Evaluation of Albuminuria HIV-Infected Patients
| Status: | Completed |
|---|---|
| Conditions: | Endocrine, Nephrology |
| Therapuetic Areas: | Endocrinology, Nephrology / Urology |
| Healthy: | No |
| Age Range: | 8 - Any |
| Updated: | 4/17/2018 |
| Start Date: | August 29, 2007 |
| End Date: | December 24, 2014 |
Prospective Evaluation of Albuminuria in HIV Positive 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.
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.
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
We found this trial at
2
sites
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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110 Irving St NW
Washington, District of Columbia 20010
Washington, District of Columbia 20010
(202) 877-7000
Washington Hosp Ctr MedStar Washington Hospital Center is a not-for-profit, 926-bed, major teaching and research...
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