Samar Bukhari

IntroductionThe prognostic value of PLA2R antibody (Ab) test in clinical practice remains unclear. We aimed to evaluate its ability in predicting hard outcomes in primary membranous nephropathy (PMN) after adjustments to conventional markers of disease activity.MethodsA total of 222 patients diagnosed with PMN from January 2003 to July 2019 having had a serum PLA2R Ab test, were included from 3 centers in the north of England. Baseline conventional markers, PLA2R-Ab-status (positive vs. negative), Ab-titer (high vs. low), and time of testing (pre-PLA2R era vs. PLA2R era) were evaluated for association with outcomes. Primary outcome was time to progression (composite of doubling of creatinine, stage 5 chronic kidney disease, or death). Secondary outcomes were time to partial remission (PR) and time to immunosuppression. Cox proportional hazard testing was used.ResultsDuring a median follow-up of 5.26 years, progression was seen in 65 (29.3%) and PR in 179 of 222 patients (80.6%). There was a clear association of estimated glomerular filtration rate (eGFR) (standardized hazard ratio [HRZ] = 0.767, P < 0.05) and urine protein-to-creatinine ratio (uPCR) (HRZ = 1.44, P < 0.005) with time to progression among all patients, and eGFR (HRZ = 0.606, P < 0.005) in Ab-positive patients. Baseline Ab-positivity was not associated with time to progression (adjusted hazard ratio [aHR] = 0.93, P = 0.71) or time to PR (aHR = 0.84, P = 0.13). Similarly, baseline high Ab-titer was not associated with time to progression (aHR = 1.07, P = 0.77) or time to PR (aHR = 0.794, P = 0.08).ConclusionOnce adjusted to conventional markers of disease activity, baseline PLA2R Ab-positivity or Ab-titer do not predict disease progression or time to PR. Further studies are needed to harness the utility of PLA2R Ab test in prognostication in PMN.

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: 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: /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.

We thank Chen et al. for their letter1 regarding our manuscript, “Impact of Time-To-Treatment on Outcomes in Autoimmune Membranous Nephropathy”2 and welcome the opportunity to clarify our conclusions and acknowledge the important nuances raised.