Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025
Clinical phenotypes and renal outcomes in PLA2R-associated membranous nephropathy: a multi-center cohort study with unsupervised cluster analysis.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Miao Jing, Zand Jaleh, Vaughan Lisa, Soler Maria Jose, Díaz Encarnación Montserrat M, Quintana Luis F, Bomback Andrew S, Thongprayoon Charat, Wooden Benjamin, Bobart Shane A, Cheungpasitporn Wisit, Fervenza Fernando C, Zand Ladan
Аннотация
BACKGROUND: Membranous nephropathy (MN) associated with phospholipase A2 receptor (PLA2R) antibodies is the most common cause of nephrotic syndrome in non-diabetic adult patients. This study investigated the relationship between clinical phenotypes and renal outcomes in this population, emphasizing the potential for phenotype-based treatment stratification.
METHODS: We conducted a retrospective, multi-center cohort study of PLA2R-positive MN. Unsupervised cluster analysis grouped patients based on clinicopathological characteristics. Primary outcomes included complete or partial remission within 2 years of biopsy and end-stage kidney disease (ESKD) or death during follow-up.
RESULTS: Among 178 patients, three distinct clusters emerged (n = 89, 70, and 19). Within 2 years of biopsy, 102 patients (57%) achieved complete or partial remission. Cluster 1, characterized by the mildest disease markers, including the lowest body mass index, serum anti-PLA2R titer, serum creatinine, proteinuria, and triglycerides, had the highest remission rate of 72%, compared with 50% in cluster 2 and 54% in cluster 3. Cluster 2 had significantly lower remission compared to cluster 1 (HR 0.64, 95% CI 0.42-0.96, P = .03); results were similar in cluster 3, albeit not statistically significant (HR 0.50, 95% CI 0.23-1.09, P = .08). Elevated anti-PLA2R levels (>100 U/ml) and proteinuria (>8 g/24-hour) predicted reduced remission (HR 0.56, 95% CI 0.36-0.88, P = .01; HR 0.43, 95% CI 0.26-0.73, P = .002, respectively), while high high-density lipoprotein levels were protective (HR 1.01, 95% CI 1.00-1.02, P = .048). Overall, 21 patients (12%) developed ESKD or died. ESKD-free survival differed significantly across clusters (log-rank test P = .04).
CONCLUSIONS: Unsupervised clustering identified distinct clinical phenotypes in PLA2R-positive MN, each associated with different renal prognoses. Phenotype-based risk stratification could enhance treatment precision, improve patient outcomes, and potentially reduce treatment-related adverse effects.
METHODS: We conducted a retrospective, multi-center cohort study of PLA2R-positive MN. Unsupervised cluster analysis grouped patients based on clinicopathological characteristics. Primary outcomes included complete or partial remission within 2 years of biopsy and end-stage kidney disease (ESKD) or death during follow-up.
RESULTS: Among 178 patients, three distinct clusters emerged (n = 89, 70, and 19). Within 2 years of biopsy, 102 patients (57%) achieved complete or partial remission. Cluster 1, characterized by the mildest disease markers, including the lowest body mass index, serum anti-PLA2R titer, serum creatinine, proteinuria, and triglycerides, had the highest remission rate of 72%, compared with 50% in cluster 2 and 54% in cluster 3. Cluster 2 had significantly lower remission compared to cluster 1 (HR 0.64, 95% CI 0.42-0.96, P = .03); results were similar in cluster 3, albeit not statistically significant (HR 0.50, 95% CI 0.23-1.09, P = .08). Elevated anti-PLA2R levels (>100 U/ml) and proteinuria (>8 g/24-hour) predicted reduced remission (HR 0.56, 95% CI 0.36-0.88, P = .01; HR 0.43, 95% CI 0.26-0.73, P = .002, respectively), while high high-density lipoprotein levels were protective (HR 1.01, 95% CI 1.00-1.02, P = .048). Overall, 21 patients (12%) developed ESKD or died. ESKD-free survival differed significantly across clusters (log-rank test P = .04).
CONCLUSIONS: Unsupervised clustering identified distinct clinical phenotypes in PLA2R-positive MN, each associated with different renal prognoses. Phenotype-based risk stratification could enhance treatment precision, improve patient outcomes, and potentially reduce treatment-related adverse effects.