To the best of our knowledge, this study is the first study in Ethiopia to assess serum bilirubin and its correlation with estimated glomerular filtration rate in the progression of chronic kidney disease among CKD patients on follow-up. Overall, 140 study participants were involved in the current study. This study showed that serum total bilirubin was significantly positively correlated with eGFR (r = 0.868, P < 0.001) amongst CKD patients. In this subject, direct bilirubin was also positively correlated with eGFR (r = 0.641, P < 0.001).
Consistent with the present study, a finding from the United Kingdom showed a strong positive correlation between serum total bilirubin and eGFR values in CKD patients (r = 0.92, P < 0.0001). Additionally, their study also found a statistically significant positive correlation (r = 0.76, P < 0.0001) between direct bilirubin and eGFR (20).
A study in Tokyo, Japan is also consistent with recent findings, showing that serum total bilirubin and indirect bilirubin, respectively, were positively correlated with eGFR values (r = 0.223, P = 0.013; r = 0.244, P = 0.007) (19).
Another supporting finding from Korea also showed a positive correlation between serum total bilirubin concentration and eGFR in all subjects (r = 0.128, P = 0.001) (21). Likewise, studies conducted in Japan agree with this finding and show a weak positive correlation between direct serum bilirubin and eGFR (r = 0.181, P < 0.001) amongst the study participants (33).
In our study the value of eGFR was positively associated (β = 0.04, P = < 0.001) with serum total bilirubin. Statistically, this can be explained as a one-unit increase in eGFR results in approximately a 0.04 increase in serum total bilirubin in CKD patients. When the stage of CKD is increasing, the value of serum bilirubin (both TB&DB) is decreasing. Therefore, patients with lower eGFR or advanced CKD had lower mean serum bilirubin. Therefore, patients with lower eGFR or advanced CKD had lower mean serum bilirubin.
Consistent with this finding, a study from China found that serum bilirubin was significantly and independently associated with eGFR values (β = 0.011, P = 0.001) (33). This fact shows that CKD patients with low eGFR value or advanced stage of CKD have lower serum bilirubin than near normal eGFR value. The proposed mechanism is that serum bilirubin inhibits the upregulation of endothelial adhesion molecules and also has anti-complement properties that prevent inflammation, the development of atherosclerosis, and the onset/progression of CKD (34).
Similarly, study from the British Journal of Biomedical Sciences also support this finding. According to this result, serum total bilirubin levels showed significant positive association (R2 = 0.90, P < 0.05) with eGFR value. This can be explained as, holding other explanatory variables constant, the 90% variability in eGFR is determined by serum total bilirubin levels and thus serum level of total bilirubin is an independent predictors of eGFR values in renal diseases (20).
Another study in Tokyo is consistent with the current findings. According to their study, patients with CKD stage-V had significantly lower median serum bilirubin values (0.3mg/dL, P < 0.01) than in those with CKD stage III-IV (0.4 mg/dL, P < 0.01) among the study population(35).
In this study, body mass index was significantly negatively correlated with serum total bilirubin (r=-0.221, P = 0.09). BMI was also negatively correlated with direct bilirubin (r=-0.233, P = 0.006) amongst the study participants. In addition, this study showed that BMI was significantly negatively correlated with total serum bilirubin in CKD subjects (β-0.007, P = 0.023).
Consistent with the current findings, the Slovenian study reported a significant negative correlation between body mass index and total serum bilirubin (r=–0.287, P = 0.013) (36). Similarly, another study from Slovenia agreed with this finding and showed that BMI was significantly associated with (β=-0.436, P < 0.05) and serum total bilirubin (37).
A study in Italy was also consistent with the current findings and suggested that BMI was inversely correlated with total serum bilirubin (β=-0.08, P = 0.001) (38). The proposed mechanism is that overexpression of heme oxygenase 1 (HO 1) leads to a marked increase in adiponectin, an anti-inflammatory adipokine. Overexpressed HO-1 also inhibits adipocyte expansion and levels of inflammatory cytokines TNF-α, IL-1β, and IL-6 in obese individuals (39).
Contrary to recent findings, the Japanese Medical School study found a negative correlation between serum total bilirubin concentration and eGFR value (β-0.186, P = 0.038). According to their findings, indirect bilirubin was also negatively correlated with eGFR values in CKD patients (β-0.196, P = 0.027) (19). This discrepancy in findings may be due to differences in the study population, as the study population at the Japanese medical school was only for type 1 diabetes.
Another conflicting finding was reported in Korea, showing that serum bilirubin was inversely correlated with eGFR values in both diabetic and non-diabetic CKD patients (β=-0.14, P < 0.001) (40). This difference may be due to differences in study design and study population. South Korea’s study design was a prospective observational study design with only stage-III and stage-IVCKD study population.