COVID-19 infection and vaccination rarely impact HLA antibody profile in waitlisted renal transplant candidates- a multicenter cohort.

Although rare, infection and vaccination can result in antibodies to human leukocyte antigens (HLA). We analyzed the effect of SARS-CoV-2 infection or vaccination on HLA antibodies in waitlisted renal transplant candidates. Specificities were collected and adjudicated if the calculated panel reactive antibodies (cPRA) changed after exposure. Of 409 patients, 285 (69.7 %) had an initial cPRA of 0 %, and 56 (13.7 %) had an initial cPRA > 80 %. The cPRA changed in 26 patients (6.4 %), 16 (3.9 %) increased, and 10 (2.4 %) decreased. Based on cPRA adjudication, cPRA differences generally resulted from a small number of specificities with subtle fluctuations around the borderline of the participating centers' cutoff for unacceptable antigen listing. All five COVID recovered patients with an increased cPRA were female (p = 0.02). In summary, exposure to this virus or vaccine does not increase HLA antibody specificities and their MFI in approximately 99 % of cases and 97 % of sensitized patients. These results have implications for virtual crossmatching at the time of organ offer after SARS-CoV-2 infection or vaccination, and these events of unclear clinical significance should not influence vaccination programs.

Evaluation of a multidisciplinary, multimodal pain management protocol following pancreas transplantation.

INTRODUCTION: Patients undergoing solid-organ transplantation demonstrate pain arising from both the surgical intervention and pre-existing comorbidities. High levels of opioid use both pre- and post-transplant are associated with unfavorable transplant outcomes. Patient education, multimodal therapy, and discharge planning have all been demonstrated to reduce opioid use after transplant. METHODS: This is a single-center, retrospective study analyzing patients before and after implementation of a multimodal, multidisciplinary pain management protocol. Morphine milligram equivalents (MMEs) use during the index transplant hospitalization and the need for opioids at discharge was compared between the pre- and post-protocol groups. RESULTS: A total of 52 patients were included in the study, 31 in the pre and 21 in the post-protocol groups. Inpatient MME use was reduced from 135.5 to 67.5 MMEs after protocol implementation. Additionally, the number of patients discharged on opioids following transplant decreased from 90.3% to 47.6%. Pain scores, length of stay (LOS), and return of bowel function was not different between groups. CONCLUSION: The implementation of a multimodal, multidisciplinary pain management protocol significantly decreased opioid use during the post-surgical hospitalization and in the 6 months following transplantation. A combination of non-opioid analgesics, patient education, and discharge planning can be beneficial elements in pancreas transplant pain management.

But Why Weight: Understanding the Implications of Obesity in Kidney Transplant.

Obesity is increasing in prevalence among candidates for kidney transplant. Understanding the influence of obesity on candidate evaluation, surgical risk, peritransplant management, and post-transplant outcomes is critical to ensuring equitable access to transplant for this growing population.

Alum irrigation for the treatment of adenovirus induced hemorrhagic cystitis in a kidney transplant recipient.

Adenovirus is a rare cause of hemorrhagic cystitis in the transplant population. We present a case of a forty-one-year-old man with end-stage renal disease who underwent living unrelated donor kidney transplant in 2016. In 2018 he presented with acute onset gross hematuria and dysuria, with serologic testing and immunohistochemical stains of biopsy specimens positive for adenovirus. He was treated with reduction in immunosuppression, cystoscopy with evacuation of clots, and alum bladder irrigation. His hematuria resolved almost immediately with no recurrence to date. This case demonstrates the efficacy and safety of alum irrigation in patients with adenovirus hemorrhagic cystitis.

Graft Function and Intermediate-Term Outcomes of Kidney Transplants Improved in the Last Decade: Analysis of the United States Kidney Transplant Database.

BACKGROUND: Previous analyses of the United States transplant database regarding long-term outcomes in kidney transplantation have shown minimal improvement in the rate of long-term graft loss. This study sought to analyze intermediate-term outcomes and graft function at 6 months in kidney transplantation in adult living and deceased donor recipients in the last decade. METHODS: Survival analysis was performed based on the year of transplant between 6 months and 3 years' posttransplant. The Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rate (eGFR) was determined at 6 months. RESULTS: The unadjusted graft survival between 6 months and 3 years improved significantly in the latter half of the decade in both deceased and living donor kidney recipients. Cox analysis showed a 33% reduction in the rate of graft loss and that the improvement in graft survival was due to similar improvements in both death-censored graft and death with graft function survival. A 10% improvement in median eGFR occurred despite worsening donor demographics over time in both donor types. This improvement in eGFR and graft survival occurred in association with a consolidation of chronic discharge immunosuppression from a variety of combinations to over 85% of recipients receiving tacrolimus and mycophenolate derivative immunosuppression. CONCLUSIONS: In the latter half of last decade graft survival improved in adult kidney transplant recipients. The improvement in graft survival occurred in temporal association with an improvement in median eGFR at 6 months and consolidation of discharge immunosuppression in most patients to tacrolimus and mycophenolate derivatives.

Longitudinal analysis of living donor kidney transplant rates in pediatric candidates in the United States.

Among adults, living donor kidney transplant rates began declining in the United States after 2004 but whether a similar decline is occurring in the pediatric candidates has not been well studied. Share 35, a change in allocation rules implemented in October of 2005, may also have influenced rates of living donation. We sought to determine whether a decline in rates was occurring in pediatric candidates and whether the Share 35 program was the cause of the decline. All children listed for a kidney transplant or transplanted with a living donor without listing between 1996 and 2011 were identified in the United States (N=14 911) of which 6046 had received a living donor transplant during follow-up. Kaplan-Meier analysis showed a decline in living donor rates in candidates listed after 2001. Logistic regression analysis for living donor kidney transplantation confirmed the timing of the drop but also showed that changes in candidate demographics and center listing practices were impacting rates. A large drop in parental donation was the main cause for the drop. The rate of living donor transplant among pediatric candidates declined after 2001 predating by 4 years the implementation of Share 35, suggesting that factors other than changes in allocation rules are responsible for the decline.

Approach to the Highly Sensitized Kidney Transplant Candidate.

For patients with ESRD, kidney transplant offers significant survival and quality-of-life advantages compared with dialysis. But for patients seeking transplant who are highly sensitized, wait times have traditionally been long and options limited. The approach to the highly sensitized candidate for kidney transplant has changed substantially over time owing to new advances in desensitization, options for paired donor exchange (PDE), and changes to the deceased-donor allocation system. Initial evaluation should focus on determining living-donor availability because a compatible living donor is always the best option. However, for most highly sensitized candidates this scenario is unlikely. For candidates with an incompatible donor, PDE can improve the prospects of finding a compatible living donor but for many highly sensitized patients the probability of finding a match in the relatively small pools of donors in PDE programs is limited. Desensitization of a living donor/recipient pair with low levels of incompatibility is another reasonable approach. But for pairs with high levels of pathologic HLA antibodies, outcomes after desensitization for the patient and allograft are less optimal. Determining the degree of sensitization by calculated panel-reactive antibody (cPRA) is critical in counseling the highly sensitized patient on expected wait times to deceased-donor transplant. For candidates with a high likelihood of finding a compatible deceased donor in a reasonable time frame, waiting for a kidney is a good strategy. For the candidate without a living donor and with a low probability of finding a deceased-donor match, desensitization on the waiting list can be considered. The approach to the highly sensitized kidney transplant candidate must be individualized and requires careful discussion among the transplant center, patient, and referring nephrologist.

The use of a DNA biobank linked to electronic medical records to characterize pharmacogenomic predictors of tacrolimus dose requirement in kidney transplant recipients.

OBJECTIVE: Tacrolimus, an immunosuppressive drug widely prescribed in kidney transplantation, requires therapeutic drug monitoring due to its marked interindividual pharmacokinetic variability and narrow therapeutic index. Previous studies have established that CYP3A5 rs776746 is associated with tacrolimus clearance, blood concentration, and dose requirement. The importance of other drug absorption, distribution, metabolism, and elimination (ADME) gene variants has not been well characterized. METHODS: We used novel DNA biobank and electronic medical record resources to identify ADME variants associated with tacrolimus dose requirement. Broad ADME genotyping was performed on 446 kidney transplant recipients, who had been dosed to a steady state with tacrolimus. The cohort was obtained from Vanderbilt's DNA biobank, BioVU, which contains linked deidentified electronic medical record data. Genotyping included Affymetrix drug-metabolizing enzymes and transporters Plus (1936 polymorphisms), custom Sequenom Massarray iPLEX Gold assay (95 polymorphisms), and ancestry-informative markers. The primary outcome was tacrolimus dose requirement defined as blood concentration to dose ratio. RESULTS: In analyses, which adjusted for race and other clinical factors, we replicated the association of tacrolimus blood concentration to dose ratio with CYP3A5 rs776746 (P=7.15×10), and identified associations with nine variants in linkage disequilibrium with rs776746, including eight CYP3A4 variants. No NR1I2 variants were significantly associated. Age, weight, and hemoglobin were also significantly associated with the outcome. In final models, rs776746 explained 39% of variability in dose requirement and 46% was explained by the model containing clinical covariates. CONCLUSION: This study highlights the utility of DNA biobanks and electronic medical records for tacrolimus pharmacogenomic research.