Non-alcoholic Fatty Liver Disease And Chronic Kidney Disease

【Objective】Nonalcoholic fatty liver disease(NAFLD)may increase the risk of chronic kidney disease(CKD),but the conclusion is controversial among different populations.In this study,two independent datasets from China and the United States(US)were used to explore the relationship between NAFLD and CKD in different populations by adjusting for the same confounding factors.Moreover,the relationship between the newly proposed metabolic(-dysfunction)associated fatty liver disease(MAFLD)and CKD was also evaluated and the diagnostic efficacy of MAFLD in real-world was also examined.【Method】1.The differences between China and the US in the relationship between CKD and NAFLD:The US dataset were retrieved from the Third National Health and Nutrition Examination Survey(NHANES III)and the Chinese dataset was from the physical examination center of Wenzhou First Hospital Affiliated of Wenzhou Medical University.The diagnosis of NAFLD was based on ultrasonography.CKD was defined as e GFR<60[ml/min/1.73m~2)]and/or proteinuria(urinary albumin creatinine ratio≥30mg/g).2.The utility of MAFLD in the real world and its impact on CKD:The NHANES database is used for this analysis.The diagnostic criteria of MAFLD were based on 2020 APSAL guidelines for the diagnosis and treatment of MAFLD.3.Statistical methods:SAS 9.4(SAS Institute,Inc,Cary,NC)was used to convert NHANES data.Medcalc 15.2.2(Med Calc Software bvba,Ostend,Belgium)was used for forests plot.R 3.6.2(https://www.r-project.org/)was used for statistics.Student t test(variable was normal distribution),Mann Whitney U test(when variable was non-normal distribution)and chi square test(when variable was dichotomous)were used to explore the differences between the two groups.Binary logistic regression analysis was used to estimate the adjusted risk of the NAFLD on CKD.The method was the enter method.The results were expressed by odds ratio(OR)and its 95%confidence interval(CI).【Result】1.The differences between China and the US in the relationship between CKDand NAFLDA total of 63274 cases were included,with 12045 from NHANES III dataset and 51229 from China dataset.The prevalence of NAFLD was 36.09%in US population and 27.12%in Chinese population(P<0.001).The prevalence of CKD in Chinese population was lower than that in US population(9.1%vs 21.7%,P<0.001).Patients with advanced CKD(stage 3-5)accounted for 62.55%of CKD patients in the US population,while only 43.24%of CKD patients in Chinese population(P<0.001).In multivariate regression,NAFLD was not associated with CKD in the US population(OR:0.952-1.052,all P>0.05),while in Chinese population NAFLD was still an independent risk factor for CKD after adjusting for age,gender,BMI,hypertension and diabetes.However,after adjusting for additional serum lipid,the correlation between NAFLD and CKD became insignificant.No significant correlation was found between NAFLD and advanced CKD(stage 3-5)in both Chinese and the US populations after adjusting for the same metabolic factors(all P>0.05).NAFLD was an independent risk factor for early renal function decline in Chinese population in all models(OR:1.245-1.513,P<0.05).After adjusting for age,gender,history of hypertension and diabetes,NAFLD was also an independent risk factor for early CKD(OR:1.043-1.272,all P value<0.05).2.The utility of MAFLD in the real world and its impact on CKDA total of 13083 subjects were included in this study.Among them 4087subjects(31.24%)were diagnosed with MAFLD,and 4347 subjects(33.23%)were diagnosed with NAFLD.Compared with NAFLD group,MAFLD group had older age,higher BMI and more metabolic factors(all P<0.05).The levels of liver enzymes,such as ALT,AST,GGT and ALP,were significantly higher in MAFLD group than those in NAFLD group(P<0.05).The percentage of CKD in MAFLD population was 26.91%,which was significantly higher than that in non-MAFLD population(18.27%,P<0.001).The proportion of CKD stage 3-5 was 16.44%,which was higher than that of non-MAFLD group(11.33%,P<0.001).Although the prevalence of CKD in MAFLD was higher than that of NAFLD(26.91%vs25.83%),there was no significant difference(P=0.279).Multivariate regression showed that MAFLD also increased the risk of early CKD,but it was not an independent risk factor of late CKD.A total of 620/13083 cases(4.74%)met the criteria of NAFLD,but did not meet the criteria of MAFLD and were classified as Non-MD-NAFLD.Of them,46cases(7.42%)were diagnosed as severe fatty liver.Compared with MAFLD,Non-MD-NAFLD with severe steatosis were nearly 8 years younger than MAFLD group(40.17±17.21 vs 48.39±15.20,P=0.002).The BMI was significantly lower in Non-MD-NAFLD group,but there was no significant difference in transaminase levels between the two groups(all P>0.05).There was no significant difference in the proportion of advanced liver fibrosis diagnosed by APRI,FIB-4 and NFS(all P>0.05).In terms of renal function,there was no significant difference in creatinine and e GFR levels between Non-MD-NAFLD and MAFLD groups,or between Non-MD-NAFLD with different fatty liver grades.According to the number of metabolic abnormalities,patients with MAFLD were divided into three groups.With the increase of metabolic abnormalities,the severity of intra-and extra-hepatic organ injury increased in patients with MAFLD.The proportion of advanced fibrosis increased with the number of metabolic abnormalities,while e GFR decreased with it(P<0.05).Compared with MAFLD patients diagnosed with obesity or metabolic dysfunction alone,the patients diagnosed with diabetes alone had most severe renal injury.【Conclusion】NAFLD increases the risk of early CKD while not the late CKD.The discrepancy between the Chinese population and the US population may due to the higher proportion of late CKD in the US population.In addition,the new definition of MAFLD helps identifying more people at risk of liver disease progression than NAFLD.There is no significant difference between NAFLD and MAFLD regarding the risk of kidney injury.Although some people with low BMI have severe hepatic steatosis,they will be missed by MAFLD because they have no metabolic risk.These people may also have severe hepatic fibrosis.As this is only a cross-sectional study,it is difficult to have a causal conclusion.More studies are needed to verify this conclusion in the future.