Metastatic Merkel Cell Carcinoma After Simultaneous Pancreas-Kidney Transplantation: Fatal Outcomes.

Merkel cell carcinoma (MCC) is a rare, highly aggressive cutaneous malignancy. Immunosuppression increases the risk of MCC and is associated with poor prognosis. Organ transplant recipients (OTR) have worse overall survival (OS) than patients with immunosuppression due to other causes. Treating MCC after organ transplantation is challenging, as checkpoint inhibitor immunotherapy, the standard of care for treating MCC, increases the risk of transplant rejection. This paper reviews the cases of two simultaneous pancreas-kidney transplant (SPKT) recipients with MCC and explores the role of immunosuppression in the development of MCC. Immunosuppression was discontinued and checkpoint inhibitor therapy was initiated in the first patient and considered by the second patient. In both cases, treatment failed, and the patients died shortly after developing metastatic MCC. These cases illustrate the need for improved multidisciplinary treatment regimens for MCC in OTRs. J Drugs Dermatol. 2024;23(5):376-377.     doi:10.36849/JDD.8234  .

Transplantation: platform to study recurrence of disease.

Beyond the direct benefit that a transplanted organ provides to an individual recipient, the study of the transplant process has the potential to create a better understanding of the pathogenesis, etiology, progression and possible therapy for recurrence of disease after transplantation while at the same time providing insight into the original disease. Specific examples of this include: 1) recurrence of focal segmental glomerulosclerosis (FSGS) after kidney transplantation, 2) recurrent autoimmunity after pancreas transplantation, and 3) recurrence of disease after orthotopic liver transplantation (OLT) for cirrhosis related to progressive steatosis secondary to jejuno-ileal bypass (JIB) surgery. Our team has been studying these phenomena and their immunologic underpinnings, and we suggest that expanding the concept to other pathologic processes and/or transplanted organs that harbor the risk for recurrent disease may provide novel insight into the pathogenesis of a host of other disease processes that lead to organ failure.

Co-delivery of VEGF and amoxicillin using LP-coated co-axial electrospun fibres for the potential treatment of diabetic wounds.

Diabetic complications present throughout a wide range of body tissues, however one of the most widely recognised complications remains to be chronic diabetic wounds. Current treatment options largely rely on standard wound treatment routines which provide no promotion of wound healing mechanisms at different physiological stages of repair. Recently materials produced using novel additive manufacturing techniques have been receiving attention for applications in wound care and tissue repair. Additive manufacturing techniques have recently been used in the interest of targeted drug delivery and production of novel materials resembling characteristics of native tissues. The potential to exploit these highly tailorable manufacturing techniques for the design of novel wound care remedies is highly desirable. In the present study two additive manufacturing techniques are combined to produce a scaffold for the treatment of diabetic wounds. The combination of microfluidic manufacturing of an antimicrobial liposome (LP) formulation and a coaxial electrospinning method incorporating both antimicrobial and proangiogenic factors allowed dual delivery of therapeutics to target both infection and lack of vascularisation at wound sites. The coaxial fibres comprised of a polyvinyl alcohol (PVA) core containing vascular endothelial growth factor (VEGF) and a poly (l-lactide-co-ε-caprolactone) (PLCL) shell blended with amoxicillin (Amox). Additionally, a liposomal formulation was produced to incorporate Amox and adhered to the surface of fibres loaded with Amox and VEGF. The liposomal loading provided the potential to deliver a much higher, more clinically relevant dose of Amox without detrimentally changing the mechanical properties of the material. The growth factor release was sustained up to 7-days in vitro. The therapeutic effect of the antibiotic loading was analysed using a disk diffusion method with a significant increase in zone diameter following LP adhesion, proving the full scaffold system had improved efficacy against both Gram-positive and Gram-negative strains. Additionally, the dual-loaded scaffolds show enhanced potential for supporting vascular growth in vitro, as demonstrated via a viability assay and tubule formation studies. Results showed a significant increase in the average total number of tubes from 10 in control samples to 77 in samples fully-loaded with Amox and VEGF.

Banff 2022 pancreas transplantation multidisciplinary report: Refinement of guidelines for T cell-mediated rejection, antibody-mediated rejection and islet pathology. Assessment of duodenal cuff biopsies and noninvasive diagnostic methods.

The Banff pancreas working schema for diagnosis and grading of rejection is widely used for treatment guidance and risk stratification in centers that perform pancreas allograft biopsies. Since the last update, various studies have provided additional insight regarding the application of the schema and enhanced our understanding of additional clinicopathologic entities. This update aims to clarify terminology and lesion description for T cell-mediated and antibody-mediated allograft rejections, in both active and chronic forms. In addition, morphologic and immunohistochemical tools are described to help distinguish rejection from nonrejection pathologies. For the first time, a clinicopathologic approach to islet pathology in the early and late posttransplant periods is discussed. This update also includes a discussion and recommendations on the utilization of endoscopic duodenal donor cuff biopsies as surrogates for pancreas biopsies in various clinical settings. Finally, an analysis and recommendations on the use of donor-derived cell-free DNA for monitoring pancreas graft recipients are provided. This multidisciplinary effort assesses the current role of pancreas allograft biopsies and offers practical guidelines that can be helpful to pancreas transplant practitioners as well as experienced pathologists and pathologists in training.

Long-term effects of average calcineurin inhibitor trough levels (over time) on renal function in a prospectively followed cohort of 150 kidney transplant recipients.

More favorable clinical outcomes with medium-term follow-up have been reported among kidney transplant recipients receiving maintenance therapy consisting of "reduced-tacrolimus (TAC) dosing," mycophenolate mofetil (MMF), and low-dose corticosteroids. However, it is not clear whether long-term maintenance therapy with reduced-calcineurin inhibitor (CNI) dosing still leads to reduced renal function. A prospectively followed cohort of 150 kidney transplant recipients randomized to receive TAC/sirolimus (SRL) versus TAC/MMF versus cyclosporine microemulsion (CSA)/SRL, plus low-dose maintenance corticosteroids, now has 20 years of post-transplant follow-up. Average CNI trough levels over time among patients who were still alive with functioning grafts at 60, 120, and 180 months post-transplant were determined and ranked from smallest-to-largest for both TAC and CSA. Stepwise linear regression was used to determine whether these ranked average trough levels were associated with the patient's estimated glomerular filtration rate (eGFR) at those times, particularly after controlling for other significant multivariable predictors. Experiencing biopsy-proven acute rejection (BPAR) and older donor age were the two most significant multivariable predictors of poorer eGFR at 60, 120, and 180 months post-transplant (p < 000001 and 0.000003 for older donor age at 60 and 120 months; p = 0.00008 and <0.000001 for previous BPAR at 60 and 120 months). Assignment to CSA also implied a significantly poorer eGFR (but with less magnitudes of effect) in multivariable analysis at 60 and 120 months (p = 0.01 and 0.002). Higher ranked average CNI trough levels had no association with eGFR at any timepoint in either univariable or multivariable analysis (p > 0.70). Long-term maintenance therapy with reduced-CNI dosing does not appear to cause reduced renal function.

Graft Failure Due to Nonadherence among 150 Prospectively-Followed Kidney Transplant Recipients at 18 Years Post-transplant: Our Results and Review of the Literature.

Background: We previously reported that graft failure due to nonadherence (GFNA) was a major cause of graft loss in kidney transplantation. Here, among 150 prospectively-followed kidney transplant recipients at 18 years post-transplant, we provide: updated (longer-term) estimates of cause-specific graft loss probabilities, risk factors for developing GFNA, and detailed characterizations of patients' overt nonadherent (NA) behavior, including timing, extent, and clinical consequences. Methods: Determination of the patient becoming NA in taking his/her immunosuppressive medications, and the underlying cause of graft loss, were determined prospectively by the attending physicians. For never-functioning-graft, GFNA, GF due to causes other than NA (Other GF), and death with a functioning graft (DWFG), cumulative incidence functions were used to estimate the cumulative probabilities of cause-specific graft loss. Cox stepwise regression was used to determine significant multivariable predictors for the hazard rate of developing GFNA. Results: GFNA was a major cause of graft loss (22/150 patients), particularly among African-American and Hispanic recipients <50 years of age-at-transplant (20/56 experienced GFNA), with estimated percentages of such patients ever developing GFNA ranging between 36.9 and 41.5%. These patients were also at a higher risk of developing Other GF. For the remaining patients (2/94 experienced GFNA), estimated percentages of ever-developing GFNA were much lower (range: 0.0−6.7%). The major cause of graft loss among recipients ≥50 years of age was DWFG; GFNA rarely occurred among older recipients. In 21/22 GFNA patients, NA behavior lasted continuously from the time of developing NA until GFNA. In total, 28/150 patients became NA, and 67.9% (19/28) occurred beyond 36 months post-transplant. A total of 25 of 28 NA patients (89.3%) developed biopsy-proven acute rejection and/or chronic rejection that was directly attributed to the NA behavior. Lastly, 25/28 admitted to NA behavior, with financial and psychological components documented in 71.4% (20/28) and 96.4% (27/28) of NA cases, respectively. Conclusions: These results highlight the importance of performing serial monitoring of patients for overt NA behavior throughout their post-transplant follow-up. Financial and psychological components to NA behavior need to be simultaneously addressed with the goal of achieving complete avoidance/elimination of NA behavior among higher risk patients.

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.

How to Deal With Kidney Retransplantation-Second, Third, Fourth, and Beyond.

Kidney transplantation is the best health option for patients with end-stage kidney disease. Ideally, a kidney transplant would last for the lifetime of each recipient. However, depending on the age of the recipient and details of the kidney transplant, there may be a need for a second, third, fourth, or even more kidney transplants. In this overview, the outcome of multiple kidney transplants for an individual is presented. Key issues include surgical approach and immunologic concerns. Included in the surgical approach is an analysis of transplant nephrectomy, with indications, timing, and immunologic impact. Allograft thrombosis, whether related to donor or recipient factors merits investigation to prevent it from happening again. Other posttransplant events such as rejection, viral illness (polyomavirus hominis type I), recurrent disease (focal segmental glomerulosclerosis), and posttransplant lymphoproliferative disease may lead to the need for retransplantation. The pediatric recipient is especially likely to need a subsequent kidney transplant. Finally, noncompliance/nonadherence can affect both adults and children. Innovative approaches may reduce the need for retransplantation in the future.

Case Report: Uroenteric Fistula in a Pediatric-en-bloc Kidney Transplant Manifests as Deceptive Watery Diarrhea and Normal Anion Gap Acidosis.

Introduction: The diagnosis of a post-surgical uroenteric fistula can be challenging and may be delayed for months after symptoms begin. A normal anion gap metabolic acidosis has been reported in up to 100% of patients after ureterosigmoidostomy, and bladder substitution using small bowel and/or colonic segments. Here, we describe a rare case of a pediatric patient who developed a uroenteric fistula from the transplant ureters into the small bowel, after an en-bloc kidney transplantation resulting in profound acidosis and deceptive watery diarrhea. Case Presentation: The patient is an 8-year-old girl with end stage kidney disease (ESKD) secondary to focal segmental glomerulosclerosis. Through a right retroperitoneal approach, she underwent a right native nephrectomy and a pediatric deceased donor en-bloc kidney transplant including two separate ureters. One month later, she had a renal allograft biopsy for suspected rejection. During the week after the biopsy, she experienced abdominal pain followed by watery diarrhea and metabolic acidosis requiring continuous bicarbonate/acetate infusions. An extensive gastro-intestinal evaluation for the cause of the diarrhea including endoscopy was inconclusive. The urine output decreased to <500 ml daily; although, the kidney function remained normal. After 2 weeks of unexplained watery diarrhea a magnetic resonance urogram with contrast was performed which demonstrated extravasation of urine from both ureters with fistulization into the small bowel. She underwent corrective surgery which identified the fistulous tract, which was resected and both ureters were re-implanted. The diarrhea and acidosis resolved, and she has maintained normal renal allograft function for over 1 year. Conclusion: An important aspect in the early diagnosis of a uroenteric fistula is the sudden onset of severe hyperchloremic metabolic acidosis that results when urine is diverted into the intestinal tract. The mechanism is similar to that described in cases of urinary diversions and/or bladder augmentation using the intestine. Important diagnostic tools are the measurements of solute excretion and pH in the urine as compared to the "watery diarrhea" or bowel output. Summary: We describe a case of a uroenteric fistula in a pediatric-en-bloc kidney transplant patient that went undiagnosed for almost 3 weeks due to the deceptive nature of the watery diarrhea which was actually urine. A uroenteric fistula should be considered in the differential diagnosis of diarrhea and hyperchloremic metabolic acidosis as a complication of kidney transplant. The simultaneous comparison of stool and urine pH and solute excretions may lead to the diagnosis, appropriate imaging and surgical intervention.

Midline Rotation of the Right Renal Hilum During Hand-Assisted Laparoscopic Living Donor Nephrectomy.

BACKGROUND/OBJECTIVES: Laparoscopic living donor nephrectomy (LLDN) of the right kidney is currently considered as part of standard of care; however, dealing with the renal hilum when performing ligation/division of its renal vessels is still a main concern. Here, we describe a simple-to-perform technique, i.e., flipping the fully mobilized right kidney to the midline so that the renal artery becomes anteriorly, which offers better visualization and easier dissection of the renal vessels (achieving maximized lengths) when performing hand-assisted LLDN of the right kidney. METHODS: Living donors who underwent hand-assisted LLDN of the right kidney, along with their respective renal transplant recipients, were included in this report. Donor characteristics included renal artery and vein lengths; recipient characteristics included creatinine at months 12 - 36. Graft vein and arterial anastomosis data were also reported. RESULTS: Nineteen living donors and 19 recipients, with median donor and recipient ages being 39 (24 - 60) and 53 (3 - 81) years, respectively, were included. None of the 38 patients had intra- or postoperative complications. Donor renal vein was anastomosed to the right external iliac vein (n = 16), right common iliac vein (n = 2), and inferior vena cava (n = 1). Gonadal vein (n = 1) and deceased donor iliac vein (n = 2) were used to increase the right renal vein length in 3 cases. Four donor kidneys had 2 arteries reconstructed side by side. None of the recipients developed any vascular or urological complications. CONCLUSIONS: The laparoscopic technique described is safe and allows better visualization of the right hilum, mainly the renal artery, and helps in stapling the renal vein and renal artery.

Randomized trial of 3 maintenance regimens (TAC/SRL vs. TAC/MMF vs. CSA/SRL) with low-dose corticosteroids in primary kidney transplantation: 18-year results.

A randomized trial of 150 primary kidney transplant recipients, initiated in May 2000, compared tacrolimus (TAC)/sirolimus (SRL) vs. TAC/mycophenolate mofetil (MMF) vs. cyclosporine microemulsion (CSA)/SRL (N = 50/group). All patients received daclizumab induction and maintenance corticosteroids. With current median follow-up of 18 years post-transplant, biopsy-proven acute rejection (BPAR) occurred less often in TAC/MMF (26% (13/50)), vs. the TAC/SRL (36% (18/50)) and CSA/SRL (34% (17/50)) arms combined (p = .23), with statistical significance favoring TAC/MMF (p = .05) after controlling for the multivariable (Cox model) effects of recipient age, recipient race/ethnicity, and donor age. First BPAR rate was clearly more favorable for TAC/MMF after stratifying patients by having 0-1 (N = 72) vs. 2-3 (N = 78) unfavorable baseline characteristics (recipient age <50 years, African American or Hispanic recipient, and donor age ≥50 years) (p = .02). Mean estimated glomerular filtration rate (eGFR), using the CKD-EPI formula, was consistently higher for TAC/MMF, particularly after controlling for the multivariable effect of donor age, throughout the first 96 months post-transplant (p ≤ .008). These differences were translated into an observed more favorable graft failure due to immunologic cause (CAI/TG) rate for TAC/MMF (p = .06), although no significant differences in overall death-uncensored graft loss were observed. Previously reported significantly higher study drug discontinuation and requirement for antilipid therapy rates in the SRL-assigned arms were maintained over time. Overall, these results at 18 years post-transplant more definitively show that TAC/MMF should be the gold standard for achieving optimal, long-term maintenance immunosuppression in kidney transplantation.

Pretransplant Levels of C-Reactive Protein, Soluble TNF Receptor-1, and CD38+HLADR+ CD8 T Cells Predict Risk of Allograft Rejection in HIV+ Kidney Transplant Recipients.

INTRODUCTION: HIV-positive (HIV+) kidney transplant recipients exhibit a 2- to 3-fold increased risk of allograft rejection. Dysregulated immune activation in HIV infection persists despite successful antiretroviral therapy and is associated with non-AIDS morbidity, including renal disease. We hypothesized that the pathological levels of inflammation and immune activation associated with chronic HIV infection could have clinical utility in the prediction of rejection in HIV+ kidney recipients. METHODS: Prospective cohort study of 22 HIV-negative (HIV-; donor) to HIV+ (recipient) kidney transplant recipients who underwent biomarker assessment pretransplant and were subsequently followed for development of acute rejection. Plasma levels of markers of inflammation (soluble tumor necrosis factor receptor 1 [sTNF-R1] and C-reactive protein [CRP]) and microbial translocation (soluble CD14 and lipopolysaccharide) were measured by enzyme-linked immunosorbent assay or chromogenic endpoint assay. Levels of activated (CD38+HLADR+) CD4+ and CD8+ T cells, and T regulatory cells (CD4+CD25highFoxP3+) were measured by flow cytometry. RESULTS: Among the biomarkers evaluated, only the pretransplant levels of sTNF-R1, CRP, and frequencies of CD38+HLADR+ CD8 T cells, were found to be at significantly higher levels among patients who experienced biopsy-proven acute rejection. Confirming our hypothesis, patients with high pretransplant levels of sTNF-R1 or activated CD8+ T cells had a significantly increased 200-day cumulative incidence of biopsy-proven acute rejection (0 vs. 38% for both; P = 0.01). Similarly, pretransplant CRP levels higher than 5 µg/ml were associated with increased risk of acute rejection within the first 6 months post-transplant (0 vs. 43%; P = 0.01). CONCLUSION: Biomarker-based identification of HIV+ recipients at increased risk for rejection might facilitate individualized induction immunosuppression regimens in this vulnerable patient population.

Identification of glomerular and podocyte-specific genes and pathways activated by sera of patients with focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) accounts for about 40% of all nephrotic syndrome cases in adults. The presence of several potential circulating factors has been suggested in patients with primary FSGS and particularly in patients with recurrent disease after transplant. Irrespectively of the nature of the circulating factors, this study was aimed at identifying early glomerular/podocyte-specific pathways that are activated by the sera of patients affected by FSGS. Kidney biopsies were obtained from patients undergoing kidney transplantation due to primary FSGS. Donor kidneys were biopsied pre-reperfusion (PreR) and a subset 1-2 hours after reperfusion of the kidney (PostR). Thirty-one post reperfusion (PostR) and 36 PreR biopsy samples were analyzed by microarray and gene enrichment KEGG pathway analysis. Data were compared to those obtained from patients with incident primary FSGS enrolled in other cohorts as well as with another cohort to correct for pathways activated by ischemia reperfusion. Using an ex-vivo cell-based assay in which human podocytes were cultured in the presence of sera from patients with recurrent and non recurrent FSGS, the molecular signature of podocytes exposed to sera from patients with REC was compared to the one established from patients with NON REC. We demonstrate that inflammatory pathways, including the TNF pathway, are primarily activated immediately after exposure to the sera of patients with primary FSGS, while phagocytotic pathways are activated when proteinuria becomes clinically evident. The TNF pathway activation by one or more circulating factors present in the sera of patients with FSGS supports prior experimental findings from our group demonstrating a causative role of local TNF in podocyte injury in FSGS. Correlation analysis with clinical and histological parameters of disease was performed and further supported a possible role for TNF pathway activation in FSGS. Additionally, we identified a unique set of genes that is specifically activated in podocytes when cultured in the presence of serum of patients with REC FSGS. This clinical translational study supports our prior experimental findings describing a potential role of the TNF pathway in the pathogenesis of FSGS. Validation of these findings in larger cohorts may lay the ground for the implementation of integrated system biology approaches to risk stratify patients affected by FSGS and to identify novel pathways relevant to podocyte injury.

Hydroxypropyl-ß-cyclodextrin protects from kidney disease in experimental Alport syndrome and focal segmental glomerulosclerosis.

Studies suggest that altered renal lipid metabolism plays a role in the pathogenesis of diabetic kidney disease and that genetic or pharmacological induction of cholesterol efflux protects from the development of diabetic kidney disease and focal segmental glomerulosclerosis (FSGS). Here we tested whether altered lipid metabolism contributes to renal failure in the Col4a3 knockout mouse model for Alport Syndrome. There was an eight-fold increase in the cholesterol content in renal cortexes of mice with Alport Syndrome. This was associated with increased glomerular lipid droplets and cholesterol crystals. Treatment of mice with Alport Syndrome with hydroxypropyl-ß-cyclodextrin (HPßCD) reduced cholesterol content in the kidneys of mice with Alport Syndrome and protected from the development of albuminuria, renal failure, inflammation and tubulointerstitial fibrosis. Cholesterol efflux and trafficking-related genes were primarily affected in mice with Alport Syndrome and were differentially regulated in the kidney cortex and isolated glomeruli. HPßCD also protected from proteinuria and mesangial expansion in a second model of non-metabolic kidney disease, adriamycin-induced nephropathy. Consistent with our experimental findings, microarray analysis confirmed dysregulation of several lipid-related genes in glomeruli isolated from kidney biopsies of patients with primary FSGS enrolled in the NEPTUNE study. Thus, lipid dysmetabolism occurs in non-metabolic glomerular disorders such as Alport Syndrome and FSGS, and HPßCD improves renal function in experimental Alport Syndrome and FSGS.

Roux-en-Y gastric bypass is an effective bridge to kidney transplantation: Results from a single center.

Body mass index (BMI) > 35-40 kg/m2 is often a contraindication, while Roux-en-Y gastric bypass (RYGB) is performed to enable kidney transplantation. This single-center retrospective study evaluated pre- and post-transplant outcomes of 31 morbidly obese patients with end-stage renal disease having RYGB before kidney transplantation between July 2009 and June 2014. Fourteen RYGB patients were subsequently transplanted. Nineteen recipients not having GB with a BMI ≥ 36 kg/m2 at transplantation were used as historical controls. Mean BMI (±SE) before RYGB was 43.5 ± 0.7 kg/m2 (range: 35.4-50.5 kg/m2 ); 87.1% (27/31) achieved a BMI < 35 kg/m2 . The percentage having improved diabetes/hypertension control was 29.0% (9/31); 25.8% (8/31) had complications (mostly minor) after RYGB. Among transplanted patients, blacks/Hispanics comprised 78.6% (11/14) and 84.2% (16/19) of RYGB and controls; 57.1% (8/14) and 63.2% (12/19) had a (mostly long-standing) pretransplant history of diabetes. While biopsy-proven acute rejection (BPAR) occurred significantly higher among RYGB vs control patients (6/14 vs 3/19, P = .03), patients developing T-cell BPAR were also significantly more likely to have a tacrolimus (TAC) trough level < 4.0 ng/mL within 3 weeks of T-cell BPAR (P = .0007). In Cox's model, the impact of having a TAC level < 4.0 ng/mg remained significant (P = .007) while the effect of RYGB was no longer significant (P = .13). Infections, graft, and patient survival were not significantly different. Despite obvious effectiveness in achieving weight loss, RYGB will need more careful post-transplant monitoring given the observed higher BPAR rate.

Never events and hospital-acquired conditions after kidney transplant.

INTRODUCTION: Never events (NE) and hospital-acquired conditions (HAC) after surgery have been designated as quality metrics in health-care by the Centres for Medicare and Medicaid Services (CMS). METHODS: The Nationwide Inpatient Sample (NIS) database 2002-2012 was used to identify patientswho underwent kidney transplant. Multivariate analysis using logistic regression was used to identify outcomes and risk factors of HAC and NE after transplantation; however, we were limited by using a retrospective database missing some important variables specified for the kidney transplant, such as some operative factors, donor factors, and cold and warm ischemia times. RESULTS: Among 35 058 patients who underwent kidney transplant, there were 11 NEs, all of which were due to retained foreign bodies. Among HAC after surgery, falling was the most common (44.9%), followed by poor glycemic control (21.7%), vascular catheter-associated infection (21%), and catheter-associated urinary tract infection (8%). HAC and NE after surgery lead to a significant increase in mortality (adjusted odds ratio [AOR] 2.49; p=0.04), hospitalization length (13 vs. 7 days; p<0.01), and total hospital charges ($231 801 vs. $146 717; p<0.01). A significantly higher risk of HAC or NE was seen for patients who had more loss of function before surgey (AOR 3.25; p<0.01) and patients expected to have higher postoperative mortality before operation (AOR 1.62; p=0.03). CONCLUSIONS: Despite the limitations of the study, we found HAC and NE significantly increase mortality, hospitalization length, and total hospital charges of kidney transplant patients. Quality improvement initiatives should target HAC and NE in order to successfully reduce or prevent these events.

Case series: Transplantation of kidneys from donors with renal artery aneurysm.

INTRODUCTION: With the present disparity between organ availability and recipient demands, we reported our experience in transplanting kidneys with renal artery aneurysm after back-table reconstruction. METHODS: Four patients were identified. The repair consisted of excision of the aneurysm with ostial closure, and for one of the cases, an ovarian vein patch was used. We reviewed the safety and outcomes of this procedure. All donors were asymptomatic before surgery and were diagnosed incidentally during living donor evaluation. The nephrectomies performed were hand-assisted laparoscopic approaches. All recipients had followup renal function and ultrasound duplex of renal artery at six and 12 months and then annually. RESULTS: The mean age of the recipients was 28.7 years (range 3-45). The mean size of the aneurysm was 7.4 ± 2.7 mm. All patients had immediate graft function with median serum creatinine of 1.9 ± 1.5 mg/dL at discharge. The average length of hospital stay was 6.25 ± 2.6 days. They also maintained good renal function with an average estimated glomerular filtration rate (eGFR) of 102.8 mL/min/1.73m2 (range 53.4-199 mL/min/1.73m2) and patent vessels at one year. One patient suffered from acute antibody-mediated rejection and lost his graft (medication non-compliance). One patient had two simultaneous benign renal cysts that were resected. Three of the kidneys were right-sided and one left. Mean cold ischemia time was 86 ± 18 minutes. No deaths have been recorded. CONCLUSIONS: Transplanting kidneys with a renal artery aneurysm after ex-vivo repair is safe and the outcomes are encouraging. Also, it may play an important role in expanding the donor pool in the face of current organ shortage.

Randomized trial of rATg/Daclizumab vs. rATg/Alemtuzumab as dual induction therapy in renal transplantation: Results at 8years of follow-up.

Our goal in using dual induction therapy is to bring the kidney transplant recipient closer (through more effectively timed lymphodepletion) to an optimally immunosuppressed state. Here, we report long-term results of a prospective randomized trial comparing (Group I,N=100) rATG/Dac (3 rATG, 2 Dac doses) vs. (Group II,N=100) rATG/Alemtuzumab(C1H) (1 dose each), using reduced tacrolimus dosing, EC-MPS, and early corticosteroid withdrawal. Lower EC-MPS dosing was targeted in Group II to avoid severe leukopenia. Median follow-up was 96mo post-transplant. There were no differences in 1st BPAR (including borderline) rates: 10/100 vs. 9/100 in Groups I and II during the first 12mo(P=0.54), and 20/100 vs. 20/100 throughout the study(P=0.90). Equally favorable renal function was maintained in both treatment arms(N.S.). While not significant, more patients in Group II experienced graft loss, 25/100 vs. 18/100 in Group I(P=0.23). Actuarial patient/graft survival at 96mo was 92%/83% vs. 85%/73% in Groups I and II(N.S.). DWFG-due-to-infection(N.S.), EC-MPS withholding-due-to-leukopenia during the first 2mo(P=0.03), and incidence of viral infections(P=0.09) were higher in Group II, whereas EC-MPS withholding-due-to-GI symptoms was higher in Group I(P=0.009). No other adverse event differences were observed. While long-term anti-rejection and renal function efficacy were demonstrated in both treatment arms, slight over-immunosuppression of Group II patients occurred.