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)

Plasma renin activity (PRA) was determined in 48 patients with diabetes mellitus in sodium balance on a 10-20 mEq. Na diet. Nine were normotensive (group I), 11 11 were hypertensive without diabetic nephropathy (group III). Results were compared with those in 16 normal subjects and 49 nondiabetic patients with essential hypertension in similar Na balance. Mean supine PRA did not differ significantly among groups I and II, normal subjects, and patients with essential hypertension. Group III diabetics had a supine PRA of 2.4 +/- 0.4 ng./ml./hr. (x +/- S.E.M.), significantly lower than the other diabetic groups (P less than 0.005) and normal subjects (P less than 0.05). Upright PRA was 12.8 +/- 2.2 in group I diabetics, similar to that in normal subjects (13.3 +/- 2.3), and 8.1 +/- 1.4 in group II diabetics, similar to that in essential hypertensives (6.8 +/- 0.8). In group III diabetics, upright PRA was 4.0 +/- 0.5, significantly lower than that in any other group. These results suggest that (1) PRA is normal in normotensive diabetics, (2) upright PRA in diabetics with hypertension but no nephropathy is similar to that in essential hypertension, and (3) patients with diabetes, hypertension, and nephropathy have "low renin hypertension," explaining the virtual absence of malignant hypertension in this group. Although the major mechanism for this low PRA may be volume expansion, indicating the need for potent diuretics, other mechanisms include hyalinization of the afferent arteriole, decreased cathecholamine stimulation of renin release, and inadequate conversion of prorenin to renin.
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PMID:Plasma renin activity and hypertension in diabetes mellitus. 97 6

To clarify the ultrastructural changes in renal proximal tubules causing microalbuminuria in the early stage of diabetic nephropathy, three different groups of rats were prepared: rats with streptozotocin (STZ)-induced diabetes given no treatment (DMut; n = 7), rats with STZ-induced diabetes treated with insulin (DMt; n = 7), and non-diabetic rats injected with citrate buffer (control; n = 7). In each group, the laboratory findings, ATP content of the renal cortex, and the size of proximal tubule cells and their nuclei and mitochondria (MT) were determined. In two weeks after the start of the study, MT in renal proximal tubules showed diffuse enlargement in the DMut group as compared with those in the control group. Renal cortical ATP content, fractional sodium excretion (FENa), urinary excretion of beta 2-microglobulin and albumin were also increased significantly in the DMut group relative to the controls. In the DMt group, most of the examined parameters returned almost to normal. There were positive correlations between each of the following parameters: hyperglycemia and MT enlargement, MT enlargement and increased cortical ATP content, increased cortical ATP content and increased FENa, increased FENa and increased urinary excretion of beta 2-microglobulin and albumin. On the basis of these results, we conclude that mitochondrial enlargement, resulting from disturbed metabolism of ATP, may reduce active transport in renal proximal tubules, which, in turn, may impair reabsorption in the tubules. This would cause urinary excretion of low-molecular-weight proteins and microalbumin in the early stage of diabetic nephropathy.
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PMID:Correlation between mitochondrial enlargement in renal proximal tubules and microalbuminuria in rats with early streptozotocin-induced diabetes. 129 Mar 23

1. It has been proposed that raised erythrocyte sodium-lithium countertransport activity in type 1 diabetic patients is associated with an increased risk of developing diabetic nephropathy. Diabetic patients with established nephropathy would therefore be expected to have high activity. 2. Standard sodium-lithium countertransport activity, sodium affinity (Km) and maximum velocity (Vmax) were measured in type 1 diabetic patients at different stages of diabetic nephropathy and in appropriately matched uncomplicated diabetic patients and normal control subjects. 3. A small proportion (15%) of patients with nephropathy had standard sodium-lithium countertransport activity higher than the control range. However, mean standard sodium-lithium countertransport activity in the diabetic patients with nephropathy [mean +/- SEM, 0.26 +/- 0.12 mmol of Li+ h-1 (l of cells)-1] was not significantly higher than in the uncomplicated diabetic patients [0.27 +/- 0.03 mmol of Li+ h-1 (l of cells)-1] or in the normal control subjects [0.25 +/- 0.02 mmol of Li+ h-1 (l of cells)-1]. 4. There were marked changes in the kinetic characteristics of the sodium-lithium countertransport in the diabetic patients with nephropathy so that there were decreases in both Km and Vmax. 5. These kinetic changes could not be attributed to an effect of either renal failure per se or the duration of diabetes. 6. The characteristic kinetic changes in sodium-lithium countertransport may indicate underlying alterations in membrane function with the onset of nephropathy in type 1 diabetes.
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PMID:Changes in erythrocyte sodium-lithium countertransport kinetics in diabetic nephropathy. 131 15

To examine the impact of metabolic control on renal responses to human atrial natriuretic peptide (hANP) in type 1 diabetes mellitus, 13 patients with HbA1 less than 8.5%, nine patients with HbA1 greater than 8.5% and ten healthy volunteers were studied. According to a randomized, single-blind trial design, 0.5 and 2.0 micrograms/kg hANP-(95-126) (Urodilatin) (Bissendorf Peptide, Hannover) or placebo were given as iv bolus injections at 90-minute intervals. Patients with HbA1 greater than 8.5% differed from those with HbA1 less than 8.5% in longer diabetes duration, more prevalent retinopathy and neuropathy and increased somatomedin C levels and urinary albumin excretion (p less than 0.05). In response to hANP, patients with HbA1 greater than 8.5% had decreased responses of urinary volume and sodium excretion in comparison to patients with HbA1 less than 8.5% (p less than 0.05) in whom renal responses to hANP did not differ from controls. Despite similar hANP levels, hANP-stimulated urinary cGMP excretion in patients was higher than in controls (p less than 0.01). Impaired renal responses to hANP in diabetes patients with insufficient glycemic control apparently contribute to the mechanisms of diabetic sodium retention. Near-normoglycemia may prevent this phenomenon which is intimately involved into the pathogenesis of diabetic nephropathy.
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PMID:[Effect of metabolic control on the renal effects of human atrial natriuretic peptide-(95-126) (urodilatin) in normotensive patients with type I diabetes mellitus]. 131 42

In order to assess the potential role of the plasma membrane sodium-proton (Na+/H+) exchanger in the pathogenesis of diabetic nephropathy, we investigated 32 insulin dependent (type 1) diabetic patients and 21 control subjects. We tested the Na+/H+ exchange as the rate of amiloride sensitive and sodium dependent volume gain of platelets suspended in sodium propionate. Patients with diabetic nephropathy had significantly increased rates of Na+/H+ exchange (0.31 +/- 0.06 s-1 x 10(-2)) when compared to those without nephropathy (0.24 +/- 0.07, p less than 0.05) or to a control group (0.23 +/- 05, p less than 0.05). Nine patients who were classified as hypertensive had a highly significant increase in the Na+/H+ exchange rates when compared to 23 non-hypertensive diabetic patients: 0.33 +/- 0.04 versus 0.24 +/- 0.06 (p less than 0.001). There was no significant correlation between the Na+/H+ exchange rates and age, diabetes duration, glycated hemoglobin or fructosamine levels on the day of the test. In summary, the data presented here demonstrate an increase in the Na+/H+ exchange rate in insulin-dependent diabetic patients with nephropathy and hypertension.
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PMID:Increased platelet sodium-proton exchange rates in insulin-dependent (type 1) diabetic patients with nephropathy and hypertension. 132 Jul 32

The findings that circulating levels of atrial natriuretic peptide (ANP) are elevated in diabetic nephropathy and that the magnitude of the urinary excretion rate of cGMP in response to hypervolemia-induced ANP release is blunted have recently been reported. The purpose of this study was to determine whether these abnormalities are associated with the down-regulation of ANP receptors. Because biologically active (A) ANP receptors in the kidney are inaccessible, we have examined the binding of (125I alpha)ANP to clearance (C) receptors on platelets obtained from patients with diabetic nephropathy. Scatchard analysis revealed a reduction in such binding sites compared with those in healthy controls: 12 +/- 2 versus 19 +/- 2 per platelet, respectively (P less than 0.001). The dissociation constant, Kd, was higher: 66.7 +/- 33.1 versus 38.5 +/- 11 pM, respectively (P less than 0.02). The reduced number of receptors could reflect the down-regulation of ANP C receptors in response to an elevation of plasma levels of ANP, the median value of which was 10.6 versus 7.1 pmol/L in controls (P less than 0.05). Alternatively, the findings could represent a primary adaptation by C receptors to elevate plasma ANP levels and increase the availability of the peptide to biologically active renal receptors. The latter adaptation would serve to mitigate the sodium retention that attends diabetic nephropathy.
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PMID:Regulation of platelet clearance receptors for atrial natriuretic peptide in diabetic nephropathy. 132 60

Increased leucocyte Na+/H+ antiport activity has previously been demonstrated in both hypertensive subjects and Type 1 diabetic patients with nephropathy and may indicate a predisposition to hypertension in such diabetic patients. We have studied intracellular pH and Na+/H+ antiport activity in cultured skin fibroblasts from diabetic patients with and without nephropathy, together with non-diabetic controls to assess if such differences persisted in cultured cells. Fibroblasts from diabetic patients with nephropathy were significantly more alkaline [median (range): 6.90 (6.82 to 7.07)] compared to both normoalbuminuric diabetic patients [6.81 (6.75 to 6.89)] or normal controls [6.82 (6.77 to 6.93)] (P < 0.001 for both). This was associated with a raised Na+/H+ antiport activity in cells from patients with nephropathy when intracellular pH (pHi) was clamped to pH 6.5, without any differences in the maximal transport capacity of the antiport at pHi 6.2. Using both intracellular pH and Na+/H+ antiport activity at pHi 6.5, patients with nephropathy were separated from uncomplicated subjects with a sensitivity of 92% and a specificity of 100%. In conclusion, the raised Na+/H+ antiport activity in cells from patients with diabetic nephropathy persists despite passaging in vitro, thus indicating a heritable component, and results mainly from an increased apparent affinity of the antiport for intracellular H+.
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PMID:Intracellular pH and Na+/H+ antiport activity of cultured skin fibroblasts from diabetics. 133 51

In hypertensive humans and the spontaneously hypertensive rat, increased cellular Na+/H+ antiport activity has been demonstrated in leukocytes, platelets, skeletal muscle, and vascular smooth muscle cells. This membrane abnormality may be associated with medial thickening of resistance vessels. A similar membrane transport abnormality has also been demonstrated in leukocytes and fibroblasts from type 1 diabetic patients with nephropathy. This membrane transport marker of hypertension may indicate a predisposition to essential hypertension in such patients and may lead to diabetic nephropathy, possibly from mesangial expansion.
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PMID:Abnormalities in Na+/H+ antiporter activity in diabetic nephropathy. 133 34

The plasma membrane Na+/H+ exchanger is a ubiquitous system which plays a role in the regulation of intracellular pH and the control of cell growth. In order to assess the potential role of this system in the pathogenesis of diabetic nephropathy, we investigate 42 normotensive insulin-dependent diabetic patients with or without microalbuminuria. We tested the platelet Na+/H+ exchange as the rate of amiloride sensitive and sodium dependent volume gain of cells suspended in sodium propionate. Urinary albumin excretion (UAE) was assayed by radioimmunoassay on a 24 h sample; the glomerular filtration rate (GFR) and the renal plasma flow were determined by 99 m Tc-DTPA and 1231 l-hippuran respectively. Thirty patients (group 1) had EUA > 30 mg/24 h (m +/- sd: 11 +/- 7 mg/24 h), 12 patients (group 2) had microalbuminuria (62 +/- 30 Mg/24 h, range from 35 to 136 mg/24 h). The platelet Na+/H+ exchange rate was significantly increased in patients of group 2: 0.34 +/- 0.01 versus 0.26 +/- 0.06 s-1 x 10(-2) (p < 0.005). There was no significant difference between these two groups regarding blood pressure (116 +/- 14/71 +/- 7 versus 119 +/- 12/73 +/- 5 mmHg), age, diabetes duration, glycated hemoglobin or fructosamine levels. On the whole population, we found a significant positive correlation between the platelet Na+/H+ exchange rate and the UAE (r = 0.57, p < 0.001) and with the glomerular filtration fraction (r = 0.43, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Activity of platelet sodium-proton exchanger, microalbuminuria and insulin-dependent diabetes]. 133 55

Our study compared the effects of an angiotensin-converting enzyme inhibitor (captopril) versus a calcium antagonist (nifedipine) on proteinuria and renal function in patients with diabetic nephropathy. A randomized follow-up study was designed. Type 2 diabetic patients, with established diabetic nephropathy (proteinuria greater than 0.5 g/24 h), were treated with nifedipine (10 patients, group A) or captopril (10 patients, group B) for 6 months. Arterial blood pressure, metabolic parameters, proteinuria and renal function were measured and compared. Mean percentage differences for glomerular filtration rate, renal plasma flow and filtration fraction between the two groups were calculated. No significant differences were observed in serum glucose, glycosylated hemoglobin (hemoglobin A1c), Na+, K+ or albumin in either group or between groups. Blood pressure decreased significantly with both treatments and mean blood pressure was significantly lower in group A compared with group B at 6 months (Mann-Whitney U-test, P = 0.03). Proteinuria was similar in both groups at randomization, but after 3 and 6 months of treatment significant reductions were observed only in the group treated with captopril (P less than 0.01). A significant decrease in filtration fraction was observed in group B with an increase in group A (Mann-Whitney U-test, P = 0.03). Multiple regression analysis identified the therapeutic agent administered as an independent variable for decrease in proteinuria. It is concluded that antihypertensive treatment with captopril, but not with nifedipine, reduced proteinuria in patients with diabetic nephropathy, although a better mean blood pressure was obtained with nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative effects of captopril versus nifedipine on proteinuria and renal function of type 2 diabetic patients. 142 58


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