Urinary Interleukin (Il)-18 as an Early Predictive Biomarker of Subclinical Proximal Tubular Dysfunction in HIV-Infected Patients Exposed to Tenofovir

Abstract

BACKGROUND Proximal tubular dysfunction (PTD) is a frequent complication of HIV-infected patients and lack of early biomarkers for PTD has impaired our ability to intervene in a timely manner considering the increasing number of HIV-infected patients in Nigeria. AIM In this present study, we tested if interleukin- 18 (lL-18) is a predictive biomarker for PTD in HIV-infected patients on tenofovir (TDF). SUBJECTS AND METHOD HIV-infected patients on tenofovir (TDF) and Non-tenofovir (N-TDF) antiretroviral therapy were recruited for this study, taking as control HIV treatment-naive patients. Exclusion criteria included pre-existing renal insufficiency and nephrotoxin use. Serial urine samples were analyzed by enzyme-linked immunosorbent assay for lL-18 in 254 HIV- infected patients at three different points (at baseline, at 4 weeks and at 12 weeks of follow-up). RESULT Using eGFR values, marked decrease in kidney function was detected only at 12 weeks in the TDF regime group (p=0.003) as compared to other study groups. In contrast, urine lL-18 increased at a much early time (at 4 weeks) particularly in the TDF regime group (p=0.000) followed by the naïve group (p=0.02) and continued to increase up to 12 weeks of follow up. This marked elevation is progressive. CONCLUSION Our results indicate that lL-18 is an early, predictive biomarker of PTD and that this biomarker may allow for the reliable early diagnosis of PTD at all times in HIV-infected patients on TDF at risk of proximal tubular dysfunction, much before the rise in serum creatinine.