Evaluation of Albuminuria HIV-Infected Patients

Problem: The appropriate approach to screening patients for early HIV-associated kidney disease is unknown. Recently, screening for microalbuminuria has been proposed; the clinical implications of finding microalbuminuria in this population are unknown, as several disease processes may contribute to microalbuminuria in this setting.

Background: Renal disease is becoming more common as patients with HIV disease live longer. Renal diseases in this population include glomerular diseases (collapsing glomerulopathy, immune complex glomerulonephritis, diabetic nephropathy, and hypertensive glomerulosclerosis) and various tubular diseases. Systemic endothelial dysfunction, occurring as part of metabolic syndrome and related disorders such as hypertension, hyperlipidemia, and insulin resistance, is also associated with microalbuminuria.

Study Objective: We wish to determine whether screening for microalbuminuria will detect early stage glomerular disease. We also wish to determine whether in some subjects renal histology is normal and microalbuminuria is a manifestation of metabolic syndrome, including HIV-associated lipodystrophy.

Design: We will use a cross-sectional study design.

Population: We will enroll 280 patients with HIV disease, to the extent practical enrolling consecutive patients in the NIAID Longitudinal HIV Clinic and the Washington Hospital Center HIV Clinic. This sample size was determined using an estimated population prevalence of microalbuminuria of 20%, with a 90% confidence interval of 5%. We will exclude patients with diabetes (as screening using urinary albumin excretion is well-established in clinical practice) and with established chronic kidney disease, defined as macroproteinuria (as these patients have been identified by a well-established screening test).

Methods: We will collect three urine samples, at three month intervals, for urine albumin/creatinine and protein/creatinine ratio. We will also collect data on blood pressure, anthropomorphometric parameters, and various serologic testing. Patients with persistent microalbuminuria will undergo renal biopsy. Using frozen blood cells, we will prepare DNA for genetic testing.

Analysis: We will determine the prevalence of microalbuminuria in the HIV population sample under study. We will determine the clinical implications of microalbuminuria, specifically how often HIV-associated collapsing glomerulopathy, HIV-associated glomerulonephritis, or other histologic disease is present. We will correlate the quantitative measure of urinary albumin with 1) the presence or absence of metabolic syndrome and with 2) various quantitative variables associated with metabolic syndrome. Finally, we will analyze kidney injury genes, in particular MYH9, to identify genes that predispose to microalbuminuria.

Future Studies: If this study suggests that the presence of microalbuminuria identifies patients who are likely to have early glomerular disease, we will consider undertaking a prospective controlled trial testing whether therapy with an angiotensin blocker can revert microalbuminuria and reduce progression to macroproteinuria.