Low incidence of de novo HLA antibodies after COVID-19 vaccination: A cohort study of patients awaiting kidney transplantation.

BACKGROUND: Antibodies against human leukocyte antigen (anti-HLA Abs) are associated with an increased risk of allograft loss. Herein, we report the prospective follow-up for anti-HLA Abs formation in 103 patients with end-stage kidney disease on the waiting list for transplantation who underwent COVID-19 vaccination. PATIENTS AND METHODS: Sera were tested before and after vaccination using Luminex technology. The cohort comprised of 62 males and 41 females with a mean age of 56 ± 14 years. The patients received BNT162b2 (80.4%), mRNA-1273 (18.5%), AZD1222 (0.40%), or ChAdOx1-S (0.80%) vaccine. Patients were tested before and within 119 ± 50, 95 ± 46 and 25 ± 26 days after the first, second, and third dose of the vaccine, respectively. RESULTS: No significant change in calculated panel reactive antibody (cPRA) after vaccination was seen. Although 98.1% of patients had no change in anti-HLA Abs profile or cPRA after vaccination, two patients (1.9%) developed de novo anti-HLA Abs against class I or II HLA antigens. In those two patients, the cPRA changed from 0% and 63% at baseline to 9% and 90% after vaccination, respectively. Both patients received the BNT162b2 mRNA-based vaccine. The earliest detected anti-HLA Abs was 18 days after the first dose. CONCLUSION: In rare cases, new anti-HLA antibodies were observed after COVID-19 vaccination, with potential implications for transplantation. The low incidence of this phenomenon is outweighed by the clinical benefits of vaccination.

Outcomes of the First and Second Hemodialysis Fistula: A Cohort Study.

RATIONALE & OBJECTIVE: Fistulas are the preferred form of hemodialysis access; however, many fistulas fail to mature into usable accesses after creation. Data for outcomes after placement of a second fistula are limited. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: People who initiated hemodialysis therapy in any of 5 Canadian dialysis programs (2004-2012) and had at least 1 hemodialysis fistula placed. PREDICTOR: Second versus initial fistula; receipt of 2 versus 1 fistula; second versus first fistula in recipients of 2 fistulas. OUTCOMES: Catheter-free fistula use during 1 year following initiation of hemodialysis therapy or following fistula creation, if created after hemodialysis therapy start; proportion of time with catheter-free use; time to catheter free use; time of functional patency. ANALYTICAL APPROACH: Logistic regression; fractional regression. RESULTS: Among the 1,091 study participants (mean age, 64±15 [SD] years; 63% men; 59% with diabetes), 901 received 1 and 190 received 2 fistulas. 38% of second fistulas versus 46% of first fistulas were used catheter free at least once. Average percentages of time that second and initial fistulas were used catheter free were 34% and 42%, respectively (OR, 0.72; 95% CI, 0.54-0.94). Compared with people who received 1 fistula, those who received 2 fistulas were less likely to achieve catheter-free use (26% vs 56%) and remain catheter free (23% vs 49% of time; OR, 0.30, 95% CI, 0.24-0.39). Among people who received 2 fistulas, the proportion of time that the second fistula was used catheter free was 11% higher with each 10% greater proportion of time that the first fistula was used catheter free (95% CI, 1%-22%). Model discrimination was modest (C index, 0.69). LIMITATIONS: Unknown criteria for patient selection for 1 or 2 fistulas; unknown reasons for prolonged catheter use. CONCLUSIONS: Outcomes of a second fistula may be inferior to outcomes of the initial fistula. First and second fistula outcomes are weakly correlated and difficult to predict based on clinical characteristics.

The Effect of Predialysis Fistula Attempt on Risk of All-Cause and Access-Related Death.

Whether the lower risk of mortality associated with arteriovenous fistula use in hemodialysis patients is due to the avoidance of catheters or if healthier patients are simply more likely to have fistulas placed is unknown. To provide clarification, we determined the proportion of access-related deaths in a retrospective cohort study of patients aged ≥18 years who initiated hemodialysis between 2004 and 2012 at five Canadian dialysis programs. A total of 3168 patients initiated dialysis at the participating centers; 2300 met our inclusion criteria. Two investigators independently adjudicated cause of death using explicit criteria and determined whether a death was access-related. We observed significantly lower mortality in individuals who underwent a predialysis fistula attempt than in those without a predialysis fistula attempt in patients aged <65 years (hazard ratio [HR], 0.49; 95% confidence interval [95% CI], 0.29 to 0.82) and in the first 2 years of follow-up in those aged ≥65 years (HR0-24 months, 0.60; 95% CI, 0.43 to 0.84; HR24+ months, 1.83; 95% CI, 1.25 to 2.67). Sudden deaths that occurred out of hospital accounted for most of the deaths, followed by deaths due to cardiovascular disease and infectious complications. We found only 2.3% of deaths to be access-related. In conclusion, predialysis fistula attempt may associate with a lower risk of mortality. However, the excess mortality observed in patients treated with catheters does not appear to be due to direct, access-related complications but is likely the result of residual confounding, unmeasured comorbidity, or treatment selection bias.

Sudden onset of parathyroid hormone-independent severe hypercalcemia from reversal of tumoral calcinosis in a dialysis patient.

BACKGROUND: Tumoral calcinosis is a rare manifestation of extraskeletal calcification, featuring large calcified cystic masses in the periarticular regions of large joints. In chronic kidney disease (CKD), this disorder is thought to evolve through a chronically elevated calcium-phosphorus solubility product leading to calcium precipitation in soft tissue. Treating tumoral calcinosis in these patients involves interventions to lower the calcium-phosphorus product such as reduction in vitamin D therapy and intensive hemodialysis regimens. CASE PRESENTATION: We report the case of a 54-year old woman with polycystic kidney disease on peritoneal dialysis with widespread tumoral calcinosis in the context of hypercalcemic tertiary hyperparathyroidism who had been on long-term alfacalcidol therapy. After withdrawal of the vitamin D analogue and initiation of daily hemodialysis, there was rapid dissolution of her tumoral calcium deposits with the abrupt onset of parathyroid hormone (PTH)-independent transient hypercalcemia that resolved once the soft tissue deposits disappeared. CONCLUSIONS: Resorption of soft tissue calcific deposits may result in transient parathyroid hormone (PTH)-independent hypercalcemia. In CKD patients, this hypercalcemia causes a decrease in the PTH level, distinguishing it from tertiary hyperparathyroidism, though PTH may not be totally suppressed, the way it is seen in PTH-independent hypercalcemia in non-CKD patients.

Antineutrophil Cytoplasmic Antibody Induction due to Infection: A Patient with Infective Endocarditis and Chronic Hepatitis C.

While antineutrophil cytoplasmic antibody (ANCA) is often used as a diagnostic marker for certain vasculitides, ANCA induction in the setting of infection is much less common. In the case of infective endocarditis, patients may present with multisystem disturbances resembling an autoimmune process, cases that may be rendered even trickier to diagnose in the face of a positive ANCA. Though not always straightforward, distinguishing an infective from an inflammatory process is pivotal in order to guide appropriate therapy. We describe an encounter with a 43-year-old male with chronically untreated hepatitis C virus infection who featured ANCA positivity while hospitalized with acute bacterial endocarditis. His case serves as a reminder of two of the few infections known to uncommonly generate ANCA positivity. We also summarize previously reported cases of ANCA positivity in the context of endocarditis and hepatitis C infections.

Progression of Kidney Disease in Kidney Transplant Recipients With a Failing Graft: A Matched Cohort Study.

Background: Few studies have assessed outcomes in transplant recipients with failing grafts as most studies have focused on outcomes after graft loss. Objective: To determine whether renal function declines faster in kidney transplant recipients with a failing graft than in people with chronic kidney disease of their native kidneys. Design: Retrospective cohort study. Setting: Alberta, Canada (2002-2019). Patients: We identified kidney transplant recipients with a failing graft (2 estimated glomerular filtration rate [eGFR] measurements 15-30 mL/min/1.73 m2 ≥90 days apart). Measurements: We compared the change in eGFR over time (eGFR with 95% confidence limits, LCLeGFRUCL) and the competing risks of kidney failure and death (cause-specific hazard ratios [HRs], LCLHRUCL). Methods: Recipients (n = 575) were compared with propensity-score-matched, nontransplant controls (n = 575) with a similar degree of kidney dysfunction. Results: The median potential follow-up time was 7.8 years (interquartile range, 3.6-12.1). The hazards for kidney failure (HR1.101.331.60) and death (HR1.211.592.07) were significantly higher for recipients, while the eGFR decline over time was similar (recipients vs controls: -2.60-2.27-1.94 vs -2.52-2.21-1.90 mL/min/1.73 m2 per year). The rate of eGFR decline was associated with kidney failure but not death. Limitations: This was a retrospective, observational study, and there is a risk of bias due to residual confounding. Conclusions: Although eGFR declines at a similar rate in transplant recipients as in nontransplant controls, recipients have a higher risk of kidney failure and death. Studies are needed to identify preventive measures to improve outcomes in transplant recipients with a failing graft.

Contexte: Peu d'études ont évalué les résultats chez les patients transplantés dont le greffon est défaillant; la majorité des études s'étant plutôt concentrées sur les résultats après la perte du greffon. Objectif: Vérifier si la fonction rénale décline plus rapidement chez les patients transplantés dont le greffon est défaillant que chez les personnes souffrant d'une insuffisance chronique sur reins natifs. Conception: Étude de cohorte rétrospective. Cadre: Alberta, Canada (2002 à 2019). Sujets: Nous avons identifié des patients transplantés dont le greffon est défaillant (défini par deux mesures du débit de filtration glomérulaire estimé [DFGe] de 15-30 ml/min/1,73 m2 à au moins 90 jours d'intervalle). Mesures: Nous avons comparé l'évolution du DFGe dans le temps (DFGe avec intervalles de confiance [IC] à 95 % inférieur et supérieur: ICIDFGeICS) et les rapports de risque d'insuffisance rénale et de décès (intervalles de rapport de risque (RR) lié à la cause: ICIRRICS). Méthodologie: Les transplantés dont le greffon est défaillant (n=575) ont été comparés à des témoins non transplantés (n=575) appariés selon le score de propension et présentant un niveau similaire de dysfonctionnement rénal. Résultats: Le temps médian de suivi potentiel était de 7,8 ans (ÉIQ: 3,6 à 12,1). Les risques d'insuffisance rénale (RR: 1,101,331,60) et de décès (RR: 1,211,592,07) étaient significativement plus élevés chez les transplantés dont le greffon est défaillant, mais le déclin du DFGe au fil du temps était similaire dans les deux groupes (receveurs: -2,60-2,27-1,94 ml/min/1,73 m2 par an; témoins: -2,52-2,21-1,90 ml/min/1,73 m2 par an). Le taux de déclin du DFGe a été associé à une insuffisance rénale terminale, mais pas au décès. Limites: Il s'agit d'une étude observationnelle rétrospective et il existe un risque de biais dû à des facteurs de confusion résiduels. Conclusion: Bien que le DFGe décline à un rythme similaire chez les transplantés dont le greffon est défaillant et les témoins non transplantés, le risque d'insuffisance rénale terminale et de décès est plus élevé pour les transplantés. D'autres études sont nécessaires pour identifier les mesures préventives qui pourraient améliorer les résultats des patients transplantés dont le greffon est défaillant.

The Influence of Age on the Likelihood of Catheter-Free Fistula Use in Hemodialysis Patients.

BACKGROUND: Clinical practice guidelines recommend arteriovenous fistulas as the preferred form of vascular access for hemodialysis. However, some studies have suggested that older age is associated with poorer fistula outcomes. OBJECTIVE: We assessed the impact of age on the outcomes of fistula creation and access-related procedures. DESIGN: This was a prospective cohort study using data collected as part of the Dialysis Measurement Analysis and Reporting (DMAR) system. SETTING: Participating Canadian dialysis programs, including Southern Alberta Renal Program, Manitoba Renal Program, Sunnybrook Health Sciences Centre (Toronto, Ontario), London Health Sciences Centre (London, Ontario), and The Ottawa Hospital (Ottawa, Ontario). PATIENTS: Incident hemodialysis patients aged 18 years and older who started dialysis between January 1, 2004, and May 31, 2012. MEASUREMENTS: The primary outcome was the proportion of all first fistula attempts that resulted in catheter-free fistula use, defined as independent use of a fistula for hemodialysis (ie, no catheter in place). Secondary outcomes included the time to catheter-free fistula use among patients with a fistula creation attempt, total number of days of catheter-free fistula use, and the proportion of a patient's hemodialysis career spent with an independently functioning fistula (ie, catheter-free fistula use). METHODS: We compared patient characteristics by age group, using t tests or Wilcoxon rank sum tests, and chi-square or Fisher exact tests, as appropriate. Logistic and fractional logistic regression were used to estimate the odds of achieving catheter-free fistula use by age group and the proportion of dialysis time spent catheter-free, respectively. RESULTS: A total of 1091 patients met our inclusion criteria (567 age ≥ 65; 524 age < 65). Only 57% of first fistula attempts resulted in catheter-free fistula use irrespective of age (adjusted odds ratio [OR]≥65vs<65: 1.01; P = .93). The median time from hemodialysis start to catheter-free use of the first fistula did not differ by age when grouped into fistulas attempted pre- and post-dialysis initiation. The adjusted rates of access-related procedures were comparable (incidence rate ratio [IRR]≥65vs<65: 0.95; P = .32). The median percentage of follow-up time spent catheter-free was similar and low in patients who attempted fistulas (<65 years: 19% vs ≥65 years: 21%; P = .85). LIMITATIONS: The relatively short follow-up time may have underestimated the benefits of fistula creation and the observational study design precludes inferences about causality. CONCLUSIONS: In our study, older patients who underwent a fistula attempt were just as likely as younger patients to achieve catheter-free fistula use, within a similar time frame, and while requiring a similar number of access procedures. However, the minority of dialysis time was spent catheter-free.

CONTEXTE: Les lignes directrices cliniques recommandent de privilégier la fistule artérioveineuse comme accès vasculaire pour l'hémodialyse. Certaines études suggèrent toutefois que les résultats seraient moins bons chez les patients âgés. OBJECTIF: Nous avons examiné l'effet de l'âge du patient sur l'issue de la création d'une fistule et sur les procédures liées à l'accès. TYPE D'ÉTUDE: Il s'agit d'une étude de cohorte prospective utilisant les données colligées par le système DMAR (Dialysis Measurement Analysis and Reporting). CADRE: Les programmes de dialyse canadiens participants, soit le Southern Alberta Renal Program, le Manitoba Renal Program, le Sunnybrook Health Sciences Centre (Toronto, Ontario), le London Health Sciences Centre (London, Ontario), et l'hôpital d'Ottawa (Ottawa, Ontario). SUJETS: Les patients adultes incidents ayant amorcé une hémodialyse entre le 1er janvier 2004 et le 31 mai 2012. MESURES: La principale mesure était la proportion de premières fistules créées ayant mené à une utilisation sans cathéter, soit à un usage indépendant pour l'hémodialyse. Les mesures secondaires incluaient le temps écoulé jusqu'à l'utilisation d'une fistule sans cathéter pour les patients ayant subi une première tentative, le nombre total de jours d'utilisation d'une fistule sans cathéter, et la proportion du temps de dialyse passé avec une fistule indépendante fonctionnelle (sans cathéter). MÉTHODOLOGIE: Nous avons comparé les caractéristiques des patients par groupe d'âge à l'aide de tests t ou de tests de somme des rangs de Wilcoxon, et de tests chi-deux ou de tests exacts de probabilité de Fisher, selon le cas. Une régression logistique et une régression logistique fractionnée ont été employées pour estimer respectivement, selon le groupe d'âge, les chances d'utiliser une fistule sans cathéter et la proportion du temps de dialyse passé sans cathéter. RÉSULTATS: Au total, 1 091 patients satisfaisaient nos critères d'inclusion (n=567 [≥65 ans]; n=524 [<65 ans]). Seulement 57 % des premières tentatives de création d'une fistule ont mené à une utilisation sans cathéter, indépendamment de l'âge (rapport de cote corrigé [RC]≥65contre<65: 1,01; p=0,93). Le temps médian jusqu'à l'utilisation sans cathéter de la première fistule créée n'a pas varié en fonction de l'âge lorsque les patients ont été groupés selon que la fistule avait été créée avant ou après l'amorce de la dialyse. Les taux corrigés de procédures liées à l'accès vasculaire étaient similaires (rapport des taux d'incidence [RTI]≥65contre<65 0,95; p=0,32); tout comme le pourcentage médian de temps de dialyse passé sans cathéter qui s'est avéré faible pour tous les patients (19 % [<65 ans] contre 21 % [≥65 ans]; p=0,85). LIMITES: La période de suivi relativement courte pourrait avoir sous-estimé les avantages de créer une fistule, et la nature observationnelle de l'étude ne permet pas de tirer de conclusions sur la causalité. CONCLUSION: Selon notre étude, les patients âgés avaient autant de chance que les plus jeunes d'utiliser la fistule sans cathéter, et ce, dans un délai semblable et avec sensiblement le même nombre de procédures liées à l'accès vasculaire. Néanmoins, la proportion du temps de dialyse passé sans cathéter était faible.

A Description of Advanced Chronic Kidney Disease Patients in a Major Urban Center Receiving Conservative Care.

BACKGROUND: Conservative/palliative (nondialysis) management is an option for some individuals for treatment of stage 5 chronic kidney disease (CKD). Little is known about these individuals treated with conservative care in the Canadian setting. OBJECTIVE: To describe the characteristics of patients treated with conservative care for category G5 non-dialysis CKD in a Canadian context. DESIGN: Retrospective chart review. SETTING: Urban nephrology center. PATIENTS: Patients with G5 non-dialysis CKD (estimated glomerular filtration rate <15 mL/min/1.73 m2). MEASUREMENTS: Baseline patient demographic and clinical characteristics of conservative care follow-up, advanced care planning, and death. METHODS: We undertook a descriptive analysis of individuals enrolled in a conservative care program between January 1, 2009, and June 30, 2015. RESULTS: One hundred fifty-four patients were enrolled in the conservative care program. The mean age and standard deviation was 81.4 ± 9.0 years. The mean modified Charlson Comorbidity Index score was 3.4 ± 2.8. The median duration of conservative care participation was 11.5 months (interquartile range: 4-25). Six (3.9%) patients changed their modality to dialysis. One hundred three (66.9%) patients died during the study period. Within the deceased cohort, most (88.2%) patients completed at least some advanced care planning before death, and most (81.7%) of them died at their preferred place. Twenty-seven (26.7%) individuals died in hospital. LIMITATIONS: Single-center study with biases inherent to a retrospective study. Generalizability to non-Canadian settings may be limited. CONCLUSIONS: We found that individuals who chose conservative care were very old and did not have high levels of comorbidity. Few individuals who chose conservative care changed modality and accepted dialysis. The proportions of engagement in advanced care planning and of death in place of choice were high in this population. Death in hospital was uncommon in this population.

CONTEXTE: Les traitements conservateurs ou soins palliatifs (sans dialyse) constituent une option thérapeutique pour certaines personnes atteintes 'd'insuffisance rénale chronique non-dialyse de catégorie 5 (IRC-ND). Toutefois, nous en savons peu au sujet des personnes inscrites à un programme de traitement conservateur dans le contexte canadien. OBJECTIF DE L'ÉTUDE: Faire le portrait des patients atteints d'IRC-ND G5, sous traitement conservateur dans un contexte canadien. TYPE D'ÉTUDE: Examen rétrospectif des dossiers médicaux. CADRE DE L'ÉTUDE: Un centre de néphrologie en milieu urbain. PATIENTS: Des patients atteints d'IRC-ND G5 (débit de filtration glomérulaire estimé à moins de 15 ml/min/1,73 m2). MESURES: Les données démographiques initiales des patients, de même que les données cliniques de suivi du traitement conservateur, de planification des soins avancés et du décès. MÉTHODOLOGIE: Nous avons entrepris l'analyse descriptive des individus inscrits à un programme de traitement conservateur pour la période s'échelonnant du 1er janvier 2009 au 30 juin 2015. RÉSULTATS: Au total, 154 patients ont été inscrits dans un programme de traitement conservateur au cours de la période étudiée. L'âge moyen des patients était de 81,4 ans avec un écart-type de ± 9,0 ans. Le score moyen à l'index de comorbidité de Charlson modifié était de 3,4 ± 2,8 et la durée médiane de participation à un programme de traitement conservateur était de 11,5 mois (écart interquartile de 4,25). Au cours de la période étudiée, six patients (3,9%) sont passés du traitement conservateur à la dialyse et 103 patients (66,9%) sont décédés. Au sein de la cohorte de patients décédés, la grande majorité (88,2%) avait complété une partie des soins avancés planifiés avant le décès. De cette même cohorte, la plupart (81,7%) sont décédés où ils l'avaient choisi alors que 27 personnes (26,7%) sont décédées à l'hôpital. LIMITES DE L'ÉTUDE: L'étude s'est tenue au sein d'un seul centre hospitalier et comporte des biais inhérents attribuables à son modèle rétrospectif. De plus, la généralisation des résultats à des paramètres non canadiens peut être limitée. CONCLUSIONS: Nous avons constaté que les personnes qui avaient opté pour un traitement conservateur étaient très âgées et présentaient peu de comorbidités. Au cours de la période étudiée, quelques patients qui avaient choisi un traitement conservateur ont changé de modalité et accepté de passer à la dialyse. Nous avons également observé que l'engagement dans la planification des soins avancés et dans le choix de l'endroit où mourir était élevé au sein de cette population, alors que le décès à l'hôpital a été plutôt rare.

Multi-Disciplinary Vascular Access Care and Access Outcomes in People Starting Hemodialysis Therapy.

BACKGROUND AND OBJECTIVES: Fistulas, the preferred form of hemodialysis access, are difficult to establish and maintain. We examined the effect of a multidisciplinary vascular access team, including nurses, surgeons, and radiologists, on the probability of using a fistula catheter-free, and rates of access-related procedures in incident patients receiving hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We examined vascular access outcomes in the first year of hemodialysis treatment before (2004-2005, preteam period) and after the implementation of an access team (2006-2008, early-team period; 2009-2011, late-team period) in the Calgary Health Region, Canada. We used logistic regression to study the probability of fistula creation and the probability of catheter-free fistula use, and negative binomial regression to study access-related procedure rates. RESULTS: We included 609 adults (mean age, 65 [±15] years; 61% men; 54% with diabetes). By the end of the first year of hemodialysis, 102 participants received a fistula in the preteam period (70%), 196 (78%) in the early-team period (odds ratios versus preteam, 1.47; 95% confidence interval, 0.92 to 2.35), and 139 (66%) in the late-team period (0.85; 0.54 to 1.35). Access team implementation did not affect the probability of catheter-free use of the fistula (odds ratio, 0.87; 95% confidence interval, 0.52 to 1.43, for the early; and 0.89; 0.52 to 1.53, for the late team versus preteam period). Participants underwent an average of 4-5 total access-related procedures during the first year of hemodialysis, with higher rates in women and in people with comorbidities. Catheter-related procedure rates were similar before and after team implementation; relative to the preteam period, fistula-related procedure rates were 40% (20%-60%) and 30% (10%-50%) higher in the early-team and late-team periods, respectively. CONCLUSION: Introduction of a multidisciplinary access team did not increase the probability of catheter-free fistula use, but resulted in higher rates of fistula-related procedures.

Hyperchloremic Metabolic Acidosis due to Cholestyramine: A Case Report and Literature Review.

Cholestyramine is a bile acid sequestrant that has been used in the treatment of hypercholesterolemia, pruritus due to elevated bile acid levels, and diarrhea due to bile acid malabsorption. This medication can rarely cause hyperchloremic nonanion gap metabolic acidosis, a complication featured in this report of an adult male with concomitant acute kidney injury. This case emphasizes the caution that must be taken in prescribing cholestyramine to patients who may also be volume depleted, in renal failure, or taking spironolactone.