Development of donor specific antibodies after SARS-CoV-2 vaccination:What do we know so far?

Vaccination against Coronavirus disease-19(COVID-19)was pivotal to limit spread,morbidity and mortality.Our aim is to find out whether vaccines against COVID-19 lead to an immunological response stimulating the production of de novo donor specific antibodies(DSAs)or increase in mean fluorescence intensity(MFI)of pre-existing DSAs in kidney transplant recipients(KTRs).This study involved a detailed literature search through December 2nd,2023 using PubMed as the primary database.The search strategy incorporated a combination of relevant Medical Subject Headings terms and keywords:"COVID-19","SARS-CoV-2 Vaccination","Kidney,Renal Transplant",and"Donor specific antibodies".The results from related studies were collated and analyzed.A total of 6 studies were identified,encompassing 460 KTRs vaccinated against COVID-19.Immunological responses were detected in 8 KTRs of which 5 had increased MFIs,1 had de novo DSA,and 2 were categorized as either having de novo DSA or increased MFI.There were 48 KTRs with pre-existing DSAs prior to vaccination,but one study(Massa et al)did not report whether pre-existing DSAs were associated with post vaccination outcomes.Of the remaining 5 studies,35 KTRs with pre-existing DSAs were identified of which 7 KTRs(20%)developed de novo DSAs or increased MFIs.Overall,no immunological response was detected in 452(98.3%)KTRs.Our study affirms prior reports that COVID-19 vaccination is safe for KTRs,especially if there are no pre-existing DSAs.However,if KTRs have pre-existing DSAs,then an increased immunological risk may be present.These findings need to be taken cautiously as they are based on a limited number of patients so further studies are still needed for confirmation.

BK viral infection: A review of management and treatment

BK viral infection remains to be a challenging post-transplant infection,which can result in kidney dysfunction.The mainstay approach to BK infection is reduction of immunosuppression.Alterations in immunosuppressive regimen with minimization of calcineurin inhibitors,use of mechanistic target of rapamycin inhibitors,and leflunomide have been attempted with variable outcomes.Over the past few years,investigators have explored potential therapeutic options for BK infection.Fluoroquinolone prophylaxis and treatment was found to have no benefit in kidney transplant recipients.The utility of cidofovir is limited by its nephrotoxicity.Intravenous immunoglobulin is becoming a popular option for treatment and prophylaxis for BK infection,as it increases the neutralizing antibody titers against the most common BK virus serotypes.Virus-specific T cell therapy is an emerging treatment option for BK viremia.In this review,we will explore management and therapeutic options for BK infection and recent evidence available in literature.

Tacrolimus confers lower acute rejection rates and better renal allograft survival compared to cyclosporine

AIM To compare the impact of tacrolimus(FK) and cyclosporine(CYA) on acute rejection and graft survival and to assess the predominant causes of graft loss between patients receiving these two calcineurin inhibitors(CNIs).METHODS Retrospective review of 1835 patients who received a kidney transplant(KTX) between 1999-2012. Patients were grouped based on initial CNI utilized: 1195 in FK group, 640 in CYA group. Data on baseline characteristics, clinical outcomes, and causes of graft loss in both groups were analyzed. RESULTS Cumulative acute rejection rates were 14% in the FK vs 24% in the CYA group. Despite more marginal donor characteristics in the FK group, these patients had better graft survival rates compared to the CYA group. Three and five year graft survival rates were 88% and 84% respectively in the FK group compared to 79% and 70% respectively in the CYA group(P < 0.001). After multivariate analysis, which controlled for confounders, FK use was a strong predictor for lower acute rejectionrates [odds ratio(OR) 0.60, 95%CI: 0.45-0.79] and better renal allograft survival(OR 0.740, 95%CI: 0.58-0.94). Death with a functioning graft was the most common cause of graft loss in both groups. Common causes of death included cardiovascular disease, infections, and malignancies. Chronic allograft nephropathy was also found to be an important cause of graft loss, being more prevalent in the CYA group. CONCLUSION The use of FK-based maintenance immunosuppression therapy is associated with a significantly lower rate of acute rejection and better graft survival compared to CYA-based regimen. Individualizing immunosuppression through risk-stratified CNI choice may lead to improved outcomes across all spectra of KTX patients.