Risk Factors for Developing Low Estimated Glomerular Filtration Rate and Albuminuria in Living Kidney Donors.

Rationale & Objective: Chronic kidney disease is associated with significant morbidity and mortality in the general population, but little is known about the incidence and risk factors associated with developing low estimated glomerular filtration rate (eGFR) and moderate-severe albuminuria in living kidney donors following nephrectomy. Study Design: Retrospective, population-based cohort study. Setting & Participants: Kidney donors in Alberta, Canada. Exposure: Donor nephrectomy between May 2001 and December 2017. Outcome: Two eGFR measurements <45 mL/min/1.73 m2 or 2 measurements of moderate or severe albuminuria from 1-year postdonation onwards that were at least 90 days apart. Analytical Approach: Associations between potential risk factors and the primary outcome were assessed using Cox proportional hazard regression analyses. Results: Over a median follow-up period of 8.6 years (IQR, 4.7-12.6 years), 47 of 590 donors (8.0%) developed sustained low eGFR or moderate-severe albuminuria with an incidence rate of 9.2 per 1,000 person-years (95% confidence interval, 6.6-11.8). The median time for development of this outcome beyond the first year after nephrectomy was 2.9 years (IQR, 1.4-8.0 years). Within the first 4 years of follow-up, a 5 mL/min/1.73 m2 lower predonation eGFR increased the hazard of developing postdonation low eGFR or moderate-severe albuminuria by 26% (adjusted HR, 1.26; 95% CI, 1.10-1.44). Furthermore, donors were at higher risk of developing low eGFR or albuminuria if they had evidence of predonation hypertension (adjusted HR, 2.52; 95% CI, 1.28-4.96) or postdonation diabetes (adjusted HR, 4.72; 95% CI, 1.54-14.50). Limitations: We lacked data on certain donor characteristics that may affect long-term kidney function, such as race, smoking history, and transplant-related characteristics. Conclusions: A proportion of kidney donors at an incidence rate of 9.2 per 1,000 person-years will develop low eGFR or albuminuria after donation. Donors with lower predonation eGFR, predonation hypertension, and postdonation diabetes are at increased risk of developing this outcome.

The purpose of this study was to understand the risk of developing kidney disease in living kidney donors after donation. We followed 590 donors in Alberta, Canada for almost 9 years. Approximately 8% of donors developed reduced kidney function (low estimated glomerular filtration rate) or increased protein in the urine (albuminuria). Donors with lower kidney function before donation, hypertension before donation, or diabetes after donation had a higher likelihood of experiencing these kidney outcomes. This research provides important insights to patients and health care providers to better support the long-term kidney health of living kidney donors.

Proton Pump Inhibitors Use in Kidney Transplant Recipients: A Population-Based Study.

Background: Kidney transplant recipients are commonly prescribed proton-pump inhibitors (PPIs), but due to concern for polypharmacy, chronic use should be limited. Objective: The objective was to describe PPI use in kidney transplant recipients beyond their first year of transplant to better inform and support deprescribing initiatives. Design: We conducted a retrospective, population-based cohort study using linked health care databases. Setting: This study was conducted in Alberta, Canada. Patients: We included all prevalent adult, kidney-only transplant recipients between April 2008 and December 2017 who received their transplant between May 2002 and December 2017. Measurements: The primary outcome was ongoing or new PPI use and patterns of use, including frequency and duration of therapy, and assessment of indication for PPI use. Methods: We ascertained baseline characteristics, covariate information, and outcome data from the Alberta Kidney Disease Network (AKDN). We compared recipients with evidence of a PPI prescription in the 3 months prior to study entry to those with a histamine-2-receptor antagonist (H2Ra) fill and those with neither. Results: We identified 1823 kidney transplant recipients, of whom 868 (48%) were on a PPI, 215 (12%) were on an H2Ra, and 740 (41%) were on neither at baseline. Over a median follow-up of 5.4 years (interquartile range [IQR] = 2.6-9.3), there were almost 45 000 unique PPI prescriptions dispensed, the majority (80%) of which were filled by initial PPI users. Recipients who were on a PPI at baseline would spend 91% (IQR = 70-98) of their graft survival time on a PPI in follow-up, and nephrologists were the main prescribers. We identified an indication for ongoing PPI use in 54% of recipients with the most common indication being concurrent antiplatelet use (26%). Limitations: Our kidney transplant recipients have access to universal health care coverage which may limit generalizability. We identified common gastrointestinal indications for PPI use but did not include rare conditions due to concerns about the validity of diagnostic codes. In addition, symptoms suggestive of reflux may not be well coded as the focus of follow-up visits is more likely to focus on kidney transplant. Conclusions: Many kidney transplant recipients are prescribed a PPI at, or beyond, the 1-year post-transplant date and are likely to stay on a PPI in follow-up. Almost half of the recipients in our study did not have an identifiable indication for ongoing PPI use. Nephrologists frequently prescribe PPIs to kidney transplant recipients and should be involved in deprescribing initiatives to reduce polypharmacy.

Contexte: On prescrit couramment des inhibiteurs de la pompe à protons (IPP) aux receveurs d'une greffe rénale; une pratique qui devrait cependant être limitée en raison de préoccupations liées à la polypharmacie. Objectif: Décrire l'utilisation des IPP chez les receveurs d'une greffe rénale au-delà de la première année post-greffe, afin de mieux informer et de soutenir les initiatives de déprescription. Type d'étude: Étude de cohorte populationnelle rétrospective réalisée à partir des bases de données couplées du système de santé. Cadre: Alberta, Canada. Sujets: Nous avons recueilli les données d'avril 2008 à décembre 2017 de tous les adultes qui avaient reçu un rein seulement entre mai 2002 et décembre 2017. Mesures: Le principal critère de jugement était la prise continue ­ ou une nouvelle ordonnance ­ d'IPP et les modalités d'utilisation, notamment la fréquence et la durée du traitement, ainsi que l'indication pour la prescription d'IPP. Méthodologie: Nous avons vérifié les caractéristiques initiales, les informations covariées et les données sur les résultats colligées dans l'Alberta Kidney Disease Network (AKDN). Nous avons comparé des receveurs présentant des preuves d'une prescription d'IPP au cours des trois mois précédant l'entrée dans l'étude à des patients avec une ordonnance d'antagonistes des récepteurs de l'histamine-2 (aRH2), ainsi qu'à des patients n'ayant aucune de ces prescriptions. Résultats: Nous avons identifié 1 823 receveurs d'une greffe rénale; 868 (48 %) recevaient un IPP, 215 (12 %) recevaient un aRH2 et 740 (41 %) ne recevaient aucun traitement à l'inclusion. Au cours d'un suivi médian de 5,4 ans (intervalle interquartile [IIQ]: 2,6-9,3), près de 45 000 ordonnances uniques d'IPP ont été délivrées, dont la majorité (80 %) avait été remplie par des utilisateurs initiaux d'IPP. Les receveurs qui prenaient des IPP à l'inclusion avaient passé 91 % (IIQ: 70-98) de leur temps de survie du greffon à prendre un IPP durant la période de suivi, et ces médicaments avaient été majoritairement prescrits par des néphrologues. Une indication justifiant l'utilisation continue d'un IPP était présente chez 54 % des receveurs; la plus courante étant l'utilisation concomitante d'un agent antiplaquettaire (26 %). Limites: Les receveurs inclus dans notre étude ont accès à une couverture médicale universelle, ce qui peut limiter la généralisabilité des résultats. Nous avons repéré des indications gastro-intestinales courantes pour l'utilisation d'IPP, mais nous n'avons pas inclus les affections rares en raison de préoccupations concernant la validité des codes diagnostiques. Aussi, les symptômes évocateurs d'un reflux pourraient ne pas être bien codés, car les visites de suivi sont plus susceptibles de porter sur la transplantation rénale. Conclusion: De nombreux receveurs d'une greffe rénale se voient encore prescrire un IPP dans l'année suivant la transplantation, ou au-delà, et sont susceptibles de continuer d'en prendre pendant le suivi. Près de la moitié des receveurs de notre étude n'avaient pas d'indication clairement identifiable de prendre un IPP en continu. Les néphrologues prescrivent fréquemment des IPP aux receveurs d'une greffe rénale et devraient être impliqués dans les initiatives de déprescription visant à réduire la polypharmacie.

Follow-up Care of Critically Ill Patients With Acute Kidney Injury: A Cohort Study.

Rationale & Objective: To evaluate follow-up care of critically ill patients with acute kidney injury (AKI). Study Design: Retrospective cohort study. Setting & Participants: Patients admitted to the intensive care unit (ICU) with AKI in Alberta, Canada from 2005 to 2018, who survived to discharge without kidney replacement therapy or estimated glomerular filtration rate <15 mL/min/1.73 m2. Exposure: AKI (defined as ≥50% or ≥0.3 mg/dL serum creatinine increase). Outcomes: The primary outcome was the cumulative incidence of an outpatient serum creatinine and urine protein measurement at 3 months postdischarge. Secondary outcomes included an outpatient serum creatinine or urine protein measurement or a nephrologist visit at 3 months postdischarge. Analytical Approach: Patients were followed from hospital discharge until the first of each outcome of interest, death, emigration from the province, kidney replacement therapy (maintenance dialysis or kidney transplantation), or end of study period (March 2019). We used non-parametric methods (Aalen-Johansen) to estimate the cumulative incidence functions of outcomes accounting for competing events (death and kidney replacement therapy). Results: There were 29,732 critically ill adult patients with AKI. The median age was 68 years (IQR, 57-77), 39% were female, and the median baseline estimated glomerular filtration rate was 72 mL/min/1.73 m2 (IQR, 53-90). The cumulative incidence of having an outpatient creatinine and urine protein measurement at 3 months postdischarge was 25% (95% CI, 25-26). At 3 months postdischarge, 64% (95% CI, 64-65) had an outpatient creatinine measurement, 28% (95% CI, 27-28) had a urine protein measurement, and 5% (95% CI, 4-5) had a nephrologist visit. Limitations: We lacked granular data, such as urine output. Conclusions: Many critically ill patients with AKI do not receive the recommended follow-up care. Our findings highlight a gap in the transition of care for survivors of critical illness and AKI.

Trimethoprim-sulfamethoxazole and the risk of a hospital encounter with hyperkalemia: a matched population-based cohort study.

BACKGROUND: Trimethoprim-sulfamethoxazole (TMP-SMX) can cause hyperkalemia by reducing renal potassium excretion. We assessed the risk of hyperkalemia after initiating TMP-SMX versus amoxicillin and determined if this risk is modified by a patient's baseline kidney function [estimated glomerular filtration rate (eGFR)]. METHODS: We conducted a population-based cohort study in Ontario, Canada involving adults ≥66 years of age newly treated with TMP-SMX (n = 58 999) matched 1:1 with those newly treated with amoxicillin (2008-2020). The primary outcome was a hospital encounter with hyperkalemia defined by a laboratory serum potassium value ≥5.5 mmol/L within 14 days of antibiotic treatment. Secondary outcomes included a hospital encounter with acute kidney injury (AKI) and all-cause hospitalization. Risk ratios (RRs) were obtained using a modified Poisson regression. RESULTS: A hospital encounter with hyperkalemia occurred in 269/58 999 (0.46%) patients treated with TMP-SMX versus 80/58 999 (0.14%) in those treated with amoxicillin {RR 3.36 [95% confidence interval (CI) 2.62-4.31]}. The absolute risk of hyperkalemia in patients treated with TMP-SMX versus amoxicillin increased progressively with decreasing eGFR (risk difference of 0.12% for an eGFR ≥60 ml/min/1.73 m2, 0.42% for eGFR 45-59, 0.85% for eGFR 30-44 and 1.45% for eGFR <30; additive interaction P < .001). TMP-SMX versus amoxicillin was associated with a higher risk of a hospital encounter with AKI [RR 3.15 (95% CI 2.82-3.51)] and all-cause hospitalization [RR 1.43 (95% CI 1.34-1.53)]. CONCLUSIONS: The 14-day risk of a hospital encounter with hyperkalemia was higher in patients newly treated with TMP-SMX versus amoxicillin and the risk was highest in patients with a low eGFR.

Using the Revised Cardiac Risk Index to Predict Major Postoperative Events for People With Kidney Failure: An External Validation and Update.

Background: People with kidney failure have high risk of postoperative morbidity and mortality. Although the revised cardiac risk index (RCRI) is used to estimate the risk of major postoperative events, it has not been validated in this population. We aimed to externally validate the RCRI and determine whether updating the model improved predictions for people with kidney failure. Methods: We derived a retrospective, population-based cohort of adults with kidney failure (maintenance dialysis or sustained estimated glomerular filtration rate < 15 mL/min per 1.73 m2) who had surgery in Alberta, Canada between 2005 and 2019. We categorized participants based on RCRI variables and assigned risk estimates of death or major cardiac events, and then estimated predictive performance. We re-estimated the coefficients for each RCRI variable and internally validated the updated model. Net benefit was estimated with decision curve analysis. Results: After 38,541 surgeries, 1204 events (3.1%) occurred. The estimated C-statistic for the original RCRI was 0.64 (95% confidence interval: 0.62, 0.65). Examination of calibration revealed significant risk overestimation. In the re-estimated RCRI model, discrimination was marginally different (C-statistic 0.67 [95% confidence interval: 0.66, 0.69]), though calibration was improved. No net benefit was observed when the data were examined with decision curve analysis, whereas the original RCRI was associated with harm. Conclusions: The RCRI performed poorly in a Canadian kidney failure cohort and significantly overestimated risk, suggesting that RCRI use in similar kidney failure populations should be limited. A re-estimated kidney failure-specific RCRI may be promising but needs external validation. Novel perioperative models for this population are urgently needed.

Contexte: Les personnes atteintes d'insuffisance rénale présentent un risque élevé de mortalité et de morbidité postopératoires. L'indice de risque cardiaque révisé (IRCR) est utilisé pour estimer le risque d'événements postopératoires majeurs, mais il n'a pas été validé au sein de cette po-pulation. Nous avons cherché à réaliser une validation externe de l'IRCR et à déterminer si une modification du modèle pourrait permettre une meilleure valeur prédictive pour les patients atteints d'insuffisance rénale. Méthodologie: Nous avons étudié rétrospectivement une cohorte populationnelle d'adultes atteints d'insuffisance rénale (sous dialyse d'entretien ou avec un débit de filtration glomérulaire estimé < 15 ml/min/1,73 m2, de façon soutenue) ayant subi une intervention chirurgicale en Alberta (Canada) entre 2005 et 2019. Les participants ont été classifiés selon les variables de l'IRCR, et une estimation du risque de décès ou d'événement cardiovasculaire majeur leur a été attribuée; la performance prédictive a ensuite été évaluée. Nous avons réestimé les coefficients pour chacune des variables de l'IRCR et nous avons validé de manière interne le modèle modifié. Le bénéfice net a été estimé avec une analyse de la courbe décisionnelle. Résultats: Après 38 541 interventions chirurgicales, des événements cardiovasculaires sont survenus dans 1 204 cas (3,1 %). La statistique C estimée obtenue avec l'IRCR initial était de 0,64 (intervalle de confiance [IC] à 95 %, de 0,62 à 0,65). Un examen de la calibration de l'indice a révélé une surestimation significative du risque. Avec le modèle d'IRCR modifié, la discrimination présentait une légère différence (statistique C de 0,67 [IC à 95 %, de 0,66 à 0,69]), bien que la calibration ait été améliorée. Pour l'indice modifié, aucun bénéfice net n'a été observé lors de l'examen des données par une analyse décisionnelle, alors qu'un préjudice était associé à l'IRCR initial. Conclusions: L'IRCR s'est révélé peu concluant dans une cohorte populationnelle de patients canadiens atteints d'insuffisance rénale et il a significativement surestimé les risques pour ces patients, ce qui suggère que l'utilisation de l'IRCR dans des populations similaires atteintes d'insuffisance rénale devrait être limitée. Un IRCR réestimé, propre à la population des patients atteints d'insuffisance rénale, pourrait être prometteur, mais requiert une validation externe. De nouveaux modèles périopératoires sont indispensables pour cette population.

Immunosuppression Considerations for Older Kidney Transplant Recipients.

PURPOSE OF REVIEW: While kidney transplantation improves the long-term survival of the majority of patients with end-stage kidney disease (ESKD), age-related immune dysfunction and associated comorbidities make older transplant recipients more susceptible to complications related to immunosuppression. In this review, we discuss appropriate management of immunosuppressive agents in older adults to minimize adverse events, avoid acute rejection, and maximize patient and graft survival. RECENT FINDINGS: Physiological changes associated with senescence can impact drug metabolism and increase the risk of posttransplant infection and malignancy. Clinical trials assessing the safety and efficacy of immunosuppressive agents in older adults are lacking. Recent findings from U.S. transplant registry-based studies suggest that risk-adjusted death-censored graft failure is higher among older patients who received antimetabolite avoidance, mammalian target of rapamycin inhibitor (mTORi)-based, and cyclosporine-based regimens. Observational data suggest that risk-adjusted mortality may be increased in older patients who receive mTORi-based and cyclosporine-based regimens but lower in those managed with T-cell induction and maintenance steroid avoidance/withdrawal. SUMMARY: Tailored immunosuppression management to improve patient and graft survival in older transplant recipients is an important goal of personalized medicine. Lower intensity immunosuppression, such as steroid-sparing regimens, appear beneficial whereas mTORi- and cyclosporine-based maintenance are associated with greater potential for adverse effects. Prospective clinical trials to assess the safety and efficacy of immunosuppression agents in older recipients are urgently needed.

Predicting Myocardial Injury and Other Cardiac Complications After Elective Noncardiac Surgery with the Revised Cardiac Risk Index: The VISION Study.

BACKGROUND: The Revised Cardiac Risk Index (RCRI) is widely used to estimate risk of cardiac complications after noncardiac surgery; its estimates do not capture myocardial injury after noncardiac surgery (MINS). We evaluated the incidence of cardiac complications including MINS across RCRI risk classes and the RCRI's ability to discriminate, before surgery, between patients who will experience these complications and those who will not. METHODS: This was a secondary analysis of a prospective cohort study of 35,815 patients ≥ 45 years old who had elective inpatient noncardiac surgery from 2007 to 2013 at 28 centres in 14 countries. The primary outcome was a composite of MINS, myocardial infarction, nonfatal cardiac arrest, or cardiac death within 30 days after surgery. The secondary outcome was this composite without MINS. RESULTS: The primary outcome occurred in 4725 patients (13.2%); its incidences across RCRI classes I (no risk factors), II (1 risk factor), III (2 risk factors), and IV (≥ 3 risk factors) were, respectively, 8.2%, 15.4%, 26.6%, and 40.2% (C-statistic for discrimination 0.65 [95% confidence interval 0.62-0.68]). The secondary outcome occurred in 1174 patients (3.3%) with incidences of 1.6%, 4.0%, 7.9%, and 12.9%, respectively (C-statistic 0.69 [0.65-0.72]). Thirty-five percent of primary outcome events and 26.9% of secondary outcome events occurred in patients with no RCRI risk factors. CONCLUSION: The RCRI alone is not sufficient to guide postoperative cardiac monitoring because 1 in 12 patients ≥ 45 years of age without any RCRI risk factors have a cardiac complication after major noncardiac surgery, and most of them would be missed without systematic troponin testing.

An International survey on living kidney donation and transplant practices during the COVID-19 pandemic.

The scope of the impact of the Coronavirus disease 19 (COVID-19) pandemic on living donor kidney transplantation (LDKT) practices across the world is not well-defined. We received survey responses from 204 transplant centers internationally from May to June 2020 regarding the impact of the COVID-19 pandemic on LDKT practices. Respondents represented 16 countries on five continents. Overall, 75% of responding centers reported that LDKT surgery was on hold (from 67% of North American centers to 91% of European centers). The majority (59%) of centers reported that new donor evaluations were stopped (from 46% of North American centers to 86% of European centers), with additional 23% of centers reporting important decrease in evaluations. Only 10% of centers reported slight variations on their evaluations. For the centers that continued donor evaluations, 40% performed in-person visits, 68% by video, and 42% by telephone. Center concerns for donor (82%) and recipient (76%) safety were the leading barriers to LDKT during the pandemic, followed by patients concerns (48%), and government restrictions (46%). European centers reported more barriers related to staff limitations while North and Latin American centers were more concerned with testing capacity and insufficient resources including protective equipment. As LDKT resumes, 96% of the programs intend to screen donor and recipient pairs for coronavirus infection, most of them with polymerase chain reaction testing of nasopharyngeal swab samples. The COVID-19 pandemic has had broad impact on all aspects of LDKT practice. Ongoing research and consensus-building are needed to guide safe reopening of LDKT programs.

Canadian Society of Transplantation and Canadian Society of Nephrology Commentary on the 2017 KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors.

PURPOSE OF REVIEW: To review an international guideline on the evaluation and care of living kidney donors and provide a commentary on the applicability of the recommendations to the Canadian donor population. SOURCES OF INFORMATION: We reviewed the 2017 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors and compared this guideline to the Canadian 2014 Kidney Paired Donation (KPD) Protocol for Participating Donors. METHODS: A working group was formed consisting of members from the Canadian Society of Transplantation and the Canadian Society of Nephrology. Members were selected to have representation from across Canada and in various subspecialties related to living kidney donation, including nephrology, surgery, transplantation, pediatrics, and ethics. KEY FINDINGS: Many of the KDIGO Guideline recommendations align with the KPD Protocol recommendations. Canadian researchers have contributed to much of the evidence on donor evaluation and outcomes used to support the KDIGO Guideline recommendations. LIMITATIONS: Certain outcomes and risk assessment tools have yet to be validated in the Canadian donor population. IMPLICATIONS: Living kidney donors should be counseled on the risks of postdonation outcomes given recent evidence, understanding the limitations of the literature with respect to its generalizability to the Canadian donor population.

JUSTIFICATION: Examiner une directive internationale sur l'évaluation et la prise en charge des donneurs vivants d'un rein et formuler un commentaire sur l'applicabilité de ces recommandations à la population des donneurs canadiens. SOURCES: Nous avons révisé le guide des pratiques cliniques relatives à l'évaluation et à la prise en charge des donneurs vivants d'un rein (Clinical Practice Guideline for Evaluation and Care of Living Kidney Donors) de 2017 du KDIGO (Kidney Disease: Improving Global Outcomes) et nous l'avons comparé aux recommandations canadiennes de 2014 du Protocole de don croisé d'un rein par donneurs participants (Kidney Paired Donation Protocol for Participating Donors). MÉTHODOLOGIE: Un groupe de travail réunissant des membres de la Société canadienne de transplantation et de la Société canadienne de néphrologie a été formé. Les membres ont été sélectionnés pour représenter tout le Canada et plusieurs sous-spécialisations relatives au don vivant d'un rein, notamment la néphrologie, la chirurgie, la transplantation, la pédiatrie et l'éthique. PRINCIPALES CONSTATATIONS: Plusieurs des recommandations du KDIGO s'harmonisent aux recommandations du protocole de don croisé d'un rein. Les chercheurs canadiens ont contribué en grande partie aux données sur l'évaluation des donneurs et des résultats utilisées pour appuyer les recommandations formulées dans les lignes directrices du KDIGO. LIMITES: Certains résultats et outils d'évaluation des risques doivent encore être validés dans la population des donneurs canadiens. CONCLUSION: Compte tenu des plus récentes données, les donneurs vivants d'un rein devraient être mis en garde concernant les risques sur leur santé post-don, tout en comprenant les limites de la littérature en ce qui concerne leur généralisabilité à la population de donneurs canadiens.

Prescription patterns of opioids and non-steroidal anti-inflammatory drugs in the first year after living kidney donation: An analysis of U.S. Registry and Pharmacy fill records.

We examined a novel database linking national donor registry identifiers to records from a US pharmaceutical claims warehouse (2007-2015) to describe opioid and NSAID prescription patterns among LKDs during the first year postdonation, divided into three periods: 0-14 days, 15-182 days, and 183-365 days. Associations of opioid and NSAID prescription fills with baseline factors were examined by logistic regression (adjusted odds ratio, LCL aORUCL ). Among 23,565 donors, opioid prescriptions were highest during days 0-14 (36.6%), but 12.6% of donors filled opioids during days 183-365. NSAID prescriptions rose from 0.5% during days 0-14 to 3.3% during days 183-365. Women filled opioids more commonly than men, and black donors filled both opioids and NSAIDs more commonly than white donors. After covariate adjustment, significant correlates of opioid prescription fills during days 183-365 included obesity (aOR,1.24 1.381.53 ), less than college education (aOR,1.19 1.311.43 ), smoking (aOR,1.33 1.451.58 ), and nephrectomy complications (aOR,1.11 1.291.49 ). NSAID prescription fills in year 1 were not associated with differences in estimated glomerular filtration rate, incidence of proteinuria or new-onset hypertension at the first and second year postdonation. Prescription fills for opioids and NSAIDs for LKDs varied with demographic and clinic traits. Future work should examine longer-term outcome implications to help inform safe analgesic regimen choices after donation.

A Propensity Score-weighted Comparison of Outcomes Between Living and Standard Criteria Deceased Donor Kidney Transplant Recipients.

BACKGROUND: Consider a theoretical situation in which 2 patients with similar baseline characteristics receive a kidney transplant on the same day: 1 from a standard criteria deceased donor, the other from a living donor. Which kidney transplant will last longer? METHODS: We conducted a population-based cohort study using linked administrative healthcare databases from Ontario, Canada, from January 1, 2005, to March 31, 2014, to evaluate several posttransplant outcomes in individuals who received a kidney transplant from a standard criteria deceased donor (n = 1523) or from a living donor (n = 1373). We used PS weighting using overlap weights, a novel weighting method that emphasizes the population of recipients with the most overlap in baseline characteristics. RESULTS: Compared with recipients of a living donor, the rate of all-cause graft failure was not statistically higher for recipients of a standard criteria deceased donor (hazard ratio, 1.1; 95% confidence interval [CI], 0.8-1.6). Recipients of a standard criteria deceased donor, compared with recipients of a living donor had a higher rate of delayed graft function (23.6% versus 18.7%; odds ratio, 1.3; 95% CI, 1.0-1.6) and a longer length of stay for the kidney transplant surgery (mean difference, 1.7 d; 95% CI, 0.5-3.0). CONCLUSIONS: After accounting for many important donor and recipient factors, we failed to observe a large difference in the risk of all-cause graft failure for recipients of a standard criteria deceased versus living donor. Some estimates were imprecise, which meant we could not rule out the presence of smaller clinically important effects.

Albuminuria, Reduced Kidney Function, and the Risk of ST - and non-ST-segment-elevation myocardial infarction.

Background Chronic kidney disease is a recognized independent risk factor for cardiovascular disease, but whether the risks of ST-segment-elevation myocardial infarction ( STEMI ) and non-ST-segment-elevation myocardial infarction ( NSTEMI ) differ in the chronic kidney disease population is unknown. Methods and Results Using administrative data from Ontario, Canada, we examined patients ≥66 years of age with an outpatient estimated glomerular filtration rate ( eGFR ) and albuminuria measure for incident myocardial infarction from 2002 to 2015. Adjusted Fine and Gray subdistribution hazard models accounting for the competing risk of death were used. In 248 438 patients with 1.2 million person-years of follow-up, STEMI , NSTEMI , and death occurred in 1436 (0.58%), 4431 (1.78%), and 30 015 (12.08%) patients, respectively. The highest level of albumin-to-creatinine ratio (>30 mg/mmol) was associated with a 2-fold higher adjusted risk of both STEMI and NSTEMI among patients with eGFR ≥60 mL/(min·1.73 m2) compared to albumin-to-creatinine ratio <3 mg/mmol. The lowest level of eGFR (<30 mL/[min·1.73 m2]) was not associated with higher STEMI risk but with a 4-fold higher risk of NSTEMI compared to those with eGFR ≥60 mL/(min·1.73 m2). The lowest eGFR (<30 mL/[min·1.73 m2]) and highest albumin-to-creatinine ratio (>30 mg/mmol) were associated with a greater than 4-fold higher risk of both STEMI and NSTEMI (subdistribution hazard models [95% confidence interval] 4.53 [3.30-6.21] and 4.42 [3.67-5.32], respectively) compared to albumin-to-creatinine ratio <3 mg/mmol and eGFR ≥60 mL/(min·1.73 m2). Conclusions Elevations in albuminuria are associated with a higher risk of both NSTEMI and STEMI , regardless of kidney function, whereas reduced kidney function alone is associated with a higher NSTEMI risk.

Duration of Living Kidney Transplant Donor Evaluations: Findings From 2 Multicenter Cohort Studies.

BACKGROUND: A prolonged living kidney donor evaluation may result in worse outcomes for transplant recipients. Better knowledge of the duration of this process may help inform future donors and identify opportunities for improvement. STUDY DESIGN: 1 prospective and 1 retrospective cohort study. SETTING & PARTICIPANTS: At 16 Canadian and Australian transplantation centers (prospective cohort) and 5 Ontario transplantation centers (retrospective cohort), we assessed the duration of living kidney donor evaluation and explored donor, recipient, and transplantation factors associated with longer evaluation times. Data were obtained from 2 sources: donor medical records using chart abstraction and health care administrative databases. PREDICTORS: Donor and recipient demographics, direct versus paired donation, center-level variables. OUTCOMES: Duration of living donor evaluation. RESULTS: The median total duration of transplantation evaluation (time from when the candidate started the evaluation until donation) was 10.3 (IQR, 6.5-16.7) months. The median duration from evaluation start until approval to donate was 7.9 (IQR, 4.6-14.1) months, and from approval until donation was 0.7 (IQR, 0.3-2.4) months, respectively. The median time between the first and last consultation among donors who completed a nephrology, surgery, and psychosocial assessment in the prospective cohort was 3.0 (IQR, 1.0-6.3) months, and between computed tomography angiography and donation was 4.8 (IQR, 2.6-9.2) months. After adjustment, the total duration of transplantation evaluation was longer if the donor participated in paired donation (6.6 [95% CI, 1.6-9.7] months) and if the recipient was referred later relative to the donor's evaluation start date (0.9 [95% CI, 0.8-1.0] months [per month of delayed referral]). Results depended on whether the recipient was receiving dialysis. LIMITATIONS: Living donor candidates who did not donate were not included and proxy measures were used for some dates in the donor evaluation process. CONCLUSIONS: The duration of kidney transplant donor evaluation is variable and can be lengthy. Better understanding of the reasons for a prolonged evaluation may inform quality improvement initiatives to reduce unnecessary delays.

Renal and cardiac assessment of living kidney donor candidates.

Living kidney donation provides the best therapeutic outcomes for eligible patients with end-stage renal disease. To ensure suitability for living kidney donation, donor candidates undergo a thorough medical, surgical, and psychosocial evaluation by a multidisciplinary transplant assessment team. Numerous guidelines are available to assist clinicians in the process of donor evaluation and selection. These guidelines outline the minimum recommended requirements for donor screening and additional tests that are indicated when abnormalities arise; however, evidence suggests that some of these additional tests might not be required in certain donor candidates. Measured glomerular filtration rate (GFR) using isotopic methods is more accurate than estimated GFR for the assessment of renal function; however, a new clinical tool might enable the identification of donor candidates for whom nuclear medicine renal scans are not needed. Persistent isolated microscopic haematuria caused by urologic or glomerular diseases can preclude donation and such abnormalities can often be identified by kidney biopsy. Cystoscopy might not be useful for young patients, however, owing to the rarity of urological cancers in this population. Currently, no evidence exists to support the notion that donor candidates at low-risk of cardiac events should undergo additional preoperative cardiovascular evaluation before donation. Reducing and/or eliminating the need for additional testing has the potential to enhance efficiency in the donor evaluation process, improve patient satisfaction, and increase access to living donor kidney transplantation.

External validation of the Revised Cardiac Risk Index and update of its renal variable to predict 30-day risk of major cardiac complications after non-cardiac surgery: rationale and plan for analyses of the VISION study.

INTRODUCTION: The Revised Cardiac Risk Index (RCRI) is a popular classification system to estimate patients' risk of postoperative cardiac complications based on preoperative risk factors. Renal impairment, defined as serum creatinine >2.0 mg/dL (177 µmol/L), is a component of the RCRI. The estimated glomerular filtration rate has become accepted as a more accurate indicator of renal function. We will externally validate the RCRI in a modern cohort of patients undergoing non-cardiac surgery and update its renal component. METHODS AND ANALYSIS: The Vascular Events in Non-cardiac Surgery Patients Cohort Evaluation (VISION) study is an international prospective cohort study. In this prespecified secondary analysis of VISION, we will test the risk estimation performance of the RCRI in ∼34 000 participants who underwent elective non-cardiac surgery between 2007 and 2013 from 29 hospitals in 15 countries. Using data from the first 20 000 eligible participants (the derivation set), we will derive an optimal threshold for dichotomising preoperative renal function quantified using the Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) glomerular filtration rate estimating equation in a manner that preserves the original structure of the RCRI. We will also develop a continuous risk estimating equation integrating age and CKD-Epi with existing RCRI risk factors. In the remaining (approximately) 14 000 participants, we will compare the risk estimation for cardiac complications of the original RCRI to this modified version. Cardiac complications will include 30-day non-fatal myocardial infarction, non-fatal cardiac arrest and death due to cardiac causes. We have examined an early sample to estimate the number of events and the distribution of predictors and missing data, but have not seen the validation data at the time of writing. ETHICS AND DISSEMINATION: The research ethics board at each site approved the VISION protocol prior to recruitment. We will publish our results and make our models available online at http://www.perioperativerisk.com. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT00512109.

The Risk of Cardiovascular Disease Is Not Increasing Over Time Despite Aging and Higher Comorbidity Burden of Kidney Transplant Recipients.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Risk factors for fracture in adult kidney transplant recipients.

AIM: To determine the general and transplant-specific risk factors for fractures in kidney transplant recipients. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Risk of Nephrectomy in Previous Living Kidney Donors.

BACKGROUND: For patients with a solitary kidney, such as living kidney donors, the surgical treatment of renal tumors may result in loss of function of the remaining kidney. METHODS: We conducted a retrospective, matched cohort study to determine the long-term risk of partial or total nephrectomy in previous living kidney donors compared to healthy nondonors. We reviewed the predonation charts for all living kidney donors in Ontario, Canada between 1992 and 2010 and linked this information to provincial healthcare databases. RESULTS: We matched 2119 donors to 21190 nondonors from the general population with similar baseline health. The median length of follow-up was 9.5 years (maximum 21.7 years). The rate of nephrectomy in follow-up was lower in donors versus nondonors (0 vs. 1.78 per 10000 person years; P = 0.037). In a subset of 1773 donors matched to 1773 healthy nondonors with renal imaging (median follow-up 7.6 years, maximum 21.0 years), the rate of nephrectomy was not statistically different in donors versus nondonors (0 vs. ≤5 per 10000 person years; P > 0.08). CONCLUSION: No living kidney donor in our cohort received a partial or total nephrectomy of their remaining kidney during our follow-up period. Although we will continue to follow people in this study, these interim results are reassuring for the safety of kidney donation.

Gout after living kidney donation: a matched cohort study.

BACKGROUND: In 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 DESIGN: Retrospective matched cohort study using large health care databases. SETTING & PARTICIPANTS: We 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. PREDICTOR: Living kidney donor nephrectomy. OUTCOMES: The 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). MEASUREMENTS: We assessed the primary outcome with health care diagnostic codes. RESULTS: Donors 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<0.001). Similarly, donors compared with nondonors were more likely to receive a prescription for allopurinol or colchicine (3.8% vs 1.3%; OR, 3.2; 95% CI, 1.5-6.7; P=0.002). Results were consistent in multiple additional analyses. LIMITATIONS: The primary outcome was assessed using diagnostic codes in health care databases. Laboratory values for serum uric acid and creatinine in follow-up were not available in our data sources. CONCLUSIONS: The findings suggest that donating a kidney modestly increases an individual's absolute long-term incidence of gout. This unique observation should be corroborated in future studies.