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

Angiotensin II plays an important role in the kidney by regulating renal flow, glomerular filtration rate, mesangial cell function, and sodium reabsorption. Blockade of the renin-angiotensin system has powerful effects on kidney function. Studies in animal models of renal failure suggest that converting enzyme inhibitors slow down the inevitable progression of the renal failure. This could be in part due to their effect on reducing glomerular pressure or by reducing glomerular hypertrophy. In patients with malignant hypertension, diabetic nephropathy, and other causes of renal failure, preliminary evidence suggests that lowering the blood pressure with angiotensin-converting enzyme (ACE) inhibitors may possibly carry some other benefits compared with other blood pressure lowering regimens. However, single drug therapy is rarely sufficient to control blood pressure in these patients. Further properly controlled randomized trials should give a clear indication of whether any particular class of drug has any advantage in slowing down the progressive renal impairment for a given lowering of blood pressure. In patients with renovascular hypertension ACE inhibitors are effective drugs in lowering blood pressure. However, in certain settings they may cause a reversible decline in renal function.
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PMID:Blood pressure, angiotensin-converting enzyme (ACE) inhibitors, and the kidney. 158 Feb 76

We evaluated the renal and hormonal responses to volume expansion induced by water immersion in subjects with diabetic nephropathy (n = 12) and in healthy control subjects (n = 9). Immersion induced similar average increments in sodium excretion (+/- 223 vs. 176 mumol/min) and comparable decrements in renovascular resistance (RVR; -15 vs. -16 U). However, whereas the control subjects responded uniformly, the response among diabetic subjects was highly variable, with a subset of patients exhibiting paradoxical antinatriuresis and vasoconstriction. Immersion was associated with marked elevation of atrial natriuretic peptide (ANP) in plasma of diabetic versus control subjects (61 +/- 9 vs. 19 +/- 2 pM, respectively; P less than 0.001). Yet for each picomolar increment in plasma ANP during immersion, the corresponding increases in urinary excretion of cyclic guanosine monophosphate (26 vs. 279 pmol/min) and sodium (9 vs. 47 mumol/min) and the reciprocal lowering of RVR (0.7 vs. 1.9 U) were blunted in the diabetic versus control group. Volume contraction in the postimmersion period was associated with disproportionate antinatriuresis and renal vasoconstriction in the diabetic group, despite a persistent elevation of ANP (29 +/- 2 vs. 16 +/- 2 pM, P less than 0.01). We propose that renal insensitivity to ANP in diabetic nephropathy could contribute to altered vasoreactivity and abnormal excretory responsiveness to changing plasma volume. Blunted natriuresis in response to ANP release and enhanced sodium retention during volume contraction could account for the expanded extracellular fluid volume that has consistently been reported to accompany the development of diabetic nephropathy.
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PMID:Atrial natriuretic peptide and response to changing plasma volume in diabetic nephropathy. 164 96

Diabetic patients who develop proteinuria show a marked increase in cardiovascular morbidity and mortality. The precise pathogenesis of human diabetic kidney disease and the factors responsible for the susceptibility to it remain, in part, obscure. However, there is now evidence that renal disease clusters in families and that genetic factors may be of central importance in determining susceptibility. Predisposition to arterial hypertension has been suggested as playing a contributory role in the development of kidney disease. Hypertrophic processes may be implicated in the susceptibility to arterial wall damage and glomerular injury in diabetes. Interestingly, fibroblasts of patients with diabetic nephropathy show a higher Na+/H+ antiport activity and a greater 3H-thymidine incorporation into DNA than fibroblasts of diabetic patients without nephropathy. The first clinical signs of renal involvement are the appearance of microalbuminuria and a small elevation in arterial pressure. Mesangial expansion accompanies these changes. Microalbuminuria is associated with abnormalities of lipoprotein profiles and higher Na+/Li+ countertransport rates. The environmental changes brought about by diabetes could lead in susceptible individuals to increased systemic and intraglomerular pressures on the one hand and to mesangial expansion on the other. These two processes would cause proteinuria and glomerulosclerosis. Lipid abnormalities may further aggravate the renal histological damage and, in combination with hypertension, contribute to the accelerated atherosclerosis typical of patients with diabetic kidney disease. A vicious circle would thus be triggered, involving reduction in renal function, further hypertension, proteinuria, glomerular obsolence and hyperlipidaemia, and eventually end-stage renal failure or premature cardiovascular death.
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PMID:Risk factors for renal and cardiovascular disease in diabetic patients. 165 64

To evaluate the importance of tubular proteinuria in diabetic nephropathy, we studied the serial changes of micro-albuminuria, microproteinuria and protein patterns by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) in 38 diabetic patients over 8 months. There was a significant correlation between the amount of micro-albuminuria measured by radio-immunoassay and the amount of microproteinuria quantitated by the Coomassie brilliant blue dye binding method (r = 0.976; p less than 0.0001). Micro-albuminuria of 50 mg/day was equivalent to microproteinuria of 190 mg/day. Among the 38 diabetic patients, 26 had micro-albuminuria above 50 mg/day, while 12 had micro-albuminuria below this level. There was a significant correlation between the amount of microproteinuria and haemoglobin A1, showing that the quantity of microproteinuria was affected by metabolic control. Diabetic patients with micro-albuminuria of above 50 mg/day have a significantly higher diastolic blood pressure than those below this level. Among the diabetic patients with micro-albuminuria of less than 50 mg/day, the amount of micro-albuminuria and microproteinuria remained constant, whereas progressive increases in micro-albuminuria and microproteinuria were observed among the 12 diabetic subjects with micro-albuminuria above 50 mg/day. These support the prognostic importance of this quantity of micro-albuminuria. The protein patterns as revealed by SDS-PAGE with Coomassie blue staining show a significant loss of low-molecular-weight proteins in 7 patients, which may therefore suggest tubular damage. The loss of tubular proteins persisted over a period of 8 months in all 7 subjects, and the amount gradually increased over this period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Eight-month longitudinal study of urinary excretion of albumin and tubular proteins in diabetic subjects. 170 39

Hypertension in type I diabetes appears to be causally related to nephropathy, whereas the relationship between hypertension and type II diabetes is more complex, hypertension being present in the absence of clinically overt nephropathy and even preceding the onset of diabetes. In the diabetic, hypertension is exquisitely sodium-sensitive. It is in diabetic nephropathy that the best evidence has been obtained that treatment of hypertension retards the progression of renal failure. Consensus is still lacking with respect to the point when antihypertensive treatment should be started and the target blood pressure that should be aimed at. Currently, there is no evidence in humans that converting enzyme inhibitors are superior to alternative antihypertensive agents in retarding progression, but tantalizing preliminary evidence on this has been reported in nondiabetic patients with renal failure.
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PMID:Preservation of renal function in diabetic patients. 172 44

Late diabetic effects are the sequelae of for a long time super elevated blood sugar levels. The diabetic nephropathy is the cause of the secondary arterial hypertension. The investigation seeks for the connections between the diabetes mellitus and the essential, that is primary hypertension. The two diseases frequently appear and clearly increase in the second half of life. Moreover, they are above average frequently associated with each other. Among brothers and sisters of diabetic hypertensives in comparison to normal cohorts clearly increased high blood pressure prevalences were found. The insulin resistance which could be proved in a great number of hypertensive and which has been known since more than two decades might be the connecting link between hypertension and diabetes mellitus. Like the obesity the essential hypertension can be associated with all degrees of an insulin hyposensitiveness. The sodium-retaining effect of the insulin might explain the increased sodium content of the body in hypertensives. The differential diagnostics of the essential hypertension should therefore seek for conditions of an insulin resistance. The type II diabetic lacks a release of bradykinin during muscle work. Thus the glucose uptake into the cell is unfavourable influenced and demands an increased insulin excretion. This genetically (?) fixed defect is found also in essential hypertensives. It could be the connecting link between the two diseases. ACE-inhibitors have via a kininase II inhibition an effect also on the bradykinin decomposition and can favourable influence the glucose uptake into the muscle. An improved insulin effect among the ACE-inhibitors was described. Therefore, they should be preferred in the treatment of hypertensive diabetics.
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PMID:[Diabetes mellitus and arterial hypertension. In search of the connecting link]. 177 26

It has been suggested previously that a decrease in urinary dopamine output might be related to a decrease in the urinary sodium excretion in subjects with diabetic nephropathy suffering from type 2 diabetes. To investigate the renal dopamine status in children with type 1 (insulin-dependent) diabetes mellitus, we measured the 24-hour urinary excretion of dopamine, norepinephrine and sodium in 12 patients with incipient nephropathy (group A, 24-hour albumin excretion rate 70-200 micrograms/min), in 20 age matched patients with normal microalbuminuria (group B, AER less than 20 micrograms/min) and in 8 healthy controls (group C). The mean values for urinary excretion of dopamine and norepinephrine were significantly lower in group A compared to groups B and C (25.6 +/- 14.8 vs. 65.9 +/- 25.5 and 73.3 +/- 18.0 micrograms/day, p less than 0.001 and 11.8 +/- 4.6 vs. 25.1 +/- 12.1 and 28.4 +/- 8.9 micrograms/day, p less than 0.01, respectively). The mean value for the urinary excretion of sodium was also significantly lower in group A than in groups B and C (98.4 +/- 24.1 vs. 206.2 +/- 59.5 and 198.1 +/- 42.8 mEq/day, p less than 0.01). The 24-hour urinary excretion of dopamine correlated significantly with the sodium excretion (r = 0.65, p less than 0.001). Arterial blood pressure was elevated in group A compared to group C (p less than 0.01). Our results suggest that a decrease in endogenous dopamine could play a role in the low urinary sodium excretion thereby resulting in sodium retention which may in turn lead to the development of higher blood pressure in diabetic children with incipient nephropathy.
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PMID:Decreased urinary excretion of dopamine and sodium in diabetic children with incipient nephropathy. 179 93

Arterial hypertension is present in 10-80% of newly diagnosed Type 2 diabetics, and in 30-50% of Type 1 diabetics after some years. In patients with overt nephropathy, correction of hypertension is associated with a reduction in the rate of decline of glomerular filtration rate. In most patients without clinical diabetic nephropathy, arterial pressure remains within normal limits as defined by usual criteria, whether or not microalbuminuria is present. Short-term studies of Type 1 diabetics with microalbuminuria suggest that angiotensin-converting enzyme inhibitors result in a fall in urinary albumin excretion rate more than calcium antagonists and diuretics. Additional studies assessing the long-term effect of different antihypertensive agents on the evolution of early diabetic nephropathy are needed before the superiority of any drug can be claimed. In addition, non pharmacological approaches, including optimal glycemic control as well as modification of dietary sodium and serum lipid profile, may alter the progressive course of elevation in arterial pressure and decline in renal function. The optimal level of blood pressure for diabetic patients remains to be determined.
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PMID:Blood pressure reduction as a preventive treatment of diabetic nephropathy. 179 16

The renal effects of the prostaglandin synthesis inhibitor naproxen was investigated in eight patients with incipient type I diabetes nephropathy. The patients were treated with 1000 mg naproxen daily for 4 days in a placebo-controlled double-blind cross-over study. Naproxen reduced urinary prostaglandin E2 (PGE2) excretion by 60%, from 276 ng/24 h to 110 ng/24 h (P less than 0.05). Plasma renin activity (PRA) was reduced by 45% (P less than 0.05). Glomerular filtration (GFR) (single bolus 99mTc-DTPA technique) and effective renal plasma flow (ERPF) (131I-Hippuran clearance) were unchanged by naproxen. Microalbuminuria and renal albumin clearance was unchanged as was also urinary excretion of sodium, glandular kallikrein and beta 2-microglobulin (beta 2-M). Our results show that albumin excretion in incipient diabetic nephropathy is not solely dependent on the renal prostaglandin system. The difference in action between naproxen in this study and indomethacin in previous reports, could be caused by renal actions of indomethacin independent of the prostaglandin system.
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PMID:Effects of short-term treatment with naproxen on kidney function in insulin-dependent diabetic patients with microalbuminuria. 181 19

Sodium lithium countertransport may be a genetic marker for arterial hypertension and for the risk of diabetic nephropathy in type 1 diabetic patients. Since various factors seem to influence the transport velocity including serum lipid alterations, erythrocytes of seven patients with severe hyperlipoproteinaemia who were chronically and intermittently treated with LDL apheresis were examined before and immediately after therapy. The LDL apheresis reduced sodium lithium countertransport significantly (0.383 vs 0.269, P less than 0.02). Therefore, we conclude that serum lipid composition must be considered when interpreting sodium lithium countertransport velocity.
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PMID:Sodium lithium countertransport is acutely influenced by heparin-induced extracorporal LDL precipitation. 190 34


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