Progress in individualizing autologous islet isolation techniques for pediatric islet autotransplantation after total pancreatectomy in children for chronic pancreatitis

Total pancreatectomy with islet autotransplantation is performed to treat chronic pancreatitis in children. Successful islet isolation must address the challenges of severe pancreatic fibrosis and young donor age. We have progressively introduced modifications to optimize enzymatic and mechanical dissociation of the pancreas during islet isolation. We evaluated 2 islet isolation metrics in 138 children—digest islet equivalents per gram pancreas tissue (IEQ/g) and digest IEQ per kilogram body weight (IEQ/kg), using multiple regression to adjust for key disease and patient features. Islet yield at digest had an average 4569 (standard deviation 2949) islet equivalent (IEQ)/g and 4946 (4009) IEQ/kg, with 59.1% embedded in exocrine tissue. Cases with very low yield (<2000 IEQ/g or IEQ/kg) have decreased substantially over time, 6.8% and 9.1%, respectively, in the most recent tertile of time compared to 19.2% and 23.4% in the middle and 34.1% and 36.4% in the oldest tertile. IEQ/g and IEQ/kg adjusted for patient and disease factors improved in consistency and yield in the modern era. Minimal mechanical disruption during digestion, warm enzymatic digestion using enzyme collagenase:NP activity ratio < 10:1, coupled with extended distension and trimming time during islet isolation of younger and fibrotic pediatric pancreases, gave increased islet yield with improved patient outcomes.     

Metabolic measures before surgery and long-term diabetes outcomes in recipients of total pancreatectomy and islet autotransplantation

In this single-center, retrospective cohort study, we aimed to elucidate simple metabolic markers or surrogate indices of β-cell function that best predict long-term insulin independence and goal glycemic HbA1c control (HbA1c ≤ 6.5%) after total pancreatectomy with islet autotransplantation (TP-IAT). Patients who underwent TP-IAT (n = 371) were reviewed for metabolic measures before TP-IAT and for insulin independence and glycemic control at 1, 3, and 5 years after TP-IAT. Insulin independence and goal glycemic control were achieved in 33% and 68% at 1 year, respectively. Although the groups who were insulin independent and dependent overlap substantially on baseline measures, an individual who has abnormal glycemia (prediabetes HbA1c or fasting glucose) or estimated IEQs/kg < 2500 has a very high likelihood of remaining insulin dependent after surgery. In multivariate logistic regression modelling, metabolic measures correctly predicted insulin independence in about 70% of patients at 1, 3, and 5 years after TP-IAT. In conclusion, metabolic testing measures before surgery are highly associated with diabetes outcomes after TP-IAT at a population level and correctly predict outcomes in approximately two out of three patients. These findings may aid in prognostic counseling for chronic pancreatitis patients who are likely to eventually need TP-IAT.     

Regulatory considerations of delayed autologous islet infusion in a 4‐year‐old child undergoing total pancreatectomy for chronic pancreatitis

In patients undergoing total pancreatectomy for chronic pancreatitis, isolation, and infusion of autologous islets must comply with Good Manufacturing Practices standards established by the Food and Drug Administration (FDA) but does not standardly require an Investigational New Drug (IND) status. We report a case of a 4‐year‐old child with severe hereditary pancreatitis who developed clinical sepsis during total pancreatectomy (TP) surgery; subsequent pancreas, islet, and blood cultures were positive for Enterococcus. Because of clinical deterioration, planned islet infusion was aborted and islets were kept viable in a culture period while the patient was stabilized. Two days later, 38 000 islet equivalents (IEQ, 2808 IEQ/kg) were infused in a second procedure. Because maintaining the islets in culture met the FDA standard for “more than minimal” tissue manipulation, an emergency IND was obtained from the FDA to permit delayed infusion. The patient tolerated islet infusion well, and subsequently has partial islet graft function with normal glucoses and minimal insulin needs. This case highlights the possibility to delay islet infusion in an emergency, the potential for success with few islets in a young child, and the need to consider regulatory complexities of islet transplant in this situation.     

Total pancreatectomy with islet cell autotransplantation in a 2-year-old child with hereditary pancreatitis due to a PRSS1 mutation

Acute recurrent and chronic pancreatitis in children carries high morbidity and burden. Compared to adults, ~75% of the cases of chronic pancreatitis in children are associated with underlying genetic mutations. The decision to intervene and the optimal timing poses unique challenges. Total pancreatectomy and islet cell autotransplantation (TPIAT) provides definitive therapy to relieve pain and improve quality of life while minimizing the risk of pancreatogenic diabetes. Substantial clinical data are available for adults; however, information on clinical outcomes in children remains scarce, particularly for very young children. Herein, we present an unusual, complex case of a 2-year-old child that underwent a successful TPIAT due to hereditary pancreatitis with an underlying mutation in PRSS1 gene, complicated by unremitting pancreatic ascites, hemorrhage, and sepsis. This is the youngest case to be reported in the literature. We provide a comprehensive report of the course and procedures implemented in this patient to guide other teams when considering these extraordinary measures in similar cases.     

Utility of arginine stimulation testing in preoperative assessment of children undergoing total pancreatectomy with islet autotransplantation

Metabolic outcomes after total pancreatectomy with islet autotransplantation (TPIAT) are influenced by the islet mass transplanted. Preclinical and clinical studies indicate that insulin and C‐peptide levels measured after intravenous administration of the beta cell secretagogue arginine can be used to estimate the available islet mass. We sought to determine if preoperative arginine stimulation test (AST) results predicted transplanted islet mass and metabolic outcomes in pediatric patients undergoing TPIAT. We evaluated the association of preoperative C‐peptide and insulin responses to AST with islet isolation metrics using linear regression, and with postoperative insulin independence using logistic regression. Twenty‐six TPIAT patients underwent preoperative AST from 2015 to 2018. The acute C‐peptide response to arginine (ACRarg) was correlated with isolated islet equivalents (IEQ; r = 0.59, P = 0.002) and islet number (IPN; r = 0.48, P = 0.013). The acute insulin response to arginine (AIRarg) was not significantly correlated with IEQ (r = 0.38, P = 0.095) or IPN (r = 0.41, P = 0.071). Neither ACRarg nor AIRarg was associated with insulin use at 6 months postoperatively. Preoperative C‐peptide response to arginine correlates with islet mass available for transplant in pediatric TPIAT patients. AST represents an additional tool before autotransplant to provide counseling on likely islet mass and to inform quality improvements of islet isolation techniques.     

Intellectual and academic outcomes after pediatric liver transplantation: Relationship with transplant‐related factors

As survival rates for pediatric liver transplant continue to increase, research attention is turning toward long‐term functional consequences, with particular interest in whether medical and transplant‐related factors are implicated in neurocognitive outcomes. The relative importance of different factors is unclear, due to a lack of methodological uniformity, inclusion of differing primary diagnoses, varying transplant policies, and organ availability in different jurisdictions. This cross‐sectional, single‐site study sought to address various methodological limitations in the literature and the paucity of studies conducted outside of North America and Western Europe by examining the intellectual and academic outcomes of Australian pediatric liver transplant recipients (N = 40). Participants displayed significantly poorer intellectual and mathematical abilities compared with the normative population. Greater time on the transplant waitlist was a significant predictor of poorer verbal intelligence, working memory, mathematical abilities, and reading but only when considering the subgroup of children with biliary atresia. These findings support reducing the time children wait for a transplant as a priority.     

Variability in endocrine cell identity in patients with chronic pancreatitis undergoing islet autotransplantation

Beta‐cell dedifferentiation as shown by cellular colocalization of insulin with glucagon and/or vimentin, and decreased expression of MAFA and/or urocortin3 has been suggested to contribute to metabolic decompensation in type 2 diabetes, and was recently described postimplantation in islet allotransplant patients. Dysglycaemia and diabetes mellitus are often encountered preoperatively in patients undergoing pancreatectomy and islet autotransplantation (PIAT). In this series of case reports, we document variation in islet phenotypic identity in three patients with chronic pancreatitis (CP) without diabetes or significant insulin resistance who subsequently underwent PIAT. Pancreas histology was examined using colocalization of endocrine hormones, mesenchymal and pan‐endocrine markers in islets, and the relative expression of MAFA and urocortin3 in insulin‐expressing cells as compared to that of nondiabetic and type 2 diabetic donors. We present results of pre‐ and posttransplant clinical metabolic testing. Varying degrees of islet‐cell dedifferentiation are identified in nondiabetic patients with CP at the time of PIAT, and may need further investigation.     

Improved outcomes of islet autotransplant after total pancreatectomy by combined blockade of IL‐1β and TNFα

The efficacy of islet transplant is compromised by a significant loss of islet mass posttransplant due to an innate inflammatory reaction. We report the use of a combination of etanercept and anakinra (ANA+ETA) to block inflammatory islet damage in 100 patients undergoing total pancreatectomy with islet autotransplant. The patients were divided into 3 groups: no treatment (control [CTL]), etanercept alone (ETA), or a combination of etanercept and anakinra (ANA+ETA). Peritransplant serum samples were analyzed for protein markers of islet damage and for inflammatory cytokines. Graft function was assessed by fasting blood glucose, basal C‐peptide, secretory unit of islet transplant objects (SUITO) index, and hemoglobin A_1c. Administration of both antiinflammatory drugs was well tolerated without any major adverse events. Reductions in interleukin‐6, interleukin‐8, and monocyte chemoattractant protein 1 were observed in patients receiving ANA+ETA compared with the CTL group, while also showing a modest improvement in islet function as assessed by basal C‐peptide, glucose, hemoglobin A_1c, and SUITO index but without differences in insulin dose. These results suggest that double cytokine blockade (ANA+ETA) reduces peritransplant islet damage due to nonspecific inflammation and may represent a promising strategy to improve islet engraftment, leading to better transplant outcomes.     

Diabetes‐free survival after extended distal pancreatectomy and islet auto transplantation for benign or borderline/malignant lesions of the pancreas

Islet autotransplant is particularly attractive to prevent diabetes after extended pancreatectomy for benign or borderline/malignant pancreas disease. Between 2008 and 2018, 25 patients underwent left extended pancreatectomy (>60%) and islet autotransplant for a neoplasm located in the pancreatic neck or proximal body. Overall, disease‐free and diabetes‐free survivals were estimated and compared with those observed in 68 nondiabetic patients who underwent distal pancreatectomy for pancreatic neoplasms without islet autotransplant. Median follow‐up was 4 years. We observed no deaths and a low morbidity (nonserious procedure‐related complications in 2 of 25 patients). Patient and insulin‐independent survival rates at 4 years were 100% and 96%, respectively. Glucose homeostasis remained within a nondiabetic range at all times for 19 (73%) of 25 patients. Preoperative glycemic level and insulin resistance were major predictors of diabetes development in these patients. Patients undergoing islet autotransplant had a longer diabetes‐free survival than did patients without islet autotransplant (P = .04). In conclusion, islet autotransplant after extended pancreatic resection for neoplasms is a safe and successful procedure for preventing diabetes.     

Patient‐reported health outcomes in long‐term lung transplantation survivors: A prospective cohort study

During the last three decades lung transplantation (LTx) has become a proven modality for increasing both survival and health‐related quality of life (HRQoL) in patients with various end‐stage lung diseases. Most previous studies have reported improved HRQoL shortly after LTx. With regard to long‐term effects on HRQoL, however, the evidence is less solid. This prospective cohort study was started with 828 patients who were on the waiting list for LTx. Then, in a longitudinal follow‐up, 370 post‐LTx patients were evaluated annually for up to 15 years. For all wait‐listed and follow‐up patients, the following four HRQoL instruments were administered: State‐Trait Anxiety Inventory, Zung Self‐rating Depression Scale, Nottingham Health Profile, and a visual analogue scale. Cross‐sectional and generalized estimating equation (GEE) analysis for repeated measures were performed to assess changes in HRQoL during follow‐up. After LTx, patients showed improvement in all HRQoL domains except pain, which remained steady throughout the long‐term follow‐up. The level of anxiety and depressive symptoms decreased significantly and remained constant. In conclusion, this study showed that HRQoL improves after LTx and tends to remain relatively constant for the entire life span.     

Total pancreaticoduodenectomy with autologous islet transplantation 14 years after liver‐contained composite visceral transplantation

Chronic pancreatitis (CP) is a severely disabling disorder with potential detrimental effects on quality of life, gut function, and glucose homeostasis. Disease progression often results in irreversible morphological and functional abnormalities with development of chronic pain, mechanical obstruction, and pancreatic insufficiency. Along with comprehensive medical management, the concept of total pancreatectomy and islet autotransplantation (TP‐AIT) was introduced 40 years ago for patients with intractable pain and preserved beta‐cell function. With anticipated technical difficulties, total excision of the inflamed‐disfigured gland is expected to alleviate the incapacitating visceral pain and correct other associated abdominal pathology. With retrieval of sufficient islet‐cell mass, the autologous transplant procedure has the potential to maintain an euglycemic state without exogenous insulin requirement. The reported herein case of CP‐induced recalcitrant pain and foregut obstruction is exceptional because of the technical challenges in performing native pancreaticoduodenectomy in close proximity to the composite visceral allograft with complex vascular and gut reconstructions. Equally novel is transplanting the auto‐islets in the liver‐contained visceral allograft. Despite intravenous nutrition shortly after birth, liver transplantation at age 13, retransplantation with liver‐contained visceral allograft at age 17 and TP‐AIT at age 31, the 38‐year‐old recipient is currently pain free with full nutritional autonomy and normal glucose homeostasis.     

Assessment of simple indices based on a single fasting blood sample as a tool to estimate beta‐cell function after total pancreatectomy with islet autotransplantation – a prospective study

We investigated six indices based on a single fasting blood sample for evaluation of the beta‐cell function after total pancreatectomy with islet autotransplantation (TP‐IAT). The Secretory Unit of Islet Transplant Objects (SUITO), transplant estimated function (TEF), homeostasis model assessment (HOMA‐2B%), C‐peptide/glucose ratio (CP/G), C‐peptide/glucose creatinine ratio (CP/GCr) and BETA‐2 score were compared against a 90‐min serum glucose level, weighted mean C‐peptide in mixed meal tolerance test (MMTT), beta score and the Igls score adjusted for islet function in the setting of IAT. We analyzed values from 32 MMTTs in 15 patients after TP‐IAT with a follow‐up of up to 3 years. Four (27%) individuals had discontinued insulin completely prior to day 75, while 6 out of 12 patients (50%) did not require insulin support at 1‐year follow‐up with HbA1c 6.0% (5.5–6.8). BETA‐2 was the most consistent among indices strongly correlating with all reference measures of beta‐cell function (r = 0.62–0.68). In addition, it identified insulin independence (cut‐off = 16.2) and optimal/good versus marginal islet function in the Igls score well, with AUROC of 0.85 and 0.96, respectively. Based on a single fasting blood sample, BETA‐2 score has the most reliable discriminant value for the assessment of graft function in patients undergoing TP‐IAT.     

Patient‐reported outcome measures for life participation in kidney transplantation: A systematic review

For many patients with end‐stage kidney disease, transplantation improves survival and quality of life compared with dialysis. However, complications and side effects in kidney transplant recipients can limit their ability to participate in activities of daily living including work, study, and recreational activities. The aim of this study was to identify the characteristics, content, and psychometric properties of the outcome measures used to assess life participation in kidney transplant recipients. We searched MEDLINE, Embase, PsycINFO, and CINAHL from inception to July 2018 for all studies that reported life participation in kidney transplant recipients. Two authors identified instruments measuring life participation and reviewed for characteristics. In total, 230 studies were included: 19 (8%) randomized trials, 17 (7%) nonrandomized trials, and 194 (85%) observational studies. Across these studies, we identified 29 different measures that were used to assess life participation. Twelve (41%) measures specifically assessed aspects of life participation (eg, disability assessment, daily activities of living), while 17 (59%) assessed other constructs (eg, quality of life) that included questions on life participation. Validation data to support the use of these measures in kidney transplant recipients were available for only 7 measures. A wide range of measures have been used to assess life participation in kidney transplant recipients, but validation data supporting the use of these measures in this population are sparse. A content relevant and validated measure to improve the consistency and accuracy of measuring life participation in research may inform strategies for transplant recipients to be better able to engage in their life activities.     

Life of patients 10 years after a successful pediatric intestinal transplantation in Europe

A multicenter Europe‐wide single‐point study in intestinal transplantation (ITx) centers was conducted to identify and describe patients surviving for more than 10 years after ITx in childhood. The health and nutritional status, care requirements and psychosocial status were recorded. Among 120 transplanted before 2005, 38 patients with a functioning graft were included. Thirty (79%) had an exclusive oral diet, seven (18%) complimentary enteral nutrition for eating disorders, and one a combination of parenteral and enteral nutrition. They received a median of five drugs daily and five had a stoma. We did not observe any catch‐up growth during the 10 years of follow‐up. In the previous five years, 22 patients needed unplanned hospitalization with a median in‐patient stay of six days. Eleven needed ongoing psychiatric follow‐ups, and nine needed other specialist follow‐ups. An increasing independency from parents was seen after the age of 18, with three having a stable employment and 31 pursuing education. Despite a good graft function, growth may not catch up. The burden of medical care remains high in the long term. This has to be closely followed in a multidisciplinary setting to improve long‐term quality of life in these patients.     

Islet damage during isolation as assessed by miRNAs and the correlation of miRNA levels with posttransplantation outcome in islet autotransplantation

High‐quality pancreatic islets are essential for better posttransplantation endocrine function in total pancreatectomy with islet autotransplantation (TPIAT), yet stress during the isolation process affects quality and yield. We analyzed islet‐enriched microRNAs (miRNAs) ‐375 and ‐200c released during isolation to assess damage and correlated the data with posttransplantation endocrine function. The absolute concentration of miR‐375, miR‐200c, and C‐peptide was measured in various islet isolation steps, including digestion, dilution, recombination, purification, and bagging, in 12 cases of TPIAT. Posttransplantation glycemic control was monitored through C‐peptide, hemoglobin A_1c, insulin requirement, and SUITO index. The amount of miR‐375 released was significantly higher during enzymatic digestion followed by the islet bagging (P < .001). Mir‐200c mirrored these changes, albeit at lower concentrations. In contrast, the C‐peptide amount was significantly higher in the purification and bagging steps (P < .001). Lower amounts of miR‐375 were associated with a lower 6‐month insulin requirement (P = .01) and lower hemoglobin A_1c (P = .04). Measurement of the absolute quantity of miRNA‐375 and ‐200c released during islet isolation is a useful tool to assess islet damage. The quantity of released miRNA is indicative of posttransplantation endocrine function in TPIAT patients.     

Trajectories of health‐related quality of life among renal transplant patients associated with graft failure and symptom distress: Analysis of the BENEFIT and BENEFIT‐EXT trials

Understanding the correlation between transplant symptoms, health‐related quality of life (HRQoL), and graft outcomes is needed to support patient‐focused drug development and posttransplant management. A post‐hoc analysis of patient‐reported outcomes from the Phase III belatacept trials was conducted in order to investigate the interrelationship between trajectories of HRQoL, symptom experience, and allograft outcomes. HRQoL and symptom experience were evaluated using Short‐Form 36 Survey (SF‐36) and Modified Transplant Symptom Occurrence and Distress Scale (MTSOSD‐59R), respectively. HRQoL was captured in 831 eligible renal transplant patients at baseline, 12, 24, and 36 months posttransplant. Following transplantation, patients reported improvements in all SF‐36 subscales compared to baseline. Latent class analysis revealed four trajectories in perceived general health, which were associated with graft failure after adjustment. Compared to patients with good perceived health, patients with fair and poor perceived health had 4.7 (95% confidence interval [CI] 1.5‐14.8, P < .01) and 19.8 (95% CI 5.9‐66.0, P < .01) times the risk of graft failure, respectively. Using multinomial logistic regression, different sets of symptoms were associated with perceived general health at baseline and 12 months posttransplant. The study supports monitoring HRQoL and symptom experience to capture each patient's health perspective, improve drug development, and optimize posttransplant management.     

Islet alloautotransplantation: Allogeneic pancreas transplantation followed by transplant pancreatectomy and islet transplantation

Simultaneous pancreas–kidney (SPK) transplantation is an important treatment option for patients with type 1 diabetes (T1D) and end‐stage renal disease (ESRD). Due to complications, in up to 10% of patients, allograft pancreatectomy is necessary shortly after transplantation. Usually the donor pancreas is discarded. Here, we report on a novel procedure to rescue endocrine tissue after allograft pancreatectomy. A 39‐year‐old woman with T1D and ESRD who had undergone SPK transplantation required emergency allograft pancreatectomy due to bleeding at the vascular anastomosis. Islets were isolated from the removed pancreas allograft, and almost 480 000 islet equivalents were infused into the portal vein. The patient recovered fully. After 3 months, near‐normal mixed meal test (fasting glucose 7.0 mmol/L, 2‐hour glucose 7.5 mmol/L, maximal stimulated C‐peptide 3.25 nmol/L, without insulin use in the preceding 36 hours) was achieved. Glycated hemoglobin while taking a low dose of long‐acting insulin was 32.7 mmol/mol hemoglobin (5.3%). When a donor pancreas is lost after transplantation, rescue β cell therapy by islet alloautotransplantation enables optimal use of scarce donor pancreata to optimize glycemic control without additional HLA alloantigen exposure.     

Long‐Term Medical and Psychosocial Outcomes in Living Liver Donors

Due to the enduring organ shortage, living donor liver transplantation has been a valuable treatment strategy for advanced liver disease patients for over 20 years. A variety of reviews have summarized the extensive data now available on medical and psychosocial risks to living donors in the aftermath of donation. However, evidence on donor medical and psychosocial outcomes beyond the first year postdonation has not been synthesized in any previous review. The evidence base on such “long‐term” outcomes has been growing in recent years. A review of this evidence would therefore be timely and could serve as an important resource to assist transplant centers in their efforts to fully educate prospective donors and gain informed consent, as well as develop appropriate postdonation clinical care and surveillance plans. We reviewed recent literature on long‐term donor outcomes, considering (a) medical outcomes, including mortality risk, rates of complications, abnormalities detected in laboratory testing, and the progress of liver regeneration; and (b) donor‐reported psychosocial outcomes reflecting physical, emotional, and interpersonal/socioeconomic well‐being, as well as overall health‐related quality of life. We summarize limitations and gaps in available evidence, and we provide recommendations for future research and clinical care activities focused on long‐term outcomes in liver donors.     

Long‐Term Immunosuppression After Solitary Islet Transplantation Is Associated With Preserved C‐Peptide Secretion for More Than a Decade

We report on two patients with type 1 diabetes (T1D) after solitary islet transplantation in 2001. They received steroid‐sparing immunosuppression (daclizumab, sirolimus, and tacrolimus according to the Edmonton protocol). Both patients became insulin independent for 2 years: Patient A, a 42‐year‐old female with a 12‐year history of T1D, received two islet infusions; patient B, a 53‐year‐old female with a 40‐year T1D history, received one islet infusion. Pretransplant, both had undetectable C‐peptide concentrations and frequent and severe hypoglycemia. Pretransplant, hemoglobin A1c (HbA1c) was 7.8% and 8.8% and insulin requirements were 0.47 and 0.33 units/kg/day, respectively. Posttransplant, C‐peptide levels remained detectable while immunosuppression was continued, but decreased over time. Insulin was re‐started 2 years posttransplant in both patients. Since patient A's glycemia and insulin requirements trended toward pretransplant levels, immunosuppression was discontinued after 13 years. This resulted in a sudden cessation of C‐peptide secretion. Patient B continues on immunosuppression, has better HbA1c, and half the insulin requirement compared to pretransplant. Both patients no longer experience severe hypoglycemia. Herein, we document blood glucose concentrations over time (>30 000 measurements per patient) and β cell function based on C‐peptide secretion. Despite renewed insulin dependence, both patients express satisfaction with having undergone the procedure.     

Association of time-updated plasma calcium and phosphate with graft and patient outcomes after kidney transplantation

Disturbances in calcium-phosphate homeostasis are common after kidney transplantation. We aimed to assess the relationship between deregulations in plasma calcium and phosphate over time and mortality and death-censored graft failure (DCGF). In this prospective cohort study, we included kidney transplant recipients with ≥2 plasma calcium and phosphate measurements. Data were analyzed using time-updated Cox regression analyses adjusted for potential confounders including time-updated kidney function. We included 2769 patients (mean age 47 ± 14 years, 42.3% female) with 138 496 plasma calcium and phosphate levels (median [IQR] 43 [31–61] measurements per patient). During follow-up of 16.3 [8.7–25.2] years, 17.2% developed DCGF and 7.9% died. Posttransplant hypercalcemia was associated with an increased risk of mortality (1.63 [1.31–2.00], p < 0.0001), but not with DCGF. Hyperphosphatemia was associated with both DCGF (2.59 [2.05–3.27], p < .0001) and mortality (3.14 [2.58–3.82], p <  .0001). Only the association between hypercalcemia and mortality remained significant in sensitivity analyses censored by a simultaneous eGFR <45 mL/min/1.73 m². Hypocalcemia and hypophosphatemia were not consistently associated with either outcome. Posttransplant hypercalcemia, even in the presence of preserved kidney function, was associated with an increased mortality risk. Associations of hyperphosphatemia with DCGF and mortality may be driven by eGFR.