Relations of liver fat with prevalent and incident chronic kidney disease in the Framingham Heart Study: A secondary analysis

Abstract

Background & Aims:Prior studies demonstrated an association between non-alcoholic fatty liver disease and chronic kidney disease (CKD), though data are conflicting.We examined the association between liver fat and prevalent and incident CKD in the Framingham Heart Study (FHS). Methods:We included FHS participants who underwent computed tomography (CT) from 2002 to 2005 (n = 1315). After excluding heavy alcohol use (n = 211) and missing covariates (n = 117), the final sample included 987 participants. For the incident CKD analysis, we excluded 73 participants with prevalent CKD. Liver fat was measured by the average liver attenuation on CT. Estimated glomerular filtration rate (eGFR) was obtained using the CKD Epidemiology Collaboration Creatinine-Cystatin C equation, and CKD was defined as eGFR < 60 ml/min/1.73 m 2 . Microalbuminuria was defined by sex-specific urinary albumin-creatinine ratio cut-offs. Multivariableadjusted regression models were performed to determine the association between liver fat and CKD. Results:The prevalence of hepatic steatosis and CKD were 19% and 14% respectively (55.9% women, mean age 60 ± 9 years). After adjusting for covariates, we observed no significant associations between liver fat and CKD, microalbuminuria or eGFR in cross-sectional analyses. We observed positive associations between liver fat, incident microalbuminuria and reduced eGFR in age-and sex-adjusted models; these relationships were not significant in multivariable-adjusted models. Conclusions:In this community-based cohort study, we did not observe significant associations between liver fat and prevalent or incident CKD with a median follow-up time of 12.5 years. The association between NAFLD and CKD may be accounted for by shared risk factors; confirmatory studies are needed.

NAFLD as a driver of chronic kidney disease

“…either by abnormal levels of serum liver enzymes or by imaging techniques) is significantly associated with an increased incidence of CKD [34][35][36][37][38][39][40][41][42][43][44][45][46] (Table 1). Notably, in most of these studies the significant association between NAFLD and increased incidence of CKD persisted even after adjustment for age, sex, obesity, hypertension, T2DM and other potential confounding factors.…”

PNPLA3 gene and kidney disease

“…Hence, the identification of further independent predictors for CKD is crucial in clinical practice. At present, there is strong evidence linking NAFLD and CKD, indicating that patients with NAFLD could need more intensive surveillance and treatment in order to reduce their risk of developing CKD [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Additionally, accumulating data also suggest the existence of an association between PNPLA3 rs738409 gene variant (which is strongly linked to the development of NAFLD and its advanced forms) and risk of CKD [23][24][25][26][27][28][29], thereby suggesting that PNPLA3 may directly influence the kidney injury [44].…”

“…In the last 5-10 years, several observational reports have documented that imaging-diagnosed NAFLD is independently associated with an increased risk of developing CKD in patients with and without T2DM [10][11][12][13][14][15][16][17][18][19][20][21][22][23]. In addition, accumulating evidence now suggests that the rs738409 G allele is associated with lower values of estimated glomerular filtration rate (eGFR) as well as with a higher risk of CKD in adults but also in adolescents and children, even after adjustment for the presence of NAFLD and multiple CKD risk factors [13,[24][25][26][27][28][29][30].…”

“…In addition, accumulating evidence now suggests that the rs738409 G allele is associated with lower values of estimated glomerular filtration rate (eGFR) as well as with a higher risk of CKD in adults but also in adolescents and children, even after adjustment for the presence of NAFLD and multiple CKD risk factors [13,[24][25][26][27][28][29][30]. This association may explain, at least in part, the epidemiological association between liver and kidney disease [10][11][12][13][14][15][16][17][18][19][20][21][22][23].…”

The Negative Association Between Non-alcoholic Fatty Liver Disease Severity and Gouty Nephropathy in a Non-diabetic Gouty Population: A Cross-Sectional Study

“…The relationship between nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) has attracted much attention, since they share similar risk factors and pathogenic mechanisms, such as insulin resistance (IR), diabetes mellitus (DM), hyperlipidemia and obesity [12][13][14][15][16][17][18]. While numbers of previous studies indicated the presence and severity of NAFLD was a potential contributory risk factor for the development and progression of CKD, recent studies suggested no adverse association between NAFLD hepatic steatosis and renal function both in general populations and diabetic individuals [19][20][21][22].…”