Alpha-1-microglobulin as an early biomarker in renal extrahepatic manifestations of hepatitis C virus infection.

Abstract

Background: Hepatitis C virus (HCV)-related nephropathy often progresses silently and is commonly underrecognized until chronic kidney disease or acute kidney injury occurs. Urinary alpha-1-microglobulin (Uα1M) is a promising early biomarker of proximal tubule dysfunction. It may help detect the subclinical renal extrahepatic manifestations of HCV earlier than traditional markers such as serum creatinine (SCr). The early renal manifestations of HCV include microalbuminuria, hematuria, tubular injury, and immune-mediated glomerulopathy.

Aim: To evaluate the efficacy of Uα1M in identifying the early kidney involvement in patients with HCV infection.

Methods: A case-control study was conducted from February 2022 to February 2024 at the Clinic of Nephrology Outpatient, Department of Internal Medicine, and Clinic of El-Rajhy Hepatitis Outpatient at Assiut University Hospitals. This study involved 158 patients aged ≥ 18 years, divided into HCV and control groups. The HCV group included 79 patients diagnosed as HCV-positive by HCV + antibodies and positive real-time polymerase chain reaction for HCV-RNA. The control group included 79 participants who were age-matched and sex-matched, and HCV-negative healthy individuals. The primary outcome was the rate of increased level of Uα1M.

Results: The two groups were comparable in age and sex distribution. The mean hemoglobin level and platelet count were significantly lower in HCV patients than in controls, respectively. Blood urea nitrogen (BUN), SCr, and estimated glomerular filtration rate (eGFR) showed no significant differences. The urinary albumin/creatinine ratio was significantly higher in HCV-positive patients, with increased prevalence of microalbuminuria and macroalbuminuria. Uα1M levels were markedly elevated in the HCV group. It correlated positively with BUN and SCr, and negatively with eGFR, aspartate aminotransferase, and alanine aminotransferase. Uα1M levels were significantly higher in patients with hematuria (P = 0.007) and those with impaired eGFR (P < 0.001) than those without these disorders. Only five HCV-positive patients underwent renal biopsy, and all showed membranoproliferative glomerulonephritis. The Uα1M levels higher than the 3.52 mg/L cutoff had strong diagnostic ability to distinguish HCV-positive from HCV-negative subjects, with an area under the curve of 0.864 (95% confidence interval: 0.801-0.913), 77.0% accuracy, 60.0% sensitivity, 93.7% specificity, 90.4% positive predictive value, and 69.8% negative predictive value (P < 0.001).

Conclusion: Uα1M served as a valuable early renal tubular biomarker for detecting subclinical kidney involvement in chronic HCV patients. It showed a moderate correlation to BUN and mild correlation to SCr and eGFR, with membranoproliferative glomerulonephritis pathology predominance in biopsied cases. In addition, it had a strong diagnostic accuracy at levels higher than a cutoff of 3.52 mg/L, reinforcing its potential for early diagnosis of renal involvement by HCV infection.