Association between outcomes at follow-up (dependent variables) and the percentage of total daily caloric intake from dinner in multiple logistic regression models.

<p>Association between outcomes at follow-up (dependent variables) and the percentage of total daily caloric intake from dinner in multiple logistic regression models.</p

Characteristics at follow-up by the percentage of total daily caloric intake from dinner.

<p>Characteristics at follow-up by the percentage of total daily caloric intake from dinner.</p

Baseline lifestyle and dietary characteristics by the percentage of total daily caloric intake from dinner.

<p>Baseline lifestyle and dietary characteristics by the percentage of total daily caloric intake from dinner.</p

Baseline clinical and laboratory characteristics by the percentage of total daily caloric intake from dinner.

<p>Baseline clinical and laboratory characteristics by the percentage of total daily caloric intake from dinner.</p

Adjusted effect estimates for non-alcoholic fatty liver disease, non-alcoholic steato-hepatitis, advanced (stage F3) fibrosis and prevalent/incident chronic kidney disease, based on individual participant data meta-analysis from 20 studies (29,282 participants).

<p>Data from all studies providing IPD were pooled together into a single dataset and effect estimates were calculated using multivariate logistic regression (cross-sectional studies) or Cox proportional hazard models (longitudinal studies). In these models, studies were incorporated as cluster and treated as random-effect, while covariates were treated as fixed-effect. The individual patient covariates entered in the models were: age, BMI, metabolic syndrome, hypertension, smoking status, diabetes, ethnicity (Asian versus non-Asian population), presence of cirrhosis, waist circumference, HOMA-IR index, duration of follow-up (for longitudinal studies). Finally, a fully adjusted model was run, with all covariates entered.</p><p>HTN, hypertension; Met Sy, metabolic syndrome; waist, waist circumference.</p>a<p>For continuous variables, median (range) of values is reported.</p>b<p>All cirrhotic individuals derive from the study by Park et al. <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001680#pmed.1001680-Park1" target="_blank">[30]</a>.</p

Cross-sectional studies connecting NAFLD to chronic kidney disease included in the meta-analysis.

<p>Studies with different definitions of NAFLD (histology, imaging, liver enzyme elevation) were analyzed separately and are grouped together.</p>a<p>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.</p>b<p>Modified 25-item <b>STROBE score</b>, 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.</p><p>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.</p

Forest plot of comparison.

<p>NAFLD versus non-NAFLD, outcome: incident chronic kidney disease in prospective studies. NAFLD was defined by imaging, histology, or liver enzyme elevation. Studies assessing NAFLD by imaging, histology, or liver enzyme elevation were considered separately.</p

Results of subgroup analysis for the outcome: chronic kidney disease.

<p>Subgroup analysis was planned a priori to assess the impact of the following items on the association between NAFLD and CKD: (1) Fulfilment of STROBE items: we planned to repeat the analysis after excluding studies not fulfilling each STROBE item (different STROBE items are described in footnote to <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001680#pmed-1001680-t001" target="_blank">Table 1</a>). (2) Diabetes: studies including exclusively non-diabetic individuals versus studies including diabetic individuals. (3) Studies simultaneously adjusting versus studies not adjusting for all the following risk factors for CKD: age and BMI and metabolic syndrome (overall or each of its components) and hypertension and smoking. (4) Study design (population-based versus community-based). (5) Ethnicity (Caucasian versus Asian). (6) Studies including only non-cirrhotic patients versus studies including cirrhotic patients. (7) Studies using the CKD-EPI versus studies using the MDRD equation to estimate GFR. (8) Outcomes related to CKD: studies assessing both eGFR and proteinuria versus studies assessing either eGFR or proteinuria. (9) Type of data available: studies with IPD versus studies with AD.</p

Longitudinal studies connecting NAFLD to chronic kidney disease included in the meta-analysis.

<p>Studies with different definitions of NAFLD (histology, imaging, liver enzyme elevation) were analyzed separately and are grouped together.</p>a<p>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.</p>b<p>Modified 25-item <b>STROBE score</b>, 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.</p><p>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.</p

Flow of study selection.

<p>STROBE score of included studies is provided as median (range).</p