Impact of Time-To-Treatment on Outcomes in Autoimmune Membranous Nephropathy

治疗时间对自身免疫性膜性肾病预后的影响

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Abstract

INTRODUCTION: Despite new treatments, kidney dysfunction in autoimmune membranous nephropathy (aMN) remains challenging. Immunosuppression is initiated after "watchful-wait" to avoid side effects in patients who might achieve spontaneous remission; however, the impact of this approach on kidney function is unclear. METHODS: This was a retrospective longitudinal cohort study of patients with new consecutive aMN from 2003 to 2019 from 3 UK centers. Patients were assigned to 5 categories, a priori based on baseline urinary protein-to-creatinine ratio (uPCR) and estimated glomerular filtration rate (eGFR). The analysis investigated change in eGFR based on these risk categories. Primary outcomes were spontaneous partial remission (SPR), rate of eGFR change before immunosuppression, and chronic kidney disease (CKD) stage 5 (CKD5). The secondary outcome was progression (composite of doubling serum creatinine, CKD5, and death). Cox proportional hazard models were used to assess association of outcomes with baseline categories. RESULTS: A total of 312 patients were included with 5.0 years median follow-up from diagnosis. A significant association was found between waiting time to immunosuppression and decline in eGFR (P < 0.001) in patients who received immunosuppression. When change was regressed against time, eGFR loss was equivalent to 7.7 ml/min per 1.73 m(2)/yr of watchful wait. In the low-risk group, 71% achieved SPR and 2.4% progressed to CKD5, whereas in the high-2 risk group, 20% achieved SPR, and 25% developed CKD5. The strongest predictor of progression to CKD5 was the eGFR at the start of immunosuppression treatment, regardless of baseline function. CONCLUSION: In patients with aMN requiring immunosuppression, delayed treatment leads to worse kidney outcomes. A simple categorization using baseline eGFR and uPCR can help predict spontaneous remission and potential kidney function decline.

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