Hypertension and Kidney Function After Living Kidney Donation.

Importance: Recent guidelines call for better evidence on health outcomes after living kidney donation. Objective: To determine the risk of hypertension in normotensive adults who donated a kidney compared with nondonors of similar baseline health. Their rates of estimated glomerular filtration rate (eGFR) decline and risk of albuminuria were also compared. Design, Setting, and Participants: Prospective cohort study of 924 standard-criteria living kidney donors enrolled before surgery and a concurrent sample of 396 nondonors. Recruitment occurred from 2004 to 2014 from 17 transplant centers (12 in Canada and 5 in Australia); follow-up occurred until November 2021. Donors and nondonors had the same annual schedule of follow-up assessments. Inverse probability of treatment weighting on a propensity score was used to balance donors and nondonors on baseline characteristics. Exposure: Living kidney donation. Main Outcomes and Measures: Hypertension (systolic blood pressure [SBP] ≥140 mm Hg, diastolic blood pressure [DBP] ≥90 mm Hg, or antihypertensive medication), annualized change in eGFR (starting 12 months after donation/simulated donation date in nondonors), and albuminuria (albumin to creatinine ratio ≥3 mg/mmol [≥30 mg/g]). Results: Among the 924 donors, 66% were female; they had a mean age of 47 years and a mean eGFR of 100 mL/min/1.73 m2. Donors were more likely than nondonors to have a family history of kidney failure (464/922 [50%] vs 89/394 [23%], respectively). After statistical weighting, the sample of nondonors increased to 928 and baseline characteristics were similar between the 2 groups. During a median follow-up of 7.3 years (IQR, 6.0-9.0), in weighted analysis, hypertension occurred in 161 of 924 donors (17%) and 158 of 928 nondonors (17%) (weighted hazard ratio, 1.11 [95% CI, 0.75-1.66]). The longitudinal change in mean blood pressure was similar in donors and nondonors. After the initial drop in donors' eGFR after nephrectomy (mean, 32 mL/min/1.73 m2), donors had a 1.4-mL/min/1.73 m2 (95% CI, 1.2-1.5) per year lesser decline in eGFR than nondonors. However, more donors than nondonors had an eGFR between 30 and 60 mL/min/1.73 m2 at least once in follow-up (438/924 [47%] vs 49/928 [5%]). Albuminuria occurred in 132 of 905 donors (15%) and 95 of 904 nondonors (11%) (weighted hazard ratio, 1.46 [95% CI, 0.97-2.21]); the weighted between-group difference in the albumin to creatinine ratio was 1.02 (95% CI, 0.88-1.19). Conclusions and Relevance: In this cohort study of living kidney donors and nondonors with the same follow-up schedule, the risks of hypertension and albuminuria were not significantly different. After the initial drop in eGFR from nephrectomy, donors had a slower mean rate of eGFR decline than nondonors but were more likely to have an eGFR between 30 and 60 mL/min/1.73 m2 at least once in follow-up. Trial Registration: ClinicalTrials.gov Identifier: NCT00936078.

Autosomal dominant ApoA4 mutations present as tubulointerstitial kidney disease with medullary amyloidosis.

Sporadic cases of apolipoprotein A-IV medullary amyloidosis have been reported. Here we describe five families found to have autosomal dominant medullary amyloidosis due to two different pathogenic APOA4 variants. A large family with autosomal dominant chronic kidney disease (CKD) and bland urinary sediment underwent whole genome sequencing with identification of a chr11:116692578 G>C (hg19) variant encoding the missense mutation p.L66V of the ApoA4 protein. We identified two other distantly related families from our registry with the same variant and two other distantly related families with a chr11:116693454 C>T (hg19) variant encoding the missense mutation p.D33N. Both mutations are unique to affected families, evolutionarily conserved and predicted to expand the amyloidogenic hotspot in the ApoA4 structure. Clinically affected individuals suffered from CKD with a bland urinary sediment and a mean age for kidney failure of 64.5 years. Genotyping identified 48 genetically affected individuals; 44 individuals had an estimated glomerular filtration rate (eGFR) under 60 ml/min/1.73 m2, including all 25 individuals with kidney failure. Significantly, 11 of 14 genetically unaffected individuals had an eGFR over 60 ml/min/1.73 m2. Fifteen genetically affected individuals presented with higher plasma ApoA4 concentrations. Kidney pathologic specimens from four individuals revealed amyloid deposits limited to the medulla, with the mutated ApoA4 identified by mass-spectrometry as the predominant amyloid constituent in all three available biopsies. Thus, ApoA4 mutations can cause autosomal dominant medullary amyloidosis, with marked amyloid deposition limited to the kidney medulla and presenting with autosomal dominant CKD with a bland urinary sediment. Diagnosis relies on a careful family history, APOA4 sequencing and pathologic studies.

The Living Kidney Donor Safety Study: Protocol of a Prospective Cohort Study.

Background: Living kidney donation is considered generally safe in healthy individuals; however, there is a need to better understand the long-term effects of donation on blood pressure and kidney function. Objectives: To determine the risk of hypertension in healthy, normotensive adults who donate a kidney compared with healthy, normotensive non-donors with similar indicators of baseline health. We will also compare the 2 groups on the rate of decline in kidney function, the risk of albuminuria, and changes in health-related quality of life. Design Participants and Setting: Prospective cohort study of 1042 living kidney donors recruited before surgery from 17 transplant centers (12 in Canada and 5 in Australia) between 2004 and 2014. Non-donor participants (n = 396) included relatives or friends of the donor, or donor candidates who were ineligible to donate due to blood group or cross-match incompatibility. Follow-up will continue until 2021, and the main analysis will be performed in 2022. The anticipated median (25th, 75th percentile, maximum) follow-up time after donation is 7 years (6, 8, 15). Measurements: Donors and non-donors completed the same schedule of measurements at baseline and follow-up (non-donors were assigned a simulated nephrectomy date). Annual measurements were obtained for blood pressure, estimated glomerular filtration rate (eGFR), albuminuria, patient-reported health-related quality of life, and general health. Outcomes: Incident hypertension (a systolic/diastolic blood pressure ≥ 140/90 mm Hg or receipt of anti-hypertensive medication) will be adjudicated by a physician blinded to the participant's donation status. We will assess the rate of change in eGFR starting from 12 months after the nephrectomy date and the proportion who develop an albumin-to-creatinine ratio ≥3 mg/mmol (≥30 mg/g) in follow-up. Health-related quality of life will be assessed using the 36-item RAND health survey and the Beck Anxiety and Depression inventories. Limitations: Donation-attributable hypertension may not manifest until decades after donation. Conclusion: This prospective cohort study will estimate the attributable risk of hypertension and other health outcomes after living kidney donation.

Contexte: Chez les personnes en bonne santé, faire don d'un rein est généralement considéré comme sûr. Il convient toutefois de mieux comprendre les effets à long terme de ce don sur la pression artérielle et la fonction rénale. Objectifs: Déterminer le risque d'hypertension chez les adultes sains et normotendus qui donnent un rein par rapport à des non-donneurs sains et normotendus ayant des indicateurs de santé de base similaires. Nous comparerons également le taux de réduction de la fonction rénale, le risque d'albuminurie et les changements dans la qualité de vie liée à la santé entre les deux groupes. Cadre type d'étude et participants: Étude de cohorte rétrospective menée sur 1 042 donneurs de rein vivants, recrutés avant la chirurgie dans 17 centres de transplantation (12 au Canada et 5 en Australie) entre 2004 et 2014. Le groupe des non-donneurs (n=396) était constitué de parents ou amis du donneur, ou de candidats donneurs non admissibles à faire un don en raison d'une incompatibilité de groupe sanguin ou lors du test de compatibilité croisée. Le suivi s'est poursuivi jusqu'en 2021 et l'analyse principale sera effectuée en 2022. Le temps de suivi médian prévu (25e percentile, 75e percentile, maximum) après le don est de 7 ans (6, 8, 15 ans). Mesures: Les donneurs et les non-donneurs ont complété le même calendrier de mesures à l'inclusion et pendant le suivi (une date simulée de néphrectomie a été attribuée aux non-donneurs). Des mesures annuelles de pression artérielle, de débit de filtration glomérulaire estimé (DFGe), d'albuminurie, de qualité de vie liée à la santé autodéclarée et de santé générale ont été obtenues. Issues principales: L'hypertension incidente (pression artérielle systolique/diastolique ≥ 140/90 mm Hg ou prise d'un médicament antihypertenseur) sera jugée par un médecin aveugle au statut de don du participant. Nous évaluerons le taux de variation du DFGe à partir de 12 mois après la date de la néphrectomie et la proportion de participants qui développeront un rapport albumine/créatinine ≥ 3 mg/mmol (≥ 30 mg/g) pendant le suivi. La qualité de vie liée à la santé sera évaluée à l'aide du questionnaire de santé RAND de 36 questions et de l'Inventaire d'anxiété et de dépression de Beck. Limites: L'hypertension attribuable au don pourrait ne pas se manifester avant des décennies après le don. Conclusion: Cette étude de cohorte prospective permettra d'estimer le risque d'hypertension attribuable au don et d'autres effets sur la santé du donneur après un don de rein.

Impact of Perioperative Complications on Living Kidney Donor Health-Related Quality of Life and Mental Health: Results From a Prospective Cohort Study.

BACKGROUND: Although living kidney donation is safe, some donors experience perioperative complications. OBJECTIVE: This study explored how perioperative complications affected donor-reported health-related quality of life, depression, and anxiety. DESIGN: This research was a conducted as a prospective cohort study. SETTING: Twelve transplant centers across Canada. PATIENTS: A total of 912 living kidney donors were included in this study. MEASUREMENTS: Short Form 36 health survey, Beck Depression Inventory and Beck Anxiety Inventory. METHODS: Living kidney donors were prospectively enrolled predonation between 2009 to 2014. Donor perioperative complications were graded using the Clavien-Dindo classification system. Mental and physical health-related quality of life was assessed with the 3 measurements; measurements were taken predonation and at 3- and 12-months postdonation. RESULTS: Seventy-four donors (8%) experienced a perioperative complication; most were minor (n = 67 [91%]), and all minor complications resolved before hospital discharge. The presence (versus absence) of a perioperative complication was associated with lower mental health-related quality of life and higher depression symptoms 3-month postdonation; neither of these differences persisted at 12-month. Perioperative complications were not associated with any changes in physical health-related quality of life or anxiety 3-month postdonation. LIMITATIONS: Minor complications may have been missed and information on complications postdischarge were not collected. No minimal clinically significant change has been defined for kidney donors across the 3 measurements. CONCLUSIONS: These findings highlight a potential opportunity to better support the psychosocial needs of donors who experience perioperative complications in the months following donation. TRIAL REGISTRATION: NCT00319579 and NCT00936078.

CONTEXTE: Bien que le don vivant d'un rein soit une procédure sécuritaire, certains donneurs souffrent tout de même de complications périopératoires. OBJECTIFS: Cette étude a examiné l'incidence des complications périopératoires sur la qualité de vie liée à la santé et les symptômes de dépression et d'anxiété rapportés par les donneurs. TYPE D'ÉTUDE: Étude de cohorte prospective. CADRE: Douze centers de transplantation à travers le Canada. SUJETS: 912 donneurs vivants d'un rein. MESURES: Un questionnaire abrégé de 36 questions sur l'état de santé, l'inventaire de dépression Beck et l'inventaire d'anxiété Beck. MÉTHODOLOGIE: Les donneurs ont été inscrits avant le don de façon prospective entre 2009 et 2014. Les complications périopératoires des donneurs ont été classées à l'aide du système de classification Clavien-Dindo. La qualité de vie liée à la santé physique et mentale a été évaluée à l'aide des trois outils de mesure; ces mesures ont été faites avant le don, puis 3 et 12 mois après le don. RÉSULTATS: Au total, 74 donneurs (8 %) ont souffert d'une complication périopératoire; la plupart étaient mineures (n = 67 [91 %]) et ont été résolues avant le congé de l'hôpital. La présence (par rapport à l'absence) d'une complication périopératoire a été associée à une plus faible qualité de vie liée à la santé mentale et à des symptômes de dépression plus graves 3 mois après le don; aucune de ces différences n'a persisté après 12 mois. Les complications périopératoires n'ont pas été associées à des changements dans la qualité de vie liée à la santé physique ou à l'anxiété 3 mois après le don. LIMITES: Certaines complications mineures ont pu être manquées. L'information sur les complications survenues après le congé n'a pas été recueillie. Dans les trois outils de mesure, aucune variation minimale cliniquement significative n'a été définie pour les donneurs d'un rein. CONCLUSION: Ces résultats soulignent une occasion de mieux répondre aux besoins psychosociaux des donneurs d'un rein qui présentent des complications périopératoires dans les mois suivant le don.

Living Kidney Donors' Financial Expenses and Mental Health.

BACKGROUND: Living kidney donors incur donation-related expenses, but how these expenses impact postdonation mental health is unknown. METHODS: In this prospective cohort study, the association between mental health and donor-incurred expenses (both out-of-pocket costs and lost wages) was examined in 821 people who donated a kidney at one of the 12 transplant centers in Canada between 2009 and 2014. Mental health was measured by the RAND Short Form-36 Health Survey along with Beck Anxiety Inventory and Beck Depression Inventory. RESULTS: A total of 209 donors (25%) reported expenses of >5500 Canadian dollars. Compared with donors who incurred lower expenses, those who incurred higher expenses demonstrated significantly worse mental health-related quality of life 3 months after donation, with a trend towards worse anxiety and depression, after controlling for predonation mental health-related quality of life and other risk factors for psychological distress. Between-group differences for donors with lower and higher expenses on these measures were no longer significant 12 months after donation. CONCLUSIONS: Living kidney donor transplant programs should ensure that adequate psychosocial support is available to all donors who need it, based on known and unknown risk factors. Efforts to minimize donor-incurred expenses and to better support the mental well-being of donors need to continue. Further research is needed to investigate the effect of donor reimbursement programs, which mitigate donor expenses, on postdonation mental health.

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.

Effect of an exercise rehabilitation program on physical function over 1 year in chronic kidney disease: an observational study.

BACKGROUND: Exercise rehabilitation may help maintain physical function in chronic kidney disease (CKD), but long-term clinical effectiveness is unknown. We evaluated the effect of an exercise rehabilitation program on physical function over 1 year in individuals with CKD. METHODS: This clinical program evaluation included adults with CKD (any stage) registered in a provincial renal program from 1 January 2011 to 31 March 2016. Attenders were referred to and attended a 10-week exercise rehabilitation program (n = 117). Nonattenders were referred, but did not attend the program (n = 133). Individuals enrolled in a longitudinal frailty study (n = 318) composed a second control group. Primary outcome: Change in physical function [short physical performance battery (SPPB) score]. Secondary outcomes included change in health-related quality of life, physical activity, exercise behaviour, hospitalization over 1 year. Predictors of improved SPPB were assessed using logistic regression. RESULTS: In sum, 53, 40 and 207 participants completed 1-year follow-up in attender, nonattender and second control groups, respectively. Baseline median SPPB [interquartile range (IQR)] scores were 10.5 (9-12), 10 (8-12) and 9 (7-11) in attender, nonattender and second control groups, respectively (P = 0.02). Mean change in SPPB score over 1 year was not significantly different between groups (P = 0.7). Attenders with baseline SPPB score <12, trended toward increased likelihood of improved SPPB score at 1 year [odds ratio (OR) 2.18; 95% confidence interval (CI) 0.95-5.02; P = 0.07]. More attenders (60%) exercised regularly at 1 year than nonattenders (35%) (P = 0.03). CONCLUSIONS: The impact of clinical exercise rehabilitation programs on physical function at 1 year needs further delineation. However, our observation of improved exercise behaviour at 1 year suggests sustained benefits with such programs in CKD.

Perioperative Complications During Living Donor Nephrectomy: Results From a Multicenter Cohort Study.

BACKGROUND: While living kidney donation is considered safe in healthy individuals, perioperative complications can occur due to several factors. OBJECTIVE: We explored associations between the incidence of perioperative complications and donor characteristics, surgical technique, and surgeon's experience in a large contemporary cohort of living kidney donors. DESIGN: Living kidney donors enrolled prospectively in a multicenter cohort study with some data collected retrospectively after enrollment was complete (eg, surgeon characteristics). SETTING: Living kidney donor centers in Canada (n = 12) and Australia (n = 5). PATIENTS: Living kidney donors who donated between 2004 and 2014 and the surgeons who performed the living kidney donor nephrectomies. MEASUREMENTS: Operative and hospital discharge medical notes were collected prospectively, with data on perioperative (intraoperative and postoperative) information abstracted from notes after enrollment was complete. Complications were graded using the Clavien-Dindo system and further classified into minor and major. In 2016, surgeons who performed the nephrectomies were invited to fill an online survey on their training and experience. METHODS: Multivariable logistic regression models with generalized estimating equations were used to compare perioperative complication rates between different groups of donors. The effect of surgeon characteristics on the complication rate was explored using a similar approach. Poisson regression was used to test rates of overall perioperative complications between high- and low-volume centers. RESULTS: Of the 1421 living kidney donor candidates, 1042 individuals proceeded with donation, where 134 (13% [95% confidence interval (CI): 11%-15%]) experienced 142 perioperative complications (55 intraoperative; 87 postoperative). The most common intraoperative complication was organ injury and the most common postoperative complication was ileus. No donors died in the perioperative period. Most complications were minor (90% of 142 complications [95% CI: 86%-96%]); however, 12 donors (1% of 1042 [95% CI: 1%-2%]) experienced a major complication. No statistically significant differences were observed between donor groups and the rate of complications. A total of 43 of 48 eligible surgeons (90%) completed the online survey. Perioperative complication rates did not vary significantly by surgeon characteristics or by high- versus low-volume centers. LIMITATIONS: Operative and discharge reporting is not standardized and varies among surgeons. It is possible that some complications were missed. The online survey for surgeons was completed retrospectively, was based on self-report, and has not been validated. We had adequate statistical power only to detect large effects for factors associated with a higher risk of perioperative complications. CONCLUSIONS: This study confirms the safety of living kidney donation as evidenced by the low rate of major perioperative complications. We did not identify any donor or surgeon characteristics associated with a higher risk of perioperative complications. TRIAL REGISTRATIONS: NCT00319579: A Prospective Study of Living Kidney Donation (https://clinicaltrials.gov/ct2/show/NCT00319579)NCT00936078: Living Kidney Donor Study (https://clinicaltrials.gov/ct2/show/NCT00936078).

CONTEXTE: Bien que le don vivant d'un rein soit sécuritaire chez un individu en santé, plusieurs facteurs sont susceptibles d'engendrer des complications périopératoires. OBJECTIF: Nous avons exploré l'association entre l'incidence des complications périopératoires et les caractéristiques du donneur, la technique chirurgicale employée et l'expérience du chirurgien au sein d'une vaste cohorte contemporaine de donneurs vivants d'un rein. TYPE D'ÉTUDE: Une étude de cohorte multicentrique où certaines données (notamment les renseignements concernant le chirurgien) ont été recueillies rétrospectivement, après l'inclusion complète des sujets (donneurs vivants d'un rein). CADRE: Des centres de transplantation au Canada (n=12) et en Australie (n=5). SUJETS: Des individus ayant fait don d'un rein entre 2004 et 2014, et les chirurgiens qui ont procédé à la néphrectomie. MESURES: Les notes médicales au dossier, opératoires et à la sortie de l'hôpital, ont été recueillies de façon prospective; les données concernant les renseignements périopératoires (peropératoires et postopératoires) ayant été extraites des notes une fois l'inclusion du sujet complétée. Les complications ont été catégorisées selon la classification de Clavien-Dindo, puis caractérisées comme étant mineures ou majeures. En 2016, les chirurgiens ayant pratiqué les néphrectomies ont été invités à répondre à un sondage en ligne au sujet de leur formation et de leur expérience. MÉTHODOLOGIE: Des modèles de régression logistique multivariée utilisant des équations d'estimation généralisées ont été employés pour comparer les taux de complications périopératoires entre les différents groupes de donneurs. L'effet exercé sur le taux de complications par les caractéristiques du chirurgien a été exploré selon une approche similaire. Une régression de Poisson a été utilisée pour évaluer et comparer les taux globaux de complications entre les centres à volume élevé et les centres à faible volume. RÉSULTATS: Des 1 421 candidats répertoriés, 1 042 individus ont subi une néphrectomie, desquels 134 (13 % [IC 95 %: 11­15 %]) ont vécu un total de 142 complications périopératoires (55 peropératoires; 87 postopératoires). La complication peropératoire la plus fréquente était une lésion à l'organe, alors qu'un iléus s'est avéré la principale complication postopératoire. Aucun donneur n'est décédé en période périopératoire. La plupart des complications rencontrées étaient mineures (90 % des 142 complications répertoriées [IC 95 %: 86­96 %]). Toutefois, 12 donneurs (1 % des 1 042 donneurs [IC 95 %: 1­2 %]) ont souffert de complications majeures. Aucune différence significative du point de vue statistique n'a été observée entre les groupes de donneurs et le taux de complications. Des 48 chirurgiens admissibles, 43 (90 %) ont répondu au sondage en ligne. Les taux de complications périoperatoires n'ont pas varié de façon significative en fonction des caractéristiques des chirurgiens, ou selon le volume de patients de l'hôpital. LIMITES: La façon d'inscrire les renseignements médicaux (opératoires ou à la sortie de l'hôpital) dans les dossiers des patients n'est pas normalisée et varie d'un chirurgien à l'autre. Certaines complications pourraient ne pas avoir été notées. Le sondage en ligne destiné aux chirurgiens a été rempli rétrospectivement, il reposait sur des déclarations volontaires et n'avait pas fait l'objet d'une validation. Nous ne disposions d'une puissance statistique que pour détecter les effets importants des facteurs associés à un risque accru de complications périopératoires. CONCLUSION: Cette étude confirme le caractère sécuritaire d'un don vivant de rein, comme en témoigne le très faible taux de complications périopératoires majeures. Nous n'avons pu établir de caractéristiques, du donneur ou du chirurgien, qui soit associées à un risque accru de complications périopératoires.

Financial Costs Incurred by Living Kidney Donors: A Prospective Cohort Study.

BACKGROUND: Approximately 40% of the kidneys for transplant worldwide come from living donors. Despite advantages of living donor transplants, rates have stagnated in recent years. One possible barrier may be costs related to the transplant process that potential willing donors may incur for travel, parking, accommodation, and lost productivity. METHODS: To better understand and quantify the financial costs incurred by living kidney donors, we conducted a prospective cohort study, recruiting 912 living kidney donors from 12 transplant centers across Canada between 2009 and 2014; 821 of them completed all or a portion of the costing survey. We report microcosted total, out-of-pocket, and lost productivity costs (in 2016 Canadian dollars) for living kidney donors from donor evaluation start to 3 months after donation. We examined costs according to (1) the donor's relationship with their recipient, including spousal (donation to a partner), emotionally related nonspousal (friend, step-parent, in law), or genetically related; and (2) donation type (directed, paired kidney, or nondirected). RESULTS: Living kidney donors incurred a median (75th percentile) of $1254 ($2589) in out-of-pocket costs and $0 ($1908) in lost productivity costs. On average, total costs were $2226 higher in spousal compared with emotionally related nonspousal donors (P=0.02) and $1664 higher in directed donors compared with nondirected donors (P<0.001). Total costs (out-of-pocket and lost productivity) exceeded $5500 for 205 (25%) donors. CONCLUSIONS: Our results can be used to inform strategies to minimize the financial burden of living donation, which may help improve the donation experience and increase the number of living donor kidney transplants.

Impact of Exercise Counseling on Physical Function in Chronic Kidney Disease: An Observational Study.

BACKGROUND: Individuals with chronic kidney disease (CKD) have low levels of physical activity and physical function. Although guidelines endorse exercise counseling for individuals with CKD, it is not yet part of routine care. OBJECTIVE: We investigated the effect of attending a real-life exercise counseling clinic (ECC) on physical function in individuals with CKD. DESIGN: Retrospective analysis of prospectively collected observational data with quasi-experimental design. SETTING AND PARTICIPANTS: Patients with all stages of CKD registered in a large provincial renal program were eligible. The exposed cohort who attended the ECC between January 1, 2011, and March 15, 2014, included 214 individuals. The control cohort included 292 individuals enrolled in an observational study investigating longitudinal change in frailty during the same time period. PREDICTOR/FACTOR: Attendance at an ECC. OUTCOMES AND MEASUREMENTS: Change in physical function as measured by Short Physical Performance Battery (SPPB) score, physical activity level (Human Activity Profile [HAP]/Physical Activity Scale for the Elderly [PASE]), and health-related quality of life (HRQOL; EQ5D/VAS) over 1 year. RESULTS: Eighty-seven individuals in the ECC cohort and 125 participants in the control cohort completed 1-year follow-up. Baseline median SPPB score was 10 (interquartile range [IQR]: 9-12) and 9 (IQR: 7-11) in the ECC and control cohorts, respectively (P < .01). At 1 year, SPPB scores were 10 (IQR: 8-12) and 9 (IQR: 6-11) in the ECC and control cohorts, respectively (P = .04). Mean change in SPPB over 1 year was not significantly different between groups: -0.33 (95% confidence interval [CI]: -0.81 to 0.15) in ECC and -0.22 (95% CI: -0.61 to 0.17) in control (P = .72). There was no significant difference in the proportion of individuals in each cohort with an increase/decrease in SPPB score over time. There was no significant change in physical activity or HRQOL over time between groups. LIMITATIONS: Quasi-experimental design, low rate of follow-up attendance. CONCLUSIONS: In this pragmatic study, exercise counseling had no significant effect on change in SPPB score, suggesting that a single exercise counseling session alone is inadequate to improve physical function in CKD.

CONTEXTE: Les personnes atteintes d'insuffisance rénale chronique (IRC) ont des capacités physiques réduites et sont généralement peu actives physiquement. Bien que les recommandations aillent dans le sens d'encourager ces patients à adopter un programme d'exercices, on observe que cela ne fait toujours pas partie de la routine de soins. OBJECTIF DE L'ÉTUDE: Mesurer l'effet de la fréquentation d'une clinique de consultation en entraînement (CCE) sur la condition physique des individus atteints d'IRC. TYPE D'ÉTUDE: Il s'agit d'un modèle d'étude quasi expérimental sous forme d'une analyse rétrospective de données observationnelles colligées prospectivement. CADRE DE L'ÉTUDE ET PARTICIPANTS: Étaient admissibles tous les patients atteints d'IRC, peu importe le stade, inscrits à un vaste programme de santé rénale provincial. La cohorte exposée, soit les patients ayant fréquenté une CCE entre le 1er janvier 2011 et le 15 mars 2014, était composée de 214 sujets. La cohorte contrôle était constituée de 292 individus participant à une étude observationnelle qui évaluait les changements longitudinaux de fragilité physique pendant la même période. FACTEUR PRÉDICTIF: La fréquentation d'une CCE. MESURES: Pendant un an, on a mesuré le niveau d'activité physique, la qualité de vie relative à l'état de santé et les changements dans les capacités physiques des participants (test SPPB - Short Physical Performance Battery Score). RÉSULTATS: Seuls 87 patients de la cohorte exposée et 125 de la cohorte contrôle ont complété le suivi. Les médianes initiales au test SPPB étaient de 10 (EI: 9-12) et de 9 (EI: 7-11) respectivement (p < 0,01). Après un an, les scores au test SPPB étaient pratiquement inchangés: médiane de 10 (EI: 8-12) pour la cohorte exposée et de 9 pour la cohorte contrôle (EI: 6-11) (p = 0,04). Pendant l'année du suivi, la variation moyenne du score au test SPPB a été semblable dans les deux groupes: −0,33 (IC 95 % −0,81 à 0,15) dans la cohorte exposée et −0,22 (IC 95 % −0,61 à 0,17) dans le groupe contrôle (p = 0,72). Au fil du temps, la proportion d'individus ayant présenté une diminution ou une augmentation du score au test SPPB était similaire dans les deux groupes; et aucun changement significatif dans le niveau d'activité physique ou la qualité de vie relative à l'état de santé n'avait été observé entre les groupes. LIMITES DE L'ÉTUDE: Les résultats sont limités par le modèle quasi expérimental de l'étude et la faible participation au suivi sur un an. CONCLUSION: Cette étude pragmatique démontre que le fait de consulter pour un programme d'entraînement n'a que peu d'effet sur le score obtenu au test SPPB. Cette observation suggère qu'une seule séance de consultation en vue d'adopter un programme d'entraînement n'est pas suffisante pour améliorer la condition physique des patients atteints d'IRC.

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.

Class II Eplet Mismatch Modulates Tacrolimus Trough Levels Required to Prevent Donor-Specific Antibody Development.

Despite more than two decades of use, the optimal maintenance dose of tacrolimus for kidney transplant recipients is unknown. We hypothesized that HLA class II de novo donor-specific antibody (dnDSA) development correlates with tacrolimus trough levels and the recipient's individualized alloimmune risk determined by HLA-DR/DQ epitope mismatch. A cohort of 596 renal transplant recipients with 50,011 serial tacrolimus trough levels had HLA-DR/DQ eplet mismatch determined using HLAMatchmaker software. We analyzed the frequency of tacrolimus trough levels below a series of thresholds <6 ng/ml and the mean tacrolimus levels before dnDSA development in the context of HLA-DR/DQ eplet mismatch. HLA-DR/DQ eplet mismatch was a significant multivariate predictor of dnDSA development. Recipients treated with a cyclosporin regimen had a 2.7-fold higher incidence of dnDSA development than recipients on a tacrolimus regimen. Recipients treated with tacrolimus who developed HLA-DR/DQ dnDSA had a higher proportion of tacrolimus trough levels <5 ng/ml, which continued to be significant after adjustment for HLA-DR/DQ eplet mismatch. Mean tacrolimus trough levels in the 6 months before dnDSA development were significantly lower than the levels >6 months before dnDSA development in the same patients. Recipients with a high-risk HLA eplet mismatch score were less likely to tolerate low tacrolimus levels without developing dnDSA. We conclude that HLA-DR/DQ eplet mismatch and tacrolimus trough levels are independent predictors of dnDSA development. Recipients with high HLA alloimmune risk should not target tacrolimus levels <5 ng/ml unless essential, and monitoring for dnDSA may be advisable in this setting.

Cognitive Impairment in Advanced Chronic Kidney Disease: The Canadian Frailty Observation and Interventions Trial.

BACKGROUND: Chronic kidney disease (CKD) affects more than one third of older adults, and is a strong risk factor for vascular disease and cognitive impairment. Cognitive impairment can have detrimental effects on the quality of life through decreased treatment adherence and poor nutrition and results in increased costs of care and early mortality. Though widely studied in hemodialysis populations, little is known about cognitive impairment in patients with pre-dialysis CKD. METHODS: Multicenter, cross-sectional, prospective cohort study including 385 patients with CKD stages G4-G5. Cognitive function was measured with a validated tool called the Montreal Cognitive Assessment (MoCA) as part of a comprehensive frailty assessment in the Canadian Frailty Observation and Interventions Trial. Cognitive impairment was defined as a MoCA score of ≤24. We determined the prevalence and risk factors for cognitive impairment in patients with CKD stages G4-G5, not on dialysis. RESULTS: Two hundred and thirty seven participants (61%) with CKD stages G4-G5 had cognitive impairment at baseline assessment. When compared to a control group, this population scored lower in all domains of cognition, with the most pronounced deficits observed in recall, attention, and visual/executive function (p < 0.01 for all comparisons). Older age, recent history of falls and history of stroke were independently associated with cognitive impairment. CONCLUSIONS: Our study uncovered a high rate of unrecognized cognitive impairment in an advanced CKD population. This impairment is global, affecting all aspects of cognition and is likely vascular in nature. The longitudinal trajectory of cognitive function and its effect on dialysis decision-making and outcomes deserves further study.

Detecting Renal Allograft Inflammation Using Quantitative Urine Metabolomics and CXCL10.

BACKGROUND: The goal of this study was to characterize urinary metabolomics for the noninvasive detection of cellular inflammation and to determine if adding urinary chemokine ligand 10 (CXCL10) improves the overall diagnostic discrimination. METHODS: Urines (n = 137) were obtained before biopsy in 113 patients with no (n = 66), mild (borderline or subclinical; n = 58), or severe (clinical; n = 13) rejection from a prospective cohort of adult renal transplant patients (n = 113). Targeted, quantitative metabolomics was performed with direct flow injection tandem mass spectrometry using multiple reaction monitoring (ABI 4000 Q-Trap). Urine CXCL10 was measured by enzyme-linked immunosorbent assay. A projection on latent structures discriminant analysis was performed and validated using leave-one-out cross-validation, and an optimal 2-component model developed. Chemokine ligand 10 area under the curve (AUC) was determined and net reclassification index and integrated discrimination index analyses were performed. RESULTS: PLS2 demonstrated that urinary metabolites moderately discriminated the 3 groups (Cohen κ, 0.601; 95% confidence interval [95% CI], 0.46-0.74; P < 0.001). Using binary classifiers, urinary metabolites and CXCL10 demonstrated an AUC of 0.81 (95% CI, 0.74-0.88) and 0.76 (95% CI, 0.68-0.84), respectively, and a combined AUC of 0.84 (95% CI, 0.78-0.91) for detecting alloimmune inflammation that was improved by net reclassification index and integrated discrimination index analyses. Urinary CXCL10 was the best univariate discriminator, followed by acylcarnitines and hexose. CONCLUSIONS: Urinary metabolomics can noninvasively discriminate noninflamed renal allografts from those with subclinical and clinical inflammation, and the addition of urine CXCL10 had a modest but significant effect on overall diagnostic performance. These data suggest that urinary metabolomics and CXCL10 may be useful for noninvasive monitoring of alloimmune inflammation in renal transplant patients.

The assessment of frailty in older people with chronic kidney disease.

PURPOSE OF REVIEW: Frailty is common in chronic kidney disease (CKD) and is a predictor of adverse outcomes. The current article reviews the most common frailty measures available, gives an overview of their use in the chronic kidney disease population, and summarizes their strengths and limitations. RECENT FINDINGS: Frailty is increasingly recognized as a potent predictor of adverse outcomes in all stages of chronic kidney disease. Recent investigations have demonstrated that the clinical perception of frailty by healthcare personnel or patients themselves is an inaccurate measure of frailty. The clinical frailty scale, a simple point-of-care tool for the assessment of frailty, has been shown to be a predictor of mortality in individuals on dialysis. SUMMARY: The Fried criteria have been most extensively used in chronic kidney disease. However, other criteria using self-reported outcomes, clinical and cognitive criteria have also been shown to predict adverse outcomes and may be more applicable in clinical settings. Many of these still require further validation in the chronic kidney disease population.

Frailty and physical function in chronic kidney disease: the CanFIT study.

BACKGROUND: Frailty, a manifestation of unsuccessful aging, is highly prevalent in people with chronic kidney disease (CKD) and is associated with comorbid conditions in cross-sectional studies. Longitudinal studies investigating the progression of frailty in those with advanced non-dialysis CKD are lacking. OBJECTIVES: Canadian Frailty Observation and Interventions Trial (CanFIT). To determine the natural history, prevalence of perceived and measured frailty and its association with dialysis treatment choices and adverse outcomes in patients with advanced CKD. DESIGN: Longitudinal observational study, designed to collect data from 600 participants over 2 years. SETTING: Interprofessional non-dialysis CKD clinics at four tertiary health care centres in central Canada. PATIENTS: People with CKD stage 4 and 5 (eGFR <30 ml/min/1.73 m(2)) who are not on dialysis at enrollment. MEASUREMENTS: Multiple Frailty Definitions: Short Physical Performance Battery (SPPB), Fried Frailty Criteria, Frailty Index. Dialysis start: In-Centre Hemodialysis, Home Hemodialysis or Peritoneal Dialysis Outcomes: Death, Opt-out or Lost to follow up. METHODS: We will perform physical and cognitive assessments annually. We plan to analyze the relationships between frailty, treatment choices and patient centered outcomes. RESULTS: We have recruited 217 participants in 2 centres; of these, 56 % had reduced physical function at baseline, as defined by the SPPB. Risk of reduced physical function was 8 fold higher in those with diabetes after adjusting for age, gender, eGFR and comorbidities. LIMITATIONS: Referred population, use of SPPB as a measure of frailty, inter-operator variability in measurement of hand grip and gait speed, cross-sectional analysis of baseline data in the subset recruited to date. CONCLUSIONS: People with advanced CKD have a high burden of reduced physical function, especially those with diabetes. We will continue enrollment into the CanFIT study to further understand the clinical history of CKD and frailty in this population.

CONTEXTE: La fragilité, une manifestation du vieillissement malheureux, est très répandue chez les personnes atteintes d'insuffisance rénale chronique (IRC) et est associée à des conditions de comorbidité dans les études transversales. Rares sont les études longitudinales destinées à étudier la progression de la fragilité chez les personnes atteintes d'IRC avancée qui ne reçoivent pas de dialyse. OBJECTIFS: Canadian Frailty Observation and Interventions Trial (CanFIT). Déterminer l'évolution naturelle, la prévalence de la fragilité perçue et mesurée, de même que son association avec les options de traitement à la dialyse et les effets indésirables sur les patients atteints d'IRC avancée. TYPE D'ÉTUDE: Étude longitudinale d'observation visant à recueillir les données de 600 patients sur deux ans. CONTEXTE: Des unités interprofessionnelles d'IRC qui ne pratiquent pas la dialyse dans quatre centres de soins tertiaires du centre du Canada. PARTICIPANTS: Des personnes atteintes d'IRC de stade 4 et 5 (R-EGF <30 ml/min/1,73 m2) qui ne recevaient pas de dialyse au moment de l'inscription. MESURES: Diverses définitions de la fragilité : le Short Physical Performance Battery (SPPB), les critères de fragilité de Fried et l'indice de fragilité. Le lieu de l'amorce de la dialyse : la dialyse en centre, la dialyse à domicile; ou les résultats de la dialyse péritonéale : le décès, le refus ou la perte de suivi. MÉTHODES: Nous effectuerons des examens physiques et cognitifs sur une base annuelle. Nous planifions analyser la relation entre la fragilité, le choix du traitement et les résultats axés sur le patient. RÉSULTATS: Nous avons recruté 217 participants dans 2 centres; parmi ceux-ci, 56 % présentaient d'entrée de jeu une réduction des fonctions physiques, telles que définies par le SPPB. Les risques de subir une réduction des fonctions physiques étaient 8 fois supérieurs chez les patients souffrant de diabète, après ajustement selon l'âge, le sexe, le R-EGF et les comorbidités. LIMITES DE L'ÉTUDE: La population désignée, le recours au SPPB pour mesurer la fragilité, la variabilité des intervenants dans la mesure de la vitesse de préhension et de marche, l'analyse transversale des données de référence du sous-ensemble recruté jusqu'à maintenant. CONCLUSIONS: Les personnes atteintes d'IRC avancée sont accablées d'une forte réduction de la fonction physique, et particulièrement celles qui sont atteintes de diabète. Nous poursuivrons l'inscription à l'étude de CanFIT afin d'approfondir les connaissances au sujet de l'évolution clinique de l'IRC et la fragilité des personnes atteintes.

Gestational hypertension and preeclampsia in living kidney donors.

BACKGROUND: Young women wishing to become living kidney donors frequently ask whether nephrectomy will affect their future pregnancies. METHODS: We conducted a retrospective cohort study of living kidney donors involving 85 women (131 pregnancies after cohort entry) who were matched in a 1:6 ratio with 510 healthy nondonors from the general population (788 pregnancies after cohort entry). Kidney donations occurred between 1992 and 2009 in Ontario, Canada, with follow-up through linked health care databases until March 2013. Donors and nondonors were matched with respect to age, year of cohort entry, residency (urban or rural), income, number of pregnancies before cohort entry, and the time to the first pregnancy after cohort entry. The primary outcome was a hospital diagnosis of gestational hypertension or preeclampsia. Secondary outcomes were each component of the primary outcome examined separately and other maternal and fetal outcomes. RESULTS: Gestational hypertension or preeclampsia was more common among living kidney donors than among nondonors (occurring in 15 of 131 pregnancies [11%] vs. 38 of 788 pregnancies [5%]; odds ratio for donors, 2.4; 95% confidence interval, 1.2 to 5.0; P=0.01). Each component of the primary outcome was also more common among donors (odds ratio, 2.5 for gestational hypertension and 2.4 for preeclampsia). There were no significant differences between donors and nondonors with respect to rates of preterm birth (8% and 7%, respectively) or low birth weight (6% and 4%, respectively). There were no reports of maternal death, stillbirth, or neonatal death among the donors. Most women had uncomplicated pregnancies after donation. CONCLUSIONS: Gestational hypertension or preeclampsia was more likely to be diagnosed in kidney donors than in matched nondonors with similar indicators of baseline health. (Funded by the Canadian Institutes of Health Research and others.).

Elevated urinary CCL2: Cr at 6 months is associated with renal allograft interstitial fibrosis and inflammation at 24 months.

BACKGROUND: We have demonstrated that 6-month urinary CCL2: Cr is a predictor of interstitial fibrosis and tubular atrophy (IFTA) on 24-month biopsy and death-censored graft loss. However, IFTA is no longer considered prognostically significant, whereas patients with graft loss frequently have interstitial fibrosis and inflammation (IF+i=ci>0+i>0). As early CCL2: Cr predicts late graft loss, the goal of this study was to determine if 6-month urinary CCL2: Cr was a predictor of IF+i at 24 months. METHODS: Urinary CCL2 at 6 months was measured with ELISA and correlated with IF+i on 24-month surveillance biopsies from a prospective, multicenter adult renal transplant cohort (n=111). RESULTS: Six-month urinary CCL2: Cr was significantly higher in IF+i and transplant glomerulopathy patients compared with normal histology at 24 months. By multivariate analysis, 6-month urinary CCL2: Cr was independently correlated with IF+i at 24 months (OR 2.78, 95% CI 1.38-6.12, AUC 0.695, P=0.003). Six-month urinary CCL2: Cr was also an independent correlate of 6-month IF+i (OR 1.99, 95% CI 1.03-4.18, AUC 0.63, P=0.04). Six-month urinary CCL2: Cr distinguished noninflamed renal tissue (normal, fibrosis) from IF+i with a sensitivity/specificity of 0.71/0.62 at a cutoff of 15 ng CCL2/mmol Cr (AUC 0.695, P=0.003, n=91). CONCLUSIONS: Urinary CCL2: Cr may be useful for the noninvasive identification of patients with or at risk for IF+i. These patients may benefit from avoidance of drug minimization/withdrawal protocols and more intensive post-transplant surveillance. Furthermore, urinary CCL2: Cr may also identify individuals who may benefit from novel interventional trials targeting IF+i.

Association of frailty and physical function in patients with non-dialysis CKD: a systematic review.

BACKGROUND: Frailty is a condition characterized by a decline in physical function and functional capacity. Common symptoms of frailty, such as weakness and exhaustion, are prevalent in patients with chronic kidney disease (CKD). The increased vulnerability of frail patients with coexisting CKD may place them at a heightened risk of encountering additional health complications. The purpose of this systematic review was to explore the link between frailty, CKD and clinical outcomes. METHODS: We searched for cross sectional and prospective studies in the general population and in the CKD population indexed in EMBASE, Pubmed, Web of Science, CINAHL, Cochrane and Ageline examining the association between frailty and CKD and those relating frailty in patients with CKD to clinical outcomes. RESULTS: We screened 5,066 abstracts and retrieved 108 studies for full text review. We identified 7 studies associating frailty or physical function to CKD. From the 7 studies, we identified only two studies that related frailty in patients with CKD to a clinical outcome. CKD was consistently associated with increasing frailty or reduced physical function [odds ratios (OR) 1.30 to 3.12]. In patients with CKD, frailty was associated with a greater than two-fold higher risk of dialysis and/or death [OR from 2.0 to 5.88]. CONCLUSIONS: CKD is associated with a higher risk of frailty or diminished physical function. Furthermore, the presence of frailty in patients with CKD may lead to a higher risk of mortality. Further research must be conducted to understand the mechanisms of frailty in CKD and to confirm its association with clinical outcomes.