Estimating Kidney Function in HIV-Infected Adults in Kenya: Comparison to a Direct Measure of Glomerular Filtration Rate by Iohexol Clearance

Abstract

BackgroundMore than two-thirds of the world's HIV-positive individuals live in sub-Saharan Africa, where genetic susceptibility to kidney disease is high and resources for kidney disease screening and antiretroviral therapy (ART) toxicity monitoring are limited. Equations to estimate glomerular filtration rate (GFR) from serum creatinine were derived in Western populations and may be less accurate in this population.MethodsWe compared results from published GFR estimating equations with a direct measure of GFR by iohexol clearance in 99 HIV-infected, ART-naïve Kenyan adults. Iohexol concentration was measured from dried blood spots on filter paper. The bias ratio (mean of the ratio of estimated to measured GFR) and accuracy (percentage of estimates within 30% of the measured GFR) were calculated.ResultsThe median age was 35 years, and 60% were women. The majority had asymptomatic HIV, with median CD4+ cell count of 355 cells/mm3. Median measured GFR was 115 mL/min/1.73 m2. Overall accuracy was highest for the Chronic Kidney Disease Epidemiology Consortium (CKD-EPI) equation. Consistent with a prior report, bias and accuracy were improved by eliminating the coefficient for black race (85% of estimates within 30% of measured GFR). Accuracy of all equations was poor in participants with GFR 60–90 mL/min/1.73 m2 (<65% of estimates within 30% of measured GFR), although this subgroup was too small to reach definitive conclusions.ConclusionsOverall accuracy was highest for the CKD-EPI equation. Eliminating the coefficient for race further improved performance. Future studies are needed to determine the most accurate GFR estimate for use in individuals with GFR <90 mL/min/1.73 m2, in whom accurate estimation of kidney function is important to guide drug dosing. Direct measurement of GFR by iohexol clearance using a filter paper based assay is feasible for research purposes in resource-limited settings, and could be used to develop more accurate GFR estimates in African populations.

Racial Disparities in Creatinine-based Kidney Function Estimates Among HIV-infected Adults

“…33 As in our study, Peralta et al showed that the diagnosis of low eGFR in Blacks was very sensitive to the race coefficient used in the GFR estimating equation in the bi-racial CARDIA cohort of young adults living in the United States. the CKD-EPI and MDRD better predicted iohexol derived GFRs when the race coefficient was removed 20 and similar results were recently described in a South African population as well. 21 Furthermore, among HIV-infected women in the WIHS cohort, eGFR was substantially lower when estimated with cystatin C compared with creatinine among Black participants, whereas cystatin C and creatinine produced similar estimates among White participants.…”

“…32 Baseline covariates were defined at entry more, several studies among Black Africans showed that removing the race coefficient improved GFR estimation compared with a gold standard. 20,21 The aim of our study was to investigate whether current eGFR equations in clinical use might systematically over-estimate the kidney function, and thus misclassify CKD status, of Black Americans with HIV. We are unaware of any large registry or cohort of Blacks living in the United States with HIV that contains gold standard GFR measures.…”

Changes in Glomerular Kidney Function Among HIV-1–Uninfected Men and Women Receiving Emtricitabine–Tenofovir Disoproxil Fumarate Preexposure Prophylaxis

“…17 The CKD-EPI equation has recently been validated in African populations and provides more accurate estimates for eGFR values in the normal range than both the Modification of Diet in Renal Disease Study and Cockoft-Gault equations when compared to a direct measure of GFR by iohexol clearance. 18,19 Serum creatinine was measured at baseline, month 1, and quarterly thereafter. For this analysis, predefined study outcomes were mean eGFR change from baseline and a decline in eGFR of ≥25% compared to baseline, as confirmed by a second measurement obtained prior to study drug discontinuation.…”

Human Immunodeficiency Virus Infection and Chronic Kidney Disease

“…A recent study suggests that the CKD-EPI equation gave the most accurate estimate of iohexol clearance in 99 cART naïve patients from Kenya. 68 Proteinuria is one of the salient indicators of ongoing renal injury and is frequently present in screening tests of HIV patients. Proteinuria may be screened using urine dipsticks or spot urine protein or albumin to creatinine ratios.…”