Evaluation of Albuminuria HIV-Infected Patients
Evaluation of Albuminuria HIV-Infected Patients
This study will examine the following: 1) how common albuminuria and proteinuria are among
 HIV-positive patients, 2) what causes albuminuria or proteinuria in these patients and 3)
 whether the condition becomes more severe over time. HIV-infected people are more likely than
 others to develop kidney disease. The earliest indicator of the possible presence of kidney
 disease is albuminuria (increased amounts of the protein albumin in the urine). A later
 indicator is the appearance of other proteins, a condition called proteinuria.

 HIV-infected patients 8 years of age and older who do not have diabetes, chronic kidney
 disease or cancer may be eligible for this study.

 Participants provide a urine sample during three visits as follows: the first upon enrollment
 in the study, a second 3 months later, and a third about 6 months after that. Blood samples
 are drawn at the first and last visits. At the first visit a medical history is taken and
 blood pressure, height, weight, waist circumference, hip circumference and upper arm skin
 thickness are measured.

 Participants who are found to have albuminuria or proteinuria are asked to undergo a kidney
 biopsy for research purposes. The procedure is optional. Participants who develop heavy
 proteinuria may be recommended to undergo a kidney biopsy in order to determine the nature of
 the kidney disease and begin treatment. The biopsy requires a 2-day hospital stay. For the
 procedure, an anesthetic is given to numb the skin and a needle is inserted and guided into
 the kidney to withdraw a small tissue sample. The needle is passed twice, and possibly three
 times. Following the procedure, the subject remains in bed rest for at least 10 hours to
 minimize the risk of excessive bleeding.
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.
-  INCLUSION CRITERIA:

 -  HIV+ adults and children greater than 8 years of age

 EXCLUSION CRITERIA:

 -  Inability or unwillingness to give consent or assent or to comply with study
 requirements

 -  Unable to return to NIH or Washington Hospital Center for two follow-up visits over a
 9-month period

 -  New opportunistic or bacterial infection within past 3 months or active opportunistic
 infection.

 -  Active malignancy, other than non-melanoma skin cancer and cutaneous Kaposi sarcoma
 not requiring treatment. Rationale: systemic inflammation may induce microalbuminuria.

 -  Diabetes by history

 -  IL-2, IL-7 or IFN-alpha therapy within past 3 months. Rationale: IL-2 and IFN-alpha
 therapy induce renal dysfunction and IL-7 may be associated with systemic
 inflammation.

 -  Non compliance, alcohol use, and drug use are conditions that make study completion
 unlikely or difficult.

 -  Diabetes (fasting glucose greater than 125 mg/dL or 2 hour oral glucose tolerance
 value greater than or equal to 200 mg/dL or current diagnosis of diabetes).

 -  Serum creatinine greater than 1.4 mg/dL.

 -  Urine protein/creatinine ratio greater than 0.5 and sustained on at least 2
 measurements.

 -  Pregnant Women