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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The small proteoglycan decorin may intercept the activity of the TGF-beta system. Decorin administration has been advocated as potential therapy in renal fibrotic diseases, because of the findings of a relative deficiency of decorin and a relative excess of TGF-beta in acute glomerulonephritis. Does a similar situation pertain in diabetic kidney disease? Activation of TGF-beta seems to be crucial to tissue injury in diabetic nephropathy, but until recently it has not been established whether decorin plays any role in the manifestations of this disease. We review evidence that a surfeit rather than a deficit in decorin expression exists in diabetic renal disease, and that there exists a negative feed-back loop whereby TGF-beta1 induces down-regulation of decorin expression. Rat and mouse mesangial cells as well as mouse proximal tubular cells in culture exhibit increased decorin mRNA levels in high ambient glucose. Decorin mRNA level in the kidney of streptozotocin-induced diabetes in mice is rapidly and significantly increased following the induction of diabetes. Thus, the available evidence suggests that renal decorin is not deficient in this disorder and hence decorin supplementation does not seem to be warranted. Rather, interception of the effects of TGF-beta seems to be an approach most likely to yield beneficial results in diabetic nephropathy.
Nephrol Dial Transplant 1999 May
PMID:What is the role of decorin in diabetic kidney disease? 1034 40

Throughout the industrialized (well-fed) world, diabetes mellitus is the most prevalent cause of end-stage renal disease (ESRD). Diabetic nephropathy is as likely to develop in long-duration non-insulin-dependent diabetes (type 2) as in insulin-dependent diabetes mellitus (type 1). Nephropathy in diabetes follows a well outlined course, starting with microalbuminuria through proteinuria, azotaemia and culminating in ESRD. Renal functional decline in diabetic nephropathy is slowed by establishment of euglycaemia and normalization of hypertensive blood pressure. Diabetic ESRD patients, compared with other causes of ESRD, sustain greater mortality and morbidity due to concomitant systemic disorders, especially coronary artery and cerebrovascular disease. A central role for glucose toxicity, especially the adverse impact of accumulated advanced glycosylated end-products (AGEs), appears likely from experimental data generated both in induced diabetic rodents and diabetic individuals. Treatment with aminoguanidine raises the possibility of blocking end-organ damage in diabetes without the necessity for correcting hyperglycaemia.
Nephrol Dial Transplant 1999
PMID:Advanced glycation end-products in diabetic nephropathy. 1038 74

Recent experimental work implicates transforming growth factor-beta (TGF-beta) as an aetiologic mediator of diabetic nephropathy and the ubiquitous glucose transporter GLUT1 as an important permissive factor for the tissue injury caused by hyperglycaemia. High ambient glucose increases GLUT1 expression and glucose transport activity when compared with physiologic glucose concentrations. Treatment of rat mesangial cells with TGF-beta up-regulates GLUT1 mRNA and protein levels and significantly increases glucose uptake. Addition of neutralizing anti-TGF-beta antibody prevents the stimulatory effects of high glucose on GLUT1 expression. Cultured rat mesangial cells transduced with the human GLUT1 gene and thus overexpressing the GLUT1 protein show marked increase in glucose uptake and the synthesis of extracellular matrix molecules, even when grown in normal ambient glucose concentrations. Thus, TGF-beta and GLUT1, two proteins that are up-regulated in glomerular mesangial cells in a hyperglycaemic milieu, can influence the expression of one another. It is therefore fair to conclude that, with successful interruption of the TGF-beta-GLUT1 axis, the beneficial effects of strict glucose control on the development of diabetic nephropathy could likely be augmented.
Nephrol Dial Transplant 1999 Dec
PMID:GLUT1 and TGF-beta: the link between hyperglycaemia and diabetic nephropathy. 1097 17

We retrospectively evaluated the factors that are prognostic in long-term continuous ambulatory peritoneal dialysis (CAPD). From 1986 to 1997, 91 CAPD patients (59 male, 32 female, mean age 48 years) entered the study. Their primary renal diseases were chronic glomerulonephritis (CGN, n = 80), diabetic nephropathy (DN, n = 10), and polycystic kidney disease (PKD, n = 1). The roles of primary renal disease, hypertension, left ventricular hypertrophy (LVH), left ventricular ejection fraction (LVEF), cardiac sympathetic activity, anemia, hypoalbuminemia, and plasma concentration of parathyroid hormone (PTH) on patient prognosis were analyzed. Among the 91 CAPD patients, 26 died during the observation period. Of these deaths, 17 resulted from cardiovascular diseases including cerebrovascular events (n = 7), myocardial infarction (n = 2), sudden death (n = 7), and aortic aneurysmal rupture (n = 1). Nine patients died of non cardiovascular events. Sclerosing encapsulating peritonitis and others, mainly cachexia, accounted for 2 and 7 of these deaths, respectively. The 5-year survival rate was 74%; the 10-year rate was 49%. The cumulative 5- and 10-year success rates of CAPD were 69% and 39%, respectively. DN, hypertension, severe LVH (more than 200 g/m2), and hypoalbuminemia were contributors to poor prognosis. Among these, DN and severe LVH were the two main predictors by Cox proportional hazards model. We conclude that CAPD patients with DN or severe LVH, or both, have a greater chance of drop-out from cardiovascular events.
Adv Perit Dial 1999
PMID:Predictors of survival in continuous ambulatory peritoneal dialysis patients: the importance of left ventricular hypertrophy and diabetic nephropathy. 1068 78

Chronic renal failure is an unusual complication of hereditary clotting disorders (HCDs), but this situation could change in the near future. The modality of dialysis for end-stage renal disease (ESRD) in patients with an HCD is a difficult choice. Hemodialysis (HD) may be considered, but intensive treatment with coagulation factors is required for vascular access execution and for each HD procedure. Peritoneal dialysis (PD) has been infrequently proposed. However, PD requires coagulation replacement therapy only during peritoneal catheter placement. The aim of this paper is to describe our experience of three patients with ESRD and HCD, successfully treated with chronic PD in the medium term. Case 1 was a 58-year-old man with moderate hemophilia A, type 2 diabetes mellitus, and hepatitis C virus (HCV) infection. His ESRD was secondary to glomerulonephritis. A double-cuff peritoneal catheter was surgically placed with pre-emptive factor VIII administration. He began treatment with continuous ambulatory peritoneal dialysis (CAPD). An inguinal hernia was repaired without complications. After eleven months of follow-up, no hemorrhage episodes have been observed and clinical outcome is optimal. Case 2 was a 46-year-old man with severe hemophilia A, type 2 diabetes mellitus, and HCV and human immunodeficiency virus (HIV) infections. He developed a diabetic nephropathy that required renal replacement therapy. A permanent silicone catheter was inserted in the left internal jugular vein, and the patient started HD treatment. Later on, PD therapy was proposed. A peritoneal catheter was implanted with simultaneous factor VIII infusion. Minimal bleeding was observed at the subcutaneous tunnel over the following 48 hours. The patient started PD treatment without complications, and two months later, remaining asymptomatic, transferred to another center. Case 3 was a 41-year-old woman diagnosed with von Willebrand disease type 2A, HCV infection, and polycystic kidney disease, who presented with ESRD. An internal arteriovenous fistula was performed under coagulation factor cover. During a fistulography, and despite coagulation factor substitutive treatment, the patient showed an important hematoma. Afterwards, PD was considered. A peritoneal catheter was implanted under coagulation factor cover. The postoperative course was uncomplicated, and the patient started CAPD treatment. During follow up, she suffered two hemoperitoneum episodes that were resolved with cold dialysate. After nine months, she uneventfully continued on PD. In conclusion, PD is the therapy of choice for patients with hereditary clotting disorders and ESRD requiring dialysis. Peritoneal dialysis therapy avoids many of the complications related to HD therapy.
Adv Perit Dial 2000
PMID:Peritoneal dialysis is the therapy of choice for end-stage renal disease patients with hereditary clotting disorders. 1104 86

The introduction of recombinant erythropoietin (Epo, epoetin) has resulted in a shift in focus from the treatment to the prevention of anaemia. This shift in treatment goals has provided nephrologists with the challenge of implementing preventative strategies in clinical practice. While this area of nephrology is still developing, a lot can be learned from the methods applied by clinicians involved in the prevention of other diseases, particularly non-insulin-dependent (type 2) diabetes mellitus. The prevention of type 2 diabetes has become a major aim of healthcare providers globally due to the epidemic proportions of the disease. In order to reverse this worrying trend, diabetologists have had to develop effective management strategies based upon their current knowledge. Nephrologists must now adopt a similar approach if the increasing threat from diabetic nephropathy is to be reversed. This should include strict normotension, the prescribing of angiotensin-converting enzyme (ACE) inhibitors, administration of lipid-lowering agents, and the near-normalization of anaemia with epoetin. However, the implementation of treatment strategies alone is unlikely to be sufficient. Indeed, an effective programme of education is required to ensure that patients understand the seriousness of their condition and remain compliant with treatment. Similarly, educating the general public may help to reduce the burden of type 2 diabetes and the subsequent problems associated with the disease, including renal disease.
Nephrol Dial Transplant 2001
PMID:Advances in nephrology: successes and lessons learnt from diabetes mellitus. 1159 Feb 57

Anaemia is an important component of diabetic nephropathy but only recently has it attracted the attention of diabetologists and nephrologists. In diabetic patients, anaemia is the result of diminished erythropoietin production and, to a lesser degree, of increased excretion of erythropoietin in the urine, whereas erythropoietin responsiveness remains unchanged. Although erythropoietin concentrations are predictive of the rate of progression of renal disease, epidemiological studies have failed to show lower haemoglobin concentrations in patients with diabetic compared with non-diabetic renal disease with impaired renal function. However, inappropriately low erythropoietin concentrations and anaemia have been reported in subcohorts of diabetic patients. Further studies are required to determine whether reversal of anaemia has beneficial effects on microvascular and macrovascular diabetic complications, particularly cardiac disease, retinopathy and peripheral arterial disease.
Nephrol Dial Transplant 2002
PMID:How should we manage anaemia in patients with diabetes? 1181 16

Renal anaemia starts earlier in the progression of chronic kidney disease (CKD) than was previously thought and is often inadequately monitored and treated. Current treatment guidelines recommend giving recombinant erythropoietin (rHuEPO) as soon as haemoglobin (Hb) concentration falls below 11 g/dl and alternative causes of anaemia have been ruled out. Recent studies show that, in practice, few patients receive rHuEPO in the pre-dialysis period and Hb concentrations are often <9 g/dl at the start of haemodialysis. This is at odds with best practice since renal anaemia is a major risk factor for left ventricular hypertrophy. Many factors other than provision of rHuEPO therapy can affect the occurrence and severity of renal anaemia. Iron deficiency is the most common cause of resistance to rHuEPO and appropriate use of iron supplementation in patients with CKD is still being debated. The acute-phase immune response has a more significant role in renal anaemia and rHuEPO resistance than previously believed, as demonstrated by the need for higher rHuEPO doses in patients with raised levels of C-reactive protein. Women often need higher doses of rHuEPO than men, which may be related to differences in androgen levels between the sexes. Low erythropoietin concentrations are a major factor in diabetic nephropathy. Correction of anaemia with rHuEPO may slow progression of CKD by reducing oxidative stress. These and other factors need to be considered for the optimal treatment of patients with anaemia of CKD.
Nephrol Dial Transplant 2002
PMID:Non-erythropoietin-based anaemia management in chronic kidney disease. 1238 56

We identified a novel gene, termed megsin, predominantly expressed in mesangial cells utilizing a 3'-directed regional cDNA library from cultured human mesangial cells. Megsin is a novel serine protease inhibitor (serpin), and the level of megsin RNA/protein expression is up-regulated in patients with IgA nephropathy or diabetic nephropathy, suggesting a link between megsin expression and the pathogenesis of mesangial expansion and/or proliferation. To assess the pathophysiological significance of megsin, we produced human megsin transgenic mice. Genetic manipulation of megsin engenders two elementary mesangial lesions, mesangial expansion and an increase in the number of mesangial cells.
Nephrol Dial Transplant 2002
PMID:Mesangial cell-predominant gene, megsin. 1238 81

The past two decades have yielded major advances in our understanding of the pathogenetic mechanisms that cause diabetic nephropathy. Of particular interest is the emerging paradigm of the recapitulation of developmental programmes within the diabetic kidney. Recently we have used the complementary techniques of suppression subtractive hybridization and Affymetrix GeneChips to assess changes in gene expression in human mesangial cells subjected to high ambient glucose concentrations and cyclic mechanical strain in vitro, the latter being models of hyperglycaemia and glomerular hypertension, respectively. In this review, we will focus on the potential role of one such differentially expressed gene, namely gremlin, in the pathogenesis of diabetic nephropathy. In the context of developmental nephrology, gremlin warrants special mention. Gremlin is a 184 amino acid protein and a member of the cysteine knot superfamily. The protein is highly conserved during evolution and is present in soluble and cell-associated forms. It belongs to a novel family of bone morphogenetic protein (BMP) antagonists that includes the head-inducing factor Cerberus and the tumour suppressor DAN. These proteins play important roles in limb development and neural crest cell differentiation. Evidence will be presented that mesangial cell gremlin expression is up-regulated by high ambient glucose, cyclic mechanical strain and transforming growth factor-beta (TGF-beta) and that gremlin may be an important modulator of mesangial cell proliferation and epithelial-mesenchymal transdifferentiation in a diabetic milieu.
Nephrol Dial Transplant 2002
PMID:Gremlin: an example of the re-emergence of developmental programmes in diabetic nephropathy. 1238 93


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