The Efficacy of Cyclophosphamide Combined with Prednisone in Membranous Nephropathy Patients with Different Cytochrome P450 2B6 Gene Polymorphisms and Analysis of Factors Influencing the Efficacy

Abstract

Objective To investigate the efficacy of cyclophosphamide combined with prednisone in membranous nephropathy (MN) patients with different cytochrome P450 (CYP) 2B6 gene polymorphisms and explore the factors influencing the efficacy. Methods We performed a prospective and interventional study including 153 outpatients diagnosed with membranous nephropathy from April 2020 to June 2020 in the Bayannur Hospital. Based on the results of CYP2B6 gene polymorphisms, patients were divided into CYP2B6*4 group (785A>G) with 93 cases and CYP2B6*5 group (1459C>T) with 60 cases, and all patients were treated with cyclophosphamide and prednisone. The efficacy of the two groups was compared, and the serum levels of antibody against thrombospondin type-1 domain-containing 7A (THSD7A-Ab), 8-hydroxy-2’-deoxyguanosine (8-OHdG) and antibody against the M-type phospholipase A2 receptor (PLA2R-Ab) determined by the enzyme-linked immunosorbent method were analyzed in the two groups before and after treatment. Results After the treatment with cyclophosphamide and prednisone, serum levels of THSD7A-Ab, 8-OHdG, and PLA2R-Ab were higher in the CYP2B6*4 group than those in the CYP2B6*5 group (All three P <0.001). The univariate Logistic regression analysis showed that CYP2B6*4 (OR = 1.727, 95% CI: 1.028–2.654. P =0.012), CYP2B6*5 (OR = 1.802, 95% CI: 1.179–2.752. P =0.031), THSD7A-Ab (OR = 1.832, 95% CI: 0.871–2.348. P =0.023), 8-OHdG (OR = 1.661, 95% CI: 1.123–2.231. P =0.009), PLA2R-Ab (OR = 1.649, 95% CI: 1.083–2.761. P =0.017) were independent influencing factors on the efficacy of MN. The multivariate Logistic regression analysis showed that CYP2B6*4 (OR = 2.009, 95% CI: 1.327–2.703. P <0.001), CYP2B6*5 (OR = 3.009, 95% CI: 1.467–5.231. P =0.005), THSD7A-Ab (OR = 1.396, 95% CI: 1.002–1.897. P =0.019), 8-OHdG (OR = 0.704, 95% CI: 0.591–0.742. P <0.001), PLA2R-Ab (OR = 2.761, 95% CI: 1.231–3.918. P =0.017) were independent factors influencing the efficacy of cyclophosphamide and prednisone on MN. Conclusion Cyclophosphamide combined with prednisone was effective in treating MN with different CYP2B6 gene polymorphisms. CYP2B6*4, CYP2B6*5, and serum levels of THSD7A-Ab, 8-OHdG, and PLA2R-Ab were independent influencing factors on the outcome of MN.

Understanding the podocyte immune responses in proteinuric kidney diseases: from pathogenesis to therapy

“…The combination of alkylating agents with steroids has demonstrated high efficacy in managing high-risk podocyte-associated proteinuric kidney diseases such as MN ( 151 ). Studies have indicated the effectiveness of the combination of cyclophosphamide with prednisone for various high-risk MN patients ( 152 ). Research indicates that high-dose cyclophosphamide suppresses CD103 + dendritic cells in a rat model, resulting in changes in their frequency, surface molecule expression, and antigen-capturing ability.…”