| Background and Objectives: Idiopathic membranous nephropathy (IMN) is thecommon form of primary nephrotic syndrome in adults. Since2000, there was noclinicopathologic study on the long-term prognosis of adult IMN patients withnephrotic-range proteinuria and declined renal function. The predictive value of pathologicvariables, clinical features, and the use of immunosuppressants on the renal survival in adultIMN has not been fully elucidated. Immunosuppression was expected to induce diseaseremission and reduce risk of progression to end-stage renal disease (ESRD) or death;however, no consensus has been reached on the efficacy and safety of immunosuppressants.Therefore, we sought to retrospectively analyze the long-term follow-up of the largest cohortof adult IMN patients from a single tertiary referral center in China. We included patientswho had nephrotic-range proteinuria and declined renal function. Besides, we performed asystematic review and meta-analysis of the efficacy and safety of immunosuppression foradult IMN with nephrotic-range proteinuria.Methods:(1) All adult IMN patients who were diagnosed by biopsy and referred to theDepartment of Nephropathy in the People’s Liberation Army General Hospital from2002to2011were evaluated for inclusion in this retrospective analysis. Only patients withnephrotic-range proteinuria and declined renal function were included. We examined thepathologic features and clinical variables at the time of renal biopsy and the variousimmunosuppressants used during follow-up to determine their independent value inpredicting the decline in renal function and progression to ESRD.(2) The Cochrane CenterRegister of Controlled Trials (CENTRAL), PubMed, EMBASE, Chinese Database, andClinical Trials Registries (Clinicaltrials.gov and World Health Organization Clinical TrialsRegistry Platform)(June2012) were searched to identify randomized controlled trials (RCT)investigating the effect of immunosuppression on adults with IMN and nephrotic-range proteinuria. The primary outcomes were all-cause mortality or risk of progression to ESRD.The secondary outcomes were complete or partial remission, proteinuria, and adverse eventsleading to withdrawals or hospitalizations.Results:(1) A total of129adult IMN patients with nephrotic-range proteinuria anddeclined renal function were included. Median follow-up was34(18-53) months。The5-year renal survival (avoiding the progression to ESRD) was82%. Age at baseline (≥60years of old) and the presence of focal segmental glomerulosclerosis (FSGS) and moderateto severe tubulointerstitial lesions (involving≥25%of renal cortex, T1+T2) wereindependent risk factors of the decline in renal function. Chronic kidney disease (CKD)stages3-4at baseline and the presence of FSGS and T1+T2were independent risk factors ofthe progression to ESRD.(2) A total of36trials (1762patients) were included in thissystematic review and meta-analysis. Corticosteroids combined with alkylating agentssignificantly reduced all-cause mortality or the risk of progression to ESRD and improvedcomplete or partial remission but inevitably resulted in more withdrawals or hospitalizations.Among alkylating agents, cyclophosphamide was safer than chlorambucil. The superiorityof cyclosporine or mycophenolate mofetil plus corticosteroids over alkylating agents pluscorticosteroids was not identified, but the above conclusion was based on four small RCTsonly, totaling <150patients. Tacrolimus and adrenocorticotropic hormone significantlyreduced proteinuria.Conclusions: This retrospective analysis showed that CKD stages3-4at baseline andthe presence of FSGS and T1+T2were independent risk factors of the decline in renalfunction and (or) the progression to ESRD in adult IMN patients with nephrotic-rangeproteinuria and declined renal function. The systematic review and meta-analysis suggestedthat alkylating agents plus corticosteroids had short-term and long-term benefits for adultIMN patients with nephrotic-range proteinuria, but resulted in more withdrawals orhospitalizations. |
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