Summary of study outcomes (n=3)
| Study | Chinnadurai et al40 | Jang et al41 | Paik et al42 |
| Primary outcomes and definition | 1. ESRD: commencement of RRT or eGFR <10 mL/min/1.73 m2 | 1. CKD progression: average annual percent change in eGFR from baseline | 1. All-cause mortality |
| 2. CKD progression: rate of change of eGFR from baseline to study end-point | 2. Cardiovascular-related mortality: death due to heart diseases (ICD-10: I00-I09, I11, I13, I20-I51) and cerebrovascular diseases (ICD-10: I60-I69) | ||
| 3. NFCVE: composite of ACS, non-fatal MIs, non-fatal cardiac arrest, coronary revascularisation, new diagnosis CCF/admission with exacerbation of CCF, new diagnosis of PVD, CVAs | |||
| 4. All-cause mortality | |||
| 5. Cardiovascular-related mortality: Ia cause of death was due to cardiac event, CVA, CCF or PVD | |||
| Secondary outcomes and definition | None | 1. NAFLD severity according to NFS: high-intermediate (NFS ≥−1.455) and low probability (NFS <−1.455) of advanced fibrosis | 1. Presence of advanced liver fibrosis: ≥1 of the following fibrosis markers—APRI>1, FIB-4 score >2.67 or NFS>0.676 |
| 2. Severity of CKD at baseline: eGFR ≥45 vs <45 mL/min/1.73 m2 (dividing stages 3a & 3b) | |||
| Cases | 1. ESRD: NAFLD n=26 (14.2%), no NAFLD n=134 (19.1%), p=0.07 | 1. Average annual percent change in eGFR from baseline: NAFLD −0.79% [−1.31 to −0.27], no NAFLD 0.30% [−0.14 to 0.76] | 1. All-cause mortality: NAFLD 54.7% (SE 3.6), no NAFLD 46.5% (SE 2.4), p<0.05 (age adjusted: NAFLD 31.0% [25.0–37.0], no NAFLD 25.9% [22.0–29.7], p=ns) |
| 2. CKD progression: NAFLD −2.54 [−7.61 to 0.31] mL/min/1.73 m2, no NAFLD −2.09 [−6.14 to 1.06] mL/min/1.73 m2 | 2. Average difference in % decline of eGFR per year NAFLD vs no NAFLD: | 2. Cardiovascular-related mortality: NAFLD 16.0% (SE 2.5), no NAFLD 16.2% (SE 1.7), p=ns (age adjusted: NAFLD 7.8% [3.7–11.9], no NAFLD 8.2% [5.6–10.9], p=ns) | |
| 3. NFCVE: NAFLD n=46 (25.1%), no NAFLD n=82 (12.3%), p<0.001 | (i) Adjusted for age, sex, year of visit: −1.09%[−1.77 to −0.41] | ||
| 4. All-cause mortality: NAFLD n=50 (27.3%), no NAFLD n=221 (33.0%), p=0.14 | (ii) Adjusted for all confounders: −1.06% [−1.73 to −0.38] | ||
| 5. Cardiovascular-related mortality: NAFLD n=10 (31.3%), no NAFLD n=67 (40.5%), p=0.36 | |||
| Risk of bias Newcastle-Ottawa Score (NOS) | Mortality NOS=8, non-fatal CVE NOS=8, CKD progression NOS=9 | NOS=9 | NOS=7 |
| Primary outcome results | 1. ESRD: total sample HR 0.99 [0.65–1.52], p=0.90; matched HR 0.64 [0.35–1.16], p=0.145 | Average difference in % decline of eGFR per year NAFLD vs no NAFLD: | 1. All-cause mortality: CKD+NAFLD+ vs no CKD/NAFLD adjusted HR 2.34 [1.91–2.87], CKD+NAFLD hour vs no CKD/NAFLD adjusted HR 2.08 [1.80–2.40], p=ns |
| 2. CKD progression: total sample p=0.09; matched p=0.58 | (i) Adjusted for age, sex, year of visit: p=0.002 | 2. Cardiovascular-related mortality: CKD+NAFLD+ vs no CKD/NAFLD adjusted HR 2.12 [1.44–3.13], CKD+NAFLD hour vs no CKD/NAFLD adjusted HR 2.43 [1.8–3.2], p=ns | |
| 3. NFCVE: total sample HR 2.07 [1.39–3.09], p<0.001; matched HR 1.85 [1.04–3.30], p=0.04 (multivariate: total sample HR 2.03 [1.33–3.13], p<0.001; matched HR 2.00 [1.10–3.66], p=0.02) | (ii) Adjusted for all confounders: p=0.002 | ||
| 4. All-cause mortality: total sample HR 0.79 [0.58–1.08], p=0.14; matched HR 0.88 [0.57–1.34], p=0.54 | |||
| 5. Cardiovascular-related mortality: HR not published | |||
| Secondary outcome results | None | 1. Adjusted average difference in annual % change in eGFR: low NFS vs no NAFLD 0.01% [−0.74 to 0.99]; high-intermediate NFS vs no NAFLD −2.12% [−2.93 to −1.31], p<0.0001 | 1. CKD+NAFLD+ advanced fibrosis (n=60) All-cause mortality: 73.1% [50.7–95.5], p=ns vs no advanced fibrosis; adjusted HR 3.49 [2.25–5.43], p=ns vs no advanced fibrosis Cardiovascular-related mortality: 14.6% [1.6–27.7], p=ns vs no advanced fibrosis; adjusted HR 2.83 [0.69–11.51], p=ns vs no advanced fibrosis |
| 2. Adjusted average difference in annual % change in eGFR among patients with eGFR <45 mL/min/1.73 m2 at baseline for patients with NAFLD vs those without: −5.61% [−11.43 to 0.59], p=0.075. | 2. CKD+NAFLD+ no advanced fibrosis (n=97) All-cause mortality: 52.1% [44.8–59.3]; adjusted HR 2.51 [1.98–3.18] Cardiovascular-related mortality: 16.5% [11.1–21.9]; adjusted HR 2.45 [1.61–3.73] |
95% CIs are shown in square brackets.
ACS, acute coronary syndrome; APRI, AST to platelet ratio index; CCF, congestive cardiac failure; CKD, chronic kidney disease; CVA, cerebrovascular accident; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; FIB-4, fibrosis-4; ICD, International Classification of Diseases; MI, myocardial infarction; NAFLD, non-alcoholic fatty liver disease; NFCVE, non-fatal cardiovascular event; NFS, NAFLD fibrosis score; PVD, peripheral vascular disease; RRT, renal replacement therapy; SE, standard error.