Prospective Evaluation of Albuminuria in HIV Positive 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
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.
Time Perspective: Prospective
Jeffrey B Kopp, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|
|Washington Hospital Center||Washington, District of Columbia 20010|