Association of Serum Bilirubin Levels With Histopathological Severity of Diabetic Nephropathy in Patients With Type 2 Diabetes: A Cross-Sectional Biopsy Study.
Prior studies have suggested that serum total bilirubin (TBil) may be linked to diabetic nephropathy (DN); however, its potential relationship with structural renal injury in histopathology has not been well defined.
The objective of the study is to explore whether physiological levels of TBil are associated with the severity of renal pathological changes in individuals with Type 2 diabetes mellitus (T2DM) and biopsy-confirmed DN.
A cross-sectional cohort of 401 individuals with T2DM and biopsy-confirmed DN was included. DN severity was determined according to the Renal Pathology Society classification and categorized as early-stage DN (Classes I-II) or advanced DN (Classes III-IV). Multivariable logistic regression was used to evaluate the association between TBil and advanced DN. TBil quartiles, restricted cubic spline modeling, subgroup and sensitivity analyses, and receiver operating characteristic curve analysis were also performed.
Among 401 biopsy-confirmed DN patients, 258 (64.3%) were classified as having advanced DN. In multivariable models, higher TBil levels were independently associated with lower odds of advanced DN after full adjustment (OR = 0.882, 95% CI 0.827-0.941; p < 0.001). When TBil was analyzed by quartiles, individuals in the highest quartile exhibited significantly lower odds of advanced-stage disease relative to those in the lowest quartile in the fully adjusted model (OR = 0.331, 95% CI 0.153-0.718; p = 0.005), with a notable dose-response pattern across quartiles (p for trend = 0.003). Restricted cubic spline analyses confirmed an inverse association between TBil levels and advanced DN. Receiver operating characteristic curve analysis identified a TBil cutoff of 9.9 μmol/L for discriminating advanced DN, with an area under the curve of 0.684. The results were broadly consistent across subgroup and sensitivity analyses.
Higher physiological TBil levels were linked to lower histopathological severity of DN in patients with Type 2 diabetes.
The objective of the study is to explore whether physiological levels of TBil are associated with the severity of renal pathological changes in individuals with Type 2 diabetes mellitus (T2DM) and biopsy-confirmed DN.
A cross-sectional cohort of 401 individuals with T2DM and biopsy-confirmed DN was included. DN severity was determined according to the Renal Pathology Society classification and categorized as early-stage DN (Classes I-II) or advanced DN (Classes III-IV). Multivariable logistic regression was used to evaluate the association between TBil and advanced DN. TBil quartiles, restricted cubic spline modeling, subgroup and sensitivity analyses, and receiver operating characteristic curve analysis were also performed.
Among 401 biopsy-confirmed DN patients, 258 (64.3%) were classified as having advanced DN. In multivariable models, higher TBil levels were independently associated with lower odds of advanced DN after full adjustment (OR = 0.882, 95% CI 0.827-0.941; p < 0.001). When TBil was analyzed by quartiles, individuals in the highest quartile exhibited significantly lower odds of advanced-stage disease relative to those in the lowest quartile in the fully adjusted model (OR = 0.331, 95% CI 0.153-0.718; p = 0.005), with a notable dose-response pattern across quartiles (p for trend = 0.003). Restricted cubic spline analyses confirmed an inverse association between TBil levels and advanced DN. Receiver operating characteristic curve analysis identified a TBil cutoff of 9.9 μmol/L for discriminating advanced DN, with an area under the curve of 0.684. The results were broadly consistent across subgroup and sensitivity analyses.
Higher physiological TBil levels were linked to lower histopathological severity of DN in patients with Type 2 diabetes.