Screening for microalbuminuria.
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Biomedical subjects
Publications and source records attributed to Jack F Wetzels.
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An accurate prediction of the prognosis of patients with idiopathic membranous nephropathy (iMN) should allow restriction of immunosuppressive treatment to patients who are at highest risk for ESRD. On the basis of retrospective studies, it has previously been suggested that the urinary excretions of beta2-microglobulin (Ubeta2m) and IgG (UIgG) are useful predictors of renal insufficiency in patients with iMN. The threshold values of 0.5 micro/min (Ubeta2m) and 250 mg/24 h (UIgG) have been validated in a new and larger patient cohort. From 1995 onward, 57 patients with iMN (38 men, 19 women; age 48 +/- 16 yr), a nephrotic syndrome, and a serum creatinine level </=1.5 mg/dl were studied prospectively. At baseline, a standardized measurement was carried out to determine renal function and protein excretion. The end point renal death was defined as a serum creatinine exceeding 1.5 mg/dl or a rise of serum creatinine of >50%. Mean (+/-SD) follow-up was 53 +/- 23 mo. Thus far, 25 (44%) of the patients have reached the end point renal death. Multivariate analysis confirmed Ubeta2m as the strongest independent predictor for the development of renal insufficiency. Sensitivity and specificity were 88 and 91%, respectively, for Ubeta2m, and both were 88% for UIgG. When the excretions of both proteins were combined, specificity improved to 97%. It is concluded that the present data validate the accuracy of Ubeta2m and of UIgG in predicting renal outcome in patients with iMN. These markers can be used to guide decisions on the start of immunosuppressive treatment.
BACKGROUND: Microalbuminuria reflects widespread vascular dysfunction in type 1 diabetes mellitus and results from increased glomerular sieving caused by changes in transglomerular pressure and/or permselectivity characteristics of the glomerular basement membrane. Increased tubular reabsorption or degradation of albumin will offset an early increase in albuminuria. We hypothesized that the infusion of atrial natriuretic peptide (ANP) as a tool to increase glomerular permeability might uncover changes in permselectivity in patients with uncomplicated type 1 diabetes. METHODS: We investigated whether these patients were characterized by endothelial and/or vascular dysfunction. We therefore studied 46 normoalbuminuric patients (urinary albumin excretion [UAE] < 10 microg/min) with type 1 diabetes and 44 healthy controls. Measurements of renal hemodynamics and albuminuria were performed before (baseline) and during the infusion of ANP (0.01 microg/kg/min). On a separate occasion, endothelial function was assessed by the intra-arterial infusion of acetylcholine (ACh), an endothelial-dependent vasodilator. RESULTS: At baseline, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were greater in patients with diabetes (GFR, 121 +/- 3 versus 106 +/- 2 mL/min/1.73 m(2); ERPF, 558 +/- 16 versus 527 +/- 13 mL/min/1.73 m(2); P < 0.001). The infusion of ANP increased filtration fraction. There were no differences in these responses between groups. UAE was significantly greater in patients with diabetes after the ANP infusion (15.8 +/- 1.4 [+183%] versus 9.5 +/- 1.3 microg/min [+96%]; P < 0.01). A subgroup of patients with diabetes with an enhanced albuminuric response (change in UAE > 2 SD of controls) to ANP infusion (mean UAE, 30.3 +/- 1.0 microg/min; 425% +/- 61%) was characterized by a diminished vasodilatory response to ACh (maximal forearm blood flow, 17.2 +/- 2.9 [+563%] versus 26.3 +/- 2.3 mL/min/dL [+800%] in patients with diabetes with a normal albuminuric response; P < 0.05). CONCLUSIONS: In a subgroup of patients with uncomplicated type 1 diabetes, an increase in glomerular permselectivity can be unmasked by the infusion of ANP. These patients are characterized by a diminished vascular response to ACh.