Evaluation of Albuminuria HIV-Infected Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00524992
First received: September 1, 2007
Last updated: March 14, 2014
Last verified: June 2013
  Purpose

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.


Condition
HIV-Associated Focal Segmental Glomerulosclerosis
HIV-Associated Collapsing Glomerulopathy
Proteinuria
Albuminuria
Renal Tubular Toxicity

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Prospective Evaluation of Albuminuria in HIV Positive Patients

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 280
Study Start Date: August 2007
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   8 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00524992

Contacts
Contact: Lilian V Howard, C.R.N.P. (301) 594-0298 lh357n@nih.gov
Contact: Jeffrey B Kopp, M.D. (301) 594-3403 jeffreyk@mail.nih.gov

Locations
United States, District of Columbia
Washington Hospital Center Recruiting
Washington, District of Columbia, United States, 20010
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Jeffrey B Kopp, M.D. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00524992     History of Changes
Other Study ID Numbers: 070212, 07-DK-0212
Study First Received: September 1, 2007
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Focal Segmental Glomerulosclerosis
Collapsing Glomerulopathy
Anti-Retroviral Toxicity
Lipodystrophy
Metabolic Syndrome
Tubular Injury
Renal Biopsy
Proteinuria
Tenofovir Toxicity
HAART Toxicity
HIV Positive
HIV-Associated Focal Segmental Glomerulosclerosis

Additional relevant MeSH terms:
Albuminuria
Glomerulosclerosis, Focal Segmental
Proteinuria
Urination Disorders
Urologic Diseases
Urological Manifestations
Signs and Symptoms
Glomerulonephritis
Nephritis
Kidney Diseases

ClinicalTrials.gov processed this record on September 11, 2014