Supplementary Material for: Increased Risk for Cardiovascular Events in Patients with Diabetic Kidney Disease and Non-Alcoholic Fatty Liver Disease

Background/Aims: Non-alcoholic fatty liver disease (NAFLD) is recognised to be a strong risk factor for causing cardiovascular disease (CVD) and chronic kidney disease (CKD), independent of the presence of diabetes mellitus. The association of NAFLD with outcomes in patients with diabetic kidney disease (DKD) has been variably reported. This study aimed to investigate the association of NAFLD with cardiovascular, renal outcomes and mortality in patients with advanced DKD (CKD 3–5, not on dialysis). Methods: This observational study was carried out on 192 patients with DKD within a cohort of 2,974 non-dialysis CKD patients, who had an ultrasound (US) of their liver done between January 2000 and end of December 2014. From these 192 patients, 149 patients (NAFLD 48 and normal US 101) were included for comparative analysis, as they had complete datasets. Patient demographics, comorbidities and blood results were collected at study baseline. Follow-up data on non-fatal cardiovascular events (NFCVE), mortality and serial estimated glomerular filtration rate (eGFR) was gathered until study end point. Cox-regression analysis was used to study the association of NAFLD with NFCVE and mortality, and linear regression analysis was used for the estimation of renal progression. Results: Median follow-up time was 69 months, similar in both groups (p = 0.09). Median eGFR was 31.6 mL/min/1.73 m2, with a median urine protein creatinine ratio of 46 g/mol. A total of 20 (41.7%) NFCVE were recorded in the NAFLD group compared to 14 (13.9%) in the normal US group. Multivariable Cox-regression analysis showed NAFLD as an independent risk factor (hazard ratio 2.95; 95% CI 1.31–6.60; p = 0.01) for NFCVE even after including all cardiovascular risks parameters that were significant in the univariable model. There was no significant difference in survival between the 2 groups over the follow-up period (log-rank test, p = 0.76). The overall rate of decline in eGFR was 3.46 mL/min/1.73 m2/year and this was not observed to be different between the groups (p = 0.65). Conclusion: In our cohort of patients with advanced DKD, NAFLD showed a strong independent association with cardiovascular outcomes. Further prospective studies are warranted to strengthen these associations and plan a strategy for screening NAFLD in this high-risk group.