Lower serum bilirubin is associated with poor renal outcome in IgA nephropathy patients

Abstract

Aims: IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis worldwide. We conducted this study to explore the relationship between serum bilirubin and renal outcome of patients with IgAN. Methods: A total of 1492 biopsy proven IgAN patients were recruited and divided into two groups according to their median serum bilirubin concentration: the low bilirubin group (serum bilirubin≤9.7umol/L, n=753) and high bilirubin group (serum bilirubin>9.7umol/L, n=739). Basic clinical characteristics were assessed at the time of renal biopsy and the relationships between serum bilirubin and the combined endpoints were analyzed. The combined endpoints were defined as a 50% decline in estimate glomerular filtration rate (e-GFR), end-stage kidney disease (ESKD), renal transplantation and/or death. In addition, propensity score matching (PSM) was then performed to improve balance and simulate randomization between patients in different groups. Kaplan-Meier survival analysis was applied to explore the role of serum bilirubin in the progression of IgAN. Three clinicopathological models of multivariate Cox regression analysis were established to evaluate the association of serum bilirubin and renal prognosis of IgAN. Results: During median 5-year follow-up period, significant differences were shown in Kaplan-Meier analysis. In the unmatched group, 189 (12.7%) patients progressed to the renal combined endpoints. Among this, 122 in 753 patients (16.2%) were in low bilirubin group and 67 in 739 patients (9.1%) were in high bilirubin group (p<0.001). After PSM, there were 134 (11.8%) patients reached the combined endpoints, which included 77 in 566 patients (14.6%) in low bilirubin group and 57 in 566 patients (10.1%) in high bilirubin group (p=0.039). The results of three models (including demographics, pathological, clinical indicators and serum bilirubin) demonstrated that a lower basic serum bilirubin level was significantly associated with a higher risk of reaching combined endpoints in IgAN patients both in unmatched and matched cohort. Conclusion: Serum bilirubin level may be negatively associated with the progression of IgAN.

Is serum hemoglobin level an independent prognostic factor for IgA nephropathy?: a systematic review and meta-analysis of observational cohort studies

“…Through full-text reviews, two conference abstracts, two duplicated data-contained articles, and two articles without enough data to estimate the HR were removed from the remaining 15 articles. Finally, we included nine studies with 10,006 patients [ 10 , 14–18 , 23–25 ] ( Figure 1 ).…”

“…In Table 1 , among the nine studies, eight were performed in Asian countries: China, Korea, and Japan [ 10 , 14–16 , 18 , 23–25 ], and one was performed in Western countries (Turkey) [ 17 ]. Six of the nine studies estimated the correlation between the decreasing Hb in serum and kidney disease progression in IgAN [ 14–18 , 23 ], in which the HR was calculated using continuous variables relative to 1 g/dL.…”

“…Six of the nine studies estimated the correlation between the decreasing Hb in serum and kidney disease progression in IgAN [ 14–18 , 23 ], in which the HR was calculated using continuous variables relative to 1 g/dL. As a dichotomous variable (defined as the below/above cutoff for anemia), the correlation between serum Hb and kidney disease progression in IgAN was investigated by six studies [ 10 , 15 , 18 , 23–25 ]. All included studies were considered high quality because of their NOS score >6 ( Supplementary file 2 ).…”

“…Two studies calculated the adjusted HR between serum Hb (as a dichotomous variable) and kidney disease progression in IgAN [ 10 , 15 ]. We also found a significant correlation between serum Hb and kidney disease progression in IgAN (HR = 1.65, 95% CI = 1.20–2.27) without evidence of heterogeneity (χ 2 = 0.01, I 2 = 0%) ( Figure 6 ).…”

Novel Function for Bilirubin as a Metabolic Signaling Molecule: Implications for Kidney Diseases

“…IgA nephropathy is a kidney disease due to excess buildup of IgA in the kidney, resulting in severe inflammation and glomerular injury. Low plasma bilirubin levels are associated with an increased incidence of ESKD and worse outcomes in patients with IgA nephropathy (77,78). In IgA vasculitis with nephritis, low plasma bilirubin is associated with greater progression of the disease (79).…”