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

The pathogenesis of diabetic nephropathy remains elusive. A role for renal prostaglandins in antagonizing the hormonal effects of renin-angiotensin II has been postulated as a putative factor leading to hyperfiltration in patients with Type 1 (insulin-dependent) diabetes mellitus. Our aim was to elucidate the effects of angiotensin II on kidney haemodynamics and on blood pressure in eight normal subjects, in nine normotensive, in nine hypertensive with normal sodium-lithium countertransport activity in erythrocytes, in seven hypertensive without and in eight hypertensive Type 1 diabetic patients with microalbuminuria and with high sodium-lithium countertransport activity in erythrocytes. Angiotensin II infusion (4 ng.kg-1.min-1 for 60 min) decreased the glomerular filtration rate to a greater extent in normal subjects (-20%), than in normotensive patients (-5% p less than 0.01), in hypertensive patients with normal sodium-lithium countertransport activity in erythrocytes (-8% p less than 0.01) in hypertensive patients with high sodium-lithium countertransport (-6% p less than 0.01) and in hypertensive microalbuminuric patients (-5% p less than 0.01) with Type 1 diabetes. The urinary excretion rate of vasodilatory prostaglandins was two-three fold higher in all patients than in normal subjects. Acute indomethacin treatment restored a normal response to angiotensin II infusion in normotensive patients, but did not change the renal haemodynamic response in normal subjects. With regard to hypertensive patients with and without microalbuminuria indomethacin treatment restored a normal response to angiotensin II in some but not all patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Impaired response to angiotensin II in type 1 (insulin-dependent) diabetes mellitus. Role of prostaglandins and sodium-lithium countertransport activity. 193 64

Blood pressure is generally normal in insulin-dependent diabetic patients in the absence of nephropathy. Despite this, exchangeable sodium is increased. Blood pressure rises with the development of incipient nephropathy, and hypertension is common in patients with overt nephropathy. Exchangeable sodium is then markedly increased, but plasma renin is not suppressed. Raised BP in diabetic nephropathy is probably sustained, in part at least, by sodium retention and inappropriate activity of the renin-angiotensin system. There is an increased prevalence of hypertension among patients with non-insulin-dependent diabetes (NIDDM). In normotensive patients, exchangeable sodium is elevated and plasma renin is suppressed. In hypertensive patients, exchangeable sodium is less markedly increased, while plasma renin is again suppressed. These findings are in contrast with those in diabetic nephropathy, and are in keeping with the hypothesis that hypertension in NIDDM is usually due to coexisting essential hypertension. Also in keeping with this suggestion is an increased prevalence of raised BP among the siblings of NIDDM patients. Prolonged hyperinsulinaemia precedes the diagnosis of NIDDM, and hypertension is often present at the time of diagnosis. Insulin resistance and compensatory hyperinsulinaemia might lead to an increase in BP by a number of putative mechanisms, such as enhancing renal sodium retention, by an effect on cell membrane ion exchange mechanisms or by enhancing activity of the sympathetic nervous system. This seems a fertile area for further research, although a causal link between insulin resistance and hyperinsulinaemia on the one hand, and raised BP on the other, remains to be proved.
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PMID:The causes of raised blood pressure in insulin-dependent and non-insulin-dependent diabetes. 195 22

Genetic predisposition to essential hypertension, as indicated by increased maximal velocity of Na+/Li+ countertransport in red cells, has been suggested as a marker for the risk of developing diabetic nephropathy. To evaluate the validity of this concept in non-insulin-dependent diabetics, we measured the maximal velocity of Na+/Li+ countertransport in red cells in 18 male diabetics suffering from proteinuria due to biopsy proven diabetic glomerulosclerosis (GFR: 51 [range 27 to 146] ml/min/1.73 m2), 17 male diabetics with normoalbuminuria, and in 18 sex-, age-, and body mass index-matched healthy control subjects. Na+/Li+ countertransport was identical in patients with and without diabetic nephropathy, 0.43 (0.24 to 0.92) versus 0.44 (0.20 to 0.83) mmol/(liter cells x hr), but was elevated compared to control subjects, 0.32 (0.09 to 0.73; P less than 0.05). Arterial blood pressure was elevated in patients with nephropathy (162/92 +/- 21/9 mm Hg) compared to normoalbuminuric patients (132/82 +/- 15/7) and control subjects (133/83 +/- 14/7 mm Hg; P less than 0.001). Our study does not support the hypothesis that the risk of diabetic nephropathy in non-insulin-dependent diabetes is associated with a genetic predisposition to hypertension. Diabetes per se seems to enhance Na+/Li+ countertransport activity.
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PMID:Red cell Na+/Li+ countertransport in non-insulin-dependent diabetics with diabetic nephropathy. 200 27

We analyzed the components of urinary proteins in 58 diabetic patients with either short duration or long-standing disease using sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (SDS-PAGE), in comparison with 21 healthy volunteers. It was found that the percentage of protein with a molecular weight (Mr) of 140 kDa was greater in diabetics with normal renal function and negative clinical proteinuria (less than 100 mg/24 h) than in normals. In patients with clinical proteinuria (greater than 100 mg/24 h), the percentage of protein with an Mr of 67 kDa (presumably albumin) was predominantly increased, while the percentage of lower Mr proteins was considerably decreased. A positive correlation existed between the total urinary protein excretion and the percentage of 67 kDa protein in diabetics without clinical proteinuria (r = 0.487, p less than 0.01), but not in normal subjects. Recovery of glycemic control led to a decrease of urine proteins with an Mr lower than 67 kDa, while deterioration of the control resulted in an increase in these proteins. The present data confirm the idea that analysis of the components of urine proteins by SDS-PAGE represents a useful approach to understanding the glomerular and tubular functions in diabetic patients. Additionally, this investigation appears to provide biochemical evidence that dysfunction of the glomerular permselectivity to plasma proteins might already have occurred in diabetic patients without clinical evidence of diabetic nephropathy.
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PMID:Analysis of urinary protein in diabetics; its clinical implications as a predictor of nephropathy. 203 31

Contrasting results have been reported regarding the prevalence of hypertension in insulin-dependent diabetes mellitus (IDDM), showing a slightly higher or normal percentage of IDDM patients with elevated blood pressure levels than in the general population. Most of the cross-sectional and prospective studies on the prevalence of hypertension in IDDM show an association between microalbuminuria and elevated blood pressure levels. However, it is not clear whether hypertension is simply secondary to kidney damage or whether hypertension occurs with or even before the development of impaired kidney function. Patients with IDDM have a higher exchangeable body Na+ pool. Na+ retention in IDDM is accounted for by several metabolic and hormonal abnormalities such as hyperglycemia, hyperketonemia, hyperinsulinemia, altered secretion, and resistance to atrial natriuretic peptide. High blood pressure appears to be dependent, at least at some phase, on expansion of extracellular fluid volume as a consequence of defects in the renal secretion of Na+ and water. On the other hand, a tendency toward Na+ retention characterizes all patients with IDDM, whereas hypertension develops only in a subgroup of diabetic patients. One possible explanation for these findings is that a genetic predisposition plays a role in creating susceptibility to hypertension and perhaps to diabetic nephropathy independent of diabetes, even if Na+ retention can further deteriorate this susceptibility to hypertension. With regard to this issue, it has recently been suggested that the risk of kidney disease in patients with IDDM is associated with a genetic predisposition to hypertension. Furthermore, diabetic nephropathy occurs in familial clusters, because diabetic siblings of nephropathic diabetic patients show a higher frequency of diabetic nephropathy than the diabetic siblings of nonnephropathic diabetic patients. One of the possible genetic markers that could be useful to identify the diabetic patients with susceptibility to hypertension and diabetic nephropathy is the Na+(-)Li+ countertransport activity in erythrocytes.
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PMID:Insulin-dependent diabetes mellitus and hypertension. 204 36

We studied erythrocyte sodium-lithium countertransport in 33 patients with Type 1 (insulin-dependent) diabetes mellitus with diabetic nephropathy, 18 patients with Type 1 diabetes without diabetic nephropathy and in 42 non-diabetic patients with various other renal diseases. No significant differences were found in sodium-lithium countertransport between these three groups (median (range) 322 (162-676) vs 321 (189-627) vs 300 (142-655) mumol.l cells-1.h-1). We conclude, that sodium-lithium countertransport cannot be used as a marker for diabetic nephropathy.
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PMID:Erythrocyte sodium-lithium countertransport is not different in type 1 (insulin-dependent) diabetic patients with and without diabetic nephropathy. 206 47

The precise pathogenesis of human diabetic kidney disease and the factors responsible for the susceptibility to it remain to be established. However, there is now evidence that renal disease clusters in families and that genetic factors are of central importance in determining liability. A predisposition to arterial hypertension has been suggested as playing a contributory role in the development of kidney disease. Genetically controlled hypertrophic processes may be implicated in the susceptibility to arterial wall damage and glomerular injury in diabetes. This suggestion derives from the observation that the 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 sign of renal damage is the appearance of microalbuminuria and of a small elevation in arterial pressure, changes associated with significant mesangial expansion. Microalbuminuria is associated with abnormalities of lipoprotein profiles possibly as a consequence of insulin-resistance-induced hyperinsulinemia. It could be postulated that the environmental changes brought about by diabetes lead in susceptible individuals to increased systemic and intraglomerular pressure on the one hand and mesangial expansion on the other. These two processes would cause proteinuria and glomerulosclerosis. Lipid abnormalities would 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 of reduction in renal function, more hypertension, more proteinuria, more glomerular obsolence, more hyperlipidemia and eventually end-stage renal failure or premature cardiovascular death.
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PMID:Mechanisms of diabetic renal and cardiovascular disease. 207 90

We have studied the long term effects of captopril therapy on proteinuria in ten patients with non-insulin-dependent diabetes mellitus with hypertension and nephropathy. There were 7 males and 3 females, with a mean age of 53.3 +/- 10.6 years. After a run-in period of two weeks, therapy with captopril was started. The following parameters were studied: serum glucose, sodium, potassium, cholesterol and triglycerides, glycosylated haemoglobin, renal function and 24 hour urine protein excretion before and at six month intervals for up to 24 months. Average BP fell significantly from 182.5 +/- 28/95 +/- 7.1 to 146 +/- 16.7/76 +/- 18.1 mmHg although no significant changes were seen in the biochemical parameters studied, except a reduction in 24 hour urine protein excretion from 3.86 +/- 2.85 to 0.88 +/- 1.08 g/24 h after 24 months of treatment (P less than 0.01). No correlation was observed between the reduction in proteinuria and any other parameters studied. Our results confirm the reduction of proteinuria in patients with type II diabetes mellitus and stable diabetic nephropathy treated with captopril. This effect was maintained for a period of 24 months.
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PMID:Long term follow-up of the effect of captopril on severe proteinuria in hypertensive diabetic patients. 209 9

The roles of blood pressure and glomerular filtration rate in the renal handling of albumin, beta 2-microglobulin and sodium were studied by partial correlation analysis in 22 patients with glomerulonephritis and in 25 patients with diabetic nephropathy. The analysis showed that in these proteinuric patients blood pressure may have an independent role in the regulation of albumin excretion in both diseases. Fractional beta 2-microglobulin clearance and fractional excretion of sodium correlated significantly in both diseases. In the diabetic patients this correlation remained strong after removing the effect of blood pressure, whereas in the patients with glomerulonephritis control of blood pressure clearly decreased the correlation. This reflects differences in the renal handling of sodium and beta 2-microglobulin in patients with diabetic nephropathy and glomerulonephritis.
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PMID:Interrelations of blood pressure, glomerular filtration rate, protein clearances and sodium excretion in patients with glomerulonephritis and diabetic nephropathy. 211 24

Because insulin shows an antinatriuretic effect in healthy humans, insulin therapy resulting in circulating hyperinsulinemia may lead to sodium retention and in turn to hypertension in individuals with insulin-dependent diabetes mellitus (IDDM). Moreover, it has been proved that atrial natriuretic peptide (ANP) plays a major role in modulating natriuresis in humans. This study investigated the relationship between insulin and ANP in modulating sodium metabolism in normotensive and hypertensive IDDM subjects compared with control groups of normotensive and hypertensive nondiabetic subjects. IDDM normotensive and hypertensive subjects had mean +/- SE duration of IDDM of 7 +/- 2 and 8 +/- 2 yr, respectively, and had no clinical features of diabetic nephropathy. All subjects received a saline infusion (2 mmol.kg-1.90 min-1) during euglycemia. IDDM normotensive and hypertensive subjects received a subcutaneous insulin infusion (15 mU.kg-1.h-1), resulting in twofold higher plasma free-insulin levels (16 +/- 2 and 19 +/- 3 microU/ml, respectively) than in nondiabetic normotensive and hypertensive subjects (7 +/- 2 and 8 +/- 2 microU/ml, respectively). During saline challenge, sodium excretion increased by 22 +/- 4% in normotensive and 49 +/- 9% in hypertensive nondiabetic subjects but by only 11 +/- 0.4% in normotensive (P less than 0.01) and 8 +/- 2% in hypertensive (P less than 0.01) IDDM subjects. The impaired natriuretic response to saline challenge was mainly due to greater rates of sodium reabsorption by kidney proximal tubules in IDDM than nondiabetic subjects. At baseline, plasma ANP concentrations were significantly higher in both IDDM groups than in control groups (normotensive IDDM and control subjects: 38 +/- 4 and 19 +/- 2 pg/ml, respectively, P less than 0.01; hypertensive IDDM and control subjects: 45 +/- 6 and 27 +/- 4 pg/ml, respectively, P less than 0.05). After saline challenge, ANP concentrations rose to 39 +/- 4 pg/ml in normotensive and 49 +/- 5 pg/ml in hypertensive control subjects, whereas no significant change above baseline value was seen in IDDM subjects. Both IDDM groups showed a 10-12% greater exchangeable Na+ pool than control subjects regardless of the presence of hypertension. Subcutaneous insulin infusion, resulting in circulating plasma free-insulin levels in normotensive control subjects comparable to those in IDDM patients, inhibited natriuresis, increased proximal tubule sodium reabsorption at the level of the kidney, and inhibited an adequate ANP stimulation by saline challenge. We conclude that hyperinsulinemia leads to increased proximal tubule sodium reabsorption and impaired ANP response during saline administration. Both mechanisms account for sodium retention in normotensive and hypertensive IDDM patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of insulin and atrial natriuretic peptide in sodium retention in insulin-treated IDDM patients during isotonic volume expansion. 213 1


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