Bladder Stones in Renal Transplant Patients: Presentation, Management, and Follow-up.

INTRODUCTION: The study aim was to analyze the presentation, management, and follow-up of renal transplant patients developing bladder calculi. METHODS: Patients who underwent renal transplant with postoperative follow-up at our institution were retrospectively analyzed (1984-2023) to assess for the development of posttransplant bladder stones. All bladder stones were identified by computerized tomography imaging and stone size was measured using this imaging modality. RESULTS: The prevalence of bladder calculi post-renal transplantation during the study window was 0.22% (N = 20/8,835) with a median time to bladder stone diagnosis of 13 years posttransplant. Of all bladder stone patients, 6 (30%) received deceased donor and 14 (70%) living donor transplants. There were 11 patients with known bladder stone composition available; the most common being calcium oxalate (N = 6). Eleven (55%) patients had clinical signs or symptoms (most commonly microhematuria). Fourteen of the bladder stone cohort patients (70%) underwent treatment including cystolitholapaxy in 12 subjects. Of these 14 patients, 9 (64%) were found to have nonabsorbable suture used for their ureteroneocystostomy closure. CONCLUSIONS: The prevalence of bladder stones post-renal transplant is low. The utilization of nonabsorbable suture for ureteral implantation was the main risk factor identified in our series. This technique is no longer used at our institution. Other factors contributing to bladder stone formation in this population warrant identification.

The Kidney Not Taken: Single-Kidney Use in Deceased Donors.

BACKGROUND: The nonuse rate for kidneys recovered from deceased donors is increasing, rising to 27% in 2023. In 10% of these cases, 1 kidney is transplanted but the mate kidney is not. STUDY DESIGN: We conducted a retrospective, single-center cohort study from December 2001 to May 2023 comparing single kidneys transplanted at our center (where the contralateral kidney was not used) to kidneys where both were transplanted separately, at least 1 of which was at our center. RESULTS: We performed 395 single deceased-donor kidney transplants in which the mate kidney was not transplanted. Primary reasons for mate kidney nonuse were as follows: no recipient located or list exhausted (33.4%), kidney trauma or injury or anatomic abnormalities (18.7%), biopsy findings (16.7%), and poor renal function (13.7%). Mean donor and recipient ages were 51.5 ± 14.2 and 60 ± 12.6 years, respectively. Mean kidney donor profile index was 73% ± 22%, and 104 donors (26.3%) had kidney donor profile index >85%. Mean cold ischemia was 25.6 ± 7.4 hours, and 280 kidneys (70.7%) were imported. Compared with 2,303 concurrent control transplants performed at our center, primary nonfunction or thrombosis (5.1% single vs 2.8% control) and delayed graft function (35.4% single vs 30.1% control) were greater with single-kidney use (both p < 0.05). Median patient and death-censored graft survival were shorter in the single group (11.6 vs 13.5 years, p = 0.03 and 11.6 vs 19 years, p = 0.003), although the former was at least double median survival on the waiting list. In patients with functioning grafts in the single-kidney group, 1-year mean serum creatinine was 1.77 ± 0.8 mg/dL and estimated glomerular filtration rate was 44.8 ± 20 mL/min/1.73 m 2 . CONCLUSIONS: These findings suggest that many mate kidneys are being inappropriately rejected, given the acceptable outcomes that can be achieved by transplanting the single kidney in appropriately selected recipients.

International Survey of Clinical Monitoring Practices in Pancreas and Islet Transplantation.

BACKGROUND: The long-term outcomes of both pancreas and islet allotransplantation have been compromised by difficulties in the detection of early graft dysfunction at a time when a clinical intervention can prevent further deterioration and preserve allograft function. The lack of standardized strategies for monitoring pancreas and islet allograft function prompted an international survey established by an International Pancreas and Islet Transplant Association/European Pancreas and Islet Transplant Association working group. METHODS: A global survey was administered to 24 pancreas and 18 islet programs using Redcap. The survey addressed protocolized and for-cause immunologic and metabolic monitoring strategies following pancreas and islet allotransplantation. All invited programs completed the survey. RESULTS: The survey identified that in both pancreas and islet allograft programs, protocolized clinical monitoring practices included assessing body weight, fasting glucose/C-peptide, hemoglobin A1c, and donor-specific antibody. Protocolized monitoring in islet transplant programs relied on the addition of mixed meal tolerance test, continuous glucose monitoring, and autoantibody titers. In the setting of either suspicion for rejection or serially increasing hemoglobin A1c/fasting glucose levels postpancreas transplant, Doppler ultrasound, computed tomography, autoantibody titers, and pancreas graft biopsy were identified as adjunctive strategies to protocolized monitoring studies. No additional assays were identified in the setting of serially increasing hemoglobin A1c levels postislet transplantation. CONCLUSIONS: This international survey identifies common immunologic and metabolic monitoring strategies utilized for protocol and for cause following pancreas and islet transplantation. In the absence of any formal studies to assess the efficacy of immunologic and metabolic testing to detect early allograft dysfunction, it can serve as a guidance document for developing monitoring algorithms following beta-cell replacement.

Early Graft Loss after Deceased-Donor Kidney Transplantation: What Are the Consequences?

BACKGROUND: Decreasing kidney discards continues to be of paramount importance for improving organ transplant access, but transplantation of nonideal deceased donor kidneys may have higher inherent risks of early graft loss (EGL). Patients with EGL (defined as graft failure within 90 days after transplant) are allowed reinstatement of waiting time according to United Network for Organ Sharing (UNOS) policy. The purpose of this study was to examine outcomes for patients experiencing EGL. STUDY DESIGN: We performed a single center retrospective review of adult deceased donor kidney transplant (DDKT)-alone recipients from 2001 to 2018, comparing those with EGL (including primary nonfunction [PNF]) to those without. RESULTS: EGL occurred in 103 (5.5%) of 1,868 patients, including 57 (55%) PNF, 25 (24%) deaths, 16 (16%) thrombosis, 3 (3%) rejection, and 2 (2%) disease recurrence. Kidney Donor Profile Index (KDPI) > 85% and donation after circulatory death (DCD) DDKTs did not increase risk of either EGL or PNF unless combined with prolonged cold ischemic time (CIT). For KDPI >85% with CIT >24 hours, the risk of EGL or PNF was tripled (EGL odds ratio [OR] 2.9, 95% CI 1.6-5.2; PNF OR3.6, 95% CI1.7-7.7). For DCD with CIT > 24 hours, increased risks were likewise seen for EGL (OR 2.4, 95% CI 1.3-4.3), and PNF (OR 3.2, 95% CI 1.5-7). One-year and 5-year patient survival rates were 60% and 50% after EGL, 80% and 73% after PNF, and 99% and 87% for controls, respectively. Only 24% of either EGL or PNF patients underwent retransplantation. CONCLUSIONS: EGL and PNF were associated with low retransplantation rates and inferior patient survival. Prolonged CIT compounds risks associated with KDPI > 85% and DCD donor kidneys. Therefore, policies promoting rapid allocation and increased local use of these kidneys should be considered.

Molecular Pathways Underlying Adaptive Repair of the Injured Kidney: Novel Donation After Cardiac Death and Acute Kidney Injury Platforms.

OBJECTIVE: To test the hypothesis that gene expression profiling in peripheral blood from patients who have undergone kidney transplantation (KT) will provide mechanistic insights regarding graft repair and regeneration. BACKGROUND: Renal grafts obtained from living donors (LD) typically function immediately, whereas organs from donation after cardiac death (DCD) or acute kidney injury (AKI) donors may experience delayed function with eventual recovery. Thus, recipients of LD, DCD, and AKI kidneys were studied to provide a more complete understanding of the molecular basis for renal recovery. METHODS: Peripheral blood was collected from LD and DCD/AKI recipients before transplant and throughout the first 30 days thereafter. Total RNA was isolated and assayed on whole genome microarrays. RESULTS: Comparison of longitudinal gene expression between LD and AKI/DCD revealed 2 clusters, representing 141 differentially expressed transcripts. A subset of 11 transcripts was found to be differentially expressed in AKI/DCD versus LD. In all recipients, the most robust gene expression changes were observed in the first day after transplantation. After day 1, gene expression profiles differed depending upon the source of the graft. In patients receiving LD grafts, the expression of most genes did not remain markedly elevated beyond the first day post-KT. In the AKI/DCD groups, elevations in gene expression were maintained for at least 5 days post-KT. In all recipients, the pattern of coordinate gene overexpression subsided by 28 to 30 days. CONCLUSIONS: Gene expression in peripheral blood of AKI/DCD recipients offers a novel platform to understand the potential mechanisms and timing of kidney repair and regeneration after transplantation.

Eversion endarterectomy of the deceased donor renal artery to prevent kidney discard.

INTRODUCTION: Deceased donor (DD) kidneys exhibiting severe atherosclerosis involving the renal artery (RA) may represent a contraindication to kidney transplantation (KT). METHODS: Eversion endarterectomy (EE) was performed as a salvage procedure to permit KT. RESULTS: We identified 17 cases (1.2% of all DD KTs during the study period) involving EE of the DD RA. Thirteen (76.5%) kidneys were imported, and mean Kidney Donor Profile Index (KDPI) was 81%. Mean DD age was 59 years, mean RA plaque length was 1.7 cm, and mean glomerulosclerosis on biopsy was 10%. Mean recipient age was 64 years, and dialysis vintage was 32 months. With a mean follow-up of 36 months, actual patient and graft survival rates were both 76.5%. One patient died early without a technical problem. Of the remaining 16 patients, 2-year patient and graft survival rates were both 100%. There were no early or late vascular complications. The incidence of delayed graft function was 35%. Mean serum creatinine and GFR levels in patients with functioning grafts at latest follow-up were 1.8 mg/dL and 40 mL/min, respectively. CONCLUSIONS: EE appears to be a safe and under-utilized procedure that may prevent discard of marginal donor kidneys and is associated with acceptable short-term outcomes.

Exocrine drainage in vascularized pancreas transplantation in the new millennium.

The history of vascularized pancreas transplantation largely parallels developments in immunosuppression and technical refinements in transplant surgery. From the late-1980s to 1995, most pancreas transplants were whole organ pancreatic grafts with insulin delivery to the iliac vein and diversion of the pancreatic ductal secretions to the urinary bladder (systemic-bladder technique). The advent of bladder drainage revolutionized the safety and improved the success of pancreas transplantation. However, starting in 1995, a seismic change occurred from bladder to bowel exocrine drainage coincident with improvements in immunosuppression, preservation techniques, diagnostic monitoring, general medical care, and the success and frequency of enteric conversion. In the new millennium, pancreas transplants are performed predominantly as pancreatico-duodenal grafts with enteric diversion of the pancreatic ductal secretions coupled with iliac vein provision of insulin (systemic-enteric technique) although the systemic-bladder technique endures as a preferred alternative in selected cases. In the early 1990s, a novel technique of venous drainage into the superior mesenteric vein combined with bowel exocrine diversion (portal-enteric technique) was designed and subsequently refined over the next ≥ 20 years to re-create the natural physiology of the pancreas with first-pass hepatic processing of insulin. Enteric drainage usually refers to jejunal or ileal diversion of the exocrine secretions either with a primary enteric anastomosis or with an additional Roux limb. The portal-enteric technique has spawned a number of newer and revisited techniques of enteric exocrine drainage including duodenal or gastric diversion. Reports in the literature suggest no differences in pancreas transplant outcomes irrespective of type of either venous or exocrine diversion. The purpose of this review is to examine the literature on exocrine drainage in the new millennium (the purported "enteric drainage" era) with special attention to technical variations and nuances in vascularized pancreas transplantation that have been proposed and studied in this time period.

Dual kidney transplants from adult marginal donors successfully expand the limited deceased donor organ pool.

BACKGROUND: The need to expand the organ donor pool remains a formidable challenge in kidney transplantation (KT). The use of expanded criteria donors (ECDs) represents one approach, but kidney discard rates are high because of concerns regarding overall quality. Dual KT (DKT) may reduce organ discard and optimize the use of kidneys from marginal donors. STUDY DESIGN: We conducted a single-center retrospective review of outcomes in adult recipients of DKTs from adult marginal deceased donors (DD) defined by limited renal functional capacity. If the calculated creatinine clearance in an adult DD was <65 mL/min, then the kidneys were transplanted as a DKT. RESULTS: Over 11.5 yr, 72 DKTS were performed including 45 from ECDs, 17 from donation after cardiac death (DCD) donors, and 10 from standard criteria donors (SCD). Mean adult DD and recipient ages were both 60 yr, including 29 DDs and 26 recipients ≥65 yr of age. Mean pre-DKT waiting and dialysis vintage times were 12 months and 25 months, respectively. Actual patient and graft survival rates were 84.7% and 70.8%, respectively, with a mean follow-up of 58 months. One yr and death-censored graft survival rates were 90% and 80%, respectively. Outcomes did not differ by DD category, recipient age, or presence of delayed graft function (DGF). Eleven patients died at a mean of 32 months post-DKT (eight with functioning grafts) and 13 other patients experienced graft losses at a mean of 33 months. The incidence of DGF was 25%; there were two cases (2.8%) of primary non-function. Mean length of initial hospital stay was 7.2 d. Mean serum creatinine and glomerular filtration rate levels at 12 and 24 months were 1.5 and 53 and 1.5 mg/dL and 51 mL/min/1.73 m(2) , respectively. DKT graft survival and function were superior to concurrent single ECD and similar to concurrent SCD KTs. Two patients underwent successful kidney retransplantation, so the dialysis-free rate in surviving patients was 87%. The proportion of total renal function transplanted from adult DD to DKT recipients was 77% compared to 56% for patients receiving single KTs. CONCLUSIONS: Dual kidney transplantation using kidneys from adult marginal DDs that otherwise might be discarded offer a viable option to counteract the growing shortage of acceptable single kidneys. Excellent medium-term outcomes can be achieved and waiting times can be reduced in a predominantly older recipient population.

Kidney transplantation, bioengineering and regeneration: an originally immunology-based discipline destined to transition towards ad hoc organ manufacturing and repair.

Kidney transplantation (KT), as a modality of renal replacement therapy (RRT), has been shown to be both economically and functionally superior to dialysis for the treatment of end-stage renal disease (ESRD). Progress in KT is limited by two major barriers: a) a chronic and burgeoning shortage of transplantable organs and b) the need for chronic immunosuppression following transplantation. Although ground-breaking advances in transplant immunology have improved patient survival and graft durability, a new pathway of innovation is needed in order to overcome current obstacles. Regenerative medicine (RM) holds the potential to shift the paradigm in RRT, through organ bioengineering. Manufactured organs represent a potentially inexhaustible source of transplantable grafts that would bypass the need for immunosuppressive drugs by using autologous cells to repopulate extracellular matrix (ECM) scaffolds. This overview discusses the current status of renal transplantation while reviewing the most promising innovations in RM therapy as applied to RRT.

The Human Pancreas as a Source of Protolerogenic Extracellular Matrix Scaffold for a New-generation Bioartificial Endocrine Pancreas.

OBJECTIVES: Our study aims at producing acellular extracellular matrix scaffolds from the human pancreas (hpaECMs) as a first critical step toward the production of a new-generation, fully human-derived bioartificial endocrine pancreas. In this bioartificial endocrine pancreas, the hardware will be represented by hpaECMs, whereas the software will consist in the cellular compartment generated from patient's own cells. BACKGROUND: Extracellular matrix (ECM)-based scaffolds obtained through the decellularization of native organs have become the favored platform in the field of complex organ bioengineering. However, the paradigm is now switching from the porcine to the human model. METHODS: To achieve our goal, human pancreata were decellularized with Triton-based solution and thoroughly characterized. Primary endpoints were complete cell and DNA clearance, preservation of ECM components, growth factors and stiffness, ability to induce angiogenesis, conservation of the framework of the innate vasculature, and immunogenicity. Secondary endpoint was hpaECMs' ability to sustain growth and function of human islet and human primary pancreatic endothelial cells. RESULTS: Results show that hpaECMs can be successfully and consistently produced from human pancreata and maintain their innate molecular and spatial framework and stiffness, and vital growth factors. Importantly, hpaECMs inhibit human naïve CD4 T-cell expansion in response to polyclonal stimuli by inducing their apoptosis and promoting their conversion into regulatory T cells. hpaECMs are cytocompatible and supportive of representative pancreatic cell types. DISCUSSION: We, therefore, conclude that hpaECMs has the potential to become an ideal platform for investigations aiming at the manufacturing of a regenerative medicine-inspired bioartificial endocrine pancreas.

Donor-derived myeloid sarcoma in two kidney transplant recipients from a single donor.

We report the rare occurrence of donor-derived myeloid sarcoma in two kidney transplant patients who received organs from a single deceased donor. There was no evidence of preexisting hematologic malignancy in the donor at the time of organ recovery. Both recipients developed leukemic involvement that appeared to be limited to the transplanted organ. Fluorescence in situ hybridization (FISH) and molecular genotyping analyses confirmed that the malignant cells were of donor origin in each patient. Allograft nephrectomy and immediate withdrawal of immunosuppression were performed in both cases; systemic chemotherapy was subsequently administered to one patient. Both recipients were in remission at least one year following the diagnosis of donor-derived myeloid sarcoma. These cases suggest that restoration of the immune system after withdrawal of immunosuppressive therapy and allograft nephrectomy may be sufficient to control HLA-mismatched donor-derived myeloid sarcoma without systemic involvement.

Renal Extracellular Matrix Scaffolds From Discarded Kidneys Maintain Glomerular Morphometry and Vascular Resilience and Retains Critical Growth Factors.

BACKGROUND: Extracellular matrix (ECM) scaffolds, obtained through detergent-based decellularization of native kidneys, represent the most promising platform for investigations aiming at manufacturing kidneys for transplant purposes. We previously showed that decellularization of the human kidney yields renal ECM scaffolds (hrECMs) that maintain their basic molecular components, are cytocompatible, stimulate angiogenesis, and show an intact innate vasculature. However, evidence that the decellularization preserves glomerular morphometric characteristics, physiological parameters (pressures and resistances of the vasculature bed), and biological properties of the renal ECM, including retention of important growth factors (GFs), is still missing. METHODS: To address these issues, we studied the morphometry and resilience of hrECMs' native vasculature with resin casting at electronic microscopy and pulse-wave measurements, respectively. Moreover, we determined the fate of 40 critical GFs post decellularization with a glass chip-based multiplex enzyme-linked immunosorbent assay array and in vitro immunofluorescence. RESULTS: Our method preserves the 3-dimensional conformation of the native glomerulus. Resin casting and pulse-wave measurements, showed that hrECMs preserves the microvascular morphology and morphometry, and physiological function. Moreover, GFs including vascular endothelial growth factor and its receptors are retained within the matrices. CONCLUSIONS: Our results indicate that discarded human kidneys are a suitable source of renal scaffolds because they maintain a well-preserved structure and function of the vasculature, as well as GFs that are fundamental to achieve a satisfying recellularization of the scaffold in vivo due to their angiogenic properties.

Prospect for kidney bioengineering: shortcomings of the status quo.

INTRODUCTION: Dialysis and renal transplantation are the only two therapeutic options offered to patients affected by end-stage kidney disease; however, neither treatment can be considered definitive. In fact, dialysis is able to replace only the filtration function of the kidney without substituting its endocrine and metabolic roles, and dramatically impacts on patient's quality of life. On the other hand, kidney transplantation is severely limited by the shortage of transplantable organs, the need for immunosuppressive therapies and a narrow half-life. Regenerative medicine approaches are promising tools aiming to improve this condition. AREAS COVERED: Cell therapies, bioartificial kidney, organ bioengineering, 3D printer and kidney-on-chip represent the most appealing areas of research for the treatment of end-stage kidney failure. The scope of this review is to summarize the state of the art, limits and directions of each branch. EXPERT OPINION: In the future, these emerging technologies could provide definitive, curative and theoretically infinite options for the treatment of end-stage kidney disease. Progress in stem cells-based therapies, decellularization techniques and the more recent scientific know-how for the use of the 3D printer and kidney-on-chip could lead to a perfect cellular-based therapy, the futuristic creation of a bioengineered kidney in the lab or to a valid bioartificial alternative.

A Single Center 11 Year Experience with 202 Pancreas Transplants in the New Millennium: Evolving Trends.

Our single center experience with pancreas transplantation (PTx) over an 11+ year period is reviewed. METHODS: We retrospectively studied outcomes in 202 consecutive PTxs in 192 patients at our center. All patients received either rabbit anti-thymocyte globulin (rATG) or alemtuzumab (Alem) induction with tacrolimus/mycophenolate mofetil and tapered steroids or early withdrawal. 179 PTxs (89%) were performed with portal-enteric and 23 with systemic-enteric drainage. RESULTS: From 11/01 to 3/13, we performed 162 simultaneous kidney-PTxs (SKPT), 35 sequential PTxs after kidney, and 5 PTx alone (40 solitary PTxs, SPT). 186 PTxs (92%) were primary and 16 were pancreas retransplants. With a mean follow-up of 5.5 years, overall patient (86% SKPT versus 87% SPT), kidney (74% SKPT versus 80% SPT), and pancreas graft survival (both 65%) rates were comparable. Causes of PTx loss were also similar between SKPT and SPT; the rates of early thrombosis were 8.6% and 5%, respectively. Acute rejection rates were similar between groups (SKPT 29% versus SPT 28%, p= not significant). A randomized trial of Alem versus rATG induction in SKPT demonstrated lower rates of acute rejection and infection in the Alem group. Consequently, Alem induction has been used exclusively in all PTxs since 2009. Early steroid elimination has been feasible in most patients. Surveillance PTx biopsy-directed immunosuppression has contributed to equivalent long-term outcomes in SKPT and SPT. Good results have been achieved in African-American patients and in patients with a type 2 diabetes phenotype. CONCLUSIONS: Excellent 5-year outcomes following PTx can be achieved as >86% of patients are alive, >87% of surviving patients are dialysis-free, 80% of surviving patients remain insulin-free, and 88% of surviving patients have detectable C-peptide levels.

Semi-xenotransplantation: the regenerative medicine-based approach to immunosuppression-free transplantation and to meet the organ demand.

Although xenografts have always held immeasurable potential as an inexhaustible source of donor organs, immunological barriers and physiological incompatibility have proved to be formidable obstacles to clinical utility. An exciting, new regenerative medicine-based approach termed "semi-xenotransplantation" (SX) seeks to overcome these obstacles by combining the availability and reproducibility of animal organs with the biocompatibility and functionality of human allografts. Compared to conventional xenotransplantation wherein the whole organ is animal-derived, SX grafts are cleansed of their antigenic cellular compartment to produce whole-organ extracellular matrix scaffolds that retain their innate structure and vascular channels. These scaffolds are then repopulated with recipient or donor human stem cells to generate biocompatible semi-xenografts with the structure and function of native human organs. While numerous hurdles must be still overcome in order for SX to become a viable treatment option for end-stage organ failure, the immense potential of SX for meeting the urgent needs for a new source of organs and immunosuppression-free transplantation justifies the interest that the transplant community is committing to the field.

Role of allograft nephrectomy following kidney graft failure: preliminary experience with pre-operative angiographic kidney embolization.

INTRODUCTION: Allograft nephrectomy (AN) is not without morbidity following graft failure (GF) in kidney transplantation (KT). METHODS: Single center retrospective review of all adult patients undergoing AN following KT, including a subset of patients who underwent pre-operative angiographic kidney embolization (PAKE). RESULTS: Over a 104 month period, 853 adult patients underwent deceased donor KT. With a median follow-up of 3.5 years, 174 patients (20.4%) developed GF and 38/174 (21.8%) underwent AN. The rate of AN was higher in patients with delayed graft function [DGF, Odds Ratio (OR) 2.15, p = 0.023] and early GF (OR 1.7, p = 0.064). For patients undergoing PAKE (n = 13, mean timing of AN 27.5 months post-KT), the estimated intra-operative blood loss was reduced from a mean of 375 ± 530 to 100 ± 162 ml (p < 0.10), mean peri-operative transfusion requirements were reduced from 3.36 ± 4.8 to 0.23 ± 0.44 units (p < 0.05), and total mean operating time was reduced from 192 ± 114 to 141 ± 38 min (p = NS) compared to 13 control patients undergoing AN in the absence of vascular thrombosis or PAKE. Mean length of hospital stay was decreased from 8.5 ± 9 to 5.5 ± 3 days (p = NS) in patients with PAKE. Surgical complication and infection rates and hospital charges were comparable. CONCLUSIONS: Delayed graft function and early GF are associated with a higher rate of AN. PAKE may result in less blood loss, fewer transfusions, reduced operating time, and shorter length of stay, which may translate into reductions in morbidity.

Pancreas transplantation: The Wake Forest experience in the new millennium.

AIM: To investigate the Wake Forest experience with pancreas transplantation in the new millennium with attention to surgical techniques and immunosuppression. METHODS: A monocentric, retrospective review of outcomes in simultaneous kidney-pancreas transplant (SKPT) and solitary pancreas transplant (SPT) recipients was performed. All patients underwent pancreas transplantation as intent-to-treat with portal venous and enteric exocrine drainage and received depleting antibody induction; maintenance therapy included tapered steroids or early steroid elimination with mycophenolate and tacrolimus. Recipient selection was based on clinical judgment whether or not the patient exhibited measureable levels of C-peptide. RESULTS: Over an 11.25 year period, 202 pancreas transplants were performed in 192 patients including 162 SKPTs and 40 SPTs. A total of 186 (92%) were primary and 16 (8%) pancreas retransplants; portal-enteric drainage was performed in 179 cases. A total of 39 pancreas transplants were performed in African American (AA) patients; of the 162 SKPTs, 30 were performed in patients with pretransplant C-peptide levels > 2.0 ng/mL. In addition, from 2005-2008, 46 SKPT patients were enrolled in a prospective study of single dose alemtuzumab vs 3-5 doses of rabbit anti-thymocyte globulin induction therapy. With a mean follow-up of 5.7 in SKPT vs 7.7 years in SPT recipients, overall patient (86% SKPT vs 87% SPT) and kidney (74% SKPT vs 80% SPT) graft survival rates as well as insulin-free rates (both 65%) were similar (P = NS). Although mortality rates were nearly identical in SKPT compared to SPT recipients, patterns and timing of death were different as no early mortality occurred in SPT recipients whereas the rates of mortality following SKPT were 4%, 9% and 12%, at 1-, 3- and 5-years follow-up, respectively (P < 0.05). The primary cause of graft loss in SKPT recipients was death with a functioning graft whereas the major cause of graft loss following SPT was acute and chronic rejection. The overall incidence of acute rejection was 29% in SKPT and 27.5% in SPT recipients (P = NS). Lower rates of acute rejection and major infection were evidenced in SKPT patients receiving alemtuzumab induction therapy. Comparable kidney and pancreas graft survival rates were observed in AA and non-AA recipients despite a higher prevalence of a "type 2 diabetes" phenotype in AA. Results comparable to those achieved in insulinopenic diabetics were found in the transplantation of type 2 diabetics with detectable C-peptide levels. CONCLUSION: In the new millennium, acceptable medium-term outcomes can be achieved in SKPT and SPTs as nearly 2/3rds of patients are insulin independent following pancreas transplantation.

Osseus metaplasia in kidney allografts as a paradigm of regenerative medicine principles.

We report the sixth case of osseous metaplasia that has occurred in the last 5 years, after a deceased-donor renal transplant was performed on a young man. While its clinical significance is unclear and probably irrelevant, osseous metaplasia is one of the most relevant principles of regenerative medicine, where every bodily district contains progenitor cells that can generate cells specific to the germ layer from which they come. After the Case Report, we review the literature and speculate on the underlying pathophysiology of osseous metaplasia. Available data seem to support the hypothesis that osteogenic precursor cells, inducing factors, and a suitable environment are key for osseous metaplasia.

Depleting antibody induction in simultaneous pancreas-kidney transplantation: a prospective single-center comparison of alemtuzumab versus rabbit anti-thymocyte globulin.

BACKGROUND: The study purpose was to analyze midterm outcomes in a prospective trial of alemtuzumab (Alem) versus rabbit anti-thymocyte globulin (rATG) induction in simultaneous pancreas-kidney transplantation (SPKT). METHODS: From February 2005 to October 2008, 46 SPKTs (45 portal-enteric drainage) were prospectively randomized as part of a larger kidney transplant study to receive either single-dose Alem (30 mg intraoperatively) or multiple-dose rATG antibody induction (starting intraoperatively, minimum three doses administered) with tacrolimus/mycophenolate ± steroids. RESULTS: Of 222 kidney transplant patients enrolled in the study, 46 received SPKTs; 28 (61%) received Alem and 18 (39%) rATG induction. Follow-up ranged from 67 to 111 months (mean 80 months). There were no significant differences between the two groups in 5 years actual patient (86% Alem vs 89% rATG), kidney (82% Alem vs 61% rATG, p = 0.17) or pancreas (68% Alem vs 56% rATG) graft survival rates. Five years death-censored kidney (92% Alem vs 69% rATG, p = 0.09) and pancreas (76% Alem vs 56% rATG, p = 0.198) graft survival rates were slightly higher in patients receiving Alem. Acute rejection (21% Alem vs 44% rATG, p = 0.12) and major infection (39% Alem vs 67% rATG, p = 0.13) rates were slightly lower in the Alem group; cytomegalovirus infections were significantly lower (0 Alem vs 17% rATG, p = 0.05). The incidence of late acute rejection was low in both groups. There were no differences in early pancreas thrombosis (3.6% Alem vs 11% rATG), postoperative bleeding (11% Alem vs 0 rATG), other surgical complications, readmissions or freedom from steroids between groups. In patients with functioning grafts, 5 years mean serum creatinine (1.4 Alem vs 1.6 mg/dl rATG), calculated abbreviated modification of diet in renal disease glomerular filtration rate (55 Alem vs 52 ml/min/1.73 m(2) rATG), hemoglobin A1c (both 5.4%) and C-peptide (2.6 Alem vs 2.3 ng/ml rATG) levels were similar. CONCLUSIONS: Single-dose Alem and multiple-dose rATG induction provide similar midterm patient survival and graft functional outcomes with no major differences in morbidity or resource utilization.