = 6 in each group: normal control (NC, alcohol treatment (At, diabetic control (DC, diabetic plus alcohol treatment (D + At, diabetic plus glibenclamide treatment (D + Gli. Alcohol treatment was given to the diabetic rats for 30 days. During the period the blood glucose levels, and body weight changes were observed at regular intervals. The antioxidant enzymes like superoxide dismutase (SOD, catalase (CAT, and malondialdehyde (MDA levels were assayed in the liver and kidney tissues. Results: The blood glucose levels were significantly (P < 0.001 elevated and body weight significantly (P < 0.001 decreased in alcohol-treated diabetic rats. SOD and CAT activities were decreased and the MDA level increased significantly (P < 0.001 in alcohol-treated diabetic rats. Histopathological studies showed that alcohol damages the liver and kidney tissues in diabetic rats. Conclusion: These finddings concluded that the consumption of alcohol in diabetic rats worsens the condition. So the consumption of alcohol by diabetic subjects may be potentially harmful.

  1. Visit-to-visit variability of blood pressure and renal function decline in patients with diabetic chronic kidney disease.

    Science.gov (United States)

    Yokota, Kei; Fukuda, Masamichi; Matsui, Yoshio; Kario, Kazuomi; Kimura, Kenjiro

    2014-05-01

    The authors previously reported that the visit-to-visit variability of blood pressure is correlated with renal function decline in nondiabetic chronic kidney disease. Little is known about the association between visit-to-visit variability and renal function decline in patients with diabetic chronic kidney disease. The authors retrospectively studied 69 patients with diabetic chronic kidney disease stage 3a, 3b, or 4. The standard deviation and coefficient of variation of blood pressure in 12 consecutive visits were defined as visit-to-visit variability of blood pressure. The median observation period was 32 months. In univariate correlation, the standard deviation and coefficient of variation of blood pressure were not significantly associated with the slope of estimated glomerular filtration rate. There was no significant association between the visit-to-visit variability of blood pressure and renal function decline in patients with diabetic chronic kidney disease, in contrast with our previous study of nondiabetic patients with chronic kidney disease.

  2. 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.

  3. 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...

  4. Prevention and management of new-onset diabetes mellitus in kidney transplantation.

    Science.gov (United States)

    Juan Khong, M; Ping Chong, Ch

    2014-04-01

    New-onset diabetes mellitus after transplantation (NODAT) is one of the complications that is increasingly occurring among kidney transplanted patients. It is associated with the risk of cardiovascular disease, graft failure and mortality. The risk of NODAT development increases with time from transplantation. Therefore, early detection and prompt action are essential in reducing the risk of NODAT and its complications. This paper aims to review the screening parameters, prevention and management strategies for NODAT in both pre- and post-transplantation conditions. The pre-transplant patient should be screened for diabetes and cardiometabolic risk factors. Blood glucose evaluation for the pre-transplantation period is important for early detection of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), which are highly associated with the incidence of NODAT. Post-kidney transplant patients should have periodical blood glucose monitoring with more frequent assessment in the initial phase. As early hyperglycaemia development is a strong predictor for NODAT, prompt intervention is needed. When NODAT develops, monitoring and control of blood glucose profile, lipid profile, microalbuminuria, diabetic complications and comorbid conditions is recommended. Immunosuppressive regimen modification may be considered as suggested by the Kidney Disease: Improving Global Outcomes (KDIGO) guideline to reverse or to improve the diabetes after weighing the risk of rejection and other potential adverse effects. Strategies for modifying immunosuppressive agents include dose reduction, discontinuation, and selection of calcineurin inhibitor (CNI), anti-metabolite agents, mammalian target of rapamycin inhibitors (mTORi), belatacept and corticosteroids. Lifestyle modification and a conventional anti-diabetic approach, as in the type 2 diabetes mellitus guidelines, are also recommended in NODAT management.

  5. MicroRNAs in kidney fibrosis and diabetic nephropathy: roles on EMT and EndMT.

    Science.gov (United States)

    Srivastava, Swayam Prakash; Koya, Daisuke; Kanasaki, Keizo

    2013-01-01

    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.

  6. Aberrant production of extracellular matrix proteins and dysfunction in kidney endothelial cells with a short duration of diabetes.

    Science.gov (United States)

    Grutzmacher, Cathy; Park, SunYoung; Zhao, Yun; Morrison, Margaret E; Sheibani, Nader; Sorenson, Christine M

    2013-01-01

    Diabetic nephropathy is the most common cause of end-stage renal disease and is a major risk factor for cardiovascular disease. In the United States, microvascular complications during diabetic nephropathy contribute to high morbidity and mortality rates. However, the cell-autonomous impact of diabetes on kidney endothelial cell function requires further investigation. Male Akita/+ [autosomal dominant mutation in the insulin II gene (Ins2)] mice reproducibly develop diabetes by 4 wk of age. Here, we examined the impact a short duration of diabetes had on kidney endothelial cell function. Kidney endothelial cells were prepared from nondiabetic and diabetic mice (4 wk of diabetes) to delineate the early changes in endothelial cell function. Kidney endothelial cells from Akita/+ mice following 4 wk of diabetes demonstrated aberrant expression of extracellular matrix proteins including decreased osteopontin and increased fibronectin expression which correlated with increased α5-integrin expression. These changes were associated with the attenuation of migration and capillary morphogenesis. Kidney endothelial cells from Akita/+ mice had decreased VEGF levels but increased levels of endothelial nitric oxide synthase(eNOS) and NO, suggesting uncoupling of VEGF-mediated NO production. Knocking down eNOS expression in Akita/+ kidney endothelial cells increased VEGF expression, endothelial cell migration, and capillary morphogenesis. Furthermore, attenuation of sprouting angiogenesis of aortas from Akita/+ mice with 8 wk of diabetes was restored in the presence of the antioxidant N-acetylcysteine. These studies demonstrate that aberrant endothelial cell function with a short duration of diabetes may set the stage for vascular dysfunction and rarefaction at later stages of diabetes.

  7. Anti-Inflammatory Therapy Modulates Nrf2-Keap1 in Kidney from Rats with Diabetes

    Science.gov (United States)

    Arellano-Buendía, Abraham Said; Tostado-González, Montserrat; García-Arroyo, Fernando Enrique; Cristóbal-García, Magdalena; Loredo-Mendoza, María Lilia; Tapia, Edilia; Sánchez-Lozada, Laura-Gabriela; Osorio-Alonso, Horacio

    2016-01-01

    This study addressed the relationship of proinflammatory cytokines and Nrf2-Keap1 system in diabetic nephropathy. The experimental groups were control, diabetic, and diabetic treated with mycophenolate mofetil (MMF). The renal function, proinflammatory and profibrotic cytokines, oxidative stress, morphology, and nephrin expression were assessed. Diabetic group showed impaired renal function in association with oxidative stress and decreased Nrf2 nuclear translocation. These results were associated with increased mesangial matrix index, interstitial fibrosis, and increased nephrin expression in cortex and urine excretion. Additionally, interleukin-1β, IL-6, and transforming growth factor-β1 were increased in plasma and kidney. MMF treatment conserved renal function, prevented renal structural alterations, and partially prevented the proinflammatory and profibrotic cytokines overexpression. Despite that MMF treatment induced nephrin overexpression in renal tissue, preventing its urinary loss. MMF salutary effects were associated with a partial prevention of oxidative stress, increased Nrf2 nuclear translocation, and conservation of antioxidant enzymes in renal tissue. In conclusion, our results confirm that inflammation is a key factor in the progression of diabetic nephropathy and suggest that treatment with MMF protects the kidney by an antioxidant mechanism, possibly regulated at least in part by the Nrf2/Keap1 system, in addition to its well-known anti-inflammatory effects. PMID:26955430

  8. Anti-Inflammatory Therapy Modulates Nrf2-Keap1 in Kidney from Rats with Diabetes

    Directory of Open Access Journals (Sweden)

    Abraham Said Arellano-Buendía

    2016-01-01

    Full Text Available This study addressed the relationship of proinflammatory cytokines and Nrf2-Keap1 system in diabetic nephropathy. The experimental groups were control, diabetic, and diabetic treated with mycophenolate mofetil (MMF. The renal function, proinflammatory and profibrotic cytokines, oxidative stress, morphology, and nephrin expression were assessed. Diabetic group showed impaired renal function in association with oxidative stress and decreased Nrf2 nuclear translocation. These results were associated with increased mesangial matrix index, interstitial fibrosis, and increased nephrin expression in cortex and urine excretion. Additionally, interleukin-1β, IL-6, and transforming growth factor-β1 were increased in plasma and kidney. MMF treatment conserved renal function, prevented renal structural alterations, and partially prevented the proinflammatory and profibrotic cytokines overexpression. Despite that MMF treatment induced nephrin overexpression in renal tissue, preventing its urinary loss. MMF salutary effects were associated with a partial prevention of oxidative stress, increased Nrf2 nuclear translocation, and conservation of antioxidant enzymes in renal tissue. In conclusion, our results confirm that inflammation is a key factor in the progression of diabetic nephropathy and suggest that treatment with MMF protects the kidney by an antioxidant mechanism, possibly regulated at least in part by the Nrf2/Keap1 system, in addition to its well-known anti-inflammatory effects.

  9. Interaction of the EGF Receptor and the Hippo Pathway in the Diabetic Kidney.

    Science.gov (United States)

    Chen, Jianchun; Harris, Raymond C

    2016-06-01

    Activation of the EGF receptor (EGFR) or the Hippo signaling pathway can control cell proliferation, apoptosis, and differentiation, and the dysregulation of these pathways can contribute to tumorigenesis. Previous studies showed that activation of EGFR signaling in renal epithelial cells can exacerbate diabetic kidney injury. Moreover, EGFR has been implicated in regulating the Hippo signaling pathway in Drosophila; thus, we examined this potential interaction in mammalian diabetic kidney disease. Yes-associated protein (YAP) is a transcriptional regulator regulated by the Hippo signaling pathway. We found YAP protein expression and phosphorylation were upregulated in diabetic mouse renal proximal tubule epithelial cells, which were inhibited in diabetic proximal tubule EGFR-knockout mice (EGFR(ptKO)) or administration of an EGFR tyrosine kinase inhibitor erlotinib. Furthermore, activation of an EGFR-PI3K-Akt-CREB signaling pathway mediated YAP gene expression and YAP nuclear translocation and interaction with the TEA domain (TEAD) transcription factor complex, which led to upregulated expression of two TEAD-dependent genes, the connective tissue growth factor and amphiregulin genes. In a renal proximal tubule cell line, either pharmacologic or genetic inhibition of EGFR, Akt, or CREB blunted YAP expression in response to high-glucose treatment. Additionally, knocking down YAP expression by specific siRNA inhibited cell proliferation in response to high glucose or exogenous EGF. Therefore, these results link the Hippo pathway to EGFR-mediated renal epithelial injury in diabetes. Copyright © 2016 by the American Society of Nephrology.

  10. Role of Oxidative Stress and Inflammatory Factors in Diabetic Kidney Disease.

    Science.gov (United States)

    Aghadavod, Esmat; Khodadadi, Samaneh; Baradaran, Azar; Nasri, Parto; Bahmani, Mahmood; Rafieian-Kopaei, Mahmoud

    2016-11-01

    Diabetic nephropathy (DN) is a serious complication of diabetes mellitus, and its prevalence has been increasing in developed countries. Diabetic nephropathy has become the most common single cause of end-stage renal disease worldwide. Oxidative stress and inflammation factors are hypothesized to play a role in the development of late diabetes complications. Chronic hyperglycemia increases oxidative stress, significantly modifies the structure and function of proteins and lipids, and induces glycoxidation and peroxidation. Therefore, hyperglycemia causes auto-oxidation of glucose, glycation of proteins, and activation of polyol mechanism. Overproduction of intracellular reactive oxygen species contributes to several microvascular and macrovascular complications of DN. On the other hand, reactive oxygen species modulates signaling cascade of immune factors. An increase in reactive oxygen species can increase the production of inflammatory cytokines, and likewise, an increase in inflammatory cytokines can stimulate the production of free radicals. Some studies have shown that kidney inflammation is serious in promoting the development and progression of DN. Inflammatory factors which are activated by the metabolic, biochemical, and hemodynamic derangements are known to exist in the diabetic kidney. This review discusses facts for oxidative stress and inflammatory factors in DN and encompasses the role of immune and inflammatory cells, inflammatory cytokines, and stress oxidative factors.

  11. Mind the gap: connexins and cell-cell communication in the diabetic kidney.

    Science.gov (United States)

    Hills, Claire E; Price, Gareth W; Squires, Paul E

    2015-02-01

    Connexins, assembled as a hexameric connexon, form a transmembrane hemichannel that provides a conduit for paracrine signalling of small molecules and ions to regulate the activity and function of adjacent cells. When hemichannels align and associate with similar channels on opposing cells, they form a continuous aqueous pore or gap junction, allowing the direct transmission of metabolic and electrical signals between coupled cells. Regulation of gap junction synthesis and channel activity is critical for cell function, and a number of diseases can be attributed to changes in the expression/function of these important proteins. Diabetic nephropathy is associated with several complex metabolic and inflammatory responses characterised by defects at the molecular, cellular and tissue level. In both type 1 and type 2 diabetes, glycaemic injury of the kidney is the leading cause of end-stage renal failure, a consequence of multiple aetiologies, including increased deposition of extracellular matrix, glomerular hyperfiltration, albuminuria and tubulointerstitial fibrosis. In diabetic nephropathy, loss of connexin mediated cell-cell communication within the nephron may represent an early sign of disease; however, our current knowledge of the role of connexins in the diabetic kidney is sparse. This review highlights recent evidence demonstrating that maintenance of connexin-mediated cell-cell communication could benefit region-specific renal function in diabetic nephropathy and suggests that these proteins should be viewed as a tantalising novel target for therapeutic intervention.

  12. Sustained kidney biochemical derangement in treated experimental diabetes: a clue to metabolic memory

    Science.gov (United States)

    de Oliveira, Antonio Anax F.; de Oliveira, Tiago F.; Bobadilla, Larissa L.; Garcia, Camila C. M.; Berra, Carolina Maria; de Souza-Pinto, Nadja C.; Medeiros, Marisa H. G.; Di Mascio, Paolo; Zatz, Roberto; de M. Loureiro, Ana Paula

    2017-01-01

    The occurrence of biochemical alterations that last for a long period of time in diabetic individuals even after adequate handling of glycemia is an intriguing phenomenon named metabolic memory. In this study, we show that a kidney pathway is gradually altered during the course of diabetes and remains persistently changed after late glycemic control in streptozotocin-induced diabetic rats. This pathway comprises an early decline of uric acid clearance and pAMPK expression followed by fumarate accumulation, increased TGF-β expression, reduced PGC-1α expression, and downregulation of methylation and hydroxymethylation of mitochondrial DNA. The sustained decrease of uric acid clearance in treated diabetes may support the prolonged kidney biochemical alterations observed after tight glycemic control, and this regulation is likely mediated by the sustained decrease of AMPK activity and the induction of inflammation. This manuscript proposes the first consideration of the possible role of hyperuricemia and the underlying biochemical changes as part of metabolic memory in diabetic nephropathy development after glycemic control. PMID:28079150

  13. Genetics of diabetic nephropathy: are there clues to the understanding of common kidney diseases?

    Science.gov (United States)

    Conway, B R; Maxwell, A P

    2009-01-01

    Diabetic nephropathy is the most common cause of end-stage renal disease in the Western world. There is evidence for a genetic susceptibility to diabetic kidney disease, but despite intensive research efforts it has proved difficult to identify the causative genes. Improvements in genotyping technologies have made genome-wide association studies (GWAS), employing hundreds of thousands of single nucleotide polymorphisms, affordable. Recently, such scans have advanced understanding of the genetics of common complex diseases, finding more than 100 novel susceptibility variants for diverse disorders including type 1 and 2 diabetes, coronary heart disease, Crohn's disease and rheumatoid arthritis. In this review, type 2 diabetes is highlighted to illustrate how genome-wide association studies have been used to study the genetics of complex multifactorial conditions; in addition, diabetic nephropathy will be used to demonstrate how similar scans could be employed to detect genetic factors predisposing to kidney disease. The identification of such variants would permit early identification of atrisk patients, enabling targeting of therapy and a move towards primary prevention. In addition, these powerful research methodologies may identify genes that were not previously known to predispose to nephropathy, thereby enhancing our understanding of the pathophysiology of renal disorders and potentially leading to novel therapeutic approaches.

  14. 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...

  15. 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).

  16. Teneligliptin in Management of Diabetic Kidney Disease: A Review of Place in Therapy

    Science.gov (United States)

    Mishra, Preetesh; Swami, Onkar C.

    2017-01-01

    Diabetes is a global health emergency of this century. Diabetic nephropathy is the most common microvascular complication associated with Type 2 Diabetes Mellitus (T2DM). T2DM has been reported as a major etiological factor in almost 45% of patients undergoing dialysis due to kidney failure. Lifestyle modifications; cessation of smoking, optimum control of blood glucose, blood pressure and lipids are required to reduce the progression of Diabetic Kidney Disease (DKD). Presently, Dipeptidyl peptidase-4 (DPP-4) inhibitors are preferred in the management of T2DM due to their established efficacy; favorable tolerability including, low risk of hypoglycaemia; weight neutrality and convenient once-a-day dosage. Present evidence suggests that linagliptin and teneligliptin can be used safely without dose adjustments in patients with T2DM with renal impairment, including End Stage Renal Disease (ESRD). There is a limited data about teneligliptin particularly in T2DM patients with renal impairment. The objective of this review is to evaluate efficacy and safety of teneligliptin in T2DM patients with renal impairment, in order to assess the current place in therapy and future prospects of teneligliptin. Reported evidence suggests that teneligliptin has consistent pharmacokinetic in mild, moderate, severe or ESRD, without any need for dose adjustments. Limited data from small sample studies of teneligliptin in DKD patients reported significant improvements in glycaemic parameters. Additionally, there is an improvement in kidney parameters like glycated albumin, urinary albumin and eGFR. There is an evidence of reduction in biomarkers of kidney impairment like P-selectin (sP-selectin), Platelet-Derived Microparticles (PDMPs) and Plasminogen Activator Inhibitor 1 (PAI-1). Clinical significance of these will be known in near future. Thus, teneligliptin has an important place of therapy in the management of T2DM with renal impairment. PMID:28273997

  17. Prevalence of Chronic Kidney Disease among Patients Attending a Specialist Diabetes Clinic in Jamaica

    Science.gov (United States)

    Ferguson, TS; Tulloch-Reid, MK; Younger-Coleman, NO; Wright-Pascoe, RA; Boyne, MS; Soyibo, AK; Wilks, RJ

    2015-01-01

    ABSTRACT Objectives: To estimate the prevalence of chronic kidney disease (CKD) among patients attending the University Hospital of the West Indies (UHWI) Diabetes Clinic and to determine the proportion of patients at high risk for adverse outcomes. Methods: We conducted a cross-sectional study among patients attending the UHWI Diabetes Clinic between 2009 and 2010. Trained nurses administered a questionnaire, reviewed dockets, and performed urinalyses. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Albuminuria was assessed using urine test strips for protein and microalbumin. Chronic kidney disease was defined as an eGFR 300 mg/g) in 62.1%. Overall prevalence of CKD was 86.3% (95% CI 80.4%, 92.2%). Based on KDIGO risk categories, 50.8% were at high risk and 17.4% at very high risk of adverse outcomes. Conclusion: Most patients at the UHWI Diabetes Clinic had CKD and were at high or very high risk of adverse outcomes. Further studies to determine the burden of CKD in other clinical settings and to identify the best strategies for preventing adverse outcomes in developing countries need to be conducted. PMID:26426170

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Early detection of diabetic kidney disease: Present limitations and future perspectives

    Institute of Scientific and Technical Information of China (English)

    Chih-Hung; Lin; Yi-Cheng; Chang; Lee-Ming; Chuang

    2016-01-01

    Diabetic kidney disease(DKD) is one of the most common diabetic complications, as well as the leading cause of chronic kidney disease and end-stage renal disease around the world. To prevent the dreadful consequence, development of new assays for diagnostic of DKD has always been the priority in the research field of diabetic complications. At present, urinary albumin-to-creatinine ratio and estimated glomerular filtration rate(eG FR) are the standard methods for assessing glomerular damage and renal function changes in clinical practice. However, due to diverse tissue involvement in different individuals, the so-called "non-albuminuric renal impairment" is not uncommon, especially in patients with type 2 diabetes. On the other hand, the precision of creatinine-based GFR estimates is limited in hyperfiltration status. These facts make albuminuria and eG FR less reliable indicators for early-stage DKD. In recent years, considerable progress has been made in the understanding of the pathogenesis of DKD, along with the elucidation of its genetic profiles and phenotypic expression of different molecules. With the help of ever-evolving technologies, it has gradually become plausible to apply the thriving information in clinical practice. The strength and weakness of several novel biomarkers, genomic, proteomic and metabolomic signatures in assisting the early diagnosis of DKD will be discussed in this article.

  1. 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.

  2. Human apolipoprotein B transgenic SHR/NDmcr-cp rats show exacerbated kidney dysfunction

    Science.gov (United States)

    ASAHINA, Makoto; SHIMIZU, Fumi; OHTA, Masayuki; TAKEYAMA, Michiyasu; TOZAWA, Ryuichi

    2015-01-01

    Nephropathy frequently co-occurs with metabolic syndrome in humans. Metabolic syndrome is a cluster of metabolic diseases including obesity, diabetes, hypertension, and dyslipidemia, and some previous studies revealed that dyslipidemia contributes to the progression of kidney dysfunction. To establish a new nephropathy model with metabolic syndrome, we produced human apolipoprotein B (apoB) transgenic (Tg.) SHR/NDmcr-cp (SHR-cp/cp) rats, in which dyslipidemia is exacerbated more than in an established metabolic syndrome model, SHR-cp/cp rats. Human apoB Tg. SHR-cp/cp rats showed obesity, hyperinsulinemia, hypertension, and severe hyperlipidemia. They also exhibited exacerbated early-onset proteinuria, accompanied by increased kidney injury and increased oxidative and inflammatory markers. Histological analyses revealed the characteristic features of human apoB Tg. SHR-cp/cp rats including prominent glomerulosclerosis with lipid accumulation. Our newly established human apoB Tg. SHR-cp/cp rat could be a useful model for the nephropathy in metabolic syndrome and for understanding the interaction between dyslipidemia and renal dysfunction in metabolic syndrome. PMID:25912321

  3. Tubular kidney function in patients with type 2 Diabetes mellitus, microalbuminuria and proteinuria

    Directory of Open Access Journals (Sweden)

    Vlatković Vlastimir

    2007-01-01

    Full Text Available Introduction: Diabetes melitus (DM and hypertension are the most frequent causes of kidney function damage. Many different tests are developed to detect reversible functional kidney changes (detection of microalbuminuria and selective urinary enzymes. Objective The aim of our study was to examine tubular kidney function in type 2 DM patients with different proteinuria levels, and to compare these results with healthy people. Method The patients with type 2 DM and creatinine clearance >80 ml/min were included in the study. According to the levels of proteinuria, the patients were classified in three groups: group I - patients with proteinuria <300 mg/24 h, and no microalbuminuria; group II - the patients with proteinuria <300 mg/24 h and microalbuminuria >20 mg/24 h; and group III- the patients with proteinuria >300 mg/24 h. The control group consisted of healthy subjects. Results The study revealed that in type 2 DM patients and normal global kidney function, fractional excretions of sodium, potassium, and phosphates as well as renal phosphate concentrations were not adequately sensitive markers to detect damage in tubular kidney function in DM. There were some changes of urate fractional excretion in these patients: this value was significantly lower in patients with microalbuminuria compared with those with proteinuria >300 mg/24 h, as well as in the control group (p<0.05. Hormone dependent tubular kidney activity, urinary osmolarity, and urea fractional excretion in all patients were within normal ranges. Conclusion It is evident that routine laboratory analyses are not sensitive markers to detect early changes of kidney function in type 2 DM.

  4. 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

  5. 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

    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...... 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...... did not restore glycemic control, to streptozotocin (STZ)‐diabetic rats using noninvasive hyperpolarized 13C‐pyruvate magnetic resonance imaging (MRI) and blood oxygenation level–dependent (BOLD) 1H‐MRI to determine renal metabolic flux and oxygen availability, respectively. Suboptimal insulin...

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

    Directory of Open Access Journals (Sweden)

    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.

  7. WJD 5th Anniversary Special Issues(2): Type 2 diabetes Inflammation in diabetic kidney disease

    Institute of Scientific and Technical Information of China (English)

    Patricia; M; García-García; María; A; Getino-Melian; Virginia; Domínguez-Pimentel; Juan; F; Navarro-Gonzalez

    2014-01-01

    Diabetes mellitus entails significant health problems worldwide.The pathogenesis of diabetes is multifactorial,resulting from interactions of both genetic and environmental factors that trigger a complex network of pathophysiological events,with metabolic and hemodynamic alterations.In this context,inflammation has emerged as a key pathophysiology mechanism.New pathogenic pathways will provide targets for prevention or future treatments.This review will focus on the implications of inflammation in diabetes mellitus,with special attention to inflammatory cytokines.

  8. Soluble Fn14 Is Detected and Elevated in Mouse and Human Kidney Disease.

    Directory of Open Access Journals (Sweden)

    M Nusrat Sharif

    Full Text Available The cytokine TWEAK and its cognate receptor Fn14 are members of the TNF/TNFR superfamily and are upregulated in tissue injury to mediate local tissue responses including inflammation and tissue remodeling. We found that in various models of kidney disease, Fn14 expression (mRNA and protein is upregulated in the kidney. These models include: lupus nephritis mouse models (Nephrotoxic serum Transfer Nephritis and MRL.Faslpr/lpr, acute kidney injury models (Ischemia reperfusion injury and Folic acid injury, and a ZSF-1 diabetic nephropathy rat model. Fn14 expression levels correlate with disease severity as measured by disease histology. We have also shown for the first time the detection of soluble Fn14 (sFn14 in the urine and serum of mice. Importantly, we found the sFn14 levels are markedly increased in the diseased mice and are correlated with disease biomarkers including proteinuria and MCP-1. We have also detected sFn14 in human plasma and urine. Moreover, sFn14 levels, in urine are significantly increased in DN patients and correlated with proteinuria and MCP-1 levels. Thus our data not only confirm the up-regulation of Fn14/TWEAK pathway in kidney diseases, but also suggest a novel mechanism for its regulation by the generation of sFn14. The correlation of sFn14 levels and disease severity suggest that sFn14 may serve as a potential biomarker for both acute and chronic kidney diseases.

  9. 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

    with the high dose (p reversible elevation of glomerular filtration rate typically found in poorly regulated insulin-dependent diabetics, but not to the moderate......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...... elevation found in well controlled diabetics....

  10. 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

    2014-01-01

    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.

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

    Institute of Scientific and Technical Information of China (English)

    Yan-Huan Feng; Ping Fu

    2016-01-01

    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 ofmonotherapy, 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 evidence-based practice.

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

    Directory of Open Access Journals (Sweden)

    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

  13. 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.

  14. 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.

  15. Urine Metabolite Profiles Predictive of Human Kidney Allograft Status.

    Science.gov (United States)

    Suhre, Karsten; Schwartz, Joseph E; Sharma, Vijay K; Chen, Qiuying; Lee, John R; Muthukumar, Thangamani; Dadhania, Darshana M; Ding, Ruchuang; Ikle, David N; Bridges, Nancy D; Williams, Nikki M; Kastenmüller, Gabi; Karoly, Edward D; Mohney, Robert P; Abecassis, Michael; Friedewald, John; Knechtle, Stuart J; Becker, Yolanda T; Samstein, Benjamin; Shaked, Abraham; Gross, Steven S; Suthanthiran, Manikkam

    2016-02-01

    Noninvasive diagnosis and prognostication of acute cellular rejection in the kidney allograft may help realize the full benefits of kidney transplantation. To investigate whether urine metabolites predict kidney allograft status, we determined levels of 749 metabolites in 1516 urine samples from 241 kidney graft recipients enrolled in the prospective multicenter Clinical Trials in Organ Transplantation-04 study. A metabolite signature of the ratio of 3-sialyllactose to xanthosine in biopsy specimen-matched urine supernatants best discriminated acute cellular rejection biopsy specimens from specimens without rejection. For clinical application, we developed a high-throughput mass spectrometry-based assay that enabled absolute and rapid quantification of the 3-sialyllactose-to-xanthosine ratio in urine samples. A composite signature of ratios of 3-sialyllactose to xanthosine and quinolinate to X-16397 and our previously reported urinary cell mRNA signature of 18S ribosomal RNA, CD3ε mRNA, and interferon-inducible protein-10 mRNA outperformed the metabolite signatures and the mRNA signature. The area under the receiver operating characteristics curve for the composite metabolite-mRNA signature was 0.93, and the signature was diagnostic of acute cellular rejection with a specificity of 84% and a sensitivity of 90%. The composite signature, developed using solely biopsy specimen-matched urine samples, predicted future acute cellular rejection when applied to pristine samples taken days to weeks before biopsy. We conclude that metabolite profiling of urine offers a noninvasive means of diagnosing and prognosticating acute cellular rejection in the human kidney allograft, and that the combined metabolite and mRNA signature is diagnostic and prognostic of acute cellular rejection with very high accuracy.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. The emerging concept of chronic kidney disease without clinical proteinuria in diabetic patients.

    Science.gov (United States)

    Halimi, J M

    2012-10-01

    The natural history of diabetic nephropathy was defined in the 1980s on the basis of longitudinal studies undertaken in patients with type 1 and type 2 diabetes. However, an increasing number of studies have indicated that certain diabetic patients do not present with the same evolution as was then defined: for example, some often have significant initial deterioration of glomerular filtration rate whereas, in others, microalbuminuria is reduced spontaneously. Chronic kidney disease (CKD) may be accompanied, rather than preceded, by macroalbuminuria, or it may develop in patients with microalbuminuria or even in those with albuminuria levels that revert to normal. CKD can also develop in patients whose albuminuria levels remain normal. Progression to macroalbuminuria is, in fact, less frequent than regression to normoalbuminuria or no change in microalbuminuria status in diabetic patients with microalbuminuria, especially in type 1 diabetes. Some experience progressive deterioration of renal function due to diabetes without developing significant proteinuria: this is seen fairly frequently and can affect 50% of patients with renal insufficiency. Such cases are more often older patients treated with renin-angiotensin system blockers who usually have a history of cardiovascular disease. Evolution to end-stage renal disease is slower in this subgroup of patients, although histological analyses may show surprisingly advanced glomerular lesions. The main parameters of surveillance remain regular monitoring of glycaemia, and control of blood pressure and the evolution of initial albuminuria levels. Nevertheless, why some patients exhibit conventional diabetic nephropathy while others have slower declines in renal function associated with normal albuminuria levels or microalbuminuria is unclear. It is hoped that the new pathological classification of diabetic nephropathy will help in our understanding of these discrepancies.

  18. Effect of mangiferin isolated from Salacia chinensis regulates the kidney carbohydrate metabolism in streptozotocin-induced diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Periyar Selvam Sellamuthu; Palanisamy Arulselvan; Balu Periamallipatti Muniappan; Murugesan Kandasamy

    2012-01-01

    Objective: The present investigation was to evaluate the possible anti-diabetic effect of mangiferin from Salacia chinensis (S. chinensis) on the activities of kidney carbohydrate metabolic enzymes in chemically induced diabetic rats. Methods: Diabetes was induced by streptozotocin (STZ) in adult male rats, as a single intraperitoneal injection at a dose of 55 mg/kg body weight. The STZ-induced diabetic rats were treated by mangiferin and glibenclamide (positive control drug) for 30 days. At the end of the experiment, the rats were sacrificed and carbohydrate metabolic enzyme activities were analyzed in the kidney. Results: Diabetic control rats showed a significant increase in the level of fasting blood glucose and also increase the activities of carbohydrate metabolic enzymes in kidney on successive days of the experiment as compared with their basal values. Daily oral administration of mangiferin showed a significant decrease in the blood glucose when compared to diabetic control. The anti-hyperglycemic effect was obtained with the dose of 40 mg/kg b.wt. In addition, treatment of mangiferin shows alteration in kidney carbohydrate metabolic enzymes including gluconeogenic enzymes like glucose-6-phosphatase and fructose-1,6-disphosphatase. These results were comparable with positive control drug, glibenclamide. Conclusions: The results obtained in this study provide evidence of the anti-diabetic potential of mangiferin, mediated through the regulation of carbohydrate key metabolic enzyme activities.

  19. Amelioration of Altered Serum, Liver, and Kidney Antioxidant Enzymes Activities by Sodium Selenite in Alloxan-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Hassan Ahmadvand

    2014-10-01

    Full Text Available Background: The aim of this study was to evaluate the possible protective effect of sodium selenite on serum, liver, and kidney antioxidant enzymes activities in alloxan-induced type 1 diabetic rats. Methods: Forty Sprague-Dawley male rats were randomly divided into four groups; Group one as control, Group two as sham-treated with sodium selenite by 1 mg/kg intraperitoneal (i.p. injections daily, Group three as diabetic untreated, and Group four as diabetic treated with sodium selenite by 1 mg/kg i.p. injections daily . Diabetes was induced in the third and fourth groups by subcutaneous alloxan injections. After eight weeks the animals were euthanized and livers and kidneys were immediately removed and used fresh or kept frozen until analysis. Before the rats were killed blood samples were also collected to measure glutathione peroxidase (GPX and catalase (CAT activities in sera. Results: Glutathione peroxidase and CAT activities serum, liver, and kidney were all significantly less in the diabetic rats than in the controls. Sodium selenite treatment of the diabetic rats resulted in significant increases in GPX activity in the kidneys and livers, and CAT activity in the sera and livers. Conclusions: Our results indicate that sodium selenite might be a potent antioxidant that exerts beneficial effects on both GPX and CAT activities in alloxan-induced type 1 diabetic rats.

  20. [Nucleoside-5'-triphosphate hydrolysis in the liver and kidney of rats with chronic alloxan diabetes].

    Science.gov (United States)

    Rusina, I M; Makarchikov, A F; Makar, E A; Kubyshin, V L

    2006-01-01

    Activity and some properties of a soluble enzyme hydrolyzing nucleoside-5'-triphosphates were studied in the liver and kidney of normal and diabetic rats. The enzyme activity was shown to be reduced by 34% (p < 0.01) in the liver extracts of diabetic animals, while no difference was observed in the kidney. When ITP was used as substrate, the apparent Michaelis constant of the enzyme was significantly lower in the liver of controls as compared to experimental rats (32.3 +/- 1.3 microM and 54.3 +/- 1.0 microM, respectively, p < 0.01). The KM values of the enzyme in the kidney were not distinguishable in both groups. NTPase exhibits maximal activity at pH 7.0 and has a broad substrate specificity with respect to different nucleoside-5'-tri- and diphosphates. Molecular mass of the enzyme was estimated by gel filtration to be 63.7 +/- 0.9 kD.

  1. 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.

  2. Introduction: Kidney Stone Research, Lessons From Human Studies

    Science.gov (United States)

    Coe, Fredric L.

    2007-04-01

    About 5% of American women and 12% of men will develop a kidney stone at some time in their life, the prevalence has been rising in both sexes. Approximately 80% of stones are composed of calcium oxalate, and calcium phosphate; 10% of struvite; 9% of uric acid; and the remaining 1% are composed of cystine or ammonium acid urate or are diagnosed as drug-related stone. Stones ultimately arise because of an unwanted phase change of these substances from liquid to solid state. In this introduction, I have outlined our current thinking of the possible mechanisms involved in stone formation based on our biopsy data collected from a series of human kidney stone formers. In addition, I have presented a set of questions as a means of focusing future research in this field.

  3. 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.

  4. 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.

  5. New Susceptibility Loci Associated with Kidney Disease in Type 1 Diabetes

    Science.gov (United States)

    Forsblom, Carol; Isakova, Tamara; McKay, Gareth J.; Williams, Winfred W.; Sadlier, Denise M.; Mäkinen, Ville-Petteri; Swan, Elizabeth J.; Palmer, Cameron; Boright, Andrew P.; Ahlqvist, Emma; Deshmukh, Harshal A.; Keller, Benjamin J.; Huang, Huateng; Ahola, Aila J.; Fagerholm, Emma; Gordin, Daniel; Harjutsalo, Valma; He, Bing; Heikkilä, Outi; Hietala, Kustaa; Kytö, Janne; Lahermo, Päivi; Lehto, Markku; Lithovius, Raija; Österholm, Anne-May; Parkkonen, Maija; Pitkäniemi, Janne; Rosengård-Bärlund, Milla; Saraheimo, Markku; Sarti, Cinzia; Söderlund, Jenny; Soro-Paavonen, Aino; Syreeni, Anna; Thorn, Lena M.; Tikkanen, Heikki; Tolonen, Nina; Tryggvason, Karl; Tuomilehto, Jaakko; Wadén, Johan; Gill, Geoffrey V.; Prior, Sarah; Guiducci, Candace; Mirel, Daniel B.; Taylor, Andrew; Hosseini, S. Mohsen; Parving, Hans-Henrik; Rossing, Peter; Tarnow, Lise; Ladenvall, Claes; Alhenc-Gelas, François; Lefebvre, Pierre; Rigalleau, Vincent; Roussel, Ronan; Tregouet, David-Alexandre; Maestroni, Anna; Maestroni, Silvia; Falhammar, Henrik; Gu, Tianwei; Möllsten, Anna; Cimponeriu, Danut; Ioana, Mihai; Mota, Maria; Mota, Eugen; Serafinceanu, Cristian; Stavarachi, Monica; Hanson, Robert L.; Nelson, Robert G.; Kretzler, Matthias; Colhoun, Helen M.; Panduru, Nicolae Mircea; Gu, Harvest F.; Brismar, Kerstin; Zerbini, Gianpaolo; Hadjadj, Samy; Marre, Michel; Groop, Leif; Lajer, Maria; Bull, Shelley B.; Waggott, Daryl; Paterson, Andrew D.; Savage, David A.; Bain, Stephen C.; Martin, Finian; Hirschhorn, Joel N.; Godson, Catherine; Florez, Jose C.; Groop, Per-Henrik; Maxwell, Alexander P.

    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 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. PMID:23028342

  6. 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.

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

    Science.gov (United States)

    Laustsen, Christoffer; Lipsø, Kasper; Ostergaard, Jakob Appel; Nørregaard, Rikke; Flyvbjerg, Allan; Pedersen, Michael; Palm, Fredrik; Ardenkjær-Larsen, Jan Henrik

    2014-12-01

    Good glycemic control is crucial to prevent the onset and progression of late diabetic complications, but insulin treatment often fails to achieve normalization of glycemic control to the level seen in healthy controls. In fact, recent experimental studies indicate that insufficient treatment 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 did not restore glycemic control, to streptozotocin (STZ)-diabetic rats using noninvasive hyperpolarized (13)C-pyruvate magnetic resonance imaging (MRI) and blood oxygenation level-dependent (BOLD) (1)H-MRI to determine renal metabolic flux and oxygen availability, respectively. Suboptimal insulin 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. The results demonstrate the importance of tight glycemic control in insulinopenic diabetes, and that insulin, when administered insufficiently, adds an additional burden on top of poor glycemic control.

  8. Diabetes Mellitus and Prediabetes on Kidney Transplant Waiting List- Prevalence, Metabolic Phenotyping and Risk Stratification Approach.

    Directory of Open Access Journals (Sweden)

    Martina Guthoff

    Full Text Available Despite a significant prognostic impact, little is known about disturbances in glucose metabolism among kidney transplant candidates. We assess the prevalence of diabetes mellitus (DM and prediabetes on kidney transplant waiting list, its underlying pathophysiology and propose an approach for individual risk stratification.All patients on active kidney transplant waiting list of a large European university hospital transplant center were metabolically phenotyped.Of 138 patients, 76 (55% had disturbances in glucose metabolism. 22% of patients had known DM, 3% were newly diagnosed. 30% were detected to have prediabetes. Insulin sensitivity and-secretion indices allowed for identification of underlying pathophysiology and risk factors. Age independently affected insulin secretion, resulting in a relative risk for prediabetes of 2.95 (95%CI 1.38-4.83 with a cut-off at 48 years. Body mass index independently affected insulin sensitivity as a continuous variable.The prevalence of DM or prediabetes on kidney transplant waiting list is as high as 55%, with more than one third of patients previously undiagnosed. Oral glucose tolerance test is mandatory to detect all patients at risk. Metabolic phenotyping allows for differentiation of underlying pathophysiology and provides a basis for early individual risk stratification and specific intervention to improve patient and allograft outcome.

  9. Kidney Disease (Nephropathy)

    Science.gov (United States)

    ... Text Size: A A A Listen En Español Kidney Disease (Nephropathy) Kidneys are remarkable organs. Inside them ... resulting in kidney disease. How Does Diabetes Cause Kidney Disease? When our bodies digest the protein we ...

  10. 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.

  11. Cholecystokinin plays a novel protective role in diabetic kidney through anti-inflammatory actions on macrophage: anti-inflammatory effect of cholecystokinin.

    Science.gov (United States)

    Miyamoto, Satoshi; Shikata, Kenichi; Miyasaka, Kyoko; Okada, Shinichi; Sasaki, Motofumi; Kodera, Ryo; Hirota, Daisho; Kajitani, Nobuo; Takatsuka, Tetsuharu; Kataoka, Hitomi Usui; Nishishita, Shingo; Sato, Chikage; Funakoshi, Akihiro; Nishimori, Hisakazu; Uchida, Haruhito Adam; Ogawa, Daisuke; Makino, Hirofumi

    2012-04-01

    Inflammatory process is involved in the pathogenesis of diabetic nephropathy. In this article, we show that cholecystokinin (CCK) is expressed in the kidney and exerts renoprotective effects through its anti-inflammatory actions. DNA microarray showed that CCK was upregulated in the kidney of diabetic wild-type (WT) mice but not in diabetic intracellular adhesion molecule-1 knockout mice. We induced diabetes in CCK-1 receptor (CCK-1R) and CCK-2R double-knockout (CCK-1R(-/-),-2R(-/-)) mice, and furthermore, we performed a bone marrow transplantation study using CCK-1R(-/-) mice to determine the role of CCK-1R on macrophages in the diabetic kidney. Diabetic CCK-1R(-/-),-2R(-/-) mice revealed enhanced albuminuria and inflammation in the kidney compared with diabetic WT mice. In addition, diabetic WT mice with CCK-1R(-/-) bone marrow-derived cells developed more albuminuria than diabetic CCK-1R(-/-) mice with WT bone marrow-derived cells. Administration of sulfated cholecystokinin octapeptide (CCK-8S) ameliorated albuminuria, podocyte loss, expression of proinflammatory genes, and infiltration of macrophages in the kidneys of diabetic rats. Furthermore, CCK-8S inhibited both expression of tumor necrosis factor-α and chemotaxis in cultured THP-1 cells. These results suggest that CCK suppresses the activation of macrophage and expression of proinflammatory genes in diabetic kidney. Our findings may provide a novel strategy of therapy for the early stage of diabetic nephropathy.

  12. Prevalence of chronic kidney disease in type 2 diabetes in primary health care unit of Udon Thani province, Thailand.

    Science.gov (United States)

    Narenpitak, Surapong; Narenpitak, Aphaphan

    2008-10-01

    To determine the prevalence of chronic kidney disease (CKD) in Type 2 diabetes and risk factors of decreased kidney function in Type 2 diabetes at primary health care unit of Udon Thani province. A descriptive cross-sectional study, cluster random sampling method was conducted from April to August 2007. Seven hundred and sixteen patients were enrolled. Medical histories, physical examinations, and blood tests for glucose, creatinine, total cholesterol, and triglyceride after 9-12 hours fasting were collected. The definition and classification of CKD are classified according to K/DOQI guideline 2002. The mean age of the diabetic patients was 58.70 +/- 9.83 years ranged from 30 to 92 years old. The mean duration of diabetes was 5.53 +/- 4.62 years, the majority (82.41%) had diabetes less than 10 years. More than half (51.82%) were obese (BMI > or = 25 kg/m2). Most of them (89.39%) had universal coverage health assurance. According to the ADA guideline 2006, the target systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol, and triglyceride level could be achieved 55.45, 52.93, 36.31, 33.66, and 45.65% respectively. The prevalence of CKD stage 3 to 5 were 27.09 and 25.28% by using C-G and MDRD formulae respectively. The duration of diabetes, diabetes with history of hypertension, triglyceride level, and diabetic retinopathy were significant independent risk factors of the presence of decreased kidney function processed by logistic regression analysis. The present study demonstrated the clinical characteristic and the prevalence of decreased kidney function in type 2 diabetes in a primary health care setting. Intensive and optimal treatment of diabetes to slow the progression of long-term complications should be effectively managed by a disciplinary team.

  13. 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.

  14. Study on Prevention and Treatment of Diabetes in Middle andAged Women with Kidney Deficiency and Bone Metabolic Disturbance

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Some researches have found out, in recent years, there usually exist calcium negative equilibrium and urinary calcium elevation in diabetes mellitus due to glucose metabolic disturbance.(1,2) On the other hand, sex hormone reduction is apparently concerned with Kidney deficiency, with worsened bone mineral substance loss resulting from Kidney Deficiency that resulted in postmenopausal osteoporosis.(3,4)  Diabetes in middle aged and elderly comes on when the women patients are in the menopausal or postmenopausal state, so the deterioration of the ovary endocrine function and the reduction of the serum estradiol level will become more remarkable, and Kidney Deficiency as well as calcium negative equilibrium will also become more obvious. For this reason, a study has been conducted on the treatment effect of combining medicinal herbs and glibenclamide in middle aged and elderly female diabetic patients.

  15. Effect of telmisartan on expression of protein kinase C-α in kidneys of diabetic mice

    Institute of Scientific and Technical Information of China (English)

    Li-jun YAO; Jian-qing WANG; Hong ZHAO; Jian-she LIU; An-guo DENG

    2007-01-01

    Aim: To investigate the effects of angiotensin receptor blocker (ARB) telmisartan on the expression and distribution of protein kinase C (PKC)-α in the kidneys of diabetic mice.Methods: Diabetic mice were induced with streptozotocin and a group of them were randomly selected for treatment with telmisartan. After 6 weeks, the expression and localization of PKC-α in the renal cortex, and the outer and inner medulla were assessed by immunohistochemistry and semiquantitative Western blotting. In addition, expressions of PKC-α, transforming growth factor-β1 (TGF-β1), and vascular endothelial growth factor (VEGF) in glomemli were measured by semiquantitative immunohistochemistry.Results: Diabetic and nor-mal mice showed similar distributions of PKC-α in the kidneys. The expression of PKC-α was found in glomeruli, epithelial cells of proximal tubules, and medullary-collecting duct, while not in the medullary and cortical thick ascending limb, and was different in the epithelial cells of proximal tubules of diabetic nephropathy (DN) mice, PKC-α was mostly translocated from the basement membrane to the apical membrane, whereas it was largely translocated from the apical membrane to the basement membrane in epithelial cells of the inner medullary-collecting duct.Western blotting detected increased expression of PKC-α in the renal cortex and outer medulla, but not in the inner medulla of DN mice. Enhanced expressions of PKC-α TGF-β, and VEGF were shown in the glomeruli of DN mice, where PKC-α exhibited a correlation to VEGF, but no correlation to TGF-β1. ARB telmisartan attenuated alterations of PKC-α as mentioned earlier in the DN mice.Conclusion: Our findings suggest that PKC-α may play a role in the pathogenesis of DN, and that the nephroprotective effects of ARB telmisartan may be partly associated with its influence on PKC-α.

  16. Extracting Three Dimensional Surface Model of Human Kidney from the Visible Human Data Set using Free Software

    CERN Document Server

    P, Kirana Kumara

    2013-01-01

    Three dimensional digital model of a representative human kidney is needed for a surgical simulator that is capable of simulating a laparoscopic surgery involving kidney. Buying a three dimensional computer model of a representative human kidney, or reconstructing a human kidney from an image sequence using commercial software, both involve (sometimes significant amount of) money. In this paper, author has shown that one can obtain a three dimensional surface model of human kidney by making use of images from the Visible Human Data Set and a few free software packages (ImageJ, ITK-SNAP, and MeshLab in particular). Images from the Visible Human Data Set, and the software packages used here, both do not cost anything. Hence, the practice of extracting the geometry of a representative human kidney for free, as illustrated in the present work, could be a free alternative to the use of expensive commercial software or to the purchase of a digital model.

  17. Urinary Excretion of Kidney Aquaporins as Possible Diagnostic Biomarker of Diabetic Nephropathy.

    Science.gov (United States)

    Rossi, Luigi; Nicoletti, Maria Celeste; Carmosino, Monica; Mastrofrancesco, Lisa; Di Franco, Antonella; Indrio, Francesca; Lella, Rossella; Laviola, Luigi; Giorgino, Francesco; Svelto, Maria; Gesualdo, Loreto; Procino, Giuseppe

    2017-01-01

    Diabetic nephropathy (DN) is a microangiopathic complication of diabetes mellitus (DM) affecting one-third of diabetic patients. The large variability in the clinical presentation of renal involvement in patients with DM makes kidney biopsy a prerequisite for a correct diagnosis. However, renal biopsy is an invasive procedure associated with risk of major complications. Numerous studies aimed to identify a noninvasive biomarker of DN but, so far, none of these is considered to be sufficiently specific and sensitive. Water channel aquaporins (AQPs), expressed at the plasma membrane of epithelial tubular cells, are often dysregulated during DN. In this work, we analyzed the urine excretion of AQP5 and AQP2 (uAQP5 and uAQP2), via exosomes, in 35 diabetic patients: 12 normoalbuminuric with normal renal function (DM), 11 with proteinuric nondiabetic nephropathy (NDN), and 12 with histological diagnosis and classification of DN. ELISA and WB analysis independently showed that uAQP5 was significantly increased in DN patients. Interestingly, linear regression analysis showed a positive correlation between uAQP5 and the histological class of DN. The same analysis, focusing on uAQP2, showed comparable results. Taken together, these data suggest a possible use of AQP5 and AQP2 as novel noninvasive biomarkers to help in classifying the clinical stage of DN.

  18. Urinary Excretion of Kidney Aquaporins as Possible Diagnostic Biomarker of Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Luigi Rossi

    2017-01-01

    Full Text Available Diabetic nephropathy (DN is a microangiopathic complication of diabetes mellitus (DM affecting one-third of diabetic patients. The large variability in the clinical presentation of renal involvement in patients with DM makes kidney biopsy a prerequisite for a correct diagnosis. However, renal biopsy is an invasive procedure associated with risk of major complications. Numerous studies aimed to identify a noninvasive biomarker of DN but, so far, none of these is considered to be sufficiently specific and sensitive. Water channel aquaporins (AQPs, expressed at the plasma membrane of epithelial tubular cells, are often dysregulated during DN. In this work, we analyzed the urine excretion of AQP5 and AQP2 (uAQP5 and uAQP2, via exosomes, in 35 diabetic patients: 12 normoalbuminuric with normal renal function (DM, 11 with proteinuric nondiabetic nephropathy (NDN, and 12 with histological diagnosis and classification of DN. ELISA and WB analysis independently showed that uAQP5 was significantly increased in DN patients. Interestingly, linear regression analysis showed a positive correlation between uAQP5 and the histological class of DN. The same analysis, focusing on uAQP2, showed comparable results. Taken together, these data suggest a possible use of AQP5 and AQP2 as novel noninvasive biomarkers to help in classifying the clinical stage of DN.

  19. Serotonin and Its Receptor as a New Antioxidant Therapeutic Target for Diabetic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Yu Yang

    2017-01-01

    Full Text Available Diabetic kidney disease (DKD is a widespread chronic microvascular complication of diabetes mellitus (DM, affects almost 30–50% of patients, and represents a leading cause of death of DM. Serotonin or 5-hydroxytryptamine (5-HT is a multifunctional bioamine that has crucial roles in many physiological pathways. Recently, emerging evidence from experimental and clinical studies has demonstrated that 5-HT is involved in the pathogenesis of diabetic vascular complications. The 5-HT receptor (5-HTR antagonists exert renoprotective effects by suppressing oxidative stress, suggesting that 5-HTR can be used as a potential target for treating DKD. In this review, therefore, we summarize the published information available for the involvement of 5-HT and 5-HTR antagonists in the pathogenesis of various diabetic complications with a particular focus of DKD. We conclude that 5-HTR is a potential therapeutic target for treating DKD, as it has been successfully applied in animal models and has currently being investigated in randomized and controlled clinical trials.

  20. Urinary Excretion of Kidney Aquaporins as Possible Diagnostic Biomarker of Diabetic Nephropathy

    Science.gov (United States)

    Rossi, Luigi; Nicoletti, Maria Celeste; Mastrofrancesco, Lisa; Di Franco, Antonella; Indrio, Francesca; Lella, Rossella; Laviola, Luigi; Giorgino, Francesco; Svelto, Maria; Gesualdo, Loreto

    2017-01-01

    Diabetic nephropathy (DN) is a microangiopathic complication of diabetes mellitus (DM) affecting one-third of diabetic patients. The large variability in the clinical presentation of renal involvement in patients with DM makes kidney biopsy a prerequisite for a correct diagnosis. However, renal biopsy is an invasive procedure associated with risk of major complications. Numerous studies aimed to identify a noninvasive biomarker of DN but, so far, none of these is considered to be sufficiently specific and sensitive. Water channel aquaporins (AQPs), expressed at the plasma membrane of epithelial tubular cells, are often dysregulated during DN. In this work, we analyzed the urine excretion of AQP5 and AQP2 (uAQP5 and uAQP2), via exosomes, in 35 diabetic patients: 12 normoalbuminuric with normal renal function (DM), 11 with proteinuric nondiabetic nephropathy (NDN), and 12 with histological diagnosis and classification of DN. ELISA and WB analysis independently showed that uAQP5 was significantly increased in DN patients. Interestingly, linear regression analysis showed a positive correlation between uAQP5 and the histological class of DN. The same analysis, focusing on uAQP2, showed comparable results. Taken together, these data suggest a possible use of AQP5 and AQP2 as novel noninvasive biomarkers to help in classifying the clinical stage of DN. PMID:28246612

  1. Hypertension and nephrotoxicity in the rate of decline in kidney function in diabetic nephropathy.

    Science.gov (United States)

    Aubia, J; Hojman, L; Chine, M; Lloveras, J; Masramon, J; Llorach, I; Cuevas, X; Puig, J M

    1987-01-01

    Serum creatinine levels were determined prospectively every 2 to 3 months in 40 patients with diabetic nephropathy for a global observation period of 864 months. The monthly creatinine increasing rate was significantly lower in normotensive periods, mean arterial pressure (MAP) less than 115 mmHg, when compared with hypertensive periods, MAP greater than 125 mmHg. No significant difference was shown in periods with borderline hypertension (MAP between 115-124 mmHg). The mean creatinine increases were of 0.036 mg/dl/month, 0.3 mg/dl/month and 0.046 mg/dl/month respectively. Normotension was associated with a slowing down of the rate of decline in renal function in this group of moderate kidney failure with an initial mean serum creatinine of 2.26 mg/dl. The exposure of patients to nephrotoxics (aminoglycosides, and possibly anesthesia) significantly accelerated the decline in renal function: 0.39 mg/dl/month and 0.17 mg/dl/month respectively according to the concomitance or not of toxics and hypertension. The reported protective effect of diabetes against aminoglycosides nephrotoxicity in experimental conditions was not reflected in our clinical results. On the contrary, we suggest a possible enhanced sensibility of the diabetic patient with diabetic nephropathy to aminoglycosides leading to an acceleration of the progression of renal failure.

  2. Thioredoxin-interacting protein regulates lipid metabolism via Akt/mTOR pathway in diabetic kidney disease.

    Science.gov (United States)

    Du, Chunyang; Wu, Ming; Liu, Huan; Ren, Yunzhuo; Du, Yunxia; Wu, Haijiang; Wei, Jinying; Liu, Chuxin; Yao, Fang; Wang, Hui; Zhu, Yan; Duan, Huijun; Shi, Yonghong

    2016-10-01

    Abnormal lipid metabolism contributes to the renal lipid accumulation, which is associated with diabetic kidney disease, but its precise mechanism remains unclear. The growing evidence demonstrates that thioredoxin-interacting protein is involved in regulating cellular glucose and lipid metabolism. Here, we investigated the effects of thioredoxin-interacting protein on lipid accumulation in diabetic kidney disease. In contrast to the diabetic wild-type mice, the physical and biochemical parameters were improved in the diabetic thioredoxin-interacting protein knockout mice. The increased renal lipid accumulation, expression of acetyl-CoA carboxylase, fatty acid synthase and sterol regulatory element binding protein-1, and phosphorylated Akt and mTOR associated with diabetes in wild-type mice was attenuated in diabetic thioredoxin-interacting protein knockout mice. Furthermore, thioredoxin-interacting protein knockout significantly increased the expression of peroxisome proliferator-activated receptor-α, acyl-coenzyme A oxidase 1 and carnitine palmitoyltransferaser 1 in diabetic kidneys. In vitro experiments, using HK-2 cells, revealed that knockdown of thioredoxin-interacting protein inhibited high glucose-mediated lipid accumulation, expression of acetyl-CoA carboxylase, fatty acid synthase and sterol regulatory element binding protein-1, as well as activation of Akt and mTOR. Moreover, knockdown of thioredoxin-interacting protein reversed high glucose-induced reduction of peroxisome proliferator-activated receptor-α, acyl-coenzyme A oxidase 1 and carnitine palmitoyltransferaser 1 expression in HK-2 cells. Importantly, blockade of Akt/mTOR signaling pathway with LY294002, a specific PI3K inhibitor, replicated these effects of thioredoxin-interacting protein silencing. Taken together, these data suggest that thioredoxin-interacting protein deficiency alleviates diabetic renal lipid accumulation through regulation of Akt/mTOR pathway, thioredoxin

  3. 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.

  4. New Experimental Models of Diabetic Nephropathy in Mice Models of Type 2 Diabetes: Efforts to Replicate Human Nephropathy

    Directory of Open Access Journals (Sweden)

    María José Soler

    2012-01-01

    Full Text Available Diabetic nephropathy (DN is the leading cause of end-stage renal disease. The use of experimental models of DN has provided valuable information regarding many aspects of DN, including pathophysiology, progression, implicated genes, and new therapeutic strategies. A large number of mouse models of diabetes have been identified and their kidney disease was characterized to various degrees. Most experimental models of type 2 DN are helpful in studying early stages of DN, but these models have not been able to reproduce the characteristic features of more advanced DN in humans such as nodules in the glomerular tuft or glomerulosclerosis. The generation of new experimental models of DN created by crossing, knockdown, or knockin of genes continues to provide improved tools for studying DN. These models provide an opportunity to search for new mechanisms involving the development of DN, but their shortcomings should be recognized as well. Moreover, it is important to recognize that the genetic background has a substantial effect on the susceptibility to diabetes and kidney disease development in the various models of diabetes.

  5. 77 FR 43096 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Diabetes Mellitus...

    Science.gov (United States)

    2012-07-23

    ... meeting will focus on ``Diabetes, Dementia, and Alzheimer's Disease.'' Any member of the public interested... at least 10 days in advance of the meeting. Interested individuals and representatives or... written copy of their oral presentation in advance of the meeting. Only one representative of an...

  6. Effect of tolvaptan in patients with chronic kidney disease due to diabetic nephropathy with heart failure.

    Science.gov (United States)

    Sato, Eiichi; Nakamura, Tsukasa; Amaha, Mayuko; Nomura, Mayumi; Matsumura, Daisuke; Yamagishi, Hidetsugu; Ono, Yuko; Ueda, Yoshihiko

    2014-01-01

    The efficacy of tolvaptan for treating heart failure has already been shown. Adequate data relating to the effect of tolvaptan on the correlation of water balance in renal disease are not available. A retrospective study was conducted on the efficacy and adverse reactions of tolvaptan for treating nephrotic syndrome.The subjects were 26 patients with chronic kidney failure due to diabetic nephropathy with heart failure who were administered tolvaptan and seen between December 2011 and October 2013. The endpoints were urinary output, physical findings, and blood analyses. The expression of aquaporin-2 in the collecting duct, which is related to the action of tolvaptan, was investigated by immunohistochemistry using the kidney tissue obtained for the diagnosis.Responses were seen in 19 of the patients. In the histopathological investigation there was severe glomerulosclerosis in patients with diabetic nephropathy, but the responders were noticeable in that they only had mild tubulointerstitial damage. Non-responders exhibited profound tubulointerstitial damage. The expression of aquaporin-2 was determined in 8 patients, of which 7 were responders who tested positive for aquaporin-2. The remaining case was a non-responder who showed no expression of aquaporin-2.Tolvaptan is considered effective for some cases of nephrotic syndrome. There are no clear parameters for predicting an effect, but the present study showed that aquaporin-2 was expressed in the epithelial cells of the collecting ducts of tolvaptan responders.

  7. Generation of kidney organoids from human pluripotent stem cells.

    Science.gov (United States)

    Takasato, Minoru; Er, Pei X; Chiu, Han S; Little, Melissa H

    2016-09-01

    The human kidney develops from four progenitor populations-nephron progenitors, ureteric epithelial progenitors, renal interstitial progenitors and endothelial progenitors-resulting in the formation of maximally 2 million nephrons. Until recently, the reported methods differentiated human pluripotent stem cells (hPSCs) into either nephron progenitor or ureteric epithelial progenitor cells, consequently forming only nephrons or collecting ducts, respectively. Here we detail a protocol that simultaneously induces all four progenitors to generate kidney organoids within which segmented nephrons are connected to collecting ducts and surrounded by renal interstitial cells and an endothelial network. As evidence of functional maturity, proximal tubules within organoids display megalin-mediated and cubilin-mediated endocytosis, and they respond to a nephrotoxicant to undergo apoptosis. This protocol consists of 7 d of monolayer culture for intermediate mesoderm induction, followed by 18 d of 3D culture to facilitate self-organizing renogenic events leading to organoid formation. Personnel experienced in culturing hPSCs are required to conduct this protocol.

  8. Generating kidney organoids from human pluripotent stem cells

    Science.gov (United States)

    Takasato, Minoru; Er, Pei X; Chiu, Han S; Little, Melissa H

    2016-01-01

    The human kidney develops from four progenitor populations; nephron progenitors, ureteric epithelial progenitors, renal interstitial progenitors and endothelial progenitors; resulting in the formation of maximally 2 million nephrons. Until recently, methods differentiating human pluripotent stem cells (hPSCs) into either nephron progenitor or ureteric epithelial progenitor had been reported, consequently forming only nephrons or collecting ducts, respectively. Here, we detail a protocol that simultaneously induces all four progenitors to generate kidney organoids within which segmented nephrons are connected to collecting ducts and surrounded by renal interstitial cells and an endothelial network. As evidence of functional maturity, proximal tubules within organoids display megalin-mediated and cubilin-mediated endocytosis, and respond to a nephrotoxicant to undergo apoptosis. This protocol consists of 7 days of monolayer culture for intermediate mesoderm induction followed by 18 days of three-dimensional culture to facilitate self-organising renogenic events leading to organoid formation. Personnel experienced in culturing hPSCs are required to conduct this protocol. PMID:27560173

  9. Relative length of human kidney as more precise measuring of normal kidney

    Directory of Open Access Journals (Sweden)

    Ilić Goran

    2010-01-01

    Full Text Available Introduction. Malformations in kidney development and kidney diseases are accompanied with changes in their size. For kidney evaluation in clinical practice, the kidney length is the most widely used measurement, since it provides the most precise results and it is easy to perform. Recently, the measurement of relative renal length has become more preferable as it takes into account the body height. The aim of this study was to measure both the absolute and relative length of normal cadaveric kidneys according to the body height, sex and age. Material and methods. In this study, we examined 95 adult cadaveric kidneys, without renal and vascular impairment, their age ranging from 23-87 years. To determine the period of the most abundant changes in kidney length, we separated them into a 10-year range. The relative renal length was calculated using the kidney length anybody height ratio (kidney/body ratio. Results. The absolute and relative length of left kidney in males was longer than the right one, with a statistically significant correlation. In females, the left kidney length was also longer than the right one, however, without a statistical significance. In contrast to the absolute length, the relative length of both kidneys did not show a significant difference between sexes, and did not manifest a significant decrease with age. There was a significant correlation between the kidney length and the subject’s height. Conclusion. The relative renal length represents kidney size better than the absolute renal length because it eliminates sex and height differences until the age of 59 year. From the seventh decade of life, there is a significant decrease in both the absolute and relative renal length.

  10. The Prognosis of Patients with Chronic Kidney Disease and Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Vladu Mihaela

    2014-09-01

    Full Text Available Background and Aims: Diabetes mellitus (DM is a chronic disease which can evolve towards devastating micro and macro-vascular complications. Chronic kidney disease (CKD is a worldwide public health problem, with adverse outcomes of kidney failure, cardiovascular disease (CVD and premature death. The aim of our study was to evaluate the prognosis in patients with DM and CKD, depending on estimated glomerular filtration rate (eGFR and albuminuria, according to the classification of Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (KDIGO from 2013 Materials and Methods: The study was epidemiological, transversal, non interventional type, with 600 subjects unselected patients divided into three subgroups: 200 patients with T1DM, 200 patients with T2DM and 200 age matched subjects without DM. The recorded data have been analyzed using the Statistic Package for Social Sciences (SPSS, the 17.00 software (IBM Corporation, Armonk, NY, United States of America. Results:. We found a statistically significant difference among the three study groups (p < 0.0001 regarding the prognosis of CKD. Conclusions: DM represents an important risk factor for the appearance of CKD but also a negative prognosis factor for the patients with CKD.

  11. Diabetes: energetics, development and human evolution.

    Science.gov (United States)

    Campbell, B C; Cajigal, A

    2001-07-01

    The recent emergence of the thrifty phenotype as an explanation for metabolic efficiency has brought evolutionary perspectives on diabetes, as represented by the thrifty genotype, under scrutiny. However, the logic of natural selection along with evidence from non-human primates supports the role for energetic constraints in the evolution of metabolic efficiency, particularly in skeletal muscle physiology. Environmental fluctuation during human evolution would have provided selective pressures for the development of efficient skeletal muscle starting prenatally and continuing throughout the lifespan. Such mechanisms including, glucose transporters, mitochondrial gene expression, leptin receptors and uncoupling proteins, should be present in all humans, though some living populations may exhibit particular 'thriftier' alleles. A focus on physical activity and the factors underlying efficient muscle physiology has implications for prevention of diabetes in both developing and developed societies. Copyright 2001 Harcourt Publishers Ltd.

  12. 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.

  13. The ratio between kidney volume and function increases with the progression of nephropathy in Type 2 diabetes.

    Science.gov (United States)

    Giordano, M; Ciarambino, T; Gesuè, L; Castellino, P; De Simone, M; Rinaldi, G; D'Amora, M; Zito, G; Paolisso, G; Coppola, L

    2009-10-01

    In Type 2 diabetes, it is not clear if renal size is constantly related to the glomerular filtration rate. In addition, it is not known if kidney volume (KV) is associated with an increased urinary albumin and IgG excretion. The relationship between kidney volume, creatinine clearance (CrCl), urinary albumin and IgG excretion in 95 Type 2 diabetic patients with different stages of nephropathy (1 - 4 Stage sec NKDF-QD) was elevated and compared to 85 non-diabetic subjects with similar degree of kidney function. In Type 2 diabetic patients the KV/CrCl ratio was increased, in comparison with the control subjects, from about 15% in Stage 1 to 53% in Stage 4. In T2D subjects, significant correlations were found between KV and urinary albumin excretion (r = 0.665, p < 0.05), and between KV and urinary IgG excretion (r = 0.800, p < 0.001). The present study finds that Type 2 diabetic subjects, are characterized by an increased ratio between KV/CrCl, throughout the different progressive stages of nephropathy. In Type 2 diabetes relationships between KV and urinary albumin and between KV and IgG excretion also were found to be significant, suggesting a role for the impaired size selectivity of proteinuria as a possible determinant of KV.

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

    Directory of Open Access Journals (Sweden)

    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

  15. Cardiorenal syndrome in patients with chronic kidney disease and diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Irina Mikhaylovna Kutyrina

    2013-11-01

    Full Text Available Aim. Combination of cardiovascular and renal disease is currently viewed as a unified cardiorenal syndrome (CRS. The aim of our study was to assess the CRS prevalence and risk factors associated with left ventricular hypertrophy (LVH in patients with pre-dialysis stages of chronic kidney disease (CKD of various etiology.Materials and Methods. We enrolled 172 patients with CKD to participate in this study. First group consisted of 83 patients with nondiabetic CKD at 2nd through 4th stage (mean age 46±15 years, 51% male and 29% female. Mean glomerular filtration rate (GFR was 37.2 ml/min (33.9–41.4 with 95% CI; creatinine plasma clearance was 2.9 mg/dl (2.6–3.2. Second group consisted of 89 patients with type 2 diabetes mellitus (T2DM and CKD at 1st–2nd stage (40% male and 60% female with albuminuria (mean age 57.3±7.1 years. Duration of diabetes in this sampling was 10.4±7.1 years. All patients underwent standard clinical examination, supplemented with echocardiography to evaluate the influence of general and CKD-related risk factors for LVH.Results. LVH was diagnosed in 37.3% of non-diabetic patients with CKD at 2nd through 4th stage. Aside from classic cardiovascular risk factors (including age, gender, arterial hypertension, family history of cardiovascular diseases, hypercholesterolemia, we observed the impact of kidney-related factors (anemia, plasma creatinine, disturbance of calcium-phosphorus metabolism. CKD progression was associated with elevation in the incidence of concentric and eccentric LVH. Patients with T2DM were diagnosed with LVH in 36% of cases. Increased myocardial mass correlated with plasma levels of uric acid, HbA1c, obesity and albuminuria. There was also a firm association between diabetic nephropathy, left ventricular myocardial remodelling and a history of cardiovascular events.Conclusion: In patients with diabetes mellitus and CKD cardiorenal syndrome develops at pre-dialysis stages due to both

  16. 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

  17. EFFECTS OF DIFFERENT AMOUNTS OF PROTEIN DIETS ON KIDNEY IN DIABETIC RATS

    Institute of Scientific and Technical Information of China (English)

    左静南; 侯积寿; 王根荣; 蒋更如; 熊祖应

    1992-01-01

    Sixty-three streptozotocin-induced diabetic rats were divided into 3 groups fed with different amounts of protein diets 7%, 20% and 40% protein in Group 1, 2 and 3 respectively for 2 months. The ratio of right kidney weight/body weight (RKW/BW), 24h urinary protein excretion (UPE), creatinine clearance (Ccr), mean glomerular diameter (MGD), and colloidal iron staining (CTS) on surface of processes of glomerular podocyte were obsrerved by the end of the experiment. The results showed that RKW/BW and UPE in Group Ⅰreduced as compared with those in Group 2 and 3. The MGD in Group 3 in creased as compared with those in Group 2 and 1. But Ccr in diabetic rats fed with different diets showed no significant difference. Finally, it was found that fusion of the glomerular epithelial cell foot processes and decreased CIS were intensified by increased dietary protein content. The present findings suggest that restriction of protein intake may be able to retard the progression of diabetic nephropathy.

  18. Albuminuria Is Associated with Left Ventricular Hypertrophy in Patients with Early Diabetic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Nan Wu

    2014-01-01

    Full Text Available Aims. Left ventricular hypertrophy (LVH and albuminuria are both markers for cardiovascular diseases (CVDs in patients with type 2 diabetes mellitus (T2DM. We speculate that albuminuria in T2DM patients with early diabetic kidney disease (DKD could predict LVH. Methods. 333 diabetic patients (219 non-DKD and 114 early DKD were enrolled. The association between albuminuria and LVMI was examined using multivariate linear regression and logistic regression. Results. The rate of LVH was significantly higher in patients with early DKD versus those without DKD (57.0% versus 32.9%; P<0.001. Multivariate linear regression analysis demonstrated that albuminuria status (no, micro-, and macroalbuminuria; P<0.001, age (P<0.001, systolic blood pressure (P=0.0578, and the use of ACEI/ARB drug (P<0.001 were independently associated with LVMI. The risks were substantially higher for LVH in the microalbuminuria group (odds ratio 2.473 (95% confidence interval 1.370–4.464 and macroalbuminuria group (odds ratio 3.940 (95% confidence interval 1.553–9.993 compared with that in non-DKD group. Concentric hypertrophy was the most common geometric pattern in patients with early DKD (36.0%, followed by eccentric hypertrophy (21.0%. Conclusions. Albuminuria is associated with higher LVMI and higher rate of LVH in patients with early phase DKD.

  19. Silencing of Histone Deacetylase 9 Expression in Podocytes Attenuates Kidney Injury in Diabetic Nephropathy

    Science.gov (United States)

    Liu, Feng; Zong, Ming; Wen, Xiaofei; Li, Xuezhu; Wang, Jun; Wang, Yi; Jiang, Wei; Li, Xiaojun; Guo, Zhongliang; Qi, Hualin

    2016-01-01

    Podocyte dysfunction is important in the onset and development of diabetic nephropathy (DN). Histone deacetylases (HDACs) have been recently proved to play critical roles in the pathogenesis of DN. As one subtype of the class IIa HDACs, HDAC9 is capable to repress/de-repress their target genes in tumor, inflammation, atherosclerosis and metabolic diseases. In the present study, we investigate whether HDAC9 is involved in the pathophysiologic process of DN, especially the podocyte injury. Firstly, we explored the expression patterns and localization of HDAC9 and found that HDAC9 expression was significantly up-regulated in high glucose (HG)-treated mouse podocytes, as well as kidney tissues from diabetic db/db mice and patients with DN. Secondly, knockdown of HDAC9 in mouse podocytes significantly suppressed HG-induced reactive oxygen species (ROS) generation, cell apoptosis and inflammation through JAK2/STAT3 pathway and reduced the podocytes injury by decreasing the expression levels of Nephrin and Podocin. Moreover, in diabetic db/db mice, silencing of HDAC9 attenuated the glomerulosclerosis, inflammatory cytokine release, podocyte apoptosis and renal injury. Collectively, these data indicate that HDAC9 may be involved in the process of DN, especially podocyte injury. Our study suggest that inhibition of HDAC9 may have a therapeutic potential in DN treatment. PMID:27633396

  20. Could metformin be used in patients with diabetes and advanced chronic kidney disease?

    Science.gov (United States)

    Chowdhury, Tahseen A; Srirathan, Danushan; Abraham, Georgi; Oei, Elizabeth L; Fan, Stanley L; McCafferty, Kieran; Yaqoob, M Magdi

    2017-02-01

    Diabetes is an important cause of end stage renal failure worldwide. As renal impairment progresses, managing hyperglycaemia can prove increasingly challenging, as many medications are contra-indicated in moderate to severe renal impairment. Whilst evidence for tight glycaemic control reducing progression to renal failure in patients with established renal disease is limited, poor glycaemic control is not desirable, and is likely to lead to progressive complications. Metformin is a first-line therapy in patients with Type 2 diabetes, as it appears to be effective in reducing diabetes related end points and mortality in overweight patients. Cessation of metformin in patients with progressive renal disease may not only lead to deterioration in glucose control, but also to loss of protection from cardiovascular disease in a cohort of patients at particularly high risk. We advocate the need for further study to determine the role of metformin in patients with severe renal disease (chronic kidney disease stage 4-5), as well as patients on dialysis, or pre-/peri-renal transplantation. We explore possible roles of metformin in these circumstances, and suggest potential key areas for further study.

  1. New-onset diabetes mellitus after kidney transplantation:Current status and future directions

    Institute of Scientific and Technical Information of China (English)

    Sneha Palepu; G V Ramesh Prasad

    2015-01-01

    A diagnosis of new-onset diabetes after transplantation(NODAT) carries with it a threat to the renal allograft,as well as the same short- and long-term implicationsof type 2 diabetes seen in the general population.NODAT usually occurs early after transplantation, andis usually diagnosed according to general populationguidelines. Non-modifiable risk factors for NODATinclude advancing age, African American, Hispanic, orSouth Asian ethnicity, genetic background, a positive family history for diabetes mellitus, polycystic kidney disease, and previously diagnosed glucose intolerance. Modifiable risk factors for NODAT include obesity and the metabolic syndrome, hepatitis C virus and cytomegalovirus infection, corticosteroids, calcineurin inhibitor drugs (especially tacrolimus), and sirolimus. NODAT affects graft and patient survival, and increases the incidence of post-transplant cardiovascular disease. The incidence and impact of NODAT can be minimized through pre- and post-transplant screening to identify patients at higher risk, including by oral glucose tolerance tests, as well as multi-disciplinary care, lifestyle modification, and the use of modified immunosuppressive regimens coupled with glucose-lowering therapies including oral hypoglycemic agents and insulin. Since NODAT is a major cause of post-transplant morbidity and mortality, measures to reduce its incidence and impact have the potential to greatly improve overall transplant success.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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...... by constant infusion technique using I125-iothalamate and 131I-hippuran. Kidney size was determined by means of ultrasound. GFR, RPF and kidney volume were increased in the diabetic patients compared to the normal controls, 144 versus 113 ml/min X 1.73 m2 (p less than 0.0005), 627 versus 523 ml/min X 1.73 m2...... (p less than 0.0025) and 278 versus 224 ml/1.73 m2 (p less than 0.0005) respectively. Combining results from diabetic patients and controls revealed a positive correlation between kidney size and GFR (r = 0.70, p less than 0.001) and between kidney size and RPF (r = 0.61, p less than 0.001). Within...

  4. African origins and chronic kidney disease susceptibility in the human immunodeficiency virus era.

    Science.gov (United States)

    Kasembeli, Alex N; Duarte, Raquel; Ramsay, Michèle; Naicker, Saraladevi

    2015-05-01

    Chronic kidney disease (CKD) is a major public health problem worldwide with the estimated incidence growing by approximately 6% annually. There are striking ethnic differences in the prevalence of CKD such that, in the United States, African Americans have the highest prevalence of CKD, four times the incidence of end stage renal disease when compared to Americans of European ancestry suggestive of genetic predisposition. Diabetes mellitus, hypertension and human immunodeficiency virus (HIV) infection are the major causes of CKD. HIV-associated nephropathy (HIVAN) is an irreversible form of CKD with considerable morbidity and mortality and is present predominantly in people of African ancestry. The APOL1 G1 and G2 alleles were more strongly associated with the risk for CKD than the previously examined MYH9 E1 risk haplotype in individuals of African ancestry. A strong association was reported in HIVAN, suggesting that 50% of African Americans with two APOL1 risk alleles, if untreated, would develop HIVAN. However these two variants are not enough to cause disease. The prevailing belief is that modifying factors or second hits (including genetic hits) underlie the pathogenesis of kidney disease. This work reviews the history of genetic susceptibility of CKD and outlines current theories regarding the role for APOL1 in CKD in the HIV era.

  5. Insulin Resistance and Chronic Kidney Disease in Patients with Type 1 Diabetes Mellitus

    Science.gov (United States)

    Vladu, Mihaela; Clenciu, Diana; Efrem, Ion Cristian; Amzolini, Anca; Micu, Simona Tudorică; Moţa, Maria

    2017-01-01

    Background and Aims. Diabetes mellitus (DM) is a chronic disease which can evolve towards devastating micro- and macrovascular complications. DM is the most frequent cause of chronic kidney disease (CKD). Insulin resistance plays an important role in the natural history of type 1 diabetes. The purpose of the study was to determine the prevalence of CKD in T1DM and the correlation with insulin resistance (IR) in patients with CKD. Materials and Methods. The study was conducted over a period of three years (2010–2013) and included patients with DM registered in the Clinical Centre of Diabetes, Nutrition and Metabolic Diseases of Dolj county. The study design was an epidemiological, transversal, noninterventional type. Finally, the study group included 200 subjects with type 1 DM. Insulin resistance (IR) was estimated by eGDR. The subjects with eGDR ≤ 7.5 mg/kg/min were considered with insulin resistance. Results. CKD was found in 44% of the patients. Analyzing statistically the presence of CKD, we found highly significant differences between patients with CKD and those without CKD regarding age and sex of the patients, the duration of diabetes, glycosylated hemoglobin (HbA1c), the estimated glucose disposal rate (eGDR), and the presence of hypertension, dyslipidemia, and hyperuricaemia. In patients with CKD, age and diabetes duration are significantly higher than in those who do not have this complication. CKD is more frequent in males than in females (50.9% men versus 34.5% women, p = 0.022). From the elements of metabolic syndrome, high blood pressure, hyperuricemia, and dyslipidemia are significantly increased in diabetic patients with CKD. eGDR value (expressed as mg·kg−1·min−1) is lower in patients with CKD than in those without CKD (15.92 versus 6.42, p CKD show higher insulin resistance than those without CKD. Conclusions. This study has shown that insulin resistance is associated with an increased risk of CKD, but, due to the cross

  6. Insulin Resistance and Chronic Kidney Disease in Patients with Type 1 Diabetes Mellitus.

    Science.gov (United States)

    Vladu, Mihaela; Clenciu, Diana; Efrem, Ion Cristian; Forțofoiu, Mircea-Cătalin; Amzolini, Anca; Micu, Simona Tudorică; Moţa, Maria; Forțofoiu, Maria

    2017-01-01

    Background and Aims. Diabetes mellitus (DM) is a chronic disease which can evolve towards devastating micro- and macrovascular complications. DM is the most frequent cause of chronic kidney disease (CKD). Insulin resistance plays an important role in the natural history of type 1 diabetes. The purpose of the study was to determine the prevalence of CKD in T1DM and the correlation with insulin resistance (IR) in patients with CKD. Materials and Methods. The study was conducted over a period of three years (2010-2013) and included patients with DM registered in the Clinical Centre of Diabetes, Nutrition and Metabolic Diseases of Dolj county. The study design was an epidemiological, transversal, noninterventional type. Finally, the study group included 200 subjects with type 1 DM. Insulin resistance (IR) was estimated by eGDR. The subjects with eGDR ≤ 7.5 mg/kg/min were considered with insulin resistance. Results. CKD was found in 44% of the patients. Analyzing statistically the presence of CKD, we found highly significant differences between patients with CKD and those without CKD regarding age and sex of the patients, the duration of diabetes, glycosylated hemoglobin (HbA1c), the estimated glucose disposal rate (eGDR), and the presence of hypertension, dyslipidemia, and hyperuricaemia. In patients with CKD, age and diabetes duration are significantly higher than in those who do not have this complication. CKD is more frequent in males than in females (50.9% men versus 34.5% women, p = 0.022). From the elements of metabolic syndrome, high blood pressure, hyperuricemia, and dyslipidemia are significantly increased in diabetic patients with CKD. eGDR value (expressed as mg·kg(-1)·min(-1)) is lower in patients with CKD than in those without CKD (15.92 versus 6.42, p insulin resistance than those without CKD. Conclusions. This study has shown that insulin resistance is associated with an increased risk of CKD, but, due to the cross-sectional design, the causal

  7. What African Americans with Diabetes or High Blood Pressure Need to Know: Get Checked for Kidney Disease

    Science.gov (United States)

    ... higher rate of kidney failure than any other group of people. At your next h​ealth care visit, make sure: You learn your GFR and the amount of albumin in your urine . Both should be checked if you have diabetes or high blood pressure. Your blood pressure and blood sugar have been ...

  8. Diabetes mellitus and chronic kidney disease amplify accumulation of tissue advanced glycation end products in patients with peripheral artery disease

    NARCIS (Netherlands)

    Lefrandt, J.D.; De Vos, L.C.; Mulder, D.J.; Dullaart, R.P.F.; Lutgers, H.L.; Lambers Heerspink, H.J.; Smit, A.J.; Kamphuisen, P.W.; Zeebregts, C.J.

    2013-01-01

    Backgrounds and aims: Diabetes mellitus (DM) and chronic kidney disease (CKD) are important risk factors for peripheral artery disease (PAD) and associated with a severely increased cardiovascular (CV) risk in these patients. DM increases production of AGEs and CKD decreases their clearance, while c

  9. Genetic risk factors affecting mitochondrial function are associated with kidney disease in people with Type 1 diabetes

    DEFF Research Database (Denmark)

    Swan, E J; Salem, R M; Sandholm, N

    2015-01-01

    AIM: To evaluate the association with diabetic kidney disease of single nucleotide polymorphisms (SNPs) that may contribute to mitochondrial dysfunction. METHODS: The mitochondrial genome and 1039 nuclear genes that are integral to mitochondrial function were investigated using a case (n = 823 in...

  10. 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:

  11. Diabetes mellitus and chronic kidney disease amplify accumulation of tissue advanced glycation end products in patients with peripheral artery disease

    NARCIS (Netherlands)

    Lefrandt, J.D.; De Vos, L.C.; Mulder, D.J.; Dullaart, R.P.F.; Lutgers, H.L.; Lambers Heerspink, H.J.; Smit, A.J.; Kamphuisen, P.W.; Zeebregts, C.J.

    2013-01-01

    Backgrounds and aims: Diabetes mellitus (DM) and chronic kidney disease (CKD) are important risk factors for peripheral artery disease (PAD) and associated with a severely increased cardiovascular (CV) risk in these patients. DM increases production of AGEs and CKD decreases their clearance, while

  12. 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...

  13. Will the future lie in multitude? A critical appraisal of biomarker panel studies on prediction of diabetic kidney disease progression

    NARCIS (Netherlands)

    Schutte, Elise; Gansevoort, Ron T.; Benner, Jacqueline; Lutgers, Helen L.; Lambers Heerspink, Hiddo J.

    2015-01-01

    Diabetic kidney disease is diagnosed and staged by albuminuria and estimated glomerular filtration rate. Although albuminuria has strong predictive power for renal function decline, there is still variability in the rate of renal disease progression across individuals that are not fully captured by

  14. Finerenone : third-generation mineralocorticoid receptor antagonist for the treatment of heart failure and diabetic kidney disease

    NARCIS (Netherlands)

    Liu, Licette C. Y.; Schutte, Elise; Gansevoort, Ron T.; van der Meer, Peter; Voors, Adriaan A.

    2015-01-01

    Introduction: The mineralocorticoid receptor antagonists (MRAs) spironolactone and eplerenone reduce the risk of hospitalizations and mortality in patients with heart failure (HF) with reduced ejection fraction (HFrEF), and attenuate progression of diabetic kidney disease. However, their use is limi

  15. Metabolomic perfusate analysis during kidney machine perfusion: the pig provides an appropriate model for human studies.

    Directory of Open Access Journals (Sweden)

    Jay Nath

    Full Text Available Hypothermic machine perfusion offers great promise in kidney transplantation and experimental studies are needed to establish the optimal conditions for this to occur. Pig kidneys are considered to be a good model for this purpose and share many properties with human organs. However it is not established whether the metabolism of pig kidneys in such hypothermic hypoxic conditions is comparable to human organs.Standard criteria human (n = 12 and porcine (n = 10 kidneys underwent HMP using the LifePort Kidney Transporter 1.0 (Organ Recovery Systems using KPS-1 solution. Perfusate was sampled at 45 minutes and 4 hours of perfusion and metabolomic analysis performed using 1-D 1H-NMR spectroscopy.There was no inter-species difference in the number of metabolites identified. Of the 30 metabolites analysed, 16 (53.3% were present in comparable concentrations in the pig and human kidney perfusates. The rate of change of concentration for 3-Hydroxybutyrate was greater for human kidneys (p<0.001. For the other 29 metabolites (96.7%, there was no difference in the rate of change of concentration between pig and human samples.Whilst there are some differences between pig and human kidneys during HMP they appear to be metabolically similar and the pig seems to be a valid model for human studies.

  16. Morphological and functional aspects of acute kidney injury after fetal programing in the offspring of diabetic rats.

    Science.gov (United States)

    Pucci, Karla Roberta Martins; Pereira Júnior, Carlos Donizete; Idaló, Priscila Barbosa; Moreira, Ana Carolina Santana Pinheiro; Rocha, Laura Penna; Rodrigues, Aldo Rogélis Aquiles; Reis, Luiz Carlos Dos; Gomes, Roseli A da Silva; Rocha, Lenaldo Branco; Guimarães, Camila Souza de Oliveira; Reis, Marlene Antônia Dos; Câmara, Niels Olsen Saraiva; Corrêa, Rosana Rosa Miranda

    2015-03-01

    To evaluate the effects of folic acid (FA)-induced renal failure in young offspring of diabetic mothers. The offspring of streptozotocin-induced diabetic dams were divided into four groups: CC (controls receiving vehicle); DC (diabetics receiving vehicle); CA (controls receiving FA solution, 250 mg/kg) and DA (diabetics receiving FA solution, 250 mg/kg). Renal function tests and morphometry results were analyzed. An increase in creatinine and urea levels was observed in CA and DA groups at two and five months. FA administration caused a significant reduction in the number of glomeruli in the offspring of diabetic dams. The diabetes group treated with FA had fewer glomeruli compared to controls at two and five months. FA caused an increase in the area of the urinary space both in controls and offspring of diabetic dams at two and five months. The number of glomeruli and area of the urinary space at two months were negatively correlated. Fetal programing promotes remarkable changes in kidney morphology and function in offspring. We suggest that the morphological changes in the kidneys are more pronounced when fetal programing is associated with newly acquired diseases, e.g. renal failure induced by FA.

  17. Simultaneous pancreas-kidney transplantation in a human immunodeficiency virus-positive recipient: a case report.

    Science.gov (United States)

    Genzini, T; Noujaim, H M; Mota, L T; Crescentini, F; Antunes, I; Di Jura, V L; Ferreira, F A Y; Muller, B F; Vetorazzo, J E; de Miranda, M P

    2010-03-01

    After the development of highly active antiretroviral therapy (HAART) for patients with human immunodeficiency virus (HIV), there has been increased interest in organ transplantation for this selected population. There is a lack of reports about pancreas transplant in HIV+ recipients. We report the case of a 43-year-old HIV+ man who presented with type 1 diabetes for 25 years and end-stage-renal disease. He underwent dialysis therapy for the prior 3 years. His CD4 count was 830 cells/mL and a negative viral load was achieved after 3 months of antiretroviral therapy. His nutritional status was favorable; no opportunistic infections had occurred. A simultaneous pancreas-kidney transplantation (SPKT) was performed from a 19-year-old deceased trauma victim. Pancreas implantation was enteric-portal drainage. No induction immunosuppression was used, but rather tacrolimus, sodium mycophenolate, and steroids. In the postoperative period, there was a delayed kidney graft function requiring hemodialysis for 14 days. On postoperative day 11, a kidney biopsy specimen showed mild rejection, which was successfully treated with steroids. The patient was discharged after 22 days; he was normoglycemic and insulin-independent with a serum creatinine value of 1.9 mg/dL. Currently, his outcome has been uneventful, without a readmission or opportunistic infections. After 5 months postoperation, the viral load is negative and the CD4 count is 460 cells/mL. The current serum creatinine level is 1.1 mg/dL; no insulin has been required. HIV has been considered to be an absolute contraindication to organ transplantation, because of the infection risk due to severe immunosuppression, to interactions between antiretroviral and immunosuppressive drugs, and to reluctance to offer an organ to a terminal patient. However, transplants in HIV+ patients have shown good results, when a patient has an acceptable CD4 level, a low viral load, and minimal antiretroviral therapy. Copyright (c) 2010

  18. Genetic Evidence for a Causal Role of Obesity in Diabetic Kidney Disease.

    Science.gov (United States)

    Todd, Jennifer N; Dahlström, Emma H; Salem, Rany M; Sandholm, Niina; Forsblom, Carol; McKnight, Amy J; Maxwell, Alexander P; Brennan, Eoin; Sadlier, Denise; Godson, Catherine; Groop, Per-Henrik; Hirschhorn, Joel N; Florez, Jose C

    2015-12-01

    Obesity has been posited as an independent risk factor for diabetic kidney disease (DKD), but establishing causality from observational data is problematic. We aimed to test whether obesity is causally related to DKD using Mendelian randomization, which exploits the random assortment of genes during meiosis. In 6,049 subjects with type 1 diabetes, we used a weighted genetic risk score (GRS) comprised of 32 validated BMI loci as an instrument to test the relationship of BMI with macroalbuminuria, end-stage renal disease (ESRD), or DKD defined as presence of macroalbuminuria or ESRD. We compared these results with cross-sectional and longitudinal observational associations. Longitudinal analysis demonstrated a U-shaped relationship of BMI with development of macroalbuminuria, ESRD, or DKD over time. Cross-sectional observational analysis showed no association with overall DKD, higher odds of macroalbuminuria (for every 1 kg/m(2) higher BMI, odds ratio [OR] 1.05, 95% CI 1.03-1.07, P < 0.001), and lower odds of ESRD (OR 0.95, 95% CI 0.93-0.97, P < 0.001). Mendelian randomization analysis showed a 1 kg/m(2) higher BMI conferring an increased risk in macroalbuminuria (OR 1.28, 95% CI 1.11-1.45, P = 0.001), ESRD (OR 1.43, 95% CI 1.20-1.72, P < 0.001), and DKD (OR 1.33, 95% CI 1.17-1.51, P < 0.001). Our results provide genetic evidence for a causal link between obesity and DKD in type 1 diabetes. As obesity prevalence rises, this finding predicts an increase in DKD prevalence unless intervention should occur. © 2015 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.

  19. Association between Hemoglobin Concentration and the Progression or Development of Albuminuria in Diabetic Kidney Disease.

    Directory of Open Access Journals (Sweden)

    Hiroshi Okada

    Full Text Available Anemia, which might contribute to pathogenesis of kidney dysfunction, is a common finding in patients with type 2 diabetes. The aim of this study was to investigate if hemoglobin concentration is associated with the degree of change in urinary albumin-creatinine ratio or the development of albuminuria in patients with type 2 diabetes.We measured hemoglobin concentration in 470 (296 men and 174 women consecutive type 2 diabetic patients without albuminuria. We performed a follow-up study to assess the progression or development of albuminuria, the interval of which was 3.0 years. Then we evaluated relationships between hemoglobin concentration and albuminuria, using multivariate linear regression analyses and logistic regression analyses.Eighty four patients developed albuminuria during follow-up duration. In multivariate analyses, hemoglobin concentration was negatively associated with a change in urinary albumin-creatinine ratio in men (ß = -0.259, P = 0.0002 and women (ß = -0.194, P = 0.030. Moreover, multivariate adjusted odds ratio associated with 1 g/L in hemoglobin for the development of albuminuria was 0.93 (95% confidence interval; 0.89-0.96 in men and 0.94 (95% confidence interval; 0.88-0.99 in women, respectively. And, multivariate analyses revealed that adjusted odds ratios for the development of albuminuria were 4.78 (95% confidence interval; 1.65-13.91 in men and 4.62 (95% confidence interval; 1.34-16.68 in women with anemia (hemoglobin < 130 g/L for men and < 120 g/L for women, which were higher than those without anemia.Low hemoglobin concentration could be a predictor for the progression and development of albuminuria in patients with type 2 diabetes.

  20. A new mouse model resembling human diabetic nephropathy: uncoupling of VEGF with eNOS as a novel pathogenic mechanism.

    Science.gov (United States)

    Nakagawa, T

    2009-02-01

    Diabetics develop a variety of histological abnormalities in the kidney. Early features include glomerular hypertrophy, glomerular basement membrane thickening, and mesangial expansion, whereas mesangiolysis, glomerular capillary aneurysm and nodular lesions develop in late phase. The goal of preventing diabetic nephropathy is important, but its achievement has been difficult due in part to a lack of an animal model for human diabetic nephropathy. Most animal models develop mild lesions in early phase diabetes, but not advanced lesions in late phase. Vascular endothelial growth factor (VEGF) mediates diabetic nephropathy, but its precise role remains to be determined. A complexity of VEGF function is that it is protective in nondiabetic renal diseases but is deleterious in diabetic nephropathy. Because diabetes is associated with endothelial dysfunction, we hypothesized that VEGF is deleterious in the setting of endothelial dysfunction. To test this hypothesis, we recently developed a new model of diabetic nephropathy in mice deficient in endothelial nitric oxide synthase (eNOS). Importantly, these mice developed the advanced lesions of diabetic nephropathy resembling to those in human diabetic nephropathy. In addition, these models also exhibit an uncoupling condition of VEGF with NO. In this review, we discuss our hypothesis which is that uncoupling of VEGF with NO causes advanced diabetic nephropathy.

  1. Decrease of FGF receptor (FGFR) and interstitial fibrosis in the kidney of streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Cheng, M F; Chen, L J; Wang, M C; Hsu, C T; Cheng, J T

    2014-01-01

    Fibrosis is the final disorder of end-stage renal disease. Activation of fibroblast growth factor (FGF) 23-klotho axis could suppress renal fibrosis in mice. Also, a marked decrease of klotho expression was observed in the kidney of streptozotocin-induced diabetic rats (STZ rats). However, relation of FGF in renal fibrosis remained unclear. This study was aimed to screen the effect of hyperglycemia on FGF receptor (FGFR) and fibrosis in kidney of rats with diabetic nephropathy and investigate this potential mechanism in cultured Madin-Darby Canine Kidney (MDCK) epithelial cells. STZ rats were used to treat with insulin or phloridzin at the dose sufficient to correct hyperglycemia for understanding the changes of renal dysfunction. The cultured MDCK cells were also used to treat with high glucose, hydrogen peroxide, or tiron in addition to transfection of siRNA to silence the klotho. Both insulin and phloridzin reversed fibrosis and FGFR expressions in kidney of STZ rats. It was confirmed in high glucose-exposed MDCK cells. However, klotho failed to modify the level of FGFR in MDCK cells. Meanwhile, FGFR was restored by tiron in MDCK cells and in diabetic rats without changing blood glucose. In conclusion, interstitial fibrosis and decreased FGFR expression are observed in the kidney of diabetic rats. This change is reversed by tiron without the correction of blood glucose. Also, klotho has no effect on expression of FGFR. Thus, decrease of oxidative stress is useful for the recovery of FGFR expression and improvement of renal fibrosis in type-1 like diabetic rats.

  2. Dietary restriction and exercise for diabetic patients with chronic kidney disease: a systematic review.

    Directory of Open Access Journals (Sweden)

    Liesbeth Van Huffel

    Full Text Available Obesity and sedentary lifestyle are major health problems and key features to develop cardiovascular disease. Data on the effects of lifestyle interventions in diabetics with chronic kidney disease (CKD have been conflicting.Systematic review.Diabetes patients with CKD stage 3 to 5. SEARCH STRATEGY AND SOURCES: Medline, Embase and Central were searched to identify papers.Effect of a negative energy balance on hard outcomes in diabetics with CKD.Death, cardiovascular events, glycaemic control, kidney function, metabolic parameters and body composition.We retained 11 studies. There are insufficient data to evaluate the effect on mortality to promote negative energy balance. None of the studies reported a difference in incidence of Major Adverse Cardiovascular Events. Reduction of energy intake does not alter creatinine clearance but significantly reduces proteinuria (mean difference from -0.66 to -1.77 g/24 h. Interventions with combined exercise and diet resulted in a slower decline of eGFR (-9.2 vs. -20.7 mL/min over two year observation; p<0.001. Aerobic and resistance exercise reduced HbA1c (-0.51 (-0.87 to -0.14; p = 0.007 and -0.38 (-0.72 to -0.22; p = 0.038, respectively. Exercise interventions improve the overall functional status and quality of life in this subgroup. Aerobic exercise reduces BMI (-0.74% (-1.29 to -0.18; p = 0.009 and body weight (-2.2 kg (-3.9 to -0.6; p = 0.008. Resistance exercise reduces trunk fat mass (-0,7±0,1 vs. +0,8 kg ±0,1 kg; p = 0,001-0,005. In none of the studies did the intervention cause an increase in adverse events.All studies used a different intervention type and mixed patient groups.There is insufficient evidence to evaluate the effect of negative energy balance interventions on mortality in diabetic patients with advanced CKD. Overall, these interventions have beneficial effects on glycaemic control, BMI and body composition, functional status and quality of life, and no harmful

  3. 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...... level was less than 9.0 g per deciliter. The primary end points were the composite outcomes of death or a cardiovascular event (nonfatal myocardial infarction, congestive heart failure, stroke, or hospitalization for myocardial ischemia) and of death or end-stage renal disease. RESULTS: Death......, and moderate anemia who were not undergoing dialysis did not reduce the risk of either of the two primary composite outcomes (either death or a cardiovascular event or death or a renal event) and was associated with an increased risk of stroke. For many persons involved in clinical decision making, this risk...

  4. Uric acid as a risk factor for progression of non-diabetic chronic kidney disease? The Mild to Moderate Kidney Disease (MMKD) Study.

    Science.gov (United States)

    Sturm, Gisela; Kollerits, Barbara; Neyer, Ulrich; Ritz, Eberhard; Kronenberg, Florian

    2008-04-01

    The kidney is one of the organs most prominently affected by aging. This can be seen by a loss of renal mass which is caused by a decrease in the number of nephrons resulting in hyperfiltration, hypertrophy and elevations in glomerular pressure. The factors influencing aging of the kidney are not fully elucidated. Epidemiological, experimental and interventional studies resulted in inconsistent results and have not firmly established whether uric acid levels affect progression of Chronic Kidney Disease (CKD). Therefore, we analyzed whether uric acid levels predict the progression of CKD in the Mild to Moderate Kidney Disease Study comprising at baseline 227 Caucasian patients aged 18-65 years with primary non-diabetic CKD of various degrees of renal impairment. Of them, 177 completed a prospective follow-up of 7 years. Primary endpoint was progression of CKD defined as doubling of baseline serum creatinine and/or terminal renal failure. Patients who reached a progression endpoint (n =6 5) were significantly older, had higher baseline serum creatinine and protein excretion rates as well as lower Glomerular Filtration Rate (GFR). Uric acid levels were only higher in patients with progression of disease when patients with uric acid-lowering drugs were excluded from the analysis. Cox regression analysis revealed that increasing uric acid levels predict disease progression only when the analysis was not adjusted for baseline kidney function parameters. As soon as we adjusted the analysis for GFR and proteinuria this association completely vanished. In summary, our prospective 7 year follow-up study in patients with non-diabetic primary CKD did not support uric acid as an independent predictor for CKD progression.

  5. Nodular lesions and mesangiolysis in diabetic nephropathy.

    Science.gov (United States)

    Wada, Takashi; Shimizu, Miho; Yokoyama, Hitoshi; Iwata, Yasunori; Sakai, Yoshio; Kaneko, Shuichi; Furuichi, Kengo

    2013-02-01

    Diabetic nephropathy is a leading cause of end-stage renal failure all over the world. Advanced human diabetic nephropathy is characterized by the presence of specific lesions including nodular lesions, doughnut lesions, and exudative lesions. Thus far, animal models precisely mimicking advanced human diabetic nephropathy, especially nodular lesions, remain to be fully established. Animal models with spontaneous diabetic kidney diseases or with inducible kidney lesions may be useful for investigating the pathogenesis of diabetic nephropathy. Based on pathological features, we previously reported that diabetic glomerular nodular-like lesions were formed during the reconstruction process of mesangiolysis. Recently, we established nodular-like lesions resembling those seen in advanced human diabetic nephropathy through vascular endothelial injury and mesangiolysis by administration of monocrotaline. Here, in this review, we discuss diabetic nodular lesions and its animal models resembling human diabetic kidney lesions, with our hypothesis that endothelial cell injury and mesangiolysis might be required for nodular lesions.

  6. Antioxidant effects of damiana (Turnera diffusa Willd. ex Schult.) in kidney mitochondria from streptozotocin-diabetic rats.

    Science.gov (United States)

    Edgar Romualdo, Esquivel-Gutiérrez; Lilia, Alcaraz-Meléndez; Rafael, Salgado-Garciglia; Alfredo, Saavedra-Molina

    2017-09-26

    The antioxidant effects of water-ethanol extract (WEE) from Turnera diffusa (damiana) in kidney mitochondria from experimental streptozotocin-induced diabetes mellitus (STZ-DM) rats was evaluated. STZ-DM rats were orally treated during three and five weeks. After experimental periods, kidney mitochondria were isolated and malondialdehyde (MDA), nitric oxide (NO•) and protein nitrosylation levels were measured. Also, blood glucose (BG) and body weight (BW) were recorded. Damiana significantly reduced the MDA and NO• levels in kidney mitochondria, although no changes in protein nitrosylation were observed and it did not have the potential to reverse the hyperglycaemia. In conclusion, WEE of T. diffusa have antioxidant properties that may prevent damage induced by mitochondrial oxidative stress in kidneys of STZ-DM rats.

  7. Using analytic morphomics to describe body composition associated with post-kidney transplantation diabetes mellitus.

    Science.gov (United States)

    Cron, David C; Noon, Kelly A; Cote, Devan R; Terjimanian, Michael N; Augustine, Joshua J; Wang, Stewart C; Englesbe, Michael J; Woodside, Kenneth J

    2017-09-01

    Better risk assessment tools are needed to predict post-transplantation diabetes mellitus (PTDM). Using analytic morphomic measurements from computed tomography (CT) scans, we aimed to identify specific measures of body composition associated with PTDM. We retrospectively reviewed 99 non-diabetic kidney transplant recipients who received pre-transplant CT scans at a single institution between 1/2005 and 5/2014. Analytic morphomic techniques were used to measure abdominal adiposity, abdominal size, and psoas muscle area and density, standardized by gender. We measured the associations of these morphomic factors with PTDM. One-year incidence of PTDM was 18%. The morphomic factors significantly associated with PTDM included visceral fat area (OR=1.84 per standard deviation increase, P=.020), body depth (OR=1.79, P=.035), and total body area (OR=1.67, P=.049). Clinical factors significantly associated with PTDM included African American race (OR=3.01, P=.044), hypertension (OR=2.97, P=.041), and dialysis vintage (OR=1.24 per year on dialysis, P=.048). Body mass index was not associated with PTDM (OR=1.05, P=.188). On multivariate modeling, visceral fat area was an independent predictor of PTDM (OR=1.91, P=.035). Analytic morphomics can identify pre-transplant measurements of body composition that are predictive of PTDM in kidney transplant recipients. Pre-transplant imaging contains a wealth of underutilized data that may inform PTDM prevention strategies. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Incidence of Diabetes Mellitus After Kidney Transplantation in Slovakia: Multicentric, Prospective Analysis.

    Science.gov (United States)

    Dedinská, L; Baltesová, T; Beňa, Ĺ; Čellár, M; Galajda, P; Chrastina, M; Jurčina, A; Kováčiková, L; Laca, L; Lacková, E; Lauková Valachová, S; Miklušica, J; Rosenberger, J; Sersenová, M; Skalová, P; Žilinská, Z; Mokáň, M

    2016-12-01

    The incidence rate of post-transplant diabetes mellitus (PTDM) after kidney transplantation (KT) is 5% to 40%. The objective of this analysis was to identify the risk factors of PTDM after KT in the Slovak Republic (SR). In the group of 133 patients/non-diabetics, we identified the risk factors of PTDM in the monitored period of 12 months from transplantation. The incidence of PTDM in the SR in 2014 was 38.3%. By logistic regression, we discovered that the age at the time of KT [odds ratio, 1.0885; 95% CI, 1.0222-1.1592; P = .0082], the value of body mass index (BMI) at the time of KT [odds ratio, 1.4606; 95% CI, 1.0099-2.1125; P = .0442], and the value of insulin resistance index (homeostatic model assessment for insulin resistance) at the time of KT [odds ratio, 2.5183; 95% CI, 1.7119-3.4692; P < .0001] represented predictive factors of PTDM. The independent risk factors of PTDM in our group were age at the time of KT of more than 60 years [HR 0.3871; 95% CI 0.1659-1.7767; P = .0281], waist circumference at the time of KT in men more than 94 cm and in women more than 80 cm [HR, 3.4833; 95% CI, 1.2789-9.4878 (P = .0146)], BMI at the time of KT [HR 3.0011; 95% CI 1.0725-8.3977 (P = .0363)], and triacylglycerols at the time of KT more than 1.7 mmol/L [HR, 2.9763; 95% CI, 1.0141-8.7352; P = .0471]. In the group of Slovak patients after kidney transplantation, the dominating risk factor for PTDM development was insulin resistance prior to KT. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Expression of a dominant negative PKA mutation in the kidney elicits a diabetes insipidus phenotype.

    Science.gov (United States)

    Gilbert, Merle L; Yang, Linghai; Su, Thomas; McKnight, G Stanley

    2015-03-15

    PKA plays a critical role in water excretion through regulation of the production and action of the antidiuretic hormone arginine vasopressin (AVP). The AVP prohormone is produced in the hypothalamus, where its transcription is regulated by cAMP. Once released into the circulation, AVP stimulates antidiuresis through activation of vasopressin 2 receptors in renal principal cells. Vasopressin 2 receptor activation increases cAMP and activates PKA, which, in turn, phosphorylates aquaporin (AQP)2, triggering apical membrane accumulation, increased collecting duct permeability, and water reabsorption. We used single-minded homolog 1 (Sim1)-Cre recombinase-mediated expression of a dominant negative PKA regulatory subunit (RIαB) to disrupt kinase activity in vivo and assess the role of PKA in fluid homeostasis. RIαB expression gave rise to marked polydipsia and polyuria; however, neither hypothalamic Avp mRNA expression nor urinary AVP levels were attenuated, indicating a primary physiological effect on the kidney. RIαB mice displayed a marked deficit in urinary concentrating ability and greatly reduced levels of AQP2 and phospho-AQP2. Dehydration induced Aqp2 mRNA in the kidney of both control and RIαB-expressing mice, but AQP2 protein levels were still reduced in RIαB-expressing mutants, and mice were unable to fully concentrate their urine and conserve water. We conclude that partial PKA inhibition in the kidney leads to posttranslational effects that reduce AQP2 protein levels and interfere with apical membrane localization. These findings demonstrate a distinct physiological role for PKA signaling in both short- and long-term regulation of AQP2 and characterize a novel mouse model of diabetes insipidus.

  10. Risk Factors for the Development and Progression of Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus and Advanced Diabetic Retinopathy.

    Science.gov (United States)

    Yun, Kyung Jin; Kim, Hye Ji; Kim, Mee Kyoung; Kwon, Hyuk Sang; Baek, Ki Hyun; Roh, Young Jung; Song, Ki Ho

    2016-12-01

    Some patients with type 2 diabetes mellitus (T2DM) do not develop diabetic kidney disease (DKD) despite the presence of advanced diabetic retinopathy (DR). We aimed to investigate the presence of DKD and its risk factors in patients with T2DM and advanced DR. We conducted a cross-sectional study in 317 patients with T2DM and advanced DR. The phenotypes of DKD were divided into three groups according to the urine albumin/creatinine ratio (uACR, mg/g) and estimated glomerular filtration rate (eGFR, mL/min/1.73 m²): no DKD (uACR HDL-C) ratio correlated positively with uACR and negatively with eGFR. Multiple linear regression analyses showed that the HbA1c-SD and TG/HDL-C ratio were significantly related with eGFR. Multiple logistic regression analyses after adjusting for several risk factors showed that HbA1c-SD and the TG/HDL-C ratio were significant risk factors for severe DKD. The prevalence of DKD was about 60% in patients with T2DM and advanced DR. HbA1c variability and TG/HDL-C ratio may affect the development and progression of DKD in these patients.

  11. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Werner, H.; Shen-Orr, Z.; Stannard, B.; Burguera, B.; Roberts, C.T. Jr.; LeRoith, D. (National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (USA))

    1990-12-01

    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 kidney 11 beta-hydroxysteroid dehydrogenase: regulation by adrenocorticotropin?

    Science.gov (United States)

    Diederich, S; Quinkler, M; Miller, K; Heilmann, P; Schoneshofer, M; Oelkers, W

    1996-03-01

    In ectopic adrenocorticotropin (ACTH) syndrome (EAS) with higher ACTH levels than in pituitary Cushing's syndrome and during ACTH infusion, the ratio of cortisol to cortisone in plasma and urine is increased, suggesting inhibition of renal 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) by ACTH or by ACTH-dependent steroids. Measuring the conversion of cortisol to cortisone by human kidney slices under different conditions, we tested the possibility of 11 beta-HSD regulation by ACTH and corticosteroids. Slices prepared from unaffected parts of kidneys removed because of renal cell carcinoma were incubated with unlabeled or labeled cortisol, and cortisol and cortisone were quantitated after HPLC separation by UV or radioactive detection. The 11 beta HSD activity was not influenced by incubation with increasing concentrations (10(-12)-10(-9) mol/l) of ACTH (1-24 or 1-39) for 1 h. Among 12 ACTH-dependent steroids tested (10(-9)-10(-6) mol/l), only corticosterone (IC50 = 2 x 10(-7) mol/l), 18-OH-corticosterone and 11 beta-OH-androstenedione showed a significant dose-dependent inhibition of 11 beta-HSD activity. The percentage conversion rate of cortisol to cortisone was concentration dependent over the whole range of cortisol concentrations tested (10(-8) - 10(-5) mol/l. A direct inhibitory effect of ACTH on 11 beta-HSD is, therefore, unlikely. The only steroids inhibiting the conversion of cortisol to cortisone are natural substrates for 11 beta-HSD. Kinetic studies show a saturation of the enzyme at high cortisol concentrations. Thus, the reduced percentage renal cortisol inactivation in EAS seems to be due mainly to overload of the enzyme with endogenous substrates (cortisol, corticosterone and others) rather than to direct inhibition of 11 beta-HSD by ACTH or ACTH-dependent steroids, not being substrates of 11 beta-HSD.

  14. 78 FR 9401 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2013-02-08

    ... Digestive and Kidney Diseases Special Emphasis Panel; R24 Collaborative Interdisciplinary Team Science-3... Digestive and Kidney Diseases Special Emphasis Panel; R24 Collaborative Interdisciplinary Team Science-8... Digestive and Kidney Diseases Special Emphasis Panel; R24 Collaborative Interdisciplinary Team...

  15. Investigating Factors Associated with Depressive Symptoms of Chronic Kidney Diseases in China with Type 2 Diabetes

    Science.gov (United States)

    Wang, Xu; Shen, Biyu; Wang, Xueqin

    2017-01-01

    Aim. To assess the depressive symptoms status of chronic kidney diseases in Nantong, China, with type 2 diabetes and to identify factors associated with depressive symptoms. Methods. In this cross-sectional analytic study, 210 type 2 diabetic patients were recruited from the Second Affiliated Hospital of Nantong University. Depressive symptoms were assessed with the depression subscale of the Hospital Anxiety and Depression Scale (HAD-D). The quality of life was measured with the RAND 36-Item Health Survey (SF-36). And the independent risk factors of depressive symptoms were assessed by using a stepwise forward model of logistic regression analysis. Results. The mean age of the study subjects was 57.66 years (SD: 11.68). Approximately 21.4% of subjects reported depressive symptoms (n = 45). Forward stepwise logistic regression analysis showed that female gender (P = 0.010), hypertension (P = 0.022), Stage IV (P = 0.003), and Stage V (P hypertension are at a marked increased risk of depressive symptoms. Providing optimal care for the psychological health of this population is vital.

  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. Gender differences in the association between HDL cholesterol and the progression of diabetic kidney disease in type 2 diabetic patients.

    Science.gov (United States)

    Hanai, Ko; Babazono, Tetsuya; Yoshida, Naoshi; Nyumura, Izumi; Toya, Kiwako; Hayashi, Toshihide; Bouchi, Ryotaro; Tanaka, Nobue; Ishii, Akiko; Iwamoto, Yasuhiko

    2012-03-01

    The impact of serum lipid abnormalities on the progression of diabetic kidney disease (DKD) remains conflicting. Furthermore, gender differences in the association between dyslipidaemia and outcome of DKD are largely unknown. We therefore conducted this single-centre observational cohort study to clarify gender differences in the association between serum lipid profiles and the progression of DKD. Seven hundred and twenty-three Japanese type 2 diabetes mellitus (T2DM) patients with normoalbuminuria or microalbuminuria, 280 women and 443 men, with a mean (± SD) age of 63 ± 11 years were studied. The endpoint was the progression to a more advanced stage of albuminuria. For statistical analyses, Cox proportional hazard model analyses were conducted. During the mean follow-up period of 4.3 years, 62 of 477 patients with normoalbuminuria and 69 of 246 patients with microalbuminuria reached the endpoint. A significant interaction between high-density lipoprotein (HDL) cholesterol and gender was detected (P(interaction) = 0.04); therefore, separate analyses were conducted for men and women. Overall, in men, the univariate Cox proportional hazard model revealed that higher triglycerides and lower HDL cholesterol levels were significantly associated with higher risk of reaching the endpoint. In the multivariate Cox proportional hazard model, only HDL cholesterol levels remained as an independent predictor of the endpoint (hazard ratio 0.391, P = 0.01). In women, no serum lipid parameters were associated with the endpoint. Lower HDL cholesterol levels seem to be associated with the progression of DKD in men but not in women.

  18. Cytotoxic Effect Of Verapamil On Human Embryonic Kidney Cell Line

    Directory of Open Access Journals (Sweden)

    Jamil L Ahmad

    2015-08-01

    Full Text Available Introduction The link between long term use of verapamil and cancer development has been suggested in literature many years back. However there are numerous controversies surrounding this association with several epidemiological studies in the positive negative and non-association between verapamil and cancer development. Aim To investigate in mechanistic terms the link between chronic use of a calcium channel blocker verapamil and cancer development using human embryonic kidney HEK293 cell line. Method Trypan blue dye exclusion cell counting and 3-amp615314 5-Dimethylthiazol-2-ylamp61533-2 5-diphenyl-tetrazolium bromide MTT assays were used to determine the proliferative as well as cytotoxic effects of verapamil. Results Verapamil had a growth inhibitory rather than proliferative effect on HEK293 cells and the growth inhibition was found to be significant p0.05. Conclusion The long term use of verapamil is associated with cellular growth inhibition and this possibly explained the rationale behind its use as part of combination chemotherapy for some human cancers.

  19. RNA-Seq analysis of glycosylation related gene expression in STZ-induced diabetic rat kidney inner medulla

    Directory of Open Access Journals (Sweden)

    Xiaoqian eQian

    2015-10-01

    Full Text Available The UT-A1 urea transporter is crucial to the kidney’s ability to generate concentrated urine. Native UT-A1 from kidney inner medulla (IM is a heavily glycosylated protein with two glycosylation forms of 97 and 117 kDa. In diabetes, UT-A1 protein abundance, particularly the 117 kD isoform, is significantly increased corresponding to an increased urea permeability in perfused IM collecting ducts, which plays an important role in preventing the osmotic diuresis caused by glucosuria. However, how the glycan carbohydrate structure change and the glycan related enzymes regulate kidney urea transport activity, particularly under diabetic condition, is largely unknown. In this study, using sugar-specific binding lectins, we found that the carbohydrate structure of UT-A1 is changed with increased amounts of sialic acid, fucose, and increased glycan branching under diabetic conditions. These changes were accompanied by altered UT-A1 association with the galectin proteins, α-galactoside glycan binding proteins. To explore the molecular basis of the alterations of glycan structures, the highly sensitive next generation sequencing (NGS technology, Illumina RNA-seq, was employed to analyze genes involved in the process of UT-A1 glycosylation using streptozotocin (STZ - induced diabetic rat kidney. Differential gene expression analysis combining quantitative PCR revealed that expression of a number of important glycosylation related genes were changed under diabetic conditions. These genes include the glycosyltransferase genes Mgat4a, the sialylation enzymes St3gal1 and St3gal4 and glycan binding protein galectin-3, -5, -8 and -9. In contrast, although highly expressed in kidney IM, the glycosyltransferase genes Mgat1, Mgat2, and fucosyltransferase Fut8, did not show any changes. Conclusions: In diabetes, not only is UT-A1 protein abundance increased but the protein’s glycan structure is also significantly changed. UT-A1 protein becomes highly sialylated

  20. Shear wave elastography imaging for assessing the chronic pathologic changes in advanced diabetic kidney disease

    Directory of Open Access Journals (Sweden)

    Hassan K

    2016-11-01

    Full Text Available Kamal Hassan,1,2 Norman Loberant,3 Nur Abbas,4 Hassan Fadi,5 Hassan Shadia,5 Khaled Khazim2 1Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, 2Department of Nephrology and Hypertension, Peritoneal Dialysis Unit – Galilee Medical Center, 3Department of Radiology, Galilee Medical Center, Nahariya, 4The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, 5Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Objective: The assessment of the grade of renal fibrosis in diabetic kidney disease (DKD requires renal biopsy, which may be associated with certain risks. To assess the severity of chronic pathologic changes in DKD, we performed a quantitative analysis of renal parenchymal stiffness in advanced DKD, using shear wave elastography (SWE imaging. Patients and methods: Twenty-nine diabetic patients with chronic kidney disease (CKD grades 3–4 due to DKD, and 23 healthy subjects were enrolled. Combined conventional ultrasound and SWE imaging were performed on all participants. The length, width, and cortical thickness and stiffness were recorded for each kidney. Results: Cortical thickness was lower in patients with DKD than in healthy subjects (13.8±2.2 vs 14.8±1.6 mm; P=0.002 and in DKD patients with CKD grade 4 than in those with grade 3 (13.0±3.5 vs 14.7±2.1 mm; P<0.001. Cortical stiffness was greater in patients with DKD than in healthy subjects (23.72±14.33 vs 9.02±2.42 kPa; P<0.001, in DKD patients with CKD grade 4 than in those with grade 3 (30.4±16.2 vs 14.6±8.1 kPa; P<0.001, and in DKD patients with CKD grade 3b, than in those with CKD grade 3a (15.7±6.7 vs 11.0±4.2 kPa; P=0.03. Daily proteinuria was higher in DKD patients with CKD grade 4 than in those with grade 3 (5.52±0.96 vs 1.13±0.72; P=0.001, and in DKD patients with CKD grade 3b, than in those with CKD grade 3a (1.59±0.59 vs 0.77±0.48; P<0.001. Cortical stiffness was inversely correlated with the

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Acute Kidney Injury in Severe Sepsis and Septic Shock in Patients with and without Diabetes Mellitus: A Multicenter Study.

    Directory of Open Access Journals (Sweden)

    Marion Venot

    Full Text Available Whether diabetes mellitus increases the risk of acute kidney injury (AKI during sepsis is controversial.We used a case-control design to compare the frequency of AKI, use of renal replacement therapy (RRT, and renal recovery in patients who had severe sepsis or septic shock with or without diabetes. The data were from the Outcomerea prospective multicenter database, in which 12 French ICUs enrolled patients admitted between January 1997 and June 2009.First, we compared 451 patients with severe sepsis or septic shock and diabetes to 3,277 controls with severe sepsis or septic shock and without diabetes. Then, we compared 318 cases (with diabetes to 746 matched controls (without diabetes. Diabetic patients did not have a higher frequency of AKI (hazard ratio [HR], 1.18; P = 0.05] or RRT (HR, 1.09; P = 0.6. However, at discharge, diabetic patients with severe sepsis or septic shock who experienced acute kidney injury during the ICU stay and were discharged alive more often required RRT (9.5% vs. 4.8%; P = 0.02, had higher serum creatinine values (134 vs. 103 µmoL/L; P<0.001 and had less often recovered a creatinine level less than 1.25 fold the basal creatinine (41.1% vs. 60.5%; P<0.001.In patients with severe sepsis or septic shock, diabetes is not associated with occurrence of AKI or need for RRT but is an independent risk factor for persistent renal dysfunction in patients who experience AKI during their ICU stay.

  3. 75 FR 65365 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2010-10-22

    ... Kidney Diseases Special Emphasis Panel, Genetics of Nephropathy Ancillary Studies. Date: November 15..., Digestive Diseases and Nutrition Research; 93.849, Kidney Diseases, Urology and Hematology...

  4. MRI-based glomerular morphology and pathology in whole human kidneys.

    Science.gov (United States)

    Beeman, Scott C; Cullen-McEwen, Luise A; Puelles, Victor G; Zhang, Min; Wu, Teresa; Baldelomar, Edwin J; Dowling, John; Charlton, Jennifer R; Forbes, Michael S; Ng, Amanda; Wu, Qi-zhu; Armitage, James A; Egan, Gary F; Bertram, John F; Bennett, Kevin M

    2014-06-01

    Nephron number (N(glom)) and size (V(glom)) are correlated with risk for chronic cardiovascular and kidney disease and may be predictive of renal allograft viability. Unfortunately, there are no techniques to assess N(glom) and V(glom) in intact kidneys. This work demonstrates the use of cationized ferritin (CF) as a magnetic resonance imaging (MRI) contrast agent to measure N(glom) and V(glom) in viable human kidneys donated to science. The kidneys were obtained from patients with varying levels of cardiovascular and renal disease. CF was intravenously injected into three viable human kidneys. A fourth control kidney was perfused with saline. After fixation, immunofluorescence and electron microscopy confirmed binding of CF to the glomerulus. The intact kidneys were imaged with three-dimensional MRI and CF-labeled glomeruli appeared as punctate spots. Custom software identified, counted, and measured the apparent volumes of CF-labeled glomeruli, with an ~6% false positive rate. These measurements were comparable to stereological estimates. The MRI-based technique yielded a novel whole kidney distribution of glomerular volumes. Histopathology demonstrated that the distribution of CF-labeled glomeruli may be predictive of glomerular and vascular disease. Variations in CF distribution were quantified using image texture analyses, which be a useful marker of glomerular sclerosis. This is the first report of direct measurement of glomerular number and volume in intact human kidneys.

  5. Dyslipoproteinemia and impairment of renal function in diabetic kidney disease: an analysis of animal studies, observational studies, and clinical trials.

    Science.gov (United States)

    Hung, Chi-Chih; Tsai, Jer-Chia; Kuo, Hung-Tien; Chang, Jer-Ming; Hwang, Shang-Jyh; Chen, Hung-Chun

    2013-01-01

    Dyslipoproteinemia is highly prevalent in diabetes, chronic kidney disease, and diabetic kidney disease (DKD). Both diabetes and chronic kidney disease (CKD) are associated with hypertriglyceridemia, lower high-density lipoprotein, and higher small, dense low-density lipoprotein. A number of observational studies have reported that dyslipidemia may be associated with albuminuria, renal function impairment, and end-stage renal disease (ESRD) in the general population, and especially in CKD and DKD patients. Diabetic glomerulopathy and the related albuminuria are the main manifestations of DKD. Numerous animal studies support the finding that glomerular atherosclerosis is the main mechanism of glomerulosclerosis in CKD and DKD. Some randomized, controlled trials suggest the use of statins for the prevention of albuminuria and renal function impairment in CKD and DKD patients. However, a large clinical study, the Study of Heart and Renal Protection (SHARP), does not support that statins could reduce ESRD in CKD. In this article, we analyze the complex association of dyslipoproteinemia with DKD and deduce its relevance from animal studies, observational studies, and clinical trials. We show that special subgroups could benefit from the statin treatment.

  6. Predictive significance of kidney myeloid-related protein 8 expression in patients with obesity- or type 2 diabetes-associated kidney diseases.

    Directory of Open Access Journals (Sweden)

    Takashige Kuwabara

    Full Text Available BACKGROUND AND OBJECTIVE: We have reported that toll-like receptor 4 (TLR4 and one of its endogenous ligands, myeloid-related protein 8 (MRP8 or S100A8, play an important role in the progression of diabetic nephropathy in mice. The aim of this study was to evaluate significance of kidney MRP8 expression in patients with obesity- or type 2 diabetes-associated kidney diseases. METHODS: In diabetic, obese or control subjects, MRP8 mRNA and protein expression levels in renal biopsy samples were determined by real-time RT-PCR and immunohistochemistry (n = 28 and 65, respectively, and their associations with baseline and prognostic parameters were analyzed. Effects of MRP8 upon pro-inflammatory gene expressions were examined using macrophages. RESULTS: Kidney MRP8 gene and protein expression levels were elevated in obese or diabetic groups compared to control group. Among all subjects, by univariate linear regression analysis, glomerular MRP8-positive cell count and tubulointerstitial MRP8-positive area at baseline were both, respectively, correlated not only with various known risk factors for diabetic nephropathy (such as systolic blood pressure, proteinuria and serum creatinine but also with extent of glomerulosclerosis and tubulointerstitial fibrosis. Independent factors predicting urinary protein levels a year later were examined by multivariate analysis, and they included glomerular MRP8-positive cell count (β = 0.59, P<0.001, proteinuria (β = 0.37, P = 0.002 and systolic blood pressure (β = 0.21, P = 0.04 at baseline, after adjustment for known risk factors. MRP8 protein expression was observed in CD68-positive macrophages and atrophic tubules. In cultured mouse macrophages, MRP8 protein induced proinflammatory cytokine expressions and also triggered auto-induction of MRP8 in a TLR4-dependent manner. CONCLUSIONS: Glomerular MRP8 expression appears to be associated with progression of proteinuria in obese or type 2

  7. Carboxy-terminal modulator protein attenuated extracellular matrix deposit by inhibiting phospho-Akt, TGF-β1 and α-SMA in kidneys of diabetic mice.

    Science.gov (United States)

    Chen, Ning; Hao, Jun; Li, Lisha; Li, Fan; Liu, Shuxia; Duan, Huijun

    2016-06-10

    Glomerulosclerosis and tubular interstitial extracellular matrix deposit and fibrosis are the main features of diabetic nephropathy, which are mediated by activation of PI3K/Akt signal pathway. Carboxy-terminal modulator protein (CTMP) is known as a negative regulator of PI3K/Akt pathway. Whether CTMP regulates renal extracellular matrix metabolism of diabetic nephropathy is still not known. Here, renal decreased CTMP, enhanced phospho-Akt (Ser 473), TGF-β1, α-SMA and extracellular matrix deposit are found in diabetic mice. Furthermore, high glucose decreases CTMP expression accompanied by enhanced phospho-Akt (Ser 473), TGF-β1 and α-SMA in cultured human renal proximal tubular epithelial cells (HKC), which are effectively prevented by transfection of pYr-ads-4-musCTMP vector. Moreover, delivery of pYr-ads-4-musCTMP vector into kidneys via tail vein of diabetic mice increases CTMP expression by 8.84 times followed by 60.00%, 76.50% and 24.37% decreases of phospho-Akt (Ser 473), TGF-β1 and α-SMA compared with diabetic mice receiving pYr-adshuttle-4 vector. Again, increased renal extracellular matrix accumulation of diabetic mice is also inhibited with delivery of pYr-ads-4-musCTMP vector. Our results indicate that CTMP attenuates renal extracellular matrix deposit by regulating the phosphorylation of Akt, TGF-β1 and α-SMA expression in diabetic mice. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Human genetics of diabetic vascular complications

    Indian Academy of Sciences (India)

    Zi-Hui Tang; Zhou Fang; Linuo Zhou

    2013-12-01

    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 important roles in the development of DVC. Genetic linkage studies have uncovered a number of genetic loci that may shape the risk of DVC. Genetic association studies have identified many common genetic variants for susceptibility to DVC. Structural variants such as copy number variation and interactions of gene × environment have also been detected by association analysis. Apart from the nuclear genome, mitochondrial DNA plays a critical role in regulation of development of DVC. Epigenetic studies have indicated epigenetic changes in chromatin affecting gene transcription in response to environmental stimuli, which provided a large body of evidence of regulating development of diabetes mellitus. Recently, a new window has opened on identifying rare and common genetic loci through next generation sequencing technologies. This review focusses on the current knowledge of the genetic and epigenetic basis of DVC. Ultimately, identification of genes or genetic loci, structural variants and epigenetic changes contributing to risk of or protection from DVC will help uncover the complex mechanism(s) underlying DVC, with crucial implications for the development of personalized medicine for diabetes mellitus and its complications.

  9. Telmisartan Ameliorates Fibrocystic Liver Disease in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease

    Science.gov (United States)

    Yoshihara, Daisuke; Kugita, Masanori; Sasaki, Mai; Horie, Shigeo; Nakanishi, Koichi; Abe, Takaaki; Aukema, Harold M.; Yamaguchi, Tamio; Nagao, Shizuko

    2013-01-01

    Human autosomal recessive polycystic kidney disease (ARPKD) produces kidneys which are massively enlarged due to multiple cysts, hypertension, and congenital hepatic fibrosis characterized by dilated bile ducts and portal hypertension. The PCK rat is an orthologous model of human ARPKD with numerous fluid-filled cysts caused by stimulated cellular proliferation in the renal tubules and hepatic bile duct epithelia, with interstitial fibrosis developed in the liver. We previously reported that a peroxisome proliferator activated receptor (PPAR)-γ full agonist ameliorated kidney and liver disease in PCK rats. Telmisartan is an angiotensin receptor blocker (ARB) used widely as an antihypertensive drug and shows partial PPAR-γ agonist activity. It also has nephroprotective activity in diabetes and renal injury and prevents the effects of drug-induced hepatotoxicity and hepatic fibrosis. In the present study, we determined whether telmisartan ameliorates progression of polycystic kidney and fibrocystic liver disease in PCK rats. Five male and 5 female PCK and normal control (+/+) rats were orally administered 3 mg/kg telmisartan or vehicle every day from 4 to 20 weeks of age. Treatment with telmisartan decreased blood pressure in both PCK and +/+ rats. Blood levels of aspartate amino transferase, alanine amino transferase and urea nitrogen were unaffected by telmisartan treatment. There was no effect on kidney disease progression, but liver weight relative to body weight, liver cystic area, hepatic fibrosis index, expression levels of Ki67 and TGF-β, and the number of Ki67- and TGF-β-positive interstitial cells in the liver were significantly decreased in telmisartan-treated PCK rats. Therefore, telmisartan ameliorates congenital hepatic fibrosis in ARPKD, possibly through the inhibition of signaling cascades responsible for cellular proliferation and interstitial fibrosis in PCK rats. The present results support the potential therapeutic use of ARBs for the

  10. Arterial flow regulator enables transplantation and growth of human fetal kidneys in rats.

    Science.gov (United States)

    Chang, N K; Gu, J; Gu, S; Osorio, R W; Concepcion, W; Gu, E

    2015-06-01

    Here we introduce a novel method of transplanting human fetal kidneys into adult rats. To overcome the technical challenges of fetal-to-adult organ transplantation, we devised an arterial flow regulator (AFR), consisting of a volume adjustable saline-filled cuff, which enables low-pressure human fetal kidneys to be transplanted into high-pressure adult rat hosts. By incrementally withdrawing saline from the AFR over time, blood flow entering the human fetal kidney was gradually increased until full blood flow was restored 30 days after transplantation. Human fetal kidneys were shown to dramatically increase in size and function. Moreover, rats which had all native renal mass removed 30 days after successful transplantation of the human fetal kidney were shown to have a mean survival time of 122 days compared to 3 days for control rats that underwent bilateral nephrectomy without a prior human fetal kidney transplant. These in vivo human fetal kidney models may serve as powerful platforms for drug testing and discovery.

  11. 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)

    Y V Khasanova

    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.

  12. Precision-cut human kidney slices as a model to elucidate the process of renal fibrosis

    NARCIS (Netherlands)

    Stribos, Elisabeth G D; Luangmonkong, Theerut; Leliveld, Anna M.; de Jong, Igle J; van Son, Willem J; Hillebrands, Jan-Luuk; Seelen, Marc A.; van Goor, Harry; Olinga, Peter; Mutsaers, Henricus A M

    Chronic kidney disease is a major health concern, and experimental models bridging the gap between animal studies and clinical research are currently lacking. Here, we evaluated precision-cut kidney slices (PCKSs) as a potential model for renal disease. PCKSs were prepared from human cortical tissue

  13. Characterization of Sitagliptin Use in Patients with Type 2 Diabetes and Chronic Kidney Disease by Cross-Sectional Analysis of a Medical Insurance Claims Database

    National Research Council Canada - National Science Library

    Brodovicz, Kimberly G; Chen, Yong; Liu, Zhiwen; Ritchey, Mary E; Liao, Jane; Engel, Samuel S

    2015-01-01

    Chronic kidney disease (CKD) is common in patients with type 2 diabetes (T2DM) and makes them particularly susceptible to safety/tolerability issues related to many classes of oral antihyperglycemic agents (OAHA...

  14. Rationale and Trial Design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes : The Occurrence of Renal Events (BEACON)

    NARCIS (Netherlands)

    de Zeeuw, Dick; Akizawa, Tadao; Agarwal, Rajiv; Audhya, Paul; Bakrise, George L.; Chin, Melanie; Krauth, Melissa; Heerspink, Hiddo J. Lambers; Meyer, Colin J.; McMurray, John J.; Parving, Hans-Henrik; Pergola, Pablo E.; Remuzzi, Giuseppe; Toto, Robert D.; Vaziri, Nosratola D.; Wanner, Christoph; Warnock, David G.; Wittes, Janet; Chertow, Glenn M.

    2013-01-01

    Background: 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

  15. 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

    National Research Council Canada - National Science Library

    Atageldiyeva, Kuralay; Fujita, Yukihiro; Yanagimachi, Tsuyoshi; Mizumoto, Katsutoshi; Takeda, Yasutaka; Honjo, Jun; Takiyama, Yumi; Abiko, Atsuko; Makino, Yuichi; Haneda, Masakazu

    2016-01-01

    ... 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...

  16. Diabetes mellitus increases the prevalence of anemia in patients with chronic kidney disease: A nested case-control study

    Science.gov (United States)

    Loutradis, Charalampos; Skodra, Alexandra; Georgianos, Panagiotis; Tolika, Panagiota; Alexandrou, Dimitris; Avdelidou, Afroditi; Sarafidis, Pantelis A

    2016-01-01

    AIM: To compare anemia prevalence between matched chronic kidney disease (CKD) patients with and without diabetes mellitus (DM) and to assess factors associated with anemia development. METHODS: This is a nested case-control study of 184 type-2 diabetic and 184 non-diabetic CKD patients from a prospectively assembled database of a Nephrology outpatient clinic, matched for gender, age and estimated glomerular filtration rate (eGFR). Prevalence of anemia (hemoglobin: Men: recombinant erythropoietin) was examined in comparison, in the total population and by CKD Stage. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with anemia. RESULTS: The total prevalence of anemia was higher in diabetics (47.8% vs 33.2%, P = 0.004). Accordingly, prevalence was higher in diabetics in CKD Stage 3 (53.5% vs 33.1%, P < 0.001) and particularly in Stage 3a (60.4% vs 26.4%, P < 0.001), whereas it was non-significantly higher in Stage 4 (61.3% vs 48.4%; P = 0.307). Serum ferritin was higher in diabetics in total and in CKD stages, while serum iron was similar between groups. In multivariate analyses, DM (OR = 2.206, 95%CI: 1.196-4.069), CKD Stages 3a, 3b, 4 (Stage 4: OR = 12.169, 95%CI: 3.783-39.147) and serum iron (OR = 0.976, 95%CI: 0.968-0.985 per mg/dL increase) were independently associated with anemia. CONCLUSION: Prevalence of anemia progressively increases with advancing stages of CKD and is higher in diabetic than matched non-diabetic CKD patients and diabetes is independently associated with anemia occurrence. Detection and treatment of anemia in diabetic CKD patients should be performed earlier than non-diabetic counterparts. PMID:27458564

  17. Baseline characteristics in the Bardoxolone methyl EvAluation in patients with Chronic kidney disease and type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Lambers Heerspink, Hiddo J; Chertow, Glenn M; Akizawa, Tadao

    2013-01-01

    Type 2 diabetes mellitus (T2DM) is the most important contributing cause of end-stage renal disease (ESRD) worldwide. Bardoxolone methyl, a nuclear factor-erythroid-2-related factor 2 activator, augments estimated glomerular filtration. The Bardoxolone methyl EvAluation in patients with Chronic k...... kidney disease and type 2 diabetes mellitus: the Occurrence of renal eveNts (BEACON) trial was designed to establish whether bardoxolone methyl slows or prevents progression to ESRD. Herein, we describe baseline characteristics of the BEACON population....

  18. Acute kidney injury after ingestion of rhubarb: secondary oxalate nephropathy in a patient with type 1 diabetes

    Directory of Open Access Journals (Sweden)

    Albersmeyer Marc

    2012-10-01

    Full Text Available Abstract Background Oxalosis is a metabolic disorder characterized by deposition of oxalate crystals in various organs including the kidney. Whereas primary forms result from genetic defects in oxalate metabolism, secondary forms of oxalosis can result from excessive intestinal oxalate absorption or increased endogenous production, e.g. after intoxication with ethylene glycol. Case presentation Here, we describe a case of acute crystal-induced renal failure associated with excessive ingestion of rhubarb in a type 1 diabetic with previously normal excretory renal function. Renal biopsy revealed mild mesangial sclerosis, but prominent tubular deposition of oxalate crystals in the kidney. Oxalate serum levels were increased. Conclusion Acute secondary oxalate nephropathy due to excessive dietary intake of oxalate may lead to acute renal failure in patients with preexisting renal disease like mild diabetic nephropathy. Attention should be payed to special food behaviors when reasons for acute renal failure are explored.

  19. Altered retinoic acid metabolism in diabetic mouse kidney identified by O isotopic labeling and 2D mass spectrometry.

    Directory of Open Access Journals (Sweden)

    Jonathan M Starkey

    Full Text Available Numerous metabolic pathways have been implicated in diabetes-induced renal injury, yet few studies have utilized unbiased systems biology approaches for mapping the interconnectivity of diabetes-dysregulated proteins that are involved. We utilized a global, quantitative, differential proteomic approach to identify a novel retinoic acid hub in renal cortical protein networks dysregulated by type 2 diabetes.Total proteins were extracted from renal cortex of control and db/db mice at 20 weeks of age (after 12 weeks of hyperglycemia in the diabetic mice. Following trypsinization, (18O- and (16O-labeled control and diabetic peptides, respectively, were pooled and separated by two dimensional liquid chromatography (strong cation exchange creating 60 fractions further separated by nano-HPLC, followed by peptide identification and quantification using mass spectrometry. Proteomic analysis identified 53 proteins with fold change >or=1.5 and pdiabetic renal cortical proteome. Western blotting and real-time PCR confirmed diabetes-induced upregulation of RALDH1, which was localized by immunofluorescence predominantly to the proximal tubule in the diabetic renal cortex, while PCR confirmed the downregulation of ADH identified with mass spectrometry. Despite increased renal cortical tissue levels of retinol and RALDH1 in db/db versus control mice, all-trans-retinoic acid was significantly decreased in association with a significant decrease in PPARbeta/delta mRNA.Our results indicate that retinoic acid metabolism is significantly dysregulated in diabetic kidneys, and suggest that a shift in all-trans-retinoic acid metabolism is a novel feature in type 2 diabetic renal disease. Our

  20. 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....

  1. Sodium Glucose Co-transporter Type 2 (SGLT2) Inhibitors: Targeting the Kidney to Improve Glycemic Control in Diabetes Mellitus

    OpenAIRE

    Bays, Harold

    2013-01-01

    Although hyperglycemia is a key therapeutic focus in the management of patients with type 2 diabetes mellitus (T2DM), many patients experience sub-optimal glycemic control. Current glucose-lowering agents involve the targeting of various body organs. Sodium glucose co-transporter type 2 (SGLT2) inhibitors target the kidney, reduce renal glucose reabsorption, and increase urinary glucose elimination, thus lowering glucose blood levels. This review examines some of the key efficacy and safety d...

  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. 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Rodwell, Graham E J; Sonu, Rebecca; Zahn, Jacob M; Lund, James; Wilhelmy, Julie; Wang, Lingli; Xiao, Wenzhong; Mindrinos, Michael; Crane, Emily; Segal, Eran; Myers, Bryan D; Brooks, James D; Davis, Ronald W; Higgins, John; Owen, Art B; Kim, Stuart K

    2004-12-01

    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.

  6. 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.

  7. Treatment of type 2 diabetes mellitus in patients with chronic kidney disease. Grupo de Trabajo para el Documento de Consenso sobre el tratamiento de la diabetes tipo 2 en el paciente con enfermedad renal crónica

    National Research Council Canada - National Science Library

    Gómez-Huelgas, Ricardo; Martínez-Castelao, Alberto; Artola, Sara; Górriz, José Luis; Menéndez, Edelmiro

    2014-01-01

    Chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) are highly prevalent chronic diseases, which represent an important public health problem and require a multidisciplinary management...

  8. Toxicity study of reclaimed water on human embryonic kidney cells.

    Science.gov (United States)

    Ren, Xianghao; Kou, Ying-Ying; Kim, Taeeung; Chae, Kyu-Jung; Ng, How Yong

    2017-08-28

    The importance of evaluating the toxic effects associated with the use of reclaimed water has been increasing. The purpose of this research was to investigate the cytotoxicity and molecular toxicity of reclaimed water on the human embryonic kidney 293 (HEK293) cells. The culture medium was synthesized using the reclaimed water samples. Wastewater treatment plant influent (WTI) and effluent (WTE), containing micropollutants at the nanogram per liter level, decreased cell proliferation (93.4-98.9% and 91.5-96.6% of the control, respectively) and increased cell damage (103.6-117.5% and 100.7-109% of the control, respectively) at all exposure times, except for a decrease in cell damage observed after an 8-h exposure to WTE. Membrane bioreactor permeate (MBRP) increased cell proliferation (102.1-106.7% of the control) and decreased cell damage at 8 and 12 h (92.4 and 98.4% of the control, respectively), but slightly increased cell damage at 24 h and later time points (101.1-104.9% of the control). All three water samples induced cell apoptosis (120.9-123.4% of the control). They also affected the expression of cell-cycle regulatory proteins (p16(INK4a), p27(Kip1), cyclin-dependent kinases 2 and 4, cyclin D1, and cyclin E) and apoptosis-related regulatory proteins (p-JNK, Bcl-2, caspase-9, and caspase-3). In conclusion, all three water samples showed cytotoxicity and molecular toxicity in the HEK293 cells, and the results of the cell-cycle and apoptosis regulatory protein expression after WTI and WTE treatments were consistent with the results of the cytotoxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease

    Science.gov (United States)

    Yale, J-F; Bakris, G; Cariou, B; Yue, D; David-Neto, E; Xi, L; Figueroa, K; Wajs, E; Usiskin, K; Meininger, G

    2013-01-01

    Aims Canagliflozin is a sodium glucose co-transporter 2 inhibitor in development for treatment of type 2 diabetes mellitus (T2DM). This study evaluated the efficacy and safety of canagliflozin in subjects with T2DM and stage 3 chronic kidney disease [CKD; estimated glomerular filtration rate (eGFR) ≥30 and canagliflozin 100 or 300 mg or placebo daily. The primary efficacy endpoint was change from baseline in HbA1c at week 26. Prespecified secondary endpoints were change in fasting plasma glucose (FPG) and proportion of subjects reaching HbA1c canagliflozin 100 and 300 mg reduced HbA1c from baseline compared with placebo at week 26 (–0.33, –0.44 and –0.03%; p canagliflozin 100 and 300 mg versus placebo (27.3, 32.6 and 17.2%). Overall AE rates were similar for canagliflozin 100 and 300 mg and placebo (78.9, 74.2 and 74.4%). Slightly higher rates of urinary tract infections and AEs related to osmotic diuresis and reduced intravascular volume were observed with canagliflozin 300 mg compared with other groups. Transient changes in renal function parameters that trended towards baseline over 26 weeks were observed with canagliflozin. Conclusion Canagliflozin improved glycaemic control and was generally well tolerated in subjects with T2DM and Stage 3 CKD. PMID:23464594

  10. Protective effects of keishibukuryogan on the kidney of spontaneously diabetic WBN/Kob rats.

    Science.gov (United States)

    Nakagawa, Takako; Goto, Hirozo; Hikiami, Hiroaki; Yokozawa, Takako; Shibahara, Naotoshi; Shimada, Yutaka

    2007-03-21

    Keishibukuryogan, one of the traditional herbal formulations, is used clinically to improve blood circulation. It consists of the following five crude drugs: Cinnamomi Cortex, Poria, Moutan Cortex, Persicae Semen and Paeoniae Radix. In this study, the effects of keishibukuryogan against renal damage in spontaneously diabetic WBN/Kob rats were examined. Oral administration of keishibukuryogan significantly attenuated urinary protein excretion and serum creatinine levels. It did not affect body weight loss and blood glucose levels, but it suppressed renal and hepatic weights of WBN/Kob rats. Keishibukuryogan also reduced fibronectin and transforming growth factor beta(1) (TGF-beta(1)) protein expression in the renal cortex. Furthermore, lipid peroxidation levels in both kidney and liver were significantly lower than those of untreated control WBN/Kob rats. Urinary excretion of 8-hydroxy-deoxyguanosine was suppressed by keishibukuryogan treatment. These results suggest that keishibukuryogan reduces oxidative stress by hyperglycemia, and that it protects renal function and suppresses fibronectin deposition induced by TGF-beta(1) production in WBN/Kob rats.

  11. Wound Chronicity, Inpatient Care, and Chronic Kidney Disease Predispose to MRSA Infection in Diabetic Foot Ulcers

    Science.gov (United States)

    Yates, Christopher; May, Kerry; Hale, Thomas; Allard, Bernard; Rowlings, Naomi; Freeman, Amy; Harrison, Jessica; McCann, Jane; Wraight, Paul

    2009-01-01

    OBJECTIVE To determine the microbiological profile of diabetes-related foot infections (DRFIs) and the impact of wound duration, inpatient treatment, and chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS Postdebridement microbiological samples were collected from individuals presenting with DRFIs from 1 January 2005 to 31 December 2007. RESULTS A total of 653 specimens were collected from 379 individuals with 36% identifying only one isolate. Of the total isolates, 77% were gram-positive bacteria (staphylococci 43%, streptococci 13%). Methicillin-resistant Staphylococcus aureus (MRSA) was isolated from 23%; risk factors for MRSA included prolonged wound duration (odds ratio 2.31), inpatient management (2.19), and CKD (OR 1.49). Gram-negative infections were more prevalent with inpatient management (P = 0.002) and prolonged wound duration (P < 0.001). Pseudomonal isolates were more common in chronic wounds (P < 0.001). CONCLUSIONS DRFIs are predominantly due to gram-positive aerobes but are usually polymicrobial and increase in complexity with inpatient care and ulcer duration. In the presence of prolonged duration, inpatient management, or CKD, empiric MRSA antibiotic cover should be considered. PMID:19587371

  12. Chronic Kidney Disease Is Positively and Diabetes Mellitus Is Negatively Associated with Abdominal Aortic Aneurysm

    Science.gov (United States)

    Uchida, Haruhito A.; Kakio, Yuki; Umebayashi, Ryoko; Okuyama, Yuka; Fujii, Yasuhiro; Ozawa, Susumu; Yoshida, Masashi; Oshima, Yu; Sano, Shunji; Wada, Jun

    2016-01-01

    Background and Aims Chronic kidney disease (CKD) and diabetes mellitus (DM) are considered as risk factors for cardiovascular diseases. The purpose of this study was to clarify the relationship of CKD and DM with the presence of abdominal aortic aneurysm (AAA). Methods We enrolled 261 patients with AAA (AAA+) and age-and-sex matched 261 patients without AAA (AAA-) at two hospitals between 2008 and 2014, and examined the association between the risk factors and the presence of AAA. Furthermore, in order to investigate the prevalence of AAA in each group, we enrolled 1126 patients with CKD and 400 patients with DM. Results The presence of CKD in patients with AAA+ was significantly higher than that in patients with AAA- (AAA+; 65%, AAA-; 52%, P = 0.004). The presence of DM in patients with AAA+ was significantly lower than that in patients with AAA- (AAA+; 17%, AAA-; 35%, P < 0.001). A multivariate logistic regression analysis demonstrated that hypertension, ischemic heart disease and CKD were independent determinants, whereas, DM was a negatively independent determinant, for the presence of AAA. The prevalence of AAA in patients with CKD 65 years old and above was 5.1%, whereas, that in patients with DM 65 years old and above was only 0.6%. Conclusion CKD is a positively associated with the presence of AAA. In contrast, DM is a negatively associated with the presence of AAA in Japanese population. PMID:27764090

  13. Regulation of podocalyxin expression in the kidney of streptozotocin-induced diabetic rats with Chinese herbs (Yishen capsule).

    Science.gov (United States)

    Fang, Jingai; Wei, Hongkun; Sun, Yanyan; Zhang, Xiaodong; Liu, Wenyuan; Chang, Qintao; Wang, Ruihua; Gong, Yuewen

    2013-04-05

    Diabetic nephropathy is an emergent issue in China with increase in patients with type II diabetes. There are several successful Chinese herbal products for the treatment of patients with diabetic nephropathy in China. However, the mechanisms mediating the biological activity of these products are still unclear. Podocalyxin is a sialoprotein critical to maintaining integrity of filtration function of glomerulus. By employing streptozotocin-induced diabetic rats and a Chinese herb formulation (Yishen capsule), we examined the regulation of podocalyxin expression in the kidney by Yishen capsule through immunofluorescent staining and reverse transcriptase polymerase chain reaction. After injection of STZ, there were significant increase in both blood glucose and urinary protein. Serum creatinine and BUN were also increased in rats with injection of STZ. Moreover, expression of podocalyxin in the glomerulus was gradually reduced after injection of STZ. There was also a loss of podocyte foot processes in the glomerular basement membrane. However, Yishen capsule or benazepril was able to restore the expression of podocalyxin and podocyte foot processes in the kidney. Although Yishen capsule could reduce urinary protein level, it has little effect on blood glucose level in the rats injected with STZ. Yishen capsule could attenuate the loss of podocalyxin in the glomerulus of rats injected with STZ.

  14. 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.

  15. Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Kidney Injury Molecule 1 (KIM1) in patients with diabetic nephropathy: a cross-sectional study and the effects of lisinopril

    DEFF Research Database (Denmark)

    Nielsen, S E; Schjoedt, K J; Astrup, A S

    2010-01-01

    Our aim was to evaluate the markers of tubulointerstitial damage, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule1 (KIM1) in Type 1 diabetic patients with different levels of albuminuria and in control subjects. In addition, the effect of renoprotective treatment...... on urinary NGAL was evaluated in diabetic nephropathy....

  16. Predictors of Health-Related Quality of Life in Patients with Co-Morbid Diabetes and Chronic Kidney Disease

    Science.gov (United States)

    Lo, Clement; Ranasinha, Sanjeeva; Gallagher, Martin; Fulcher, Gregory; Kerr, Peter G.; Russell, Grant; Teede, Helena; Usherwood, Tim; Walker, Rowan; Zoungas, Sophia

    2016-01-01

    Background People living with diabetes and chronic kidney disease (CKD) experience compromised quality of life. Consequently, it is critical to identify and understand factors influencing their health-related quality of life (HRQoL). This study examined factors associated with HRQoL among patients with diabetes and CKD. Methods A cross sectional study among adults with comorbid diabetes and CKD (eGFR <60 mL/min/1.73m2) recruited from renal and diabetes clinics of four large tertiary referral hospitals in Australia was performed. Each participant completed the Kidney Disease Quality of Life (KDQoL ™ -36) questionnaire, which is comprised of two composite measures of physical and mental health and 3 kidney disease specific subscales with possible scores ranging from 0 to 100 with higher values indicating better HRQoL. Demographic and clinical data were also collected. Regression analyses were performed to determine the relationship between HRQoL and potential predictor factors. Results A total of 308 patients were studied with a mean age of 66.9 (SD = 11.0) years and 70% were males. Mean scores for the physical composite summary, mental composite summary, symptom/problem list, effects of kidney disease and burden of kidney disease scales were 35.2, 47.0, 73.8, 72.5 and 59.8 respectively. Younger age was associated with lower scores in all subscales except for the physical composite summary. Female gender, obese or normal weight rather than overweight, and smoking were all associated with lower scores in one or more subscales. Scores were progressively lower with more advanced stage of CKD (p<0.05) in all subscales except for the mental composite summary. Conclusion In patients with diabetes and CKD, younger age was associated with lower scores in all HRQoL subscales except the physical composite summary and female gender, obese or normal weight and more advanced stages of CKD were associated with lower scores in one or more subscales. Identifying these factors will

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 76 FR 14672 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2011-03-17

    ... Kidney Diseases Special Emphasis Panel; PAR09-247 Ancillary Clinical Studies: Nephropathy and Urinary..., Endocrinology and Metabolic Research; 93.848, Digestive Diseases and Nutrition Research; 93.849, Kidney...

  19. VARIATIONS OF MIDDLE SEGMENTAL ARTERY OF HUMAN KIDNEY AND CLINICAL SIGNIFICANCE

    Directory of Open Access Journals (Sweden)

    Gyan Prakash Mishra

    2015-12-01

    Full Text Available Aim: To assess the arterial pattern of middle segmental artery and its relation with collecting system in the human kidneys. Materials and Methods: We studied 50 fresh human Kidneys by corrosion cast techniques. We used different colour coded moulding granules of butyl butyrate, red for artery, blue for vein and black for collecting system of the human kidneys. 20% solution of butyl butyrate in acetone was injected into renal vessels and ureter of each kidney. Injected kidneys were kept immersed in concentrated Potassium Hydroxide solution for corrosion to obtain the endocasts. These endocasts were cleaned under the running tap water and observed macroscopically. Results: We observed three types of variations in arterial pattern of middle segmental artery namely Middle Segmental Artery Type-1 (MSAT1, Middle Segmental Artery Type-2 (MSAT2, Middle Segmental Artery Type-3 (MSAT3 and they were seen in 29(58%, 14(28%, 6(12% kidneys respectively. We also observed three different variations in relation between middle segmental artery and collecting system namely Middle Segmental Artery Group-1 (MSAG1, Middle Segmental Artery Group-2 (MSAG2, Middle Segmental Artery Group-3 (MSAG3 and they were seen in 32%, 24%, 42% kidneys respectively. Conclusion: Anatomical knowledge of these variations is of valuable contribution for uro-surgeon in performing more and more conservative renal surgeries which lead to preservation of healthy and functional renal parenchyma and prevent intraoperative and post-operative complications.

  20. Blockade of the formation of insoluble ubiquitinated protein aggregates by EGCG3"Me in the alloxan-induced diabetic kidney.

    Directory of Open Access Journals (Sweden)

    Shuxian Cai

    Full Text Available BACKGROUND: Renal accumulation of reactive carbonyl compounds (RCCs has been linked to the progression of diabetic nephropathy. We previously demonstrated that carbonyl stress induces the formation of amino-carbonyl cross-links and sharply increases the content of β-sheet-rich structures, which is the seed of insoluble aggregates formation, and tea catechin (--epigallocatechin 3-gallate (EGCG can reverse this process in vitro and in vivo. In this study, methylated derivative (--epigallocatechin-3-O-(3-O-methyl-gallate (EGCG3"Me was hypothesized to neutralize carbonyl stress mediating the formation of insoluble ubiquitinated protein (IUP aggregates, and reduce the early development of diabetic nephropathy. METHODS AND RESULTS: Diabetes was induced in mice by intraperitoneally injecting alloxan monohydrate (200 mg/kg/d twice and administering EGCG3"Me by gavage for 15 d. Reagent case and western blot results showed that, in diabetic kidneys, the carbonyl proteins in the serum increased; and in insoluble protein fraction, 4-hydroxynonenal-modified proteins, IUP aggregates and p62 accumulated; FT-IR study demonstrated that the lipid content, anti-parallel β-sheet structure and aggregates increased. EGCG3"Me treatment could effectively reverse this process, even better than the negative control treatment. CONCLUSIONS: EGCG3"Me exhibiting anti-β-sheet-rich IUP aggregate properties, maybe represents a new strategy to impede the progression of diabetic nephropathy and other diabetic complications.

  1. Pesticides and human diabetes: a link worth exploring?

    Science.gov (United States)

    Swaminathan, K

    2013-11-01

    It is no exaggeration to claim that the 'diabetes epidemic' has become a 'runaway train' causing huge health and economic consequences, especially in the developing nations. Traditionally, the risk factors for diabetes have largely focused on genetics and lifestyle. Great emphasis is placed on lifestyle measures and finding novel pharmacological treatment options to combat diabetes, but there is increasing evidence linking environmental pollutants, especially pesticides, to the development of insulin resistance and Type 2 diabetes. Pesticide use has increased dramatically worldwide and the effects of pesticides on glucose metabolism are too significant for a possible diabetogenic link to be dismissed. The aim of this review article was to assess the links between pesticides and human diabetes with the goal of stimulating further research in this area. © 2013 The Author. Diabetic Medicine © 2013 Diabetes UK.

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

    Science.gov (United States)

    Kretzler, Matthias; Keller, Benjamin J.; 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.

    2015-01-01

    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. PMID:26305897

  3. 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.

  4. 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.

  5. Plasma concentrations of extracellular matrix protein fibulin-1 are related to cardiovascular risk markers in chronic kidney disease and diabetes

    Directory of Open Access Journals (Sweden)

    Scholze Alexandra

    2013-01-01

    Full Text Available Abstract Background Fibulin-1 is one of a few extracellular matrix proteins present in blood in high concentrations. We aimed to define the relationship between plasma fibulin-1 levels and risk markers of cardiovascular disease. Methods Plasma fibulin-1 was determined in subjects with chronic kidney disease (n = 32; median age 62.5, inter-quartile range 51 – 73 years and 60 age-matched control subjects. Among kidney disease patients serological biomarkers related to cardiovascular disease (fibrinogen, interleukin 6, C-reactive protein were measured. Arterial applanation tonometry was used to determine central hemodynamic and arterial stiffness indices. Results We observed a positive correlation of fibulin-1 levels with age (r = 0.38; p = 0.033, glycated hemoglobin (r = 0.80; p = 0.003, creatinine (r = 0.35; p = 0.045, and fibrinogen (r = 0.39; p = 0.027. Glomerular filtration rate and fibulin-1 were inversely correlated (r = −0.57; p = 0.022. There was a positive correlation between fibulin-1 and central pulse pressure (r = 0.44; p = 0.011 and central augmentation pressure (r = 0.55; p = 0.001. In a multivariable regression model, diabetes, creatinine, fibrinogen and central augmentation pressure were independent predictors of plasma fibulin-1. Conclusion Increased plasma fibulin-1 levels were associated with diabetes and impaired kidney function. Furthermore, fibulin-1 levels were associated with hemodynamic cardiovascular risk markers. Fibulin-1 is a candidate in the pathogenesis of cardiovascular disease observed in chronic kidney disease and diabetes.

  6. Oral Administration of N-Acetyl-seryl-aspartyl-lysyl-proline Ameliorates Kidney Disease in Both Type 1 and Type 2 Diabetic Mice via a Therapeutic Regimen.

    Science.gov (United States)

    Nitta, Kyoko; Shi, Sen; Nagai, Takako; Kanasaki, Megumi; Kitada, Munehiro; Srivastava, Swayam Prakash; Haneda, Masakazu; Kanasaki, Keizo; Koya, Daisuke

    2016-01-01

    Kidney fibrosis is the final common pathway of progressive kidney diseases including diabetic nephropathy. Here, we report that the endogenous antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), the substrate of angiotensin-converting enzyme (ACE), is an orally available peptide drug used to cure kidney fibrosis in diabetic mice. We utilized two mouse models of diabetic nephropathy, streptozotocin- (STZ-) induced type 1 diabetic CD-1 mice and type 2 diabetic nephropathy model db/db mice. Intervention with the ACE inhibitor imidapril, oral AcSDKP, or imidapril + oral AcSDKP combination therapy increased urine AcSDKP levels. AcSDKP levels were significantly higher in the combination group compared to those of the other groups. AcSDKP oral administration, either AcSDKP alone or in addition to imidapril, ameliorated glomerulosclerosis and tubulointerstitial fibrosis. Plasma cystatin C levels were higher in both models, at euthanasia, and were restored by all the treatment groups. The levels of antifibrotic miRs, such as miR-29 or let-7, were suppressed in the kidneys of both models; all treatments, especially the combination of imidapril + oral AcSDKP, restored the antifibrotic miR levels to a normal value or even higher. AcSDKP may be an oral antifibrotic peptide drug that would be relevant to combating fibroproliferative kidney diseases such as diabetic nephropathy.

  7. Pilot Study: Association of Traditional and Genetic Risk Factors and New-Onset Diabetes Mellitus Following Kidney Transplantation

    Science.gov (United States)

    Chakkera, H.A.; Hanson, R.L.; Raza, S.M.; DiStefano, J.K.; Millis, M.P.; Heilman, R.L.; Mulligan, D.C.; Reddy, K.S.; Mazur, M.J.; Hamawi, K.; Moss, A.A.; Mekeel, K.L.; Cerhan, J.R.

    2012-01-01

    Introduction New-onset diabetes mellitus, which occurs after kidney transplant and type 2 diabetes mellitus (T2DM), shares common risk factors and antecedents in impaired insulin secretion and action. Several genetic polymorphisms have been shown to be associated with T2DM. We hypothesized that transplant recipients who carry risk alleles for T2DM are “tipped over” to develop diabetes mellitus in the posttransplant milieu. Methods We investigated the association of genetic and traditional risk factors present before transplantation and the development of new-onset diabetes mellitus after kidney transplantation (NODAT). Markers in 8 known T2DM-linked genes were genotyped using either the iPLEX assay or allelic discrimination (AD)-PCR in the study cohort testing for association with NODAT. We used univariate and multivariate logistic regression models for the association of pretransplant nongenetic and genetic variables with the development of NODAT. Results The study cohort included 91 kidney transplant recipients with at least 1 year posttransplant follow-up, including 22 who developed NODAT. We observed that increased age, family history of T2DM, pretransplant obesity, and triglyceridemia were associated with NODAT development. In addition, we observed positive trends, although statistically not significant, for association between T2DM-associated genes and NODAT. Conclusions These findings demonstrated an increased NODAT risk among patient with a positive family history for T2DM, which, in conjunction with the observed positive predictive trends of known T2DM-associated genetic polymorphisms with NODAT, was suggestive of a genetic predisposition to NODAT. PMID:20005362

  8. Human kidney proximal tubule-on-a-chip for drug transport and nephrotoxicity assessment.

    Science.gov (United States)

    Jang, Kyung-Jin; Mehr, Ali Poyan; Hamilton, Geraldine A; McPartlin, Lori A; Chung, Seyoon; Suh, Kahp-Yang; Ingber, Donald E

    2013-09-01

    Kidney toxicity is one of the most frequent adverse events reported during drug development. The lack of accurate predictive cell culture models and the unreliability of animal studies have created a need for better approaches to recapitulate kidney function in vitro. Here, we describe a microfluidic device lined by living human kidney epithelial cells exposed to fluidic flow that mimics key functions of the human kidney proximal tubule. Primary kidney epithelial cells isolated from human proximal tubule are cultured on the upper surface of an extracellular matrix-coated, porous, polyester membrane that splits the main channel of the device into two adjacent channels, thereby creating an apical 'luminal' channel and a basal 'interstitial' space. Exposure of the epithelial monolayer to an apical fluid shear stress (0.2 dyne cm(-2)) that mimics that found in living kidney tubules results in enhanced epithelial cell polarization and primary cilia formation compared to traditional Transwell culture systems. The cells also exhibited significantly greater albumin transport, glucose reabsorption, and brush border alkaline phosphatase activity. Importantly, cisplatin toxicity and Pgp efflux transporter activity measured on-chip more closely mimic the in vivo responses than results obtained with cells maintained under conventional culture conditions. While past studies have analyzed kidney tubular cells cultured under flow conditions in vitro, this is the first report of a toxicity study using primary human kidney proximal tubular epithelial cells in a microfluidic 'organ-on-a-chip' microdevice. The in vivo-like pathophysiology observed in this system suggests that it might serve as a useful tool for evaluating human-relevant renal toxicity in preclinical safety studies.

  9. Integrating traditional Chinese medicine healthcare into diabetes care by reducing the risk of developing kidney failure among type 2 diabetic patients: a population-based case control study.

    Science.gov (United States)

    Hsu, Pei-Chien; Tsai, Yueh-Ting; Lai, Jung-Nien; Wu, Chien-Tung; Lin, Shun-Ku; Huang, Chung-Yu

    2014-10-28

    Our previous study indicated that the traditional Chinese medicine (TCM) formula Liu-Wei-Di-Huang-Wan, which consists of six type of herbs, namely Rehmannia glutinosa (Gaertn.) DC., root, dried; Cornus officinalis Siebold & Zucc., fructus, dried; Dioscorea oppositifolia L., root, dried; Alisma plantago-aquatica subsp. orientale (Sam.) Sam., tuber, dried; Paeonia × suffruticosa Andrews, bark, dried; Poria cocos (Fr.) Wolf., sclerotium, dried, is the most frequently prescribed herbal formula used to treat type 2 diabetes patients. The aim of the study was to evaluate the integration of TCM into diabetes care in terms of how it reduces the risk of developing kidney failure. The Taiwan׳s National Health Insurance Research Database (NHIRD) provided detailed information of health care services for each patient and covers 98% of all Taiwan residents as of 2007. Case and control subjects were selected from the NHIRD. Two multivariable logistic regression models were constructed in order to explore two types of exposure assessments including prescription of TCMs (model 1) and prescription of different estimated dosages of Liu-Wei-Di-Huang-Wan (model 2). Using logistic regression model 1, having used TCMs was independently associated with a decreased risk of kidney failure by multivariable analysis (OR=0.69, 95% CI: 0.61-0.77). Using logistic regression model 2, there was no difference between non-Liu-Wei-Di-Huang-Wan TCM users and Liu-Wei-Di-Huang-Wan TCM users in terms of the risk of developing kidney failure. Furthermore, there was also no linear dose-response trend when we used exposure to prescribed Liu-Wei-Di-Huang-Wan as a continuous variable (for non-Liu-Wei-Di-Huang-Wan TCM users, OR=0.68, 95% CI: 0.60-0.77; for TCM users consuming 1-30 g of Liu-Wei-Di-Huang-Wan, OR=0.69, 95% CI: 0.54-0.87; for >30 g of Liu-Wei-Di-Huang-Wan, OR=0.84, 95% CI: 0.49-1.44). Integrating TCM healthcare into diabetes care was found to be associated with a decreased risk of developing

  10. Protocol for a pilot randomised controlled trial of metformin in pre-diabetes after kidney transplantation: the Transplantation and Diabetes (Transdiab) study.

    Science.gov (United States)

    Alnasrallah, Basil; Pilmore, Helen; Manley, Paul

    2017-08-23

    Post-transplant diabetes mellitus (PTDM) is a common complication of kidney transplantation and is associated with significant morbidity and mortality. In the general population, metformin has been used for diabetes prevention in high-risk individuals. Improving insulin sensitivity is one of many proven favourable effects of metformin. Despite the high incidence of PTDM in kidney transplant recipients, there is a lack of evidence for the role of metformin in the prevention of diabetes in this setting. METHODS AND ANALYSIS: Transplantation and Diabetes (Transdiab) is a single-centre, unblinded, pilot randomised controlled trial assessing the feasibility, tolerability and efficacy of metformin after renal transplantation in patients with impaired glucose tolerance (IGT). Participants will undergo an oral glucose tolerance test in the 4-12 weeks post-transplantation; those with IGT will be randomised to standard care or standard care and metformin 500 mg twice daily, and followed up for 12 months. The primary outcomes of the study will be the feasibility of recruitment, the tolerability of metformin assessed using the Gastrointestinal Symptom Rating Scale at 3 and 12 months, and the efficacy of metformin assessed by morning glucose and glycated haemoglobin at 3, 6, 9 and 12 months. Despite the significant morbidity and mortality of PTDM, there are currently no randomised clinical trials assessing pharmacological interventions for its prevention after kidney transplantation. The Transdiab trial will thus provide important data on the feasibility, safety, tolerability and efficacy of metformin after renal transplantation in patients with IGT; this will facilitate undertaking larger multicentre trials of interventions to reduce the incidence or severity of diabetes after kidney transplantation. This study has been approved by the Northern B Health and Disability Ethics Committee of the Ministry of Health in New Zealand. On study completion, results are expected to be

  11. 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

  12. Influence of glycemic excursion on urinary albumin excretion and inflammatory factor in early diabetes kidney disease patients

    Institute of Scientific and Technical Information of China (English)

    Xuan Cao; Ding-Ping Yang

    2016-01-01

    Objective:To research the influence of glycemic excursion on the level of urinary albumin excretion and inflammatory factor in early diabetes kidney disease patients.Methods:From January to December in 2015, 96 confirmed cases of early diabetes kidney disease were collected. Continuous Glucose Monito Ring System CGMS, produced by American MiniMed Inc) was used to monitor 72 h blood glucose. The influence of MAGE on the level of urinary albumin excretion, IGF-1, FKN, IL-6, TNF-α, hs-CRP and inflammatory indexes was compared.Results:Compared cases of stable blood sugar (MAGE<5.0 mmol/L) with unstable ones (MAGE≥5.0 mmol/L), the difference of UAER and 1,5-AG had statistical significance, while HbA1c and FA had no significant difference. Pearson correlation analysis between MAGE and UAER resulted in strong correlation. And also the front inflammatory factor including IGF-1, FKN, IL-6, TNF-α, hs-CRP all showed lower level than the cases of MAGE≥5.0 mmol/L.Conclusion:Glycemic excursion may accelerate development of kidney injury through inflammatory factors.

  13. Developmental morphology of the human fetus kidney : Observation by light and electron microscope

    OpenAIRE

    1998-01-01

    The author observed the human fetus kidney at the fetal age of 3 weeks, 5 weeks and 6 month in utero by means of light and electron microscope in order to add some new findings to the already known knowledge. Especially, the metanephros, metanephric blastema, nephrogenic zone of the cortex and blood-urine barrier which consists of glomerulus, capillary vessel, basement membrane, podocyte and mesangium cells are observed and then physiological significance of the kidney are also discussed. On ...

  14. Studies of melatonin effects on epithelia using the human embryonic kidney-293 (HEK-293) cell line

    OpenAIRE

    Chan, CWY; Y. Song; Ailenberg, M; Wheeler, M.; Pang, SF; Brown, GM; Silverman, M.

    1997-01-01

    The expression of melatonin receptors (MR) of the Mel(1a) subtype in basolateral membrane of guinea pig kidney proximal tubule suggests that melatonin plays a role in regulating epithelial functions. To investigate the cellular basis of melatonin action on epithelia, we sought to establish an appropriate in vitro culture model. Epithelial cell lines originating from kidneys of dog (MDCK), pig (LLC-PK1), opossum (OK), and human embryo (HEK- 293) were each tested for the presence of MR using 2-...

  15. Role of vitamin D in diabetes mellitus and chronic kidney disease

    Institute of Scientific and Technical Information of China (English)

    Akio; Nakashima; Keitaro; Yokoyama; Takashi; Yokoo; Mitsuyoshi; Urashima

    2016-01-01

    Approximately 30%-50% of people are recognized to have low levels of vitamin D,and insufficiency and deficiency of vitamin D are recognized as global health problems worldwide.Although the presence of hypovitamin D increases the risk of rickets and fractures,low vitamin D levels are also associated with hypertension,cancer,and cardiovascular disease.In addition,diabetes mellitus(DM) and chronic kidney disease(CKD) are also related to vitamin D levels.Vitamin D deficiency has been linked to onset and progression of DM.Although in patients with DM the relationship between vitamin D and insulin secretion,insulin resistance,and β-cell dysfunction are pointed out,evidence regarding vitamin D levels and DM is contradictory,and well controlled studies are needed.In addition,vitamin D influences the renin-angiotensin system,inflammation,and mineral bone disease,which may be associated with the cause and progression CKD.There is increasing evidence that vitamin D deficiency may be a risk factor for DM and CKD;however,it remains uncertain whether vitamin D deficiency also predisposes to death from DM and CKD.Although at this time,supplementation with vitamin D has not been shown to improve glycemic control or prevent incident DM,clinical trials with sufficient sample size,study periods,and optimal doses of vitamin D supplementation are still needed.This review focuses on the mechanism of vitamin D insufficiency and deficiency in DM or CKD,and discusses the current evidence regarding supplementation with vitamin D in patients with these diseases.

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

    Energy Technology Data Exchange (ETDEWEB)

    Waer, M.; Vanrenterghem, Y.; Roels, L.; Ang, K.K.; Bouillon, R.; Lerut, T.; Gruwez, J.; van der Schueren, E.; Vandeputte, M.; Michielsen, P.

    1987-03-01

    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.

  17. Comparative Efficacy and Safety of Antihypertensive Agents for Adult Diabetic Patients with Microalbuminuric Kidney Disease: A Network Meta-Analysis.

    Science.gov (United States)

    Huang, Rongzhong; Feng, Yuxing; Wang, Ying; Qin, Xiaoxia; Melgiri, Narayan Dhruvaraj; Sun, Yang; Li, Xingsheng

    2017-01-01

    Antihypertensive treatment mitigates the progression of chronic kidney disease. Here, we comparatively assessed the effects of antihypertensive agents in normotensive and hypertensive diabetic patients with microalbuminuric kidney disease. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were systematically searched for randomized controlled trials (RCTs) comparing oral antihypertensive agents in adult diabetic patients with microalbuminuria. The primary efficacy outcome was reduction in albuminuria, and the primary safety outcomes were dry cough, presyncope, and edema. Random-effects pairwise and Bayesian network meta-analyses were performed to produce outcome estimates for all RCTs, only hypertensive RCTs, or only normotensive RCTs. Surface under the cumulative ranking (SUCRA) probability rankings were calculated for all outcomes. Sensitivity analyses on type 2 diabetes status, age, or follow-up duration were also performed. A total of 38 RCTs were included in the meta-analyses. The angiotensin-converting enzyme inhibitor-calcium channel blocker (ACEI-CCB) combination therapy of captopril+diltiazem was most efficacious in reducing albuminuria irrespective of blood pressure status. However, the ACEI-angiotensin receptor blocker (ACEI-ARB) combination therapy of trandolapril+candesartan was the most efficacious in reducing albuminuria for normotensive patients, while the ACEI-CCB combination therapy of fosinopril+amlodipine was the most efficacious in reducing albuminuria for hypertensive patients. The foregoing combination therapies displayed inferior safety profiles relative to ACEI monotherapy with respect to dry cough, presyncope, and edema. With respect to type 2 diabetic patients with microalbuminuria, the Chinese herbal medicine Tangshen formula followed by the ACEI ramipril were the most efficacious in reducing albuminuria. Trandolapril+candesartan appears to be the most efficacious intervention for reducing albuminuria for

  18. Comparative Efficacy and Safety of Antihypertensive Agents for Adult Diabetic Patients with Microalbuminuric Kidney Disease: A Network Meta-Analysis

    Science.gov (United States)

    Huang, Rongzhong; Feng, Yuxing; Wang, Ying; Qin, Xiaoxia; Melgiri, Narayan Dhruvaraj; Sun, Yang; Li, Xingsheng

    2017-01-01

    Background Antihypertensive treatment mitigates the progression of chronic kidney disease. Here, we comparatively assessed the effects of antihypertensive agents in normotensive and hypertensive diabetic patients with microalbuminuric kidney disease. Methods MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were systematically searched for randomized controlled trials (RCTs) comparing oral antihypertensive agents in adult diabetic patients with microalbuminuria. The primary efficacy outcome was reduction in albuminuria, and the primary safety outcomes were dry cough, presyncope, and edema. Random-effects pairwise and Bayesian network meta-analyses were performed to produce outcome estimates for all RCTs, only hypertensive RCTs, or only normotensive RCTs. Surface under the cumulative ranking (SUCRA) probability rankings were calculated for all outcomes. Sensitivity analyses on type 2 diabetes status, age, or follow-up duration were also performed. Results A total of 38 RCTs were included in the meta-analyses. The angiotensin-converting enzyme inhibitor-calcium channel blocker (ACEI-CCB) combination therapy of captopril+diltiazem was most efficacious in reducing albuminuria irrespective of blood pressure status. However, the ACEI-angiotensin receptor blocker (ACEI-ARB) combination therapy of trandolapril+candesartan was the most efficacious in reducing albuminuria for normotensive patients, while the ACEI-CCB combination therapy of fosinopril+amlodipine was the most efficacious in reducing albuminuria for hypertensive patients. The foregoing combination therapies displayed inferior safety profiles relative to ACEI monotherapy with respect to dry cough, presyncope, and edema. With respect to type 2 diabetic patients with microalbuminuria, the Chinese herbal medicine Tangshen formula followed by the ACEI ramipril were the most efficacious in reducing albuminuria. Conclusions Trandolapril+candesartan appears to be the most efficacious intervention

  19. Effects of ethanol extract of propolis on histopathological changes and anti-oxidant defense of kidney in a rat model for type 1 diabetes mellitus.

    Science.gov (United States)

    Sameni, Hamid Reza; Ramhormozi, Parisa; Bandegi, Ahmad Reza; Taherian, Abbas Ali; Mirmohammadkhani, Majid; Safari, Manouchehr

    2016-07-01

    Oxidative stress has a key role in the pathogenesis of diabetes. Propolis and its constituents have a wide range of medicinal properties against oxidative stress. In the present study, we evaluated the anti-oxidant effects of ethanolic extracts of propolis on kidneys in diabetes mellitus rats. A total of 40 male Wistar rats were randomly divided into the following five groups: control, diabetes mellitus, diabetes mellitus with vehicle treatment, diabetes mellitus with propolis treatment (100 mg/kg) and diabetes mellitus with propolis treatment (200 mg/kg). Diabetes mellitus in rats was induced by intraperitoneal injection of streptozotocin (60 mg/kg). Diabetic groups were treated with vehicle or ethanolic extracts of Iranian propolis for 6 weeks. Serum concentration of malondialdehyde, superoxide dismutase and glutathione peroxidase were measured. The results showed that Iranian propolis significantly inhibited bodyweight loss in diabetes mellitus rats. The propolis extracts significantly reduced serum glucose levels and kidney weight in diabetes mellitus rats (P propolis extracts significantly reduced the malondialdehyde content, and increased the activity of superoxide dismutase and glutathione peroxidase (P propolis extract significantly reduced the glomerular basement membrane thickness and glomerular area. The present study results showed that the Iranian propolis extract could enhance the anti-oxidant levels and histopathological changes in the kidneys of rats. The final results showed that most of the favorable effects of propolis are mediated by a reduction of blood glucose levels in diabetic animals. © 2015 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  20. Will the future lie in multitude? A critical appraisal of biomarker panel studies on prediction of diabetic kidney disease progression.

    Science.gov (United States)

    Schutte, Elise; Gansevoort, Ron T; Benner, Jacqueline; Lutgers, Helen L; Lambers Heerspink, Hiddo J

    2015-08-01

    Diabetic kidney disease is diagnosed and staged by albuminuria and estimated glomerular filtration rate. Although albuminuria has strong predictive power for renal function decline, there is still variability in the rate of renal disease progression across individuals that are not fully captured by the level of albuminuria. Therefore, research focuses on discovering and validating additional biomarkers that improve risk stratification for future renal function decline and end-stage renal disease in patients with diabetes, on top of established biomarkers. Most studies address the value of single biomarkers to predict progressive renal disease and aim to understand the mechanisms that underlie accelerated renal function decline. Since diabetic kidney disease is a disease encompassing several pathophysiological processes, a combination of biomarkers may be more likely to improve risk prediction than a single biomarker. In this review, we provide an overview of studies on the use of multiple biomarkers and biomarker panels, appraise their study design, discuss methodological pitfalls and make recommendations for future biomarker panel studies.

  1. Lipoprotein(a) predicts a new onset of chronic kidney disease in people with Type 2 diabetes mellitus.

    Science.gov (United States)

    Yun, J-S; Ahn, Y-B; Song, K-H; Yoo, K-D; Park, Y-M; Kim, H-W; Ko, S-H

    2016-05-01

    We investigated the association between lipoprotein(a) [Lp(a)] level and new-onset chronic kidney disease (CKD) in patients with Type 2 diabetes. We conducted a prospective cohort study from March 2003 to December 2004 with a median follow-up time of 10.1 years. Patients aged 25-75 years with Type 2 diabetes and without CKD [estimated glomerular filtration rate (eGFR) ≥ 90 ml/min/1.73 m(2) ) were consecutively enrolled. The eGFR was measured at least twice every year , and new-onset CKD was defined as a decreased eGFR status of diabetes were 53.3 ± 9.6 and 7.5 ± 6.0 years, respectively. The baseline eGFR was 101.8 ± 11.3 ml/min/1.73 m(2) . After adjusting for multiple confounding factors, a Cox hazard regression analysis revealed that the third tertile of Lp(a) was significantly associated with the development of CKD during the observation period when compared with the first tertile [hazard ratio 2.12 (95% confidence interval 1.33-3.36); P = 0.001). In this prospective, longitudinal, observational cohort study, we demonstrated that the Lp(a) level was an independent prognostic factor for the future development of CKD in patients with Type 2 diabetes. © 2015 Diabetes UK.

  2. Inhibition of kidney proximal tubular glucose reabsorption does not prevent against diabetic nephropathy in type 1 diabetic eNOS knockout mice.

    Directory of Open Access Journals (Sweden)

    Muralikrishna Gangadharan Komala

    Full Text Available BACKGROUND AND OBJECTIVE: Sodium glucose cotransporter 2 (SGLT2 is the main luminal glucose transporter in the kidney. SGLT2 inhibition results in glycosuria and improved glycaemic control. Drugs inhibiting this transporter have recently been approved for clinical use and have been suggested to have potential renoprotective benefits by limiting glycotoxicity in the proximal tubule. We aimed to determine the renoprotective benefits of empagliflozin, an SGLT2 inhibitor, independent of its glucose lowering effect. RESEARCH DESIGN AND METHODS: We induced diabetes using a low dose streptozotocin protocol in 7-8 week old endothelial nitric oxide (eNOS synthase knockout mice. We measured fasting blood glucose on a monthly basis, terminal urinary albumin/creatinine ratio. Renal histology was assessed for inflammatory and fibrotic changes. Renal cortical mRNA transcription of inflammatory and profibrotic cytokines, glucose transporters and protein expression of SGLT2 and GLUT1 were determined. Outcomes were compared to diabetic animals receiving the angiotensin receptor blocker telmisartan (current best practice. RESULTS: Diabetic mice had high matched blood glucose levels. Empagliflozin did not attenuate diabetes-induced albuminuria, unlike telmisartan. Empagliflozin did not improve glomerulosclerosis, tubular atrophy, tubulointerstitial inflammation or fibrosis, while telmisartan attenuated these. Empagliflozin did not modify tubular toll-like receptor-2 expression in diabetic mice. Empagliflozin did not reduce the upregulation of macrophage chemoattractant protein-1 (MCP-1, transforming growth factor β1 and fibronectin mRNA observed in the diabetic animals, while telmisartan decreased transcription of MCP-1 and fibronectin. Empagliflozin increased GLUT1 mRNA expression and telmisartan increased SGLT2 mRNA expression in comparison to untreated diabetic mice. However no significant difference was found in protein expression of GLUT1 or SGLT2 among the

  3. 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.

  4. Kidneys cytomembranes stability in pregnant women with type 1 diabetes and pregnancy outcomes dependingon the method of insulin delivery

    Directory of Open Access Journals (Sweden)

    Zul'fiya Raisovna Alimetova

    2012-12-01

    Full Text Available Objective. To evaluate of kidney cytomembranes stability during pregnancy and its outcomes in patients with diabetes mellitus type on type 1 with different stages of diabetic nephropathy (DN according to the route of insulin administration.Materials and Methods. We study 100 pregnant women with type 1 diabetes with the introduction of insulin in the mode of multiple subcutaneous injections (MSII and with portable dispenser with a continuous subcutaneous insulin infusion (CSII. DN stage determined by the level of albumin in the daily urine. Cytomembranes stability assessment conducted on daily excretion of ethanolamine and phospholipids with urine in each trimester. Pregnancy outcomes were analyzed in 52 patients with type 1 diabetes. In the group of pregnant women with delivery at term 38-40 weeks we also analyzed the status of newborns.Results. Indicators of cytomembranes stability of kidneys in pregnant women on CSII consistent with those in healthy pregnant women (p>0.05 the whole pregnancy, regardless of the level of daily urinary albumin excretion. There were no differences in cytomembrana stability of kidneys between the group of patients on MSII with normal albumin excretion (NAU and the control group regardless to the gestational age (p>0.05. With the introduction of insulin in the mode of MSII on the stage of microalbuminuria (MAU in the 3rd trimester we found the increase of ethanolamine excretion as compared to control groupy (U=8,00, p=0.012 and the group on CSII with a similar stage of nephropathy (U=2.00, p=0.033. In patients with proteinuria (PU in the group on the MSII in the third trimester phospholipids excretion is increased with a daily urine (U=27,5, p=0.03 and U=22,00, p=0.07 for patients MSII and CSII, respectively. The use of an insulin pump allowed to prolong gestational period, even in severe proteinuric stage of nephropathy. Manifestations of diabetic fetopathy as macrosomia, hypoglycemia in the fetus at birth time

  5. [Treatment of type 2 diabetes mellitus in patients with chronic kidney disease. Grupo de Trabajo para el Documento de Consenso sobre el tratamiento de la diabetes tipo 2 en el paciente con enfermedad renal crónica].

    Science.gov (United States)

    Gómez-Huelgas, Ricardo; Martínez-Castelao, Alberto; Artola, Sara; Górriz, José Luis; Menéndez, Edelmiro

    2014-01-21

    Chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) are highly prevalent chronic diseases, which represent an important public health problem and require a multidisciplinary management. T2DM is the main cause of CKD and it also causes a significant comorbidity with regard to non-diabetic nephropathy. Patients with diabetes and kidney disease represent a special risk group as they have higher morbi-mortality as well as higher risk of hypoglycemia than diabetic individuals with a normal kidney function. Treatment of T2DM in patients with CKD is controversial because of the scarcity of available evidence. The current consensus report aims to ease the appropriate selection and dosage of antidiabetic treatments as well as the establishment of safety objectives of glycemic control in patients with CKD.

  6. ESTIMATING TOTAL GLOMERULAR NUMBER IN HUMAN KIDNEYS WITH A PHYSICAL DISECTOR/FRACTIONATOR COMBINATION

    Directory of Open Access Journals (Sweden)

    Kelli J Johnson

    2011-05-01

    Full Text Available End-stage renal disease (ESRD has emerged as a major health issue for Australian Aborigines. This phenomenon is paralleled in other populations that have adopted a Westernised lifestyle, including African Americans. It has been suggested that abnormal glomerular hypertrophy (glomerulomegaly is an important predisposing factor for ESRD. The pathogenesis of glomerulomegaly remains unknown. It may represent a compensatory hypertrophic response to decreased nephron endowment during fetal development. Alternatively, glomerulomegaly may represent an abnormal haemodynamic/metabolic response to repeated infections, including renal infections during postnatal life. Since glomerular number and size are important issues associated with ESRD, an optimum quantitative method is required for estimating these parameters in human kidneys. The total number of glomeruli in the normal human kidney appears to vary by a factor of three or more, ranging from approximately 300,000 to more than 1 million. Recently, unbiased stereological methods for estimating total glomerular number in kidneys have been developed. The general aim of the present study was to evaluate (in terms of precision and efficiency a stereological method for estimating total glomerular number in human kidneys; the physical disector/fractionator combination. This method provided consistent estimates of total glomerular number. Estimates of total glomerular number obtained for four human kidneys ranged from 364,161 to 586,094 (coefficients of variation 9.2% to 20.0%. Mean glomerular volume for the four kidneys ranged from 6.04 to 10.32 μm3 x 106. These results indicate that this method is a precise and consistent method for estimating total glomerular number in human kidneys. The simple sampling technique developed in this study will be employed in future studies to determine if there is a difference in total glomerular, and hence nephron, number between Australian Aborigines and Caucasians, and

  7. Evaluation of renographic and metabolic parameters in human kidney transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez, A. [Barcelone, Univ. (Spain). Lab. of Biophysics and Bioengineering; Vigues, F.; Franco, E. [Hospital of Bellvitge, Bellvitge (Spain). Service of Urology; Puchal, R. [Hospital of Bellvitge, Bellvitge (Spain). Service of Nuclear Medicine; Bartrons, R.; Ambrosio, S. [Barcelona, Univ. (Spain). Faculty of Odontology, Laboratory of Biochemistry

    1997-03-01

    Background: the aim of this work is to demonstrate that the value of the mean transit time (MTT) obtained from the {sup 99m}Tc-MAG3 renogram deconvolution is related to the levels of adenine nucleotides determined in cortical biopsies from transplanted kidneys. Methods: the functional state was estimated by means of the MTT and the initial height (HO) of the renal retention function obtained from the {sup 99m}Tc-MAG3 renogram deconvolution and by the measure of adenine nucleotides obtained from biopsies. We studied 30 kidney graft recipients, 25 normal functioning grafts (NFG) and 5 with acute tubular necrosis (ATN). Results: the MTT is significantly longer for ATN (p<0.001). The initial uptake values (HO) are significantly lower for ATN (p<0.001). The sum of adenine nucleotides (SAN) is significantly greater for NFG than for ATN (p<0.001). The values of the MTT seem to reflect the energy state of the cells in transplanted kidney. Conclusion: the analysis of MTT may be indicative of the functional metabolic recovery and thus it may be predictive of the renal graft function at least in the same extent than the biochemical analysis of a cortical renal biopsy immediately after blood reperfusion of the tissue.

  8. High glucose repatterns human podocyte energy metabolism during differentiation and diabetic nephropathy

    Science.gov (United States)

    Imasawa, Toshiyuki; Obre, Emilie; Bellance, Nadège; Lavie, Julie; Imasawa, Tomoko; Rigothier, Claire; Delmas, Yahsou; Combe, Christian; Lacombe, Didier; Benard, Giovanni; Claverol, Stéphane; Bonneu, Marc; Rossignol, Rodrigue

    2017-01-01

    Podocytes play a key role in diabetic nephropathy pathogenesis, but alteration of their metabolism remains unknown in human kidney. By using a conditionally differentiating human podocyte cell line, we addressed the functional and molecular changes in podocyte energetics during in vitro development or under high glucose conditions. In 5 mM glucose medium, we observed a stepwise activation of oxidative metabolism during cell differentiation that was characterized by peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α)–dependent stimulation of mitochondrial biogenesis and function, with concomitant reduction of the glycolytic enzyme content. Conversely, when podocytes were cultured in high glucose (20 mM), stepwise oxidative phosphorylation biogenesis was aborted, and a glycolytic switch occurred, with consecutive lactic acidosis. Expression of the master regulators of oxidative metabolism transcription factor A mitochondrial, PGC-1α, AMPK, and serine–threonine liver kinase B1 was altered by high glucose, as well as their downstream signaling networks. Focused transcriptomics revealed that myocyte-specific enhancer factor 2C (MEF2C) and myogenic factor 5 (MYF5) expression was inhibited by high glucose levels, and endoribonuclease-prepared small interfering RNA–mediated combined inhibition of those transcription factors phenocopied the glycolytic shift that was observed in high glucose conditions. Accordingly, a reduced expression of MEF2C, MYF5, and PGC-1α was found in kidney tissue sections that were obtained from patients with diabetic nephropathy. These findings obtained in human samples demonstrate that MEF2C-MYF5–dependent bioenergetic dedifferentiation occurs in podocytes that are confronted with a high-glucose milieu.—Imasawa, T., Obre, E., Bellance, N., Lavie, J., Imasawa, T., Rigothier, C., Delmas, Y., Combe, C., Lacombe, D., Benard, G., Claverol, S., Bonneu, M., Rossignol, R. High glucose repatterns human podocyte energy

  9. Assessment of Myo‌inositol and Crocin Effects on RAGE and TGF? Gene Expression in the Kidney of Streptozotocin Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    S. Sadat Heidary

    2014-07-01

    Full Text Available Introduction & Objective: Diabetic nephropathy is one of the micro vascular complications of uncontrolled diabetes. Chronic hyperglycemia results in the formation of glycated proteins and activation of pathways leading to diabetic nephropathy. Increasing RAGE and TGF? production in the kidney tissue is a major pathway involved in diabetic complications. In this survey, the effect of myoinositol and Crocin on RAGE and TGF? expression in the kidney of diabetic rats was studied. Materials & Methods: In this experimental study after rendering rats with diabetes with strepto-zotocin, they were treated with oral 1% myoinositol and injection of 100 mg/kg BW crocin for 12 weeks. Changes in both RAGE and TGF? expressions in the kidney tissue were as-sessed by semi-quantitative RT-PCR method. The data was analyzed by SPSS 18 software and one way ANOVA and Tukey statisticaly tests. Results: Crocin administration caused a significant reduction in the RAGE and TGF? expres-sion in comparison with the untreated diabetic rats. Oral administration of myoinositol could not induce any significant changes in the expression of both genes in the diabetic rats. Conclusion: According to the results of this study, crocin has the ability to block pathways leading to diabetic nephropathy through reducing RAGE and TGF? expression in the kidney tissue, maybe through its ability to reduce the serum glucose and AGEs, and antioxidant ac-tivity. Considering the positive effects of myoinositol in diabetic complications in previous studies, more studies are needed to find the mechanism of its action. (Sci J Hamadan Univ Med Sci 2014; 21 (2:122-130

  10. 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

    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...... to control metabolic diseases by modifying the gut microbiota....... = 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...

  11. Lessons From the KK-Ay Mouse, a Spontaneous Animal Model for the Treatment of Human Type 2 Diabetic Nephropathy.

    Science.gov (United States)

    Tomino, Yasuhiko

    2012-01-01

    Diabetic nephropathy is a major cause of end-stage kidney disease (ESKD) in patients with type 1 and type 2 diabetes throughout the world. In human glomeruli, expansion of diffuse mesangial matrices, exudative lesions and/or segmental nodular sclerosis are pathological features of diabetic nephropathy. There have been many reports on the pathogenesis and treatment of type 2 diabetes using various animal models. It appears that KK-Ay mice, especially in terms of their immunohistological findings, are a suitable animal model for human type 2 diabetic nephropathy. Many compounds have been reported to be advanced glycation end product (AGE) inhibitors such as aminoguanidine, angiotensin II receptor inhibitors and pyridoxamine, and these are useful in therapeutic interventions for reducing AGEs. Pyridoxamine ameliorates lipid peroxidation and insulin resistance in KK-Ay mice. Combination therapy with angiotensin converting inhibitors (ACE-I) and angiotensin II type 1 receptor blockers (ARB), including an ARB and 1,25-dihydroxyvitamin D3, i.e. anti-hypertensive and anti-reactive oxygen species effects, or with eicosapentaenoic acid (EPA), i.e. anti-microinflammation effect, have shown efficacy in the treatment of diabetic nephropathy in KK-Ay mice. It appears that KK-Ay mice are a useful spontaneous animal model for the evaluation of pathogenesis and treatment in patients with type 2 diabetic nephropathy.

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

    Directory of Open Access Journals (Sweden)

    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

  13. Human intestinal microbiota and type 1 diabetes.

    Science.gov (United States)

    Vaarala, Outi

    2013-10-01

    The role of intestinal microbiota in immune-mediated diseases, such as type 1 diabetes, has deservedly received a lot of attention. Evidently, changes in the intestinal microbiota are associated with type 1 diabetes as demonstrated by recent studies. Children with beta-cell autoimmunity have shown low abundance of butyrate-producing bacteria and increase in the abundance of members of the Bacteroidetes phylum in fecal microbiota. These alterations could explain increased gut permeability, subclinical small intestinal inflammation, and dysregulation of oral tolerance in type 1 diabetes. However, these studies do not provide evidence of the causative role of the gut microbiota in the development of beta-cell autoimmunity, yet. In animal models, the composition of gut microbiota modulates the function of both innate and adaptive immunity, and intestinal bacteria are regulators of autoimmune diabetes. Thus, prevention of type 1 diabetes could, in the future, be based on the interventions targeted to the gut microbiota.

  14. Nrf2 activators as potential modulators of injury in human kidney cells

    Directory of Open Access Journals (Sweden)

    Amandla Atilano-Roque

    2016-01-01

    Full Text Available Cisplatin is a chemotherapeutic agent used in the treatment of solid tumors, with clinical use often complicated by kidney toxicity. Nuclear factor (erythroid-derived-2-like 2 (Nrf2 is a transcription factor involved in kidney protectant effects. The purpose of this study was to determine whether the Nrf2 activators oltipraz, sulforaphane, and oleanolic acid could protect human kidney cells against cisplatin-induced injury and to compare the protective effects between three Nrf2 activators. Human proximal tubule cells (hPTC and human embryonic kidney 293 cells (HEK293 were exposed to cisplatin doses in the absence and presence of Nrf2 activators. Pre- and delayed-cisplatin and Nrf2 activator exposures were also assessed. Cell viability was enhanced with Nrf2 activator exposures, with differences detected between pre- and delayed-treatments. Both sulforaphane and oltipraz increased the expression of anti-oxidant genes GCLC and NQO1. These findings suggest potential human kidney protective benefits of Nrf2 activators with planned exposures to cisplatin.

  15. The TCM Kidney-nourishing Method for Protection of Brain in Patients with Diabetic Encephalopathy

    Institute of Scientific and Technical Information of China (English)

    Liang Xiaochun

    2007-01-01

    @@ The concept of diabetic encephalopathy was taken shape in 1960s and it mainly refers to the damage to the gnosic function by diabetes. The damage to gnosia for patients with Type Ⅰ diabetes is mainly shown in the fields of conceptually reasoning ability,the information-processing speed and the ability to obtain new technology.

  16. Plasma Triglycerides and HDL-C Levels Predict the Development of Diabetic Kidney Disease in Subjects With Type 2 Diabetes: The AMD Annals Initiative.

    Science.gov (United States)

    Russo, Giuseppina T; De Cosmo, Salvatore; Viazzi, Francesca; Pacilli, Antonio; Ceriello, Antonio; Genovese, Stefano; Guida, Pietro; Giorda, Carlo; Cucinotta, Domenico; Pontremoli, Roberto; Fioretto, Paola

    2016-12-01

    Despite the achievement of blood glucose, blood pressure, and LDL cholesterol (LDL-C) targets, the risk for diabetic kidney disease (DKD) remains high among patients with type 2 diabetes. This observational retrospective study investigated whether diabetic dyslipidemia-that is, high triglyceride (TG) and/or low HDL cholesterol (HDL-C) levels-contributes to this high residual risk for DKD. Among a total of 47,177 patients attending Italian diabetes centers, 15,362 patients with a baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m(2), normoalbuminuria, and LDL-C ≤130 mg/dL completing a 4-year follow-up were analyzed. The primary outcome was the incidence of DKD, defined as either low eGFR (30% and/or albuminuria. Overall, 12.8% developed low eGFR, 7.6% an eGFR reduction >30%, 23.2% albuminuria, and 4% albuminuria and either eGFR 30%. TG ≥150 mg/dL increased the risk of low eGFR by 26%, of an eGFR reduction >30% by 29%, of albuminuria by 19%, and of developing one abnormality by 35%. HDL-C 30%, with a 24% higher risk of developing albuminuria and a 44% risk of developing one abnormality. These associations remained significant when TG and HDL-C concentrations were examined as continuous variables and were only attenuated by multivariate adjustment for numerous confounders. In a large population of outpatients with diabetes, low HDL-C and high TG levels were independent risk factors for the development of DKD over 4 years. © 2016 by the American Diabetes Association.

  17. 78 FR 36554 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2013-06-18

    ... and Kidney Diseases Special Emphasis Panel; Artificial Pancreas SBIR Applications. Date: July 31, 2013... Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory Committee Act, as... Kidney Diseases Special Emphasis Panel; Gene-Environment Interactions in TEDDY. Date: July 25, 2013....

  18. 77 FR 2076 - National Institute of Diabetes and Digestive and Kidney Diseases Notice of Closed Meetings

    Science.gov (United States)

    2012-01-13

    ... Digestive and Kidney Diseases Special Emphasis Panel; Artificial Pancreas Review. Date: February 22-23, 2012... Diseases Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory Committee Act, as... Kidney Diseases Special Emphasis Panel; NIDDK DEM Fellowship Review. Date: January 31-February 1,...

  19. Impact of D-pinitol on the attenuation of proinflammatory cytokines, hyperglycemia-mediated oxidative stress and protection of kidney tissue ultrastructure in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Sivakumar, Selvaraj; Palsamy, Periyasamy; Subramanian, Sorimuthu Pillai

    2010-10-06

    Oxidative stress plays a crucial role in the progression and development of diabetes and its complications due to chronic hyperglycemia. The present study was aimed to investigate the kidney tissue protective nature of d-pinitol, a cyclitol present in soybean, by assessing the key markers of hyperglycemia-mediated oxidative stress, proinflammatory cytokines and ultrastructural alterations in streptozotocin-induced diabetic rats. Oral administration of d-pinitol (50mg/kg body weight/day) for 30 days to diabetic group of rats showed a significant elevation in the level of total protein and significant decline in the levels of blood urea, serum uric acid, creatinine and advanced glycation endproducts (AGEs) and kidney proinflammatory cytokines such as TNF-alpha, IL-1beta, IL-6, NF-kappaB p65 subunit and nitrite. Further, d-pinitol administration elicited a significant attenuation in the activities of kidney enzymatic antioxidants such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) and the levels of kidney non-enzymatic antioxidants such as vitamin E, vitamin C and reduced glutathione (GSH) in the diabetic group of rats, with a concomitant decline in the levels of kidney lipid peroxides, hydroperoxides and protein carbonyls. The histological and ultrastructural observations on the kidney tissues also confirmed the renoprotective nature of d-pinitol. Thus the present study demonstrated the renoprotective nature of d-pinitol by attenuating the hyperglycemia-mediated proinflammatory cytokines and antioxidant competence in kidney tissues of streptozotocin-induced diabetic rats.

  20. Insulin-producing cells from adult human bone marrow mesenchymal stem cells control streptozotocin-induced diabetes in nude mice.

    Science.gov (United States)

    Gabr, Mahmoud M; Zakaria, Mahmoud M; Refaie, Ayman F; Ismail, Amani M; Abou-El-Mahasen, Mona A; Ashamallah, Sylvia A; Khater, Sherry M; El-Halawani, Sawsan M; Ibrahim, Rana Y; Uin, Gan Shu; Kloc, Malgorzata; Calne, Roy Y; Ghoneim, Mohamed A

    2013-01-01

    Harvesting, expansion, and directed differentiation of human bone marrow-derived mesenchymal stem cells (BM-MSCs) could provide an autologous source of surrogate β-cells that would alleviate the limitations of availability and/or allogenic rejection following pancreatic or islet transplantation. Bone marrow cells were obtained from three adult type 2 diabetic volunteers and three nondiabetic donors. After 3 days in culture, adherent MSCs were expanded for two passages. At passage 3, differentiation was carried out in a three-staged procedure. Cells were cultured in a glucose-rich medium containing several activation and growth factors. Cells were evaluated in vitro by flow cytometry, immunolabeling, RT-PCR, and human insulin and c-peptide release in responses to increasing glucose concentrations. One thousand cell clusters were inserted under the renal capsule of diabetic nude mice followed by monitoring of their diabetic status. At the end of differentiation, ∼5-10% of cells were immunofluorescent for insulin, c-peptide or glucagon; insulin, and c-peptide were coexpressed. Nanogold immunolabeling for electron microscopy demonstrated the presence of c-peptide in the rough endoplasmic reticulum. Insulin-producing cells (IPCs) expressed transcription factors and genes of pancreatic hormones similar to those expressed by pancreatic islets. There was a stepwise increase in human insulin and c-peptide release by IPCs in response to increasing glucose concentrations. Transplantation of IPCs into nude diabetic mice resulted in control of their diabetic status for 3 months. The sera of IPC-transplanted mice contained human insulin and c-peptide but negligible levels of mouse insulin. When the IPC-bearing kidneys were removed, rapid return of diabetic state was noted. BM-MSCs from diabetic and nondiabetic human subjects could be differentiated without genetic manipulation to form IPCs that, when transplanted, could maintain euglycemia in diabetic mice for 3 months

  1. 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...

  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. Therapeutic effect of phytoecdysteroids rich extract from Ajuga iva on alloxan induced diabetic rats liver, kidney and pancreas.

    Science.gov (United States)

    Hamden, Khaled; Ayadi, Fatma; Jamoussi, Kamel; Masmoudi, Hatem; Elfeki, Abdelfattah

    2008-01-01

    In the current study, the effect of Ajuga iva extract on blood glucose, lipid profile, hepatic and renal toxicity and antioxidant enzyme activities in alloxan-induced diabetic rats was investigated. Diabetes was confirmed by measuring the glucoserua concentration 15 days after alloxan administration. Ajuga iva extract was administrated orally 3 weeks after alloxan injection. Our results investigate that Ajuga iva extract supplementation increased the levels of both enzymatic antioxidant (superoxide dismutase, catalase and glutathione peroxidase) and metals antioxidants (iron, copper, magnesium, calcium) and decreased lipid peroxidation level (TBARs). Besides Ajuga iva ameliorated diabetes provoked hepatic and renal toxicity appeared by a lower level in total and direct bilirubin, urea, creatinine, triglyceride (TG), cholesterol and a higher level in HDL-cholesterol. Besides, the activities of phosphatase alkalines (PAL), aspartate and lactate transaminase (AST & ALT) were decreased. The benefices effects of phytoecdysteroids of Ajuga iva confirmed by histological observation in pancreatic tissues. In conclusion, Ajuga iva phytoecdysteroids supplements seem to be beneficial for correcting the hyperglycemia and preventing diabetic complications in liver, pancreas and kidneys.

  4. Linagliptin is associated to increased treatment adherence and satisfaction in elderly outpatients with diabetes and advanced chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Franco Gregorio

    2016-11-01

    Full Text Available The treatment of diabetes in frail elderly patients with decreased renal function is challenging and insufficiently supported by evidence. Due to their good tolerability and low hypoglycemic risk, oral dipeptidyl peptidase- 4 (DPP-4 inhibitors have emerged as a reasonable option for glycemic control in the elderly. The aim was to evaluate the efficacy and safety of linagliptin, a long acting, oral DPP-4 inhibitor with a predominantly nonrenal elimination route, in elderly patients with severe chronic kidney disease (CKD. This was a retrospective, observational study in outpatients with type 2 diabetes and advanced-stage CKD (estimated glomerular filtration rate <30 mL/min per 1.73 m2 referring to a diabetes clinic in Italy. Patients were switched from basal insulin to oral linagliptin 5 mg once daily and observed for 14 months. Assessed variables included glycemic control (HbA1c target, 7.5%-8.0%, adherence to treatment (Morisky questionnaire and patient satisfaction (diabetes treatment satisfaction questionnaire. Adverse events, including hypoglycemic episodes, were also recorded. Thirty patients [mean (±standard deviation age 70.2 (±8.2 years, HbA1c 7.6% (±0.3, fasting blood glucose 173.9 (±23.5 mg/dL] with type-2 diabetes and advanced CKD were included. The switch to linagliptin did not affect significantly glycemic control, was well tolerated and associated with a reduction in hypoglycemic episodes. Adherence to treatment was better with linagliptin than basal insulin and patient satisfaction significantly improved after switching. Linagliptin appears as a valid option for glycemic control in elderly diabetes patients with severe CKD in treatment with low-dose insulin. However adequately designed longterm studies are needed to confirm these findings.

  5. Chronic Kidney Disease (CKD)

    Science.gov (United States)

    ... CKD treated? Kidney-friendly diet for CKD What causes chronic kidney disease (CKD)? Anyone can get CKD. Some people are ... and high blood pressure are the most common causes of CKD. If you have diabetes or high blood pressure, ...

  6. 从肝肾同源论治糖尿病肾病%Treatment of Diabetic Nephropathy from Theory of Liver and Kidney Sharing the Same Origin

    Institute of Scientific and Technical Information of China (English)

    于佳; 李伟

    2016-01-01

    The physiological functions and pathological relationships of the liver and kidney were the theo-retical basis for the treatment of diabetic nephropathy from "the liver and kidney sharing the same origin". In physiology,the relationships between the liver and kidney manifested as mother generating child and essence and blood sharing the same origin. In pathology,the liver and kidney affected each other such as kidney Yin deficiency leading to liver Yin deficiency and visa versa,namely both deficiency of liver Yin and kidney Yin which should be treated simultaneously. The etiology and pathogenesis of diabetic nephropathy were explained according to the theory of "the liver and kidney sharing the same origin" such as liver dysfunction resulting in disharmony between Qi and blood,disorder of child-organ affecting the mother-organ,both deficiency of liver Yin and kidney Yin. For example,kidney deficiency leading to vital essence loss could affect the child-organ,involving the liver. So we put forward the prevention concept and treatment method of diabetic nephropathy according to "the liver and kidney sharing the same origin" and kidney was the emphasis in treating the liver and kidney simultaneously. The main treatment principles in-cluded nourishing water to enrich wood,i.e. nourishing kidney essence and replenishing kidney Yin to en-rich liver Yin.%从肝肾同源论治糖尿病肾病,在生理上肝肾为母子相生、精血同源;病理上肝肾相互影响,肾阴虚致肝阴不足,肝阴虚耗致肾阴亦不足,即肝肾同病,故治疗上肝肾同治.文章基于肝肾同源理论阐释糖尿病肾病的病因病机,如肝失疏泄,则气血失和,"子病及母",肝肾同病;如肾虚则精微不藏而走泄,可"母病及子",累及于肝.在肝肾同源的理论指导下,认为肝肾同治的重点在治肾,滋水涵木,即养肾精、补肾阴,寓补肝于补肾之中.

  7. CD74 in kidney disease

    Directory of Open Access Journals (Sweden)

    Lara eValiño-Rivas

    2015-09-01

    Full Text Available CD74 (invariant MHC class II regulates protein trafficking and is a receptor for macrophage migration inhibitory factor (MIF and D-dopachrome tautomerase (D-DT/MIF-2. CD74 expression is increased in tubular cells and/or glomerular podocytes and parietal cells in human metabolic nephropathies, polycystic kidney disease, graft rejection and kidney cancer and in experimental diabetic nephropathy and glomerulonephritis. Stressors like abnormal metabolite (glucose, lyso-Gb3 levels and inflammatory cytokines increase kidney cell CD74. MIF activates CD74 to increase inflammatory cytokines in podocytes and tubular cells and proliferation in glomerular parietal epithelial cells and cyst cells. MIF overexpression promotes while MIF targeting protects from experimental glomerular injury and kidney cysts, and interference with MIF/CD74 signaling or CD74 deficiency protected from crescentic glomerulonephritis. However, CD74 may protect from interstitial kidney fibrosis. Furthermore, CD74 expression by stressed kidney cells raises questions about the kidney safety of cancer therapy strategies delivering lethal immunoconjugates to CD74-expressing cells. Thus, understanding CD74 biology in kidney cells is relevant for kidney therapeutics.

  8. AN ANALYSIS OF THE MICROSTRUCTURE CHARACTERISTICS IN HUMAN KIDNEY WITH ULTRASONIC BACKSCATTERING

    Institute of Scientific and Technical Information of China (English)

    Yan Bige; Ta Dean; Wang Rong

    2005-01-01

    Objective To investigate the microstructure characteristics in human kidney with the WD cepstrum of ultrasonic backscattering. Methods By using this method, an analysis of the backscattering signals of normal and pathological human kidney in vitro was made and the mean spacing of the scatterers of biological soft tissues was estimated, then compared the means of this new approach with the means of the AR cepstrum. Results The results show that the mean spacings of the scatterers of the two different kidney tissues are noticeably different, which reveals the fact that the WD cepstrum works more effective than the AR cepstrum in showing the features of the microstructure of soft tissues. Conclusion The WD cepstrum is an effective mean to analyze the ultrasonic scattering signals and determine the features of the mean spacing of the scatterers of soft tissues. This method provides more available clinical diagnosis and improves the results of mean spacing of the scatterers of soft tissues.

  9. 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

    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....... 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...

  10. 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

  11. 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.

  12. 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

  13. Raman spectroscopy of human vitreous collagen in diabetic retinopathy

    Science.gov (United States)

    Sebag, Jerry; Nie, Shuming; Reiser, Karen M.; Yu, Nai-Teng

    1992-08-01

    In diabetes nonenzymatic glycation alters collagen throughout the body resulting in the histopathology that underlies diabetic disease in several organs. In the eye such changes in vitreous collagen could contribute to vitreous degeneration and the progression of proliferative diabetic retinopathy. Previous studies have demonstrated early glycation and advanced endproducts in the vitreous of humans with proliferative diabetic retinopathy. Near-infrared Fourier-transform Raman spectroscopy was performed on vitreous obtained at surgery from diabetic patients and from non-diabetic control subjects. The findings were compared to measurements obtained in untreated and glycated (in vitro) rat-tail tendon collagen. The results demonstrated substantial changes in diabetic vitreous collagen resulting from glycation, most likely advanced glycation endproducts. This approach appears to be useful as a means of characterizing the molecular changes induced by diabetes. Furthermore, this technique could be developed as a way of quantifying these changes in vivo in several tissues, so as to gauge the severity of non-enzymatic glycation and monitor the response to therapy.

  14. 75 FR 29773 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2010-05-27

    ... Pregnancy. Date: June 10, 2010. Time: 3:30 p.m. to 5 p.m. Agenda: To review and evaluate grant applications...; 93.848, Digestive Diseases and Nutrition Research; 93.849, Kidney Diseases, Urology and...

  15. 77 FR 14405 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2012-03-09

    ... Interdisciplinary Team Science in NIDDK Research Areas. Date: March 30, 2012. Time: 11:30 a.m. to 1 p.m. Agenda: To... Kidney Diseases Special Emphasis Panel; Collaborative Interdisciplinary Team Science R24-5. Date: April...

  16. 76 FR 77545 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2011-12-13

    ... Special Emphasis Panel, Nutrition Obesity Research Centers (P30). Date: March 12-13, 2012. Time: 8 a.m. to... and Nutrition Research; 93.849, Kidney Diseases, Urology and Hematology Research, National Institutes...

  17. 77 FR 9671 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2012-02-17

    ... Kidney Diseases Special Emphasis Panel; Liver Tissue and Cell Distribution System. Date: March 15, 2012... Call). Contact Person: Maria E. Davila-Bloom, Ph.D., Scientific Review Officer, Review Branch,...

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

    Science.gov (United States)

    2016-07-01

    TECHNOLOGY? These studies identify a new target for the treatment of diabetic nephropathy . Studies with the NFAT inhibitor 11R- VIVIT will provide further...cells. In Aim 2, we will determine the role of CRT in mouse models of diabetic nephropathy . In year 2, we developed stably transduced HK-2 cells using...by western blot for fibronectin. 15. SUBJECT TERMS Diabetic nephropathy , calreticulin, TGF-beta, endoplasmic reticulum stress, fibrosis 16. SECURITY

  19. Horizon 2020 in Diabetic Kidney Disease: The Clinical Trial Pipeline for Add-On Therapies on Top of Renin Angiotensin System Blockade

    Directory of Open Access Journals (Sweden)

    Maria Vanessa Perez-Gomez

    2015-06-01

    Full Text Available Diabetic kidney disease is the most frequent cause of end-stage renal disease. This implies failure of current therapeutic approaches based on renin-angiotensin system (RAS blockade. Recent phase 3 clinical trials of paricalcitol in early diabetic kidney disease and bardoxolone methyl in advanced diabetic kidney disease failed to meet the primary endpoint or terminated on safety concerns, respectively. However, various novel strategies are undergoing phase 2 and 3 randomized controlled trials targeting inflammation, fibrosis and signaling pathways. Among agents currently undergoing trials that may modify the clinical practice on top of RAS blockade in a 5-year horizon, anti-inflammatory agents currently hold the most promise while anti-fibrotic agents have so far disappointed. Pentoxifylline, an anti-inflammatory agent already in clinical use, was recently reported to delay estimated glomerular filtration rate (eGFR loss in chronic kidney disease (CKD stage 3–4 diabetic kidney disease when associated with RAS blockade and promising phase 2 data are available for the pentoxifylline derivative CTP-499. Among agents targeting chemokines or chemokine receptors, the oral small molecule C-C chemokine receptor type 2 (CCR2 inhibitor CCX140 decreased albuminuria and eGFR loss in phase 2 trials. A dose-finding trial of the anti-IL-1β antibody gevokizumab in diabetic kidney disease will start in 2015. However, clinical development is most advanced for the endothelin receptor A blocker atrasentan, which is undergoing a phase 3 trial with a primary outcome of preserving eGFR. The potential for success of these approaches and other pipeline agents is discussed in detail.

  20. Comparison of Gait Speed and Peripheral Nerve Function Between Chronic Kidney Disease Patients With and Without Diabetes

    Science.gov (United States)

    2017-01-01

    Objective To compare overall physical function, including gait speed and peripheral nerve function, between diabetic chronic kidney disease (CKD) patients and nondiabetic CKD patients and to investigate the association between gait speed and peripheral nerve function in CKD patients. Methods Sixty adult CKD patients (35 with and 25 without diabetes), who received maintenance hemodialysis (HD), were included in this study. Demographic data, past medical history, current medical condition and functional data—usual gait speed, vibration perception threshold for the index finger (VPT-F) and the great toe (VPT-T), activity of daily living (ADL) difficulty, and peripheral neuropathy (PN) along with the degree of its severity—were collected and compared between the two groups. Correlations between the severity of PN and the impairment of other functions were identified. Results Diabetic CKD patients showed significantly slower gait speed (p=0.029), impaired sensory function (VPT-F, p=0.011; VPT-T, p=0.023), and more frequent and severe PN (number of PN, pdiabetes. Usual gait speed had a significant negative correlation with the severity of PN (rho=−0.249, p=0.013). By contrast, VPT-F (rho=0.286, p=0.014) and VPT-T (rho=0.332, p=0.035) were positively correlated with the severity of PN. ADL difficulty was comparatively more frequent in the patients with more severe PN (p=0.031). Conclusion In CKD patients with maintenance HD, their gait speed, sensory functions, and peripheral nerve functions were all significantly impaired when they have diabetes, and the severity of PN was negatively correlated with their gait speed, sensory function, and ADL function. Adverse effects of diabetes impacted physical performance of CKD patients. The physical disability of those patients might be attributable to PN and its severity.

  1. Thiazolidinediones and Risk of Long-Term Dialysis in Diabetic Patients with Advanced Chronic Kidney Disease: A Nationwide Cohort Study.

    Directory of Open Access Journals (Sweden)

    Yu-Hsin Chen

    Full Text Available Thiazolidinediones (TZDs reduce urinary albumin excretion and proteinuria in diabetic nephropathy. The effect of TZDs on hard renal outcome in diabetic patients with chronic kidney disease (CKD is unknown. We investigate the association of TZDs and risk of long-term dialysis or death in diabetic patients with advanced CKD. The nationwide population-based cohort study was conducted using Taiwan's National Health Insurance Research Database. From January 2000 to June 2009, 12350 diabetic patients with advanced CKD (serum creatinine levels greater than 6 mg/dL but not yet receiving renal replacement therapy were selected for the study. We used multivariable Cox regression models and a propensity score-based matching technique to estimate hazard ratios (HRs for development of long-term dialysis and the composite outcome of long-term dialysis or death for TZD users (n=1224 as compared to nonusers (n=11126. During a median follow-up of 6 months, 8270 (67.0% patients required long-term dialysis and 2593 (21.0% patients died before starting long-term dialysis. Using propensity score matched analysis, we found TZD users were associated with a lower risk for long-term dialysis (HR, 0.80; 95% confidence interval [CI], 0.74-0.86 and the composite outcome of long-term dialysis or death (HR, 0.85; 95% CI, 0.80-0.91. The results were consistent across most patient subgroups. Use of TZDs among diabetic patients with advanced CKD was associated with lower risk for progression to end-stage renal disease necessitating long-term dialysis or death. Further randomized controlled studies are required to validate this association.

  2. Tubular kidney injury molecule-1 (KIM-1) in human renal disease

    NARCIS (Netherlands)

    van Timmeren, M. M.; van den Heuvel, M. C.; Bailly, V.; Bakker, S. J. L.; van Goor, H.; Stegeman, C. A.

    2007-01-01

    KIM-1, a transmembrane tubular protein with unknown function, is undetectable in normal kidneys, but is markedly induced in experimental renal injury. The KIM-1 ectodomain is cleaved, detectable in urine, and reflects renal damage. KIM-1 expression in human renal biopsies and its correlation with ur

  3. Targeting cellular drivers and counter-regulators of hyperglycaemia- and transforming growth factor-β1-associated profibrotic responses in diabetic kidney disease.

    Science.gov (United States)

    Docherty, Neil G; Murphy, Madeline; Martin, Finian; Brennan, Eoin P; Godson, Catherine

    2014-09-01

    Diabetic kidney disease occurs in >30% of patients with type 2 diabetes mellitus and is characterized at source by a maladaptive response in the renal parenchyma to exposure to a glucotoxic-lipotoxic diabetic milieu that courses coincident with hypertension. The consequence of these maladaptive responses is progressive renal injury, which is exacerbated by the development of a chronic inflammatory infiltrate associated with the development of tubulointerstitial fibrosis. The evolution of tubulointerstitial fibrosis is correlated with the loss of functional renal mass and descent towards renal failure. Transforming growth factor-β1 (TGF-β1) is a recognized mediator of the profibrotic response of mesangial cells and renal tubular epithelial cells to hyperglycaemia. While euglycaemia remains the goal in the treatment of type 2 diabetes mellitus, the prevention, arrest and reversal of microvascular complications, such as diabetic kidney disease, may be assisted by pharmacological modulation of the effectors of glucotoxicity, such as TGF-β1. This review focuses on describing how, through reductionist in vitro experimentation focusing on TGF-β1-related responses to hyperglycaemia, we have identified induced in high glucose-1 (IHG-1), induced in high glucose-2 (IHG-2/Grem1) and the lipoxin-inducible microRNA let-7c as potential targets for harnessing new therapeutic approaches to limit the bioactivity of TGF-β1 in diabetic kidney disease.

  4. 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 ...

  5. Evaluation of “Dream Herb,” Calea zacatechichi, for Nephrotoxicity Using Human Kidney Proximal Tubule Cells

    Directory of Open Access Journals (Sweden)

    Miriam E. Mossoba

    2016-01-01

    Full Text Available A recent surge in the use of dietary supplements, including herbal remedies, necessitates investigations into their safety profiles. “Dream herb,” Calea zacatechichi, has long been used in traditional folk medicine for a variety of purposes and is currently being marketed in the US for medicinal purposes, including diabetes treatment. Despite the inherent vulnerability of the renal system to xenobiotic toxicity, there is a lack of safety studies on the nephrotoxic potential of this herb. Additionally, the high frequency of diabetes-associated kidney disease makes safety screening of C. zacatechichi for safety especially important. We exposed human proximal tubule HK-2 cells to increasing doses of this herb alongside known toxicant and protectant control compounds to examine potential toxicity effects of C. zacatechichi relative to control compounds. We evaluated both cellular and mitochondrial functional changes related to toxicity of this dietary supplement and found that even at low doses evidence of cellular toxicity was significant. Moreover, these findings correlated with significantly elevated levels of nephrotoxicity biomarkers, lending further support for the need to further scrutinize the safety of this herbal dietary supplement.

  6. Evaluation of “Dream Herb,” Calea zacatechichi, for Nephrotoxicity Using Human Kidney Proximal Tubule Cells

    Science.gov (United States)

    Flynn, Thomas J.; Vohra, Sanah; Wiesenfeld, Paddy; Sprando, Robert L.

    2016-01-01

    A recent surge in the use of dietary supplements, including herbal remedies, necessitates investigations into their safety profiles. “Dream herb,” Calea zacatechichi, has long been used in traditional folk medicine for a variety of purposes and is currently being marketed in the US for medicinal purposes, including diabetes treatment. Despite the inherent vulnerability of the renal system to xenobiotic toxicity, there is a lack of safety studies on the nephrotoxic potential of this herb. Additionally, the high frequency of diabetes-associated kidney disease makes safety screening of C. zacatechichi for safety especially important. We exposed human proximal tubule HK-2 cells to increasing doses of this herb alongside known toxicant and protectant control compounds to examine potential toxicity effects of C. zacatechichi relative to control compounds. We evaluated both cellular and mitochondrial functional changes related to toxicity of this dietary supplement and found that even at low doses evidence of cellular toxicity was significant. Moreover, these findings correlated with significantly elevated levels of nephrotoxicity biomarkers, lending further support for the need to further scrutinize the safety of this herbal dietary supplement. PMID:27703475

  7. Kidney Dysplasia

    Science.gov (United States)

    ... Disease Ectopic Kidney Medullary Sponge Kidney Kidney Dysplasia Kidney Dysplasia What is kidney dysplasia? Kidney dysplasia is a condition in which ... Kidney dysplasia in one kidney What are the kidneys and what do they do? The kidneys are ...

  8. Relationship between Serum Uric Acid Levels and Kidney Arteriole Resistance in Patients with Type 2 Diabetes Associated with Hypertension

    Institute of Scientific and Technical Information of China (English)

    Wu Wodong; Mai Ciguang; Liang Weixiang; Xie Yinong; Liao Zhida; Yang Junqing

    2005-01-01

    Objectives To investigate the relationship between serum uric acid levels and arteriole resistance detected with the color Doppler energy imaging (CDEI) and to explore the risks of impaired regulation of vascular tone by uric acid in kidneys of hypertension patients. Methods In 12 healthy control cases, 28 non-diabetic hypertension (nNIDDM +H) cases and 25 type 2 diabetic hypertension (NIDDM+H) cases, uric acid (UA)levels were measured with uricase-peroxidase method.Arteriole resistance index (RI) and pulsate index (PI) in separate sections of renal artery included MAR,SRA, IRA were detected using CDEI with 2.1~4.2 Hz Doppler transducer in kidneys. Results In comparison,UA was significantly higher in non-diabetic hypertension group and diabetic hypertension group than in control group (P < 0.01, separately). UA levels was also significantly higher in NIDDM +H group than in nNIDDM +H, P < 0.029. RI in separate sections of renal artery was significantly higher in nNIDDM+H, or NIDDM+H group than in control group ( all P < 0.01 ),and it was significantly higher in NIDDM +H than nNIDDM +H groups (P < 0.05 and P < 0.01). In nNIDDM +H and NIDDM +H groups UA levels and IRA-RI could be elevated significantly following with the impaired heart function being aggravated (X2=13.028, P=0.005, X2=13.29, P=0.004); the dosage of HCT being increased ( X2 =14.216, P=0.001, X2 =14.661, P=0.001); the levels of GHbA1 being excessed unnormally (P=0.000). The correlation between UA and IRA-RI in both hypertension groups were directly related, in nNIDDM+H group r=0.842, P=0.000, in NIDDM+H group, r=0.797, P=0.000. Conclusions Uric acid levels and IRA-RI in hyper-tension patients were directly related. Uric acid levels and IRA-RI could be partly dependent on the severity of heart dysfunction, diuretic dose, and serum glucose status of diabete patients in long-term. Uric acid and the xanthine oxidase metabolic pathway may contribute to impaired regulation of arteriole tone in

  9. Oxygen metabolic competition in the lactic acidotic diabetic kidney: A point of no return?

    DEFF Research Database (Denmark)

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

    2016-01-01

    Diabetic nephropathy is directly related to renal hypoxia, with an increased mitochondrial uncoupling and increased energy demand to maintain normal renal function. Lowering the oxygen content in inspired air has shown to worsen the prognostic outcome of diabetic patients independent of glycemic...

  10. 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.

  11. Cumulative Effects of Hypertension, Dyslipidemia, and Chronic Kidney Disease on Carotid Atherosclerosis in Chinese Patients with Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Chuang Yuan

    2014-01-01

    Full Text Available Aims. The aim of this study is to determine the extent of carotid atherosclerosis in Chinese patients with type 2 diabetes in relation to the cumulative atherosclerosis risk factors using ultrasonography. Methods. The presence of hypertension, dyslipidemia, and chronic kidney disease (CKD was documented in 106 Chinese subjects with type 2 diabetes. Subjects with 0, 1, and ≥2 additional atherosclerosis risk factors were assigned into groups 1, 2, and 3, respectively (n=17, 49, and 40, resp.. Using ultrasound, the carotid arteries were assessed for the presence of carotid plaque, plaque score, intima-media thickness (IMT, and carotid arterial stiffness. Results. With the adjustment for age and gender, the presence of plaque and plaque score were significantly higher in groups with more atherosclerosis risk factors (P 60 years old (odds ratio = 2.75; 95% CI: 1.26–6.0 and the presence of hypertension (odds ratio = 2.48; 95% CI: 1.11–5.58, dyslipidemia (odds ratio = 2.41; 95% CI: 1.05–5.51, and CKD (odds ratio = 7.80; 95% CI: 1.46–41.72 could independently predict higher plaque score (P<0.05. Conclusions. Hypertension, dyslipidemia, and CKD in Chinese patients with type 2 diabetes have cumulative effects on the burden of carotid plaque.

  12. Significance and Expression of Serum and Glucocorticoid-inducible Kinase in Kidney of Mice with Diabetic Nephropathy

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To investigate the expression and the role of three isoforms of Serum and Glucocorticoidinducible Kinase (SGK) in experimental diabetic nephropathy (DN), 12 male C57BL/6 mice of 8-weeks-old were divided into two groups. Streptozotocin (STZ)-induced diabetic nephropathy and normal controls were analyzed at the end of the 4th week after the induction of diabetes. Renal hemodynamics and histological studies were performed. The expression of SGK1 mRNA, SGK2 mRNA and SGK3 mRNA of kidney cortex were measured by RT-PCR, and the cortical SGK1 protein was detected with Western blotting. Our results showed that the blood glucose, blood HbA1c, 24-h urinary protein, creatinine clearance and the renal index were all increased in DN group. More extracellular matrix (ECM) accumulation was observed. The level of cortical SGK1 mRNA and protein were up-regulated in DN group in comparison with control group. SGK2 and SGK3 mRNA were elevated in DN mice. In DN, mRNA level of three SGK isoforms and SGK1 protein were increased significantly. It is concluded that SGKs may contribute to the early renal injury of DN.

  13. 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...

  14. Effect of passage number on electrophoretic mobility distributions of cultured human embryonic kidney cells

    Science.gov (United States)

    Kunze, M. E.

    1985-01-01

    A systematic investigation was undertaken to characterize population shifts that occur in cultured human embryonic kidney cells as a function of passage number in vitro after original explantation. This approach to cell population shift analysis follows the suggestion of Mehreshi, Klein and Revesz that perturbed cell populations can be characterized by electrophoretic mobility distributions if they contain subpopulations with different electrophoretic mobilities. It was shown that this is the case with early passage cultured human embryo cells.

  15. Beneficial Effect of 7-O-Galloyl-D-sedoheptulose, a Polyphenol Isolated from Corni Fructus, against Diabetes-Induced Alterations in Kidney and Adipose Tissue of Type 2 Diabetic db/db Mice

    Directory of Open Access Journals (Sweden)

    Chan Hum Park

    2013-01-01

    Full Text Available Traditional medicines are being focused on as possible treatments for diabetes and its complications because of their negligible toxic and/or side effects. In line with this, our group has reported that Corni Fructus, a traditional medicine considered exhibiting beneficial effects on liver and kidney functions, possessed an antidiabetic effect via ameliorating glucose-mediated metabolic disorders. To add to these findings, we screened the iridoid glycoside fraction containing morroniside and loganin, and low molecular weight polyphenol fraction containing 7-O-galloyl-d-sedoheptulose (GS from Corni Fructus. To our knowledge, GS is a compound only detected in Corni Fructus, and its biological activity has been poorly understood until now. For these reasons, we examined whether GS has an ameliorative effect on diabetic changes using type 2 diabetic db/db mice. Our findings suggest that GS has a beneficial effect on the pathological state of the serum, kidney, and adipose tissue related to diabetic damage.

  16. Beneficial Effect of 7-O-Galloyl-D-sedoheptulose, a Polyphenol Isolated from Corni Fructus, against Diabetes-Induced Alterations in Kidney and Adipose Tissue of Type 2 Diabetic db/db Mice

    Science.gov (United States)

    Park, Chan Hum; Noh, Jeong Sook; Park, Jong Cheol; Yokozawa, Takako

    2013-01-01

    Traditional medicines are being focused on as possible treatments for diabetes and its complications because of their negligible toxic and/or side effects. In line with this, our group has reported that Corni Fructus, a traditional medicine considered exhibiting beneficial effects on liver and kidney functions, possessed an antidiabetic effect via ameliorating glucose-mediated metabolic disorders. To add to these findings, we screened the iridoid glycoside fraction containing morroniside and loganin, and low molecular weight polyphenol fraction containing 7-O-galloyl-d-sedoheptulose (GS) from Corni Fructus. To our knowledge, GS is a compound only detected in Corni Fructus, and its biological activity has been poorly understood until now. For these reasons, we examined whether GS has an ameliorative effect on diabetic changes using type 2 diabetic db/db mice. Our findings suggest that GS has a beneficial effect on the pathological state of the serum, kidney, and adipose tissue related to diabetic damage. PMID:24348717

  17. Renal (pro)renin receptor contributes to development of diabetic kidney disease through transforming growth factor-β1-connective tissue growth factor signalling cascade.

    Science.gov (United States)

    Huang, Jiqian; Matavelli, Luis C; Siragy, Helmy M

    2011-04-01

    1. Transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) are expressed in renal glomeruli, and contribute to the development of diabetic nephropathy. Recently, we showed that (pro)renin receptor (PRR) is upregulated in the kidneys of the streptozocin (STZ)-induced diabetes rat model. We hypothesized that in the presence of hyperglycaemia, increased renal PRR expression contributes to enhanced TGF-β1-CTGF signalling activity, leading to the development of diabetic kidney disease. 2. In vivo and in vitro studies were carried out in Sprague-Dawley rats and rat mesangial cells (RMC). PRR blockade was achieved in vivo by treating STZ induced diabetes rats with the handle region peptide (HRP) of prorenin and in vitro by HRP or PRR siRNA in RMC. Angiotensin AT1 receptor blockade was achieved by valsartan treatment. 3. Results showed that expression of PRR, TGF-β1 and CTGF were upregulated in diabetic kidneys and RMC exposed to high glucose. Glucose exposure also induced PRR phosphorylation, a process that was inhibited by HRP, valsartan or PRR siRNA. HRP and valsartan significantly attenuated renal TGF-β1 and CTGF expression in diabetic animals and high glucose treated RMC. Similar results were observed in high glucose exposed RMC in response to PRR siRNA. TGF-β receptor blockade decreased CTGF expression in RMC. Combined administration of valsartan and PRR siRNA showed further reduction of TGF-β1 and CTGF expression in RMC. 4. In conclusion, PRR contributes to kidney disease in diabetes through an enhanced TGF-β1-CTGF signalling cascade.

  18. Chronic administration of EP4-selective agonist exacerbates albuminuria and fibrosis of the kidney in streptozotocin-induced diabetic mice through IL-6.

    Science.gov (United States)

    Mohamed, Riyaz; Jayakumar, Calpurnia; Ramesh, Ganesan

    2013-08-01

    Diabetic nephropathy is currently the most common cause of end-stage renal disease in the western world. Exacerbated inflammation of the kidney is known to contribute acceleration of nephropathy. Despite increased COX-2-mediated production of prostanoid metabolite PGE2, knowledge on its involvement in the progression of diabetic kidney disease is not complete. Here, we show the cross talk of the PGE2-EP4 pathways and IL-6 in inducing albuminuria and fibrosis in an animal model of type 1 diabetes. Hyperglycemia causes enhanced COX-2 expression and PGE2 production. Administration of PGE2 receptor EP4-selective agonist ONO-AE1-329 for 12 weeks exacerbated fibrosis and albuminuria. Diabetes-induced expression of inflammatory cytokines TNFα and TGFβ1 was enhanced in EP4 agonist-treated mice kidney. In addition, urinary excretion of cytokines (TNFα and IL-6) and chemokines (MCP-1 and IP-10) were significantly more in EP4-treated mice than vehicle-treated diabetes. Diabetes-induced collagen I and CTGF expression were also significantly higher in EP4-treated mice. However, EP4 agonist did not alter macrophage infiltration but increased cytokine and chemokine production in RAW264.7 cells. Interestingly, EP4-induced IL-6 expression in the kidney was localized in proximal and distal tubular epithelial cells. To confirm further whether EP4 agonist increases fibrosis and albuminuria through an increase in IL-6 expression, IL-6-knockout mice were administered with EP4 agonist. IL-6-knockout mice were resistant to EP4-induced exacerbation of albuminuria and diabetes and EP4-induced fibrosis. Our data suggest that EP4 agonist through IL-6 induces glomerulosclerosis and interstitial fibrosis, and IL-6 represents a new factor in the EP4 pathway.

  19. The directed differentiation of human iPS cells into kidney podocytes.

    Science.gov (United States)

    Song, Bi; Smink, Alexandra M; Jones, Christina V; Callaghan, Judy M; Firth, Stephen D; Bernard, Claude A; Laslett, Andrew L; Kerr, Peter G; Ricardo, Sharon D

    2012-01-01

    The loss of glomerular podocytes is a key event in the progression of chronic kidney disease resulting in proteinuria and declining function. Podocytes are slow cycling cells that are considered terminally differentiated. Here we provide the first report of the directed differentiation of induced pluripotent stem (iPS) cells to generate kidney cells with podocyte features. The iPS-derived podocytes share a morphological phenotype analogous with cultured human podocytes. Following 10 days of directed differentiation, iPS podocytes had an up-regulated expression of mRNA and protein localization for podocyte markers including synaptopodin, nephrin and Wilm's tumour protein (WT1), combined with a down-regulation of the stem cell marker OCT3/4. In contrast to human podocytes that become quiescent in culture, iPS-derived cells maintain a proliferative capacity suggestive of a more immature phenotype. The transduction of iPS podocytes with fluorescent labeled-talin that were immunostained with podocin showed a cytoplasmic contractile response to angiotensin II (AII). A permeability assay provided functional evidence of albumin uptake in the cytoplasm of iPS podocytes comparable to human podocytes. Moreover, labeled iPS-derived podocytes were found to integrate into reaggregated metanephric kidney explants where they incorporated into developing glomeruli and co-expressed WT1. This study establishes the differentiation of iPS cells to kidney podocytes that will be useful for screening new treatments, understanding podocyte pathogenesis, and offering possibilities for regenerative medicine.

  20. The directed differentiation of human iPS cells into kidney podocytes.

    Directory of Open Access Journals (Sweden)

    Bi Song

    Full Text Available The loss of glomerular podocytes is a key event in the progression of chronic kidney disease resulting in proteinuria and declining function. Podocytes are slow cycling cells that are considered terminally differentiated. Here we provide the first report of the directed differentiation of induced pluripotent stem (iPS cells to generate kidney cells with podocyte features. The iPS-derived podocytes share a morphological phenotype analogous with cultured human podocytes. Following 10 days of directed differentiation, iPS podocytes had an up-regulated expression of mRNA and protein localization for podocyte markers including synaptopodin, nephrin and Wilm's tumour protein (WT1, combined with a down-regulation of the stem cell marker OCT3/4. In contrast to human podocytes that become quiescent in culture, iPS-derived cells maintain a proliferative capacity suggestive of a more immature phenotype. The transduction of iPS podocytes with fluorescent labeled-talin that were immunostained with podocin showed a cytoplasmic contractile response to angiotensin II (AII. A permeability assay provided functional evidence of albumin uptake in the cytoplasm of iPS podocytes comparable to human podocytes. Moreover, labeled iPS-derived podocytes were found to integrate into reaggregated metanephric kidney explants where they incorporated into developing glomeruli and co-expressed WT1. This study establishes the differentiation of iPS cells to kidney podocytes that will be useful for screening new treatments, understanding podocyte pathogenesis, and offering possibilities for regenerative medicine.