Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Iron accumulates within proximal tubular lysosomes in several models of renal disease and may play a role in the progression of proteinuric chronic renal disease by the generation of reactive oxygen species. In this study, tubular iron was examined at an ultrastructural level by energy dispersive x-ray spectrometry in streptozotocin (STZ) and BB diabetic rats, and in humans with diabetic nephropathy, and compared to their respective nondiabetic controls. Substantial amounts of iron accumulated in the secondary lysosomes of proximal tubules in STZ diabetic rats (4.16 +/- 0.47 iron-containing lysosomes/microns 2 x 10(-3) tubular area vs. 0.90 +/- 0.29 in controls, p < 0.001). Proximal tubular iron was related independently with urinary protein and transferrin excretion, suggesting increased cellular uptake of iron from the tubular fluid. Lysosomal iron accumulation was also associated with tubular damage (r = 0.55, p < 0.001). Minimal amounts of tubular iron were observed in BB diabetic and nondiabetic littermates. In humans with diabetic nephropathy, increased proximal tubular lysosomal iron concentration (35.6 +/- 13.0 mg% Fe vs. 9.5 +/- 2.7, p < 0.05) and numbers of iron-containing lysosomes were observed compared to nondiabetic controls, and the latter correlated with elevation of serum creatinine (r = 0.94, p = 0.016). These results suggest that filtered iron enters proximal tubular lysosomes across the brush-border membrane and are consistent with a role for iron in causing the tubular damage of diabetic nephropathy.
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PMID:Lysosomal iron accumulation in diabetic nephropathy. 805 20

Urinary iron excretion rate(u-FeER, microgram/min) in urine at night time from 58 patients with non-insulin dependent diabetes mellitus and 8 controls was measured by atomic absorption. The patients were divided into three groups according to urinary albumin excretion rate(u-AER), namely, Group I(n = 44): less than 20 micrograms/min of u-AER; Group II(n = 9): 20 < or = u-AER < 200 micrograms/min; Group III(n = 5): more than 200 micrograms/min of u-AER. The u-FeER in group III(56.3 +/- 14.8 ng/min, mean +/- SEM) was significantly higher than that in controls (4.0 +/- 1.6ng/min), group I(8.3 +/- 1.6 ng/min) and group II(18.5 +/- 6.5ng/min). The increase of u-FeER in group III indicates that urinary iron may at least partly play a role in development of diabetic nephropathy.
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PMID:[Increased urinary iron excretion rate in patients with non-insulin dependent diabetes mellitus]. 899 Sep 41

The importance of iron in renal injury is derived from the ease with which iron is reversibly oxidized or reduced, enabling it to participate in the production of free radicals. Experimental evidence for the role of oxidants and iron in progressive renal disease falls into two broad categories. First, considerable data implicate oxidants in the proteinuria of glomerular disease. To the extent that proteinuria is an important determinant of progression, reduction of proteinuria would result in retardation of progression. Evidence also suggests a role of oxidants and iron in diabetic nephropathy, a major cause of end-stage kidney disease. Second, more direct studies have examined the role of oxidants and iron in models of progressive renal disease. These studies include the demonstration of increased iron in the kidney in models of progressive kidney disease; enhanced generation of oxidants, providing a mechanism by which iron can be mobilized; and more direct evidence of the beneficial effect of iron-deficient diets and iron chelators. Although the collective information on the role of oxidants and iron derived from in vitro studies and animal models of glomerular disease and progressive renal failure is impressive, control studies of patients are needed to show the efficacy of antioxidants and/or iron chelators in retarding the progression of renal failure and may offer an important therapeutic modality to patients with renal disease.
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PMID:Role of iron in progressive renal disease. 1115 58

BACKGROUND: Transferrinuria is thought to be a marker for early stages of diabetic nephropathy. Transferrin has also been proposed as a mediator of tubular toxicity because the reabsorption of transferrin results in the release of reactive iron in proximal tubular cells, promoting the formation of hydroxyl radicals. We evaluated the role of urinary transferrin excretion in diabetic patients with early nephropathy by comparing tubulointerstitial injury in renal biopsy specimens. PATIENTS AND METHODS: 45 type 2 diabetic patients with normoalbuminuria (urinary albumin excretion <30 mg/24 h) or microalbuminuria (30-300 mg/24 h) were studied. All patients with microalbuminuria underwent renal biopsy, and the severity of the tubulo-interstitial lesions was determined by a semiquantitative estimate of interstitial fibrosis, tubular atrophy, and interstitial inflammatory infiltrates. Subjects were classified into group A (normoalbuminuria, n=25), group B (microalbuminuria without tubulointerstitial changes, n=11) or group C (microalbuminuria with tubulointerstitial changes, n=9). RESULTS: Urinary transferrin excretion (UTf), as well as UTf/creatinine clearance (Ccr), and transferrin clearance (CTf/Ccr), was significantly higher in groups B and C than in group A, and it was significantly higher in group C than in group B. There were no significant differences in urinary albumin excretion or mesangial expansion rate (MR% estimated by quantitative morphometric studies) between groups B and C. Although urinary beta2-microglobulin excretion was significantly higher in group C than in groups A and B, urinary N-acetyl-beta-D-glucosaminidase activity was significantly higher in groups B and C than in group A. CONCLUSIONS: Increased transferrinuria in the microalbuminuric stage may lead to the development of tubulointerstitial injuries in type 2 diabetic patients.
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PMID:Transferrinuria in type 2 diabetic patients with early nephropathy and tubulointerstitial injury. 1202 Jun 27

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.
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PMID:Non-erythropoietin-based anaemia management in chronic kidney disease. 1238 56

Diabetic nephropathy has become the leading cause of uremia. Several lines of evidence suggest dietary factors other than protein intake have a substantial role in the progression of diabetic nephropathy to end-stage renal disease. The present investigation was initiated to evaluate whether a carbohydrate-restricted, low-iron-available, polyphenol-enriched (CR-LIPE) diet may delay and improve the outcome of diabetic nephropathy to a greater extent than standard protein restriction. To this aim, 191 diabetic patients, all with type 2 diabetes, were randomized to either CR-LIPE or standard protein restriction and the following outcomes monitored: doubling of serum creatinine, cumulative incidence of end-stage renal disease, and all cause mortality. Over a mean follow-up interval of 3.9 +/- 1.8 years, serum creatinine concentration doubled in 19 patients on CR-LIPE (21%) and in 31 control subjects (39%) (P < 0.01). Renal replacement therapy or death occurred in 18 patients on CR-LIPE (20%) and in 31 control subjects (39%) (P < 0.01). These differences were independent from follow-up interval, sex, mean arterial blood pressure, HbA(1c), initial renal dysfunction, and angiotensin system inhibitor use. In conclusion, CR-LIPE was 40-50% more effective than standard protein restriction in improving renal and overall survival rates.
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PMID:A low-iron-available, polyphenol-enriched, carbohydrate-restricted diet to slow progression of diabetic nephropathy. 1296 32

The 36th Annual Meeting of the American Society of Nephrology, held in San Diego, California, USA, November 12-17, 2003, presented the newest advances in basic and clinical nephrology science. Several presentations and symposia discussed many new aspects of the management of type 2 diabetic nephropathy as well as the recent advances in the treatment of secondary hyperparathyroidism in chronic kidney disease patients with cinacalcet HCl, a calcimimetic agent. New drugs that are under development for the treatment of renal anemia, such as the continuous erythropoiesis receptor activator (CERA), or for the treatment of pure red cell aplasia, a rare but severe complication of the erythropoietic treatment, were considered. The long-term safety of i.v. iron replacement therapy was also analyzed. The recent results of the Dialysis Outcomes and Practice Patterns Study (DOPPS), a large, multinational, observational study in hemodialysis patients were presented. Some complications of renal transplantation, recent advances in immunosuppressive agents and the experience of renal transplant in HIV patients recipients were also reviewed during the congress. The 36th Annual Meeting of the American Society of Nephrology offered the newest advances in basic and clinical nephrology science and was attended by more than 11,000 nephrologists from around the world. This year's sessions included 45 basic and clinical science symposia, 22 clinical nephrology conference sessions, 17 official symposia, as well as oral communications and poster sessions.
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PMID:Update in nephrology. Highlights from the 36th Annual Meeting of the American Society of Nephrology. 1498 72

Anaemia is a common complication of chronic kidney disease (CKD). It is often more severe and occurs at an earlier stage in patients with diabetic nephropathy than in patients with CKD of other causes. This anaemia results from erythropoietin deficiency, which seems to develop in patients with type 1 diabetes even at relatively "normal" levels of serum creatinine. Early erythropoietin- deficiency anaemia occurs in both type 1 and type 2 diabetes, although the prevalence may be higher in type 1 diabetes. However, numerically most patients with erythropoietin-deficiency anaemia have type 2 diabetes as it is a much more common disease. There is also a greater prevalence in women than men but this is not related to iron stores. In addition, erythropoietin-deficiency anaemia is associated with the presence of autonomic neuropathy in patients with diabetes. Small studies have suggested that recombinant human erythropoietin (rhEPO; epoetin) treatment is effective in correcting erythropoietin-deficiency anaemia in patients with diabetes. Additionally, rhEPO therapy improves quality of life and well-being in these patients. Studies also suggest that treatment with rhEPO to restore a normal haematocrit ameliorates orthostatic hypotension. Given the high cardiovascular risk in patients with diabetic nephropathy, it is important to determine in prospective clinical trials whether early anaemia correction can also improve cardiovascular outcomes.
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PMID:Anaemia in diabetes. 1510 43

Oxidants derived either from leukocytes in proliferative glomerular nephritis or from resident glomerular cells in nonproliferative glomerulonephritis have been shown to have several biologic effects relevant to chronic kidney disease. These include: the ability of oxidants to damage glomerular basement membrane (GBM) and to directly induce proteinuria; effects that would lead to a fall in the glomerular filtration rate; and effects that would account for the morphologic changes observed in chronic kidney disease. In experimental models the role of oxidants has been demonstrated in both proliferative glomerulonephritis (e.g., anti-GBM antibody disease) as well as experimental models of minimal change disease and membranous nephropathy. Oxidants have also been shown to be an important mediator of the various pathways that have been implicated in diabetic nephropathy. Antioxidants and iron chelators have also been shown to retard functional and morphologic changes observed in progressive kidney disease. Taken together, these experimental studies suggest an important role of oxidants in chronic kidney disease.
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PMID:Oxidants and iron in chronic kidney disease. 1546 4

Diabetes mellitus is associated with altered iron homeostasis in both human and animal diabetic models. Iron is a metal oxidant capable of generating reactive oxygen species (ROS) and has been postulated to contribute to diabetic nephropathy. Two proteins involved in iron metabolism that are expressed in the kidney are the divalent metal transporter, DMT1 (Slc11a2), and the Transferrin Receptor (TfR). Thus, we investigated whether renal DMT1 or TfR expression is altered in diabetes, as this could potentially affect ROS generation and contribute to diabetic nephropathy. Rats were rendered diabetic with streptozotocin (STZ-diabetes) and renal DMT1 and TfR expression studied using semi-quantitative immunoblotting and immunofluorescence. In STZ-diabetic Sprague-Dawley rats, renal DMT1 expression was significantly reduced and TfR expression increased after 2 weeks. DMT1 downregulation was observed in both proximal tubules and collecting ducts. Renal DMT1 expression was also decreased in Wistar rats following 12 weeks of STZ-diabetes, an effect that was fully corrected by insulin-replacement but not by cotreatment with the aldose reductase inhibitor, sorbinil. Increased renal TfR expression was also observed in STZ-diabetic Wistar rats together with elevated cellular iron accumulation. Together these data demonstrate renal DMT1 downregulation and TfR upregulation in STZ-diabetes. Whilst the consequence of altered DMT1 expression on renal iron handling and oxidant damage remains to be determined, the attenuation of the putative lysosomal iron exit pathway in proximal tubules could potentially explain lysosomal iron accumulation reported in human diabetes and STZ-diabetic animals.
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PMID:Altered expression of iron transport proteins in streptozotocin-induced diabetic rat kidney. 1587 45


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