CKD Risk Increased in Patients With Metabolic Dysfunction-Associated Fatty Liver Disease

In 2017, approximately 700 million individuals worldwide were diagnosed with chronic kidney disease (CKD), accounting for approximately 1.2 million deaths. CKD is a major public health issue and is associated with the risk of progression to end-stage renal disease (ESRD), a life-threatening condition requiring renal replacement therapy or kidney transplantation for survival. Patients with ESRD face poor overall survival as well as significant psychologic and economic burdens. 

Nonalcoholic fatty liver disease (NAFLD) is defined by excessive fat accumulation in the liver not associated with excessive alcohol use, viral hepatitis, or drugs. The estimated incidence of NAFLD in the general population is 25% to 30%; a large proportion of those with NAFLD have metabolic comorbidities. A panel of hepatologists has suggested a change in nomenclature to metabolic dysfunction-associated fatty liver disease (MAFLD).  

Results of studies have suggested an association between NAFLD and an increase in the risk of CKD. However, there are few data available on the association between MAFLD and the risk of CKD. A 2023 systematic review demonstrated a positive association between MAFLD and CKD, but, according to researchers in China, the evidence was predominantly generated from cross-sectional studies that did not determine causality. Two researchers in China, Wanghao Liu, MD, PhD, and Xiaoying Sun, MD, PhD, conducted a meta-analysis of cohort studies to provide updated data on the risk of CKD in patients with MAFLD. Results were reported in BMC Nephrology. 

Two independent reviewers searched the PubMed, CENTRAL, Embase, Scopus, and Web of Science databases from the earliest possible date to May 17, 2024. The search query utilized was developed from a combination of heading terms and keywords: ((((Metabolic dysfunction-associated fatty liver disease) OR (MAFLD)) OR (liver steatosis)) OR (Fatty liver)) AND ((chronic kidney disease) OR (renal disease)). 

The search query among the 5 databases revealed 15,077 studies. A total of 9,533 were duplicates and were removed electronically. Records from the remaining 5,544 studies were screened, and 30 articles were selected for full-text review. Those articles were matched against inclusion criteria, resulting in the identification of 8 studies incorporating 9 cohorts, with a combined sample size of 598,531. 

Most of the eligible studies were conducted in Asian populations from Japan, China, and Korea; one study included a cohort from the UK Biobank. Patients with baseline CKD were excluded from all 8 studies. The standard definition of MAFLD was used in all included studies: fatty liver on hepatic ultrasonography and at least 1 of the following 3 conditions: (1) overweight; (2) type 2 diabetes mellitus; (3) at least 2 of 7 metabolic conditions (increased waist circumference, blood pressure, triglycerides, high-sensitivity C-reactive protein level, or insulin resistance; decreased high-density lipoprotein-cholesterol; and prediabetes).  

CKD was defined as the presence of 1 of 3 measures: (1) estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m²; (2) proteinuria; or (3) urine albumin/creatinine ratio of 30 mg/g or greater. Median follow-up ranged from 4.6 to 12.9 years. Results of all studies suggested that MAFLD was a significant risk factor for CKD. 

Results of pooled analysis of all 9 cohorts revealed that MAFLD was an independent predictor of CKD (hazard ratio [HR], 1.38; 95% CI, 1.24-1.53; I2=95%). There was no publication bias noted on Egger’s test (P=0.72). The results remained consistent in sensitivity analyses, and there was no change in results after the exclusion of any study. 

In subgroup analyses, there was no change in the significance of effect size based on study design (prospective or retrospective), country of origin, incidence of CKD in the cohort (>10% or ≤10%), or whether the study adjusted for cardiovascular disease, diabetes mellitus, hypertension, eGFR, and smoking status.  

Subgroup analyses examining the risk of CKD were conducted based on sex, definition of MAFLD including at least one metabolic abnormality, eGFR calculated using the Chronic Kidney Disease-Epidemiology Collaboration equation, participants 40 to 70 years of age, and patients with healthy lifestyle factors. Results demonstrated an increase in the risk of CKD in all subgroups. Notably, when the cohort was distributed based on the number of healthy lifestyle factors, a lower number of factors was found to increase the risk of CKD.  

Using data available from different subgroups, the researchers also conducted separate analyses for men, women, and an overweight category (yes or no). Results of meta-analysis revealed that MAFLD was a risk factor for CKD in men (HR, 1.38; 95% CI, 1.22-1.56; I2=86%) and women (HR, 1.51; 95% CI, 1.25-1.82; I2=87%) and in overweight (HR, 1.41; 95% CI, 1.20-1.66; I2=89%) and non-overweight cohorts (HR, 1.35; 95% CI, 1.20-1.53; I2=9%). 

The authors cited some limitations to the study findings, including the small number of studies eligible for the meta-analysis, the possibility of bias due to the retrospective design of some of the studies, variations in the CKD definition among the studies, and variations in duration of follow-up. Also cited were the possibility that several unknown confounders had been missed and that the study cohorts were primarily limited to Asian populations, with only one study from Europe. Finally, the researchers noted that due to insufficient data in the eligible studies, they were unable to examine the relationship between the severity of MAFLD at baseline and disease duration and the risk of CKD. 

In conclusion, the researchers said, “Evidence for good-quality cohort studies shows that MAFLD is a risk factor for CKD. The association seems persistent irrespective of sex, body mass index, and other CKD risk factors. Further investigations are needed to explore if the risk of CKD varies with the severity of MAFLD. Also, MAFLD patients need to be counseled and closely monitored for the development of CKD.”   

Source: BMC Nephrology