| ObjectiveIgA nephropathy(IgAN)is not only a common primary glomerular disease in China,but also a common renal disease all over the world.It is one of the main diseases causing renal failure.According to statistics,approximately 30%-40%of IgAN patients will develop progressive renal function decline within 20 years after diagnosis,resulting in end-stage renal disease(ESRD),requiring renal dialysis or kidney transplantation.The incidence of IgAN is significantly different in different regions,and the incidence in Asian population is significantly higher than that in white and black population.In addition,the therapeutic effect and prognosis of different individuals are significantly different.IgAN not only brings huge economic and psychological burden to individuals and families,but also has a great impact on the development of society.Therefore,early diagnosis and treatment,and accurate judgement of disease progression are very important.The pathogenesis of IgAN is complex.The most widely accepted at present is"four-stroke theory",in which oxidative stress response plays an important role.As an endogenous metabolite of heme,bilirubin has powerful antioxidant,anti-inflamm atory and cell protective effects.Studies have shown that bilirubin may have renal protective function due to its unique biological character.The increase of bilirubin level may play a protective role in the development of IgAN and chronic kidney disease(CKD).However,studies conducted in the United States including adult population and outpatients showed that serum bilirubin was negatively correlated with estimated glomerular filtration rate(eGFR)and positively correlated with urinary protein excretion.It suggests that serum bilirubin may be a risk factor for the development of IgAN.In view of previous research results,the effect of bilirubin on IgAN is still uncertain.And there were few reports on the relationship between bilirubin and IgAN in the past.In this study,the clinicopathological characteristics and prognosis of IgAN patients with different serum total bilirubin levels were compared.We explore the relationship between serum total bilirubin and IgAN,so as to provide new theoretical basis and treatment ideas for clinical work.MethodsA total of 385 patients with primary IgAN diagnosed by renal biopsy in the Department of Nephrology,the First Affiliated Hospital of Zhengzhou University from May 1,2016 to May 31,2018 were enrolled in this study.General data,laboratory indicators,renal pathological indicators,and the last follow-up records were collected.Patients were divided into four groups according to the interquartile of baseline serum total bilirubin(TBIL)levels at renal biopsy.End-point evevts were defined as:① permanent eGFR<15ml/(min-1.73m2)and/or renal dialysis and/or renal transplantation and/or all-cause death;② eGFR decreased by more than 50%from baseline at renal biopsy.Follow-up was from the time of renal biopsy to the occurrence of the end-point events or to September 2021.The differences in clinicopathological characteristics and prognosis of the four groups were compared,and the correlations between TBIL and renal indicators were analyzed.The differences in renal survival rates of patients with different TBIL levels were compared.The effect of TBIL on renal outcomes was analyzed when TBIL was used as a continuous and grouped variable.Results1.Comparison of general data and laboratory indicators:① There were 385 IgAN patients in the study,including 200 males(51.9%)and 185 females(48.1%).②According to the interquartile of baseline serum total bilirubin levels at renal biopsy,the patients were divided into four groups:there were 95 cases in group Q1(TBIL<5.5μmol/L);there were 96 cases in group Q2(5.5μmol/L≤TBIL<7.6μmol/L);there were 97 cases in group Q3(7.6μmol/L≤TBIL<10.6μmol/L);there were 97 cases in group Q4(TBIL≥10.6μmol/L).There were statistical differences in ALT,serum calcium,serum phosphorus,blood urea nitrogen,serum creatinine,glomerular filtration rate,albumin,total cholesterol,24-hour urinary protein,urinary white blood cell count,the using rate of hormone/immunosuppressive ’gents,the using rate of RAAS inhibitors,and the incidence of end-point events among all groups(P<0.05).There were statistical differences in ALT between group Q1 and group Q3(P<0.05).There were statistical differences in blood calcium,albumin and the incidence of end-point events between group Q1 and group Q2,group Q1 and group Q3,group Q1 and group Q4(P<0.05).There were statistical differences in serum phosphorus,serum creatinine,glomerular filtration rate,24-hour urinary protein,the using rate of hormone/immunosuppressive agents and the using rate of RAAS inhibitors between group Q1 and group Q3,group Q1 and group Q4(P<0.05).There were statistical differences in blood urea nitrogen between group Q1 and group Q3,group Q1 and group Q4,group Q2 and group Q3,group Q2 and group Q4(P<0.05).There were statistical differences in total cholesterol between group Q1 and group Q4(P<0.05).There were no statistical differences in urinary white blood cell count between the four groups(P>0.05).Patients in the high level groups had higher using rate of RAAS inhibitors,lower using rate of hormone/immunosuppressive agents,lower incidence of end-point events and better clinical indicators.There were no statistical differences in age,sex,smoking,alcohol consumption,diabetes,cardiovascular disease,cerebrovascular disease,systolic blood pressure,diastolic blood pressure,mean arterial pressure,AST,fasting blood glucose,serum uric acid,triglyceride,high-density lipoprotein and urinary red blood cell count(P>0.05).2.Comparison of pathological indicators:there were statistical differences in glomerular segmental sclerosis or adhesion(S)and tubular atrophy/interstitial fibrosis(T)among all groups(P<0.05).There were statistical differences in T lesions between group Q1 and group Q4(P<0.05),the degree of T lesion in high level group was lighter than that in low level group.There were no statistical differences in S lesions among the four groups(P>0.05).There were no statistical differences in mesangial cell proliferation(M),endothelial cell proliferation(E),cellular or fibrous crescents(C)among all groups(P>0.05).3.Correlation between serum total bilirubin levels and renal indicators:① the baseline levels of blood urea nitrogen,serum creatinine and 24-hour urinary protein were significantly negatively correlated with the baseline levels of serum total bilirubin(r<0,P<0.05),the baseline levels of glomerular filtration rate and albumin were significantly positively correlated with the baseline levels of serum total bilirubin(r>0,P<0.05).②the last levels of serum creatinine and 24-hour urinary protein were significantly negatively correlated with the baseline levels of serum total bilirubin(r<0,P<0.05),the last levels of glomerular filtration rate and albumin were significantly positively correlated with the baseline levels of serum total bilirubin(r>0,P<0.05).4.Comparison of prognosis:At the end of follow-up,there were 56 patients(14.5%)entered the end-point events,and the cases of group Q1,group Q2,group Q3 and group Q4 were 36(37.9%),11(11.5%),6(6.2%)and 3(3.1%)respectively.With the increase of serum total bilirubin,the cumulative renal survival rate gradually increased,and the high level group was higher than that in the low level group,the differences were statistically significant(Log-rank P<0.05).5.Analysis of influencing factors of IgAN patients entering end-point events:①In univariate Cox regression analysis,Age,systolic blood pressure,diastolic blood pressure,mean arterial pressure,ALT,AST,blood phosphorus,blood urea nitrogen,serum creatinine,glomerular filtration rate,serum uric acid,24-hour urinary protein,TBIL(continuous variables),TBIL(grouped ariables),M1,T1,T2,C2,hormone/immunosuppressive agents,and RAAS inhibitors were all associated with the end-point events in IgAN patients(P<0.05).② In multivariate Cox regression analysis,when TBIL was used as a continuous or grouped variable,high level was an independent protective factor for IgAN patients entering the end-point events(P<0.05),and the protective factors remained after adjusting age,sex,systolic blood pressure,diastolic blood pressure,mean arterial pressure,ALT,AST,blood phosphorus,blood urea nitrogen,serum creatinine,glomerular filtration rate,serum uric acid,24-hour urinary protein,M,T,C,hormone/immunosuppressive agents,and RAAS inhibitors.Conclusions1.IgA nephropathy patients with higher total bilirubin levels had milder clinicopathological indicators and better renal outcomes.2.Serum total bilirubin is an independent protective factor for IgA nephropathy.It can predict better renal outcomes. |
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