Development And Optimization Of Prognostic Models Of PLA2R-associated Membranous Nephropathy

Part I Development and evaluation of prognostic model of PLA2 Rassociated membranous nephropathyBackground & Objective:Membranous nephropathy(MN)represents a spectrum of diseases characterized by great heterogeneity in pathogenesis,course and prognosis,in which M-type phospholipase A2 receptor(PLA2R)associated MN is the most common subtype.However,few studies have directly focused on the prognosis in PLA2R-associated MN till now.Currently,the prediction of renal outcome in PLA2R-associated MN patient is frequently made by general risk stratification of MN in kidney disease: improving global outcomes(KDIGO)2021 clinical practice guideline which ignores renal pathology and is not specific to PLA2 Rassociated MN.To fill the gap,our group developed a clinicopathological multifactor prognostic model for renal outcome in PLA2R-associated MN,as well its nomogram.Methods:A retrospective cohort study enrolling 262 newly diagnosed PLA2R-associated MN individuals who underwent native kidney biopsy at our center was conducted.The outcome was kidney disease progression defined as ≥ 30% estimate glomerular filtration rate(e GFR)decline from baseline and/or the onset of end-stage renal disease.The follow-up time was not less than 12 months.The demographics,laboratory data,renal pathology at baseline and prognosis information of these patients were collected.The associations of these variables above,especially renal pathological lesions,with outcome were analyzed.Then the clinicopathological multivariate prognostic model 1 was developed by binary logistic regression and compared with the MN risk stratification model derived from 2021 KDIGO clinical practice guideline in multiple dimensions.Finally,a nomogram was drawn according to the clinicopathological model 1.Results:During a median follow-up time of 24.5 months,22(8.4%)individuals suffered kidney disease progression.After adjusting for potential confounders,grade I-III total renal chronicity score(TRCS)was independently associated with the outcome(odd ratio: 3.170,95% confidence interval: 1.040-9.659,P = 0.042).The clinicopathological model 1 for the outcome included a total of four variables,which were age ≥ 60 years,diabetes mellitus,serum anti-PLA2 R antibodies(s PLA2Rab)> 50 RU/ml,and grade I-III TRCS.Comparing the clinicopathological model 1 with the KDIGO model in the study cohort,it was found that the former was significantly better than the latter in terms of overall situation,accuracy,consistency of prediction,clinical application value and so on.Conclusion:Grade I-III TRCS associates with worse renal survival in PLA2R-associated MN independently.Compared with the risk stratification of MN in the KDIGO guideline,the clinicopathological model 1 can assist doctors to better predict the outcome in patients with PLA2R-associated MN.Part II Optimization and evaluation of prognostic models of PLA2R-associated membranous nephropathyBackground & Objective:On the basis of the first part of the study,additional predictors were introduced to clinicopathological models for better prediction.Methods:The research methods were similar to those in first part of the study.The primary outcome was kidney disease progression(defined uniformly as above),and the secondary outcomes were no remission in proteinuria or e GFR rapid decline.Variables that could predict progression of other diseases but were rarely used in PLA2R-associated MN were put into consideration as target variables,and the relations between them and outcomes were evaluated.The target variables proved to be independent risk factors for the primary outcome were introduced into the binary logistic regression individually as independent variables to construct new clinicopathological models,which would compare to the previous prognostic models in multiple dimensions.Finally,nomograms were drawn according to the clinicopathological models.Results:According to the statistical analysis,evidence from research and clinical significance,the target variables explored in this part were non-high-density lipoprotein cholesterol(n HDL-C)≥ 7.065 mmol/L,fibrinogen(FIB)≥ 5.66 g/L and neutrophil-to-lymphocyte ratio(NLR)≥ 2.984.After adjusting for potential confounders,n HDL-C ≥ 7.065 mmol/L,FIB ≥ 5.66 g/L and NLR ≥ 2.984 were independent risk factors for the primary outcome(odd ratio were 3.381,4.671,2.931;95% confidence intervals were 1.295-8.826,1.663-13.117,1.054-8.151;P = 0.013,0.004,0.039,respectively).Among the clinicopathological models 2-4 established around these new predictors,clinicopathological model 4 had the best prediction,which included age ≥ 60 years old,s PLA2 Rab > 50 RU/ml,NLR ≥ 2.984,n HDL-C ≥ 7.065 mmol/L,FIB ≥ 5.66 g/L,and grade I-III TRCS.Conclusion:After adding of new predictors,the clinicopathological multivariate prognostic models of PLA2R-associated MN optimized significantly.In particular,the clinicopathological model 4 possessed the best predictive performance,which can serve clinical practice in greater level.