Non-Alcoholic Fatty Liver Disease and Clinical Outcomes in Chronic Kidney Disease

Rajkumar Chinnadurai; James Ritchie; Darren Green; Philip A. Kalra

Disclosures

Nephrol Dial Transplant. 2019;34(3):449-457. 

In This Article

Abstract and Introduction

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is an independent risk factor associated with cardiovascular disease (CVD) and incidence of chronic kidney disease (CKD). NAFLD is threatening to become a major public health problem in association with the metabolic syndrome. The association of NAFLD with outcomes in patients with advanced CKD has not been evaluated. In this study, the prevalence of NAFLD and its impact on cardiovascular and renal outcomes and mortality were determined in a large secondary care CKD cohort.

Methods: The study was conducted on 1148 CKD patients within a cohort of 3061 CKD patients, who had undergone ultrasound imaging of the liver over a 15-year period. A propensity-matched population from within the cohort was also included. Cox regression analysis was used to study the association of NAFLD with cardiovascular events, end-stage renal disease and mortality and linear regression analysis for CKD progression.

Results: The prevalence of NAFLD was 17.9%. The median duration of follow-up after scanning was 5.4 years, with a median estimated glomerular filtration rate (eGFR) of 33.5 mL/min/1.73 m2 in this population. NAFLD proved to be a strong independent risk factor for cardiovascular events [hazard ratio (HR) 2.03; 95% confidence interval (CI) 1.33–3.13; P < 0.01] but it was not associated with all-cause mortality (HR 0.79; 95% CI 0.58–1.08; P = 0.14) or CKD progression (P = 0.09 for rate of decline of eGFR slope). Patients with CKD are known to have high cardiovascular risk; the propensity-matched analysis showed that NAFLD increased this cardiovascular risk (HR 2.00; CI 1.10–3.66; P < 0.05).

Conclusions: NAFLD has a strong independent association with cardiovascular events, even in an advanced CKD cohort with high comorbidity. The implication is that routine screening for NAFLD may be warranted in CKD populations to enable targeted interventions for CVD prevention in higher risk patients.

Introduction

Non-alcoholic fatty liver disease (NAFLD) is a condition characterized by the accumulation of fat in the liver of people who take minimal or no alcohol. It incorporates a spectrum of conditions ranging from simple steatosis to steatohepatitis, advanced fibrosis and cirrhosis. NAFLD is emerging as the most common cause of chronic liver disease worldwide.[1] The global prevalence of NAFLD is believed to be as high as 25%.[2] In Europe, the prevalence in the general population has been shown to be between 2% and 44%.[3] The prevalence is observed to be much higher (24–69.5%) in patients with diabetes mellitus.[4–6] The variation in prevalence estimates relates to the methods used in the diagnosis of NAFLD.

The association between NAFLD, chronic kidney disease (CKD) and cardiovascular disease (CVD) has been of increasing interest in recent years. Despite being regarded as the hepatic component of the metabolic syndrome, which includes diabetes, hypertension and obesity, NAFLD has been shown to be an independent risk factor associated with CVD.[7–9] In patients with NAFLD, a high incidence and prevalence of CKD have been observed[10,11] and a strong association between the two conditions has been reported.[12–14] Several pro-inflammatory and oxidative stress mechanisms have been postulated to explain the relationship between these two conditions.[15,16]

CKD is a global public health problem, affecting >25% of individuals above the age of 65 years in Western adult populations.[17] The US Renal Data System reports that over 670 000 people in the USA received some form of renal replacement therapy (RRT) at the end of 2014, and this number is predicted to reach 2.2 million by 2030.[18] CKD in itself is an independent risk factor for CVDs,[19–21] and the majority of patients do not reach end-stage renal disease (ESRD) due to the high risk of mortality associated with cardiovascular events.[22] The presence of NAFLD in advanced CKD patients is likely to compound their cardiovascular risk.

Although several studies have reported on the associations of NAFLD with CKD in patients with normal or near-normal kidney function, research on the association in patients with advanced CKD (Stages 3–5) has been scarce. The impact of NAFLD on CKD progression and mortality in this group has not been well explored. Our study was conducted to gain insight into the prevalence of NAFLD in advanced CKD and to investigate whether NAFLD had any influence on three primary outcomes (i) all-cause mortality, (ii) non-fatal cardiovascular events (NFCVEs) and (iii) rate of progression of CKD in a large cohort of non-dialysis CKD patients.

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