High Prevalence of Signs of Renal Damage Despite Normal Renal Function in a Cohort of HIV-Infected Patients: Evaluation of Associated Factors

Abstract

Renal disorders are an emerging problem in HIV-infected patients. We performed a cross-sectional study of the first 1000 HIV-infected patients attended at our HIV unit who agreed to participate. We determined the frequency of renal alterations and its related risk factors. Summary statistics and logistic regression were applied. The study sample comprised 970 patients with complete data. Most were white (94%) and men (76%). Median (IQR) age was 48 (42-53) years. Hypertension was diagnosed in 19%, dyslipidemia in 27%, and diabetes mellitus in 3%. According to the Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) equation, 29 patients (3%) had an eGFR < 60 ml/min/1.73 m 2 ; 18 of them (62%) presented altered albumin/creatinine and protein/creatinine (UPC or UAC) ratios. Of the patients with eGFR > 60 mL/min, it was present in 293 (30%), 38 of whom (7.1%) had UPC > 300 mg/g. Increased risk of renal abnormalities was correlated with hypertension (OR, 1.821 [95%CI, 1.292;2.564]; p = 0.001), age (OR, 1.015 [95%CI, 1.001;1.030], per one year; p = 0.040), and use of tenofovir disoproxil fumarate (TDF) plus protease inhibitor (PI), (OR, 1.401 [95%CI, 1.078;1.821]; p = 0.012). Current CD4 cell count was a protective factor (OR, 0.9995 [95%CI, 0.9991;0.9999], per one cell; p = 0.035). A considerable proportion of patients presented altered UPC or UAC ratios, despite having an eGFR > 60 mL/min. CD4 cell count was a protective factor; age, hypertension, and use of TDF plus PIs were risk factors for renal abnormalities. Based on our results, screen of renal abnormalities should be considered in all HIV-infected patients to detect these alterations early.

Effect of Tenofovir Disoproxil Fumarate on Incidence of Chronic Kidney Disease and Rate of Estimated Glomerular Filtration Rate Decrement in HIV-1–Infected Treatment-Naïve Asian Patients: Results from 12-Year Observational Cohort

“…Although this study investigated the incidence of CKD, the data on urinalysis were not available. Because persistent proteinuria is one of the diagnostic criteria for CKD and proteinuria can present in patients with normal eGFR value, 32 our findings of CKD incidence (20.6 per 1000 person-years) might be underestimated. Second, although we focused on the investigation of Asian patients, most study subjects were Japanese men, and only a small number of females were included.…”

HIV Infection, Tenofovir, and Urine α1-Microglobulin: A Cross-sectional Analysis in the Multicenter AIDS Cohort Study

“…5,6 Although pre-marketing studies suggested a favorable safety profile, 7 TDF use has been associated with the development of acute kidney injury, proteinuria, chronic kidney disease (CKD), and the Fanconi syndrome of proximal tubular dysfunction. 8–12 Kidney biopsy series of patients with TDF-associated kidney injury have demonstrated flattening of proximal tubular epithelial cells and widespread mitochondrial abnormalities. 13,14 Notably, the active drug, tenofovir, is eliminated in urine through active secretion by proximal tubular epithelial cells, 15 with tenofovir influx and efflux mediated by organic anion transporters and multidrug resistance proteins, respectively.…”

Kidney Disease in HIV: Moving beyond HIV-Associated Nephropathy

“…13,56,57 Although clinical trials have reported minimal nephrotoxicity, 53,58 observational studies have shown that TDF is associated with higher risks of AKI, proteinuria, nephrogenic diabetes insipidus, and CKD. 14,15,[59][60][61][62][63][64][65][66] Among 10,841 HIV-positive United States veterans, each year of TDF exposure was associated with a 34% higher risk of proteinuria, a 33% higher risk of CKD, and an 11% higher risk of rapid kidney function decline. 14 A subsequent metaanalysis of 17 studies reported faster kidney function decline (23.9 ml/min) and slightly increased risk of AKI (risk difference of 0.7%) among TDF versus non-TDF users.…”