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)

Proteinuria has been analysed in 334 maturity-onset diabetics and 80 matched controls. Proteinuria measured in the recumbent position exceeded 100 mug/min in 53% of the diabetic population. The percentage of excessive proteinuria increased with duration of the disease. Sex and age had no influence. Out of 55 first year diabetics, 49% had abnormal quantitative proteinuria; this is in contrast to 76 longterm diabetics (over 12 years) of whom 38% had proteinuria under 100 mug/min. Electrophoresis and immuno-electrophoresis showed a glomerular pattern in 40%, a tubular pattern in 15% and a mixed pattern in 8% of all the diabetics. 32% of the diabetics with quantitatively normal proteinuria were abnormal qualitatively, and this may be the first manifestation of diabetic nephropathy. Thirty-eight other patients had a normal electrophoretic pattern in spite of increased proteinuria. Proteinuria levels were significantly associated with hematuria, bacteriuria and reduced GFR, but not with leukocyturia, insulin dependence and hypertension. Upright position increased the proteinuria to a greater degree amongst the patients with normal proteinuria. We discuss the role of increased filtration pressure and glomerular permeability in modifying proteinuria in diabetes. Sensitive quantitative and qualitative proteinuria determinations are important tools both in early diagnosis of diabetic nephropathy in clinical practice and in epidemiological studies.
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PMID:[Proteinuria in mature diabetic patients. Quantitative and qualitative analysis]. 121 95

Diabetes mellitus can lead, along the years of its course, to chronic renal failure in a high proportion of cases. An early risk-indicator of later diabetic nephropathy is the presence of microalbuminuria, but it usually takes about fifteen to twenty years to appear. Before that, no clinical signs can disclose the underlying alterations of glomerular basement membrane that will eventually bring forth overt nephropathy. The usefulness of the altered excretion of isoenzymes of amylase as an early marker of the glomerular charge selectivity was tested in 202 juvenile onset insulin-dependent diabetics, compared with 51 normal subjects matched for age and sex. The diabetic patients studied showed increased excretion of salivary amylase into urine. The salivary to pancreatic amylase ratio of concentrations in urine was always below 1 in normal subjects, and was increased over 1 in 33.2% of diabetics, although microalbuminuria was present only in 26.2% of patients. The excretion of other proteins was within reference values in the majority of cases, indicating that the kidney was not seriously affected in those patients. Moreover, the altered salivary to pancreatic amylase ratio in urine was more prevalent than microalbuminuria (36.6% vs 18%) in the first decade of the evolution of the diabetes. These results indicate that the ratio of excretions of both isoamylases into urine is a more sensible and earlier marker of altered glomerular charge barrier for anionic proteins.
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PMID:Utility of filtration markers to monitor the quality of glomerular function. 128 36

Divergent findings in recent clinical and experimental studies have caused considerable controversy as to whether or how elevated plasma levels of human atrial natriuretic peptide (hANP) may contribute to the pathogenesis of diabetic nephropathy in type I diabetic patients. Therefore, we decided to examine potential changes of urinary albumin excretion (UAE), urinary excretion of alpha-1-microglobulin (A-1-M), mean arterial blood pressure (MAP), hANP levels, creatinine clearance and HbA1 in the course of a prospective one-year study in 19 patients (13 females, six males, age 29 +/- 2 years). All patients had intensified insulin treatment. Seven patients at increased risk for eventually developing nephropathy (group 1) were identified by repeatedly showing elevated UAE ( > 30 mg/24 h). The other patients served as controls (group 2). Patients in group 1 differed from those in group 2 in increased A-1-M (maximal difference, 10.1 +/- 1.5 vs. 5.5 +/- 1.0 mg/l, p < 0.01). In the second half of the study, 43% of the MAP measurements in group 1 exceeded 100 mmHg in comparison to 19% in group 2 (p < 0.01). Simultaneously, 38% of the hANP levels in plasma in group 1 were higher than 25 pg/ml (upper limit of normal range) in comparison to 15% in group 2 (p < 0.05). There were no differences in creatinine clearance between both groups. 58% of the HbA1 concentrations measured in group 1 in the course of the study exceeded 8.5% in comparison to 47% in group 2 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The role of human atrial natriuretic peptide on pathogenesis of nephropathy in patients with type I diabetes mellitus]. 128 23

Diabetes mellitus (DM)-linked metabolic alterations and hypertension concomitantly accelerate or precipitate cerebrovascular and coronary heart disease, nephropathy, retinopathy and widespread macroangiopathy, thereby conferring to diabetic patients a very high risk of morbidity, disability and early death. Therefore, the long-term care for diabetic patients should be aimed at concomitant metabolic and blood pressure (BP) control. Dietary measures are indispensable; a high fibre, low fat, low salt diet is recommended, complemented with caloric restriction and physical exercise when body weight is above the ideal. Antidiabetic pharmacotherapy involves an unresolved dilemma. The desired achievement of euglycemia necessitates effective levels of insulin, but hyperinsulinemia (due to parenteral [over]treatment in insulin-dependent DM) is suspected to promote atherogenesis and represents a coronary risk factor and perhaps even facilitates hypertension. Considering antihypertensive pharmacotherapy, thiazide-type or loop diuretics are problematic drugs in DM because they can aggravate metabolic alterations. These agents also seem to exert only a limited preventive or regressive effect on left ventricular hypertrophy (LVH); beta-blockers are also not considered ideal, since they decrease the awareness of hypoglycemia and tend to promote glucose intolerance. Unselective beta-blockers in particular promote peripheral ischemia and insulin-induced hypoglycemia, while beta-blockers without intrinsic sympathomimetic activity lower serum HDL-cholesterol. Calcium antagonists and ACE inhibitors have equivalent antihypertensive efficacy, do not impair carbohydrate and lipid homeostasis or peripheral perfusion and can effectively improve LVH. Certain ACE inhibitors may even slightly ameliorate abnormal insulin sensitivity and plasma glucose levels. While alpha-blockers share most of these desirable properties, these agents are more prone to precipitate orthostatic hypotension in the diabetic patient. The non-thiazide diuretic indapamide and the serotonin2-antagonist ketanserin also combine antihypertensive efficacy with metabolic neutrality. The ultimate goal of therapy is to improve life prognosis. In essential hypertension, conventional drug treatment based on diuretics in high dosage satisfactorily reduced cerebrovascular but not coronary complications or sudden death. In diabetic patients, the influence of antihypertensive therapy on prognosis has not been assessed prospectively. Based on retrospective analyses, Warram et al reported a 3.8 times higher mortality in diabetics treated with diuretics alone, than in diabetics with untreated hypertension (Arch Intern Med. 1991;151:1350). H. H. Parving calculated that effective BP control in patients with diabetic nephropathy might reduce 10 year-mortality from about 65 to 20 percent (J Hypertension. 1990; 8[Suppl 7]:187).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Antihypertensive therapy in diabetic patients. 128 10

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

Points of agreement: (1) In IDDM, hypertension occurs in patients who have already developed nephropathy, probably in the microalbuminuric phase. (2) Hypertension is an important accelerator of the development of diabetic nephropathy. (3) Hypertension, obesity and NIDDM are often associated, and insulin resistance is commonly observed in all three states. (4) Antihypertensive therapy retards the development of diabetic nephropathy in IDDM and reduces proteinuria in NIDDM. (5) The choice of antihypertensive agent in the diabetic patient must be based upon the efficacy of the drug as well as avoidance of side effects including deleterious influence on glucose, insulin and lipid levels and renoprotection. (6) Carefully conducted long-term comparative trials between different classes of antihypertensive drugs in microalbuminuric IDDM and NIDDM patients are essential. Points of major controversy: (1) Detection of IDDM patients prone to the development of diabetic nephropathy can be performed by measuring specific parameters such as erythrocyte Na(+)-Li+ countertransport activity. (2) Insulin resistance is a pathogenic mechanism rather than purely an association with hypertension and obesity. (3) A certain class of antihypertensive agents--ACE inhibitors--confers a specific renoprotective effect in diabetic nephropathy, in addition to its effects upon systemic blood pressure. (4) Reduction of blood pressure should be considered in the normotensive microalbuminuric diabetic patient. (5) Microalbuminuria is a sufficient 'surrogate endpoint' for the progression of renal failure.
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PMID:Meeting report of the International Society of Hypertension Conference on Hypertension and Diabetes. 131 6

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 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

A double blind crossover trial was performed on the effect of enalapril on urinary albumin excretion (UAE) in normotensive insulin dependent diabetics. Nineteen normoalbuminuric (UAE < 30 mg/24 h) and 17 microalbuminuric patients (UAE > 30 and < 300 mg/4 h) were studied; all patients had post prandial blood glucose levels < 180 mg/dl, HbA1 < 11% and none had chronic diabetic complications. Both groups had similar age, years of diabetes, body mass index and protein ingestion (70 g/day). Fifty percent of patients in each group received 5 mg/day of enalapril or placebo during one year, and during the second year the therapy was switched. No changes were observed in blood pressure, post prandial blood glucose, HbA1 and plasma electrolytes during the study period. A reduction in creatinine clearance, within normal limits, in both groups of patients treated with enalapril and no modifications with placebo were observed. UAE decreased significantly in normo and microalbuminuric patients initially treated with enalapril from 19 +/- 8 to 8 +/- 2 and from 71 +/- 19 to 39 +/- 12 mg/24 h respectively. These values increased during the placebo period to 23 +/- 6 and 47 +/- 13 mg/24 h respectively. Among those initially treated with placebo, UAE increased only in normoalbuminurics from 19 +/- 7 to 28 +/- 9 mg/24 h. During subsequent treatment with enalapril, UAE decreased in both groups. It is concluded that, in this group of patients, enalapril decreases UAE, possibly preventing the progression to severe forms of diabetic nephropathy.
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PMID:[Reversibility of early stage diabetic nephropathy]. 134 Sep 38

A possible association of cardiovascular risk factors and early diabetic nephropathy was investigated in 32 patients. Microalbuminuria (radioimmunoassay), total and HDL cholesterol and triglycerides (enzymatic methods), glycosylated hemoglobin (colorimetric methods), Apo A1 and B (immunonephelometric) and LDL were measured. Microalbuminuria was present in 28% of patients. Compared to subjects with no microalbuminuria they had increased levels of cholesterol (200.2 +/- 13.5 (SE) vs 168.6 +/- 9.4 mg/dl, p < 0.025) and LDL cholesterol (171.9 +/- 14.1 vs 137.4 +/- 9.1 mg/dl, p < 0.025). Systolic blood pressure was also higher in patients with microalbuminuria (127.8 +/- 3.9 vs 114.5 +/- 2.8 mmHg, p < 0.01). Microalbuminuria was correlated to the level of diastolic blood pressure (r = 0.74, p < 0.025). Thus, persistent microalbuminuria in insulin dependent diabetic patients is associated to cardiovascular risk factors which may explain the increased cardiovascular morbidity and mortality in these patients.
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PMID:[Persistent microalbuminuria in insulin-dependent diabetics and cardiovascular risk factors]. 134 15


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