Association Between the Dialysate Bicarbonate and the Pre-dialysis Serum Bicarbonate Concentration in Maintenance Hemodialysis: A Retrospective Cohort Study.

Background: It is unclear whether the use of higher dialysate bicarbonate concentrations is associated with clinically relevant changes in the pre-dialysis serum bicarbonate concentration. Objective: The objective is to examine the association between the dialysate bicarbonate prescription and the pre-dialysis serum bicarbonate concentration. Design: This is a retrospective cohort study. Setting: The study was performed using linked administrative health care databases in Ontario, Canada. Patients: Prevalent adults receiving maintenance in-center hemodialysis as of April 1, 2020 (n = 5414) were included. Measurements: Patients were grouped into the following dialysate bicarbonate categories at the dialysis center-level: individualized (adjustment based on pre-dialysis serum bicarbonate concentration) or standardized (>90% of patients received the same dialysate bicarbonate concentration). The standardized category was stratified by concentration: 35, 36 to 37, and ≥38 mmol/L. The primary outcome was the mean outpatient pre-dialysis serum bicarbonate concentration at the patient level. Methods: We examined the association between dialysate bicarbonate category and pre-dialysis serum bicarbonate using an adjusted linear mixed model. Results: All dialysate bicarbonate categories had a mean pre-dialysis serum bicarbonate concentration within the normal range. In the individualized category, 91% achieved a pre-dialysis serum bicarbonate ≥22 mmol/L, compared to 87% in the standardized category. Patients in the standardized category tended to have a serum bicarbonate that was 0.25 (95% confidence interval [CI] = -0.93, 0.43) mmol/L lower than patients in the individualized category. Relative to patients in the 35 mmol/L category, patients in the 36 to 37 and ≥38 mmol/L categories tended to have a serum bicarbonate that was 0.70 (95% CI = -0.30, 1.70) mmol/L and 0.87 (95% CI = 0.14, 1.60) mmol/L higher, respectively. There was no effect modification by age, sex, or history of chronic lung disease. Limitations: We could not directly confirm that all laboratory measurements were pre-dialysis. Data on prescribed dialysate bicarbonate concentrations for individual dialysis sessions were not available, which may have led to some misclassification, and adherence to a practice of individualization could not be measured. Residual confounding is possible. Conclusions: We found no significant difference in the pre-dialysis serum bicarbonate concentration irrespective of whether an individualized or standardized dialysate bicarbonate was used. Dialysate bicarbonate concentrations ≥38 mmol/L (vs 35 mmol/L) may increase the pre-dialysis serum bicarbonate concentration by 0.9 mmol/L.

Contexte: On ignore si des concentrations plus élevées de bicarbonate dans le dialysat sont associées à des changements cliniquement significatifs dans le taux de bicarbonate sérique prédialyse. Objectif: Examiner l'association entre la prescription de bicarbonate du dialysat et le taux de bicarbonate sérique prédialyse. Conception: Étude de cohorte rétrospective. Cadre: Étude réalisée en Ontario (Canada) à partir des données administratives de santé. Sujets: Ont été inclus les adultes prévalents qui recevaient une hémodialyse chronique en centre le 1er avril 2020 (n=5 414). Mesures: Les sujets ont été regroupés dans les catégories suivantes de concentration en bicarbonate dans le dialysat utilisée dans leur unité de dialyse: individualisée (ajustée selon le taux de bicarbonate sérique prédialyse) ou normalisée (même concentration pour >90% des sujets). La catégorie « standardisée ¼ a été stratifiée selon la concentration: 35 mmol/L, 36 à 37 mmol/L et ≥38 mmol/L. Le principal critère d'évaluation était le taux moyen de bicarbonate sérique prédialyse en ambulatoire au niveau du patient. Méthodologie: Nous avons examiné l'association entre la catégorie de concentration en bicarbonate du dialysat et le taux de bicarbonate sérique prédialyse à l'aide d'un modèle linéaire mixte corrigé. Résultats: Pour toutes les catégories de concentration en bicarbonate du dialysat, le taux moyen de bicarbonate sérique prédialyse était dans la plage normale. Dans la catégorie « individualisée ¼, 91% des sujets avaient un taux de bicarbonate sérique prédialyse de ≥22 mmol/L, comparativement à 87% dans la catégorie « standardisée ¼. Les patients de la catégorie « standardisée ¼ tendaient à avoir un taux de bicarbonate sérique de 0,25 mmol/L (IC 95%: -0,93 à 0,43) inférieur à celui des patients de la catégorie « individualisée ¼. Comparé aux patients de la catégorie 35 mmol/L, les patients des catégories 36 à 37 mmol/L et ≥38 mmol/L tendaient respectivement à avoir un taux de bicarbonate sérique de 0,70 mmol/L (IC 95%: -0,30 à 1,70) et de 0,87 mmol/L (IC 95%: 0,14 à 1,60) plus élevé. L'âge, le sexe ou les antécédents de maladie pulmonaire chronique n'ont pas semblé modifier l'effet. Limites: Il n'a pas été possible de confirmer directement que toutes les mesures de laboratoire avaient été effectuées avant la dialyse. Les données sur les concentrations de bicarbonate prescrites pour les séances de dialyse individuelles n'étaient pas disponibles, ce qui peut avoir conduit à une classification erronée. De plus, l'observance d'une pratique d'individualisation n'a pas pu être mesurée. Une confusion résiduelle est possible. Conclusion: Nous n'avons observé aucune différence significative dans les taux de bicarbonate sériques prédialyse, qu'on ait utilisé une concentration individualisée ou standardisée de bicarbonate dans le dialysat. L'utilisation d'un dialysat à ≥38 mmol/L (c. 35 mmol/L) de bicarbonate peut entraîner une hausse de 0,9 mmol/L du taux de bicarbonate sérique prédialyse.

Pathways for Diagnosing and Treating CKD-Associated Pruritus: A Narrative Review.

Purpose of Review: Chronic kidney disease (CKD)-associated pruritus is a common, persistent, and distressing itch experienced by patients across the CKD spectrum. Although the disorder is associated with adverse outcomes and poor health-related quality of life, it remains underdiagnosed and undertreated. The purpose of this narrative review is to offer health care providers guidance on how to effectively identify, assess, and treat patients with CKD-associated pruritus, with the goal of reducing symptom burden and improving patient-important outcomes, such as quality of life (QoL). Sources of Information: A panel of nephrologists and researchers from across Canada and the United States was assembled to develop this narrative review based on the best available data, current treatment guidelines, and their clinical experiences. Methods: A panel of nephrologists who actively care for patients with pruritus receiving dialysis from across Canada was assembled. Two researchers from the United States were also included based on their expertise in the diagnosis and management of CKD-associated pruritus. Throughout Spring 2023, the panel met to discuss key topics in the identification, assessment, and management of CKD-associated pruritus. Panel members subsequently developed summaries of the pertinent information based on the best available data, current treatment guidelines, and added information on their own clinical experiences. In all cases, approval of the article was sought and achieved through discussion. Key Findings: This narrative review provides pragmatic guidance addressing: (1) methods for screening CKD-associated pruritus, (2) assessing severity, (3) management of CKD-associated pruritus, and (4) suggested areas for future research. The panel developed a 3-pillar framework for proactive assessment and severity scoring in CKD-aP: systematic screening for CKD-associated pruritus (pillar 1), assessment of pruritus intensity (pillar 2), and understanding the impact of CKD-associated pruritus on the patient's QoL (pillar 3). Management of CKD-associated pruritus can include ensuring optimization of dialysis adequacy, achieving mineral metabolism targets (ie, calcium, phosphate, and parathyroid hormone). However, treatment of CKD-associated pruritus usually requires additional interventions. Patients, regardless of CKD-associated pruritus severity, should be counseled on adequate skin hydration and other non-pharmacological strategies to reduce pruritus. Antihistamines should be avoided in favor of evidence-based treatments, such as difelikefalin and gabapentin. Limitations: A formal systematic review (SR) of the literature was not undertaken, although published SRs were reviewed. The possibility for bias based on the experts' own clinical experiences may have occurred. Key takeaways are based on the current available evidence, of which head-to-head clinical trials are lacking. Funding: This work was funded by an arm's length grant from Otsuka Canada Pharmaceutical Inc. (the importer and distributer of difelikefalin in Canada). LiV Medical Education Agency Inc. provided logistical and editorial support.

Motif de la revue: Le prurit associé à l'insuffisance rénale chronique (IRC) est une démangeaison cutanée fréquente, persistante et invalidante que les patients de tout le specter de l'IRC peuvent ressentir. Bien que le prurit soit associé à des effets indésirables et à une mauvaise qualité de vie liée à la santé, il demeure sous-diagnostiqué et sous-traité. L'objectif de cette revue narrative est d'offrir des conseils aux professionnels de la santé sur la façon d'identifier, d'évaluer et de traiter efficacement les patients atteints de prurit associé à l'IRC; ceci dans le but de réduire la charge des symptômes et d'améliorer les résultats importants pour les patients, notamment leur qualité de vie (QdV). Sources de l'information: Un comité de néphrologues et de chercheurs de partout au Canada et des États-Unis a été constitué pour élaborer la présente revue narrative à partir des meilleures données disponibles, des lignes directrices actuelles pour le traitement et de leurs expériences cliniques. Méthodologie: Un groupe de néphrologues canadiens qui s'occupent activement de patients dialysés souffrant de prurit a été constitué. Deux chercheurs des États-Unis ont été inclus au groupe en raison de leur expertise dans le diagnostic et la prise en charge du prurit associé à l'IRC. Le comité s'est réuni tout au long du printemps 2023 pour discuter de sujets clés en lien avec l'identification, l'évaluation et la prise en charge du prurit associé à l'IRC. Les membres du comité ont par la suite rédigé des résumés des informations pertinentes en se basant sur les meilleures données disponibles et les lignes directrices actuelles pour le traitement, auxquels ils ont ajouté des informations issues de leurs propres expériences cliniques. Dans tous les cas, l'approbation du manuscrit a été sollicitée et obtenue par discussion. Principaux résultats: Cette revue narrative offre des conseils pragmatiques sur les points suivants: (1) les méthodes de dépistage du prurit associé à l'IRC; (2) l'évaluation de sa gravité; (3) sa prise en charge; et (4) les domaines suggérés pour de futures recherches. Le comité a développé un cadre à trois piliers pour l'évaluation proactive du prurit associé à l'IRC et l'établissement d'un score de gravité: le dépistage systématique du prurit associé à l'IRC (pilier 1), l'évaluation de son intensité (pilier 2) et la compréhension de son impact sur la QdV du patient (pilier 3). La prise en charge du prurit associé à l'IRC peut inclure l'optimisation de l'adéquation de la dialyse et l'atteinte des cibles du métabolisme minéral (c.-à-d. calcium, phosphate et hormone parathyroïdienne). Cependant, son traitement nécessite habituellement des interventions supplémentaires. Les patients, quelle que soit la gravité du prurit associé à l'IRC, devraient être avisés d'hydrater adéquatement leur peau et informés des autres stratégies non pharmacologiques afin de réduire le prurit. On devrait éviter les antihistaminiques et les remplacer par des traitements fondés sur des données probantes comme la difélikéfaline et la gabapentine. Limites: Aucune revue systématique de la littérature n'a été formellement entreprise, bien que les revues systématiques publiées aient été examinées. La possibilité d'un biais fondé sur les expériences cliniques des experts est envisageable. Les principales conclusions de cette étude sont fondées sur les données probantes actuellement disponibles, pour lesquelles il n'existe pas d'essais cliniques comparatifs. Financement: Ces travaux ont été financés par une subvention indépendante d'Otsuka Canada Pharmaceutical Inc. (l'importateur et distributeur de la difélikéfaline au Canada). Un soutien logistique et éditorial a été fourni par liV Medical Education Agency Inc.

Impact of Prior Abdominal Procedures on Peritoneal Dialysis Catheter Outcomes: Findings From the North American Peritoneal Dialysis Catheter Registry.

RATIONALE & OBJECTIVE: A history of prior abdominal procedures may influence the likelihood of referral for peritoneal dialysis (PD) catheter insertion. To guide clinical decision making in this population, this study examined the association between prior abdominal procedures and outcomes in patients undergoing PD catheter insertion. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults undergoing their first PD catheter insertion between November 1, 2011, and November 1, 2020, at 11 institutions in Canada and the United States participating in the International Society for Peritoneal Dialysis North American Catheter Registry. EXPOSURE: Prior abdominal procedure(s) defined as any procedure that enters the peritoneal cavity. OUTCOMES: The primary outcome was time to the first of (1) abandonment of the PD catheter or (2) interruption/termination of PD. Secondary outcomes were rates of emergency room visits, hospitalizations, and procedures. ANALYTICAL APPROACH: Cumulative incidence curves were used to describe the risk over time, and an adjusted Cox proportional hazards model was used to estimate the association between the exposure and primary outcome. Models for count data were used to estimate the associations between the exposure and secondary outcomes. RESULTS: Of 855 patients who met the inclusion criteria, 31% had a history of a prior abdominal procedure and 20% experienced at least 1 PD catheter-related complication that led to the primary outcome. Prior abdominal procedures were not associated with an increased risk of the primary outcome (adjusted HR, 1.12; 95% CI, 0.68-1.84). Upper-abdominal procedures were associated with a higher adjusted hazard of the primary outcome, but there was no dose-response relationship concerning the number of procedures. There was no association between prior abdominal procedures and other secondary outcomes. LIMITATIONS: Observational study and cohort limited to a sample of patients believed to be potential candidates for PD catheter insertion. CONCLUSION: A history of prior abdominal procedure(s) does not appear to influence catheter outcomes following PD catheter insertion. Such a history should not be a contraindication to PD. PLAIN-LANGUAGE SUMMARY: Peritoneal dialysis (PD) is a life-saving therapy for individuals with kidney failure that can be done at home. PD requires the placement of a tube, or catheter, into the abdomen to allow the exchange of dialysis fluid during treatment. There is concern that individuals who have undergone prior abdominal procedures and are referred for a catheter might have scarring that could affect catheter function. In some institutions, they might not even be offered PD therapy as an option. In this study, we found that a history of prior abdominal procedures did not increase the risk of PD catheter complications and should not dissuade patients from choosing PD or providers from recommending it.

Predicting Urgent Dialysis at Ambulance Transport to the Emergency Department Using Machine Learning Methods.

Hemodialysis patients frequently require ambulance transport to the hospital for dialysis. Some patients require urgent dialysis (UD) within 24 hours of transport to hospital to avoid morbidity and mortality. UD is not available in all hospitals; therefore, predicting patients who need UD prior to hospital transport can help paramedics with destination planning. In this paper, we developed machine learning models for paramedics to predict whether a patient needs UD based on patient characteristics available at the time of ambulance transport. This paper presented a study based on ambulance data collected in Halifax, Canada. Given that relatively few patients need UD, a class imbalance problem is addressed by up-sampling methods and prediction models are developed using multiple machine learning methods. The achieved prediction scores are F1-score=0.76, sensitivity=0.76, and specificity=0.97, confirming that models can predict UD with limited patient characteristics.

Characterizing Cluster-Based Frailty Phenotypes in a Multicenter Prospective Cohort of Kidney Transplant Candidates.

Frailty is associated with a higher risk of death among kidney transplant candidates. Currently available frailty indices are often based on clinical impression, physical exam or an accumulation of deficits across domains of health. In this paper we investigate a clustering based approach that partitions the data based on similarities between individuals to generate phenotypes of kidney transplant candidates. We analyzed a multicenter cohort that included several features typically used to determine an individual's level of frailty. We present a clustering based phenotyping approach, where we investigated two clustering approaches-i.e. neural network based Self-Organizing Maps (SOM) with hierarchical clustering, and KAMILA (KAy-means for MIxed LArge data sets). Our clustering results partition the individuals across 3 distinct clusters. Clusters were used to generate and study feature-level phenotypes of each group.

Ensemble Clustering to Generate Phenotypes of Kidney Transplant Donors and Recipients.

In this paper we investigate the generation of phenotypes for kidney transplant donors and recipients to assist with decision making around organ allocation. We present an ensemble clustering approach for multi-type data (numerical and categorical) using two different clustering approaches-i.e., model based and vector quantization based clustering. These clustering approaches were applied to a large, US national deceased donor kidney transplant recipient database to characterize members of each cluster (in an unsupervised fashion) and to determine whether the subsequent risk of graft failure differed for each cluster. We generated three distinct clusters of recipients, which were subsequently used to generate phenotypes. Each cluster phenotype had recipients with varying clinical features, and the risk of kidney transplant graft failure and mortality differed across clusters. Importantly, the clustering results by both approaches demonstrated a significant overlap. Utilization of two distinct clustering approaches may be a novel way to validate unsupervised clustering techniques and clustering can be used for organ allocation decision making on the basis of differential outcomes.

The Association of Intra-Abdominal Adhesions with Peritoneal Dialysis Catheter-Related Complications.

BACKGROUND: This study investigated the association of intra-abdominal adhesions with the risk of peritoneal dialysis (PD) catheter complications. METHODS: Individuals undergoing laparoscopic PD catheter insertion were prospectively enrolled from eight centers in Canada and the United States. Patients were grouped based on the presence of adhesions observed during catheter insertion. The primary outcome was the composite of PD never starting, termination of PD, or the need for an invasive procedure caused by flow restriction or abdominal pain. RESULTS: Seven hundred and fifty-eight individuals were enrolled, of whom 201 (27%) had adhesions during laparoscopic PD catheter insertion. The risk of the primary outcome occurred in 35 (17%) in the adhesion group compared with 58 (10%) in the no adhesion group (adjusted HR, 1.64; 95% confidence interval [CI], 1.05 to 2.55) within 6 months of insertion. Lower abdominal or pelvic adhesions had an adjusted HR of 1.80 (95% CI, 1.09 to 2.98) compared with the no adhesion group. Invasive procedures were required in 26 (13%) and 47 (8%) of the adhesion and no adhesion groups, respectively (unadjusted HR, 1.60: 95% CI, 1.04 to 2.47) within 6 months of insertion. The adjusted odds ratio for adhesions for women was 1.65 (95% CI, 1.12 to 2.41), for body mass index per 5 kg/m 2 was 1.16 (95% CI, 1.003 to 1.34), and for prior abdominal surgery was 8.34 (95% CI, 5.5 to 12.34). Common abnormalities found during invasive procedures included PD catheter tip migration, occlusion of the lumen with fibrin, omental wrapping, adherence to the bowel, and the development of new adhesions. CONCLUSIONS: People with intra-abdominal adhesions undergoing PD catheter insertion were at higher risk for abdominal pain or flow restriction preventing PD from starting, PD termination, or requiring an invasive procedure. However, most patients, with or without adhesions, did not experience complications, and most complications did not lead to the termination of PD therapy.

Association Between First Post-operative Day Urine Output Following Kidney Transplantation and Short-Term and Long-Term Outcomes: A Retrospective Cohort Study.

Background: The relationship between post-operative urine output (UO) following kidney transplantation and long-term graft function has not been well described. Objective: In this study, we examined the association between decreased UO on post-operative day 1 (POD1) and post-transplant outcomes. Design: This is a retrospective cohort study. Setting: Atlantic Canada. Patients: Patients from the 4 Atlantic Canadian provinces (Nova Scotia, New Brunswick, Newfoundland, and Prince Edward Island) who received a live or deceased donor kidney transplant from 2006 through 2019 through the multiorgan transplant program at the Queen Elizabeth II Health Sciences Centre (QEII) hospital in Halifax, Nova Scotia. Measurements: Using multivariable Cox proportional hazards models, we assessed the association of low POD1 UO (defined as ≤1000 mL) with death-censored graft loss (DCGL). In secondary analyses, we used adjusted logistic regression or Cox models as appropriate to assess the impact of UO on delayed graft function (DGF), prolonged length of stay (greater than the median for the entire cohort), and death. Results: Of the 991 patients included, 151 (15.2%) had a UO ≤1000 mL on POD1. Low UO was independently associated with DCGL (hazard ratio [HR] = 4.00, 95% confidence interval [CI] = 95% CI = 1.55-10.32), DGF (odds ratio [OR] = 45.25, 95% CI = 23.00-89.02), and prolonged length of stay (OR = 5.06, 95% CI = 2.95-8.69), but not death (HR = 0.81, 95% CI = 0.31-2.09). Limitations: This was a single-center, retrospective, observational study and therefore has inherent limitations of generalizability, data collection, and residual confounding. Conclusions: Overall, reduced post-operative UO following kidney transplantation is associated with an increased risk of DCGL, DGF, and prolonged hospital length of stay.

Contexte: Le lien entre la diurèse postopératoire après une transplantation rénale et la fonction du greffon à long terme n'a pas été bien décrit. Objectif: Dans cette étude, nous avons examiné l'association entre la diminution de la diurèse au jour 1 postopératoire et les résultats après la transplantation. Conception: Étude de cohorte rétrospective. Cadre: Canada atlantique. Patients: Des patients des quatre provinces du Canada atlantique (Nouvelle-Écosse, Nouveau-Brunswick, Terre-Neuve et Île-du-Prince-Édouard) ayant reçu une greffe de rein provenant d'un donneur vivant ou décédé entre 2006 et 2019 dans le cadre du programme de transplantation multiorganes de l'hôpital QEII d'Halifax (Nouvelle-Écosse). Mesures: À l'aide de modèles à risques proportionnels de Cox multivariés, nous avons évalué l'association entre une faible diurèse (définie comme ≤ 1 000 ml) et la perte du greffon censurée par le décès (PGCD). Dans les analyses secondaires, nous avons utilisé des modèles de Cox ou des modèles de régression logistique ajustés, selon le cas, pour évaluer l'effet de la diurèse sur la fonction retardée du greffon, la durée prolongée du séjour (supérieure à la médiane pour l'ensemble de la cohorte) et le décès. Résultats: Des 991 patients inclus, 151 (15,2%) présentaient une diurèse inférieure à 1 000 ml au jour 1 postopératoire. Une faible diurèse a été indépendamment associée à la PGCD (rapport de risque [RR]: 4,00; IC 95 %: 1,55-10,32), à une fonction retardée du greffon (rapport de cotes [RC]: 45,25; IC 95 %: 23,00-89,02) et à un séjour prolongé à l'hôpital (RC: 5,06; IC 95 %: 2,95-8,69), mais pas au décès (RR: 0,81; IC 95 %: 0,31-2,09). Limites: Il s'agissait d'une étude observationnelle rétrospective monocentrique. L'étude présente ainsi des limites inhérentes à la généralisabilité, à la collecte des données et aux facteurs confondants résiduels. Conclusion: Dans l'ensemble, une diminution de la diurèse postopératoire après une transplantation rénale est associée à un risque accru de PGCD et de fonction retardée du greffon, ainsi qu'à un séjour prolongé à l'hôpital.

Outcomes of Integrated Home Dialysis Care: Results From the Canadian Organ Replacement Register.

RATIONALE & OBJECTIVE: The integrated home dialysis model proposes the initiation of kidney replacement therapy (KRT) with peritoneal dialysis (PD) and a timely transition to home hemodialysis (HHD) after PD ends. We compared the outcomes of patients transitioning from PD to HHD with those initiating KRT with HHD. STUDY DESIGN: Observational analysis of the Canadian Organ Replacement Register (CORR). SETTINGS & PARTICIPANTS: All patients who initiated PD or HHD within the first 90 days of KRT between 2005 and 2018. EXPOSURE: Patients transitioning from PD to HHD (PD+HHD group) versus patients initiating KRT with HHD (HHD group). OUTCOME: (1) A composite of all-cause mortality and modality transfer (to in-center hemodialysis or PD for 90 days) and (2) all hospitalizations (considered as recurrent events). ANALYTICAL APPROACH: A propensity score analysis for which PD+HHD patients were matched 1:1 to (1) incident HHD patients ("incident-match" analysis) or (2) HHD patients with a KRT vintage at least equivalent to the vintage of PD+HHD patients at the transition time ("vintage-matched" analysis). Cause-specific hazards models (composite outcome) and shared frailty models (hospitalization) were used to compare groups. RESULTS: Among 63,327 individuals in the CORR, 163 PD+HHD patients (median of 1.9 years in PD) and 711 HHD patients were identified. In the incident-match analysis, compared to the HHD patients, the PD+HHD group had a similar risk of the composite outcome (HR, 0.88 [95% CI, 0.58-1.32]) and hospitalizations (HR, 1.04 [95% CI, 0.76-1.41]). In the vintage-match analysis, PD+HHD patients had a lower hazard for the composite outcome (HR, 0.61 [95% CI, 0.40-0.94]) but a similar hospitalization risk (HR, 0.85 [95% CI, 0.59-1.24]). LIMITATIONS: Risk of survivor bias in the PD+HHD cohort and residual confounding. CONCLUSIONS: Controlling for KRT vintage, the patients transitioning from PD to HHD had better clinical outcomes than the incident HHD patients. These data support the use of integrated home dialysis for patients initiating home-based KRT. PLAIN-LANGUAGE SUMMARY: The integrated home dialysis model proposes the initiation of dialysis with peritoneal dialysis (PD) and subsequent transition to home hemodialysis (HHD) once PD is no longer feasible. It allows patients to benefit from initial lifestyle advantages of PD and to continue home-based treatments after its termination. However, some patients may prefer to initiate dialysis with HHD from the outset. In this study, we compared the long-term clinical outcomes of both approaches using a large Canadian dialysis register. We found that both options led to a similar risk of hospitalization. In contrast, the PD-to-HHD model led to improved survival when controlling for the duration of kidney failure.

Urinary exosomal miRNA signature of IgA nephropathy: a case-control study.

IgA nephropathy is the most common primary glomerulonephritis worldwide and can progress to end-stage kidney disease (ESKD). The current "gold standard" for diagnosis is kidney biopsy, which is invasive and associated with morbidity. miRNAs are small, non-coding endogenous RNA that may serve as non-invasive biomarkers, and that are found in urinary exosomes. Thus far, there is a paucity of studies of the miRNA profile for the diagnosis of IgA nephropathy. Hence, we aimed to study the urinary exosomal miRNA signature of Indian patients with IgA nephropathy. Fifty biopsy-proven IgA nephropathy patients, 50 healthy controls and 25 patients with ESKD (IgA nephropathy) were recruited over 2 years (2020-2022). Urinary exosomes were isolated from which miRNA was extracted . Analysis of urinary exosomal miRNA was done using the digital multiplexed nCounter® human v3 miRNA Expression Assay which contains 799 unique miRNA barcodes. Candidate miRNAs were identified using Lasso regression and consensus clustering. The mean age of IgA nephropathy patients was 36.32 ± 3.067 years, mean creatinine was 2.26 ± 0.318 mg/dl and mean proteinuria was 2.69 ± 0.64 g/day. Compared to healthy controls, the majority (N = 150) of miRNAs were significantly downregulated. Five candidate miRNAs (hsa.miR.146b.3p, hsa.miR.599, hsa.miR.4532, hsa.miR.664b.5p and hsa.miR.221.5p) were able to differentiate between IgA nephropathy cases and controls (AUC > 0.90); the presence of all 5 was associated with 100% specificity and sensitivity for diagnosing IgA nephropathy cases. This study of Indian patients identified that there was a significant difference in the urinary exosomal miRNA profile between IgA nephropathy cases and healthy controls, suggesting that miRNAs may be valuable in the non-invasive diagnosis of IgA nephropathy.

Transforming healthcare delivery: a descriptive study of a novel provider-to-provider virtual care platform.

Introduction: Addressing challenges in access to specialty care, particularly long wait times and geographic disparities, is a pressing issue in the Canadian healthcare system. This study aimed to evaluate the impact and feasibility of provider-to-provider phone consultations between primary care providers (PCPs) and specialists using a novel virtual care platform in Nova Scotia (Virtual Hallway). Methods: We conducted a cross-sectional survey over 5 months, involving 211 PCPs and 34 specialists across Nova Scotia. The survey assessed the need for formal in-person referrals as well as clinician satisfaction. Statistical methods included descriptive statistics and the one-sample t-test. Results: We found that 84% of provider-to-provider phone consultations negated the need for an in-person specialist referral. It was also reported that 90% of patients that did require in-person consultation had enhanced care while they awaited an in-person appointment with a specialist. Very high levels of satisfaction were reported among both PCPs and specialists, and there was a noticeable increase in billing volumes related to these consultations as measured by provincial billing codes. Conclusion: The findings indicate that provider-to-provider phone consultations are feasible, well-accepted and also effective in reducing the need for in-person specialist visits. This approach offers a promising avenue for alleviating waitlist burdens, enhancing the quality of care, and improving the overall efficiency of healthcare delivery.

Development of the Nova Scotia Potential Donor Audit (PDA) Tool and 2020 Historic Performance Database: Lessons Learned From the First 1000 Medical Record Reviews.

Background: Legislation and accountability frameworks are key components of high-performing deceased-donation systems. In 2021, Nova Scotia (NS), Canada, became the first jurisdiction in North America to enact deemed consent legislation and concurrently implemented mandatory referral legislation similar to that found in other Canadian provinces. Frontline financial resources were provided by the government to support the development of program infrastructure, including implementation of means to evaluate system performance. Methods: The Organ Donation Program (ODP), in collaboration with other stakeholders, developed a Potential Donor Audit (PDA) tool and database for referral intake and manual performance audits. Medical record reviews of deaths in the year before legislative change were conducted to pilot and revise the PDA and evaluate missed donation opportunities. Results: The NS PDA was piloted on 1028 patient deaths. Of 518 patients (50.4%) who met clinical triggers for referral to the ODP, 72 (13.9%) were referred (86.1% missed referral rate). One hundred sixty-three patients met the NS definition of a potential donor; 53 (32.5%) were referred (110 missed potential donors). Referral consent rates reached 71.7% (n = 38 of 53 approaches). The actualized donation rate reported by Canadian Blood Services was 29.9 donors per million population (n = 34 donors). Discussion: We documented high rates of missed referrals and missed potential donors before the enactment of mandatory referral and deemed consent legislation. Conclusions: The ODP has intentionally broadened clinical criteria for referral to shift the responsibility of identifying medically suitable potential donors from bedside clinicians to organ donation specialists. Lessons learned from our experience developing a PDA include the importance of early involvement of multiple stakeholders and ongoing modification of fields and workflow based on data availability and utility for clinical, educational, research, and reporting purposes.

Variability in Reporting eGFR at Dialysis Initiation in Canada: A Research Letter.

Background: Estimated glomerular filtration rate (eGFR) at dialysis initiation is increasingly recognized as a key quality indicator (QI) for patients with end-stage kidney disease (ESKD). Specifically, guidelines recommend assessing deferral of dialysis initiation until symptoms arise or if the eGFR is ≤6 mL/min/1.73 m2. Despite the recognition of the importance of this QI, how eGFR at the time of dialysis initiation is defined, collected, and tracked at dialysis centers across Canada remains unknown. Objectives: To identify how provincial renal programs define eGFR at dialysis initiation, to compare practice across Canadian provinces, and to determine if there is a consistent benchmark for deferred dialysis start. Design: Cross-sectional survey distributed to the medical leads of each provincial renal program, administered from July 2021 to November 2021. Quebec was not included given it did not yet participate in Canadian Organ Replacement Register (CORR) data submission. Setting: The survey was designed and distributed by the Canadian Society of Nephrology Quality Improvement & Implementation Science Committee (CSN-QUIS) Indicator Working Group. Methods: The survey asked respondents on how eGFR is defined, collected, reported, and perceived barriers to QI data collection. The National Senior Renal Leaders Forum helped identify the key provincial medical leads to disseminate the survey for completion. Results: Surveys were distributed to the medical leads of the 9 provincial renal programs that participate in CORR. In total, there were 8 responses. Five provinces submit eGFR for all new dialysis starts and 3 provinces only submit this information for chronic patients. There is variation in determining when a patient with acute kidney injury requiring dialysis is classified as a chronic patient. Four provinces use a 30-day trigger, 3 provinces use a 90-day trigger, and the patient's nephrologist makes this determination in 1 province. The creatinine used for the eGFR at dialysis initiation was the value measured on the first dialysis session (ie, day 0) for 5 provinces; the last outpatient clinic creatinine value in 2 provinces, and 1 province did not have a standard definition. Three provinces did not have a benchmark target for eGFR at dialysis initiation, 1 province had a target of <9.5 mL/min/1.73 m2, 3 provinces had a target of <10 mL/min/1.73 m2, 1 province had a target of <15 mL/min/1.73 m2. All 8 responding provincial medical leads support the establishment of a national benchmark for this measure. Limitations: This survey was restricted to provincial medical leads and therefore is unable to determine practice at individual dialysis sites. The survey was not anonymous, so it may be subject to conformity bias. Conclusions: There is wide variability in how eGFR at dialysis initiation is measured and reported across Canada. Additionally, there is no consensus on a benchmark target for an intent-to-defer dialysis strategy. Standardization of target eGFR at dialysis initiation may facilitate national reporting and quality improvement initiatives.

Contexte: Le débit de filtration glomérulaire estimé (DFGe) à l'amorce de la dialyse est de plus en plus reconnu comme un indicateur clé de la qualité (IQ) chez les patients atteints d'insuffisance rénale terminale (IRT). Plus précisément, les lignes directrices recommandent d'évaluer la possibilité de reporter l'initiation de la dialyse jusqu'à l'apparition des symptômes ou l'atteinte d'un DFGe égal ou inférieur à 6 ml/min/1,73 m2. Bien qu'on reconnaisse l'importance de cet IQ, on ignore encore comment le DFGe est défini, mesuré et suivi au moment de l'initiation de la dialyse dans les centres de dialyse canadiens. Objectifs: Déterminer la façon dont les programmes rénaux provinciaux définissent le DFGe à l'initiation de la dialyse, comparer les pratiques en cours dans les différentes provinces canadiennes et déterminer s'il existe une cible de référence commune pour une initiation différée de la dialyse. Conception: Un sondage transversal distribué entre juillet et novembre 2021 aux directeurs médicaux de chaque programme provincial de soins rénaux. Le Québec n'a pas été inclus puisque la province n'a pas encore participé au Registre canadien des insuffisances et des transplantations d'organes (RCITO). Cadre: Le sondage a été conçu et distribué par le Groupe de travail sur les indicateurs du Quality Improvement & Implementation Science Committee de la Société canadienne de néphrologie (CSN-QUIS). Méthodologie: Les répondants au sondage devaient décrire la façon dont le DFGe est défini, mesuré et rapporté, ainsi que les obstacles perçus à la collecte de données sur les IQ. Le sondage a été distribué aux directeurs médicaux provinciaux identifiés par le biais du National Senior Renal leaders Forum. Résultats: Le sondage a été distribué aux directeurs médicaux des neuf programmes provinciaux de soins rénaux participant au RCITO; huit ont répondu. Cinq provinces soumettent le DFGe pour toute nouvelle initiation d'un traitement de dialyse; trois provinces ne soumettent cette information que pour les patients atteints d'insuffisance rénale chronique. Il existe des différences entre les provinces dans la détermination du moment où un patient passe de l'insuffisance rénale aiguë nécessitant une dialyse à l'insuffisance rénale chronique. Quatre provinces utilisent un délai de 30 jours, trois provinces utilisent un délai de 90 jours et dans la dernière province, cette détermination est faite par le néphrologue du patient. Dans cinq des huit provinces sondées, le taux de créatinine utilisé pour établir le DFGe à l'initiation de la dialyse est la valeur mesurée à la première séance de dialyse (au jour 0); deux provinces utilisent la valeur de créatinine mesurée lors de la dernière visite en ambulatoire, et une province n'a pas de définition normalisée. Trois provinces n'ont pas de cible de référence pour le DFGe à l'initiation de la dialyse; cette cible est de moins de 9,5 ml/min/1,73 m2 dans une province, de moins de 10 ml/min/1,73 m2 dans trois provinces, et de moins de 15 ml/min/1,73 m2 dans une province. Les huit responsables médicaux provinciaux ayant répondu au sondage appuient l'établissement d'une valeur de référence nationale pour cette mesure. Limites: Ce sondage n'a été envoyé qu'aux directions médicales provinciales, par conséquent, il ne permet pas de déterminer les pratiques en cours dans chaque site de dialyse. Le sondage n'étant pas anonyme, il pourrait comporter un biais de conformité. Conclusion: Il existe une grande variabilité au Canada dans la façon dont le DFGe est mesuré et rapporté au début de la dialyse. On observe en outre une absence de consensus quant à une cible de référence pour une stratégie d'initiation différée de la dialyse. La normalisation de la valeur cible de DFGe au début de la dialyse pourrait faciliter les initiatives nationales de déclaration et d'amélioration de la qualité.

Reducing Dietary Acid With Fruit and Vegetables Versus Oral Alkali in People With Chronic Kidney Disease (ReDACKD): A Clinical Research Protocol.

Background: Individuals with chronic kidney disease (CKD) can develop metabolic acidosis which, in turn, is associated with faster progression of CKD and an increased need for dialysis. Oral sodium bicarbonate (the current standard of care therapy for metabolic acidosis) is poorly tolerated leading to low adherence. Base-producing or alkalizing Fruit and vegetables have potential as an alternative treatment for metabolic acidosis as they have been shown to reduce acid load arising from the diet. Objective: This trial will evaluate the feasibility of providing base-producing fruit and vegetables as a dietary treatment for metabolic acidosis, compared with oral sodium bicarbonate. Design: A 2-arm, open-label, dual-center, randomized controlled feasibility trial. Setting: Two Canadian sites: a nephrology clinic in Winnipeg, Manitoba, and a nephrology clinic in Halifax, Nova Scotia. Participants: Adult participants with G3-G5 CKD and metabolic acidosis. Measurements: Participants will undergo baseline measurements and attend 5 study visits over 12 months at which they will have a measurement of feasibility criteria as well as blood pressure, blood and urine biochemistry, 5-repetition chair stand test (STS5), and questionnaires to assess quality of life and symptoms. Furthermore, participants fill out Automated Self-Administered 24-hour recalls (ASA-24) in the beginning, middle, and end of trial. Methods: A total of 40 eligible participants will be randomized 1:1 to either base-producing fruit and vegetables (experimental) group or sodium bicarbonate (control) group, beginning from a daily dose of 1500 mg. Limitations: Using self-administered dietary assessments, lack of supervision over the consumption of study treatments and the possible disappointment of the control group for not receiving fruit and vegetables would be considered as limitations for this study. However, we are planning to undertake proper practices to overcome the possible limitations. These practices are discussed throughout the article in detail. Conclusions: This study will generate data on base-producing fruit and vegetables consumption as a dietary treatment for metabolic acidosis in CKD. The data will be used to design a future multi-center trial looking at slowing CKD progression in people with metabolic acidosis. Trial Registration: This study is registered on clinicaltrials.gov with the identifier NCT05113641.

Contexte: Les personnes atteintes d'insuffisance rénale chronique (IRC) courent le risque de développer une acidose métabolique, laquelle est associée à une progression plus rapide de l'IRC et à un besoin accru de dialyse. La prise de bicarbonate de sodium par voie orale (la norme actuelle de traitement de l'acidose métabolique) est mal tolérée, ce qui se traduit par une faible adhérence. Les fruit et légumes basiques ou alcalifiants ont un potentiel de traitement alternatif pour l'acidose métabolique, car il a été démontré qu'ils peuvent réduire la charge acide provenant de l'alimentation. Objectif: cet essai permettra d'évaluer la faisabilité d'un traitement alimentaire de l'acidose métabolique, en misant sur la consommation de fruit et légumes basiques ou alcalifiants, par rapport à la prise de bicarbonate de sodium par voie orale. Type d'étude: essai de faisabilité contrôlé, randomisé, ouvert, à deux bras, mené dans deux centres. Cadre: deux sites canadiens, soit une clinique de néphrologie à Winnipeg (Manitoba) et une autre à Halifax (Nouvelle-Écosse). Sujets: des patients adultes atteints d'IRC de stade G3-G5 et d'acidose métabolique. Mesures: les participants seront soumis à des mesures initiales et devront se présenter à cinq visites d'étude réparties sur 12 mois. Au cours de chacune, les patients subiront une mesure des critères de faisabilité, une mesure de la pression artérielle, un bilan sanguin et urinaire, un test de lever de chaise à cinq répétitions (STS5 ­ Five Times Sit to Stand Test) et devront répondre à des questionnaires évaluant la qualité de vie et les symptômes. Les participants devront également utiliser un outil en ligne de rappels alimentaires de 24 heures autoadministrés et automatisés (ASA24 ­ Automated Self-Administered 24-hours) au début, à mi-parcours et à la fin de l'essai. Méthodologie: 40 patients admissibles seront randomisés (1:1) dans le groupe expérimental (fruit et légumes basiques ou alcalifiants) ou dans le groupe témoin (bicarbonate de sodium) avec une dose quotidienne initiale de 1 500 mg. Limites: l'utilisation d'outils d'évaluation alimentaire autoadministrés, le manque de supervision de la consommation des traitements à l'étude et la possible déception du groupe témoin de ne pas recevoir de fruit et légumes constituent des limites pour cette étude. Nous prévoyons cependant adopter des pratiques appropriées pour surmonter ces possibles limites. Ces pratiques sont discutées plus en détail dans le manuscrit. Conclusion: cette étude produira des données sur la consommation de fruit et légumes basiques ou alcalifiants comme traitement alimentaire pour l'acidose métabolique en contexte d'IRC. Ces données seront utilisées pour concevoir un futur essai multicentrique visant à ralentir la progression de l'IRC chez les personnes atteintes d'acidose métabolique. Enregistrement de l'essai: Cette étude a reçu l'approbation du Conseil d'éthique de la recherche en santé de l'Université du Manitoba (HS24768 [B2021:025]) et est enregistrée sur ClinicalTrials.gov avec l'identifiant NCT05113641.

Patient and Provider Gender and Kidney Transplant Referral in Canada: A Survey of Canadian Healthcare Providers.

BACKGROUND: Referral for kidney transplant (KT) is variable, with women often disadvantaged. This study aimed to better characterize Canadian transplant referral practices and identify potential differences by respondent and/or patient gender using surveys targeted at healthcare practitioners (HCPs) involved in KT. METHODS: Surveys consisting of 25 complex patient cases representing 7 themes were distributed to KT HCPs across Canada (March 3, 2022-April 27, 2022) using national nephrology/transplant society email registries. Respondents were asked whether they would refer the patient for transplant. Two identical surveys were created, differing only by gender/gender pronouns used in each case. Multivariable logistic regression was used to assess the association of respondent demographics and patient themes (including case gender) with the odds of transplant referral (overall and stratifying by respondent gender). RESULTS: Overall, the referral rate was 58.0% among 97 survey respondents (46.4% male). Case themes associated with a lower likelihood of referral included adherence concerns (adjusted odds ratio [aOR] 0.65; 95% confidence interval [CI], 0.45-0.94), medical complexity (aOR 0.57; 95% CI, 0.38-0.85), and perceived frailty (aOR 0.63; 95% CI, 0.47-0.84). Respondent gender was not associated with differences in KT referral (aOR 0.91; 95% CI, 0.65-1.26 for male versus female respondents) but modified the association of frailty (less referral for male than female respondents, P = 0.005) and medical complexity (less referral for female than male respondents, P = 0.009) with referral. There were no differences in referral rate by case gender ( P = 0.82). CONCLUSIONS: KT referral practices vary among Canadian HCPs. In this study, there were no differences in likelihood of transplant referral by candidate gender.

The Impact of Combined Warm and Cold Ischemia Time on Post-transplant Outcomes.

Background: Prolonged warm ischemia time (WIT) and cold ischemia time (CIT) are independently associated with post-transplant graft failure; their combined impact has not been previously studied. We explored the effect of combined WIT/CIT on all-cause graft failure following kidney transplantation. Methods: The Scientific Registry of Transplant Recipients was used to identify kidney transplant recipients from January 2000 to March 2015 (after which WIT was no longer separately reported), and patients were followed until September 2017. A combined WIT/CIT variable (excluding extreme values) was separately derived for live and deceased donor recipients using cubic splines; for live donor recipients, the reference group was WIT 10 to <23 minutes and CIT >0 to <0.42 hours, and for deceased donor recipients the WIT was 10 to <25 minutes and CIT 1 to <7.75 hours. The adjusted association between combined WIT/CIT and all-cause graft failure (including death) was analyzed using Cox regression. Secondary outcomes included delayed graft function (DGF). Results: A total of 137 125 recipients were included. For live donor recipients, patients with prolonged WIT/CIT (60 to ≤120 minutes/3.04 to ≤24 hours) had the highest adjusted hazard ratio (HR) for graft failure (HR = 1.61, 95% confidence interval [CI] = 1.14-2.29 relative to the reference group). For deceased donor recipients, a WIT/CIT of 63 to ≤120 minutes/28 to ≤48 hours was associated with an adjusted HR of 1.35 (95% CI = 1.16-1.58). Prolonged WIT/CIT was also associated with DGF for both groups although the impact was more driven by CIT. Conclusions: Combined WIT/CIT is associated with graft loss following transplantation. Acknowledging that these are separate variables with different determinants, we emphasize the importance of capturing WIT and CIT independently. Furthermore, efforts to reduce WIT and CIT should be prioritized.

Contexte: La période prolongée d'ischémie à chaud (WIT­warm ischemia time) et la période prolongée d'ischémie à froid (CIT­cold ischemia time) ont été associées de façon indépendante à une défaillance du greffon post-transplantation, mais leur effet combiné n'a jamais été étudié. Nous avons examiné l'effet combiné WIT/CIT sur la défaillance du greffon toutes causes confondues après une transplantation rénale. Méthodologie: Le Scientific Registry of Transplant Recipients a été utilisé pour identifier les receveurs d'une greffe de rein entre janvier 2000 et mars 2015 (date après laquelle la WIT n'a plus été rapportée séparément). Les patients ont été suivis jusqu'en septembre 2017. Une variable combinée WIT/CIT (excluant les valeurs extrêmes) a été dérivée de façon isolée pour les donneurs vivants et les donneurs décédés à l'aide d'une fonction spline cubique. La WIT du groupe référence pour les donneurs vivants se situait entre 10 et <23 minutes, et la CIT entre 0 et <0,42 heure; pour les donneurs décédés, la WIT se situait entre 10 et <25 minutes, et la CIT entre 1 et <7,75 heures. L'association corrigée entre une combinaison WIT/CIT et la défaillance du greffon toutes causes confondues (y compris le décès) a été analysée à l'aide de la régression de Cox. Les résultats secondaires incluaient une reprise retardée de la fonction du greffon (RRFG). Résultats: Un total de 137 125 receveurs d'un rein a été inclus. Dans le groupe des receveurs d'un organe provenant d'un donneur vivant, les patients avec une WIT/CIT prolongée (60 à ≤120 minutes/3,04 à ≤24 heures) présentaient un risque relatif corrigé plus élevé de défaillance du greffon (RRc: 1,61; IC 95 %: 1,14-2,29) par rapport au groupe de référence. Dans le groupe des receveurs d'un organe provenant d'un donneur décédé, une combinaison WIT/CIT de 63 à ≤120 minutes/28 à ≤48 heures a été associée à un RRc de 1,35 (IC 95 %: 1,16-1,58). La WIT/CIT prolongée a également été associée à une RRFG pour les deux groupes, bien que cet effet ait été davantage influencé par la CIT. Conclusion: La combinaison WIT/CIT est associée à la perte du greffon après la transplantation. Sachant qu'il s'agit de variables distinctes avec des déterminants différents, nous soulignons l'importance de rapporter la WIT et la CIT de façon indépendante. Qui plus est, les efforts visant à réduire la WIT et la CIT devraient être prioritaires.

Development of a consortium to examine organ donation legislative and system reforms: A report from the LEADDR consortium.

In April 2019, the province of Nova Scotia became the first jurisdiction in North America to pass legislation that incorporated deemed consent for deceased organ donation. The reform included many other important updates, including the hierarchy for consent, enabled donor and recipient contact, and mandatory referral of potential deceased donors. Additionally, system reforms were implemented to improve the deceased donation system in Nova Scotia. A collection of national colleagues identified the magnitude of the opportunity to develop a comprehensive strategy to measure and evaluate the impact of the legislative and system reforms. This article describes the successful development of a consortium from both national and provincial jurisdictions that included experts from a variety of backgrounds and clinical and administrative disciplines. In describing the creation of this group, we hope to offer our case example as a model for the evaluation of other health system reforms from a multidisciplinary perspective.

Single cell G-protein coupled receptor profiling of activated kidney fibroblasts expressing transcription factor 21.

BACKGROUND AND PURPOSE: Activated fibroblasts deposit fibrotic matrix in chronic kidney disease (CKD) and G-protein coupled receptors (GPCRs) are the most druggable therapeutic targets. Here, we set out to establish a transcriptional profile that identifies activated kidney fibroblasts and the GPCRs that they express. EXPERIMENTAL APPROACH: RNA sequencing and single cell qRT-PCR were performed on mouse kidneys after unilateral ureteral obstruction (UUO). Candidate expression was evaluated in mice with UUO or diabetes or injected with adriamycin or folic acid. Intervention studies were conducted in mice with diabetes or UUO. Correlative histology was performed in human kidney tissue. KEY RESULTS: Transcription factor 21 (Tcf21)+ cells that expressed 2 or 3 of Postn, Acta2 and Pdgfra were highly enriched for fibrogenic genes and were defined as activated kidney fibroblasts. Tcf21+ α-smooth muscle actin (α-SMA)+ interstitial cells accumulated in kidneys of mice with UUO or diabetes or injected with adriamycin or folic acid, whereas renin-angiotensin system blockade attenuated increases in Tcf21 in diabetic mice. Fifty-six GPCRs were up-regulated in single Tcf21+ kidney fibroblasts, the most up-regulated being Adgra2 and S1pr3. Adenosine receptors, Adora2a/2b, were up-regulated in Tcf21+ fibroblasts and the adenosine receptor antagonist, caffeine decreased Tcf21 upregulation and kidney fibrosis in UUO mice. TCF21, ADGRA2, S1PR3 and ADORA2A/2B were each detectable in α-SMA+ interstitial cells in human kidney samples. CONCLUSION AND IMPLICATIONS: Tcf21 is a marker of kidney fibroblasts that are enriched for fibrogenic genes in CKD. Further analysis of the GPCRs expressed by these cells may identify new targets for treating CKD. LINKED ARTICLES: This article is part of a themed issue on Translational Advances in Fibrosis as a Therapeutic Target. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.22/issuetoc.