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

End Stage Renal Disease (ESRD) is a common consequence of diabetic nephropathy (DN). DN is the major cause of death in patients with IDDM, accounting for greater than 40% of deaths with this form of diabetes. There is no clearly documented therapeutic technique that will prevent or reverse progressive renal damage in IDDM. While pancreatic transplantation and "cure" of diabetes in experimental animals may be associated with some histological reversal of renal pathology, this has not been documented in humans. Most studies agree that once diabetic renal disease is present (as documented by proteinuria), progression is inevitable, albeit the rate of progression may be altered by different therapeutic methods. There is considerable hope that "tight metabolic control" will prevent the initial damage that leads to DN and ESRD, but evidence remains inconclusive. There is some evidence that careful monitoring for microalbuminuria will allow for very early detection of damage and alterations in therapy. Our studies have documented a decrease in both morbidity and mortality in IDDM in patients who have been competitive athletes, suggesting that promotion of physical fitness may be a valuable means of delaying progression of renal disease while control of BP delays progression. Early detection and aggressive therapy is recommended. Some studies utilizing diets low in sodium and/or protein appear beneficial but more studies are needed before pediatric application.
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PMID:Can management strategies alter the course of diabetic nephropathy? 263 85

The effects of monotherapy with nicardipine, 20 mg three times a day, have been investigated in a 1-year study of 26 elderly (greater than 60 years) patients with hypertension with various types of renal dysfunction and seven without renal dysfunction. Parameters measured included blood pressure, blood chemistry (serum creatinine, uric acid, blood urea nitrogen, blood glucose total cholesterol, and electrolytes), plasma renin activity, and plasma aldosterone concentration. Nicardipine was effective in reducing blood pressure in all patients with diabetic nephropathy, parenchymal renal diseases, or hypertensive nephropathy, and in those without renal dysfunction. Serum creatinine and blood urea nitrogen levels were slightly elevated in some patients whose pretreatment serum creatinine level was greater than 2 mg/dl, regardless of the type of nephropathy. However, it was not determined whether this effect was the result of a reduction in blood pressure induced by nicardipine. Serum sodium, potassium, total cholesterol, and blood glucose levels were unchanged by the administration of nicardipine. Changes in plasma renin activity and aldosterone levels were not significant. These results suggest that nicardipine can be used safely in elderly patients with hypertension with renal dysfunction, regardless of the type of nephropathy.
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PMID:Effects of nicardipine on blood pressure and renal function in elderly hypertensive patients with renal dysfunction. 264 83

Angiotensin converting enzyme (ACE) inhibitors are useful in the treatment of hypertension. However, acute renal deterioration may occur in some conditions where angiotensin plays a crucial role in the regulation of the glomerular filtration rate (GFR), such as volume depletion, severe stenosis of both renal arteries and stenosis of the renal artery of a single functioning kidney. Acute renal failure induced by ACE inhibition may develop without a reduction in systemic blood pressure it is enhanced by prior sodium depletion and is reversible when treatment is withdrawn. The relative superiority of ACE inhibitors in slowing the progression of chronic parenchymal renal disease remains to be demonstrated, although promising results have been reported in patients with diabetic nephropathy.
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PMID:Angiotensin converting enzyme inhibitors and renal function. 268 4

Diabetes may be associated with systolic hypertension secondary to atherosclerosis, renal hypertension secondary to diabetic nephropathy, and essential hypertension. The latter is by far the most prevalent, and a wealth of epidemiologic data suggests that such an association is independent of age and obesity. Considerable evidence indicates that the link between diabetes and essential hypertension is hyperinsulinemia. Thus, when hypertensive subjects, whether obese or of normal body weight, are compared to age- and weight-matched normotensive controls, a heightened plasma insulin response to a glucose challenge is found consistently. A state of cellular resistance to insulin action subtends the observed hyperinsulinism. With the use of the glucose clamp technique coupled with tracer glucose infusion and indirect calorimetry, it can be shown that the insulin resistance of essential hypertension is located in peripheral tissues (muscle), is limited to nonoxidative pathways of glucose disposal, and is directly correlated with the severity of hypertension. The reasons for the association of insulin resistance and essential hypertension can be sought in at least four general types of mechanisms--sodium retention, sympathetic nervous system overactivity, disturbed membrane ion transport, and altered muscle fiber composition. Physiologic maneuvers such as caloric restriction in the overweight individual and regular physical exercise can improve tissue sensitivity to insulin; good preliminary evidence shows that these measures can also lower blood pressure in both normotensive and hypertensive individuals. A strong case can therefore be made for the use of physiologic intervention in the treatment of essential hypertension.
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PMID:The association of essential hypertension and diabetes. 268 84

Hypertension may eventually develop in response to chronic slight retention of sodium and expansion of the extracellular fluid volume, either due to intrinsic pathology or to neurohormonal influences of the kidneys. As almost half of all juvenile diabetic patients sooner or later will develop diabetic nephropathy and hypertension, data are discussed which tend to indicate that renal sodium metabolism is altered already early during the course of diabetes. Compared to healthy subjects the absolute total tubular sodium reabsorption is increased by approximately 30-40 per cent, as is the filtered sodium load. Insulin may stimulate sodium reabsorption in man through an effect on the distal nephron segment. However, by means of combined lithium and 51Cr-labelled EDTA clearances it has been clearly demonstrated that the excess sodium reabsorption in ambulatory insulin-dependent diabetics exclusively takes place in the proximal tubules, while the distal tubular function appears normal. In these studied patients the extracellular fluid volume was also significantly increased. The increased fractional sodium reabsorption of the proximal tubules remains unaffected by increasing duration of diabetes and is also demonstrable in patients with overt diabetic nephropathy. Glucose is reabsorbed in the early portion of the proximal tubules coupled to Na+ transport, utilizing a common carrier protein. An increased load of glucose will therefore be expected to induce an increase in the proximal tubular reabsorption rate of sodium and water, at least as long as the proximal tubular reabsorption capacity for glucose is not exceeded to a degree inducing significant osmotic diuresis. This deviation from normal in proximal renal sodium and fluid handling may be relevant to the development of hypertension in long-term insulin-dependent diabetes.
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PMID:Renal sodium metabolism in relation to hypertension in diabetes. 269 46

Disorders of fluid and electrolyte metabolism in elderly diabetics were studied. High frequency of hyperkalemia (20.8%), hypomagnesemia (14.6%), hypocalcemia (13.7%), hyperphosphatemia (8.6%), hyponatremia (8.1%) and hyperchloremia (7.2%) was observed among 332 elderly diabetics. Furthermore, hyperkalemia, hyperphosphatemia, hyponatremia, hyperchloremia, hypercalcemia and hypermagnesemia were more frequent in diabetics with renal insufficiency (serum Cr greater than or equal to 1.5 mg/dl) than in diabetics with normal renal function (serum Cr less than or equal to 1.4 mg/dl). In addition, statistically significant negative correlation were observed between plasma glucose levels and serum levels of sodium and chloride in diabetics with normal renal function. These results clearly demonstrated that the most important causal factor of electrolyte disorders in elderly diabetics might be the renal dysfunction due to diabetic nephropathy and/or nephrosclerosis. Moreover, glucose intolerance is also one of the causal factors for hyponatremia and hypochloremia. Disorders of fluid and electrolyte metabolism were manifest in 31 diabetic patients with hyperosmolar non-ketotic coma. The frequency of patients with abnormally elevated serum levels of sodium, potassium and chloride, and patients with abnormally lowered serum levels of calcium was high in this morbid state. Water and sodium deficit, examined in 11 cases of hyperosmolar non-ketotic coma, was 4780 +/- 2100 ml (107 +/- 43 ml/kg body weight) and 290 +/- 170 mEq (6.8 +/- 4.2 mEq/kg body weight), respectively. However, no significant deficit of potassium was observed in the patients. Statistically significant positive correlations between water deficit and serum Cr levels and with serum effective osmolarity were observed. However, there were no significant correlations between water deficit and plasma glucose levels, serum sodium levels and serum osmolarity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Disorders of fluid and electrolyte metabolism in elderly diabetics]. 279 74

We measured the urinary excretions of dopamine, noradrenaline and adrenaline, their conjugated metabolites, urinary excretion of sodium and creatinine clearance simultaneously in 21 patients with Type 2 (non-insulin-dependent) diabetes and 6 normal subjects. The mean (+/- SEM) value for urinary excretion of dopamine (52.4 +/- 8.8 micrograms/day) in diabetic patients with nephropathy (Group C, n = 12) was significantly lower (P less than 0.01) than in the normal subjects (Group A, 179.7 +/- 15.5 micrograms/day) and in diabetic patients without nephropathy (Group B, n = 9, 131.5 +/- 16.5 micrograms/day). The mean values for the urinary excretions of noradrenaline and adrenaline were also significantly lower (P less than 0.01) in Group C than in Groups A and B. In addition, the mean urinary excretion of conjugated metabolite of dopamine in Group C was significantly lower (P less than 0.05) than in Group A. There was a trend toward the observation that the mean 24-h urinary excretion of sodium in Group C (121.6 less than 12.9 mEq) was lower as compared with that in Group A (140.8 +/- 8.9 mEq) or B (150.7 +/- 17.9 mEq). A multiple regression analysis revealed that the 24-h urinary excretion of dopamine correlated significantly with creatinine clearance, systolic (P less than 0.01) and diastolic (P less than 0.05) blood pressures. The results indicate that synthesis or secretion of renal dopamine might decrease with a progression of diabetic nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Urinary dopamine, noradrenaline and adrenaline in type 2 diabetic patients with and without nephropathy. 292 52

To explore a possible link between diabetic nephropathy and the enhanced activity of the polyol pathway known to occur in diabetes, we examined several pertinent metabolic parameters in glomeruli isolated from control and streptozotocin-diabetic rats and assessed whether changes observed in diabetic glomeruli could be prevented by the oral administration of the aldose reductase inhibitor sorbinil. We found that glomerular polyol content is significantly increased in diabetes, whereas glomerular myo-inositol content is significantly reduced. The sorbitol accumulation and myo-inositol depletion were both completely prevented by sorbinil, which was given throughout the duration of diabetes. Activity of the membrane-bound sodium/potassium adenosine triphosphatase (Na-K-ATPase) was decreased in diabetic samples; this change was also completely prevented by sorbinil. Erythrocyte deformability is another factor that has been implicated in the pathogenesis of microangiopathic complications. The ability of red blood cells to undergo an adaptation in shape that permits passage through the smallest vessels is impaired in diabetes. Using blood from control, diabetic, and sorbinil-treated diabetic rats, we found that erythrocyte deformability was decreased in diabetic samples and that sorbinil treatment significantly improved this parameter. Thus, if the glomerular consequences of sorbitol accumulation, myo-inositol depletion, reduced Na-K-ATPase activity, and decreased erythrocyte deformability are pathogenetically implicated in diabetic nephropathy, the ability of sorbinil to impact on these changes suggests that it could favorably impact on the nephropathic process.
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PMID:Aldose reductase, glomerular metabolism, and diabetic nephropathy. 300 26

Only one third of patients with juvenile-onset insulin-dependent diabetes seem to be susceptible to diabetic nephropathy. To test whether this susceptibility is related to a predisposition to hypertension, we investigated the association of nephropathy with markers of risk for hypertension. We randomly selected 89 patients with insulin-dependent diabetes from a roster of children and adolescents who were seen between 1968 and 1972 at about the time the diagnosis was made. These 89 patients were recalled for examination, as young adults, in 1986 and 1987. Patients with nephropathy (cases, n = 33) were compared with controls without nephropathy (n = 56). Having a parent with hypertension tripled the risk of nephropathy (odds ratio, 3.7; 95 percent confidence interval, 1.4 to 10.1). Moreover, cases had significantly higher values for maximal velocity of lithium-sodium countertransport in red cells than controls (mean maximal velocity +/- SE, 0.51 +/- 0.04 vs. 0.38 +/- 0.02 mmol per liter of cells per hour; P less than 0.05). The excess risk associated with both these indicators of a predisposition to hypertension was evident principally in patients with poor glycemic control during their first decade of diabetes; the odds ratios were 4.5 (95 percent confidence interval, 1.1 to 18.7) for patients with a parental history of hypertension and 7.7 (95 percent confidence interval, 1.8 to 33.8) for patients with a maximal velocity of lithium-sodium countertransport greater than or equal to 0.35 mmol per liter of cells per hour. We conclude that the risk of renal disease in patients with juvenile-onset insulin-dependent diabetes is associated with a genetic predisposition to hypertension. Predisposition to hypertension appears to increase susceptibility for renal disease principally in patients with poor glycemic control.
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PMID:Predisposition to hypertension and susceptibility to renal disease in insulin-dependent diabetes mellitus. 333 1

Susceptibility to diabetic nephropathy may be related to a predisposition to arterial hypertension. We have studied the activity of sodium-lithium countertransport in red cells, a marker of risk for essential hypertension, in white European adults with insulin-dependent diabetes and diabetic nephropathy, a matched group of patients with diabetes without renal disease, and nondiabetic patients with renal disease. Measures of metabolic control and concentrations of plasma free insulin and growth hormone were similar in the two diabetic groups. The degree of impairment in renal function was similar in the diabetic and nondiabetic patients with renal disease. Body-mass index and plasma potassium concentrations were similar in all three groups. Diastolic blood pressure was elevated to a similar degree in the two groups with renal disease, as compared with that in the diabetic patients without renal disease. The rates of sodium-lithium countertransport in red cells were significantly higher in the diabetic patients with renal disease (mean +/- SD, 0.55 +/- 0.19 mmol of lithium per liter of red cells per hour) than in the diabetic patients without renal disease (0.33 +/- 0.16; P less than 0.005) and in the nondiabetic patients with renal disease (0.31 +/- 0.14; P less than 0.001). Predisposition to hypertension, as indicated by elevated sodium-lithium countertransport activity in red cells, may serve as a marker for the risk of renal disease in patients with insulin-dependent diabetes.
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PMID:Increased sodium-lithium countertransport activity in red cells of patients with insulin-dependent diabetes and nephropathy. 333 2


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