Association between physiological serum total bilirubin concentrations and the progression of diabetic nephropathy

Abstract

Purpose: To analyze the relationship between physiological serum total bilirubin (STB) concentrations and the progression of diabetic nephropathy (DN).

Methods: The clinical features and pathological data of 159 patients with diabetic nephropathy confirmed by renal biopsy were retrospectively analyzed. They were divided into low bilirubin group (80 cases) and high bilirubin group (79 cases) according to the median of STB level. Clinical and pathological data of the two groups were collected and compared. The patients were followed up from the date of renal biopsy to June 30, 2024. Kaplan-Meier method and log-rank test was used to perform survival analysis. Univariate and multivariate Cox regression risk model were used to analyze the risk factors of diabetic nephropathy. A restricted cubic spline model was used to show the nonlinear association between STB and DN.

Results: When compared with physiologically high bilirubin group, patients in low bilirubin group might had higher level of serum creatinine, blood urea nitrogen, 24h urinary protein, urinary albumin to creatinine ratio (UACR), fibrinogen (Fib) and higher rate of K-W nodules, renal tubular atrophy, renal interstitial inflammation and lower level of eGFR, hemoglobin, PLT, suggesting that low bilirubin group had more severe indicators. Spearman correlation analysis showed that STB was positive associated with eGFR (r = 0.270, P < 0.001) while negative associated with serum BUN (r = -0.236, P = 0.003), serum creatinine(r=-0.256, P < 0.001), 24h urine protein(r = -0.257, P < 0.001), UACR (r = -0.287, P < 0.001) and Fib (r = -0.398, P < 0.001). The Kaplan Meier analysis revealed that high STB had a higher possibility of renal survival rate when compared with lower STB (P = 0.013). After univariate and multivariate Cox regression analysis, STB (HR = 0.445, P = 0.001), hemoglobin (HR = 0.983, P = 0.002), age (HR = 0.977,P = 0.033) and ACEI/ARB (HR = 0.340, P = 0.001) were independently protective factors for the DN progression, while serum creatinine (HR = 1.003, P =0.001), 24h urine protein (HR = 1.088, P = 0.005) and cholesterol (HR = 1.104, P = 0.002) were risk factors for DN progression. The restricted cubic spline model showed that there was a significant nonlinear association between DN progression and STB level when it was less than 6.085 µmol/L.

Conclusions: Our findings suggest that STB may serve as a potential biomarker for the progression of diabetic nephropathy. Lower STB levels may help identify high-risk patients who could benefit from earlier or more intensive interventions to slow disease progression.

Keywords: diabetic nephropathy; progression; restricted cubic spline; risk factor; serum total bilirubin.

Figure 1

Correlation between STB and renal function indicators calculated by Spearman association analysis. (a, STB was positive associated with eGFR; b, STB was negative associated with serum BUN; c, STB was negative associated with serum creatinine; d, STB was negative associated with 24h urine protein; e, STB was negative associated with urinary albumin to creatinine ratio; f, STB was negative associated with Fib).

Figure 2

The higher STB had a higher possibility of renal survival rate when compared with lower STB calculated by the Kaplan Meier analysis.

Figure 3

The independent protective factors and risk factors for the DN progression calculated by multivariate Cox regression.

Figure 4

Continuous association of STB with the DN progression by a restricted cubic spline. STB was independently associated with the DN progression when it less than 6.085mmol/L. The restricted cubic spline was plotted using five default knots. The P-value for the nonlinear association was 0.010.