Perinephric Transplant Myelolipoma: A Case Report of a Rare Entity.

BACKGROUND: Myelolipomas are benign tumors usually found in adrenal glands. They can also be found extra-adrenally, either in 1 or multiple locations. Perinephric transplant myelolipoma has rarely been reported in the English literature. There's only been 1 instance of such a case reported in a kidney transplant patient, which was found on the explanted kidney. We report a case involving an asymptomatic patient with an ill-defined perinephric transplant mass. METHODS: The mass was then identified as myelolipoma on biopsy. The patient was then managed conservatively with serial imaging and laboratory testing. RESULTS: At the time of our report, the patient continues to have stable renal function and is doing well 24 months after the mass was first identified. CONCLUSIONS: We report the first case of perinephric transplant myelolipoma in a patient with ongoing stable renal allograft function. Based on our case report, we recommended that conservative management with serial imaging and routine testing be considered for patients with perinephric transplant myelolipoma.

Impact of Converting from Immediate-Release Tacrolimus to Envarsus on BK Viremia Incidence in Kidney Transplant Patients with Rapid Metabolism.

BACKGROUND BK infections have been observed more frequently among people who are rapid metabolizers. The tacrolimus c/d ratio identifies rapid metabolizers after transplantation. Envarsus has a lower peak drug level exposure than tacrolimus and is more pronounced in rapid metabolizers. This study hypothesized that less exposure to high tacrolimus levels through use of Envarsus would reduce the incidence of BK infections. MATERIAL AND METHODS This study prospectively converted 43 consecutive kidney transplant recipients (identified as rapid metabolizers by c/d ratio of.

Making the Cut: Parathyroidectomy Before or After Kidney Transplantation?

BACKGROUND: Hyperparathyroidism is common in patients with end-stage kidney disease and may persist after kidney transplantation (KT). Parathyroidectomy (PTx) is curative, but whether PTx should be performed before or after KT remains controversial. There is concern that PTx can adversely affect renal allograft function if performed post-KT and result in persistent hypocalcemia. This study evaluated outcomes and postoperative complications of PTx before and after KT at our institution. METHODS: We performed a retrospective review of patients at our center (1/2012-2/2019) who had PTx either pre-KT or post-KT. Data on patient demographics, surgical outcomes, and postoperative complications of PTx were collected. RESULTS: Ninety-eight patients were included in this study, with 23 patients undergoing PTx before KT and 75 after KT. The length of follow-up after KT was 67.7 ± 25.5 months. In post-KT PTx patients, 30-day allograft function was unchanged after PTx. Calcium oxalate and phosphate crystals were less common on allograft biopsies in pre-KT PTx patients (10.0% vs. 34.8%, p = 0.038). Patients in the pre-KT group required more calcium supplementation after PTx than the post-KT group (p < 0.001). At one-year post-PTx, 17 (19.1%) patients required > 1000 mg elemental calcium per day and 7 (7.9%) patients required > 2000 mg/day. There was no difference in surgical success or postoperative complications between the two groups. CONCLUSIONS: Parathyroidectomy before or after kidney transplantation does not adversely affect allograft function. The incidence of persistent hypocalcemia was low. Parathyroidectomy is safe and effective either before or after kidney transplantation.

COVID-19 Vaccination and Remdesivir are Associated With Protection From New or Increased Levels of Donor-Specific Antibodies Among Kidney Transplant Recipients Hospitalized With COVID-19.

Alloimmune responses in kidney transplant (KT) patients previously hospitalized with COVID-19 are understudied. We analyzed a cohort of 112 kidney transplant recipients who were hospitalized following a positive SARS-CoV-2 test result during the first 20 months of the COVID-19 pandemic. We found a cumulative incidence of 17% for the development of new donor-specific antibodies (DSA) or increased levels of pre-existing DSA in hospitalized SARS-CoV-2-infected KT patients. This risk extended 8 months post-infection. These changes in DSA status were associated with late allograft dysfunction. Risk factors for new or increased DSA responses in this KT patient cohort included the presence of circulating DSA pre-COVID-19 diagnosis and time post-transplantation. COVID-19 vaccination prior to infection and remdesivir administration during infection were each associated with decreased likelihood of developing a new or increased DSA response. These data show that new or enhanced DSA responses frequently occur among KT patients requiring admission with COVID-19 and suggest that surveillance, vaccination, and antiviral therapies may be important tools to prevent alloimmunity in these individuals.

Avoiding surveillance biopsy: Use of a noninvasive biomarker assay in a real-life scenario.

PURPOSE: TruGraf™ blood test measures a specific gene expression signature in peripheral blood mononuclear cells for noninvasive assessment of kidney transplant recipients (KTRs) with stable renal function, excluding subclinical acute rejection (subAR) with high degree of confidence. Study objective was to correlate TruGraf™ test with 6-month surveillance biopsy (SBx). METHODS: Prospective, single-center study of 116 consecutive KTRs with SBx performed at 6 months post-transplant..TruGraf™ done at time of SBx; results compared with histology (Banff 2017) for concordance. RESULTS: Of 116 enrollees, 26 excluded, absent biopsy (n = 17), test quality control issues (n = 9), leaving 90 KTRs-66% deceased donor kidneys, 58% African American, and 59% male. TruGraf™ result negative in 67 subjects; 54 had normal biopsy, indicating SBx could have been avoided. Eight subjects had true positive result where biopsy justified. Unnecessary biopsy would have been performed in 15 subjects with false-positive TruGraf™, and subAR missed in 13 subjects with false-negative test. In overall population of 90 patients, SBx would have been avoided in 54 (60%). CONCLUSIONS: Implementation of TruGraf™ testing in a "real-world" cohort at the time of SBx identified a significant proportion of KTRs that could have avoided SBx.

Redefining the Influence of Ethnicity on Simultaneous Kidney and Pancreas Transplantation Outcomes: A 15-year Single-center Experience.

OBJECTIVE: To examine the largest single-center experience of simultaneous kidney/pancreas transplantation (SPK) transplantation among African-Americans (AAs). BACKGROUND: Current dogma suggests that AAs have worse survival following SPK than white recipients. We hypothesize that this national trend may not be ubiquitous. METHODS: From August 30, 1999, through October 1, 2014, 188 SPK transplants were performed at the University of Alabama at Birmingham (UAB) and 5523 were performed at other US centers. Using Kaplan-Meier survival estimates and Cox proportional hazards regression, we examined the influence of recipient ethnicity on survival. RESULTS: AAs comprised 36.2% of the UAB cohort compared with only 19.1% nationally (P < 0.01); yet, overall, 3-year graft survival was statistically higher among UAB than US cohort (kidney: 91.5% vs 87.9%, P = 0.11; pancreas: 87.4% vs 81.3%; P = 0.04, respectively) and persisted on adjusted analyses [kidney adjusted hazard ratio (aHR): 0.58, 95% confidence interval (95% CI) 0.35-0.97, P = 0.04; pancreas aHR: 0.54, 95% CI 0.34-0.85, P = 0.01]. Among the UAB cohort, graft survival did not differ between AA and white recipients; in contrast, the US cohort experienced significantly lower graft survival rates among AA than white recipients (kidney 5 years: 76.5% vs 82.3%, P < 0.01; pancreas 5 years: 72.2% vs 76.3%, P = 0.01; respectively). CONCLUSION: Among a single-center cohort of SPK transplants overrepresented by AAs, we demonstrated similar outcomes among AA and white recipients and better outcomes than the US experience. These data suggest that current dogma may be incorrect. Identifying best practices for SPK transplantation is imperative to mitigate racial disparities in outcomes observed at the national level.

Albuminuria and Allograft Failure, Cardiovascular Disease Events, and All-Cause Death in Stable Kidney Transplant Recipients: A Cohort Analysis of the FAVORIT Trial.

RATIONALE & OBJECTIVE: Cardiovascular disease (CVD) is common and overall graft survival is suboptimal among kidney transplant recipients. Although albuminuria is a known risk factor for adverse outcomes among persons with native chronic kidney disease, the relationship of albuminuria with cardiovascular and kidney outcomes in transplant recipients is uncertain. STUDY DESIGN: Post hoc longitudinal cohort analysis of the Folic Acid for Vascular Outcomes Reduction in Transplantation (FAVORIT) Trial. SETTING & PARTICIPANTS: Stable kidney transplant recipients with elevated homocysteine levels from 30 sites in the United States, Canada, and Brazil. PREDICTOR: Urine albumin-creatinine ratio (ACR) at randomization. OUTCOMES: Allograft failure, CVD, and all-cause death. ANALYTICAL APPROACH: Multivariable Cox models adjusted for age; sex; race; randomized treatment allocation; country; systolic and diastolic blood pressure; history of CVD, diabetes, and hypertension; smoking; cholesterol; body mass index; estimated glomerular filtration rate (eGFR); donor type; transplant vintage; medications; and immunosuppression. RESULTS: Among 3,511 participants with complete data, median ACR was 24 (Q1-Q3, 9-98) mg/g, mean eGFR was 49±18 (standard deviation) mL/min/1.73m2, mean age was 52±9 years, and median graft vintage was 4.1 (Q1-Q3, 1.7-7.4) years. There were 1,017 (29%) with ACR < 10mg/g, 912 (26%) with ACR of 10 to 29mg/g, 1,134 (32%) with ACR of 30 to 299mg/g, and 448 (13%) with ACR ≥ 300mg/g. During approximately 4 years, 282 allograft failure events, 497 CVD events, and 407 deaths occurred. Event rates were higher at both lower eGFRs and higher ACR. ACR of 30 to 299 and ≥300mg/g relative to ACR < 10mg/g were independently associated with graft failure (HRs of 3.40 [95% CI, 2.19-5.30] and 9.96 [95% CI, 6.35-15.62], respectively), CVD events (HRs of 1.25 [95% CI, 0.96-1.61] and 1.55 [95% CI, 1.13-2.11], respectively), and all-cause death (HRs of 1.65 [95% CI, 1.23-2.21] and 2.07 [95% CI, 1.46-2.94], respectively). LIMITATIONS: No data for rejection; single ACR assessment. CONCLUSIONS: In a large population of stable kidney transplant recipients, elevated baseline ACR is independently associated with allograft failure, CVD, and death. Future studies are needed to evaluate whether reducing albuminuria improves these outcomes.

Renal function with cyclosporine C2 monitoring, enteric-coated mycophenolate sodium and basiliximab: a 12-month randomized trial in renal transplant recipients.

BACKGROUND: Cyclosporine exposure, as estimated by the area under the curve (AUC), predicts outcomes in renal transplantation. Cyclosporine concentration at two h post-dose (C(2)) has been shown to be the most reliable, single-point surrogate marker for AUC. The objective of this study was to measure renal function beyond month 2 post-transplant using two different C(2) maintenance targets in combination with enteric-coated mycophenolate sodium (EC-MPS), corticosteroids, and basiliximab induction. METHODS: In this open-label, multicenter trial, renal transplant recipients entered one of two randomized groups at day 61 post-transplant: group A (higher-C(2) range) or group B (lower-C(2) range). RESULTS: Patients (164) were recruited, and 141 patients were entered the randomized groups (group A, n = 66; group B, n = 75). At 12 months, the mean calculated creatinine clearance was significantly greater in group B than in group A (79.2 vs. 71.0 mL/min, p < 0.05). Biopsy-proven acute rejection occurred in 14.7% patients in group B and in 24.2% patients in group A (n.s.). During the 12-month trial, 17.7% patients discontinued EC-MPS because of adverse events. Group B (44.0%) had fewer serious adverse events when compared with group A (62.1%; p = 0.04). Overall patient and graft survival were 99.4% and 95.7% respectively. Among 99 high-risk patients (i.e., African-American race, previous transplant, PRA >35% or >4 HLA mismatches), mean creatinine clearance at 12 months was 65.6 mL/min and biopsy-proven rejection occurred in 20.2% patients. CONCLUSIONS: Low cyclosporine C(2) levels are associated with improved renal function compared with higher C(2) levels when used in conjunction with EC-MPS, steroids and basiliximab induction. EC-MPS with low cyclosporine C(2) levels, corticosteroids and basiliximab provides excellent renal function with good efficacy even in high-risk patients.

Posttransplant lymphoproliferative disorder among renal transplant patients in relation to the use of mycophenolate mofetil.

BACKGROUND: The introduction of increasingly effective immunosuppressants has raised the question of whether posttransplant lymphoproliferative disorder (PTLD), a complication of immunosuppression, would become more frequent. This study assessed the risk of PTLD in relation to immunosuppression during a period that saw the introduction and eventual market dominance of mycophenolate mofetil (MMF). METHODS: A case-control study was conducted at 23 U.S. transplant centers. All participants received a renal-only transplant on or after July 1, 1995. PTLD cases were reported by centers and confirmed by central review. The United Network for Organ Sharing (UNOS) supplemented case ascertainment and identified controls matched on center, transplant date, and age. Center personnel abstracted risk factor and therapy data for cases and up to four controls per case. Cases and controls were compared, using a matched multivariate analysis, to assess the impact of MMF as one component of triple-therapy adjusted for other drug therapies and known risk factors. RESULTS: Data were collected for 108 PTLD cases and 404 controls. PTLD risk for individuals on triple therapy with MMF was similar to the risk experienced by individuals on triple therapy with no MMF (adjusted odds ratio=1.19; 95% CI 0.55-2.55). There was no dose response relationship between MMF and PTLD risk. CONCLUSIONS: Use of MMF was not associated with an increase in PTLD among patients who received triple immunosuppressive therapy, but an excess in risk as large as 155% or a reduction in risk by as much as 45% cannot be ruled out.

Association of CD20+ infiltrates with poorer clinical outcomes in acute cellular rejection of renal allografts.

We undertook a study to ascertain the relationship between the presence of CD20-positive B-lymphocytes in renal allografts undergoing acute cellular rejection and graft survival. We identified 27 patients transplanted between January 1, 1998 and December 31, 2001, with biopsy-proven Banff 1-A or Banff 1-B rejection in the first year after transplantation, and stained the specimens for CD20 and C4d. At least 4 years of follow-up data were available for each patient studied. Six patients had CD20-positive B-cell clusters in the interstitium, and 21 patients were negative for CD20 infiltrates. The CD20-positive group was significantly more likely to have steroid-resistant rejection and reduced graft survival compared to CD20-negative controls. This study supports prospective identification of CD20-positive B-cell clusters in biopsy-proven rejection and offers a therapeutic rationale for a trial of monoclonal anti-CD20 antibody in such patients.