Copyright ©The Author(s) 2021.
World J Gastroenterol. May 7, 2021; 27(17): 1864-1882
Published online May 7, 2021. doi: 10.3748/wjg.v27.i17.1864
Table 1 Incidence and prevalence of chronic kidney disease in patients with varying degrees of non-alcoholic fatty liver disease severity
NAFLD diagnostic modalities
Musso et al[12]. A meta-analysis of 33 studies201463902Liver biopsy, abdominal ultrasound, elevated liver enzymes (1) 20 cross-sectional studies: Nearly two-fold increased risk of CKD in patients with NAFLD (OR 2.12, 95%CI 1.69-2.66); (2) 11 longitudinal studies: 1.8-fold increased risk of CKD in patients with NAFLD (HR 1.79, 95%CI 1.65–1.95); and (3) advanced fibrosis associated with increased prevalence (OR 5.20, 95%CI 3.14-8.61) and incidence (HR 3.29, 95%CI 2.30-4.71) of CKD in patients with NAFLD
Mantovani et al[13]. A meta-analysis of 9 studies201896595Abdominal ultrasound; FLI; serum GGTIncidence of CKD: (1) 1.4-fold increased long-term risk (HR 1.37, 95%CI 1.20–1.53) in patients with NAFLD with a median follow-up period of 5.2 years; and (2) 1.5-fold increased risk (HR 1.50, 95%CI 1.25-1.74) in patients with severe NAFLD (defined as NFS ≥ -1.455 or serum GGT ≥ 109 U/L)
Park et al[14]. Retrospective Cohort with Propensity Score Matching (1:3)2019262619ICD-9Incidence of CKD: 1.4-fold increased risk (aHR 1.41; 95%CI, 1.36-1.46) in patients with NAFLD after adjusting for demographics, baseline covariates, and ACEi/ARB use; Risk of incident CKD increases as the severity of NAFLD increases: (1) compensated cirrhosis (aHR, 1.47; 95%CI 1.36-1.59); and (2) decompensated cirrhosis (aHR, 2.28; 95%CI 2.12-2.46)
Table 2 Summary of studies assessing non-hepatic risk factors for chronic kidney disease in patients with non-alcoholic fatty liver disease
Risk factor(s)
Önnerhag et al[147]Older age2019120Biopsy-proven NAFLD vs non-NAFLDHigher prevalence of CKD in patients ≥ 55 years old
Targher et al[20]Diabetes mellitus20082103NAFLD and T2DM vs T2DM onlyPatients with NAFLD and T2DM independently associated with increased risk of CKD (OR 1.87; 95%CI 1.3-4.1, P = 0.020)
Targher et al[33]Diabetes mellitus2010301NAFLD and T1DM vs T1DM onlyPatients with NAFLD and T1DM independently associated with increased risk of CKD
Jang et al[29]Elevated baseline eGFR, HTN, and current smoking20181525NAFLD vs Non-NAFLDThe decline in eGFR associated with NAFLD appeared to be stronger among patients who were current smokers, hypertensive, and lower eGFR at baseline
Table 3 Summary of studies assessing non-invasive scoring systems for advanced fibrosis to assess risk for chronic kidney disease in patients with nonalcoholic fatty liver disease
Scoring system(s) assessed
Ciardullo et al[82]20202770APRI, FIB-4, FLI, NFSNAFLD-related fibrosis as measured with FIB-4 associated with CKD (P < 0.01)
Hsieh et al[6]202011376NFSHigher NFS associated with impaired eGFR (P < 0.0001)
Choi et al[81]201911836APRI, BARD, FIB-4, FLIFIB-4 (P = 0.0258) most precise in predicting kidney dysfunction
Önnerhag et al[79]2019144APRI, BARD, NFS, FIB-4High-risk NFS (P < 0.001), FIB-4 (P < 0.001), APRI (P = 0.008) predict CKD
Wijarnpreecha et al[80]20184142APRI, BARD, NFS, FIB-4High/intermediate probability of liver fibrosis on NFS (AUC = 0.75) and FIB-4 (AUC = 0.77) independently predict CKD
Huh et al[23]20176238FLINAFLD cut-off for NAFLD is an independent RF for CKD (P < 0.0001)
Table 4 Summary of Interventions for patients with nonalcoholic fatty liver disease and chronic kidney disease
Decreasing WHRChon et al[43]. 12-yr prospective cohort20206137A decrease in the WHR of more than 5% in patients with NAFLD leads to a significantly reduced risk of CKD development, even in non-obese patientsSerial Monitoring WHR may be beneficial in identifying patients with NAFLD at risk of developing CKD and reduction can ameliorate the progression
Weight lossVilar-Gomez et al[94]. Post-hoc analysis 2017261Improvement in liver histology due to weight loss linked to improved renal outcomes, even after adjusting for medication profile, diabetes, and hypertensionAdvocate for weight loss
SGLT2 InhibitorsShimizu et al[96]. RCT201957SGLT inhibitor (Dapagliflozin) improved liver steatosis in patients with T2DM and NAFLD and attenuates liver fibrosis in patients with NAFLD-related advanced fibrosis Although data is not sufficient, consider using SGLT2 inhibitors in T2DM patients with NAFLD and CKD
Perkovic et al[95]. CREDENCE trial20194401SGLT2 inhibitor (Canagliflozin) decreased the risk of renal failure in patients with T2DM and CKD
GLP-1Armstrong et al[100]. LEAN trial201652Liraglutide led to weight loss, glycemic control, and histological resolution of NASHGLP-1’s in NASH is considered effective in improving components of MetS, however, long-term studies are needed to determine NASH-related outcomes
Tuttle et al[101]. AWARD-7 trial2018577Once-weekly dulaglutide is associated with reduced decline in eGFR, while being as effective as insulin in achieving glycemic controlGLP-1 is a safe option for patients with CKD and is associated with slower progression of CKD
Coenzyme Q10Farhangi et al[109] and Farsi et al[110]. RCT2014[109] and 2016[110]44[109] and 41[110]100 mg of oral CoQ10/d improve biochemical variables of NAFLD after 4 wk[109] and 12 wk[110] of treatmentDue to lack of data in patients with both NAFLD and CKD, the benefit of CoQ10 supplementation is unknown; however, in separate trials with regards to both NAFLD and CKD, CoQ10 supplementation is beneficial
Yeung et al[111]. RCT201515Oral CoQ10 supplementation in patients with CKD showed significant improvement in serum creatinine when compared to placebo