Renal Alterations in Chronic Liver Disease

Inflammatory chronic liver diseases (CLD), including nonalcoholic steatohepatitis (NASH), alcohol-associated liver disease (ALD), hepatitis C virus (HCV), and a combination of ALD with HCV (ALD/HCV), account for nearly 2 million deaths annually. The global prevalence of CLD is a major public health concern due to its ability to alter the predicted pharmacokinetics of xenobiotics, which may lead to nephrotoxicity. Each of these CLD etiologies can cause a disruption in drug disposition and elimination through hepatic dysfunction, including expression changes in drug metabolizing enzymes and transporters. This altered disposition, specifically by transporters, may lead to an increase in plasma retention, a decrease in biliary excretion, and result in an increase in systemic exposure to nephrotoxic compounds. Additionally, CLD can elicit changes in renal physiology, such as decreased glomerular filtration rate, further influencing the elimination of xenobiotics. However, despite increasing evidence that liver dysfunction impacts renal physiology, there is limited supportive clinical information, due to limited diagnosis of liver disease, complexity in liver disease etiology, and inadequacy of renal function tests. Consequently, human renal transporter alterations in CLD etiologies were unknown until recently. In this study, I collated a unique cohort of renal biopsies were identified through extensive medical and social history examinations from patients with CLD etiologies, including nonalcoholic fatty liver disease (NAFLD), NASH, ALD, HCV, and ALD/HCV. With the aim to overcome diagnostic barriers and improve future study limitations, immune regulators that had altered transcriptional expression in each etiology were identified. Expression changes were validated with quantitative protein expression and demonstrated an increase for complement C1q C chain (C1QC) in NASH, ALD, HCV, and ALD/HCV (42.9± 16.6; 38.8± 18.4; 39.0± 13.5; 40.1± 20.1 pmol/mg protein) relative to control (19.2± 10.4 pmol/mg protein; p