Prognostic Factors In MPO-ANCA-associated Vasculitis With Renal Involvement

Objective:This study aimed to identify clinical and histologic prognostic indicators of mortality and poor renal outcome in patients with MPO-ANCA-associated vasculitis with renal involvement by analyzing their baseline clinical and pathological data.Methods:A total of 67 patients presenting with MPO-ANCA-associated vasculitis with renal involvement were included at the Insititute of Nephrology,the Second Hospital of Jilin University from Sep 2012 to May 2018.All patients met the criteria of 2017EULAR/ACR and 2012 Chapel Hill Conference definition for AAV.All patients were p-MPO-ANCA positive by both IIF assay and ELISA assay.All patients were entered into the study when a newly diagnosed AAV with renal involvement was established.Exclusion criteria were define as follows: patients with secondary vasculitis;patients with comorbid renal diseases;patients complicated with other autoimmune diseases.Two outcomes of interest were measured: patient survival and renal survival after1-year followup.Data were collected retrospectively about clinical,laboratory examination,organ involved,renal pathology,pulmonary imaging,induction therapy,etc.Multivariate logistic regression analysis were conducted for identifying the independent risk factors of mortality and poor renal outcome.Analysis was performed with SPSS 24 software.Results:Part 1.Predictors of mortality with 67 patients of MPO-ANCA-associated vasculitis with renal involvement.1.General data: 67 AAV patients were enrolled in this research.The survivor group comprised 48 patients(71.6%)while the nonsurvivor group comprised 19patients(28.4%).Of the 67 patients,27 were male and 40 were female.The sex ratio(male vs famale)is about 1:1.5.Average age is 65.85 years at diagnosis.24 patients(35.8%)required dialysis at presentation.3 of them(12.5%)were weaned off dialysis.The Five-Factor Score(FFS)was ?2 in 56 cases(83.6%).In a univariate analys,the nonsurvivors had higher FFS(P<0.05).There was no significant difference between the two groups about age,gender,smoking,dialysis vatiables(P>0.05).The propotion of survival at 1 year was 71.6%.Among 19 nosurvival patients,17 deaths(89.5%)occurred within the first 3 months after diagnosis.9 of deaths(47.4%)were related to severe infections;7 of them(36.8%)were related to active vasculitis;2 of deaths(10.5%)were related to cardiovascular events;1 of deaths(5.3%)was related to cerebral hemorrhage.2.Onset symptoms and extrarenal manifestations:Median time from onset of symptoms to admission was 3.0 months.Time from onset of symptoms to admission >6 months was in 25 patients(37.3%).Onset symptoms were as follows:40 cases(59.7%)of cough/sputum/hemoptysis,34 cases(50.7%)of fever,25 cases(37.3%)of dyspnea/chest distress,20 cases(29.9%)of edema/hypourocrinia,20 cases(29.9%)of hypodynamia,15 cases(22.4%)of nausea/vomiting,etc.Onset symptoms were not significantly different between the two groups(P>0.05).The extrarenal involvement of organs were as follows: 55 cases(82.1%)of lung,among which 34cases(50.7%)of interstitial lung disease(ILD),38 cases(56.7%)of heart,30 cases(44.8%)of digestive system,13 cases(19.4%)of nerve system,9 cases(13.4%)of eye,6 cases(9.0%)of skin,5 cases(7.5%)of ear/nose/throat.Extrarenal involvement of organs was not statistical different between the two groups(P>0.05).3.Laboratory examination:(1)General laboratory examination: 57 patients(85.1%)displayed anemia,of which 39(58.2%)presented moderate to severe anemia.38 patients(56.7%)displayed increased leukocyte count.19 patients(28.4%)displayed increased platelet count.The survivors had higher platelet level(P<0.05).61 patients(91.0%)displayed hypoproteinemia.There was no significant difference between the two groups about hemoglobin,leukocyte count,neutrophil count,serum albumin,blood lipid,D-dimer,procalitonin(PCT)vatiables(P>0.05).(2)Immunological and inflammatory laboratory examination: Median MPO-ANCAtiter reached upper limit value in our center(200 RU/mL).25 patients(25/55;45.5%)displayed decreased C3.52 cases(52/54;96.3%)displayed increased ESR and55(55/60;91.7%)displayed increased CRP.23 cases(23/57;40.4%)presented RF positive,while 19 cases(19/61;31.1%)presented ANA positive.No statistical difference was found between the two groups about MPO-ANCA titer,C3,IgG,ESR,CRP,RF-positive,ANA-positive vatiables(P>0.05).4.Renal laboratory and histopathologic characteristics: Of all 67 AAV patients with renal involvement,51 presented(76.1%)increased SCr level.The SCr level >500umol/L was in 29 patients(43.3%).The eGFR <15mL/min was in 38 cases(56.7%).Hematuria presented in 65 patients(97.0%).Proteinuria existed in 60 cases(89.6%),of which heavy proteinuria was in 5 cases(5/40;12.5%).Median 24-h urinary protein was 1.73 g.23 renal pathological materials was available.The patient distribution across the Berden classes was as follows: 8(34.8%)were focal,5(21.7%)were crescentic,4(17.4%)were sclerotic,and 6(26.1%)were mixed.15 specimens(65.2%)had some evidence of glomerular necrosis.There was no significant difference between the two groups about renal items(P>0.05).5.Pulmonary imaging characteristics and function tests: 55 lungs of 67 cases(82.1%)were involved,which mainly manifested as patchy foci 36(36/57;63.2%),ground-glass opacity 20(20/57;35.1%),emphysema 12(12/57;21.1%),reticular pattern/honeycombing 11(11/57;19.3%)and secondary pleural effusion 22(22/57;38.6%).Of 11 cases whose pulmonary function data were available,10 cases(90.9%)displayed diffusion dysfunction,among which 9 cases(81.8%)complicated with ventilation dysfunction.No significant difference was found between the two groups about pulmonary items(P>0.05).6.Induction therapy: 62 patients(92.5%)received induction corticosteroids and24(35.8%)of them received glucocorticoid pulse therapy.There were more patients received glucocorticoid pulse therapy in the nonsurvivor group(P<0.05).35 patients(52.2%)combined with CTX in induction treatment stage,with orally/introvenouslly ratio about 3.5:1.There was no difference between the two groups about induction therapy statistically(P>0.05).7.Independent factor analysis about mortality: After adjustment for interstitial lung disease and glucocorticoid pulse therapy,high FFS was an independent risk factor of mortality(OR=2.557,95%CI 1.152~5.679,P<0.05).Part 2.Predictors of poor renal outcome with 50 patients of MPO-ANCA-associated vasculitis with renal involvement.1.General data: Of 50 AAV patients whose renal outcomes were available,21 were male and 29 were female.Average age is 65.16 years.The propotion of renal survival at 1 year was 64.0%.The non-endpoint group comprised 32 patients while the endpoint group comprised 18 patients.Among 18 patients entered renal endpoint,15(15/18;83.3%)remained on dialysis once diagnosed,with other 3 cases(3/18;16.7%)whose eGFR remained <15mL/min.Patients with severe renal dysfunction had higher FFS and higher propotion of blood pressure elevation(P<0.05).No significant difference was found between the two groups about age,gender,smoking(P>0.05).2.Onset symptoms and extrarenal manifestations: The non-endpoint group inclined to manifest as fever at presentation.The endpoint group inclined to manifest as edema/hypourocrinia(P<0.05).No significant difference about other symptoms and extrarenal manifestations was found(P>0.05).3.Laboratory examination:(1)General laboratory examination:The non-endpoint group had higher platelet count,while the endpoint group had lower hemoglobin(P<0.05).No statistical difference was found about leukocyte count,neutrophil count,serum albumin,blood lipid,D-dimer,procalitonin(PCT)vatiables(P>0.05).(2)Immunological and inflammatory laboratory examination: ESR was faster in the endpoint group(P<0.05).No statistical difference between the two groups about MPO-ANCA titer,C3,IgG,CRP,RF-positive,ANA-positive was found(P>0.05).4.Renal laboratory: The hazard of progression to ESRD was significantly in those with lower eGFR,higher urinary protein and higher urine erythrocyte at entry(P<0.01).No significant difference was found about average length of kidney(P>0.05).5.Renal histopathologic characteristics: Of all patients,17 renal pathological materials were available,with 8 in the endpoint group and 9 in the non-endpoint group.In the endpoint group,the pattern of glomerular injury according to the Berden schema was mainly categorized as sclerotic and crescentic in both 37.5% of cases.Nevertheless,in the non-endpoint group,the pattern was mainly classified as focal(77.8%).The difference was statistically significant(P<0.01).10 specimens(58.8%)had some evidence of glomerular necrosis.Almost all patients showed different degree of tubular atrophy,interstitial fibrosis and interstitial inflammation.The hazard of progression to severe renal disfunction was significantly higher in those with more global sclerosis,less nomal-appearing glomeruli and higher degree of interstitial fibrosis(P<0.05).4 specimens(23.5%)had some evidence of arteriolar wall necrosis.2 specimens(11.8%)were immunofluorescence positive.No statistical difference was found about glomerular necrosis,tubular atrophy,interstitial inflammation,arteriolar wall necrosis,immunofluorescence positive between two groups(P>0.05).6.Induction therapy: All patients received induction corticosteroids,and 13 of them(26.0%)received glucocorticoid pulse therapy.27 patients(54.0%)combined with CTX in induction treatment stage,with orally/introvenouslly ratio was about2.5:1.There was no significant difference between the two groups about induction therapy(P>0.05).7.Independent factor analysis about poor renal outcome: Lower baseline eGFR was an independent risk factor of poor renal outcome(OR=0.807,95%CI 0.674~0.967,P<0.05).Conclusion:1.The propotion of survival at 1 year was 71.6%.17 deaths(89.5%)occurred within the first 3 months after diagnosis.High FFS was an independent risk factor of mortality.2.The propotion of renal survival at 1 year was 64.0%.Lower baseline eGFR was an independent risk factor of poor renal outcome.