Clinico-pathological Characteristics And Long-term Outcomes Of Adult Minimal Change Disease

Background and objectives:Minimal change disease(MCD)is a common cause of nephrotic syndrome in adult people.Recent studies revealed that a substantial proportion of adult patients with MCD continue to have disease flares,and medical problems after diagnosis are common.MCD is generally thought to have no changes in light microscopy,and extensive foot process effacement can be found in electron microscopy.However there can be global sclerotic glomeruli(GSG),tubulointerstitial and vascular changes in adult MCD,especially in the older,as a result of aging and chronic hypertension.The potential influences of these histological signs on MCD are rarely studied.We retrospectively investigated clinical and pathological features of adult MCD in our hospital,and explored risk factors for remission,relapse and long-term prognosis of MCD.Methods:We retrospectively studied patients(>18 years old)with first-presented nephrotic syndrome and biopsy-proven primary MCD,from January 1,2002 to December 31,2015,in our institution.Baseline clinical and pathological data were collected.The renal tubular atrophy(TA),interstitial fibrosis(IF),and interstitial inflammation(?)were graded according to the cortical area affected:absence(0%),mild(1%-25%),moderate(26%-50%),severe(>50%).Remission,relapse,drug side effects,renal survival and all-cause death were followed.Results:1.207 patients were enrolled.Average age at biopsy were 38.0(26.5-49.0)years old,proteinuria were 5.6(3.7-7.7)g/d,serum albumin were 19.7(17.2-23.1)g/1,serum creatine73.2(61.1-84.6)?mol/1,and estimated glomerular filtration rate(eGFR)were 103.7(90.9-115.1)ml/(min· 1.73 m2).48(23.2%)patients had hematuria,53(25.6%)had acute kidney injury(AKI).38(18.4%)had hypertension and 2(1.0%)had diabetes.Compared with the non-older group,the older MCD(?60 years old)had lower baseline eGFR,and were more likely to have AKI and hypertension(p<0.05).After 8 weeks of treatment,143(80.3%)MCD achieved complete remission,5(2.8%)achieved partial remission,30(16.9%)did not achieve either complete or partial remission.The 8 week remission rate was missing in 29 patients.After 16 weeks of treatment,191(92.3%)achieved complete remission,12(5.8%)had partial remission,and 4(1.9%)showed primary steroid resistance.After an average of 60.4(41.2-82.5)months of follow-up,117(56.5%)patients had no relapse,55(26.6%)had infrequent relapses,31(15%)frequently relapsed or were steroid dependent.The average time from renal biopsy to the first relapse was 17(10.0-24.0)months.187(90.3%)patients were treated with corticosteroid alone,6(2.9%)were treated with non-steroid immunosuppressive drugs,and 14(6.8%)were treated with steroids combined with immunosuppressive agents.A total of 25(12.1%)patients received impulse therapy.11(5.3%)patients were hospitalized for severe infection,and 8(3.9%)had femoral head necrosis.In 207 MCD patients,the proportion of GSG,TA,IF,II and arteriolar hyalinosis(AH)were 17.4%,37.7%,40.1%,38.6%and 10.1%,respectively.All renal tubulointerstitial changes were mild(<25%).No moderate or severe changes were found.Univariate regression analysis and multivariate regression showed that these pathological changes were positively correlated with age.In addition,GSG,TA and IF were also associated with hypertension,and AH was associated with hypertension and diabetes.Univariate regression analysis showed that baseline eGFR and II were associated with lower complete remission rate after 16 weeks(P<0.05).After adjusting age,serum albumin,proteinuira,eGFR,and treatment,II was an independent risk factor for lower complete remission rate after 16 weeks(adjusted OR,0.2;95%CI,0.1-1.0;P=0.048).Univariate Cox proportional hazards model analysis suggested that male and non-steroid immunosuppressive therapy without corticosteroid were associated with relapse(P<0.05).Multivariate Cox proportional hazards model showed that male was an independent risk factors for relapse(adjusted HR,2;95%CI,1.3-3.1;P=0.003).Compared with the corticosteroid therapy,non-steroid immunosuppressive drugs alone is an independent risk factor for relapse(adjusted HR,4.4;95%CI,1.5-13.1;P=0.007).5 patients died who mainly died of malignant tumor,infection and nephrotic complications.Different treatment response influences survival prognosis(Log rank test p=0.0004),and the patient survival of steroid resistance was the worst.The survival of patients with AH is poor(Log rank test p=0.037).The association between initial therapeutic regimen,GSG,TA,IF,II and patient survival did not have statistic significance(Log rank test p>0.05).Only 1 patients progressed to ESRD,and the renal survival of steroid resistance was poor(Log rank test P<0.001).The association between initial therapeutic regimen,GSG,TA,IF,IIAH and renal survival did not have statisticsignificance(Log rank test p>0.05).Conclusion:1.Although the majority of adult MCD are sensitive to steroids,a few of them showed steroid resistance and nearly half of the patients relapsed after achieving remission.Some of the patients showed frequent relapses or steroid dependence.Male and non-steroid immunosuppressive drugs without steroid were independent risk factors for relapse.The renal survival is good,but there were still some patients died.The main causes of death were malignant tumor,infection and complications of nephropthy.2.The older MCD(?60 years old)had lower baseline eGFR,and were more likely to have AKI and hypertension.Age does not influence the remission and relapse of MCD.3.There can be GSG,TA,IF,? and AH in adult MCD which are associated with aging,hypertension and diabetes,and these pathological changes do not influence the remission and relapse of MCD.However,? is an independent risk factor for lower complete remission rate after16 weeks.