Abstract
Cryptococcus is the most common etiology of adult meningitis in Africa. Amphotericin B deoxycholate remains paramount to treatment, despite toxicities, including acute kidney injury (AKI). We assessed the ability of the following urine markers to predict AKI in patients who received amphotericin B: urine neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC), tissue inhibitor of metalloproteinases-2 (TIMP-2), and protein. One hundred and thirty human immunodeficiency virus (HIV)-infected participants with cryptococcal meningitis were enrolled and received amphotericin and fluconazole for 2 weeks. We defined AKI as glomerular filtration rate (GFR) < 60 mL/min/1.73 m2; measured urine NGAL, CysC, TIMP-2, and protein; and explored AKI incidence, risk factors, and associations with mortality using Cox proportional hazards models. Participants were 48% female with a median age of 35 years, a median CD4 count of 21 cells/μL, and 44% died within 12 months. Incident AKI occurred in 42% and was associated with mortality (adjusted hazard ratio [aHR] = 2.8; P < .001). Development of AKI was associated with female sex (P = .04) and with higher CD4 count (49 vs 14 cells/μL; P < .01). Urine protein level in the highest quartile independently predicted AKI and mortality (aHR = 1.64, P = .04; aHR = 2.13, P = .02, respectively). Urine NGAL levels in the highest quartile independently predicted AKI (aHR = 1.65; P = .04). Acute kidney injury occurred in 42% of patients, and AKI was associated with mortality. Urine biomarkers, specifically urine protein, may be useful for antecedent prediction of amphotericin-associated AKI but need further evaluation.
Highlights
Cryptococcus is the most common etiology of adult meningitis in Africa
Acute kidney injury occurred in 42% of patients, and acute kidney injury (AKI) was associated with mortality
Cryptococcal meningitis is a disseminated fungal infection caused by Cryptococcus species and remains a major cause of mortality in human immunodeficiency virus (HIV)– infected persons, especially in resource-limited settings [1]
Summary
One hundred and thirty human immunodeficiency virus (HIV)–infected participants with cryptococcal meningitis were enrolled and received amphotericin and fluconazole for 2 weeks. We defined AKI as glomerular filtration rate (GFR) < 60 mL/ min/1.73 m2; measured urine NGAL, CysC, TIMP-2, and protein; and explored AKI incidence, risk factors, and associations with mortality using Cox proportional hazards models. Baseline and follow-up serum creatinine concentrations were measured at regular intervals as per the COAT trial protocol (5–6 time points during amphotericin treatment and at 1 and 2 weeks after completion of amphotericin therapy). We included 130 participants with stored urine samples, which were collected a median of 4 (interquartile range [IQR] = 4–5) days from diagnosis of cryptococcal meningitis (which is similar to time from amphotericin initiation: median = 4; IQR = 4–5 days), and measured NGAL, CysC, and TIMP-2 by enzyme-linked immunosorbent assay (R&D Systems) and protein and creatinine (Beckman Coulter DXC 800) on stored urine samples. We examined the association of incident AKI with 12-month mortality using time-updated Cox proportional hazards models. Written informed consent was obtained to participate in the COAT trial, as previously described [22]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
