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)

This study was undertaken to define the renal hemodynamic changes that mediate the acute response to an oral protein load. Three groups of subjects were studied: (1) disease-free subjects; (2) patients with chronic renal disease of various causes, except for diabetes mellitus, documented by history and/or renal biopsy; and (3) patients with diabetes mellitus, that is, a history of hyperglycemia requiring antihyperglycemic therapy. All subjects were studied before (baseline) and after (test) ingestion of a protein load. Glomerular filtration rate and effective renal plasma flow were evaluated by inulin and para-amino-hippurate, respectively. In the disease-free subjects, the mean baseline glomerular filtration rate and renal plasma flow were 122 +/- 10 ml/minute/1.73 m2 and 644 +/- 64 ml/minute/1.73 m2, whereas test glomerular filtration rate and renal plasma flow were 151 +/- 15 ml/minute/1.73 m2 and 791 +/- 111 ml/minute/1.73 m2, respectively. In patients with chronic renal disease, the test glomerular filtration rate and renal plasma flow were related to the severity of the disease. The more severe the disease, the lower the absolute test values and the smaller the increment from baseline to test values. Patients with diabetes mellitus had a paradoxic response to ingestion of a protein load. Glomerular filtration rate fell while renal plasma flow remained unchanged. This response was observed in all diabetic patients regardless of the type of diabetes or whether clinical evidence of diabetic nephropathy was absent, minimal, or severe.
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PMID:Renal hemodynamic changes in humans. Response to protein loading in normal and diseased kidneys. 377 88

The effect was studied of blood pressure lowering treatment on renal failure and albuminuria (UAE) in patients with type I diabetes (IDDM) and imminent nephropathy as well as in patients with over diabetic nephropathy. The group of 24 patients with imminent nephropathy was subdivided: 1. twelve patients with borderline or overt hypertension with mean BP lowered not below 100 mmHg, and 2. twelve patients with BP within the normal limits, taking no hypotensive agents. In the other group of 12 patients with overt diabetic nephropathy hypertension was lowered below 105 mmHg and kept so for at least two years. All patients estimated their glycemia and glycosuria by themselves, ate 0.8 g protein/kg/24 h and about 100 mmol Na/24h. Under hospital conditions the following were estimated: albuminuria, glomerular filtration rate (51Cr EDTA) and effective renal blood flow (131I hippurate). The same examinations were repeated 1 year and 2 years later. The lowering of BP below 100 mmHg in patients with imminent diabetic nephropathy significantly lowered microalbuminuria without changing GFR, ERPF despite good or satisfactory compensation of diabetes. Maintaining BP below 105 mmHg for 2 years did not prevent the patients with overt nephropathy to develop progressive renal failure despite the rate of GFR deterioration and of the increase of albuminuria slowed down.
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PMID:[Effect of treatment of arterial hypertension on renal function in patients with imminent and overt diabetic nephropathy]. 773 1

Angiotensin-converting enzyme inhibitors and angiotensin II (AngII) type 1 receptor blockers lower proteinuria and preserve renal function in diabetic nephropathy (DN). The antiproteinuric effects are greater than their blood pressure reduction, involving the sieving properties of the glomerular filter. In DN, glomerular staining for heparan sulfate proteoglycans is decreased. AngII inhibits heparan sulfate synthesis. Also, heparins modulate AngII signaling in glomerular cells, inhibiting aldosterone synthesis and lowering proteinuria in DN. Is the antiproteinuric effect of heparins due to its interference with the renin-angiotensin-aldosterone system? Ten volunteers each with DN and glomerulonephritis and control subjects were examined before and after low-dosage enoxaparin. Renal hemodynamics were determined with (99m)Tc-DTPA and (131)I-hippurate clearance. Glomerular filtration rate (GFR), effective renal plasma flow, mean arterial pressure, and heart rate were measured at baseline and during AngII infusion before and after enoxaparin while on normal salt and salt restriction. Enoxaparin did not lower aldosterone levels. GFR remained stable in all groups. AngII caused a significant decrease in effective renal plasma flow, whereas mean arterial pressure and heart rate increased significantly. Enoxaparin did not influence the AngII-induced changes of renal hemodynamics during normal salt intake or salt restriction. All groups showed identical responses to AngII before and after enoxaparin. In patients with diabetes, enoxaparin caused a significant decrease in proteinuria. It is concluded that the antiproteinuric effect of heparins in DN cannot be explained via interaction with the renin-angiotensin-aldosterone system. The absence of hemodynamic changes combined with reduced proteinuria point to intrinsic alterations in the glomerular filter. The effects were seen only in DN, not in glomerulonephritis.
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PMID:Proteinuria-lowering effect of heparin therapy in diabetic nephropathy without affecting the renin-angiotensin-aldosterone system. 1769 88

Diabetic nephropathy (DN) is a serious metabolic disease, and comprehensive understanding of its complex mechanism will help in preventing the onset and progression of DN. To reveal the systemic metabolic changes associated with renal injury, we performed 1H NMR-based metabonomic and multivariate analyses to analyze serum and urine obtained from a nonhuman primate model of DN. Our results indicated that DN monkeys exhibited a distinct metabolic profile, including higher levels of VLDL/LDL, lipids, unsaturated lipids, uric acid, allantoin, fumarate and hippurate, as well as lower levels of HDL, alanine, glutamate, pyruvate, formate, tyrosine, histidine and NAD+. The disturbed metabolic pathways were further identified, including NAD+ metabolism, purine metabolism, oxidative stress, lipid metabolism, and renal tubular reabsorption. This study highlights that NMR-based metabonomics provides insight into the underlying pathways in the pathogenesis and progression of DN at the metabolic level.
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PMID:1H NMR-based metabonomic analysis of serum and urine in a nonhuman primate model of diabetic nephropathy. 2422 70

Countering the diabetes pandemic and consequent complications, such as nephropathy, will require better understanding of disease mechanisms and development of new diagnostic methods. Animal models can be versatile tools in studies of diabetic renal disease when model pathology is relevant to human diabetic nephropathy (DN). Diabetic models using endothelial nitric oxide synthase (eNOS) knock-out mice develop major renal lesions characteristic of human disease. However, it is unknown whether they can also reproduce changes in urinary metabolites found in human DN. We employed Type 1 and Type 2 diabetic mouse models of DN, i.e. STZ-eNOS(-/-) C57BLKS and eNOS(-/-) C57BLKS db/db, with the goal of determining changes in urinary metabolite profile using proton nuclear magnetic resonance (NMR). Six urinary metabolites with significantly lower levels in diabetic compared to control mice have been identified. Specifically, major changes were found in metabolites from tricarboxylic acid (TCA) cycle and aromatic amino acid catabolism including 3-indoxyl sulfate, cis-aconitate, 2-oxoisocaproate, N-phenyl-acetylglycine, 4-hydroxyphenyl acetate, and hippurate. Levels of 4-hydroxyphenyl acetic acid and hippuric acid showed the strongest reverse correlation to albumin-to-creatinine ratio (ACR), which is an indicator of renal damage. Importantly, similar changes in urinary hydroxyphenyl acetate and hippurate were previously reported in human renal disease. We demonstrated that STZ-eNOS(-/-) C57BLKS and eNOS(-/-) C57BLKS db/db mouse models can recapitulate changes in urinary metabolome found in human DN and therefore can be useful new tools in metabolomic studies relevant to human pathology.
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PMID:Alterations of urinary metabolite profile in model diabetic nephropathy. 2549 15