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Solid organ transplant recipients (SOTR) with a pretransplant malignancy (PTM) are at increased risk for cancer recurrence. However, it is unclear whether differences in survival and incidence of posttransplant de novo malignancies exist between recipients with PTM and those without PTM. We designed a systematic review to synthesize all available evidence assessing these outcomes.A systematic search was performed in MEDLINE, EMBASE, and Cochrane Library to identify studies comparing the following outcomes in SOTR by PTM status: (1) all-cause mortality, (2) cancer-specific mortality, and (3) incidence of posttransplant de novo malignancy. Risk of bias was assessed using the Newcastle-Ottawa Scale.Thirty-two cohort studies were included. Recipients with PTM were at increased risk of all-cause mortality compared to recipients without PTM (pooled hazard ratio [HR], 1.51; 95% confidence interval [CI], 1.27-1.81). Similarly, recipients with PTM were 3 times more likely to die of cancer (pooled HR, 3.13; 95% CI, 2.29-4.27). The pooled HR for developing posttransplant de novo malignancy was also increased (HR, 1.92; 95% CI, 1.52-2.42). The association of all-cause mortality and SOTR with PTM did not vary by transplanted organ.Pretransplant malignancy is associated with increased risk of all cause-mortality, cancer-specific mortality and of developing de novo malignancies after transplantation compared with those without PTM. These results reaffirm the need for careful selection of transplant recipients with PTM. Tailored screening and management strategies should be developed for this group of patients.

Cardiovascular death remains the leading cause of mortality in kidney transplant recipients. Cardiovascular events are associated with significant morbidity. However, current trends in cardiovascular events after kidney transplantation are poorly understood.We conducted a retrospective study using healthcare databases in Ontario, Canada, to determine whether the incidence of cardiovascular events after kidney transplantation has changed from 1994 to 2009. Our primary endpoint was a 3-year composite outcome of posttransplant death or major cardiovascular event (myocardial infarction, coronary angioplasty, coronary artery bypass graft surgery, stroke).Recipients (n = 4954) were older and had more baseline comorbidity in recent years. A total of 445 recipients (9.0%) died or experienced a major cardiovascular event within 3 years of transplantation. There was no significant change in the incidence of the composite outcome or death-censored cardiovascular events over time (P = 0.41 and 0.92, respectively). After adjusting for age, sex, and comorbidities, the risk of death or major cardiovascular event steadily declined across the years of transplant (2006-2009 adjusted hazard ratio, 0.70; P = 0.009; referent 1994-1997). When recipients were matched on age, sex, and date of cohort entry to members of the general population and to the chronic kidney disease population, the risk was lowest in the general population and highest in the chronic kidney disease population.Despite transplant centers accepting recipients who are older with more comorbidities in recent years, the 3-year cumulative incidence of death or major cardiovascular event has remained stable over time.

You are a charge nurse in a large hemodialysis unit in Ontario.One of the clerical staff has approached you today to assist withan update to her statistics on new and existing patients in yourunit. You are asked to clarify the cause of death for one patientand to clarify the date of transfer to the home dialysis programfor peritoneal dialysis on another patient. Finally, you are asked toremind the nurse practitioner (NP) to complete a registration formfor another patient who has just started chronic hemodialysis inyour unit. While you know the collection of data is important, thereare lots of patients to look after and you feel frustrated by havingto take time away from planning urgent hemodialysis requests--which are your priority--to source out information to complete aform. You reflect on this need for statistical data and wonder wherethe information on this form ends up and how it helps your patientswho are living with end stage kidney disease (ESKD).

Despite increasing evidence about the role of donor-specific human leukocyte antigen (HLA) antibodies in transplant outcomes, the incidence and impact of de novo donor-specific antibodies (dnDSA) after lung transplantation remains unclear.To describe the incidence, characteristics, and impact of dnDSA after lung transplantation.We investigated a single-center cohort of 340 lung transplant recipients undergoing transplant during 2008 to 2011. All patients underwent HLA-antibody testing quarterly pretransplant and at regular intervals over the first 24 months after transplant. The patients received modified immunosuppression depending on their pretransplant sensitization status. Risk factors for dnDSA development, as well as the associations of dnDSA with patient survival and chronic lung allograft dysfunction (CLAD), were determined using multivariable analysis.The cumulative incidence of dnDSA was 47% at a median of 86 days (range, 44-185 d) after lung transplantation. Seventy-six percent of recipients with dnDSA had DQ-DSA. Male sex and the use of ex vivo lung perfusion were associated with an increased risk of dnDSA, whereas increased HLA-DQB1 matching was protective. DQ-dnDSA preceded or coincided with the diagnosis of CLAD in all cases. Developing dnDSA (vs. no dnDSA) was associated with a twofold increased risk of CLAD (hazard ratio, 2.04; 95% confidence interval, 1.13-3.69). This association appeared to be driven by the development of DQ-dnDSA.dnDSA are common after lung transplantation, with the majority being DQ DSA. DQ-dnDSA are associated with an increased risk of CLAD. Strategies to prevent or treat DQ-dnDSA may improve outcomes for lung transplant recipients.

We lack consensus on the clinical value, frequency, and timing of bone mineral density (BMD) testing in kidney transplant recipients. This study sought to determine practice patterns in BMD testing across kidney transplant centres in Ontario, Canada, and to compare the frequency of testing in kidney transplant recipients to non-transplant reference groups.Using healthcare databases from Ontario, Canada we conducted a population-based cohort study of adult kidney transplant recipients who received a transplant from 1994-2009. We used logistic regression to determine if there was a statistically significant difference across transplant centres in the decision to perform at least one BMD test after transplantation, adjusting for covariates that may influence a physician's decision to order a BMD test. We used the McNemar's test to compare the number of recipients who had at least one BMD test to non-transplant reference groups (matching on age, sex, and date of cohort entry).In the first 3 years after transplant, 4821 kidney transplant recipients underwent 4802 BMD tests (median 1 test per recipient, range 0 to 6 tests), costing $600,000 (2014 CAD equivalent dollars). Across the six centres, the proportion of recipients receiving at least one BMD test varied widely (ranging from 15.6 to 92.1 %; P 0.001). Over half (58 %) of the recipients received at least one BMD test post-transplant, a value higher than two non-transplant reference groups (general population with a previous non-vertebral fracture [hip, forearm, proximal humerus], 13.8 %; general population with no previous non-vertebral fracture, 8.5 %; P value0.001 for each of the comparisons).There is substantial practice variability in BMD testing after transplant. New high-quality information is needed to inform the utility, optimal timing, and frequency of BMD testing in kidney transplant recipients.À ce jour, il n’existe aucun consensus sur la pertinence, au plan clinique, de demander une analyse de la densité minérale osseuse (DMO) chez les receveurs d’une greffe de rein, non plus que sur la fréquence ni le moment opportun pour y soumettre les patients après leur intervention.L’étude avait pour but d’établir un schéma de pratique pour la mesure de la DMO dans plusieurs centres de transplantation rénale en Ontario, au Canada. On a également voulu comparer la fréquence de ces analyses chez les patients ayant reçu une greffe rénale par rapport à un groupe de référence constitué de patients non transplantés.Il s’agit d’une étude rétrospective par cohorte représentative de la population, qui s’est tenue dans six centres de transplantation rénale en Ontario, au Canada.Il s’agit d’une cohorte de patients ayant reçu une greffe du rein entre 1994 et 2009.Les renseignements sur la fréquence, le coût total et les variations dans le nombre d’analyses de la DMO pour une période couvrant les trois années suivant la greffe ont été compilés dans chacun des six centres. La fréquence des analyses de la DMO chez les patients greffés a été comparée à la fréquence de ces mêmes tests pratiqués chez les sujets de groupes témoins, apparentés sur les plans de l’âge, du sexe et de la date de leur admission dans la cohorte, mais n’ayant pas subi une greffe du rein.L’analyse par régression logistique a été utilisée pour établir la présence de différences significatives du point de vue statistique entre les six centres de transplantation en regard de la décision d’effectuer au moins un test de DMO à la suite d’une greffe rénale. L’analyse a tenu compte des covariables qui pouvaient influencer les médecins traitants au moment de décider de procéder ou non à un test de DMO sur leurs patients greffés. Le test McNemar a été utilisé pour comparer le nombre de patients greffés ayant été soumis à une analyse de leur DMO par rapport au groupe témoin.À l’intérieur d’une période de trois ans suivant leur transplantation, un total de 4802 analyses de DMO ont été demandées parmi les 4821 patients greffés du rein répertoriés dans les six centres participant à l’étude. La valeur médiane se situait à un test par patient sur une échelle allant de 0 à 6 tests par patient. Le coût total évalué pour ces 4802 analyses de DMO était de 600 000 CDN en 2014. La proportion de receveurs de greffe ayant été soumis à une analyse de leur DMO a fluctué considérablement d’un centre de transplantation à l’autre, avec des pourcentages variant de 15,6 % à 92,1 % (Les renseignements concernant les médicaments d’ordonnance administrés aux participants étaient incomplets et les valeurs de DMO étaient manquantes dans plusieurs cas. De plus, le faible taux de fractures subies par les participants ne permet pas d’établir une relation entre la valeur de DMO mesurée et le risque de fractures.Une variabilité importante a été constatée dans la pratique d’analyses de la DMO à la suite d’une transplantation rénale. Davantage de données sont nécessaires pour discuter de la pertinence d’effectuer ce test chez les receveurs de greffe rénale, ainsi que pour établir le moment opportun et la fréquence à laquelle les y soumettre après l’intervention.

Summary Background and objectives Guidelines promote early fistula creation to avoid central venous catheter use. This practice may lead to fistula creations in patients who never receive dialysis. The objective of this study was to estimate the risk of fistula nonuse with long-term follow-up. Design, setting, participants, & measurements Administrative health data identified 1929 predialysis adults who had their first fistula creation between April of 2002 and March of 2006. Patients were followed for a minimum of 2 years or until they began dialysis, received a kidney transplant, or died. Results The median follow-up times in patients who started dialysis, died without receiving dialysis, and remained in predialysis were 6.1, 11.5, and 38.7 months, respectively. Eighty-one percent of patients initiated dialysis; 9% of patients died without receiving dialysis, and 10% of patients remained predialysis. Forty percent of patients had their first fistula creation 3–12 months before initiating dialysis (the recommended window). Thirty percent were created within 90 days of starting dialysis; 30% were created more than 1 year before starting dialysis, and 10% were created more than 2 years before starting dialysis. Older patients, females, and patients with less comorbidity were not as likely to initiate dialysis after incident fistula creation. Conclusions Most patients who underwent fistula creation before starting dialysis eventually received dialysis with extended follow-up, but the risk was significantly modified by age, sex, and comorbidity. Many patients had fistula creations earlier or later than recommended.

Summary Background and objectives The long-term effect of immunosuppressive therapy (IS) on kidney survival in idiopathic membranous nephropathy (MGN) is debated. The introduction of renin angiotensin blockade, rigorous BP control, and the increasing age at presentation of patients with MGN adds further uncertainty. Given these important changes, we sought to determine whether implementation of IS has altered outcome. Design, setting, participants, & methods We prospectively evaluated 280 incident MGN patients from three distinct 10-year periods starting from 1975. Results We found expected changes in treatment regimens but also variations in age, renal function, severity of proteinuria, and BP at presentation over this time. Outcomes did not differ over time if these significant variations in clinical characteristics were not accounted for across the eras. The effect of IS in the 57 patients treated with currently recommended regimens was assessed using propensity adjustment to address selection bias and the effect of newer, conservative therapies. A propensity score estimating the probability of receiving IS permitted the pairing of 39 treated patients with controls with similar high risk of progression of clinical features. Using this approach, IS was associated not only with remissions in proteinuria but also with substantially improved renal survival. Conclusions The study confirms that patient presenting characteristics and management regimens have changed significantly over time and the natural history of MGN has been altered. A study of propensitymatched patients confirms that current recommendations for IS have improved outcomes in MGN patients at high risk of progression. Clin J Am Soc Nephrol 6: 1591–1598, 2011. doi: 10.2215/CJN.11001210

Background. Anemia and mineral and bone disorders (MBD) are both important and common complications in kidney transplant recipients. Studies in patients with chronic kidney disease indicated a possible independent association of higher serum phosphorus with anemia, but similar associations have not been examined in kidney transplant recipients. We hypothesized that higher serum phosphorus is associated with anemia independent of other components of MBD. Methods. We examined the association of serum phosphorus with hemoglobin level and the prevalence of anemia in a prevalent cohort of 992 kidney transplant recipients in a single outpatient transplant center. Associations were examined in linear and logistic regression models with adjustment for demographic and comorbid conditions for various known risk factors of anemia, including measures of iron deficiency, inflammation, and components of MBD including serum levels of 25(OH) vitamin D, parathyroid hormone, and fibroblast growth factor 23. Results. In multivariable adjusted regression models, a 1 standard deviation (0.8 mg/dL) higher serum phosphorus level was associated with 0.26 g/dL lower blood hemoglobin concentration (95% confidence intervals ―0.36 to ―0.15, P

The increasing need for kidney transplants has led to innovations such as donor exchange programs. These programs offer transplant recipients with incompatible donors an opportunity to receive a compatible kidney. They also provide an alternative to costly desensitization protocols that have unproven long-term outcomes. Donor exchange programs have multiple options including simple two-pair exchanges, more complicated domino exchanges, or chain donations. The United States is currently limited by regional programs that provide for kidney donor exchanges. However, with the increasing public interest in and need for kidney transplants, general nephrologists will be approached with questions about these donor exchange programs. The goal of this review is to discuss donor exchange programs including their role in expanding the donor pool, the various types of exchanges, regional centers that provide these programs, and the process involved in patient enrollment. A general knowledge of donor exchange programs will help providers in discussing options with patients approaching end-stage kidney disease and transplant.

This study characterizes the exclusion of patients with chronic kidney disease (CKD) in randomized clinical trials of drug treatment for bladder, breast, colorectal, lung, and prostate cancer.

Deceased donor kidney allocation in the United States is guided by the Kidney Donor Risk Index (KDRI). The generalizability of the KDRI beyond the United States has not been widely studied.To assess the generalizability of the KDRI in a cohort of non-US (Canadian) deceased donor kidney transplant recipients.Population-based retrospective cohort study.Ontario, Canada.Recipients of deceased donor kidneys from January 1, 2005, to March 31, 2011.Using administrative data, we analyzed a cohort of deceased donor kidney recipients in Ontario, Canada. The Kaplan-Meier method and Cox proportional hazards models were used to assess the relationship between KDRI and the outcomes of graft loss and death. KDRI was modeled continuously and categorically. The ability of models with KDRI to predict recipient outcomes beyond donor age was also explored. Model discrimination was assessed usingA total of 1299 consecutive deceased donor kidney transplant recipients were included. The median follow-up was 5.5 years. Mean donor age increased from 27 to 64 years across ascending KDRI quintiles. The adjusted relative hazards (95% confidence interval) for total graft loss from Q2 to Q5 (referent = Q1) were 1.27 (0.89-1.80), 1.58 (1.13-2.22), 1.43 (1.01-2.02), and 2.15 (1.54-2.99), respectively. Increased relative hazards across KDRI quintiles were also observed for death-censored graft loss, but not death with graft function. All-cause mortality was increased for the highest KDRI quintile only. In this cohort, a model with KDRI performed better than a model with donor age alone (Large health care databases may have precluded the complete capture of covariate data.In conclusion, the KDRI is generalizable to Canadian patients in Ontario and may help inform risk assessment beyond donor age. The performance of KDRI in other non-US settings, and the need for additional model refinement, warrants further study.Aux États-Unis, l’attribution des reins provenant de donneurs décédés est guidée par l’indiceDéterminer s’il est possible de généraliser l’indice KDRI à une cohorte canadienne de receveurs d’un rein provenant d’un donneur décédé.Il s’agit d’une étude de cohorte rétrospective.La province de l’Ontario, au Canada.Les patients ayant reçu un rein provenant d’un donneur décédé entre le 1À l’aide des données administratives provinciales de l’Ontario (Canada), nous avons analysé une cohorte de receveurs d’un rein provenant d’un donneur décédé. Des modèles des risques proportionnels de Cox et la méthode de Kaplan-Meier ont été employés pour quantifier la relation entre l’indice KDRI et le risque de perte du greffon ou de décès du patient. L’indice KDRI a été modélisé de façon continue et par quintiles. On a également étudié la validité prédictive des modèles employant l’indice KDRI concernant les résultats du receveur au-delà d’une prédiction basée uniquement sur l’âge du donneur. Le pouvoir discriminant des modèles a été analysé par la surface sous la courbe à cinq ans post-intervention.Un total de 1 299 receveurs d’une greffe de rein provenant d’un donneur décédé ont été inclus dans l’étude. La durée médiane du suivi s’établissait à 5,5 ans. L’âge moyen des donneurs passait de 27 ans au quintile inférieur à 64 ans au quintile supérieur. Le risque relatif corrigé (IC 95 %) de perte totale du greffon du Q2 au Q5 (référence = Q1) s’établissait respectivement à 1,27 (0,89; 1,80), 1,58 (1,13; 2,22), 1,43 (1,01; 2,02), et 2,15 (1,54; 2,99). Une augmentation du risque relatif a également été observée pour tous les quintiles dans les cas de perte du greffon censurée au décès du patient, mais pas dans les cas de décès du patient dont le greffon était toujours fonctionnel. Le taux de mortalité toutes causes confondues s’est accru dans le quintile supérieur seulement. Au sein de cette cohorte, le modèle basé sur l’indice KDRI a mieux prédit l’issue des patients que le modèle basé uniquement l’âge du donneur (p=0,009).Vu la grande taille des bases de données en santé, il est possible que la saisie des covariables soit incomplète.L’indice KDRI est généralisable aux patients ontariens et pourrait contribuer à éclairer l’évaluation des risques plus efficacement qu’en ne considérant que l’âge du donneur. La valeur prédictive de l’indice KDRI hors des États-Unis et la nécessité de perfectionner le modèle justifient des études plus approfondies.

Cardiac magnetic resonance (CMR) imaging accurately and precisely measures left ventricular (LV) mass and function. Identifying mechanisms by which LV mass change and functional improvement occur in some end-stage kidney disease (ESKD) patients may help to appropriately target kidney transplant (KT) recipients for further investigation and intervention. The concentration of serum adiponectin, a cardiovascular biomarker, increases in cardiac failure, its production being enhanced by B-type natriuretic peptide (BNP), and both serum adiponectin and BNP concentrations decline posttransplantation.We tested the hypothesis that kidney transplantation alters LV characteristics that relate to serum adiponectin concentrations.Prospective and observational cohort study.The study was performed at 3 adult kidney transplant and dialysis centers in Ontario, Canada.A total of 82 KT candidate subjects were recruited (39 to the KT group and 43 to the dialysis group). Predialysis patients were excluded.Subjects underwent CMR with a 1.5-tesla whole-body magnetic resonance scanner using a phased-array cardiac coil and retrospective vectorographic gating. LV mass, LV ejection fraction (LVEF), LV end-systolic volume (LVESV), and LV end-diastolic volume (LVEDV) were measured by CMR pre-KT and again 12 months post-KT (N = 39), or 12 months later if still receiving dialysis (N = 43). LV mass, LVESV, and LVEDV were indexed for height (mWe performed a prospective 1:1 observational study comparing KT candidates with ESKD either receiving a living donor organ (KT group) or waiting for a deceased donor organ (dialysis group).Left ventricular mass index change was -1.98 ± 5.5 and -0.36 ± 5.7 g/mFew biomarkers of cardiac function were measured to fully contextualize their role during changing kidney function. Limited intrapatient biomarker sampling and CMR measurements precluded constructing dose-response curves of biomarkers to LV mass and function. The CMR timing in relation to dialysis was not standardized.The LVESVI and LVEDVI but not LVMI or LVEF improve post-KT. LVMI and LVEF change is independent of renal function and adiponectin. As adiponectin correlates with NT-proBNP post-KT, improved renal function through KT restores the normal heart-endocrine axis.L’imagerie par résonnance magnétique (IRM) cardiaque mesure avec précision et exactitude la masse et la fonction du ventricule gauche (VG). L’identification des mécanismes par lesquels la variation de la masse et l’amélioration de la fonction du VG se produisent chez certains patients atteints d’insuffisance rénale terminale (IRT) pourrait contribuer à cibler adéquatement les receveurs d’une greffe rénale, en vue d’investiguer et d’intervenir de façon plus poussée. La concentration d’adiponectine sérique, un biomarqueur cardiovasculaire, augmente lors d’une défaillance cardiaque, sa production étant rehaussée par le peptide natriurétique de type B (BNP), et les concentrations d’adiponectine et de BNP diminuent après la transplantation.Nous avons testé l’hypothèse selon laquelle la greffe rénale modifierait les caractéristiques du VG et que ceci serait en lien avec la concentration d’adiponectine sérique.Il s’agit d’une étude de cohorte observationnelle et prospective.L’étude a eu lieu dans trois centres de dialyse et de transplantation rénale pour adultes en Ontario (Canada).Un total de 82 candidats à la greffe ont été recrutés (39 patients dans le groupe transplantation rénale [TR] et 43 sujets dans le groupe de patients dialysés [dialyse]). Les patients en pré-dialyse ont été exclus.Les sujets ont été soumis à une IRM à l’aide d’un scanner pour le corps entier de 1,5 Tesla utilisant une bobine cardiaque en réseau phasé et une synchronisation d’images vectographiques rétrospective. La masse du VG, la fraction d’éjection du VG (FEVG), le volume télésystolique du VG (VTSVG) et le volume télédiastolique du VG (VTDVG) ont été mesurés par IRM avant la greffe et 12 mois post-greffe (n=39) ou 12 mois plus tard si le patient était toujours dialysé (n=43). La masse du VG, le VTSVG et le VTDGV ont été indexés pour la taille du patient (mNous avons procédé à une étude observationnelle prospective comparant, dans un rapport d’un pour un (1:1), des candidats à la greffe rénale atteints d’IRT qui devaient soit recevoir un rein d’un donneur vivant (groupe de TR), soit attendre un organe d’un donneur décédé (groupe de dialyse).Les variations de l’IMVG se situaient à -1,98 ± 5,5 g/mTrop peu de biomarqueurs de la fonction cardiaque ont été mesurés pour permettre de contextualiser pleinement leur rôle lors d’un changement dans la fonction rénale. L’échantillonnage limité de biomarqueurs intra-patients de même que le faible nombre de mesures d’IRM ont empêché l’établissement de courbes dose-réponse des biomarqueurs pour la masse et la fonction du VG. Enfin, la synchronisation de l’IRM par rapport à la dialyse n’était pas standardisée.Contrairement à l’IMVG et à la FEVG, l’IVTSVG et l’IVTDVG se sont améliorés après la greffe rénale. Les variations observées pour l’IMVG et la FEVG sont indépendantes de la fonction rénale et de la concentration sérique d’adiponectine. Étant donné que l’adiponectine corrèle avec le NT-proBNP post-greffe, l’amélioration de la fonction rénale par la greffe rétablit l’axe normal cœur-système endocrinien.

Functional disability is defined as the need for assistance with self-care tasks.To document changes in functional status over time among older prevalent renal transplant recipients.Single center, prospective, follow-up study.Single center, tertiary care transplant center.Patients, with a functioning kidney transplant, aged 65 years or older who underwent assessment of functional status approximately 12 months previously.Validated tools used included Barthel Index, the Lawton-Brody Scale of Instrumental Activities of Daily Living, the Timed Up and Go test, the Veterans Specific Activity Questionnaire, the Mini-Cog, and dynamometer handgrip strength.Outpatient assessment by a trained observer.Of the 82 patients previously studied, 64 (78%) patients participated in the follow-up study (mean age 70.5 ± 4.4 years, 58% male, 55% diabetic). Among those completing functional status measures, 32 (50%) had functional disability at baseline. Over the 1-year period, 11 (17%) of these patients experienced progressive functional decline, 6 (9%) exhibited no change, and 15 (23%) had functional recovery. Eleven patients (17%) initially independent, developed new-onset disability. One of the strongest predictors of progressive functional decline was having 1 or more falls in the previous year.Assessments were performed only on 2 occasions separated by approximately 1 year.Fluctuations in disability states are common among older adults living with renal transplants. Episodes of functional disability may place individuals at higher risk of persistent and/or progressive disability.La déficience fonctionnelle se définit comme le besoin pour une personne d’être assistée dans ses activités et soins quotidiens.L’étude visait à documenter les variations dans l’état fonctionnel qui se constatent au fil du temps chez les personnes âgées receveuses d’une greffe rénale.Il s’agit d’une étude de suivi prospective qui s’est tenue dans un seul centre de soins tertiaires en transplantation.Une cohorte de patients âgés de 65 ans et plus ayant reçu une greffe rénale et dont l’évaluation de l’état fonctionnel avait été faite dans les 12 mois précédant l’intervention.Les outils validés suivants ont servi à colliger les données : l’indice Barthel, l’échelle d’activités instrumentales de la vie courante de Lawton (L’évaluation des patients externes a été effectuée par un observateur formé à cet effet.Des 82 patients étudiés précédemment, 64 (78 %) ont participé à l’étude de suivi; leur âge moyen était de 70,5 ± 4,4 ans, 58 % étaient des hommes et 55 % souffraient de diabète. Parmi les patients qui ont complété les mesures de l’état fonctionnel, 32 (50 %) présentaient des déficiences fonctionnelles au départ. Au cours de l’année, 11 (17 %) patients ont vu leur état fonctionnel décliner progressivement, 6 (9 %) n’ont connu aucun changement de leur état et 15 (23 %) ont vu leur capacité fonctionnelle rétablie. Par ailleurs, au cours de la même période, on a constaté l’apparition d’une nouvelle incapacité pour onze patients (17 %) considérés au départ comme indépendants. On a observé que le fait d’avoir chuté une ou plusieurs fois au cours de l’année précédente s’avérait l’un des meilleurs facteurs prédictifs d’un déclin fonctionnel progressif.L’évaluation des patients n’a été réalisée qu’à deux reprises, et celles-ci étaient séparées d’une période d’environ un an.Les variations de l’état fonctionnel sont fréquentes chez les personnes âgées ayant subi une transplantation rénale. Les épisodes d’incapacité fonctionnelle sont susceptibles d’exposer le patient à un plus grand risque de déclin fonctionnel persistant ou progressif.

Use of administrative data for outcomes assessment in living kidney donors is increasing given the rarity of complications and challenges with loss to follow-up.To assess the validity of living donor nephrectomy in health care administrative databases compared with the reference standard of manual chart review.Retrospective cohort study.5 major transplant centers in Ontario, Canada.Living kidney donors between 2003 and 2010.Sensitivity and positive predictive value (PPV).Using administrative databases, we conducted a retrospective study to determine the validity of diagnostic and procedural codes for living donor nephrectomies. The reference standard was living donor nephrectomies identified through the province's tissue and organ procurement agency, with verification by manual chart review. Operating characteristics (sensitivity and PPV) of various algorithms using diagnostic, procedural, and physician billing codes were calculated.During the study period, there were a total of 1199 living donor nephrectomies. Overall, the best algorithm for identifying living kidney donors was the presence of 1 diagnostic code for kidney donor (ICD-10 Z52.4) and 1 procedural code for kidney procurement/excision (1PC58, 1PC89, 1PC91). Compared with the reference standard, this algorithm had a sensitivity of 97% and a PPV of 90%. The diagnostic and procedural codes performed better than the physician billing codes (sensitivity 60%, PPV 78%).The donor chart review and validation study was performed in Ontario and may not be generalizable to other regions.An algorithm consisting of 1 diagnostic and 1 procedural code can be reliably used to conduct health services research that requires the accurate determination of living kidney donors at the population level.Les professionnels de la santé se fient de plus en plus aux données administratives pour évaluer l’issue de l’opération chez les donneurs de rein vivants, étant donné la rareté des complications et les défis posés par la perte des patients au cours du suivi.Nous souhaitions évaluer la validité des données de néphrectomies sur donneur vivant rapportées dans les bases de données administratives en santé comparativement à la norme de référence qui consiste à consigner les données manuellement dans les dossiers médicaux.Il s’agit d’une étude de cohorte rétrospective.L’étude a été menée dans l’un des cinq principaux centres de transplantation d’Ontario, au Canada.La cohorte était composée de donneurs de rein vivants dont la néphrectomie a eu lieu entre 2003 et 2010.Sensibilité et valeur prédictive positive (VPP).Dans le cadre d’une étude rétrospective menée à l’aide de bases de données administratives, nous avons examiné la validité des codes de diagnostic et des codes d’intervention dans les cas de néphrectomie sur donneur vivant. Les données de l’organisme ontarien d’approvisionnement en organes, vérifiées manuellement par analyse des dossiers médicaux, ont servi de norme de référence. On a déterminé les paramètres fonctionnels (la sensibilité et la VPP) de plusieurs algorithmes basés sur les codes de diagnostic, les codes d’intervention et les codes de facturation.Il y a eu 1 199 néphrectomies sur donneur vivant pendant la période couverte par l’étude. Globalement, le meilleur algorithme de repérage des donneurs de rein vivants combinait i) un code de diagnostic attribué à un donneur de rein (ICD-10 Z52.4) et ii) un code d’intervention attribué à l’ablation ou au prélèvement rénal (1PC58, 1PC89, 1PC91). En comparaison avec la norme de référence, cet algorithme présente une sensibilité de 97 % et une VPP de 90 %. Les codes de diagnostic et d’intervention se sont avérés de meilleurs indicateurs que les codes de facturation du médecin (sensibilité de 60 %; VPP de 78 %).L’examen des dossiers médicaux des donneurs et l’étude de validation ayant été menés en Ontario, ses conclusions peuvent ne pas être transposables à d’autres régions.Un algorithme combinant un code de diagnostic et un code d’intervention s’est avéré fiable pour le dénombrement des donneurs de rein vivants dans la population générale en contexte de recherche en santé.

Delayed graft function (DGF) associates with an increased risk for graft failure, but its link with death with graft function (DWGF) is unknown. We used the US Renal Data System to assemble a cohort of all first, adult, deceased-donor kidney transplant recipients from January 1, 1998, through December 31, 2004. In total, 11,542 (23%) of 50,246 recipients required at least one dialysis session in the first week after transplantation. Compared with patients without DGF, patients with DGF were significantly more likely to die with a functioning graft (relative hazard 1.83 [95% confidence interval 1.73 to 1.93] and 1.53 [95% CI 1.45 to 1.63] for unadjusted and fully adjusted models, respectively). The risk for DWGF was slightly higher among women with DGF than among men. There was no significant heterogeneity among other subgroups, and the results were robust to sensitivity analyses. Acute rejection within the first year attenuated the DGF–DWGF association. Cardiovascular and infectious deaths were slightly more prevalent in the DGF group, but the relative hazards of cause-specific death were similar between DWGF and deaths during total follow-up. In summary, DGF associates with an increased risk for DWGF; the mechanisms underlying the negative impact of DGF require further study.

Background. There is a paucity of population-level data on the long-term outcomes of kidney transplants from deceased donors with a history of diabetes mellitus (DM). Methods. We examined the association of donor DM with graft and patient survival in 66,654 deceased donor kidney transplant recipients (KTR) from January 1, 1994, to December 31, 2003, in the United States. KTR receiving kidneys from DM versus non-DM donors were compared in the total study population and in a 1:1 propensity score-matched cohort. Results. A total of 2302 KTR received kidneys from DM donors over the study period. Older and female recipients, increased donor age, longer cold ischemia time, and transplants after 2000 were associated with a greater odds of receiving a DM donor. After propensity score matching, Cox proportional hazards models revealed hazard ratios of 1.11 (95% CI: 1.02-1.22), 1.17 (95% CI: 1.04-1.33), and 1.06 (95% CI: 0.94-1.18) for graft failure, death-censored graft failure, and patient mortality, respectively. No significant effect measure modification was seen across various patient subgroups. Longer duration of donor DM was generally associated with an increased risk of adverse outcomes. The results were robust to several sensitivity analyses. Conclusions. The long-term graft survival of KTR with DM donors is significantly inferior to non-DM donors, but the absolute difference is small. DM donors do not adversely impact patient survival. This suggests that DM donors may be effectively used to expand the donor pool, but evidence-based guidelines on the appropriate selection of these donors are needed.

Solid organ transplantation is the preferred treatment for patients with end-stage organ failure. Although much progress has been made over the past decade, some patients still require early readmission after their initial hospital discharge. Early hospital readmission is an important metric for health care quality. It is often measured in nontransplant medical and surgical conditions but has only recently been applied to organ transplantation.We performed a structured MEDLINE search to retrieve, review, and summarize original studies on the incidence, risk factors, outcomes, and prevention of early hospital readmissions after kidney, liver, and kidney-pancreas transplantation. Early hospital readmission was defined as readmission to hospital within 30 days of discharge from the transplant hospitalization.The risk of early readmission varies by organ type, (highest in liver transplants and lowest in kidney transplants). Causes for early hospital readmission are most commonly due to surgical, immunologic, or infectious complications. Risk factors associated with early hospital readmission often reflect pretransplant comorbidity, and many of these factors may not be modifiable. Early hospital readmission is also associated with decreased graft and patient survival.Early hospital readmission after transplantation is common and associated with adverse outcomes. The potential for preventing early hospital readmissions and the impact on patient outcomes remain unclear. Current evidence suggests that some, but not all, early hospital readmissions after transplantation may be prevented.

BACKGROUND Donors at increased risk of transmitting viral infections are a potential source of transplantable organs. Studies demonstrate that organs from increased risk donors (IRDs) are associated with excellent outcomes. However, considerable variation in practice likely exists. METHODS We performed a cross-country survey of Canadian Organ Transplant centers to determine organ utilization practices from IRDs. RESULTS Of 40 surveys sent to transplant programs across Canada, 24 (60%) were returned. Of those, 60.9% (15/24) had a formal policy for their use, and 21.7% (5/24) had never accepted an IRD. Only 41.7% (10/24) had access to timely nucleic acid testing (NAT), and respondents were more likely to accept IRD if NAT was available. For example the likelihood of using organs from an intravenous drug user increased from 12.5% (4/24) with serology negative donors to 70.8% (17/24) if NAT was available and the donor had no increased activity within the window period (P < 0.001). Only 37.5% (9/24) discussed the use of IRDs with candidates at listing, with 54.2% (13/24) stating that having a standardized consent would increase utilization of IRDs. CONCLUSIONS The results suggest that availability of NAT would increase IRD utilization. In addition written policies and procedures on IRD use and the consent process would be recommended in many Canadian centers.

The broader use of combined expanded criteria donor and donation after circulatory death (ECD/DCD) kidneys may help expand the deceased donor pool. The purpose of our study was to evaluate discard rates of kidneys from ECD/DCD donors and factors associated with discard.ECD/DCD donors and kidneys were evaluated from January 1, 2000 to March 31, 2011 using data from the Scientific Registry of Transplant Recipients. The kidney donor risk index was calculated for all ECD/DCD kidneys. Multivariable logistic regression models were used to determine risk factors for discarding both donor kidneys. The Kaplan-Meier product limit method and the log-rank statistic were used to assess the cumulative probability of graft failure for transplants from ECD/DCD donors where the mate kidney was discarded versus both kidneys were used.There were 896 ECD/DCD donors comprising 1792 kidneys. Both kidneys were discarded in 44.5% of donors, whereas 51.0% of all available kidneys were discarded. The kidney donor risk index scores were higher among donors of discarded versus transplanted kidneys (median, 1.82; interquartile range, 1.60, 2.07 versus median, 1.67; interquartile range, 1.49, 1.87, respectively; P0.001); however, the distributions showed considerable overlap. The adjusted odds ratios for discard were higher among donors who were older, diabetic, AB blood type, and hepatitis C positive. The cumulative probabilities of total graft failure at 1, 3, and 5 years were 17.3%, 36.5%, and 55.4% versus 13.8%, 24.7%, and 40.5% among kidneys from donors where only one versus both kidneys were transplanted, respectively (log rank P=0.04).Our study shows a significantly higher discard rate for ECD/DCD kidneys versus prior reports. Some discarded ECD/DCD kidneys may be acceptable for transplantation. Additional studies are needed to evaluate the factors that influence decision making around the use of ECD/DCD kidneys.

Several studies suggest a link between post-transplant hypomagnesemia and new-onset diabetes after transplantation (NODAT), but this relationship remains controversial. We conducted a retrospective cohort study of 948 nondiabetic kidney transplant recipients from January 1, 2000, to December 31, 2011, to examine the association between serum magnesium level and NODAT. Multivariable Cox proportional hazards models were fitted to evaluate the risk of NODAT as a function of baseline (at 1 month), time-varying (every 3 months), and rolling-average (i.e., mean for 3 months moving at 3-month intervals) serum magnesium levels while adjusting for potential confounders. A total of 182 NODAT events were observed over 2951.2 person-years of follow-up. Multivariable models showed an inverse relationship between baseline serum magnesium level and NODAT (hazard ratio [HR], 1.24 per 0.1 mmol/L decrease; 95% confidence interval [95% CI], 1.05 to 1.46; P=0.01). The association with the risk of NODAT persisted in conventional time-varying (HR, 1.32; 95% CI, 1.14 to 1.52; P

Purpose of review The field of kidney transplantation has made impressive progress, which has led to marked improvements in both patient and allograft survival. The economic and ethical consequences of these advances have recently garnered increasing attention in the medical literature. This review highlights key articles published in 2005 and 2006. Recent findings Major areas of focus in the health economics literature pertaining to kidney transplantation include the most cost-effective strategies for immunosuppressive therapies, the management of posttransplant complications, and the optimal utilization of the current pool of deceased-donor kidneys. Ethical challenges include various aspects of living donation, strategies to expand the donor pool, and the impact of financial policies for immunosuppressive agents on long-term patient and allograft survival. Summary Given the rising demand for kidney transplantation within a setting of scarce resources, the economic and ethical dimensions of transplant medicine are of increasing interest to patients, providers, and payers. Research in these areas will help uncover ways to utilize this important medical technology in the most ethical and cost-effective manner.

Statins have anti-inflammatory effects, modify endothelial function and improve peripheral insulin resistance. We hypothesized that statins influence the development of new-onset diabetes mellitus in renal transplant recipients. The records of all previously non-diabetic adults who received an allograft in Toronto between January 1, 1999 and December 31, 2001 were reviewed with follow-up through December 31, 2002. All patients receiving cyclosporine or tacrolimus, mycophenolate mofetil and prednisone were included. New-onset diabetes was diagnosed by the Canadian Diabetic Association criteria: fasting plasma glucose > or =7.0 mmol/L or 2-h postprandial glucose > or =11.1 mmol/L on more than two occasions. Statin use prior to diabetes development was recorded along with other variables. Cox proportional hazards models analyzing statin use as a time-dependent covariate were performed. Three hundred fourteen recipients met study criteria, of whom 129 received statins. New-onset diabetes incidence was 16% (n = 49). Statins (p = 0.0004, HR 0.238[0.109-0.524]) and ACE inhibitors/ARB (p = 0.01, HR 0.309[0.127-0.750]) were associated with decreased risk. Prednisone dose (p = 0.0001, HR 1.007[1.003-1.010] per 1 mg/d at 3 months), weight at transplant (p = 0.02, HR 1.022[1.003-1.042] per 1 kg), black ethnicity (p = 0.02, HR 1.230[1.023-1.480]) and age > or =45 years (p = 0.01, HR 2.226[1.162-4.261]) were associated with increased diabetes. Statin use is associated with reduced new-onset diabetes development after renal transplantation.

Epstein-Barr virus (EBV) D+/R- organ transplant recipients are a high-risk group for developing post-transplant lymphoproliferative disease (PTLD). Little data are available for prevention in the adult EBV mismatched population. We conducted a retrospective study of EBV D+/R- organ transplants performed during 2002-2014. Of the 153 patients identified, 82.4% patients received antiviral prophylaxis with valganciclovir for a median of 4.5 months (range: 0.8-22 months) and 36.6% underwent viral load monitoring in the first post-transplant year. EBV viremia developed in 67.2% monitored patients. In viremic patients, immunosuppression was reduced in 20/37(54.1%) in response to viremia and 17/37 (45.9%) received therapeutic dose valganciclovir. In patients with EBV viremia who received valganciclovir and/or had a reduction in immunosuppression and had sufficient viral load time points (n=31), 28 (90.3%) had a significant decline in viral load at day 14 (median log decline 0.49 (0.24-0.64), P

Importance Observational studies have associated patent ductus arteriosus (PDA) ligation among preterm infants with adverse neonatal outcomes and neurodevelopmental impairment in early childhood, with a resultant secular trend away from surgical treatment. However, to our knowledge, studies have inadequately addressed sources of residual bias, including survival bias and major neonatal morbidities arising before exposure to ligation. Objective Evaluate the association between PDA ligation vs medical management and neonatal and neurodevelopmental outcomes. Design, Setting, and Participants This retrospective cohort study of preterm infants younger than 28 weeks gestational age born between January 1, 2006, and December 31, 2012, with clinical and echocardiography diagnoses of hemodynamically significant PDA was conducted at 3 tertiary neonatal intensive care units and affiliated follow-up programs. Exposure Surgical ligation vs medical management. Main Outcomes and Measures The primary outcome was a composite of death or neurodevelopmental impairment (NDI) at 18 to 24 months corrected age. Secondary outcomes included death before discharge, NDI, moderate-severe chronic lung disease, and severe retinopathy of prematurity. Multivariable logistic regression analysis was used to adjust for perinatal and postnatal confounders. Results Of 754 infants with hemodynamically significant PDA (mean [standard deviation] gestational age 25.7 [1.2] weeks and birth weight 813 [183] grams), 184 (24%) underwent ligation. Infants who underwent ligation had a higher frequency of morbidities before PDA closure, including sepsis, necrotizing enterocolitis, and a dependence on mechanical ventilation. After adjusting for perinatal characteristics and preligation morbidities, there was no difference in the odds of death or NDI (adjusted odds ratio (aOR), 0.83; 95% CI, 0.52-1.32), NDI (aOR, 1.27; 95% CI, 0.78-2.06), chronic lung disease (aOR, 1.36; 95% CI, 0.78-2.39) or severe retinopathy of prematurity (aOR, 1.61; 95% CI, 0.85-3.06). Ligation was associated with lower odds of mortality (aOR, 0.09; 95% CI, 0.04-0.21). Conclusions and Relevance Patent ductus arteriosus ligation among preterm neonates younger than 28 weeks gestational age was not associated with the composite outcome of death or NDI, and there were no differences in chronic lung disease, retinopathy of prematurity, or NDI among survivors. Mortality was lower among infants who underwent ligation, though residual survival bias could not be excluded. Previously reported associations of ligation with increased morbidity may be because of bias from confounding by indication.

Objective For various reasons, people of Chinese (China, Hong Kong or Taiwan) and South Asian (Indian subcontinent) ancestry (the two largest ethnic minority groups in Ontario, Canada) may be less likely to register for deceased organ donation than the general public, and their families may be less likely to consent for deceased organ donation at the time of death. Methods We conducted two population-based studies: (1) a cross-sectional study of deceased organ donor registration as of May 2013, and (2) a cohort study of the steps in proceeding with deceased organ donation for patients who died in hospital from October 2008 to December 2012. Results A total of 49 938 of 559 714 Chinese individuals (8.9%) and 47 774 of 374 291 South Asians (12.8%) were registered for deceased organ donation, proportions lower than the general public (2 676 260 of 10 548 249 (25.4%). Among the 168 703 Ontarians who died in a hospital, the families of 33 of 81 Chinese (40.1%; 95% CI: 30.7%-51.6%) and 39 of 72 South Asian individuals (54.2%; 95% CI: 42.7-65.2%) consented for deceased organ donation, proportions lower than the general public (68.3%; 95% CI: 66.4%-70.0%). Conclusions In Ontario, Canada Chinese and South Asian individuals are less likely to register and their families are less likely to consent to deceased organ donation compared to the remaining general public. There is an opportunity to build support for organ and tissue donation in these two large ethnic communities in Canada.

Importance BK virus infection is a significant complication of modern immunosuppression used in kidney transplantation. Viral reactivation occurs first in the urine (BK viruria) and is associated with a high risk of transplant failure. There are currently no therapies to prevent or treat BK virus infection. Quinolone antibiotics have antiviral properties against BK virus but efficacy at preventing this infection has not been shown in prospective controlled studies. Objective To determine if levofloxacin can prevent BK viruria in kidney transplant recipients. Design, Setting, and Participants Double-blind, placebo-controlled randomized trial involving 154 patients who received a living or deceased donor kidney-only transplant in 7 Canadian transplant centers between December 2011 and June 2013. Interventions Participants were randomly assigned to receive a 3-month course of levofloxacin (500 mg/d; n = 76) or placebo (n = 78) starting within 5 days after transplantation. Main Outcomes and Measures The primary outcome was time to occurrence of BK viruria (detected using quantitative real-time polymerase chain reaction) within the first year after transplantation. Secondary outcomes included BK viremia, peak viral load, rejection, and patient and allograft survival. Results The mean follow-up time was 46.5 weeks in the levofloxacin group and 46.3 weeks in the placebo group (27 patients had follow-up terminated before the end of the planned follow-up period or development of viruria because the trial was stopped early owing to lack of funding). BK viruria occurred in 22 patients (29%) in the levofloxacin group and in 26 patients (33.3%) in the placebo group (hazard ratio, 0.91; 95% CI, 0.51-1.63; P = .58). There was no significant difference between the 2 groups in regard to any of the secondary end points. There was an increased risk of resistant infection among isolates usually sensitive to quinolones in the levofloxacin group vs placebo (14/24 [58.3%] vs 15/45 [33.3%], respectively; risk ratio, 1.75; 95% CI, 1.01-2.98) as well as a nonsignificant increased risk of suspected tendinitis (6/76 [7.9%] vs 1/78 [1.3%]; risk ratio, 6.16; 95% CI, 0.76-49.95). Conclusions and Relevance Among kidney transplant recipients, a 3-month course of levofloxacin initiated early following transplantation did not prevent BK viruria. Levofloxacin was associated with an increased risk of adverse events such as bacterial resistance. These findings do not support the use of levofloxacin to prevent posttransplant BK virus infection. Trial Registration clinicaltrials.gov Identifier:NCT01353339

Background With rates of obesity among patients with chronic kidney disease (CKD) mirroring that of the general population, there is growing interest in offering bariatric surgery to these patients. We sought to determine the safety of bariatric surgery in this patient population. Methods Patients who underwent selected laparoscopic bariatric procedures between 2005 and 2011. Estimated glomerular filtration rate (eGFR) was calculated and divided into stages of CKD. Procedures included Roux-en-Y gastric bypass (RYGB), laparoscopic adjustable gastric band (LAGB), and laparoscopic sleeve gastrectomy (SG). Univariable analysis and multivariable adjustment was used to compare complication rates across stages of eGFR. Results A total of 64,589 patients were included: 64.5% underwent RYGB, 29.8% LAGB, and 5.7% SG. A total of 61.7% of patients had normal eGFR (Stage 1), 32.0% were stage 2, 5.3% were stage 3, and 1.0% were stage 4/5. After adjusting for relevant patient characteristics, there was a trend toward increasing complications from stage 1 to stage 4/5 CKD among RYGB, LAGB, and SG groups, but none were statistically significant. Similarly, major complications generally increased across stages of CKD for each procedure, but was only significant for RYGB comparing stage 3 to stage 1 (OR 1.22; 95% CI: 1.01–1.47; P = .042) and risk difference .96% (95% CI: .03–1.96). Considering only stage 4/5 CKD, overall (P = .114) and major complications (P = .032) were highest in the RYGB group, followed by SG and LAGB. Conclusion More advanced stages of CKD do not appear to be statistically associated with an increased risk of 30-day postoperative complications.

OBJECTIVE: To characterize the 90-day risk of hospitalization with pneumonia among patients treated with different anti-hypertensive drug classes. DESIGN: Population based cohort study using five linked databases. PARTICIPANTS: Individuals over the age of 65 who filled a new outpatient prescription for one of four anti-hypertensive medications: ACE inhibitors (n = 86 775), ARBs (n = 33,953), calcium channel blockers (CCB, n = 34,240), beta blockers (BB, n = 35,331) and thiazide diuretics (n = 64 186). PRIMARY OUTCOME: Hospitalization with pneumonia within 90 days of a qualifying prescription. We adjusted for ten a priori selected covariates, including age, sex, diabetes and number of visits to a family doctor. RESULTS: Baseline characteristics of the groups were relatively well matched, except for age, sex, diabetes and frequency of family doctor visits. 128 of the 86 775 patients (0.15%) initiated on an ACE inhibitor and 43 of the 33953 patients (0.13%) of patients initiated on an ARB were hospitalized with pneumonia in the subsequent 90 days. 135 of 64 186 patients (0.21%) initiated on a thiazide, 112 of 35 331 patients (.32%) initiated on a BB, and 89 of 34 240 (0.26%) patients initiated on a CCB achieved the primary outcome. Compared to calcium channel blockers, ACE inhibitors (adjusted OR 0.61, 95% CI 0.46 to 0.81) and ARBs (adjusted OR 0.52, 95% CI 0.36 to 0.76) were associated with a lower risk of pneumonia. No benefit was seen with thiazides (adjusted OR 0.87, 95% CI 0.66 to 1.14) or beta blockers (adjusted OR 1.21, 95% CI 0.91 to 1.60). CONCLUSION: Initiating medications that block the renin angiotensin system, compared to other anti-hypertensive medications, is associated with a small absolute reduction in the 90 day risk of hospitalization with pneumonia.

BackgroundIn the general population, high serum uric acid concentration is a risk factor for gout. It is unknown whether donating a kidney increases a living donor’s risk of gout as serum uric acid concentration increases in donors after nephrectomy.Study DesignRetrospective matched cohort study using large health care databases.Setting & ParticipantsWe studied living kidney donors who donated in 1992 to 2010 in Ontario, Canada. Matched nondonors were selected from the healthiest segment of the general population. 1,988 donors and 19,880 matched nondonors were followed up for a median of 8.4 (maximum, 20.8) years.PredictorLiving kidney donor nephrectomy.OutcomesThe primary outcome was time to a diagnosis of gout. The secondary outcome in a subpopulation was receipt of medications typically used to treat gout (allopurinol or colchicine).MeasurementsWe assessed the primary outcome with health care diagnostic codes.ResultsDonors compared with nondonors were more likely to be given a diagnosis of gout (3.4% vs 2.0%; 3.5 vs 2.1 events/1,000 person-years; HR, 1.6; 95% CI, 1.2-2.1; P

Canadian patients receiving intensive home hemodialysis (IHHD; ≥16 hours per week) have survival comparable to that of deceased donor kidney transplant recipients in the United States, but a comparison with Canadian kidney transplant recipients has not been conducted. We conducted a retrospective cohort study of consecutive, adult IHHD patients and kidney transplant recipients between 2000 and 2011 at a large Canadian tertiary care center. The primary outcome was time-to-treatment failure or death for IHHD patients compared with expanded criteria, standard criteria, and living donor recipients, and secondary outcomes included hospitalization rate. Treatment failure was defined as a permanent switch to an alternative dialysis modality for IHHD patients, and graft failure for transplant recipients. The cohort comprised 173 IHHD patients and 202 expanded criteria, 642 standard criteria, and 673 living donor recipients. There were 285 events in the primary analysis. Transplant recipients had a reduced risk of treatment failure/death compared with IHHD patients, with relative hazards of 0.45 (95% confidence interval [95% CI], 0.31 to 0.67) for living donor recipients, 0.39 (95% CI, 0.26 to 0.59) for standard criteria donor recipients, and 0.42 (95% CI, 0.26 to 0.67) for expanded criteria donor recipients. IHHD patients had a lower hospitalization rate in the first year of treatment compared with standard criteria donor recipients and in the first 3 months of treatment compared with living donor and expanded criteria donor recipients. In this cohort, kidney transplantation was associated with superior treatment and patient survival, but higher early rates of hospitalization, compared with IHHD.

Although the United States possesses one of the most comprehensive transplant registries in the world, nationally representative data on how transplant care is structured and delivered is lacking. Therefore, we surveyed all 208 adult kidney transplant centers in the United States, excluding 37 pediatric and 58 inactive adult centers. Respondents were asked about the characteristics of their kidney transplant programs (25 items), the structure and process of care (18 items), coordination of care (10 items) and the characteristics of transplant physicians and surgeons (9 items). The survey was completed by directors of 156 transplant centers (75% response). The results demonstrated significant variation between centers in several domains. Sixty-five percent of transplant centers do not have a dedicated transplant pharmacist in outpatient care. Two-thirds of transplant centers do not see the kidney transplant recipients at least monthly during the first year. Less than 30% of centers perform either joint sit-down or walking rounds between nephrology and transplant surgery. There was significant variation in the structure and process of care in kidney transplantation. This implies variation in the use of resources at the transplant centers. This variation should be studied to determine best practices associated with optimal kidney allograft and patient survival.

Individuals with moderate-to-severe reduced renal function have greater risk of gastrointestinal bleeding than those with normal renal function. We conducted a retrospective matched cohort study to assess whether living kidney donors share a similar risk. We reviewed pre-donation charts for living kidney donations from 1992 to 2009 in Ontario, Canada, and linked this information to healthcare databases. We selected healthy non-donors from the general population and matched ten non-donors to every donor. Of the 2009 donors and 20,090 matched non-donors, none had evidence of gastrointestinal bleeding prior to cohort entry. The cohort was followed for a median of 8.4 yr (maximum 19.7 yr; loss to follow-up

Background Literature on the timing of rabbit antithymocyte globulin (rATG) induction and its effects on kidney transplant outcomes is limited. The manufacturer recommends that the first dose be given intra-operatively, however this may present clinical practice risks and challenges. Our objective was to assess the impact of the timing of the first dose of rATG on kidney transplant outcomes. Methods Incident kidney transplant recipients (KTR) from January 2002 to December 2009 receiving the first dose of rATG post-operatively (Post, n = 353) or before reperfusion (Pre, n = 124) were evaluated. Outcomes assessed included eGFR at 1-year, delta eGFR (12 versus 1 month), and incidence of biopsy-proven acute rejection, graft loss, death, and a composite of the time-to-event outcomes. The impact of timing on outcomes was adjusted for potential confounders and assessed using linear and Cox regression models. Results Among 435 KTR surviving with function to 12 months post-transplant, there was no significant difference in mean estimated glomerular filtration rate or eGFR (55.0 versus 56.7 mL/min, P = 0.46) and delta eGFR (1.8 versus 0.3 mL/min, P = 0.40) in Post versus Pre groups, respectively. At a median follow-up of 3 years, the composite endpoint (time to first biopsy-proven acute rejection, graft loss, or death) was similar by timing group (adjusted HR = 0.94; 95% CI: 0.58, 1.53, P = 0.81) in the total study population. Conclusions Timing of rATG had no appreciable impact on clinically relevant endpoints in this study cohort. These results support consideration of more flexible timing of the first dose of rATG induction in KTR.

Delayed graft function (DGF), most commonly defined as the need for dialysis in the first 7 days post-transplant, continues to be a common problem in the modern era of kidney transplantation. Multiple complex biochemical and structural changes occur at the cellular level as a result of ischemia and reperfusion injury of the allograft, which predispose recipients to DGF. Several transplant, donor, and recipient factors have been found to be associated with an increased risk of DGF. This chapter will provide an overview of these risk factors as well as a practical approach to the clinical evaluation of DGF. A number of preventive and therapeutic interventions such as the use of certain preservation solutions, pulsatile machine perfusion, vasodilatory drugs, and immunosuppressive agents have been extensively studied with variable results. These interventions, as well as the quality of the evidence supporting their use, will also be reviewed. Finally, this chapter will highlight the short- and long-term consequences of DGF, with a particular emphasis on the association between DGF, graft survival, and death with graft function.

In the last decade, the number of patients starting dialysis after a failed kidney transplant has increased substantially. These patients appear to be different from their transplant-naïve counterparts, and so may be the timing of dialysis therapy initiation. An increasing number of studies suggest that in transplant-naïve patients, later dialysis initiation is associated with better outcomes. Very few data are available on timing of dialysis reinitiation in failed transplant recipients, and they suggest that an earlier return to dialysis therapy tended to be associated with worse survival, especially among healthier and younger patients and women. Failed transplant patients may also have unique issues such as continuation of immunosuppression versus withdrawal or the need for remnant allograft nephrectomy with regard to dialysis reinitiation. These patients may have a different predialysis preparation work-up, worse blood pressure control, higher or lower serum phosphorus levels, lower serum bicarbonate concentration, and worse anemia management. The choice of dialysis modality may also represent an important question for these patients, even though there appears to be no difference in mortality between patients starting peritoneal versus hemodialysis. Finally, failed transplant patients returning to dialysis appear to have a higher mortality rate compared with transplant-naïve incident dialysis patients, especially in the first several months of dialysis therapy. In this review, we will summarize the available data related to the timing of dialysis initiation and outcomes in failed kidney transplant patients after returning to dialysis. © 2013 Wiley Periodicals, Inc.

Background BK virus infection has emerged as a major complication in kidney transplantation leading to a significant reduction in graft survival. There are currently no proven strategies to prevent or treat BK virus infection. Quinolone antibiotics, such as levofloxacin, have demonstrated activity against BK virus. We hypothesize that administration of a quinolone antibiotic, when given early post-transplantation, will prevent the establishment of BK viral replication in the urine and thus prevent systemic BK virus infection. Methods/design The aim of this pilot trial is to assess the efficacy, safety and feasibility of a 3-month course of levofloxacin in the kidney transplant population. This is a multicenter, randomized, double-blind, placebo-controlled trial with two parallel arms conducted in 11 Canadian kidney transplant centers. A total of 154 patients with end-stage renal disease undergoing kidney transplantation will be randomized to receive a 3-month course of levofloxacin or placebo starting in the early post-transplant period. Levofloxacin will be administered at 500 mg po daily with dose adjustments based on kidney function. The primary outcome will be the time to occurrence of BK viruria within the first year post-transplantation. Secondary outcomes include BK viremia, measures of safety (adverse events, resistant infections,Clostridium difficile-associated diarrhea), measures of feasibility (proportion of transplanted patients recruited into the trial), proportion of patients adherent to the protocol, patient drop-out and loss to follow-up,and use of quinolone antibiotics outside of the trial protocol. Discussion Results from this pilot study will provide vital information to design and conduct a large, multicenter trial to determine if quinolone therapy decreases clinically meaningful outcomes in kidney transplantation. If levofloxacin significantly reduces BK viruria and urine viral loads in kidney transplantation, it will provide important justification to progress to the larger trial. If the full trial shows that levofloxacin significantly reduces BK infection and improves outcomes, its use in kidney transplantation will be strongly endorsed given the lack of proven therapies for this condition. Trial registration This trial was funded by the Canadian Institutes of Health Research (grant number:222493) and is registered at ClinicalTrials.gov (NCT01353339).

Objective We evaluated the validity of physician billing claims to identify deceased organ donors in large provincial healthcare databases. Methods We conducted a population-based retrospective validation study of all deceased donors in Ontario, Canada from 2006 to 2011 (n = 988). We included all registered deaths during the same period (n = 458,074). Our main outcome measures included sensitivity, specificity, positive predictive value, and negative predictive value of various algorithms consisting of physician billing claims to identify deceased organ donors and organ-specific donors compared to a reference standard of medical chart abstraction. Results The best performing algorithm consisted of any one of 10 different physician billing claims. This algorithm had a sensitivity of 75.4% (95% CI: 72.6% to 78.0%) and a positive predictive value of 77.4% (95% CI: 74.7% to 80.0%) for the identification of deceased organ donors. As expected, specificity and negative predictive value were near 100%. The number of organ donors identified by the algorithm each year was similar to the expected value, and this included the pre-validation period (1991 to 2005). Algorithms to identify organ–specific donors performed poorly (e.g. sensitivity ranged from 0% for small intestine to 67% for heart; positive predictive values ranged from 0% for small intestine to 37% for heart). Interpretation Primary data abstraction to identify deceased organ donors should be used whenever possible, particularly for the detection of organ-specific donations. The limitations of physician billing claims should be considered whenever they are used.

Objective The objective of this study was to examine the factors that influence decision-making to forgo transplantation in favour of remaining on nocturnal haemodialysis (NHD). Design A grounded theory approach using in-depth telephone interviewing was used. Setting Participants were identified from 2 tertiary care renal programmes in Canada. Participants The study participants were otherwise eligible patients with end-stage renal disease who have opted to remain off of the transplant list. A total of 7 eligible participants were interviewed. 5 were male. The mean age was 46 years. Analysis A constant comparative method of analysis was used to identify a core category and factors influencing the decision-making process. Results In this grounded theory study of people receiving NHD who refused kidney transplantation, the core category of ‘why take a chance when things are going well?’ was identified, along with 4 factors that influenced the decision including ‘negative past experience’, ‘feeling well on NHD’, ‘gaining autonomy’ and ‘responsibility’. Conclusions This study provides insight into patients' thought processes surrounding an important treatment decision. Such insights might help the renal team to better understand, and thereby respect, patient choice in a patient-centred care paradigm. Findings may also be useful in the development of education programmes addressing the specific concerns of this population of patients.

Importance Solid-organ transplant recipients (SOTRs) are at greater risk of developing some cancers than the general population; however, because they are also at increased risk of mortality from noncancer causes, the effect of transplantation on cancer mortality is unclear. Objective To describe cancer mortality in SOTRs and to assess whether SOTRs are at increased risk of cancer mortality compared with the general population. Design, Setting, and Participants Population-based cohort study of patients who underwent solid-organ transplantation in Ontario, Canada, between 1991 and 2010 with 85 557 person-years of follow-up through December 31, 2011. Solid-organ transplantation was identified using the national transplant register and linked to the provincial cancer registry and administrative databases. The analysis was conducted between November 2013 and February 2015. Exposure Solid-organ transplantation. Main Outcomes and Measures Cancer mortality for SOTRs was compared with that of the general population using standardized mortality ratios (SMRs). Mortality and cause of death were ascertained by record linkage between the Canadian Organ Replacement Register, the Ontario Cancer Registry, and the Office of the Registrar General of Ontario death database. Results A total of 11 061 SOTRs were identified, including 6516 kidney, 2606 liver, 929 heart, and 705 lung transplantations. Recipients had a median (interquartile range) age of 49 (37-58) years, and 4004 (36.2%) were women. Of 3068 deaths, 603 (20%) were cancer related. Cancer mortality in SOTRs was significantly elevated compared with the Ontario population (SMR, 2.84 [95% CI, 2.61-3.07]). The risk remained elevated when patients with pretransplant malignant neoplasms (n = 1124) were excluded (SMR, 1.93 [95% CI, 1.75-2.13]). The increased risk was observed irrespective of transplanted organ. The SMR for cancer death after solid-organ transplantation was higher in children (SMR, 84.61 [95% CI, 52.00-128.40]) and lower in patients older than 60 years (SMR, 1.88 [95% CI, 1.62-2.18]) but remained elevated compared with the general population at all ages. Conclusions and Relevance Cancer death rate in SOTRs was increased compared with that expected in the general population; cancer was the second leading cause of death in these patients. Advances in prevention, clinical surveillance, and cancer treatment modalities for SOTRs are needed to reduce the burden of cancer mortality in this population.

Background: Early initiation of chronic dialysis (starting dialysis with higher vs lower kidney function) has risen rapidly in the past 2 decades in Canada and internationally, despite absence of established health benefits and higher costs. In 2014, a Canadian guideline on the timing of dialysis initiation, recommending an intent-to-defer approach, was published. Objective: The objective of this study is to evaluate the efficacy and safety of a knowledge translation intervention to promote the intent-to-defer approach in clinical practice. Design: This study is a multicenter, 2-arm parallel, cluster randomized trial. Setting: The study involves 55 advanced chronic kidney disease clinics across Canada. Patients: Patients older than 18 years who are managed by nephrologists for more than 3 months, and initiate dialysis in the follow-up period are included in the study. Measurements: Outcomes will be measured at the patient-level and enumerated within a cluster. Data on characteristics of each dialysis start will be determined by linkages with the Canadian Organ Replacement Register. Primary outcomes include the proportion of patients who start dialysis early with an estimated glomerular filtration rate greater than 10.5 mL/min/1.73 m2 and start dialysis in hospital as inpatients or in an emergency room setting. Secondary outcomes include the rate of change in early dialysis starts; rates of hospitalizations, deaths, and cost of predialysis care (wherever available); quarterly proportion of new starts; and acceptability of the knowledge translation materials. Methods: We randomized 55 multidisciplinary chronic disease clinics (clusters) in Canada to receive either an active knowledge translation intervention or no intervention for the uptake of the guideline on the timing of dialysis initiation. The active knowledge translation intervention consists of audit and feedback as well as patient- and provider-directed educational tools delivered at a comprehensive in-person medical detailing visit. Control clinics are only exposed to guideline release without active dissemination. We hypothesize that the clinics randomized to the intervention group will have a lower proportion of early dialysis starts. Limitations: Limitations include passive dissemination of the guideline through publication, and lead-time and survivor bias, which favors delayed dialysis initiation. Conclusions: If successful, this active knowledge translation intervention will reduce early dialysis starts, lead to health and economic benefits, and provide a successful framework for evaluating and disseminating future guidelines. Trial Registration: ClinicalTrials.gov , NCT02183987

To determine the general and transplant-specific risk factors for fractures in kidney transplant recipients.We conducted a cohort study of all adults who received a kidney-only transplant (n = 2723) in Ontario, Canada between 2002 and 2009. We used multivariable Cox proportional hazards regression to determine general and transplant-specific risk factors for major fractures (proximal humerus, forearm, hip, and clinical vertebral). The final model was established using the backward elimination strategy, selecting risk factors with a P-value ≤ 0.2 and forcing recipient age and sex into the model. We also assessed risk factors for other fracture locations (excluding major fractures, and fractures involving the skull, hands or feet).There were 132 major fractures in the follow-up (8.1 fractures per 1000 person-years). General risk factors associated with a greater risk of major fracture were older recipient age [adjusted hazard ratio (aHR) per 5-year increase 1.11, 95%CI: 1.03-1.19] and female sex (aHR = 1.81, 95%CI: 1.28-2.57). Transplant-specific risk factors associated with a greater risk of fracture included older donor age (5-year increase) (aHR = 1.09, 95%CI: 1.02-1.17) and end-stage renal disease (ESRD) caused by diabetes (aHR = 1.72, 95%CI: 1.09-2.72) or cystic kidney disease (aHR = 1.73, 95%CI: 1.08-2.78) (compared to glomerulonephritis as the reference cause). Risk factors across the two fracture locations were not consistent (major fracture locations vs other). Specifically, general risk factors associated with an increased risk of other fractures were diabetes and a fall with hospitalization prior to transplantation, while length of time on dialysis, and renal vascular disease and other causes of ESRD were the transplant-specific risk factors associated with a greater risk of other fractures.Both general and transplant-specific risk factors were associated with a higher risk of fractures in kidney transplant recipients. Results can be used for clinical prognostication.

Background/Aims: Home nocturnal hemodialysis (HNHD) has several benefits. However, patients that require caregiver assistance for dialysis may be at risk for poor outcomes. In an effort to determine if HNHD can be extended to assisted patients, an analysis of their outcomes is important. Methods: We examined a single-center cohort of patients that started and completed HNHD training between 01 January 2003 and 31 December 2010 (last follow-up 01 July 2011). Patients were classified as ‘dependent' if they required caregiver assistance for dialysis. The primary outcome was time to first hospitalization, technique failure, or death for dependent versus independent patients. Secondary outcomes included hospitalization rate and hospital days. Results: A total of 152 patients were included in this study. Dependent patients (n = 47) were older (51 vs. 42 years), more likely to have diabetic end-stage renal disease (26 vs. 8%) and had higher Charlson Comorbidity Index scores (4 vs. 3) compared to independent patients (n = 105). In an adjusted analysis there was no significant difference in the time to composite outcome for dependent versus independent patients (relative hazard 1.25; 95% confidence interval, CI, 0.76-2.04). Adjusted incidence rate ratios for hospitalizations (1.58; 95% CI 0.95-2.65) and hospital days (1.84; 95% CI 0.78-4.34) were not significantly different for dependent versus independent patients. Conclusion: Our study suggests that outcomes of caregiver-assisted versus independent HNHD patients are likely driven by differences in case mix. The need for caregiver assistance alone should not be a deterrent to HNHD.

IgA nephropathy (IgAN) accounts for a far higher proportion of end-stage renal disease (ESRD) in Asia compared with North America. It is not known whether this is entirely because of differences in disease prevalence or a higher risk of disease progression. The lack of a racially diverse population cohort followed longitudinally has previously precluded the ability to address this question. To determine whether Asians in North America with IgAN are at higher risk for ESRD, we analyzed a cohort of 202 patients of self-reported Pacific Asian origin and 467 of other origin from the Toronto GN Registry followed up for a median of 46.4 months. The primary outcome of ESRD (dialysis, transplantation, or eGFR below 15) was analyzed using Cox regression analysis. Baseline eGFR was 59.6 ml/min/1.73 m(2), and median proteinuria was 1.8 g/day. ESRD occurred in 213 patients. By univariable analysis, the risk of ESRD was similar between the two groups (hazard ratio 0.98, 95% CI 0.73, 1.31); however, after adjusting for age, gender, eGFR, medication use, blood pressure, and proteinuria, the risk of ESRD was significantly higher in Pacific Asian individuals (hazard ratio 1.56, 95% CI 1.10, 2.22). This was supported by a significant 1.62 ml/min/1.73 m(2)/year faster rate of eGFR decline (95% CI -3.19, -0.5) and an increased risk of a reduction in eGFR by half (hazard ratio 1.81, 95% CI 1.25, 2.62). Thus, in a large multiracial cohort of patients with IgAN, individuals of Pacific Asian origin have a higher risk of progression to ESRD.

Given the increased student interest in health research and the need to implement health research initiatives, the Multi-Organ Transplant Student Research Training Program provides student trainees with the opportunity to contribute to health research initiatives in transplant care. Program quality initiatives achieved include the development of a clinical research database, knowledge exchange, performance measurement tools, and health research projects. The program promotes collaboration between academic and healthcare institutions to integrate research and education into clinical practice.

Delayed graft function (DGF) has a negative impact on graft survival in donation after brain death (DBD) but not for donation after cardiac death (DCD) kidneys. However, older donor age is associated with graft loss in DCD transplants. We sought to examine the interaction between donor age and DGF in DBD kidneys. This is a single-center, retrospective review of 657 consecutive DBD recipients transplanted between 1990 and 2005. We stratified the cohort by decades of donor age and studied the association between DGF and graft failure using Cox models. The risk of graft loss associated with DGF was not significantly increased for donor age below 60 years (adjusted hazard ratio [aHR] 1.12, 1.51, and 0.90, respectively, for age

The kidney is the most common transplanted organ, accounting for almost all living donor transplantations and most deceased donor organ transplantations. The organ shortage has caused policymakers in many nations to debate the merits of adopting presumed consent legislation as a way to increase donor organ donation from deceased donors.To compare characteristics and kidney transplantation rates for countries with presumed consent for deceased organ donation with countries with explicit consent.A longitudinal study of international kidney transplantation from 1997 to 2007.44 nations performing kidney transplantation.Recipients of deceased and living kidney donor transplants.Rates of transplantation of kidneys from deceased and living donors.National characteristics, such as population size, proportion of the population self-identified as Catholic, per capita gross domestic product, health expenditures, and physician density, varied widely for the 22 nations with presumed consent and the 22 nations with explicit consent. Deceased donor kidney transplantation rates were higher in nations with presumed consent (median, 22.6 transplantations per million population [pmp]; interquartile range [IQR], 9.3 to 33.8) versus nations with explicit consent (median, 13.9 transplantations pmp; IQR, 3.6 to 23.1). Living donor kidney transplantation rates were lower in nations with presumed consent (median, 2.4 transplantations pmp; IQR, 1.7 to 4.3) versus nations with explicit consent (median, 5.9 transplantations pmp; IQR, 2.3 to 12.2). The findings were consistent when nations were classified according to per capita gross domestic product, health expenditures, and physician density.As with any observational study, associations may not be causal.Nations with presumed consent have higher rates of deceased donor kidney transplantation than nations with explicit consent. Any nation deciding to adopt presumed consent should carefully consider and reduce any negative effect on rates of living donation.Canadian Institutes of Health Research and Lawson Health Research Institute.

The link between delayed graft function (DGF) and death with graft function (DWGF) in living donor kidney transplant recipients presently is unknown.Retrospective cohort study.44,630 adult living donor kidney recipients (first transplants only) in the US Renal Data System from January 1, 1994, to December 31, 2004.DGF, defined as the need for dialysis therapy in the first week after transplant.Time to DWGF.Kaplan-Meier curves were constructed to assess the impact of DGF on DWGF. Recipients with DGF were 1:1 propensity score matched to those without DGF, and time-dependent Cox proportional hazards models were used to examine factors associated with DWGF. Subgroup and sensitivity analyses also were conducted.DWGF occurred in 3,878 patients during 3.9 years' (median) follow-up. In patients with DGF, survival with graft function at 1, 3, 5, and 10 years was 91.9%, 86.8%, 81.6%, and 61.7%, respectively (in patients without DGF, these values were 98.0%, 95.2%, 91.6%, and 80.1%, respectively; P0.001 compared with the DGF group). In a fully adjusted time-dependent Cox model, HRs for DWGF in patients with DGF (vs without DGF) were 6.55 (95% CI, 4.78-8.97), 3.55 (95% CI, 2.46-5.11), 2.07 (95% CI, 1.53-2.81), and 1.48 (95% CI, 1.26-1.73) at 0-1, 1-3, 3-12, and longer than 12 months posttransplant, respectively. Propensity score analysis showed similar results. Inferences were unchanged after adjustment for kidney function and acute rejection at 6 months and 1 year posttransplant. Cardiovascular and infectious causes of DWGF were more prevalent in patients with DGF. The association was more marked in female recipients and robust to various sensitivity analyses.The impact of lesser decreases in early graft function could not be evaluated.DGF is associated with an increased risk of DWGF in living donor kidney recipients. The mechanisms underlying this relation require further study.