A Study of Long-Term Outcome of Mycophenolate Dose Modulation in Renal Allograft Recipients with Sars-Cov2 Infection during Covid-19 Pandemic

ABSTRACT

BACKGROUND: A significant reduction of acute rejection rates was observed after using Mycophenolate mofetil (MMF) in renal transplant recipients (RTR). However side-effects like hematological and gastrointestinal intolerance often occur when MMF is used in routine doses. MMF dose reduction is required during its side-effects or coexisting infection in RTR. The outcome of MMF dose modulation in RTR is not well established AIM OF THE STUDY COVID-19 pandemic has given an opportunity to study the effect of MMF dose modulation on graft function as large number of RTR who had COVID-19 received MMF dose reduction or discontinuation. This study's objective was to determine whether MMF dose reduction or discontinuation was associated with the effect on allograft function after renal transplantation. We included all RTR who had an infection with SARS-CoV2 and received MMF dose reduction or discontinuation METHODS: We prospectively collected data of renal transplant recipients developing COVID-19 infection during the first and second covid waves. Management including decision on admission immunosuppression modulation antibiotics were done based on clinician'S discretion subject to logistics and the prevailing guidelines by the ISOT. All patients were followed up for minimum 15 months for graft dysfunction biopsy rate biopsy-proven acute rejection ( BPAR). The effect of immunosuppression modulation - MMF cessation (Group A) Vs MMF reduction/no manipulation (Group B) and its bearing on the incidence of rejection and was compared. Additional factors such as follow - up sub therapeutic CNI levels development of DSA ( when done ) steroid increment were studied regression model. Kaplan - Meier survival curves for 24 months drawn. RESULT(S) Among 251 renal transplant patients with SARSCoV2 infection, 38 patients died during Index admission. 45 patients have not completed for 15 months. 168 patients completed 15 month follow - up. Among them, antimetabolite were reduced in 115 (68.5%), stopped in 42 (25%), not manipulated in 5 ( 3%) and 6 patients were not on anti-metabolites and hence excluded from present analysis. Of the 162 patients, MMF had been stopped for 2 weeks or until presumed clinical recovery in 42 patients ( Group A) and the rest in 120 patients ( Group B). Mean age was 41.18 ( i' +/- 12.8), and 75.6% had mild COVID. Median duration of followup was 18 months ( 14q1-22q3 months). Total readmission rate was 66 (40.7%) (Group A 21 (50%) Vs Group B 45 (37.5%). Graft biopsy was done in 16% of patients. 9.3% patients had acute rejection (11.9% Vs 8.3%, p 0.05). Among those who had rejection, ABMR was seen in 2, ACR in 3, CABMR in 5 and combined rejection in 1 CONCLUSION(S) MMF dose modulation to tackle an infectious episode may be associated with graft dysfunction and rejection on follow-up and close follow-up is needed in any patient in whom MMF dose in manipulated.