Parathyroid Allotransplantation: Report of Outcomes in 3 Patients.

BACKGROUND: Hypoparathyroidism is a relatively rare endocrine disorder defined as inadequate parathyroid hormone (PTH) secretion leading to a clinical syndrome characterized by hyperphosphatemia and hypocalcemia. This condition has high morbidity; patients present with a heterogeneous range of emotional, mental, and physical symptoms. We present our experience with PTH transplantation, using parathyroid glands surgically removed in the setting of secondary hyperparathyroidism, with a description of the clinical course, immunosuppressive management, and surgical technique. METHODS: Between 2017 and 2021, 3 patients underwent parathyroid allotransplantation at the University of Illinois at Chicago. The 2 outcomes of interest were (1) symptomatic relief and improvement in calcium levels and (2) time to graft failure, defined as the presence of undetectable PTH levels. RESULTS: All 3 patients experienced dramatic improvement in their debilitating symptoms, even though 2 patients required repeated PTH transplantation procedures. One patient had a remarkable course with symptom resolution, normalization of PTH levels, and a great reduction in calcium supplementation. CONCLUSION: The use of hyperplastic glands from patients with secondary hyperparathyroidism undergoing 4-gland parathyroidectomy with autotransplantation represents an important source. However, a uniform definition of graft viability and prospective studies with long follow-ups are needed to address how much parathyroid tissue is optimally transplanted and the need for immunosuppression. Most patients affected by hypoparathyroidism are successfully managed by medical treatment; however, some do not respond to therapy and present debilitating symptoms related to hypocalcemia. This subgroup may benefit from parathyroid allotransplantation. Our 3 patients had remarkable improvement in their symptoms with the adoption of hyperplastic glands. Two out of 3 patients required multiple procedures to sustain symptom control.

Impact of early corticosteroid withdrawal on simultaneous pancreas-kidney transplant long-term outcomes: Single center experience and comparison to the International Pancreas Transplant Registry.

BACKGROUND: There remains a paucity of modern data comparing early steroid withdrawal (ESW) versus chronic corticosteroid (CCS) immunosuppression in simultaneous pancreas kidney (SPK) transplant recipients with long-term follow-up. Therefore, the purpose of this study is to assess the effectiveness and tolerability of ESW compared to CCS post-SPK. METHODS: This was a retrospective single-center matched comparison with the International Pancreas Transplant Registry (IPTR). Patients from University of Illinois Hospital (UIH) represented the ESW group and were compared to those matched CCS patients from the IPTR. Included patients were adult recipients of a primary SPK transplant between 2003 and 2018 within the US receiving rabbit anti-thymocyte globulin induction. Patients were excluded if they had early technical failures, missing IPTR data, graft thrombosis, re-transplant, or positive crossmatch SPK. RESULTS: A total of 156 patients were matched and included in the analysis. Patients were predominantly African American (46.15%) males (64.1%) with Type 1 diabetes etiology (92.31%). Overall pancreas allograft survival (hazard ratio [HR] = .89, 95% confidence interval [CI] .34-2.30, p = .81) and kidney allograft survival (HR = .80, 95%CI .32-2.03, p = .64) were similar between the two groups. Immunologic pancreas allograft loss was statistically similar at 1-year (ESW 1.3% vs. CCS 0%, p = .16), 5-year (ESW 1.3% vs. CCS 7.7%, p = .16), and 10-year (ESW 11.0% vs. CCS 7.7%, p = .99). The 1-year (ESW 2.6% vs. CCS 0%, p > .05), 5-year (ESW 8.3% vs. CCS 7.0%, p > .05), and 10-year (ESW 22.7% vs. CCS 9.9%, p = .2575) immunologic kidney allograft loss were also statistically similar. There was no difference in 10-year overall patient survival (ESW 76.2% vs. CCS 65.6%, p = .63). CONCLUSIONS: No differences were found between allograft or patient survival post-SPK when comparing an ESW or CCS protocol. Future assessment is needed to determine differences in metabolic outcomes.

Surgical opioid-avoidance protocol: a postoperative pharmacological multimodal analgesic intervention in diverse patient populations.

INTRODUCTION: This study evaluated the effect of a surgical opioid-avoidance protocol (SOAP) on postoperative pain scores. The primary goal was to demonstrate that the SOAP was as effective as the pre-existing non-SOAP (without opioid restriction) protocol by measuring postoperative pain in a diverse, opioid-naive patient population undergoing inpatient surgery across multiple surgical services. METHODS: This prospective cohort study was divided into SOAP and non-SOAP groups based on surgery date. The non-SOAP group had no opioid restrictions (n=382), while the SOAP group (n=449) used a rigorous, opioid-avoidance order set with patient and staff education regarding multimodal analgesia. A non-inferiority analysis assessed the SOAP impact on postoperative pain scores. RESULTS: Postoperative pain scores in the SOAP group compared with the non-SOAP group were non-inferior (95% CI: -0.58, 0.10; non-inferiority margin=-1). The SOAP group consumed fewer postoperative opioids (median=0.67 (IQR=15) vs 8.17 morphine milliequivalents (MMEs) (IQR=40.33); p<0.01) and had fewer discharge prescription opioids (median=0 (IQR=60) vs 86.4 MMEs (IQR=140.4); p<0.01). DISCUSSION: The SOAP was as effective as the non-SOAP group in postoperative pain scores across a diverse patient population and associated with lower postoperative opioid consumption and discharge prescription opioids.

Pain Interference in End Stage Kidney Disease is Associated with Changes in Gut Microbiome Features Before and After Kidney Transplantation.

BACKGROUND: Pain, a common debilitating symptom among kidney transplant recipients (KTRs), is among the most common and undertreated symptoms after kidney transplantation. AIMS: Characterize associations between gut microbiome features and pain interference before and after kidney transplantation. DESIGN: Longitudinal, repeated measures study, collecting fecal specimens and pain interference data pretransplant and 3 months posttransplant. SETTING: Participants were recruited at the kidney transplant clinic at the University of Illinois Hospital & Health Sciences System. PARTICIPANTS/SUBJECTS: 19 living donor kidney transplant recipients. METHODS: We assessed fecal microbial community structure with shotgun metagenomic sequencing; we used pain interference scores derived from the Patient-Reported Outcomes Measurement Information System-57. RESULTS: We measured a reduction in the Shannon diversity index in both groups after transplantation but observed no significant differences between groups at either time point. We did observe significant differences in fecal microbial Bray-Curtis similarity index among those reporting pain interference pre- transplant versus no pain interference at 3-months posttransplant (R = .306, p = .022), and between pain interference groups at posttransplant (R = .249, p = .041). Pairwise models showed significant differences between groups posttransplant in relative abundances of several taxa, including a 5-fold reduction.ßin Akkermansia among those with pain interference and a higher relative abundance of taxa associated with chronic inflammation in those with pain interference posttransplant. Functional gene analysis identified two features that were significantly enriched in those with pain interference, including a peptide transport system gene. CONCLUSIONS: Gut microbiota community structure differs between groups with and without pain interference at 3 months after kidney transplantation. Several taxa involved in intestinal barrier integrity and chronic inflammation were associated with posttransplant pain.

Consensus recommendations for use of maintenance immunosuppression in solid organ transplantation: Endorsed by the American College of Clinical Pharmacy, American Society of Transplantation, and the International Society for Heart and Lung Transplantation.

Advances in maintenance immunosuppression over the past three decades have improved solid organ transplantation outcomes dramatically. Uninterrupted access to immunosuppression is paramount to minimize rejection and maintain allograft and patient survival. There is no standardized approach to maintenance immunosuppression management. Agents used vary based on transplanted organ, center-specific protocol, provider expertise, insurance formularies, ability to cover co-pays, recipient characteristics and tolerability. Published data reflects this heterogeneity. Despite this limitation, maintenance immunosuppression usage cross pollinates between organ groups with standard of care agents often being used off-label, making medication access a challenge for many transplant recipients. A multidisciplinary panel of American transplant clinicians was formed to review published literature on maintenance immunosuppression with the goal to formulate consensus recommendations for their use in specific organ groups. These consensus recommendations are intended to provide transplant clinicians with a summary of literature on maintenance immunosuppression in the modern era and to support transplant team members working to secure medication access for patients.

Consensus recommendations for use of maintenance immunosuppression in solid organ transplantation: Endorsed by the American College of Clinical Pharmacy, American Society of Transplantation, and International Society for Heart and Lung Transplantation: An executive summary.

Advances in maintenance immunosuppression over the past three decades have improved solid organ transplantation outcomes dramatically. Uninterrupted access to immunosuppression is paramount to minimize rejection and maintain allograft and patient survival. Agents used vary based on transplanted organ, center-specific protocol, provider expertise, insurance formularies, ability to cover co-pays, recipient characteristics and tolerability. Published data reflects this heterogeneity. Despite these obstacles, the information about maintenance immunosuppression use cross pollinates between organ groups with standard of care agents often being used off-label, making medication access a challenge for many transplant recipients. A multidisciplinary panel of American transplant clinicians was formed to review published literature on maintenance immunosuppression with the goal to formulate consensus recommendations for their use in specific organ groups. These consensus recommendations are intended to provide transplant clinicians with a summary of literature on maintenance immunosuppression in the modern era, and to support transplant team members working to secure medication access for patients.

Implications for body weight extremes in solid organ transplantation.

The pharmacokinetic profiles of medications are altered in overweight and underweight patients, but few studies have described these differences in patients with body mass index extremes. As solid organ transplant programs expand their candidate selection criteria to accommodate a growing population of patients with weight extremes, it has become imperative to understand and evaluate the impact weight extremes have on the pharmacokinetics of life-sustaining immunosuppression in this population. This review will describe pharmacokinetic and dosing considerations for weight extremes in solid organ transplant recipients, including changes following bariatric surgeries, non-pharmacologic and pharmacologic management strategies for weight loss and gain, and potential drug-drug interactions with popular weight management products.

Factors Influencing Emergency Department Utilization and Hospital Re-Admissions in a Predominantly Obese, Racially Diverse Urban Renal Transplant Population.

INTRODUCTION: Early emergency department and hospital re-admissions are common in renal transplant recipients, but data are lacking in unique populations. Study Aim: The purpose of this study was to identify patient risk factors for multiple acute care utilization events within the first year of renal transplantation. DESIGN: This was a single-center, retrospective cohort study of adult renal transplant recipients between 9/2013-9/2016. Patients were compared across number of emergency department visits and by hospital re-admissions. Diagnoses were categorized. Univariate and multivariate logistic regression was used to assess risk for multiple acute care utilization events within the first 12 months post-transplant. RESULTS: A total of 216 patients were analyzed and were on average 50.5 (SD 13.9) years old, redominantly Black (49.77%) with an average body mass index of 33.33 (9.8) and were recipients of deceased donor renal transplants (61.11%). A total of 105 (48.6%) patients visited the emergency epartment and 119 (55.1%) patients had a hospital readmission. Patients having a body mass index >35 kg/m2 did not differ across emergency department visit or hospitalization groups. Delayed graft function (OR 2.86, 95% CI 1.07-7.65) and previous renal transplant (OR 2.77, 95% CI 1.04-7.39) were significantly associated with multiple acute care utilizations. DISCUSSION: Acute care utilization following renal transplantation was similar to previously reported experiences. Obesity did not impact use of acute care resources or patient outcomes. Strategies addressing potential preventable emergency visits and hospital re-dmissions should be promoted.

Discharge medication procurement and education after kidney transplantation.

Adherence to immunosuppressant medications is a key determinant of success following organ transplantation. Medication procurement and education are precursory. In March 2018, Medicare announced a rule change interpreted to prohibit delivery of Part B-covered immunosuppressive drugs to hospitals. A subsequent Medicare announcement clarified that immunosuppressive drug delivery to hospitals is acceptable, effective April 2019. To promulgate the perceived importance of medication delivery to hospitals among key providers of transplant discharge education, a 25-question descriptive survey was distributed between May and July 2018 to pharmacists affiliated with each active US kidney transplant program (n = 238). Survey goals were to describe discharge medication procurement practices, discharge medication teaching practices, and attitudes toward the value of medication education. A total of 155 responses were received from 115 different transplant centers. A majority (93%) of respondents require discharge medications to be onsite prior to hospital discharge. A majority (81%) of respondents use discharge medications during medication education. Acquisition of immunosuppressant medications and their delivery to the inpatient environment prior to discharge for the purpose of medication education is a common practice, is viewed as important, and serves to enhance discharge education, ensure safe transitions of care, and encourage medication adherence.

Pancreas Transplantation From Pediatric Donors: A Single-Center Experience.

BACKGROUND: Pancreas allografts from pediatric donors are considered less suitable due to the increased risk of surgical complications and reduced islet cell mass that may compromise function. METHODS: All pancreatic transplants, procured from donors younger than 18 years, between January 2007 and March 2017, were included in the analysis. The grafts were subdivided into 3 groups by donor's weight: less than 30 kg, 30 to 60 kg, greater than 60 kg. Analysis of patient and graft survival was done between the groups, and subsequently between the pediatric cohort and the adult-donor control group. RESULTS: Sixty-three pediatric-donor pancreas transplants were performed. The mean donor age and weight were of 12.10 ± 4.13 years and 47.8 ± 21.3 kg. Excellent metabolic control was achieved in 59 (93.65%) patients at the time of discharge and at a mean 5 year follow up, with the average hemoglobin A1c of 5.30 ± 0.61% and blood glucose level of 102.75 ± 20.70 mg/dL in those with a functioning graft. Nine graft losses were registered, of which one (1.6%) was due to arterial thrombosis. Eight (12.7%) patients experienced rejection. Overall graft survival and patient survival were of 85.7% and 92.1%, respectively, at a median follow-up of 37.07 months (minimum, 0.19 to maximum, 119.57). No differences among the 3 groups were identified. Long-term patient and allograft survival was comparable to that of the adult-donor pancreatic transplants. CONCLUSIONS: Pediatric-donor pancreas demonstrated excellent short-term outcomes with no surgical complications and promising long-term outcomes despite the smaller islet mass. Pancreata from pediatric donors should not be marginalized and can offset worsening organ shortage.

Pancreas Transplantation From Pediatric Donors: A United Network for Organ Sharing Registry Analysis.

BACKGROUND: Pancreas grafts from pediatric donors are still considered "not ideal." Perceived concerns are related to low islet mass and potential for graft thrombosis. METHODS: The study evaluated all pancreas transplants from January 2000 to May 2015 using the Organ Procurement and Transplant Network database. Comparative analysis of recipient and graft survival was performed between pediatric (≤18 years) and adult donors. In the pediatric group, the outcomes were stratified based on donor age (≤6, 7-12, and 13-18 years) and weight (<30, 30-95, and >95 kg). RESULTS: In the selected era, 18 430 pancreas transplants were performed from 4915 pediatric donors (27%). Short-term graft and patient survivals were comparable between pediatric and adult donors. Ten-year patient and graft survivals were higher in the pediatric donor group: (70% and 54% vs 68% and 51%, P = 0.001). However, very-low-weight pediatric donors (<30 kg) resulted in worse graft survival in the long term (44% at 10 years, P = 0.006). CONCLUSIONS: Pediatric donor pancreas transplants had comparable patient and graft survival to the adult donor transplants. However, the islet mass of very small donors could influence long-term graft survival if the weights of donors and recipients are not properly matched. Usage of "very small" pediatric donors was not associated with higher incidence of technical complications or early graft loss.

Simultaneous Living Donor Kidney and Parathyroid Allotransplantation: First Case Report and Review of Literature.

BACKGROUND: Congenital hypoparathyroidism can be severely debilitating for patients, leading to renal failure at young age. Parathyroid transplantation may represent a permanent parathyroid replacement therapy. In patients already on immunosuppression for other organ transplant, there is little additional risk involved with parathyroid allotransplantation. METHODS: Robotic assisted transaxillary single parathyroidectomy is performed on a living donor also donating a kidney to her sibling. RESULTS: Recipient total serum PTH levels became detectable after 3 days from the procedure and maintained for 9 months after transplant with minimal calcium supplementation after the procedure. Literature review and previous results are summarized. CONCLUSIONS: Obtaining a parathyroid gland and a kidney from the same donor reduces the exposure to different HLA antigens. The combined procedure using minimally invasive surgery is safe, with the additional cosmetic advantage and convenience for the willing donor. In the setting of need for immunosuppression, additional transplantation to treat the cause is safe and justified in the recipients.

Assessing pharmacologic and nonpharmacologic risks in candidates for kidney transplantation.

PURPOSE: Pharmacotherapy concerns and other factors with a bearing on patient selection for kidney transplantation are discussed. SUMMARY: The process of selecting appropriate candidates for kidney transplantation involves multidisciplinary assessment to evaluate a patient's mental, social, physical, financial, and medical readiness for successful surgery and good posttransplantation outcomes. Transplantation pharmacists can play important roles in the recognition and stratification of pharmacologic and nonpharmacologic risks in prospective kidney transplant recipients and the identification of issues that require a mitigation strategy. Key pharmacotherapy-related issues and considerations during the risk assessment process include (1) anticoagulation concerns, (2) cytochrome P-450 isoenzyme-mediated drug interactions, (3) mental health-related medication use, (4) chronic pain-related medication use, (5) medication allergies, (6) use of hormonal contraception and replacement therapy, (7) prior or current use of immunosuppressants, (8) issues with drug absorption, (9) alcohol use, (10) tobacco use, (11) active use of illicit substances, and (12) use of herbal supplements. Important areas of nonpharmacologic risk include vaccine delivery, infection prophylaxis and treatment, and socially related factors such as nonadherent behavior, communication barriers, and financial, insurance, or transportation challenges that can compromise posttransplantation outcomes. CONCLUSION: Consensus opinions of practitioners in transplantation pharmacy regarding the pharmacologic and nonpharmacologic factors that should be considered in assessing candidates for kidney transplantation are presented.

Interleukin-2 receptor blockade with humanized monoclonal antibody for solid organ transplantation.

IMPORTANCE OF THE FIELD: Induction therapy has reduced the incidence of acute rejection compared with historical standards. The potency of currently available induction immunosuppression is not without risk and should be carefully considered. Induction with daclizumab, an IL-2 receptor antagonist, has been used safely and effectively for over 10 years across different transplant types. As a result of daclizumab use, transplant centers are able to implement steroid-sparing or calcineurin minimization protocols. Unfortunately, the manufacturing costs have resulted in withdrawal of this agent from the market reducing the options for patients undergoing transplantation. AREAS COVERED IN THIS REVIEW: This review will update the reader on recently published daclizumab studies in adult solid organ transplant recipients, focusing on comparative studies with other induction agents. WHAT THE READER WILL GAIN: This paper will provide a summary of comparative studies between daclizumab and other induction therapies focusing on their efficacy and safety. TAKE HOME MESSAGE: Novel applications, such as long-term use in combination with calcineurin-inhibitor dose reduction and its value in the treatment of acute or chronic rejection have yet to be explored. Since daclizumab has been withdrawn from the market, future IL-2 receptor blockade will have to be achieved with basiliximab, which is a chimeric, monoclonal antibody directed against the same epitope.

ABO incompatible renal transplantation in an HIV-seropositive patient.

To date, there have been no reports of successful ABO blood group incompatible renal transplantation in HIV patients. We describe a case of a 47-year-old African American man with end-stage renal disease secondary to HIV-induced nephropathy who underwent a live unrelated (spouse) donor ABO blood group incompatible transplant using an intravenous immunoglobulin/plasmapheresis preconditioning regimen with interleukin-2 receptor antagonist induction along with tacrolimus and mycophenolate mofetil maintenance. The postoperative course was complicated by two acute cellular rejection (Banff Ia) episodes that were successfully managed with corticosteroid boluses and the addition of corticosteroids to maintenance immunosuppression. Antibody-mediated rejection was not observed on biopsy. The patient reached a serum creatinine nadir of 2.0 mg/dL on postoperative day 20, which has now been maintained for 170 days. His current CD4 count was 410 cells/microL.