Table 1. Cross-sectional studies connecting NAFLD to chronic kidney disease included in the meta-analysis.
| Author [REF] | Study characteristicsa | CVD risk factors | Liver disease diagnosis and prevalence | CKD diagnosis and prevalence | Adjustments | Study Data [STROBE score]b |
| Campos [27] | Hospital; n = 197; mean age 43 y; male 16%; Asian 0% | Smokers 26%; DM 26%; HTN 56%; Mean BMI 48 kg/m2; Met Sy 24% | Histology; NAFLD 63%, NASH 32% | eGFR<60 ml/min/1.73 m2 (CKD-EPI); 10% | Age, gender, BMI, waist circumference, HTN, Met sy | IPD [22] |
| Yilmaz [28] | Hospital; n = 87; mean age 47 y; male 55%; Asian 0% | Smokers 16%; DM 0%; HTN 30%; Mean BMI 30 kg/m2; Met Sy 37% | Histology; NAFLD 100%,NASH 67% | eGFR<60 ml/min/1.73 m2 (CKD-EPI) or AER 30–300 mg/d; 16% | Age, gender, BMI, waist circumference, BP, Tg, HDL-C, HOMA, smoking prediabetes, Met Sy | IPD [21(v)] |
| Targher 2010 [29] | Hospital; n = 160; mean age 51 y; male 63%; Asian 0% | Smokers 21%; DM 6%; HTN 60%; Mean BMI 27 kg/m2; Met Sy 29% | Histology; NASH 100% | eGFR<60 ml/min/1.73 m2 (MDRD) or ACR≥30 mg/g; 14% | Age, gender, BMI, waist circumference, Tg, smoking, HOMA, Met Sy diabetes, BP | AD [22] |
| Park 2011 [30] | Hospital; n = 562; mean age 53 y; male 68%; Asian 56% | Smokers 53%; DM 25%; HTN 30%; Mean BMI 30 kg/m2; Met Sy NA | All cirrhotic:12% NASH-related; 88% of other aetiologies;Matched for MELD and Child-Pugh score | eGFR<60 ml/min/1.73 m2 (MDRD); 17% | Obesity, DM, HTN, smoking, cardiovascular disease | IPD [21(s)] |
| Yasui [31] | Hospital; n = 169; mean age 54 y; male 59%; Asian 100% | Smokers 23%; DM 31%; HTN 34%; Mean BMI 26 kg/m2; Met Sy 30% | Histology;NAFLD 100%, NASH 53% | eGFR<60 ml/min/1.73 m2 (CKD-EPI) or morning dipstick proteinuria ≥1+; 14% | BMI, HTN, waist circumference, low HDL-C, high Tg, smoking, DM | IPD [22] |
| Musso [32] | Hospital; n = 80; mean age 48 y; male 67%; Asian 0% | Smokers 28%; DM 0%; HTN 52%; Mean BMI 25 kg/m2; Met Sy 31% | Histology;NAFLD 50%, NASH 25% | eGFR<60 ml/min/1.73 m2 (CKD-EPI) or AER≥30 mg/d; 20% | Age, gender, BMI, waist circumference, HTN, smoking, Met Sy | IPD [22] |
| Francque [33] | Hospital; n = 230; mean age 48 y; male 37%; Asian 0% | Smokers 25%; DM 0%; HTN 50%; Mean BMI 39 kg/m2; Met Sy 47% | HistologyNAFLD 100%NASH 52% | eGFR<60 ml/min/1.73 m2 (CKD-EPI) or overt proteinuria (>300 mg/d); 9% | Age, BMI, HTN, waist circumference, smoking, Met Sy | IPD [22] |
| Machado [34] | Hospital; n = 144; mean age 42 y; male 16%; Asian 0% | Smokers 28%; DM 26%; HTN 54%; Mean BMI 46 kg/m2; Met Sy 48% | HistologyNAFLD 100%NASH 25% | eGFR<60 ml/min/1.73 m2 (CKD-EPI); 6% | Age, AST, GGT, OSAS, BMI, waist circumference, HTN, smoking, Met Sy | IPD [22] |
| Kim [35] | Hospital; n = 96; mean age 39 y; male 71%; Asian 100% | Smokers 31%; DM 0%; HTN 54%; Mean BMI 28.5 kg/m2; Met Sy 56% | HistologyNAFLD 100%NASH 56% | eGFR<60 ml/min/1.73 m2 (modified MDRD) or morning dipstick proteinuria ≥1+; 25% | Age, BMI, HTN waist circumference, smoking, Met Sy, dyslipidaemia | IPD [22] |
| Targher Diabetologia [36] | Population; n = 2,103; mean age 61 y; male 62%; Asian 0% | Smokers 23%; DM 100%; HTN 66%; Mean BMI 27 kg/m2; Met Sy 52% | Ultrasound;67% | eGFR<60 ml/min/1.73 m2 (MDRD) or ACR≥30 mg/g; 13.5% | Age, gender, BMI, waist circumference, HTN, smoking, LDL.C, Tg, DM duration, HbA1c, medications, microalbuminuria, retinopathy | AD [22] |
| Casoinic [37] | Hospital; n = 145; mean age 61 y; male 59%; Asian 0% | Smokers 28%; DM 100%; HTN 55%; Mean BMI 28 kg/m2; Met Sy 80% | Ultrasound;51% | eGFR<60 ml/min/1.73 m2 (CKD-EPI) or ACR 30–300 mg/g; 10% | Age, gender, C-reactive protein | AD [21(p)] |
| Hwang [38] | Population; n = 1,361; mean age 48 y; male 71%; Asian 100% | Smokers 43%; DM 30%; HTN 15%; Mean BMI 25 kg/m2; Met Sy 21% | Ultrasound;43% | eGFR<60 ml/min/1.73 m2 (CKD-EPI) or ACR 30–300 mg/g; 16% | Age, gender, BMI, waist circumference, Tg, LDL-C, AST, ALT, GGT, HOMA,HTN, HbA1c, smoking, Met Sy | AD [22] |
| Targher Diab Med [39] | Hospital; n = 343; mean age 44 y; male 45%; Asian 0% | Smokers 23%; DM 100%; HTN 43%; Mean BMI 24 kg/m2; Met Sy 46% | Ultrasound;53% | eGFR<60 ml/min/1.73 m2 (MDRD) or ACR≥30 mg/g; 40% | Age, gender, BMI, physical activity, family history of CVD, sys BP, Tg, HDL-C, smoking, DM duration, HbA1c, medications, microalbuminuria, eGFR | AD [22] |
| Sirota [40] | Population; n = 11,469; mean age 42 y; male 45%; Asian 3.6% | Smokers 24%; DM 7%; HTN 25%; Mean BMI 25 kg/m2; Met Sy 28% | Ultrasound;36% | eGFR<60 ml/min/1.73 m2 (MDRD) or ACR≥30 mg/g; 25% | Age, gender, race, HTN, DM, sys BP, waist circumference, Tg, HDL-C, HOMA | AD [21(g)] |
| Li [41] | Population; n = 1,412; mean age 43 y; male 64%; Asian 100% | Smokers 42%; DM 0%; HTN 17%; Mean BMI 24 kg/m2; Met Sy 11% | Ultrasound;33% | eGFR<60 ml/min/1.73 m2 (CKD-EPI) or morning dipstick proteinuria ≥1+; 5% | Age, gender, BMI, alcohol intake, smoking, sleep quality, physical activity, BP, Tg, cholesterol, Met Sy, AST, ALT | IPD [20(s, t)] |
| Armstrong [42] | Population; n = 146; mean age 57 y; male 38%; Asian 5% | Smokers NA; DM 0%; HTN 36%; Mean BMI 28.8 kg/m2; Met Sy NA | Ultrasound;50% | eGFR<60 ml/min/1.73 m2 (CKD-EPI); 25% | BMI, HTN | IPD [22] |
| Xia [43] | Population; n = 1,141; mean age 62 y; male 43%; Asian 100% | Smokers 15%; DM 19%; HTN 38%; Mean BMI 24 kg/m2; Met Sy 32% | Ultrasound;41% | eGFR<60 ml/min/1.73 m2 (MDRD) or ACR>30 mg/g; 12% | Age, BMI, smoking, HTN, Met Sy, uric acid | IPD [22] |
| Ahn [44] | Populatiion; n = 1,706; mean age 58 y; male 55%; Asian 100% | Smokers 15%; DM 9%; HTN 38%; Mean BMI 24 kg/m2; Met Sy 26% | Ultrasound;32% | eGFR<60 ml/min/1.73 m2 (MDRD) or morning dipstick proteinuria ≥1+; 25% | Age, gender, BMI, smoking, waist circumference, AST, ALT, GGT, HTN, high TG, low HDL-C, DM | AD [21(v)] |
| Anjaneya [45] | Hospital; n = 200; mean age 50 y; male 50%; Asian 100% | Smokers 17%; DM 0%; HTN 32%; Mean BMI 23 kg/m2; Met Sy 22% | Ultrasound;50% | eGFR<60 ml/min/1.73 m2 (MDRD) or AER 30–300 mg/d; 47% | No adjustment | AD [20(p, s)] |
| Targher NMCD 2010 [46] | Population; n = 13,188; mean age 43 y; male 47%; Asian 4% | Smokers 24%; DM 8%; HTN 28%; Mean BMI 25 kg/m2; Met Sy 27% | Liver enzyme (GGT) elevation;10% | eGFR<60 ml/min/1.73 m2 (MDRD) or ACR≥30 mg/d; 14% | Age, gender, ethnicity, smoking, HTN, DM, lipid-lowering medications, BMI, waist circumference, fasting plasma glucose, total cholesterol, LDL-C, HDL-C, Tg, AST, ALT, alcohol intake, HOMA | AD [22] |
Studies with different definitions of NAFLD (histology, imaging, liver enzyme elevation) were analyzed separately and are grouped together.
Asian ethnicity was defined by birth within boundaries delineated West by the Red Sea, the Suez Canal, the Dardanelles strait, the Bosphorus the Caucasus and the Urals and East by the Bering Sea, the Japan and Indonesian archipelagos.
Modified 25-item STROBE score, with the item(s) not satisfied by the study indicated in parentheses: (a) title and abstract informative and balanced; (b) background/rationale stated in the introduction; (c) objective(s) specified in the introduction; (d) study design correctly and presented early in the paper; (e) setting, locations, and relevant dates described; (f) eligibility criteria, methods of selection, and follow-up described; (g) diagnostic criteria, outcomes, exposures, predictors, potential confounders, and effect modifiers for all variables clearly defined. Specifically, regarding the definition of NAFLD: for radiological assessment: radiological exam performed by radiologists blinded to clinical data and following pre-specified, standardized criteria to detect steatosis; for histological assessment of NAFLD: adequate biopsy specimen (fragment length ≥1.5 cm with >6 portal tracts) and liver biopsy processed and scored by blinded pathologist according to standard criteria; (h) sources of data and details of methods of measurement given for each variable of interest; (i) any efforts to address potential sources of bias described; (j) how the study size was arrived at clearly explained; (k) how quantitative variables were handled in the analyses clearly explained; (l) all statistical methods, how missing data and loss to follow-up were addressed, any sensitivity analyses clearly described; (m) numbers of individuals at each stage of study reported; (n) characteristics of study participants, number of participants with missing data, average, and total follow-up time clearly described; (o) outcome events or summary measures over time reported; (p) unadjusted and confounder-adjusted estimates and their precision (e.g., 95% CI) reported; (q) analyses of subgroups and interactions, and sensitivity analyses reported; (r) key results with reference to study objectives summarised; (s) limitations of the study discussed; (t) cautious overall interpretation of results given; (u) generalizability (external validity) of the study results discussed; (v) source of funding and role of the funders described.
ACR, albumin-to-creatinine ratio; AER, albumin excretion rate; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BP, blood pressure; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; DM, diabetes mellitus; GGT, gamma-glutamyltransferase; HDL-C, high density lipoprotein cholesterol; HTN, hypertension; LDL-C, low density lipoprotein cholesterol; MELD, model for end-stage liver disease; Met Sy, metabolic syndrome; NA, not available; OSAS, obstructive sleep apnoea; Tg, triglycerides.