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)

An elevated urinary albumin excretion (termed microalbuminuria) has been proposed as a predictor for later development of clinical diabetic nephropathy (hypertension, falling glomerular filtration rate [GFR], and urinary albumin excretion greater than 300 mg/24 h). However, review of the original reports on the predictability of microalbuminuria revealed a concomitant presence of elevated BP and a propensity to falling GFR. Thus, the predictability of microalbuminuria rests on the added evaluation of BP and GFR. Additional investigation is needed to address the possibility that microalbuminuria and either a rising BP or a falling GFR or both indicates established diabetic nephropathy rather than predicting its development.
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PMID:The predictive value of microalbuminuria. 291 61

Hyperfiltration is a very characteristic feature in insulin-dependent diabetes. Hyperfiltration is to some extent associated with long-term glycemic control but the correlation is not very strong. Long-term hyperfiltration may play a role in the genesis of late diabetic nephropathy, but it is difficult to distinguish effects of hyperfiltration per se from effects of poor metabolic control. Long-term hyperfiltration without diabetes does not produce nephropathy. It is hypothesized that IDDM patients who do not show considerable hyperfiltration in spite of poor metabolic control may be those who are to some extent protected against late diabetic nephropathy, but other mechanisms may also be involved in the renal protection of these patients, who survive long-term diabetes without nephropathy. On the other hand, those with poor metabolic control combined with hyperfiltration are likely to develop nephropathy. In addition, it is suggested that the metabolic aberrations in diabetes, with the subsequent changes in the biochemistry of the glomerular wall, are permissive and absolutely required for the development of diabetic nephropathy. Of note, diabetic glomerulopathy in NIDDM occurs without significant hyperfiltration and extreme hyperfiltration in the one-kidney-model (without diabetes) does not produce nephropathy. Nonglycemic modalities of intervention, resulting in reduced hyperfiltration, e.g., low-protein diet or administration of somatostatin analogues, deserves interest as new potential ways of preventing or postponing diabetic nephropathy. Also intervention with aldose-reductase inhibitors may be an important therapeutic modality for those patients in whom good metabolic control is not obtainable. It is now well-established that antihypertensive treatment, including ACE-inhibition, reduces rate of decline in GFR in patients with already established nephropathy. In addition, protein excretion is diminished in IDDM patients with incipient diabetic nephropathy by antihypertensive treatment where GFR is well-preserved during treatment. No data are available for NIDDM.
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PMID:Comparative renal pathophysiology relevant to IDDM and NIDDM patients. 306 56

Some cardiovascular (heart rate and mean arterial pressure), and renal (glomerular filtration rate-GFR; renal plasma flow-RPF; filtration fraction-FF; blood urea nitrogen-BUN and albuminuria) parameters, coupled with morphologic examination, was undertaken in early (2 months) and late (6 months) stage of streptozotocin-induced diabetes mellitus in rats. The results showed a temporally (early) bradycardia and gradually increase of blood pressure with morphologic changes typical for diabetic cardiopathy. The increased GFR (by 92%), associated with significantly decreased RPF (by 37%), increased FF (by 133%), increased kidney weight/body weight ratio (by 88%), increased BUN (by 52%) and distinct albuminuria (13.53 +/- 2.08 mg/24 h/100 g b. w.), together with typical morphologic changes, suggested the development of diabetic nephropathy which was progressive with the duration of the disease.
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PMID:Pathogenesis of cardiovascular disorders in streptozotocin-induced diabetes in rat. I. Cardiovascular, renal and morphologic changes in different stages of diabetes. 306 11

Protein intake has been suggested to influence progression of renal disease by affecting intraglomerular pressures and flows. The renal disease of the diabetic mouse (C57BL/Ks/db/db) has been proposed as a suitable model of human diabetic nephropathy. Ten diabetic mice and ten non-diabetic controls were placed on 1 of 3 protein intakes, 4%, 27% and 50%, and serial functional measurements were made at 2 to 3 week intervals until week 20. All diabetic animals showed similar degrees of hyperglycemia. The creatinine clearances were generally higher in the diabetic mice than the controls, except the 4% protein intake diabetic group, until week 20 when the 27% db/db mice showed a significant decline (p less than 0.05) compared to the control mice. Albumin excretion was significantly higher in the 27% and 50% protein intake db/db mice than the controls. Again the 4% group showed albuminuria not different from the control animals. Histologic studies at 20 weeks showed minimal abnormalities in the normal and 4% protein intake diabetic group. The 27% and 50% intake diabetic mice showed a progressive increase in severity of mesangial matrix expansion with segmental sclerosis. Electron microscopy confirmed these findings. Immunofluorescence microscopy showed a marked increase in mesangial immunoglobulin G and M. With similar degree of hyperglycemia, higher protein intake was associated with more severe histologic changes, greater albuminuria and early decline in GFR. Thus protein intake can markedly affect the progression of renal disease in the diabetic mouse.
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PMID:Effect of varied protein intake on the nephropathy of the diabetic mouse (C57BL/s J db/db). 330 29

Relative low serum levels of parathormone (PTH) and low incidence of secondary hyperparathyroidism have been reported in diabetic uremic patients. The pathogenesis of this reported resistance to uremic secondary hyperparathyroidism in diabetes remains controversial. We have measured the serum C-terminal parathormone (C-PTH) renal phosphorus threshold (TmPO4) and nephrogenous cyclic AMP (N-cCAMP), in 2-hour urine collection in 22 patients with diabetic nephropathy with moderate chronic renal failure and in 27 controls with similar creatinine clearance values (18.16 +/- 9.14 and and 19.1 +/- 8.47 ml/min). In spite of the lower levels of serum C-PTH (1.07 +/- 0.43 ng/ml) diabetic patients exhibited an increased phosphaturia (TmPO4: 1.97 +/- 0.9 mg/100 ml GFR) when compared with the control group (C-PTH: 2.01 +/- 1.17 mg/ml, and TmPO4: 2.5 +/- 0.7 ml GFR). When the C-PTH values were plotted against the logarithm of creatinine clearance values, both groups showed a significant linear relationship reflecting the progressive increase in PTH when GFR fell. This progressive parathyroid stimulus was also present in diabetic patients but in a lower intensity. We believe that increased phosphaturia in diabetics with moderate chronic renal failure may be a major factor in precluding the appearance of secondary hyperparathyroidism in these patients once they reach the dialysis and transplantation programs.
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PMID:Relative hyperphosphaturia in diabetic chronic renal failure: a protective factor of hyperparathyroidism. 367 Feb 26

Glomerular filtration rate (GFR, single bolus 51Cr-EDTA technique), serum creatinine and serum beta 2-microglobulin concentrations were measured simultaneously in 49 insulin-dependent diabetics with diabetic nephropathy. GFR ranged from 148 to 23 ml/min/1.73 m2. Inverse serum concentrations of creatinine and beta 2-microglobulin showed a significant correlation with GFR over the whole range of values, r = 0.87 and r = 0.90, respectively (p less than 0.001). In the 31 patients with a GFR less than 80 ml/min/1.73 m2, serum concentration of creatinine and beta 2-microglobulin were within the normal range in 12 and 9 patients, respectively. With GFR below 60 ml/min/1.73 m2, all patients had elevated serum beta 2-microglobulin concentrations, while 24% of the patients still had normal creatinine concentration. Linear regression analysis between log GFR and log serum beta 2-microglobulin showed a better relationship than between log GFR and log serum creatinine, slope -0.90 and -0.57, respectively, p less than 0.01. A prospective study for up to 70 months was performed in 18 of the patients. The study showed a closer relationship between the individual rate of decline in log GFR and log serum beta 2-microglobulin compared to log GFR versus log serum creatinine, p less than 0.01. Neither serum creatinine nor serum beta 2-microglobulin can be used as methods for screening of early impairment of renal function (GFR less than 80 ml/min/1.73 m2 in diabetic nephropathy. Our study suggests that serum beta 2-microglobulin is more ideal endogenous marker for GFR estimation than serum creatinine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Monitoring progression of diabetic nephropathy. 389 Mar 16

Forty percent of patients with insulin-dependent diabetes will develop nephropathy during the course of their disease, thus being the most important single disorder leading to end-stage renal failure (ESRF). Intensive metabolic control delays onset of diabetic nephropathy, the first omen of which is appearance of subclinical albuminuria, also termed microalbuminuria. Moreover, it is now established that intensive treatment of hypertension reduces rate of decline in GFR and thus postpones ESRF. When uremia eventually sets in, a range of biochemical and endocrine abnormalities can be included among those characteristics of diabetes mellitus per se. These include elevated plasma levels of growth hormone, glucagon and free fatty acids, which may participate in the uremic insulin resistance superimposed on the preexisting diabetic carbohydrate intolerance. Hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) are two established modalities of renal replacement therapy in diabetes mellitus. Controlled clinical trials for comparison of CAPD versus HD treatment of diabetics are, however, still needed. The survival rate is approximately 80 and 65-95% in insulin-dependent diabetic patients at 1 year during treatment with HD and CAPD, respectively. However, it is general experience that diabetics on CAPD exhibit a glycemic control, superior to that attained during HD. It has not been proved that patient survival after cadaveric renal transplantation is better than on dialysis. The degree of vascular heart disease seems to be the major determinant for survival of kidney-transplanted diabetic patients.
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PMID:End-state renal failure in diabetic nephropathy: pathophysiology and treatment. 391 47

The purpose of our prospective study was to evaluate the long-term effect of aggressive antihypertensive treatment on glomerular filtration rate and albuminuria in young female and male patients with insulin-dependent diabetes mellitus with diabetic nephropathy and blood pressure greater than 90 mm Hg. Eight patients received treatment with metoprolol (200-400 mg/day), hydralazine (100-200 mg/day), and furosemide (80-500 mg/day). The untreated control group consisted of eight patients matched for age (mean 32 years), diabetes duration (mean 17 years), and sex (two female and six male patients). All patients except one had diabetic retinopathy. Glomerular filtration rate was measured after a single intravenous injection of 51Cr-labeled ethylenediaminetetraacetic acid. Urinary albumin concentration was determined with a radial immunodiffusion method. The investigations were performed two to four times per year in each patient. The mean observation period was 59 and 27 months in the treated and untreated groups respectively. Due to a considerable rise in arterial blood pressure, it was considered unethical to prolong the observation in the untreated group. Arterial blood pressure rose from 140/96 +/- 4/1 to 150/100 +/- 3/2 mm Hg; albuminuria increased from 1517 +/- 502 to 1911 +/- 120 micrograms/min; and glomerular filtration rate decreased by a mean of 0.84 +/- 0.17 ml/min/mo in the untreated group. Antihypertensive treatment induced blood pressure reduction 151/100 +/- 3/2 to 131/87 +/- 2/1 mm Hg; diminished albuminuria 1467 +/- 515 to 729 +/- 65 micrograms/min; and caused a slow rate of decline in GFR, mean 0.37 +/- 0.08 ml/min/mo.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of long-term antihypertensive treatment on kidney function in diabetic nephropathy. 407 29

Intrinsic membrane properties of the glomerular capillary wall were evaluated in 20 diabetic patients, who had heavy proteinuria and reduced GFR, and in 15 healthy control subjects. The glomerular sieving coefficients were determined for narrow dextran fractions with molecular radii between 20 and 64 A. GFR determinants were directly measured or indirectly estimated. These quantities were then subjected to a theoretical analysis based upon (1) a mathematical model of glomerular ultrafiltration and (2) a pore model of transmembrane solute transport. The results indicated that in patients with diabetic nephropathy and glomerular ultrafiltration coefficient (0.02 vs. 0.16 ml . sec-1 . mm Hg-1 . 1.73m-2), effective pore area-to-pore length (2.6 x 10(6) vs. 20.0 x 10(6) cm), and mean pore radius (56.8 vs. 58.0 A) are all reduced relative to normal control subjects. It is suggested that (1) hypofiltration in advanced diabetic nephropathy results, in part, from reduction of the surface area available for filtration, while (2) proteinuria is a consequence of either loss of electrostatic barrier function, of isolated focal disruptions within the glomerular filtration barrier, or a combination thereof.
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PMID:Glomerular function in advanced human diabetic nephropathy. 618 Feb 14

The authors present a contemporary picture of the pathogenesis and clinical course of diabetic nephropathy in type I diabetics describing the stages of the disease and the possible evidence for reversibility of the kidney damage with tight metabolic control. During the so-called latency period, which is clinically non-detectable, the predominant functional abnormalities (increase in GFR with sub-clinical glomerular proteinuria) can be corrected by strict control although there is no evidence for the regression of the associated anatomical changes such as the enlarged filtration area. As for the described increase in thickness of the glomerular basement membrane, from experimental data and pancreatic transplants in man, delay in its development and to some extent regression of the glomerular lesions can be expected. The problem of how the renal lesions in experimental diabetes mirror the changes in the human kidney is discussed. During the symptomatic period, with intermittent and subsequently constant proteinuria and progressive decline in renal function, which are observed in only about 30% of type I diabetics, the role of arterial hypertension and its effective control is emphasized. Finally, the renal failure period is indicative of irreversible damage to the kidneys. The progression from its early to its late stages is variable between different patients but each individual patient shows a constant rate of deterioration. The evidence for the efficacy of medical treatment in slowing down its progression is very limited at present but much can be done to improve the quality of life by dietary measures, treatment of fluid overload and hypertension. When the end-stage diabetic kidney disease is reached, with serum creatinine above 8 mg/dl, renal transplantation from a living donor offers a good chance for a relatively acceptable quality of life for years. In conclusion, it is stressed that the morbidity of diabetic nephropathy could eventually be reduced through effective control of the metabolic abnormalities of diabetes with the methods presently available.
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PMID:The natural history of diabetic nephropathy in type I diabetes and the role of metabolic control in its prevention, reversibility and clinical course. 634 25


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