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Acute Kidney Injury and Urinary Biomarkers in Human Immunodeficiency Virus-Associated Cryptococcal Meningitis
Charlotte Schutz1,2, David R Boulware3, Katherine Huppler-Hullsiek4
1Department of Medicine, Faculty of Health Sciences, and.
Background:
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.
Methods:
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.
Results:
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).
Conclusions:
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.
Insights
Acute kidney injury (AKI) affects 42% of cryptococcal meningitis patients treated with amphotericin B. Urine protein and neutrophil gelatinase-associated lipocalin (NGAL) show potential for predicting AKI and mortality in these patients.
Area of Science:
- Infectious Diseases
- Nephrology
- Pharmacology
Background:
- Cryptococcus is a leading cause of adult meningitis in Africa.
- Amphotericin B deoxycholate is a primary treatment but carries risks, including acute kidney injury (AKI).
- Predictive biomarkers for AKI in patients receiving amphotericin B are needed.
Purpose of the Study:
- To evaluate urine neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC), tissue inhibitor of metalloproteinases-2 (TIMP-2), and protein as predictors of AKI.
- To determine the incidence, risk factors, and mortality associations of AKI in HIV-infected patients with cryptococcal meningitis.
Main Methods:
- 130 HIV-infected patients with cryptococcal meningitis received amphotericin B and fluconazole.
- AKI was defined as glomerular filtration rate (GFR) < 60 mL/min/1.73 m².
- Urine NGAL, CysC, TIMP-2, and protein levels were measured; AKI incidence, risk factors, and mortality were analyzed using Cox proportional hazards models.
Main Results:
- 42% of patients developed AKI, which was associated with increased mortality (aHR = 2.8).
- AKI development was linked to female sex and higher CD4 counts.
- High urine protein levels predicted both AKI and mortality (aHR = 1.64 and 2.13, respectively).
- High urine NGAL levels predicted AKI (aHR = 1.65).
Conclusions:
- AKI is common (42%) and a significant mortality predictor in this patient group.
- Urine protein and NGAL show promise as early predictors of amphotericin B-associated AKI.
- Further research is warranted to validate these urine biomarkers for clinical use.
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