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)

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

Diabetic nephropathy is more common in patients with a positive family history of hypertension and with elevated red blood cell sodium-lithium countertransport, a marker of risk for essential hypertension. To evaluate whether there is a relationship between this cation transport system and indicators of risk of renal and cardiovascular complications in diabetic patients before the development of clinical proteinuria, we studied 31 type 1 (insulin-dependent) diabetic patients with arterial hypertension, without clinical proteinuria and 12 normotensive normoalbuminuric diabetic patients. Sodium-lithium countertransport activity was significantly higher in hypertensive patients (0.43 +/- 0.03 mmol/l RBC x hr) than in normotensive patients (0.23 +/- 0.03; P less than 0.001). To better explore the nature of the association between this transport system and arterial hypertension, hypertensive patients were divided in two groups, with high (greater than 0.41 mmol/l RBC x hr) or normal (less than 0.41) sodium-lithium countertransport activity. The two groups of hypertensive diabetics were similar in age, sex, body mass index and blood pressure levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clustering of risk factors in hypertensive insulin-dependent diabetics with high sodium-lithium countertransport. 151 8

Experimental animal studies have demonstrated a renal protective effect of ACE inhibition therapy in diabetes mellitus and the remnant kidney model of chronic renal failure. The mechanism of this effect is secondary, at least in part, to the drugs' effects on glomerular hemodynamics. In addition, there is further evidence to suggest that ACE inhibitors may influence other pathogenic mechanisms of progressive renal insufficiency. Preliminary data in clinical studies suggest that ACE inhibition therapy decreases proteinuria and may ameliorate the decline of the glomerular filtration rate in diabetic nephropathy and progressive renal insufficiency of other etiologies. However, before this conclusion can be definite, a large, prospective, randomized clinical trial is required to compare ACE inhibitors to conventional antihypertensive agents. Since calcium channel blockers are metabolically neutral in that they do not increase serum cholesterol or glucose levels and generally do not cause orthostatic hypotension, they may be ideal agents for such a comparison study.
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PMID:Progressive renal insufficiency: the role of angiotensin converting enzyme inhibitors. 155 7

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

In an investigation into the effect of prostaglandin E1 on proteinuria in nephrotic diabetic nephropathy, five patients were treated with 40 micrograms prostaglandin E1 administered intravenously over 2 h twice daily for 4 weeks. The following parameters were compared before and after treatment: protein excretion in urine; total serum protein concentration; serum albumin concentration; creatinine clearance; blood urea nitrogen; and serum creatinine content. A further five patients with nephropathy resulting from non-insulin-dependent diabetes mellitus were selected as controls. Analysis of the results using Student's t-test showed no significant change in any of the parameters before and after treatment.
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PMID:Influence of prostaglandin E1 on slight proteinuria in non-azotaemic diabetics. 156 24

Renal pathological changes of diabetes include thickening of all renal extracellular basement membranes and the mesangial matrix and, to a lesser extent, mesangial cell expansion. Two renal lesions appear critical in diabetic nephropathy. Mesangial expansion out of proportion to the size of the glomerulus is related to proteinuria, hypertension, and declining GFR. Arteriolar hyalinosis is related to global glomerulosclerosis, and both are correlated with the clinical features of nephropathy. By the time renal dysfunction is clinically detectable, these lesions tend to be advanced. Interstitial volume may be increased in insulin-dependent diabetes mellitus, particularly in areas containing sclerotic glomeruli or marked tubular atrophy. Parallel findings were documented for type I membranoproliferative glomerulonephritis in which the increased mesangial volume fraction was related to decreased GFR, increased glomerular permeability to protein, and hypertension. As in diabetes, the cortical interstitial volume fraction is correlated with functional abnormalities in type I membranoproliferative glomerulonephritis. Thus, in both of these chronic glomerular disorders, mesangial expansion and interstitial expansion are associated with disordered renal function. Thus, it is not true that glomerular structural changes correlate poorly with glomerular function. Whether it is the glomerular or interstitial pathology or both that is causally responsible for the dysfunction requires further study.
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PMID:Renal structure and function in insulin-dependent diabetes mellitus and type I membranoproliferative glomerulonephritis in humans. 160 Jan 34

Serum and urinary concentrations of type IV collagen and laminin were measured by enzyme-linked immunosorbent assay (ELISA) in diabetic patients and compared with normal control subjects. In diabetic patients with proteinuria or with renal insufficiency, serum and urinary concentrations of type IV collagen were higher than those of control subjects (p less than 0.005). Furthermore urinary concentrations of type IV collagen and laminin were significantly higher in diabetes, even in the absence of nephropathy, than in normal controls (p less than 0.05). Urinary concentrations of type IV collagen in patients with diabetes and microalbuminuria (0.73 +/- 0.11 mg mmol-1) were significantly higher than in diabetic patients without nephropathy (0.40 +/- 0.060 mg mmol-1) (p less than 0.025). Urinary concentrations of type IV collagen may have a role as an indicator of early diabetic nephropathy. Serum concentrations of type IV collagen in diabetic patients with retinopathy were significantly higher than in normal controls (p less than 0.025). However, urinary concentrations of type IV collagen (p less than 0.05) and serum concentrations of laminin (p less than 0.025) were significantly higher in diabetic patients than normal controls and the difference between patients with and without retinopathy was not significant.
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PMID:Serum and urinary concentrations of type IV collagen and laminin as a marker of microangiopathy in diabetes. 160 Jul 9

The prognosis for the patient with diabetic nephropathy has improved considerably during the last decade. This is due to identification and treatment of different risk factors. Elevated blood pressure has turned out to be a major risk factor in established diabetic nephropathy. The impact of metabolic control has also been demonstrated. Lipid abnormalities have recently been identified as a possible factor that accelerates loss of renal function. The role of renal hemodynamic alterations is probably also important. Their contribution can indirectly be assessed by studying the effects of pharmacologic therapy. Angiotension converting enzyme inhibitors reduce proteinuria by a mechanism independent of systemic blood pressure and there is suggestive evidence that they preserve renal function to a greater degree than other antihypertensive agents.
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PMID:Determinants of progressive renal disease in diabetes mellitus. 161 66

Metabolism of proteins which compose capillary basement membrane is altered in diabetic patients. In the kidney, this leads to an impaired permselectivity of glomerular basement membrane and consequently to onset of proteinuria. Proteinuria which is often increased by hemodynamic factors, initiates and promotes the development of diabetic glomerusclerosis. Aside from near-normal metabolic control, special antihypertensive treatment can reduce proteinuria and retard loss of kidney function in proteinuric diabetic patients. The beneficial effect of ACE-inhibitors on course of diabetic nephropathy is generally thought to be a consequence of decreased systemic and intraglomerular pressure. However, recent longterm studies in Type I and Type II diabetic patients with nephropathy showed that ACE-inhibition can reduce proteinuria independent from their hemodynamic effects and, thus, improves the filtration properties of glomerular basement membrane. This may be due to an influence of ACE-inhibition on metabolism of basement membrane proteins.
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PMID:[ACE inhibitor effects on structure and function of the glomerular basement membrane]. 161 91


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