Predictors of Humoral Response to mRNA COVID19 Vaccines in Kidney Transplant Recipients: A Longitudinal Study—The COViNEPH Project

Background: The efficacy of SARS-CoV-2 vaccination among kidney transplant recipients (KTR) is low. The main goal of this study was to analyze factors that may influence the humoral response to vaccination. Methods: We analyzed the titer magnitude of IgG antibodies directed against spike (S)-SARS-CoV-2 antigen after the second dose of the mRNA vaccine in 142 infection naïve KTR (83 men, i.e., 58.4%) with a median age (IQR) of 54 (41–63), and 36 respective controls without chronic kidney disease. mRNA-1273 or BNT162b2 were applied in 26% and 74% of KTR, respectively. Results: S-specific immune response (seroconversion) was seen in 73 (51.41%) of KTR, and in all controls 36 (100%). Independent predictors of no response were elder age, shorter transplantation vintage, and a more than two-drug immunosuppressive protocol. In subgroup analyses, the seroconversion rate was highest among KTR without MMF/MPS treatment (70%), treated with no more than two immunosuppressants (69.2%), treated without corticosteroid (66.7%), younger patients aged <54 years (63.2%), and those vaccinated with the mRNA-1273 vaccine (62.16%). The independent predictors of higher S-antibody titer among responders were younger age, treatment with no more than two immunosuppressants, and the mRNA-1273 vaccination. Conclusions: Our study confirmed a low rate of seroconversion after vaccination with the mRNA vaccine in KTR. The major modifiable determinants of humoral response were the composition of the immunosuppressive protocol, as well as the type of vaccine. The latter could be taken into consideration when initial vaccination as well as booster vaccination is considered in KTR.

MO289IS THERE A ROLE OF INTERSTITIAL CHANGES ON THERAPY OUTCOME AMONG PATIENTS WITH FOCAL-SEGMENTAL GLOMERULAR SCLEROSIS AND MINIMAL CHANGE DISEASE?

Background and Aims It is well-known that interstitial changes in patients with focal-segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) are linked with disease chronicity and progression. The aim of this study was to analyze is there any connection between interstitial changes and outcome after “first line” therapy in patients with FSGS/MCD. Method From 2014 till 2019, biopsy proven diagnosis of FSGS/MCD was established in 40 patients. Interstitial changes were classified in three groups as following: 0-w/o changes; 1-mild changes; 2-severe changes. Patients with nephrotic syndrome (No=29) were treated with prednisolone (1mg/kg) and after six months we have registered therapy outcome as: CR-complete remission; PR-partial remission; EX-death; NO-no effect. Results Among treated patients (age 50.4±15.3 years, 15 men), CR was achieved in 10 patients (34.5%) and 6 out of these 10 (60%) had no interstitial changes. Partial remission was observed in 11 patients (37.9%), in 4 patients (13.8%) therapy did not have any effect, and 4 patients (13.8%) deceased (table 1). All patients in EX and NO group had interstitial changes. There were no significant difference in age, gender, proteinuria, albuminaemia, creatinine and glycaemia levels between groups except for hemoglobin levels that were significantly lower in EX group than in others (∑ 15.144; p=0.002) and urea levels that were significantly higher in EX group (∑ 138.057; p=0.024). Conclusion Patients with FSGS/MCD respond well on standard immunosuppressive protocol, particularly in absence of interstitial changes what may increase the chance for achieving complete remission.

Prevention of Chronic Rejection of Marginal Kidney Graft by Using a Hydrogen Gas-Containing Preservation Solution and Adequate Immunosuppression in a Miniature Pig Model

In clinical kidney transplantation, the marginal kidney donors are known to develop chronic allograft rejection more frequently than living kidney donors. In our previous study, we have reported that the hydrogen gas-containing organ preservation solution prevented the development of acute injuries in the kidney of the donor after cardiac death by using preclinical miniature pig model. In the present study, we verified the impact of hydrogen gas treatment in transplantation with the optimal immunosuppressive protocol based on human clinical setting by using the miniature pig model. Marginal kidney processed by hydrogen gas-containing preservation solution has been engrafted for long-term (longer than 100 days). A few cases showed chronic rejection reaction; however, most were found to be free of chronic rejection such as graft tissue fibrosis or renal vasculitis. We concluded that marginal kidney graft from donor after cardiac death is an acceptable model for chronic rejection and that if the transplantation is carried out using a strict immunosuppressive protocol, chronic rejection may be alleviated even with the marginal kidney.

CSA-Induced PRES after Heart Transplantation—Report of Two Cases and Review

Background Posterior reversible encephalopathy syndrome (PRES) is a rare neurological disease possibly associated with the use of calcineurin inhibitors (CNI) like cyclosporine A. Case Description The case of a patient who developed severe PRES under CNI therapy shortly after heart transplantation is presented here. Cerebral computed tomography led to the diagnose of PRES in our patient. New therapy strategy with a quadruple immunosuppressive protocol (cortisone, mycophenolate mofetil, low-dose CNI, and a mechanistic target of rapamycin inhibitor) was started. Conclusion Under the quadruple therapy, a neurologic recovery occurred. In PRES, the presented alternative therapy strategy may lead to improving neurological conditions and preserved transplant organ functions.

Future strategies to improve short- and long-term outcomes of renal transplantation in dogs

ABSTRACT: Transplants for cats with naturally occurring renal disease have been introduced into clinical practice, but canine renal transplantation represents a greater challenge because of the lack of a balanced immunosuppressive protocol, difficulty in selecting compatible canine kidney donors, and absence of transplantation monitoring protocols. This and other important factors will be discussed in this review to help improve short- and long-term outcomes for renal transplantation in dogs.

P1731ABO INCOMPATIBLE DONOR KIDNEY TRANSPLANTATION IN PORTUGAL

Background and Aims ABO incompatiblitity was considered a barrier to kidney transplant. However, the shortage of available organs for transplantation and the excellent long term results further establish ABO-incompatible (ABOi) as a safe and effective therapeutic strategy. The aim of the present study was to evaluate the outcomes of ABOi transplantation in terms of graft survival and function, rejection episodes and infections complications. Method The authors present a single center retrospective observational study, that include the analyse of 12 patients who underwent ABOi kidney transplantation between November 2014 and July 2019. All patients received Rituximab (375mg/m2) pre-operation and started Tacrolimus, Mycophenolate Mofetil and Prednisolone one week before surgery. Plasmapheresis was done to remove anti-A or B antibodies until their titles were &lt;1:8 during the first post-operative week and &lt;1:16 at the second. Results : A total of 12 patients were included in the study, 75,0% male with 43 years (IQR 31-50) The most common blood group mismatch was A to O (n=4; 33%). In the first year, 2 of patients (17%) developed acute rejection. The follow-up time was 17 months (IQR 7-36). Five patients (42%) developed infectious complications. None patients developed cytomegalovirus or BK polyomavirus infections. At the end graft and patient survival were 100%. Conclusion ABOi kidney transplantation has become a routine procedure. By this approach, about 30% of living donors who were refused in the past can now donate their kidneys and thereby significantly expand the living donor pool. Immunosuppressive protocol of this Center can be considered safe.

Natural history of mineral metabolism, bone turnover and bone mineral density in de novo renal transplant recipients treated with a steroid minimization immunosuppressive protocol

The skeletal effects of renal transplantation are not completely understood, especially in patients managed with a steroid minimization immunosuppressive protocol and long term. We enrolled 69 adult transplant recipients (39 males; ages 51.1 ± 12.2 years), free of antiresorptive therapy and managed with a steroid minimization immunosuppressive protocol, into a 5-year prospective observational study to evaluate changes in areal bone mineral density (aBMD), mineral metabolism and bone remodelling. Dual energy X-ray absorptiometry, laboratory parameters of mineral metabolism (including parathyroid hormone, sclerostin and fibroblast growth factor 23) and non-renal cleared bone turnover markers (BTMs) (bone-specific alkaline phosphatase, trimeric N-terminal propeptide and tartrate-resistant acid phosphatase 5b) were assessed at baseline and 1 and 5 years post-transplantation. The mean cumulative methylprednisolone exposure at 1 and 5 years amounted to 2.5 ± 0.8 and 5.8 ± 3.3 g, respectively. Overall, bone remodelling activity decreased after transplantation. Post-transplant aBMD changes were minimal and were significant only in the ultradistal radius during the first post-operative year {median −2.2% [interquartile range (IQR) −5.9–1.2] decline, P = 0.01} and in the lumbar spine between Years 1 and 5 [median 1.6% (IQR −3.2–7.0) increase, P = 0.009]. BTMs, as opposed to mineral metabolism parameters and cumulative corticosteroid exposure, associated with aBMD changes, both in the early and late post-transplant period. Most notably, aBMD changes inversely associated with bone remodelling changes. In summary, in de novo renal transplant recipients treated with a steroid minimization immunosuppressive protocol, BMD changes are limited, highly variable and related to remodelling activity rather than corticosteroid exposure.