Urinary neutrophil gelatinase‐associated lipocalin: A novel biomarker for predicting chronic kidney disease in patients with nonalcoholic fatty liver disease

Abstract

Abstract Aims Nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are common diseases worldwide. Reports of a high prevalence of CKD in NAFLD patients have been documented. Urinary neutrophil gelatinase‐associated lipocalin (NGAL) is a reliable biomarker for renal dysfunction, and it is recommended for early detection of acute kidney injury (AKI) in cirrhotic patients. Currently, there is no evidence for using urine NGAL to predict CKD in NAFLD patients. We aim to determine the proportion of CKD and identify the predictive value of NGAL and other factors associated with CKD in these patients. Methods A single‐center, cross‐sectional study was conducted between July 2018 and December 2019 in consecutive NAFLD patients diagnosed by transient elastography (TE) or liver biopsy at a tertiary care university hospital in Bangkok, Thailand. Advanced liver fibrosis is defined as fibrosis stages 3–4. The definition of CKD is estimated glomerular filtration rate (eGFR) <60 ml⋅min−1⋅1.73 m−2 based on the Kidney Disease Improving Global Outcomes (KDIGO) guideline 2012. Urine NGAL level was measured by enzyme linked immunosorbent assay technique. Results A total of 101 NAFLD patients were included with a mean age of 54 ± 16 years. Among these patients, 14 (13.9%), 13 (12.9%), and 32 (31.7%) had fibrosis stages 2, 3, and 4, respectively. Nine percent (9 of 101) of patients with NAFLD with a mean eGFR of 42.66 ± 17.42 ml⋅min−1⋅1.73 m−2. The statistically significant factors associated with CKD were a higher level of urine NGAL (55.1 [25.15–150.60] vs. 15.1 [9.67–25.15] ng/ml; p = 0.006), a higher level of TE (17.3 [6.85–46.20] vs. 7.7 [5.6–11.7] kPa; p = 0.038), and a presence of advanced fibrosis (77.8% vs. 40.7%; p = 0.041), compared to those without CKD. Urine NGAL was the only significant factor associated with CKD in NAFLD patients. The cutoff level of urine NGAL at 36.75 ng/ml showed odds ratio of 21.27 (95% CI: 3.97–113.82; p < 0.001) and 1.02 (95% CI: 1.00–1.04; p = 0.024) by univariate and multivariate analyses, respectively. The selected urine NGAL cutoff demonstrated a sensitivity and specificity of 77.8% and 85.9% for predicting CKD, respectively. Conclusions The proportion of CKD in NAFLD patients was 9% and the presence of advanced fibrosis was a significant risk factor associated with CKD. Additionally, urine NGAL was significantly associated with CKD in NAFLD patients using a cutoff level of 36.75 ng/ml for predicting CKD with acceptable sensitivity and specificity. A larger prospective cohort study is needed to validate our findings.

Keywords

• chronic kidney disease
• nonalcoholic fatty liver disease
• urinary neutrophil gelatinase‐associated lipocalin