High FIB4 index is an independent risk factor of diabetic kidney disease in type 2 diabetes

Abstract

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) may be linked to development of chronic kidney diseases (CKD). The FIB4 index, a noninvasive liver fibrosis score, has been reported to predict CKD in non-diabetic patients, but there are no reports yet in diabetic cases. Therefore, we evaluated the prognostic impact of FIB4 index on the risk of developing diabetic kidney disease (DKD) in Japanese patients with type 2 diabetes in a retrospective cohort study. We assessed patients with type 2 diabetes with an eGFR ≥ 60 mL/min/1.73 m² and without dipstick positive proteinuria (≥ 1 +) at their first visit to our department. Participants were divided into two groups based on the FIB4 index at their first visit: FIB4 index > 1.3 and FIB4 index ≤ 1.3. The primary endpoint was defined as a decrease in eGFR < 60 mL/min/1.73 m² or the onset of proteinuria during the course of treatment. The average age of all 584 type 2 diabetic participants (360 [61.6%] men) was 55 ± 11 years. There were 187 patients in the FIB4 index group > 1.3 (32.0%) and the median observation period was 6.0 (3.8-11.0) years. Kaplan-Meier survival analysis indicated that the risks of developing DKD, eGFR < 60 and proteinuria were all higher in FIB4 index > 1.3 patients than in FIB4 ≤ 1.3 patients. In the Cox regression analysis, an FIB4 index > 1.3 was a significant predictor for onset of DKD (HR 1.54, 95% CI 1.15-2.08) and proteinuria (HR 1.55, 95% CI 1.08-2.23), but not for an eGFR < 60 (HR 1.14, 95% CI 0.79-1.99). To the best of our knowledge, this is the first study to demonstrate that an FIB4 index > 1.3 has a prognostic impact on the development of CKD and proteinuria in type 2 diabetic patients. This warrants further investigation of the prognostic impact of the development of DKD or proteinuria.

Figure 1

Flow chart for study recruitment. Total of 1197 patients with type 2 diabetes mellitus were selected from two Japanese centers on medical records. HBV hepatitis B virus hepatitis, HCV hepatitis C virus hepatitis. Patients diagnosed with liver cirrhosis and heavy drinker (consumption of ethanol less than 20 g/day for women and 30 g/day for men) had been excluded in advance.

Figure 2

Kaplan Meier curves for the development of (A) diabetic kidney disease (DKD: eGFR < 60 mL/min/1.73 m² or proteinuria), (B) eGFR < 60 mL/min/1.73 m², and (C) proteinuria in type 2 diabetic patients with FIB4 index > 1.3 (red lines) or ≤ 1.3 (blue lines).

Figure 3

Univariate and Cox proportional hazard ratios of FIB4 index > 1.3 for the development of (A) diabetic kidney disease (DKD: eGFR < 60 mL/min/1.73 m² or proteinuria), (B) eGFR < 60 mL/min/1.73 m², and (C) proteinuria in type 2 diabetic patients. Cox proportional hazard models were adjusted for age, sex, BMI, baseline HbA1c, baseline eGFR, smoking and drinking status (current or past), comorbidities (hypertension, dyslipidemia) and anti-diabetic and anti-hypertensive medications. 95% CI 95% confidence interval.

Figure 4

Cox proportional hazard ratios of FIB4 index > 1.3 for the development of (A) diabetic kidney disease (DKD: eGFR < 60 mL/min/1.73 m² or proteinuria), (B) eGFR < 60 mL/min/1.73 m², and (C) proteinuria in type 2 diabetic patients. Cox proportional hazard models were adjusted for age, sex, BMI, a HbA1c time dependent covariate, baseline eGFR, smoking and drinking status (current or past), comorbidities (hypertension, dyslipidemia) and anti-diabetic and anti-hypertensive medications. 95% CI 95% confidence interval. N = 312.

Figure 5

Time dependent receiver operating characteristic curve (ROC) analysis of FIB4 index for development of DKD, eGFR and proteinuria. Models included with or without FIB4 index were anlyzed by area under the curve (AUC) of ROC analysis. Model covariants except FIB4 index included age, sex, BMI, baseline HbA1c, baseline eGFR, smoking and drinking status (current or past), comorbidities (hypertension, dyslipidemia) and anti-diabetic and anti-hypertensive medications. P values were for comparisons between model with or without FIB4 index.