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NAFLD Is Independent Kidney Disease
Risk Factor in People With Cirrhosis
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AASLD-The Liver Meeting, November 4-8, 2022, Washington, DC
Mark Mascolini
Nonalcoholic fatty liver disease (NAFLD) independently boosted risk of chronic kidney disease (CKD) in a large prospective study of people with cirrhosis [1]. And CKD independently raised the risk of death 8-fold in this comparison of 897 people with NAFLD cirrhosis and 1116 controls with non-NAFLD cirrhosis.
Higher portal pressure and systemic vasodilation drive recurrent acute kidney injury and CKD in people with cirrhosis, noted researchers from New Delhi's Institute of Liver and Biliary Sciences who conducted the new study. But no research assesses incidence and risk factors for CKD in people with NAFLD cirrhosis or the impact of systemic inflammation, portal pressure, and hemodynamic alterations on development of CKD.
The New Delhi team addressed those issues in a prospective cohort study that ran from August 2014 to March 2022. The study group consisted of people with stable decompensated cirrhosis who had hepatic venous pressure gradient (HVPG) measured at enrollment and follow-up for CKD development until death or liver transplant. The study excluded people under 18 years old and those with kidney or liver transplant, HIV infection, hepatocellular carcinoma, extrahepatic malignancy, severe extrahepatic disease (including CKD, severe cardiopulmonary disease, and psychiatric disorders), portal or hepatic vein thrombosis, urinary tract infection, or obstructive uropathy.
Among 2053 people enrolled, 897 had NAFLD cirrhosis and 1116 had non-NAFLD cirrhosis. The NAFLD group was significantly older (average 53.1 vs 47.7), had a significantly lower proportion of men (77% vs 83%), a significantly higher proportion with diabetes (17.3% vs 1.4%), and a significantly higher proportion of obese people (40.2% vs 1.2%) (P < 0.001 for all differences). The NAFLD group had a significantly lower MELD-Na score (model for end-stage liver disease-sodium), a significantly lower Child-Turcotte-Pugh score, and a significantly lower neutrophil-to-lymphocyte ratio (a marker of inflammation).
Arterial pressure was significantly higher in the NAFLD cirrhosis group (average 76.8 vs 75.1 mm Hg), who had a significantly higher HVPG (16.7 vs 15.7 mm Hg) and a significantly lower cardiac index (3.6 vs 3.8 L/min/m2) (P < 0.001 for all differences).
CKD developed in 333 people (37%) with NAFLD cirrhosis and 364 (33%) with non-NAFLD cirrhosis. A much higher proportion of NAFLD participants than non-NAFLD participants had eGFR-determined CKD stage 5 (31% vs 13%), and a much lower proportion of the NAFLD group had CKD stage 3A (16% vs 33%) (P < 0.001 overall). Similar proportions in each group had stage 3B or 4 CKD.
In a competing-risk survival analysis, cumulative incidence of CKD was significantly higher in people with NAFLD cirrhosis than in those with non-NAFLD cirrhosis through more than 30 months of follow-up (P = 0.0001). To identify risk factors for CKD, the researchers used competing-risk survival analysis, with death and liver transplant as the competing risks. This analysis linked NAFLD cirrhosis to a 20% higher risk of CKD (adjusted subdistribution hazard ratio [asHR]) 1.21, 95% confidence interval [CI] 1.03 to 1.43).
Other independent predictors of CKD in this competing-risk analysis were older age (asHR 1.03, 95% CI 1.02 to 1.04), male gender (asHR 1.65, 95% CI 1.30 to 2.09), diabetes (asHR 1.40 95% CI 1.14 to 1.72), hypertension (asHR 1.77, 95% CI 1.02 to 3.06), MELD-Na (asHR 1.05, 95% CI 1.03 to 1.06), grade 2 or 3 ascites (asHR 1.52, 95% CI 1.15 to 2.01), prior acute kidney injury (asHR 1.82, 95% CI 1.51 to 2.24), neutrophil-to-lymphocyte ratio (asHR 1.10, 95% CI 1.05 to 1.16), and systemic vascular resistance index (the only inverse association, asHR 0.39, 95% CI 0.33 to 0.47).
Cox regression analysis tied CKD to an 8-fold higher risk of death in these people with cirrhosis (aHR 8.19, 95% CI 5.72 to 11.71). Other mortality predictors were grade 2 or 3 ascites, MELD-Na, neutrophil-to-lymphocyte ratio, and systemic vascular resistance index (again the only inverse association).
The researchers concluded that NAFLD is an independent risk factor for newly diagnosed CKD in people with cirrhosis. They proposed that higher tubulointerstitial inflammation with NAFLD cirrhosis could be the mechanism behind development of CKD. This study also identified other independent predictors of CKD in people with cirrhosis: older age, degree of systemic vasodilation, diabetes, liver disease severity, and prior acute kidney injury.
Reference
1. Maiwall R, Pasulapeti SSR, Sarin SK, et al. Non-alcoholic fatty liver disease drives the development of chronic kidney disease in patients with cirrhosis-a prospective cohort study. AASLD-The Liver Meeting, November 4-8, 2022, Washington, DC. Abstract 73.
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