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

Orluwene Cg Deebii N

doi:10.4172/2155-6113.1000497

Abstract

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. In this present study, we tested if interleukin- 18 (IL-18) is a predictive biomarker for PTD in HIV-infected patients on tenofovir (TDF) and Non-tenofovir (N-TDF) antiretroviral therapy and taking as control HIV treatment naive patients. Exclusion criteria included pre-existing renal insufficiency and nephrotoxin used. Serial urine samples were analyzed by enzyme-linked immunosorbent assay for IL-18 in 254 HIV- infected patients at three different points (at baseline, at 4 weeks and at 12 weeks of fellow-up). Using eGFR values, marked decreased in kidney function was detected only at 12 weeks in the TDF regimen group (p=0.003) as compared to other study groups. In contrast, urine IL-18 increased at a much early time (at 4 weeks) particularly in the TDF regimen group (p=0.000) follow by the naive group (p=0.02) and continued to increase up to 12 weeks of follow up. This marked elevation is believed to be progressive. Our results indicate that IL-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

Highlights

Interleukin (IL)–18 is an 18.3-kDa cytokine with proinflammatory and immune-enhancing properties derived by enzymatic cleavage of a 23kDa precursor that is produced in monocytic cells
In this study Estimated glomerular filtration rate increased only slightly at 12 weeks of exposure in the TDF regimen group pointing a delay in the detection of proximal tubular dysfunction compared to interleukin- 18 (IL-18) that shows a marked increased at 4 weeks
In comparison with the N-TDF regimen group, it was observed that IL-18 levels decreased sharply with time, suggesting that N-TDF antiretroviral therapy does not caused proximal tubular dysfunction but may offer remedy to the harmed caused by the HIV itself on the kidney

Summary

Introduction

Interleukin (IL)–18 is an 18.3-kDa cytokine with proinflammatory and immune-enhancing properties derived by enzymatic cleavage of a 23kDa precursor that is produced in monocytic cells. It has been found to be released by the proximal tubular cells of the kidney during the event of their damage by nephrotoxic drugs such as tenofovir (TDF) [1]. Proximal tubular dysfuntion (PTD) is typically diagnosed by detecting increases in serum creatinine. Serum creatinine is an unreliable indicator during acute changes in kidney function owing to several reasons. Serum creatinine concentrations might not change until about 50% of kidney function has already been lost. Serum creatinine does not accurately reflect kidney function until a steady state has been reached, which could take several days

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