Changes In Practice Pattern,Therapeutic Efficacy And Outcomes In Chinese Patients With Lupus Nephritis From 1994 To 2010

Lupus nephritis(LN),which affects over half of systemic lupus erythematosus(SLE),is associated with a poor outcome in patients with renal involvement.Up to 25 percent of LN patients will progress to end stage renal disease(ESRD)within 10 years after their diagnosis.Prompt management with effective immunosuppressive agents could control the disease activity and slow down the loss of renal function.In this regard,tremendous efforts have been made to develop more efficacious treatments over the decades.The initial introduction of cyclophosphamide(CTX)and mycophenolate mofetil(MMF)for LN treatment made a positive impact on this disease.Both medications are recommended for induction therapy of Class III and IV LN patients.A number of other regimens have also been assessed in clinical trials such as calcineurin inhibitors(CNIs),multi-target therapy(corticosteroids,MMF,and tacrolimus),and biologic agents.Advances in treatment regimens over the past decades have changed medical care for LN patients,but no previous study has quantified the impact of evolution of practice pattern on outcome.Research from the U.S.Renal Data System found that the rates of end-stage lupus nephritis stopped increasing between 1995 and 2010 and declined in the last decade.Since LN patient outcomes vary among different racial backgrounds and geographical regions,data from China is warranted.Therefore,we aimed to assess trends in therapeutic effects,and long-term outcomes of biopsy-proven LN patients admitted to the National Clinical Research Center of Kidney Diseases,Jinling Hospital from 1994 to 2010.Part I:Trends in Practice Pattern in Chinese Patients with Lupus Nephritis Objective:To evaluate the changes of patient characteristics,histological pattern and treatment modalities of Chinese lupus nephritis(LN)patients.Methods:Patients with biopsy-proven LN in the Nanjing Glomerulonephritis Registry at the National Clinical Research Center of Kidney Diseases from 1994 to 2010 were investigated.Patients were stratified in three groups according to the period of renal biopsy:1994-1998,1999-2004,and 2005-2010.Patient characteristics at renal biopsy and histological pattern were compared between groups.Changes in treatment pattern were analyzed in different pathologic classifications.Results:A total of 1945 LN patients were included in the analysis(182 from 1994-1998,584 from 1999-2004,1179 from 2005-2010).The SLE duration and LN duration before renal biopsy was shorter in the later periods.LN patients in the earlier periods had higher values of serum creatinine and higher rates of high chronicity index at biopsy,while the patients in the later study periods presented with higher levels of SLE-DAI,proteinuria,urine RBC and lower levels of C3 and C4.More therapeutic options had emerged from 1994 to 2010.Among proliferative LN patients,the proportion of patients who received CTX increased from 28.5%in 1994-1998 to 35.4%in 1999-2004,and then decreased to 25.6%in 2005-2010(P for trend=0.014).CTX was still one of the main induction therapies in 2005-2010.The use of MMF increased from 15.6%to 25.4%in 2005-2010(P fortrend=0.001)and the use of multi-target therapy increased from 0%to 25.5%(P for trend<0.001).The rates of Tripterygium wilfordii(TW)combined with corticosteroids decreased from 40.4%to 14.5%(P for trend<0.001).The treatment pattern in class II and class V LN patients remain unchanged.The use of angiotensin converting enzyme inhibitors(ACEI)or angiotensin receptor blockers(ARB)increased significantly in proliferative LN and class V LN patients.Conclusion:From 1994 to 2010,chronic disease and late conditions were more common in the earlier periods while the manifestations were more active in the later periods.More LN patients received early diagnosis and early management.More evidence-based LN therapies in clinical practice were used in China.Great improvement in treatment patterns have been made among proliferative LN patients.Part II:Trends in Therapeutic Efficacy and Outcomes in Chinese Patients with Lupus NephritisObjective:To evaluate the trends of therapeutic efficacy and outcomes in Chinese patients with lupus nephritis(LN).Methods:Patients with biopsy-proven LN in the Nanjing Glomerulonephritis Registry were investigated.Patients were stratified in three groups according to the period of renal biopsy:1994-1998,1999-2004,and 2005-2010.Treatment response,renal relapse,and renal outcome were compared.Results:From 1994 to 2010,the cumulative probability of overall response(complete remission or partial remission)at 6 months increased from 33.6%to 75.7%(HR 3.00,95%CI 2.44-3.67,P for trend<0.001).The cumulative probability of complete remission increased from 10.3%to 25.1%(HR 2.92,95%CI 2.26-3.76,P for trend<0.001).The overall rate of renal relapse decreased from 62.3%to 39.3%.The hazard ratios for renal relapse decreased over time(1999-2005 vs.1994-1998 HR 0.88,95%CI 0.67-1.16;2005-2010 vs.1994-1998 HR 0.72,95%CI 0.55-0.95;P for trend=0.01).The 5-year renal survival rates were 92.6%,90.6%and 94.3%;the 10-year renal survival rates were 81.7%,86.2%and 89.3%,respectively.In the COX regression model with time dependent virables,no significant difference in renal otcome was found between 1994-1998 and 1999-2004 within 10 years.Before 4.5 years,no significant difference in renal outcome was found between 1999-2004 and 2005-2010;however,the hazard ratios(HRs)for ESRD began to decrease after 4.5 years.The HRs for ESRD at 5 years was 0.71(95%Cl 0.29-1.73,1994-1998 vs.1999-2004[reference])and 0.44(95%CI 0.20-0.93,2005-2010 vs.1999-2004[reference]).The HRs for ESRD at 10 years was 1.13(95%CI 0.41-4.19)and 0.13(95%CI 0.04-0.44),respectively.The risk of ESRD decreased after 4.5 years.In the subgroup analysis,there were no changes in response rates,relapse rates and hazard ratios for ESRD among male patients.Conclusions:From 1994 to 2005,increases in response rate were observed in Chinese LN patients.Meanwhile,renal relapse decreased and long-term renal survival increased.We should pay more attention to male LN patients.The optimistic trends in patient outcomes encourage the application of more evidence-based LN therapies in clinical practice in China.