Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Non-insulin-dependent diabetes is associated with a 2-3 fold increased risk of cardiovascular disease. The poor relationship between this risk and either glycaemic control or diabetes duration suggests that some other aspect of the diabetic state, and not hyperglycaemia per se, mediates this risk. This other aspect of diabetes does not comprise alterations in recognized cardiovascular risk factors such as blood pressure or lipids, as the major component of the excess risk is in those diabetics with low levels of the other risk factors. It thus appears that there may be some factors that predispose both to diabetes and to cardiovascular disease. In insulin-dependent diabetics most of the excess risk of cardiovascular disease occurs in subjects with proteinuria, and microalbuminuria or proteinuria in non-insulin-dependent diabetics also substantially increases cardiovascular risk. Although changes in recognized risk factors in diabetics with nephropathy may partly explain these observations, we and others have shown that microalbuminuric non-diabetics also have a markedly increased prevalence of cardiovascular disease and substantially increased cardiovascular mortality. The observations that in insulin-dependent diabetics nephropathy shows family clustering and that these patients have elevated sodium lithium counter-transport rate, a possible genetic marker for the vascular complications of hypertension, have led to the suggestion that microalbuminuria may be a marker of a genetic predisposition to vascular disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Microalbuminuria: a genetic link between diabetes and cardiovascular disease? 148 48

Diabetic renal disease is a clinical syndrome in which proteinuria is followed by the development of renal failure, and is commonly associated with the concomitant development of hypertension. In insulin-dependent diabetic (IDDM) patients, hypertension often first appears in the microalbuminuric phase of diabetic nephropathy whereas in non-insulin-dependent diabetic (NIDDM) patients, hypertension often antecedes nephropathy and may precede the diagnosis of diabetes. Antihypertensive regimens including diuretics, vasodilators such as hydralazine, beta-blockers and ACE inhibitors reduce proteinuria and delay the decline in renal function in IDDM patients with established nephropathy. No such data are as yet available for calcium antagonists. In microalbuminuric diabetic patients with hypertension, conventional antihypertensive agents, ACE inhibitors and calcium antagonists have been shown to decrease urinary albumin excretion. In the diabetic patient with normal blood pressure and microalbuminuria, there is much less information. It appears likely that ACE inhibitors reduce or retard the rate of increase in albuminuria in these patients. The effect on ultimately delaying or preventing renal failure remains unknown although the preliminary evidence is encouraging. Data on calcium antagonists remain inconclusive with some reports suggesting an increase in proteinuria with the dihydropyridine calcium antagonists. However, a recent longer term study suggested that nifedipine may prevent the rise in albuminuria which is generally observed in the untreated normotensive microalbuminuric subject.
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PMID:The management of diabetic proteinuria. Which antihypertensive agent? 150 44

Urinary albumin excretion rate (AER) was measured in non-diabetic controls (n = 143) and newly diagnosed impaired glucose tolerant (IGT, n = 64) and non-insulin-dependent (type 2) diabetic patients (n = 146). AER progressively increased from non-diabetic [3.7 (1.1-51.3) micrograms/min, median (5-95th centile)] to IGT [4.8 (1.3-53.7)] and diabetic [7.3 (1.4-91.6)] groups. Eight percent of non-diabetic, 19% of IGT and 23% of type 2 diabetic patients showed 'microalbuminuria' (AER, 20-200 micrograms/min) (non-diabetic vs diabetic P less than 0.01, non-diabetic vs IGT NS, IGT vs diabetic NS). AER was directly related to waist-hip ratio (P less than 0.001) and HbA1 (P less than 0.01) in diabetic patients; 80% of diabetic patients with microalbuminuria were men (P less than 0.06 compared to 'normoalbuminuric' diabetic patients). Association of AER with waist-hip ratio was present in men as well as women. Thus, in the newly diagnosed type 2 Indian diabetic patients AER is associated with central obesity in addition to its well known association with hyperglycaemia. Our findings offer a possible explanation for the increased risk of proteinuria in diabetic men than in women because men are centrally more obese. It could also explain previous reports of higher AER in migrant Asian diabetic patients in the U.K. compared to native white Caucasian diabetic patients because Asians are known to be more centrally obese.
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PMID:Urinary albumin excretion rate (AER) in newly-diagnosed type 2 Indian diabetic patients is associated with central obesity and hyperglycaemia. 151 62

Heparan sulfate proteoglycans (HSPG) are negatively charged constituents of the renal extracellular matrix including the glomerular basement membrane (GBM) and mesangial matrix. Biochemical and functional studies of patients with type-1 insulin dependent diabetes mellitus (IDDM) suggest that alterations of HSPG may occur in diabetic nephropathy. We have utilized a specific cytochemical method and electron microscopy to quantitate the distribution of HSPG in the GBM of 10 normal people and in 16 IDDM patients with a spectrum of clinical and structural changes. Enzyme incubation studies of normal infant kidney demonstrated that heparitinase removed 94% of the stainable anionic sites in the lamina rara externa (LRE) and 77% of the sites in the lamina rara interna (LRI) of the GBM. In contrast, incubation in the enzyme chondroitinase ABC did not reduce the number of sites in the LRE but reduced the number of sites in the LRI by 26%. The HSPG anionic sites in normal subjects were distributed in the LRE as 20.9 +/- 1.3, and in the LRI as 13.1 +/- 2.2 per micron GBM length. Anionic sites were slightly reduced (19.6 +/- 1.3, P less than 0.04) in the LRE of IDDM patients with normal urinary albumin excretion rates (UAE), or microalbuminuria, and were reduced in both the LRE and LRI of IDDM patients with clinical proteinuria (13.1 +/- 2.3, P less than 0.001 and 8.9 +/- 2.1, P less than 0.001, respectively). The number of anionic sites in the LRE and LRI, respectively, correlated with UAE (r = +0.78, P less than 0.001, r = +0.58, P less than 0.02), with GBM thickness (LRE, r = +0.81, P less than 0.001; LRI, r = +0.67, P less than 0.01) and with the volume fraction of mesangium (LRE, r = +0.59, P less than 0.02; LRI, r = +0.58, P less than 0.03). These data confirm earlier biochemical findings of a reduction of HSPG in the GBM in advanced diabetic nephropathy but do not provide evidence for the loss of HSPG in the GBM as a mechanism for early microalbuminuria.
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PMID:Heparan sulfate proteoglycan in the glomerular basement membrane in type 1 diabetes mellitus. 151 88

Less than a quarter of the patients with juvenile-onset IDDM develop diabetic nephropathy during the first 20 years of diabetes. To study the determinants of this complication, we selected patients who had come with newly diagnosed IDDM to the Joslin Clinic between 1967 to 1972, and we examined them in 1986 to 1988, that is, 15 to 21 years after onset of diabetes. Using a case control design we compared three groups of cases, that is, advanced nephropathy (N = 43), only microalbuminuria (N = 41), and hypertension alone (N = 17), with a group of controls who remained normoalbuminuric and normotensive despite the long duration of IDDM (N = 61). In comparison with controls, patients with advanced nephropathy had more parents with hypertension (odds ratio 3.8), higher Vmax values of Na/Li countertransport in red blood cells (odds ratio 10.0 for the highest tertile), and higher mean arterial pressure during adolescence and early adulthood (odds ratio 3.1 for those above the median). They also had significantly poorer glycemic control during their first 12 years of diabetes. Patients with hypertension alone were similar to those with advanced nephropathy with regard to markers of predisposition to hypertension but differed from them with regard to glycemic control, having the best glycemic control of all the study groups. Patients who developed only microalbuminuria during 15 to 21 years of IDDM (some of whom will progress to overt proteinuria later) did not differ significantly from controls with regard to predisposition to hypertension. In conclusion, predisposition to hypertension is a major risk factor for the development of advanced diabetic nephropathy and essential hypertension during the first 20 years of IDDM.
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PMID:Predisposition to hypertension: risk factor for nephropathy and hypertension in IDDM. 151 93

A cohort of 63 Type 1 insulin-dependent diabetic patients were first characterized for overnight urinary albumin excretion rate (AER) in 1967. In 1981, seven out of eight (87%) patients with initial AER greater than or equal to 30 less than or equal to 140 micrograms/min (microalbuminuria) developed clinical proteinuria compared to only 2 out of 55 (4%) patients with initial AER less than 30 micrograms/min. The same cohort of patients was reassessed in 1990 after a total follow-up period of 23 years. The aim was to investigate the role of microalbuminuria in the prediction of total/cardiovascular mortality and the development of renal failure, in addition to clinical proteinuria. The initially microalbuminuric patients had a significantly higher risk of developing not only clinical proteinuria (relative risk 9.3, 95% C.I. 1.36 to 3.10, P less than 0.05), but also of dying from a cardiovascular cause (relative risk 2.94, 95% C.I. 1.18 to 7.34, P less than 0.05). The rate of progression to renal failure was higher but not significantly so in the microalbuminuric (2 of 8) compared to the normoalbuminuric (4 of 53) group (relative risk 3.31, 95% C.I. 0.72 to 15.24, NS). In insulin-dependent diabetic patients microalbuminuria is a powerful predictor of clinically overt diabetic renal disease as well as cardiovascular mortality.
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PMID:Prognostic significance of microalbuminuria in insulin-dependent diabetes mellitus: a twenty-three year follow-up study. 151 6

The prevalence of raised Na+/Li+ countertransport (CT) activity (greater than 0.41 mmol/liter RBC/hr) was assessed in 185 consecutive insulin-dependent diabetic patients attending an outpatient diabetic clinic. Normoalbuminuria was defined as an overnight albumin excretion rate (AER) of less than 20 micrograms/min (N = 121), microalbuminuria as AER between 20 and 150 micrograms/min (N = 35) and macroalbuminuria as AER greater than or equal to 150 micrograms/min (N = 29). The prevalence of elevated Na+/Li+CT (greater than 0.41 mmol/liter RBC/hr) was 21.5, 42.8 and 51.7% (P = 0.0005), in patients with normo-, micro- and macroalbuminuria, respectively. In the whole group, Na+/Li+CT was significantly related to mean blood pressure (MBP; rs = 0.37, P less than 0.001) and AER (rs = 0.38, P less than 0.001). In a multiple regression analysis the significant correlates of AER, as a continuous variable, or of proteinuria (micro + macroalbuminuria), as a categorical variable, were Na+/Li+CT, MBP, duration of diabetes and glycosylated hemoglobin (HbA1). The frequency of normoalbuminuric patients with high Na+/Li+CT activity fell with duration of diabetes. The risk of proteinuria was significantly greater in patients with raised Na+/Li+CT compared to those with Na+/Li+CT within the normal range (odds ratio 3.8, 95% CI, 1.9 and 7.8). A relative excess of patients with proteinuria (micro + macroalbuminuria) was found in the group with elevated Na+/Li+CT and HbA1 above the median value (8.05%) of the whole population (chi 2 = 9.7, P less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevalence of raised sodium-lithium countertransport activity in type 1 diabetic patients. 151 10

Nephropathies associated with human immunodeficiency syndrome (HIVAN) are characterized by gross proteinuria, lack of change in blood pressure, and various histologic lesions. The present study prospectively measured microalbuminuria in 72 HIV-seropositive patients (3 asymptomatic, 32 AIDS-related complex, 37 AIDS) screened for Phase I clinical pharmacology studies. There were 14 patients (19.4%) that had abnormal urinary levels of microalbumin; 7 of these patients (50%) had proteinuria similar to those values found in diabetic nephrotic syndrome. Microalbumin levels were not correlated with race, sex, risk factors of AIDS, disease history, or concurrent drug therapy. In contrast, urinary microalbumin levels were correlated with CD 4 T-cell and WBC counts, tumor necrosis factor alpha and beta 2-microglobulin levels, suggesting an association between AIDS progression and microalbuminuria. By monitoring urinary microalbumin levels, those patients susceptible to the development of nephrotic syndrome could be identified and prophylactic measures initiated.
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PMID:Incidence of microalbuminuria in ambulatory patients with acquired immunodeficiency syndrome. 151 82

In a double-blind, randomized trial with 26 male white patients with essential hypertension in World Health Organization Stages I and II, we examined the impact of calcium entry blockade (5 to 10 mg/day isradipine, N = 14) and beta-blockade (100 to 200 mg/day metoprolol, N = 12) on early markers of hypertensive nephropathy before and after 7 weeks' treatment. Excretion of total protein, albumin, alpha 1-microglobuline, and N-acetyl-beta-glucosaminidase (NAG) were measured in the 24-h urine by radial immunodiffusion and fluorimetric method, respectively. Before therapy, 8 of 26 patients had microproteinuria (31%), six had microalbuminuria (22%), six had elevated urinary NAG activity (22%), and three had elevated alpha 1-microglobulin excretion (11%). In these subjects anti-hypertensive therapy led to a fall in proteinuria (296 +/- 56 v 127 +/- 116 mg/day, P less than .01), albuminuria (44 +/- 24 v 25 +/- 12 mg/day, P less than .05), and NAG excretion (45 +/- 22 v 28 +/- 5, P less than .05). The higher the pretreatment value, the greater the fall was in proteinuria (r = +0.55, P less than .01), albuminuria (r = 0.80, P less than .001), and NAG excretion (r = 0.60, P less than .01). We did not observe any significant difference in clinical characteristics, blood pressure, or urinary excretion of protein, albumin, or NAG between the two treatment groups, either before or after therapy. Thus, antihypertensive therapy reduced excretion of total protein, albumin, and NAG activity in hypertensive patients with elevated pretreatment values, potentially indicating reversal of early hypertensive nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Impact of antihypertensive therapy with isradipine and metoprolol on early markers of hypertensive nephropathy. 153 71

Diabetic nephropathy typically presents more than a decade after diagnosis of diabetes and correlates with the duration of poorly controlled disease. Diabetic nephropathy begins as glomerular hypertension and hyperfiltration, followed by microalbuminuria and the development of hypertension, overt proteinuria, nephrotic syndrome, and a progressive decline in the glomerular filtration rate. Increasing expansion of the glomerular mesangium correlates with loss of function, resulting in uremia. This process eventually leads to the need for dialysis or renal transplantation in 30 percent of patients with insulin-dependent diabetes. By lowering intraglomerular pressure through enhanced glycemic control, inhibition of angiotensin and limitation of protein intake, severe nephropathy may be prevented, delayed or even partially reversed. Treatment must stress control of hypertension.
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PMID:Diabetic nephropathy: early detection, prevention and management. 155 42


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