Chronic Kidney Disease Is Independently Associated With Increased Mortality in Patients With Nonalcoholic Fatty Liver Disease

James Paik; Pegah Golabi; Zahra Younoszai; Alita Mishra; Gregory Trimble; Zobair M. Younossi


Liver International. 2019;39(2):342-352. 

In This Article

Abstract and Introduction


Background & Aims: Nonalcoholic fatty liver disease and chronic kidney disease share similar pathophysiologic features. Our aim was to assess the association between different stages of chronic kidney disease and mortality in patients with nonalcoholic fatty liver disease.

Methods: Third National Health and Nutrition Examination Survey-linked mortality files were utilized. Nonalcoholic fatty liver disease was diagnosed by hepatic ultrasound and chronic kidney disease was defined according to the Kidney Disease Improving Global outcomes guideline. Multivariable Cox proportional hazard model was used to assess the effect of chronic kidney disease on overall and cardiovascular mortality.

Results: Total cohort included 11 695 adult participants; mean age 43.3 years, 48.4% male, 76.4% white, 18.6% had nonalcoholic fatty liver disease and 9.3% had chronic kidney disease. 5.6% had diabetes, 21.3% had hypertension, 4.3% had cardiovascular disease. Compared to subjects without chronic kidney disease or nonalcoholic fatty liver disease, nonalcoholic fatty liver disease patients with chronic kidney disease were more likely to be older, had less income, and higher prevalence of comorbidities (all P < 0.001). Prevalence of chronic kidney disease among nonalcoholic fatty liver disease cohort was 11.31%. Compared to non-nonalcoholic fatty liver disease group, patients with nonalcoholic fatty liver disease had higher rates of stage 1, 2 and 3a chronic kidney disease, but similar rates for stage 3b, 4 and 5. Mortality rate was 18.5% in 17 years. Among nonalcoholic fatty liver disease cohort, the presence of chronic kidney disease stages 2-3a (HR = 2.31, 95% CI: 1.70-3.15) and stages 3b-5 (HR = 4.83, 95% CI: 2.40-9.71) were independently associated with increased overall mortality.

Conclusions: Among patients with nonalcoholic fatty liver disease, moderate to advanced stages of chronic kidney disease are associated with overall mortality. Identification of chronic kidney disease in nonalcoholic fatty liver disease has important prognostic implications.


Chronic kidney disease (CKD) is a major public health problem that can lead to high mortality, morbidity and healthcare costs.[1,2] CKD is strongly associated with metabolic complications such as cardiovascular diseases (CVD) and the presence of CKD places individuals at increased risk for overall and cardiovascular (CV) mortality.[1–3]

Nonalcoholic fatty liver disease (NAFLD) is an important liver disease associated with metabolic syndrome (MS).[4–8] Recent data suggest that the global prevalence of NAFLD is around 25%.[9] In the United States, the prevalence of NAFLD, diagnosed by ultrasonography or proton magnetic resonance spectroscopy, has been estimated to be between 21% and 34%.[6,10] Patients with the sub-type of NAFLD that can be classified as nonalcoholic steatohepatitis (NASH) are at the greatest risk for advanced liver disease.[11] On the other hand, all patients with NAFLD are at increased risk for CVD.[12–14] In fact, cardiovascular disease is the main cause of mortality in patients with NAFLD.[12–17]

A number of chronic diseases share common risk factors with NAFLD and are considered the extrahepatic manifestation (EHM) of NAFLD.[4–9,11–13,18,19] In this context, NAFLD and CKD share many features of the metabolic syndrome, namely, diabetes mellitus (DM), insulin resistance (IR), obesity, hyperlipidaemia (HL) and HTN.[20,21] Additionally, both are associated with an increased risk of cardiovascular diseases.[20,21] Despite this linkage, this relationship and its association with mortality using a population-based data has not been fully assessed. Therefore, the aim of this study was to assess these potential associations using the Third National Health and Nutrition Examination Survey, 1988–1994 (NHANES) and linked mortality database. We also used the most recent guidelines for the diagnosis and classification of CKD developed by the Kidney Disease Outcomes Quality Initiative (KDOQI).[22,23]