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

Abstract

Background: Among human immunodeficiency virus (HIV)-infected youth, the role of renal disease (RD) and its management has become increasingly important as these children/adolescents mature into young adults. The 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 youth followed for ≥ 48 months were 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: Of the 1,874 at-risk children enrolled in the study, 428 (23 %) developed RLE, which persisted in 229 of these (54 %). CD4 percentages of <25 % [hazard ratio (HR) 0.63, p < 0.002) and an HIV viral load of >100,000 copies/ml (HR 0.31, p < 0.01) were associated with reduced rates of resolution, while in most cases exposure to highly active antiretroviral therapy (HAART)/nephrotoxic HAART prior to or subsequent to RLE 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 those with RLE.

Conclusions: Advanced HIV disease predicted persistence of RLE in HIV-infected youth. Persistent RLE were useful for identifying RD.

Figure 1. Impact of persistent or resolved renal laboratory abnormalities on development of new renal disease diagnoses

The Flow chart depicts the outcome in developing new renal diagnosis based on renal laboratory screening tests that persist or resolve. There were 1874 children in the study cohort with no renal laboratory abnormalities nor renal diagnosis at study entry. During follow-up, 428 (23%) developed new renal laboratory abnormalities while 1446 (77%) did not. Of those cases with new renal laboratory abnormalities, 229 (54%) had persistence of abnormal laboratory renal studies with 35 (15.3%) developing a new renal diagnosis. In contrast, 199 (46%) had resolution of their abnormal renal studies with only 5 (2.5%) developing a new renal diagnosis. In the 1446 (77%) cases that never developed new renal laboratory abnormalities, there were 39 (2.7%) who developed renal diagnosis.

Figure 2

Sensitivity (Black bar), Specificity(White bar), Positive(Dark Gray bar) and Negative(Light Gray bar) Predictive Values of Abnormal Renal Lab Events(Panel A) in the source population(1874) and Persistent Renal Lab Events (Panel B) in the group with RLE (428) for New Renal Diagnoses.