Prevalence of Proteinuria and Chronic Kidney Disease in Pediatric HIV-Infected Patients
Condition: Chronic Kidney Failure; AIDS-Associated Nephropathy; HIV Infections
MeSH terms: AIDS-Associated Nephropathy; Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Proteinuria; Kidney Failure, Chronic
Study type: Observational

Summary: 
      Among adults with Human Immunodeficiency Virus (HIV) and Acquired Immunodeficiency Syndrome
      (AIDS), Chronic Kidney Disease (CKD) has previously been reported to occur in approximately
      10% of children with HIV-infection. The frequency of CKD, its causes, and its natural history
      in children and adolescents with HIV-infection have not been systematically studied,
      particularly in the era of new anti-retroviral medications. The primary aim of this study is
      to determine the how common pediatric HIV-infected individuals have evidence of persistent
      proteinuria and CKD.
    

Detailed description: 
      Human Immunodeficiency Virus-infection has been a significant cause of pediatric morbidity
      and mortality since it was first identified in the early 1980s. In 1997, HIV became the
      fourth leading cause of death among children 1 to 4 years of age. As of December 2001, there
      were 9,074 children under the age of 13 years who have been diagnosed with AIDS in the United
      States and its territories, and an additional 3,923 children with HIV-infection under the age
      of 13 years. Human Immunodeficiency Virus-infection and AIDS do not affect children equally
      in the United States. Whereas whites comprise 61% of the pediatric population, they represent
      only 15-20% of children with HIV or AIDS. In contrast, African-Americans account for only 14%
      of the US pediatric population, but they represent 60-65% of children with HIV or AIDS. The
      prevalence rate of AIDS among African-American children in 2001 was 14 times greater than
      among white children, and 7 times higher than among Hispanic children.

      A variety of renal, electrolyte, and acid-base disturbances have been described in patients
      with HIV-infection. These abnormalities may be associated with the HIV-infection itself,
      opportunistic infections, antiviral medications, or unrelated primary disorders. Proteinuria
      may serve as an early indicator of HIV-associated nephropathy (HIVAN), the pathologic renal
      lesions associated with HIV-infection itself. Autopsy data in adults with HIV-infection or
      AIDS have demonstrated a prevalence of HIVAN of between 1 and 15%. The prevalence of HIVAN in
      the pediatric population has been reported between 7 and 15%. The racial disparity seen in
      the AIDS population has also been described in the pediatric HIVAN population. Reports of
      HIVAN in pediatric populations found that 137 of 155 children (89%) in Miami, Florida and 208
      of 217 children (96%) in Washington, DC were African-American.

      The medical progress made in the treatment of HIV infection with highly active antiretroviral
      therapies (HAART) has led to a dramatic decline in the incidence of death among adults with
      HIV-infection. By 1999, however, HIV became the third leading cause of end-stage renal
      disease (ESRD) among African-Americans aged 20 to 64 years. In contrast to the declining
      incidence of HIV-infection in the adult population, the incidence of ESRD due to HIVAN has
      decreased much slower for unknown reasons. The incidence of pediatric AIDS cases also has
      been declining over the past decade, from 952 new cases diagnosed in 1992 to only 101 in
      2001. The impact of the declining incidence of pediatric AIDS cases upon the incidence of
      pediatric HIVAN remains unknown. The progression of pediatric HIVAN appears to occur more
      slowly than the adult HIVAN population, with a mean time from initial diagnosis of HIVAN to
      ESRD of 8 to 20 months. Mortality is high in the pediatric HIV-infected population, with
      nearly 80% of pediatric patients with HIVAN dying.

      For this study, we seek to estimate the prevalence of CKD in HIV-infected patients overall
      and within specific racial groups.

      Participants will be screened with a first-morning macroscopic urinalysis for the detection
      of proteinuria, and a semi-quantitative measurement of proteinuria using urine
      protein-to-creatinine and urine microalbumin-to-creatinine ratios. Those patients who have
      proteinuria of greater than or equal to 1+ on a first-morning macrourinalysis, or a urine
      protein-to-creatinine ratio of > 0.20 or a urine microalbumin-to-creatinine ratio of > 30
      mcg/mg of creatinine, will have a repeat first-morning macroscopic urinalysis, and urine
      protein-to-creatinine and urine microalbumin-to-creatinine ratios performed 3 months later.
      Prior to the obtaining of any of the urine samples, those participants who are taking
      angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB)
      therapy for their anti-proteinuric or anti-hypertensive effects will discontinue their
      medication for 2 weeks prior to the urine sample collection. After collecting the
      first-morning urine sample, the study participant may resume his/her prior ACEI or ARB at the
      previously prescribed dose and schedule. Those patients who have fixed proteinuria on a
      first-morning macroscopic urinalysis on 2 occasions separated by 3 months will be referred to
      the Pediatric Nephrology Clinic for further evaluation for proteinuria and/or CKD. The
      calculated GFR will be determined using the most recent serum creatinine and patient height
      from the medical record using the Schwartz formula. Chronic Kidney Disease will be defined,
      as in the NKF KDOQI guidelines.
    

Time perspective: Prospective
Keywords: Pediatrics; Chronic Kidney Failure; HIV; Acquired Immunodeficiency Syndrome; AIDS-Associated Nephropathy