Donor kidney volume measured by computed tomography is a strong predictor of recipient eGFR in living donor kidney transplantation.

PURPOSE: The effect of living donor kidney allograft size on recipient outcomes is not well understood. In this study, we sought to investigate the relationship between preoperatively measured donor kidney volume and recipient estimated glomerular filtration rate (eGFR) in living donor kidney transplantation (LDKT). METHODS: We studied computed tomography (CT) donor kidney volumes and recipient outcomes for 438 LDKTs at the Toronto General Hospital between 2007 and 2016. Estimated glomerular filtration rate (eGFR) was calculated at 1, 3, and 6 months and a multivariable linear regression model was fitted to study the effect of donor kidney volume on recipient eGFR. RESULTS: The mean volume and weight of the donated kidneys were 157.3 (± 32.3) cc and 186.7 (± 48.7) g, respectively. Kidney volume was significantly associated with eGFR on multivariable analysis (P < 0.001). Specifically, for every 10 cc increase in kidney volume, there was a 1.68 mL/min, 1.25 mL/min and 0.97 mL/min rise in recipient eGFR at 1, 3, and 6 months, respectively. CONCLUSIONS: Donor kidney volume is a strong independent predictor of recipient eGFR in LDKT, and therefore, may be a valuable addition to predictive models of eGFR after transplant. Further research may determine if the inclusion of donor kidney volume in matching algorithms can improve recipient outcomes.

Association between uric acid, renal haemodynamics and arterial stiffness over the natural history of type 1 diabetes.

AIMS: To examine the relationship between normal plasma uric acid (PUA) levels, renal haemodynamic function, arterial stiffness and plasma renin and aldosterone over a wide range of type 1 diabetes (T1D) durations in adolescents, young adults and older adults. MATERIALS AND METHODS: PUA, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), vascular stiffness parameters (aortic augmentation index [AIx], carotid AIx, carotid femoral pulse wave velocity [cfPWV]), and plasma renin and aldosterone were measured during a euglycaemic clamp in people with T1D: 27 adolescents (mean ± SD age 16.8 ± 1.9 years), 52 young adults (mean ± SD age 25.6 ± 5.5 years) and 66 older adults (mean ± SD age 65.7 ± 7.5 years). RESULTS: PUA was highest in patients with the longest T1D duration: 197 ± 44 µmol/L in adolescents versus 264 ± 82 µmol/L in older adults (P < 0.001). Higher PUA correlated with lower GFR only in older adults, even after correcting for age, glycated haemoglobin and sex (ß = -2.12 ± 0.56; P = 0.0003), but not in adolescents or young adults. Higher PUA correlated with lower carotid AIx (ß = -1.90, P = 0.02) in adolescents. In contrast, PUA correlated with higher cfPWV (P = 0.02) and higher plasma renin (P = 0.01) in older adults with T1D. CONCLUSIONS: The relationship between higher PUA with lower GFR, increased arterial stiffness and renin angiotensin aldosterone system (RAAS) activation was observed only in older adults with longstanding T1D. T1D duration may modify the association between PUA, renal haemodynamic function and RAAS activation, leading to renal vasoconstriction and ischaemia. Further work must determine whether pharmacological PUA-lowering prevents or reverses injurious haemodynamic and neurohormonal sequelae of longstanding T1D, thereby improving clinical outcomes.

The relationships between markers of tubular injury and intrarenal haemodynamic function in adults with and without type 1 diabetes: Results from the Canadian Study of Longevity in Type 1 Diabetes.

OBJECTIVE: Our aim was to define the relationships between plasma biomarkers of kidney injury and intrarenal haemodynamic function (glomerular filtration rate [GFR], effective renal plasma flow [ERPF], renal vascular resistance [RVR]) in adults with type 1 diabetes (T1D). METHODS: The study sample comprised patients with longstanding T1D (duration ≥50 years), among whom 44 were diabetic kidney disease (DKD) resistors (eGFR >60 mL/min/1.73 m2 and <30 mg/d urine albumin excretion) and 22 had DKD, in addition to 73 control participants. GFRINULIN and ERPFPAH were measured, RVR was calculated, and afferent (RA )/efferent (RE ) areteriolar resistances were derived from Gomez equations. Plasma neutrophil gelatinase-associated lipocalin (NGAL), ß2 microglobulin (B2M), osteopontin (OPN) and uromodulin (UMOD) were measured using immunoassay kits from Meso Scale Discovery. RESULTS: Plasma NGAL, B2M and OPN were higher and UMOD was lower in DKD patients vs DKD resistors and non-diabetic controls. In participants with T1D, plasma NGAL inversely correlated with GFR (r = -0.33; P = 0.006) and ERPF (r = -0.34; P = 0.006), and correlated positively with RA (r = 0.26; P = 0.03) and RVR (r = 0.31; P = 0.01). In participants without T1D, NGAL and B2M inversely correlated with GFR (NGAL r = -0.18; P = 0.13 and B2M r = -0.49; P < 0.0001) and with ERPF (NGAL r = -0.19; P = 0.1 and B2M r = -0.42; P = 0.0003), and correlated positively with RA (NGAL r = 0.19; P = 0.10 and B2M r = 0.3; P = 0.01) and with RVR (NGAL r = 0.20; P = 0.09 and B2M r = 0.34; P = 0.003). Differences were significant after adjusting for age, sex, HbA1c, SBP and LDL. There were statistical interactions between T1D status, B2M and intrarenal haemodynamic function (P < 0.05). CONCLUSIONS: Elevated NGAL relates to intrarenal haemodynamic dysfunction in T1D, whereas elevated NGAL and B2M relate to intrarenal haemodynamic dysfunction in adults without T1D. These data may define a diabetes-specific interplay between tubular injury and intrarenal haemodynamic dysfunction.

Ethnic background is associated with no live kidney donor identified at the time of first transplant assessment-an opportunity missed? A single-center retrospective cohort study.

Patients from ethnocultural minorities have reduced access to live donor kidney transplant (LDKT). To explore early pretransplant ethnocultural disparities in LDKT readiness, and the impact of the interactions with the transplant program, we assessed if patients had a potential live donor (LD) identified at first pretransplant assessment, and if patients with no LD initially received LDKT subsequently. Single-center, retrospective cohort of adults referred for kidney transplant (KT) assessment. Multivariable logistic regression assessed the association between ethnicity and having a potential LD. Cox proportional hazard analysis assessed the association between no potential LD initially and subsequent LDKT. Of 1617 participants, 66% of Caucasians indicated having a potential LD, compared with 55% of South Asians, 44% of African Canadians, and 41% of East Asians (P < 0.001). In multivariable logistic regression analysis, the odds of having a potential LD identified was significantly lower for African, East and South Asian Canadians. No potential LD at initial KT assessment was associated with lower likelihood of LDKT subsequently (hazard ratio [HR], 0.14; [0.10-0.19]). Compared to Caucasians, African, East and South Asian and African Canadians are less likely to have a potential LD identified at first KT assessment, which predicts a lower likelihood of subsequent LDKT.

Standardization and alignment of data capture practices to clinical processes in the evaluation of living kidney donor candidates.

The Living Kidney Donation Program at the Toronto General Hospital, University Health Network sought to develop a comprehensive, secure, accurate, and up-to-date information system for the purposes of quality improvement, research, and performance evaluation. The Comprehensive Living Kidney Donor Database (CLiKeD) houses comprehensive demographic, medical, psychosocial, and evaluation data on living kidney donor candidates abstracted from multiple health information sources. Data are routinely audited to ensure high data quality. Over 3,500 living kidney donor candidates are currently included in CLiKeD. The development of this data system will allow for regular performance assessments of the program, implementation of quality improvement initiatives, and the completion of high-impact, clinically relevant research. In addition, the conception and development of CLiKeD has been instrumental in improving documentation of personal health information at the point of care.

The weekend effect: transplantation is not "immune".

The "weekend effect" has been widely studied in various health care settings, but it has received less attention in the field of transplantation. The study by Mohan et al. reveals that this phenomenon exists in discard rates for deceased donor kidneys in the United States. These findings emphasize the importance of reducing unexplained variations in kidney discard rates, especially in light of the ongoing shortage of transplantable organs.

Duodenal leaks after pancreas transplantation with enteric drainage - characteristics and risk factors.

Pancreas-kidney transplantation with enteric drainage has become a standard treatment in diabetic patients with renal failure. Leaks of the graft duodenum (DL) remain a significant complication after transplantation. We studied incidence and predisposing factors of DLs in both simultaneous pancreas-kidney (SPK) and pancreas after kidney (PAK) transplantation. Between January 2002 and April 2013, 284 pancreas transplantations were performed including 191 SPK (67.3%) and 93 PAK (32.7%). Patient data were analyzed for occurrence of DLs, risk factors, leak etiology, and graft survival. Of 18 DLs (incidence 6.3%), 12 (67%) occurred within the first 100 days after transplantation. Six grafts (33%) were rescued by duodenal segment resection. Risk factors for a DL were PAK transplantation sequence (odds ratio 3.526, P = 0.008) and preoperative immunosuppression (odds ratio 3.328, P = 0.012). In the SPK subgroup, postoperative peak amylase as marker of preservation/reperfusion injury and recipient pretransplantation cardiovascular interventions as marker of atherosclerosis severity were associated with an increased incidence of DLs. CMV-mismatch constellations showed an increased incidence in the SPK subgroup, however without significance probability. Long-term immunosuppression in PAK transplantation is a major risk factor for DLs. Early surgical revision offers the chance of graft rescue.

Cardiometabolic and Kidney Protection in Kidney Transplant Recipients With Diabetes: Mechanisms, Clinical Applications, and Summary of Clinical Trials.

Kidney transplantation is the therapy of choice for patients with end-stage renal disease. Preexisting diabetes is highly prevalent in kidney transplant recipients (KTR), and the development of posttransplant diabetes is common because of a number of transplant-specific risk factors such as the use of diabetogenic immunosuppressive medications and posttransplant weight gain. The presence of pretransplant and posttransplant diabetes in KTR significantly and variably affect the risk of graft failure, cardiovascular disease (CVD), and death. Among the many available therapies for diabetes, there are little data to determine the glucose-lowering agent(s) of choice in KTR. Furthermore, despite the high burden of graft loss and CVD among KTR with diabetes, evidence for strategies offering cardiovascular and kidney protection is lacking. Recent accumulating evidence convincingly shows glucose-independent cardiorenal protective effects in non-KTR with glucose-lowering agents, such as sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists. Therefore, our aim was to review cardiorenal protective strategies, including the evidence, mechanisms, and rationale for the use of these glucose-lowering agents in KTR with diabetes.

New insights into the pathogenesis of cellular crescents.

PURPOSE OF REVIEW: This review discusses the recent evidence that intrinsic glomerular cells including podocytes, parietal epithelial cells and progenitor cells within Bowman's capsule contribute to cellular crescents. RECENT FINDINGS: Using a variety of newer molecular markers and lineage tracing experiments, investigators have clearly demonstrated that glomerular cells play a key role in the development and progression of cellular crescents in experimental and human disease. SUMMARY: Crescentic glomerulonephritis is associated with significant morbidity and mortality. Current therapies target the immune system. The recent finding that nonimmune cells also play a role in crescent formation highlights the need to identify alternate and complimentary therapeutic strategies.

Use of the Living Kidney Donor Profile Index in the Canadian Kidney Transplant Recipient Population: A Validation Study.

BACKGROUND: The Living Kidney Donor Profile Index (LKDPI) was derived in a cohort of kidney transplant recipients (KTR) from the United States to predict the risk of total graft failure. There are important differences in patient demographics, listing practices, access to transplantation, delivery of care, and posttransplant mortality in Canada as compared with the United States, and the generalizability of the LKDPI in the Canadian context is unknown. OBJECTIVE: The purpose of this study was to externally validate the LKDPI in a large contemporary cohort of Canadian KTR. DESIGN: Retrospective cohort validation study. SETTING: Toronto General Hospital, University Health Network, Toronto, Ontario, Canada. PATIENTS: A total of 645 adult (≥18 years old) living donor KTR between January 1, 2006 and December 31, 2016 with follow-up until December 31, 2017 were included in the study. MEASUREMENTS: The predictive performance of the LKDPI was evaluated. The outcome of interest was total graft failure, defined as the need for chronic dialysis, retransplantation, or death with graft function. METHODS: The Cox proportional hazards model was used to examine the relation between the LKDPI and total graft failure. The Cox proportional hazards model was also used for external validation and performance assessment of the model. Discrimination and calibration were used to assess model performance. Discrimination was assessed using Harrell's C statistic and calibration was assessed graphically, comparing observed versus predicted probabilities of total graft failure. RESULTS: A total of 645 living donor KTR were included in the study. The median LKDPI score was 13 (interquartile range [IQR] = 1.1, 29.9). Higher LKDPI scores were associated with an increased risk of total graft failure (hazard ratio = 1.01; 95% confidence interval [CI] = 1.0-1.02; P = .02). Discrimination was poor (C statistic = 0.55; 95% CI = 0.48-0.61). Calibration was as good at 1-year posttransplant but suboptimal at 3- and 5-years posttransplant. LIMITATIONS: Limitations include a relatively small sample size, predicted probabilities for assessment of calibration only available for scores of 0 to 100, and some missing data handled by imputation. CONCLUSIONS: In this external validation study, the predictive ability of the LKDPI was modest in a cohort of Canadian KTR. Validation of prediction models is an important step to assess performance in external populations. Potential recalibration of the LKDPI may be useful prior to clinical use in external cohorts.

CONTEXTE: L'indice Living Kidney Donor Profile Index (LKDPI) est employé pour prédire le risque de perte du greffon et dérive d'une cohorte de receveurs d'une greffe rénale (RGR) aux États-Unis. Il existe toutefois d'importantes différences entre le Canada et les États-Unis quant aux données démographiques des patients, aux pratiques relatives aux listes, à l'accès à une transplantation, à la prestation des soins et à la mortalité post-transplantation. La généralisation de l'indice LKDPI en contexte canadien demeure inconnue. OBJECTIF: L'objectif de cette étude était de valider l'indice LKDPI à l'externe, dans une vaste cohorte de RGR canadiens. TYPE D'ÉTUDE: Une étude de validité menée de façon rétrospective. CADRE: L'hôpital général de Toronto, membre du réseau universitaire de santé de Toronto (Ontario), Canada. SUJETS: Ont été inclus 645 adultes RGR provenant d'un donneur vivant entre le 1er janvier 2006 et le 31 décembre 2016 avec suivi s'étant poursuivi jusqu'au 31 décembre 2017. MESURES: La performance prédictive de l'indice LKDPI a été évaluée. Le principal résultat d'intérêt était la perte du greffon, telle que définie par le besoin de dialyse à vie, par une nouvelle transplantation ou par le décès du patient avec un greffon fonctionnel. MÉTHODOLOGIE: Un modèle des risques proportionnels de Cox a été employé pour quantifier la relation entre l'indice LKDPI et la perte du greffon. Le modèle des risques proportionnels de Cox a également servi à la validation externe et à la mesure de la performance du modèle prédictif. La discrimination et l'étalonnage ont été utilisés pour évaluer la performance du modèle. La discrimination a été mesurée à l'aide de la statistique c de Harrell et l'étalonnage a été évalué graphiquement en comparant les probabilités prévues et observées de perte du greffon. RÉSULTATS: Un total de 645 RGR provenant d'un donneur vivant ont été inclus. Le score médian de l'indice était de 13 (ÉIQ: 1,1; 29,9). Un score élevé pour l'indice LKDPI a été associé à un risque accru de perte du greffon [Rapport de risque : 1,01 (IC 95 % : 1,0; 1,02), P = 0,02]. La discrimination s'est avérée faible [statistique c : 0,55 (IC 95 % : 0,48; 0,61)], et l'étalonnage était bon un an après l'intervention, mais sous-optimal trois ans et cinq ans après la greffe. LIMITES: La taille de l'échantillon était relativement faible, les probabilités prévues utilisées pour évaluer l'étalonnage n'étaient disponibles que pour les scores entre 0 et 100, et certaines données manquantes ont été traitées par imputation. CONCLUSION: La valeur prédictive de l'indice LKDPI s'est avérée modeste dans la cohorte de RGR canadiens analysée pour cette étude de validité externe. La validation des modèles prédictifs est une étape essentielle pour évaluer leur performance dans des populations externes. Il conviendrait de réétalonner l'indice LKDPI avant son utilization clinique dans des cohortes externes.

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.

Epidemiology of Kidney Discard from Expanded Criteria Donors Undergoing Donation after Circulatory Death.

BACKGROUND AND OBJECTIVES: The broader use of combined expanded criteria donor and donation after circulatory death (ECD/DCD) kidneys may help expand the deceased donor pool. The purpose of our study was to evaluate discard rates of kidneys from ECD/DCD donors and factors associated with discard. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: ECD/DCD donors and kidneys were evaluated from January 1, 2000 to March 31, 2011 using data from the Scientific Registry of Transplant Recipients. The kidney donor risk index was calculated for all ECD/DCD kidneys. Multivariable logistic regression models were used to determine risk factors for discarding both donor kidneys. The Kaplan-Meier product limit method and the log-rank statistic were used to assess the cumulative probability of graft failure for transplants from ECD/DCD donors where the mate kidney was discarded versus both kidneys were used. RESULTS: There were 896 ECD/DCD donors comprising 1792 kidneys. Both kidneys were discarded in 44.5% of donors, whereas 51.0% of all available kidneys were discarded. The kidney donor risk index scores were higher among donors of discarded versus transplanted kidneys (median, 1.82; interquartile range, 1.60, 2.07 versus median, 1.67; interquartile range, 1.49, 1.87, respectively; P<0.001); however, the distributions showed considerable overlap. The adjusted odds ratios for discard were higher among donors who were older, diabetic, AB blood type, and hepatitis C positive. The cumulative probabilities of total graft failure at 1, 3, and 5 years were 17.3%, 36.5%, and 55.4% versus 13.8%, 24.7%, and 40.5% among kidneys from donors where only one versus both kidneys were transplanted, respectively (log rank P=0.04). CONCLUSIONS: Our study shows a significantly higher discard rate for ECD/DCD kidneys versus prior reports. Some discarded ECD/DCD kidneys may be acceptable for transplantation. Additional studies are needed to evaluate the factors that influence decision making around the use of ECD/DCD kidneys.