Outcomes of kidney transplant recipients who underwent pre-transplant bariatric surgery for severe obesity: a long-term follow-up study.

BACKGROUND: Kidney transplantation (KT) is the preferred therapy for end-stage renal disease (ESRD). While a major cause for ESRD, obesity is also a key obstacle to candidacy for KT. Bariatric surgery, particularly sleeve gastrectomy (SG), is increasingly used to improve access to KT in patients with obesity, but the literature especially on outcomes post-KT remains lacking. We aimed to provide a long-term follow-up analysis of efficacy and outcomes of a previously described cohort of patients with obesity, who had SG as a means for access to KT. METHODS: This is a single-center retrospective follow-up study of 32 patients with advanced chronic kidney disease or ESRD, who were referred and underwent SG between 2013 and 2018 as an access strategy to KT. The primary outcome was successful KT. Ninety-day outcomes, long-term graft function, and changes in weight and obesity-related comorbidities after KT were assessed. Descriptive statistics are presented as count (percentage) or median (interquartile range). RESULTS: At baseline, 18 (56%) were male with a median age and BMI of 51 (11) years and 42.3 (5.2) kg/m2, respectively. Median follow-up time post-SG was 53 (58) months. At last follow-up, 23 (72%) patients received KT. Median time to KT was 16 (20) months and BMI was 34.0 (5.1) kg/m2 at time of transplant. At KT, 13 (57%) and 20 (87%) had diabetes and hypertension, respectively. Median follow-up post-KT was 16 (47) months. There was one graft loss requiring return to dialysis. At 5-year post-KT, median serum creatinine was 136 (66) µmol/l. At last follow-up post-KT, median BMI remained at 33.7 (7.6) kg/m2. Among patients with diabetes and hypertension, 7/13 (54%) and 5/20 (25%) had either improvement or remission of their comorbidities, respectively. CONCLUSION: SG is an effective strategy to improve access to KT in patients with severe obesity. Transplant recipients also continue to benefit from sustained weight loss and improved related comorbidities that may positively impact their graft function after KT.

Successful surgical weight loss with laparoscopic sleeve gastrectomy for morbid obesity prior to kidney transplantation.

Morbid obesity in kidney transplant (KT) candidates is associated with increased complications and graft failure. Multiple series have demonstrated rapid and significant weight loss after laparoscopic sleeve gastrectomy (LSG) in this population. Long-term and post-transplant weight evolutions are still largely unknown. A retrospective review was performed in eighty patients with end-stage kidney disease (ESKD) who underwent LSG in preparation for KT. From a median initial BMI of 43.7 kg/m2 , the median change at 1-year was -10.0 kg/m2 . Successful surgical weight loss (achieving a BMI < 35 kg/m2 or an excess body weight loss >50%) was attained in 76.3% and was associated with male gender, predialysis status, lower obesity class and lack of coronary artery disease. Thirty-one patients subsequently received a KT with a median delay of 16.7 months. Weight regain (increase in BMI of 5 kg/m2 postnadir) and recurrent obesity (weight regain + BMI > 35) remain a concern, occurring post-KT in 35.7% and 17.9%, respectively. Early LSG should be considered for morbidly obese patients with ESKD for improved weight loss outcomes. Early KT after LSG does not appear to affect short-term surgical weight loss. Candidates with a BMI of up to 45 kg/m2 can have a reasonable expectation to achieve the limit within 1 year.

Safety and efficacy of the sleeve gastrectomy as a strategy towards kidney transplantation.

BACKGROUND: Obese individuals suffering from advanced chronic kidney disease (CKD) may be precluded from accessing kidney transplantation. Bariatric surgery is an effective treatment for obesity and related conditions but its use in those with severe CKD remains limited due to morbidity concerns. We aimed to evaluate the safety and efficacy of sleeve gastrectomy (SG) in patients with severe CKD as a bridging strategy towards kidney transplant candidacy. METHODS: This is a single-center retrospective study of a prospectively collected database of obese patients referred by the multi-organ transplant team for surgical weight loss, who underwent SG during 2013-2018. The primary outcome was 90-day major morbidity. Secondary outcomes included weight loss, and successful kidney transplantation. Descriptive statistics are expressed as count (percent) or median (interquartile range). RESULTS: 32 patients met inclusion criteria. 18 (56%) were male with a median age and BMI of 51 (11) years and 42.3 (5.2) kg/m2, respectively. 29 (91%) patients were on dialysis for a median duration of 28 months before SG. Diabetes, hypertension, and dyslipidemia were present in 15 (47%), 25 (78%), and 21 (66%) patients, respectively. At 90 days after SG, there were no leaks, reoperations, or mortality. The median length of stay was 2 (1.3) days. At 1 year, change in BMI and percent excess weight loss (EWL) were -9.8 (3.7) kg/m2 and 56% (27), respectively. In the year after SG, 20 (63%) patients were listed for transplant. 14 (44%) underwent successful kidney transplantation. One patient died while waiting for transplant. At time of transplant, median change in BMI and EWL were -9.0 (5.5) kg/m2 and 59% (30), respectively. After transplant, no patient required dialysis at a median follow-up of 17 (32) months. CONCLUSION: SG is safe and effective for weight loss and bridging to candidacy for kidney transplantation in patients with severe CKD. The acceptable safety and efficiency of SG in this high-risk population makes it an optimal choice as a bridging procedure.

Renal resistance thresholds during hypothermic machine perfusion and transplantation outcomes - a retrospective cohort study.

Renal resistance (RR), of allografts undergoing hypothermic machine perfusion (HMP), is considered a measure of organ quality. We conducted a retrospective cohort study of adult deceased donor kidney transplant (KT) recipients whose grafts underwent HMP. Our aim was to evaluate whether RR is predictive of death-censored graft failure (DCGF). Of 274 KT eligible for analysis, 59% were from expanded criteria donor. RR was modeled as a categorical variable, using a previously identified terminal threshold of 0.4, and 0.2 mmHg/ml/min (median in our cohort). Hazard ratios (HR) of DCGF were 3.23 [95% confidence interval (CI): 1.12-9.34, P = 0.03] and 2.67 [95% CI: 1.14-6.31, P = 0.02] in univariable models, and 2.67 [95% CI: 0.91-7.86, P = 0.07] and 2.42 [95% CI: 1.02-5.72, P = 0.04] in multivariable models, when RR threshold was 0.4 and 0.2, respectively. Increasing risk of DCGF was observed when RR over the course of HMP was modeled using mixed linear regression models: HR of 1.31 [95% CI: 1.07-1.59, P < 0.01] and 1.25 [95% CI: 1.00-1.55, P = 0.05], in univariable and multivariable models, respectively. This suggests that RR during HMP is a predictor of long-term KT outcomes. Prospective studies are needed to assess the survival benefit of patients receiving KT with higher RR in comparison with staying wait-listed.

Impact of acute kidney injury following liver transplantation on long-term outcomes.

BACKGROUND: The incidence of acute kidney injury (AKI) after liver transplantation (LTx) ranges from 17% to 94%. AKI is associated with prolonged hospitalization and increased early mortality. In our cohort study, we examined the impact of AKI on long-term patient survival and on the incidence of stage 4-5 chronic kidney disease (CKD). METHODS: We studied 491 LTx recipients at a single center between 1990 and 2012. We identified 278 pts (56.6%) with AKI defined as either an increase in serum creatinine (SCr) ≥26.5 µmol/L within 48 hour or elevation in SCr 1.5× baseline within 7 days (KDIGO criteria). RESULTS: In a multivariable Cox proportional hazards model, survival was worse in patients with AKI (HR: 1.41, 95% CI 1.03-1.92). Severe (stage 3) AKI was associated with worse patient survival (HR: 2.29, 95% CI 1.46-3.58). The risk of developing stage 4-5 CKD was also higher in patients with AKI (17.5% vs 9.1%) with a HR of 2.39 (95% CI 1.27-4.47). Delaying initiation of calcineurin inhibitors >48H was not associated with a decreased risk of CKD. CONCLUSIONS: Our findings suggest that AKI after LTx is associated with poor long-term outcomes, including worse survival and higher incidence of CKD stage 4-5. Strategies to prevent and manage LTx patients with AKI need to be developed.

Early renal function recovery and long-term graft survival in kidney transplantation.

Following kidney transplantation (KTx), renal function improves gradually until a baseline eGFR is achieved. Whether or not a recipient achieves the best-predicted eGFR after KTx may have important implications for immediate patient management, as well as for long-term graft survival. The aim of this cohort study was to calculate the renal function recovery (RFR) based on recipient and donor eGFR and to evaluate the association between RFR and long-term death-censored graft failure (DCGF). We studied 790 KTx recipients between January 1990 and August 2014. The last donor SCr prior to organ procurement was used to estimate donor GFR. Recipient eGFR was calculated using the average of the best three SCr values observed during the first 3 months post-KTx. RFR was defined as the ratio of recipient eGFR to half the donor eGFR. 53% of recipients had an RFR ≥1. There were 127 death-censored graft failures (16%). Recipients with an RFR ≥1 had less DCGF compared with those with an RFR <1 (HR 0.56; 95% CI 0.37-0.85; P = 0.006). Transplant era, acute rejection, ECD and DGF were also significant determinants of graft failure. Early recovery of predicted eGFR based on donor eGFR is associated with less DCGF after KTx.

RORγt inverse agonist TF-S14 inhibits Th17 cytokines and prolongs skin allograft survival in sensitized mice.

Chronic antibody mediated rejection (AMR) is the major cause of solid organ graft rejection. Th17 contributes to AMR through the secretion of IL17A, IL21 and IL22. These cytokines promote neutrophilic infiltration, B cell proliferation and donor specific antibodies (DSAs) production. In the current study we investigated the role of Th17 in transplant sensitization. Additionally, we investigated the therapeutic potential of novel inverse agonists of the retinoic acid receptor-related orphan receptor gamma t (RORγt) in the treatment of skin allograft rejection in sensitized mice. Our results show that RORγt inverse agonists reduce cytokine production in human Th17 cells in vitro. In mice, we demonstrate that the RORγt inverse agonist TF-S14 reduces Th17 signature cytokines in vitro and in vivo and leads to blocking neutrophilic infiltration to skin allografts, inhibition of the B-cell differentiation, and the reduction of de novo IgG3 DSAs production. Finally, we show that TF-S14 prolongs the survival of a total mismatch grafts in sensitized mice. In conclusion, RORγt inverse agonists offer a therapeutic intervention through a novel mechanism to treat rejection in highly sensitized patients.

Policies and practice of solid organ donation amongst people living with HIV in Canada: time for education and re-evaluation.

The numbers of organ donors in Canada and the USA fall short of increasing demand, resulting in increased morbidity, poor health outcomes, higher medical costs and death of many individuals waitlisted for transplantation. In the US, since 2013 when the US HIV Organ Policy Equity (HOPE) Act lifted the ban on organ donation between people living with HIV, the option of using organs from People with HIV became a reality. In Canada, HIV diagnosis was an exclusion criterion to organ donation until 2017, when permission was granted if requirements for 'exceptional distribution' could be met. Still, donation of organs from people with HIV poses challenges. Herein, we overview policies involving donors with HIV in Canada in order to inform healthcare providers, researchers and the community. We also advocate for the need to reassess these policies, highlight educational needs and engage interest in advancing research to inform policy reforms.

Postoperative delirium in the intensive care unit predicts worse outcomes in liver transplant recipients.

BACKGROUND: Delirium is common in intensive care unit patients and is associated with worse outcome. OBJECTIVE: To identify early risk factors for delirium in patients admitted to the intensive care unit following orthotopic liver transplantation (OLT). METHODS: An observational study of patients admitted to the intensive care unit from January 2000 to May 2010 for elective or semi-elective OLT was conducted. The primary end point was delirium in the intensive care unit. Pre- and post-transplantation and intraoperative factors potentially associated with this outcome were examined. RESULTS: Of the 281 patients included in the study, 28 (10.03%) developed delirium in the intensive care unit at a median of two days (interquartile range one to seven days) after OLT. According to multivariate analysis, independent risk factors for delirium were intraoperative transfusion of packed red blood cells (OR 1.15 [95% CI 1.01 to 1.18]), renal replacement therapy during the pretransplantation period (OR 13.12 [95% CI 2.82 to 72.12]) and Acute Physiologic and Health Evaluation (APACHE) II score (OR per unit increase 1.10 [95% CI 1.03 to 1.29]). Using Cox proportional hazards models adjusted for baseline covariates, delirium was associated with an almost twofold risk of remaining in hospital, a fourfold increased risk of dying in hospital and an almost threefold increased rate of death by one year. CONCLUSION: Intraoperative transfusion of packed red blood cells, pretransplantation renal replacement therapy and APACHE II score are predictors for the development of delirium in intensive care unit patients post-OLT and are associated with increased hospital lengths of stay and mortality.

Hepatitis C infection and hepatocellular carcinoma in liver transplantation: a 20-year experience.

BACKGROUND: Hepatitis C infection (HCV) and hepatocellular carcinoma (HCC), the two main causes of liver transplantation (LT), have reduced survival post-LT. The impact of HCV, HCC and their coexistence on post-LT survival were assessed. METHODOLOGY: All 601 LT patients from 1992 to 2011 were reviewed. Those deceased within 30 days (n = 69) and re-transplants (n = 49) were excluded. Recipients were divided into four groups: (a) HCC-/HCV-(n = 252) (b) HCC+/HCV- (n = 58), (c) HCC-/HCV+ (n = 106) and (d) HCC+/HCV+ (n = 67). Demographics, the donor risk index (DRI), Model for End-Stage Liver Disease (MELD) score, survival, complications and tumour characteristics were collected. Statistical analysis included anova, chi-square, Fisher's exact tests and Cox and Kaplan-Meier for overall survival. RESULTS: Groups were comparable with regards to baseline characteristics, but HCC patients were older. After adjusting for age, MELD, gender and the donor risk index (DRI), survival was lower in the HCC+/HCV+ group (59.5% at 5 yrs) and the hazard ratio (HR) was 1.90 [95% confidence interval (CI),1.24-2.95, P = 0.003] and 1.45 (95% CI, 0.99-2.12, P = 0.054) for HCC-/HCV+. HCC survival was similar to controls (HR 1.18, 95% CI, 0.71-1.93, P = 0.508). HCC+/HCV- patients exceeded the Milan criteria (50% versus 31%, P < 0.04) and had more micro-vascular invasion (37.5% versus 20.6%, P = 0.042). HCC+/HCV+ versus HCC+/HCV- survival remained lower (HR 1.94, 95% CI, 1.06-3.81, P = 0.041) after correcting for tumour characteristics and treatment. CONCLUSION: HCV patients had lower survival post-LT. HCC alone had no impact on survival. Patient survival decreased in the HCC+/HCV+ group and this appears to be as a consequence of HCV recurrence.

Discovery, Synthesis, and In Vitro Characterization of 2,3 Derivatives of 4,5,6,7-Tetrahydro-Benzothiophene as Potent Modulators of Retinoic Acid Receptor-Related Orphan Receptor γt.

Retinoic acid receptor-related orphan receptor γt (RORγt) is a nuclear receptor that is expressed in a variety of tissues and is a potential drug target for the treatment of inflammatory and auto-immune diseases, metabolic diseases, and resistant cancer types. We herein report the discovery of 2,3 derivatives of 4,5,6,7-tetrahydro-benzothiophene modulators of RORγt. We also report the solubility in acidic/neutral pH, mouse/human/dog/rat microsomal stability, Caco-2, and MDR1-MDCKII permeabilities of a set of these derivatives. For this group of modulators, inverse agonism by steric clashes and push-pull mechanisms induce greater instability to protein conformation compared to agonist lock hydration. Independent of the two mechanisms, we observed a basal modulatory activity of the tested 2,3 derivatives of 4,5,6,7-tetrahydro-benzothiophene toward RORγt due to the interactions with the Cys320-Glu326 and Arg364-Phe377 hydrophilic regions. The drug discovery approach reported in the current study can be employed to discover modulators of nuclear receptors and other globular protein targets.

Native nephrectomy prior to pediatric kidney transplantation: biological and clinical aspects.

BACKGROUND: Pre-transplant nephrectomy is performed to reduce risks to graft and recipient. The aims of this study were to evaluate (1) indications, surgical approach, and morbidity of native nephrectomy and (2) the effects of kidney removal on clinical and biological parameters. METHODS: This study was designed as a single-center retrospective cohort study in which 49 consecutive patients with uni- or bilateral native nephrectomies were identified from a total of 126 consecutive graft recipients in our pediatric kidney transplantation database between 1992 and 2011. Demographic, clinical, and laboratory details were extracted from charts and electronic records, including operation reports and pre- and post-operative clinic notes. RESULTS: Of the 49 nephrectomized patients, 47% had anomalies of the kidneys and urinary tract, 22% had cystinosis, 12% had focal segmental glomerulosclerosis, and 6% had congenital nephrotic syndrome. Nephrectomy decisions were based on clinical judgment, taking physiological and psychosocial aspects into consideration. Nephrectomy was performed in patients with polyuria (>2.5 ml/kg/h) and/or large proteinuria (>40 mg/m(2)/h), recurrent urinary tract infection or (rarely) hypertension. Urine output decreased from (median) 3.79 to 2.32 ml/kg/h (-34%), and proteinuria from 157 to 100 mg/m(2)/h (-40%) after unilateral nephrectomy (p=0.005). After bilateral nephrectomy, serum albumin, protein and fibrinogen concentrations normalized in 93, 73, and 55% of nephrectomized patients, respectively. Clinically relevant procedure-related complications (peritoneal laceration, hematoma) occurred in five patients. CONCLUSION: In summary, we demonstrate quantitatively that native nephrectomy prior to transplantation improved serum protein levels and anticipated post-transplant fluid intake needs in select children, reducing the risk of graft hypoperfusion and its postulated consequences for graft outcome.

TFNR2 in Ischemia-Reperfusion Injury, Rejection, and Tolerance in Transplantation.

Tumor necrosis factor receptor 2 (TNFR2) has been shown to play a crucial role in CD4+ T regulatory cells (CD4+Tregs) expansion and suppressive function. Increasing evidence has also demonstrated its role in a variety of immune regulatory cell subtypes such as CD8+ T regulatory cells (CD8+ Tregs), B regulatory cells (Bregs), and myeloid-derived suppressor cells (MDSCs). In solid organ transplantation, regulatory immune cells have been associated with decreased ischemia-reperfusion injury (IRI), improved graft survival, and improved overall outcomes. However, despite TNFR2 being studied in the context of autoimmune diseases, cancer, and hematopoietic stem cell transplantation, there remains paucity of data in the context of solid organ transplantation and islet cell transplantation. Interestingly, TNFR2 signaling has found a clinical application in islet transplantation which could guide its wider use. This article reviews the current literature on TNFR2 expression in immune modulatory cells as well as IRI, cell, and solid organ transplantation. Our results highlighted the positive impact of TNFR2 signaling especially in kidney and islet transplantation. However, further investigation of TNFR2 in all types of solid organ transplantation are required as well as dedicated studies on its therapeutic use during induction therapy or treatment of rejection.

Extracellular Vesicles From Kidney Allografts Express miR-218-5p and Alter Th17/Treg Ratios.

Delayed graft function (DGF) in kidney transplantation is associated with ischemic injury and carries long term functional and immunological risks. Extracellular vesicles (EV) released from allografts may signal a degree of ischemic stress, and are thought to play an important role in the development of anti-donor immunity. Here, we show that kidney perfusate-derived extracellular vesicles (KP-EV) express donor-specific human leukocyte antigen. KP-EV from kidneys that experience DGF increase the T-helper 17 (Th17) to T-regulatory (Treg) ratio in third party peripheral blood mononuclear cells to a greater degree than those from kidneys with immediate function. We report miR-218-5p upregulation in KP-EV of kidney transplant recipients with DGF. Levels of miR-218-5p in KP-EV inversely correlated with recipient eGFR at multiple time points following transplantation. Additionally, the degree of increase in Th17/Treg ratio by KP-EV positively correlated with miR-218-5p expression in KP-EV samples. Taken together, these data provide evidence that KP-EV may contribute to modulating immune responses in transplant recipients. This could lead to novel intervention strategies to inhibit DGF in order to improve graft function and survival.

Association of preoperative parameters with postoperative mortality and long-term survival after liver transplantation.

BACKGROUND: The ability of Child-Turcotte-Pugh (CTP) or Model for End-Stage Liver Disease (MELD) scores to predict recipient survival after liver transplantation is controversial. This analysis aims to identify preoperative parameters that might be associated with early postoperative mortality and long-term survival after liver transplantation. METHODS: We studied a total of 15 parameters, using both univariate and multivariate models, among adults who underwent primary liver transplantation. RESULTS: A total of 458 primary adult liver transplants were performed. Fifty-seven (12.44%) patients died during the first 3 postoperative months and composed the early mortality group. The remaining 401 patients composed the long-term patient survival group. The parameters that were identified through univariate analysis to be associated with early postoperative mortality were CTP score, MELD score, bilirubin, creatinine, international normalized ratio and warm ischemia time (WIT). In all multivariate models, WIT retained its statistical significance. The 10-year long-term survival was 65%. The parameters that were identified to be independent predictors of long-term survival were the recipient's sex (improved survival in women, p = 0.005), diagnosis of hepatocellular cancer (p=0.015) and recipient's age (p=0.024). CONCLUSION: Either CTP or MELD score, in conjunction with WIT, might have a role in predicting early postoperative mortality after liver transplantation, whereas the recipient's sex and the absence of hepatocellular cancer are associated with improved long-term survival.

Relative decrease in hemoglobin and outcomes in patients undergoing kidney transplantation surgery: A retrospective cohort study.

BACKGROUND: Recent surgical literature suggests that a relative decrease in hemoglobin (ΔHb) is predictive of adverse outcomes regardless of the absolute level. We aimed to examine the association between perioperative ΔHb and kidney transplantation (KT) outcomes. METHODS: This was a retrospective cohort study of transplant recipients, where ΔHb = [Hb0- Hb1Hb0]x 100 (Hb0 = hemoglobin pre-KT and Hb1 = lowest hemoglobin 24-h post-KT). The main outcome of interest was immediate graft function (IGF). RESULTS: Of the 899 eligible patients, 38% experienced IGF, and ΔHb was associated with 36% lower odds of IGF. Also, ΔHb was associated with higher all-cause graft failure and longer length of stay but not death-censored graft failure or mortality. ΔHb ≥30% was the threshold beyond which the odds of IGF were significantly lower even if Hb1 was ≥7 g/dL. CONCLUSION: ΔHb is associated with inferior outcomes independent of Hb1; whether it can be used to guide transfusion practices should be explored.

Unresectable pancreatic adenocarcinoma: do we know who survives?

BACKGROUND: This study attempts to define clinical predictors of survival in patients with unresectable pancreatic adenocarcinoma (UPA). METHODS: A retrospective study of 94 consecutive patients diagnosed with UPA from 2001 to 2006 was performed. Using data for these patients, a symptom score was devised through a forward stepwise Cox proportional hazards model based on four weighted criteria: weight loss of >10% of body weight; pain; jaundice, and smoking. The symptom score was subsequently validated in a distinct cohort of 32 patients diagnosed with UPA in 2007. RESULTS: In the original cohort, the overall median survival was 9.0 months (95% confidence interval [CI] 7.6-10.4). This altered to 10.3 months (95% CI 6.1-14.5) in patients with locally advanced disease, and 6.6 months (95% CI 4.2-9.0) in patients with distant metastasis. Median survival was 14.6 months (95% CI 13.1-16.1) in patients with a low symptom (LS) score and 6.3 months (95% CI 4.1-8.5) in patients with a high symptom (HS) score. A total of 73% of LS score patients survived beyond 9 months, compared with only 38% of HS score patients (P<0.001). The discrimination of the LS score was greater than that of any conventional method, including imaging. The validation cohort confirmed the discriminative ability of the symptom score for survival. CONCLUSIONS: A simple and clinically meaningful point-based symptom score can successfully predict survival in patients with UPA.

Predicting Clinical Outcome in Expanded Criteria Donor Kidney Transplantation: A Retrospective Cohort Study.

BACKGROUND: The gaps in organ supply and demand necessitate the use of expanded criteria donor (ECD) kidneys. OBJECTIVE: To identify which pre-transplant and post-transplant predictors are most informative regarding short- and long-term ECD transplant outcomes. DESIGN: Retrospective cohort study. SETTING: Single center, Quebec, Canada. PATIENTS: The patients were 163 consecutive first-time ECD kidney only transplant recipients who underwent transplantation at McGill University Health Centre (MUHC) between January 1, 2008 and December 31, 2014 and had frozen section wedge procurement biopsies. MEASUREMENTS: Short-term graft outcomes, including delayed graft function and 1-year estimated glomerular filtration rate (eGFR), as well as long-term outcomes including all-cause graft loss (defined as return to dialysis, retransplantation, and death with function). METHODS: Pre-transplant donor, recipient, and transplant characteristics were assessed as predictors of transplant outcomes. The added value of post-transplant predictors, including longitudinal eGFR, was also assessed using time-varying Cox proportional hazards models. RESULTS: In univariate analyses, among the pre-transplant donor characteristics, histopathologic variables did not show evidence of association with delayed graft function, 1-year post-transplant eGFR or all cause graft loss. Recipient age was associated with all-cause graft loss (hazard ratio: 1.038 [95% confidence interval: 1.002-1.075] and the model produced only modest discrimination (C-index: 0.590; standard error [SE]: 0.045). Inclusion of time-dependent post-transplant eGFR improved the model's prediction accuracy (C-index: 0.711; SE = 0.047). Pre-transplant ECD characteristics were not associated with long-term survival, whereas post-transplant characteristics allowed better model discrimination. LIMITATIONS: Single-center study, small sample size, and potential incomplete capture of all covariate data. CONCLUSIONS: Incorporation of dynamic prediction models into electronic health records may enable timely mitigation of ECD graft failure risk and/or facilitate planning for renal replacement therapies. Histopathologic findings on preimplantation biopsies have a limited role in predicting long-term ECD outcomes. TRIAL REGISTRATION: Not applicable.

CONTEXTE: Les écarts entre l'offre et la demande d'organes nécessitent le recours à des donneurs répondant à des critères élargis (DCÉ). OBJECTIF: Déterminer les prédicteurs pré- et post-transplantation qui s'avèrent les plus instructifs quant aux résultats à court et à long terme des greffes d'organes provenant de DCÉ. TYPE D'ÉTUDE: Étude de cohorte rétrospective. CADRE: Étude monocentrique tenue au Québec (Canada). SUJETS: L'étude porte sur 163 patients consécutifs greffés d'un rein seulement au center universitaire de santé McGill (CUSM) entre le 1er janvier 2008 et le 31 décembre 2014. L'organe reçu provenait d'un DCÉ et la biopsie avait été effectuée sur des sections congelées de l'organe. MESURES: Les résultats à court terme, notamment la reprise retardée de la fonction du greffon et le débit de filtration glomérulaire estimé (DFGe) après un an. Les résultats à long terme dont la perte du greffon toute cause (retour en dialyse, retransplantation ou décès avec greffon fonctionnel). MÉTHODOLOGIE: Les caractéristiques du donneur, du receveur et de la transplantation ont été examinées avant l'intervention comme prédicteurs de l'issue de la greffe. Des modèles des risques proportionnels de Cox variant dans le temps ont servi à évaluer la valeur ajoutée des prédicteurs post-greffe, notamment du DFGe longitudinal. RÉSULTATS: Dans l'analyse univariée des caractéristiques pré-transplantation, les variables histopathologiques n'ont montré aucune association avec la fonction retardée du greffon, le DFGe un an après la greffe ou la perte du greffon. L'âge du receveur a été associé à la perte du greffon toute cause (RR : 1,038 [IC 95 % : 1,002-1,075]) et le pouvoir discriminant du modèle s'est avéré modeste (indice C : 0,590; ÉT = 0,045). L'inclusion du DFGe post-greffe en fonction du temps a amélioré la précision prédictive du modèle (indice C : 0,711; ÉT = 0,047). Les caractéristiques pré-greffe du DCÉ n'ont pas été associées à la survie à long terme, alors que les caractéristiques post-greffe ont permis d'améliorer le pouvoir discriminant du modèle. LIMITES: Étude monocentrique sur un faible échantillon et dont la saisie des données sur les covariables est potentiellement incomplète. CONCLUSION: L'incorporation de modèles prédictifs dynamiques aux dossiers médicaux électroniques pourrait permettre, en temps opportun, d'atténuer les risques de défaillance du greffon provenant d'un DCÉ et faciliter la planification d'une thérapie de remplacement rénal. Les résultats histopathologiques des biopsies pré-transplantation jouent un rôle mineur pour prédire les résultats à long terme des DCÉ. ENREGISTREMENT DE L'ESSAI: Sans objet.

Renal actinomycosis presenting as uro-cutaneous fistula.

Renal actinomycosis is a rare clinical entity. Diagnosis is usually made after resection. A 36-year-old male presented with uro-cutaneous fistula and left xanthogranulomatous pyelonephritis. He was offered left open radical nephrectomy. Intra-operatively, there was "woody" inflammation of the left kidney fistulizing to the splenic flexure of the colon. We successfully resected it and a segment of the colon that had fistulized. His tissue cultures grew Actinomyces odontolyticus. Post-operatively, he received 6 weeks of intravenous beta-lactam antibiotic. He recovered well without any complications. In conclusion, renal actinomycosis can be challenging to diagnose, operate and eradicate. Perioperative considerations are presented for successful management.

Primary hyperoxaluria: clinical course, diagnosis, and treatment after kidney failure.

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive metabolic disorder resulting in the overproduction of plasma oxalate. Although the enzymatic defect is in hepatocyte peroxisomes, uncontrolled levels of oxalate result in calcium oxalate deposition in multiple organs. Because the primary route of elimination of oxalate is renal excretion, high levels are found in urine, which results in supersaturation and crystal nucleation. Patients typically present with recurrent nephrolithiasis and nephrocalcinosis. If not diagnosed early, end-stage renal disease (ESRD) and systemic calcium oxalate deposition can occur. Once ESRD develops, intensive dialysis therapy is unable to keep pace with the high oxalate production, and the preferred therapeutic intervention is combined kidney-liver transplantation. Here, we report a young man with a history of recurrent nephrolithiasis who presented to us with ESRD and subsequently developed manifestations of systemic oxalosis. The diagnosis of PH1 must be considered in the differential diagnosis of patients presenting with ESRD with a history of recurrent nephrolithiasis. The diagnosis of PH1 is more challenging in patients with ESRD, for whom urinary oxalate levels are often normal or only modestly increased because of decreased glomerular filtration, and recurrent nephrolithiasis is no longer the dominant clinical feature.