Chronic Kidney Disease Associated with Perinatal HIV infection in Children and Adolescents

BACKGROUND: This study describes the incidence, clinical and demographic characteristics, and spectrum of chronic kidney disease (CKD) in youths with perinatal HIV-1 infection. METHODS: Retrospective analysis between May 1993 and December 2006 of subjects with renal disease followed in the Pediatric AIDS Clinical Trials Group 219/219C multicenter study examining long-term consequences of perinatal HIV infection. Diagnosis confirmation was made utilizing a questionnaire mailed to research sites. Participants with CKD of other etiology than HIV were excluded. Outcome measures were biopsy-diagnosed CKD and, in absence of biopsy, HIV-associated nephropathy (HIVAN) using established clinical criteria. RESULTS: Questionnaires on 191 of 2,102 participants identified 27 cases of CKD: 14 biopsy-diagnosed and six clinical cases of HIVAN, and seven biopsy-diagnosed cases of immune complex-mediated kidney disease (lupus-like nephritis, three; IgA nephropathy, two; membranous nephropathy, two). Incidence rates for CKD associated with HIV in pre-HAART (1993–1997) and HAART (1998–2002, 2003–2006) eras were 0.43, 2.84 and 2.79 events per 1000 person years, respectively. In multivariable analysis, Black race and viral load ≥ 100,000 copies/ml (rate ratios 3.28 and 5.05, p ≤ 0.02) were associated with CKD. CONCLUSIONS: A variety of immune complex-mediated glomerulonephritides and HIVAN occurs in this population. Black race and uncontrolled viral replication are risk factors for CKD associated with HIV

Incidence of Persistent Renal Dysfunction in Human Immunodeficiency Virus-Infected Children

BACKGROUND: Survival of HIV-infected children continues to increase and the use of antiretrovirals (ARVs) is expanding; however there are few data regarding the incidence of renal dysfunction and associated risk factors among HIV-infected children and youth. METHODS: A total of 2102 children enrolled in Pediatric AIDS Clinical Trials Group Study 219/219C, were followed and assessed prospectively for >30 months. Occurrence of clinical events and laboratory abnormalities were recorded using standardized criteria and forms. Therapeutic decisions were made by clinicians at each site. Occurrence of persistent renal laboratory abnormalities was the main outcome measure. RESULTS: Four hundred forty-six (22%) enrollees exhibited at least one persistent renal laboratory abnormality. Elevated serum creatinine (Cr) was more common than persistent proteinuria (15% vs. 8%). The incidence of new renal laboratory abnormalities was 3.7 events per 100 person-years with rates increasing between 1993 and 2005. Older age (≥6 years vs. <6 years), Hispanic ethnicity, and Black non-Hispanic race were associated with increased risk of renal dysfunction, but CDC clinical class and plasma HIV RNA levels were not. Subjects exposed to ARV regimens containing tenofovir and/or indinavir had approximately twice the risk of developing renal dysfunction compared with persons exposed to other ARVs. The risk of renal dysfunction was also elevated for other antivirals (hazard ratio = 5.4) and amphotericin B (hazard ratio = 28). CONCLUSIONS: Persistent renal function abnormalities occur frequently in HIV-infected children. Improved survival, Black race and Hispanic ethnicity, and exposure to tenofovir, indinavir, and other antimicrobial agents increase the risk for renal dysfunction. All HIV-infected children should be monitored closely for evidence of renal disease

Predictors of resolution and persistence of renal laboratory abnormalities in pediatric HIV infection

BACKGROUND: Among HIV infected youth, the role of renal disease (RD) and its management has become more important as children/adolescents age into young adulthood. Identification of predictors of abnormal renal laboratory events (RLE) may be helpful in the management of their HIV infection and its associated renal complications.” METHODS: Data collected from HIV-infected children and youth followed for ≥48 months was analyzed to identify predictors of resolution versus persistence of RLE and determine the utility of RLE to predict the onset of RD. Analysis included descriptive and inferential methods using a multivariable extended Cox proportional hazards model. RESULTS: 428 of 1874 at risk children (23%) developed RLE, which persisted in 229 of 428(54%). CD4<25% (hazard ratio[HR] 0.63, p<0.002) and HIV viral load>100,000 copies/ml (HR 0.31, p<0.01) were associated with reduced rates of resolution. Exposure to HAART/nephrotoxic HAART prior to or subsequent to RLE in most cases were not. Persistence of RLE was 88% sensitive for identifying new RD. Negative predictive values for RD were >95% for both the at risk cohort and in those with RLE. CONCLUSIONS: Advanced HIV disease predicted persistence of RLE in HIV-infected youth. Persistent RLE were useful for identifying RD