Background: Chronic kidney disease (CKD) affects over 10% of the global population. A genetic diagnosis can be identified in about 30% of pediatric and 10-30% of adults, informing treatment, prognosis, and family-based risk assessment. However, access to renal genetics services remains limited across many healthcare systems. Objectives: To characterize the clinical and genetic landscape of CKD in patients referred for genetic evaluation within a Canadian single-centre nephrology-genetics program, and to evaluate the diagnostic yield and clinical utility of an integrated renal genetics clinic. Methods: We conducted a retrospective study of 206 probands referred for suspected hereditary kidney disease to the McGill University Health Centre Renal Genetics Clinic between 2019 and 2024. Genetic testing was performed in accredited laboratories, predominantly through comprehensive multi-gene panels or phenotype-directed exome sequencing. All reported variants were classified according to the ACMG/AMP criteria, and variants of uncertain significance were reevaluated post hoc using standardized quantitative and evidence-tier frameworks to determine whether they trended toward "likely pathogenic" ("hot") or "likely benign" ("cold"), without implying formal reclassification. Results: A molecular diagnosis was established in 34.5% of probands (71/206), implicating pathogenic or likely pathogenic variants across 35 genes representing diverse monogenic kidney disease etiologies. The highest diagnostic yields were observed in cystic nephropathy (51.9%), tubulopathy (38.5%), and glomerulopathy (35.6%). Genetic results affected clinical management in 23.9% of diagnosed cases, leading to changes in treatment for 16.9%, modification of transplant management in 5.6%, informed living donor risk assessment in 14.1%, and facilitated cascade testing in 66.2% of families. CKD of unknown etiology comprised 28% of the cohort, with a genetic diagnosis reached in 25.9% of these cases. Variants of uncertain significance (VUS) were reported in 39.3% of probands, with higher overall variant burden and lower diagnostic yields among individuals of non-European ancestry. Post hoc internal reassessment stratified 67.4% of VUS as mid or lower confidence ("cold") and 31.4% as higher confidence ("hot") or likely pathogenic. Conclusions: In a diverse urban population, integration of a dedicated renal genetics service within nephrology care achieved high diagnostic yield, substantially influenced management, and facilitated family risk assessment. Structured referral pathways and multidisciplinary variant interpretation optimize the clinical utility of genetic testing in CKD. ### Competing Interest Statement All authors have completed the ICMJE uniform disclosure form and declare: support for the submitted work as follows: T. M. Kitzler reports institutional funding from the SickKids New Investigator Research Grant (NI21-1159); the following authors report financial relationships with organizations that might have an interest in the submitted work in the previous three years: A. Alam has served as site principal investigator on studies sponsored by Otsuka Canada and Vertex and received consulting fees and honoraria from Otsuka Canada; D. Blum has served on advisory boards for Otsuka and Bayer; M. Cantarovich has received honoraria from Sanofi for a speaker tour; T. Takano has served on an Otsuka Canada advisory board and received honoraria from Chugai Pharma; T. M. Kitzler received a one-time honorarium from Otsuka Canada; R. Sapir-Pichhadze reports institutional support to the MUHC Foundation from Paladin for a fellowship and honoraria from The Transplantation Society and the Banff Foundation; no other authors have financial relationships with organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. ### Funding Statement This work was supported by a Fonds de recherche du Québec - Santé Junior 1 Clinician-Scientist Award to T.K. and the SickKids New Investigator Research Grant (NI21-1159). Z.S. received a Canadian Institutes of Health Research Doctoral Research Award. Dr. Sandal is supported by the Fonds de recherche du Québec - Santé Junior 1. The funders had no role in study design, data collection, analysis, interpretation, or manuscript preparation ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: McGill University Health Centre Research Ethics Board gave ethical approval for this work (Protocol 2025-10930). The same board gave ethical approval for participant reanalysis and expanded testing, and for the presentation of case-specific clinical information (Protocol 2023-9387). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All non-identifiable participant data underlying the results are available from the corresponding author upon reasonable request

Peritoneal dialysis-related infections, including peritonitis, exit site infections, and tunnel infections, remain an important cause of morbidity and technique failure. While peritonitis is usually the most frequent and morbid event among the infectious complications, exit site and tunnel infections are relevant and concerning complications of peritoneal dialysis. This chapter will focus on the risk factors for their occurrence, as well as optimal strategies for their prevention and management.

Purpose of review: Kidney disease is present in almost half of Canadian patients with type 2 diabetes (T2D), and it is also the most common first cardiorenal manifestation of T2D. Despite clear guidelines for testing, opportunities are being missed to identify kidney diseases, and many Canadians are therefore not receiving the best available treatments. This has become even more important given recent clinical trials demonstrating improvements in both kidney and cardiovascular (CV) endpoints with sodium-glucose cotransporter 2 (SGLT2) inhibitors and a nonsteroidal mineralocorticoid receptor antagonist, finerenone. The goal of this document is to provide a narrative review of the current evidence for the treatment of diabetic kidney disease (DKD) that supports this new standard of care and to provide practice points. Sources of information: An expert panel of Canadian clinicians was assembled, including 9 nephrologists, an endocrinologist, and a primary care practitioner. The information the authors used for this review consisted of published clinical trials and guidelines, selected by the authors based on their assessment of their relevance to the questions being answered. Methods: Panelists met virtually to discuss potential questions to be answered in the review and agreed on 10 key questions. Two panel members volunteered as co-leads to write the summaries and practice points for each of the identified questions. Summaries and practice points were distributed to the entire author list by email. Through 2 rounds of online voting, a second virtual meeting, and subsequent email correspondence, the authors reached consensus on the contents of the review, including all the practice points. Key findings: It is critical that DKD be identified as early as possible in the course of the disease to optimally prevent disease progression and associated complications. Patients with diabetes should be routinely screened for DKD with assessments of both urinary albumin and kidney function. Treatment decisions should be individualized based on the risks and benefits, patients’ needs and preferences, medication access and cost, and the degree of glucose lowering needed. Patients with DKD should be treated to achieve targets for A1C and blood pressure. Renin-angiotensin-aldosterone system blockade and treatment with SGLT2 inhibitors are also key components of the standard of care to reduce the risk of kidney and CV events for these patients. Finerenone should also be considered to further reduce the risk of CV events and chronic kidney disease progression. Education of patients with diabetes prescribed SGLT2 inhibitors and/or finerenone is an important component of treatment. Limitations: No formal guideline process was used. The practice points are not graded and are not intended to be viewed as having the weight of a clinical practice guideline or formal consensus statement. However, most practice points are well aligned with current clinical practice guidelines.

Key Points In a large multinational cohort of PD patients, any GAS use was not associated with an increased risk of all-organism peritonitis. For peritonitis, risks were particularly high among certain classes of organisms particularly for Gram-negative, enteric, and streptococcal peritonitis episodes. The association with enteric peritonitis appeared to be stronger among H2RA users. Background Peritonitis is a major peritoneal dialysis–related complication. We determined whether gastric acid suppression (GAS) (proton pump inhibitor [PPI] or histamine-2 receptor antagonists [H2RAs]) use was associated with all-cause and organism-specific peritonitis in peritoneal dialysis patients. Methods In the Peritoneal Dialysis Outcomes and Practice Patterns Study (595 facilities, eight countries, years 2014–2022), associations between GAS use and time to first episode of all-cause peritonitis were examined using Cox proportional hazards models. The primary exposure of interest was GAS and secondarily PPI or H2RA use. Secondary outcomes were organism-specific peritonitis, peritonitis cure rates, and death. Results Among patients ( N =23,797) at study baseline, 6020 (25.3%) used PPIs, and 1382 (5.8%) used H2RAs. Overall risks of GAS use and peritonitis risk (adjusted hazard ratio [AHR]=1.05, 95% confidence interval [CI], 0.98 to 1.13]) and use of PPI (AHR 1.06 [95% CI, 0.99 to 1.14]) or H2RA (AHR 1.02 [95% CI, 0.88 to 1.18]) did not reach statistical significance. In organism-specific analyses, GAS users displayed higher peritonitis risks for Gram-negative (AHR 1.29, 95% CI, 1.05 to 1.57), Gram-positive (AHR 1.15, 95% CI, 1.01 to 1.31), culture-negative (AHR 1.20, 95% CI, 1.01 to 1.42), enteric (AHR 1.23, 95% CI, 1.03 to 1.48), and particularly Streptococcal (AHR 1.47, 95% CI, 1.15 to 1.89) peritonitis episodes. GAS was also associated with higher overall mortality (AHR 1.13 [95% CI, 1.05 to 1.22]). Conclusion The association between GAS use and peritonitis risk was weaker (hazard ratio [HR] 1.05 [0.98 to 1.13]) than for streptococcal (HR 1.57 [1.15 to 1.89]) and Gram-negative (HR 1.29 [1.05 to 1.57]) peritonitis. A better understanding of mechanisms surrounding the differential effects of GAS subtype on peritonitis risks is needed. Clinicians should be cautious when prescribing GAS. The impact of GAS deprescribing on peritonitis risk requires further evaluation.

Peritoneal dialysis (PD)-related infection is a major complication of PD, accounting for 47% of technique failure in a recent Peritoneal Dialysis Outcomes and Practice Patterns Study. PD infection is also an outcome of utmost importance to patients and their caregivers. As such, optimising our strategies to prevent, diagnose and treat peritonitis is paramount. In this issue of Peritoneal Dialysis International, Li et al. have published updated 2022 International Society for Peritoneal Dialysis (ISPD) peritonitis guidelines on prevention and treatment, which expand significantly upon the information provided in the 2016 peritonitis guidelines. Among other updates, these new guidelines highlight the importance of more standardised definitions of peritonitis-related outcomes, update our peritonitis targets to a more stringent standard and provide new antibiotic recommendations in light of evolving resistance patterns of many organisms. One of the issues that has become increasingly clear over time is that studies of peritonitis in PD patients suffer from a lack of consistency in the reporting of characteristics of peritonitis episodes and of peritonitis outcome measures. For example, a recent review of 77 studies on PD peritonitis published between 2007 and 2018 showed that nearly onethird of studies did not specify how peritonitis was defined, and the reporting of concomitant exit site infection/tunnel infection as well as peritonitis-related hospitalisation and death was highly variable. Furthermore, the definition of some peritonitis categories and outcomes has never been formally clarified. This updated peritonitis guideline provides standardised definitions for outcomes such as medical cure and peritonitis-associated catheter removal, haemodialysis transfer, hospitalisation and death. Consistent use of such standardised definitions in clinical practice and in research will allow for better benchmarking of an individual centre’s performance relative to others and will facilitate comparison of clinical studies on PD peritonitis in the future. In addition, some important new entities have been defined, including pre-PD peritonitis, which allows us to distinguish PD peritonitis occurring between PD catheter insertion and initiation of PD from that occurring once PD has been initiated. By separating out peritonitis occurring before initiation of PD, programmes can better identify what practice changes might improve early peritonitis rates. An important update in the 2022 ISPD peritonitis guidelines is the revision of PD peritonitis targets. In the 2016 peritonitis guidelines, it was recommended that a programme’s peritonitis rate should not exceed 0.5 peritonitis episodes per patient-year at risk. This target has now been reduced to 0.4 peritonitis episodes per patient-year based on improvements in peritonitis prevention strategies that have led to decreasing peritonitis rates in many countries over time. The culture-negative peritonitis target has also been revised from <20% of peritonitis episodes to <15%. In addition, a new target has been added to those above, namely the percentage of patients free of peritonitis per unit time (target >80% per year). In the realm of PD peritonitis prevention, the 2022 guidelines reinforce previously recommended peritonitis prevention strategies including antibiotic prophylaxis prior to PD catheter insertion, at the exit site and prior to invasive gastrointestinal and genitourinary procedures, as well as antifungal prophylaxis. Additions include some more recent data on patient training highlighting the importance of direct inspection of PD technique, as well as new sections on prophylactic antibiotics for wet contamination, minimising peritonitis risk with pets in the home, and other modifiable peritonitis risk factors including hypokalaemia and use of H2-antagonists. While we continue to try to identify new peritonitis prevention strategies, we should not forget about promoting the strategies that have already been proven to be of benefit. This was highlighted by a study published in 2019 in which there was marked facility and country variation in the use of strategies such as exit

A 62-year-old woman undergoing peritoneal dialysis (PD) presented to the clinic with severe abdominal pain and cloudy PD fluid. Seven days prior, she inadvertently broke aseptic technique when tightening a leaking connection of her PD catheter tubing. Cloudy fluid that was drained from her PD catheter was sent for laboratory analysis. What would you do next?

RATIONALE & OBJECTIVE:Peritoneal dialysis (PD)-associated peritonitis is a significant PD-related complication. We describe the likelihood of cure after a peritonitis episode, exploring its association with various patient, peritonitis, and treatment characteristics.STUDY DESIGN:Observational prospective cohort study.SETTING & PARTICIPANTS:1,631 peritonitis episodes (1,190 patients, 126 facilities) in Australia, New Zealand, Canada, Japan, Thailand, the United Kingdom, and the United States.EXPOSURE:Patient characteristics (demographics, patient history, laboratory values), peritonitis characteristics (organism category, concomitant exit-site infection), dialysis center characteristics (use of icodextrin and low glucose degradation product solutions, policies regarding antibiotic self-administration), and peritonitis treatment characteristics (antibiotic used).OUTCOME:Cure, defined as absence of death, transfer to hemodialysis (HD), PD catheter removal, relapse, or recurrent peritonitis within 50 days of a peritonitis episode.ANALYTICAL APPROACH:Mixed-effects logistic models.RESULTS:Overall, 65% of episodes resulted in a cure. Adjusted odds ratios (AOR) for cure were similar across countries (range, 54%-68%), by age, sex, dialysis vintage, and diabetes status. Compared with Gram-positive peritonitis, the odds of cure were lower for Gram-negative (AOR, 0.41 [95% CI, 0.30-0.57]), polymicrobial (AOR, 0.30 [95% CI, 0.20-0.47]), and fungal (AOR, 0.01 [95% CI, 0.00-0.07]) peritonitis. Odds of cure were higher with automated PD versus continuous ambulatory PD (AOR, 1.36 [95% CI, 1.02-1.82]), facility icodextrin use (AOR per 10% greater icodextrin use, 1.06 [95% CI, 1.01-1.12]), empirical aminoglycoside use (AOR, 3.95 [95% CI, 1.23-12.68]), and ciprofloxacin use versus ceftazidime use for Gram-negative peritonitis (AOR, 5.73 [95% CI, 1.07-30.61]). Prior peritonitis episodes (AOR, 0.85 [95% CI, 0.74-0.99]) and concomitant exit-site infection (AOR, 0.41 [95% CI, 0.26-0.64]) were associated with a lower odds of cure.LIMITATIONS:Sample selection may be biased and generalizability may be limited. Residual confounding and confounding by indication limit inferences. Use of facility-level treatment variables may not capture patient-level treatments.CONCLUSIONS:Outcomes after peritonitis vary by patient characteristics, peritonitis characteristics, and modifiable peritonitis treatment practices. Differences in the odds of cure across infecting organisms and antibiotic regimens suggest that organism-specific treatment considerations warrant further investigation.

Introduction: Peritoneal dialysis (PD)-related peritonitis is one of the leading causes of discontinuation of PD and is considered a critically important outcome for patients on PD. However, there is no universally accepted method of measuring this outcome in clinical trials.Methods: We convened an online consensus workshop to establish a core outcome measure for PD -related peritonitis in clinical trials.Results: A total of 53 participants, including 18 patients and caregivers, from 12 countries engaged in breakout discussions in this workshop. Transcripts were analyzed thematically. We identified the following 3 themes: (i) feasibility and applicability across diverse settings, which reflected the difficulty with implementing laboratory-based measures in resource-limited environments; (ii) ensuring validity, which included mini-mizing false positives and considering the specificity of symptoms; and (iii) being meaningful and tangible to patients, which meant that the measure should be easy to interpret, reflect the impact that symptoms have on patients, and promote transparency by standardizing the reporting of peritonitis among dialysis units.Conclusion: A core outcome measure for PD-related peritonitis should include both symptom-based and laboratory-based criteria. Thus, the International Society for Peritoneal Dialysis (ISPD) definition of perito-nitis is acceptable. However, there should be consideration of reporting suspected peritonitis in cases where laboratory confirmation is not possible. The measure should include all infections from the time of catheter insertion and capture both the rate of infection and the number of patients who remain peritonitis free. A core outcome measure with these features would increase the impact of clinical trials on the care and decision-making of patients receiving PD.

RATIONALE & OBJECTIVE:Peritoneal dialysis (PD)-related peritonitis carries high morbidity for PD patients. Understanding the characteristics and risk factors for peritonitis can guide regional development of prevention strategies. We describe peritonitis rates and the associations of selected facility practices with peritonitis risk among countries participating in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS).STUDY DESIGN:Observational prospective cohort study.SETTING & PARTICIPANTS:7,051 adult PD patients in 209 facilities across 7 countries (Australia, New Zealand, Canada, Japan, Thailand, United Kingdom, United States).EXPOSURES:Facility characteristics (census count, facility age, nurse to patient ratio) and selected facility practices (use of automated PD, use of icodextrin or biocompatible PD solutions, antibiotic prophylaxis strategies, duration of PD training).OUTCOMES:Peritonitis rate (by country, overall and variation across facilities), microbiology patterns.ANALYTICAL APPROACH:Poisson rate estimation, proportional rate models adjusted for selected patient case-mix variables.RESULTS:2,272 peritonitis episodes were identified in 7,051 patients (crude rate, 0.28 episodes/patient-year). Facility peritonitis rates were variable within each country and exceeded 0.50/patient-year in 10% of facilities. Overall peritonitis rates, in episodes per patient-year, were 0.40 (95% CI, 0.36-0.46) in Thailand, 0.38 (95% CI, 0.32-0.46) in the United Kingdom, 0.35 (95% CI, 0.30-0.40) in Australia/New Zealand, 0.29 (95% CI, 0.26-0.32) in Canada, 0.27 (95% CI, 0.25-0.30) in Japan, and 0.26 (95% CI, 0.24-0.27) in the United States. The microbiology of peritonitis was similar across countries, except in Thailand, where Gram-negative infections and culture-negative peritonitis were more common. Facility size was positively associated with risk for peritonitis in Japan (rate ratio [RR] per 10 patients, 1.07; 95% CI, 1.04-1.09). Lower peritonitis risk was observed in facilities that had higher automated PD use (RR per 10 percentage points greater, 0.95; 95% CI, 0.91-1.00), facilities that used antibiotics at catheter insertion (RR, 0.83; 95% CI, 0.69-0.99), and facilities with PD training duration of 6 or more (vs <6) days (RR, 0.81; 95% CI, 0.68-0.96). Lower peritonitis risk was seen in facilities that used topical exit-site mupirocin or aminoglycoside ointment, but this association did not achieve conventional levels of statistical significance (RR, 0.79; 95% CI, 0.62-1.01).LIMITATIONS:Sampling variation, selection bias (rate estimates), and residual confounding (associations).CONCLUSIONS:Important international differences exist in the risk for peritonitis that may result from varied and potentially modifiable treatment practices. These findings may inform future guidelines in potentially setting lower maximally acceptable peritonitis rates.

The patient was an 82-year-old man known for hypertension, hyperlipidemia, and gout who was diagnosed with follicular lymphoma 5 years before nephrology consultation. His lymphoma did not require therapy until 2 years before presentation, when his disease progressed clinically and radiographically with worsening lymphadenopathy. At that time, he completed 8 cycles of rituximab, cyclophosphamide, vincristine, and prednisolone, with near-complete remission. Three weeks before the nephrology consultation, a repeat computed tomography scan showed a significant progression of abdominal lymphadenopathy and a lymph node biopsy confirmed transformation into diffuse large B-cell lymphoma. Magnetic resonance imaging of the brain was suggestive of central nervous system involvement. He received 1 cycle of gemcitabine and dexamethasone as well as brain irradiation.

BACKGROUND:Cardiac troponins are the preferred biomarker to diagnose myocardial injury. Complicating the interpretation of serial troponins in patients with end-stage renal disease, it has been shown that the hemodialysis procedure results in a small but significant decline in high-sensitivity cardiac troponins (hs-cTnT). This raises the possibility that continuous renal replacement therapy (CRRT) might similarly alter cardiac troponin levels and affect their interpretation when cardiac ischemia is being considered.OBJECTIVE:We sought to determine the effect of CRRT on hs-cTnT levels over time in a group of patients without active myocardial injury.DESIGN:Prospective, observational study.SETTING:Single tertiary care hospital, Montreal, Quebec.PATIENTS:Ten critically ill patients with acute kidney injury (AKI) undergoing CRRT. Cardiac ICU (intensive care unit) patients and acute coronary syndrome patients were excluded from the study. The CRRT prescription was at the discretion of the treating intensivist and relatively high doses were used in this study.MEASUREMENTS:The hs-cTnT levels were drawn pre-CRRT, within 6 hours of initiation, and approximately every 6 hours thereafter along with routine CRRT blood work.METHODS:Changes in hs-cTnT, creatinine, and albumin levels were recorded over the course of CRRT. Mean change in serum analyte concentration and 95% confidence interval was determined for specified time intervals relative to baseline, with paired t tests used to determine statistical significance.RESULTS:Among the 10 patients included in the study, the cause of AKI was primarily acute tubular necrosis from septic shock or hemorrhagic shock. Compared with baseline hs-cTnT levels prior to CRRT initiation, mean hs-cTnT level fell by 42% at 5 to 10 hours post-CRRT initiation, followed by a plateauing of levels for the duration of time on CRRT.LIMITATIONS:Single-center study only applicable to hs-cTnT assay.CONCLUSIONS:This study demonstrates a significant decrease in hs-cTnT within 5 to 10 hours of CRRT initiation. This suggests that interpretation of cardiac troponin changes during CRRT must take into consideration the timing of dialysis initiation relative to the time of sample collection.

BACKGROUND:Peritoneal dialysis (PD)-related infections lead to significant morbidity. The International Society for Peritoneal Dialysis (ISPD) guidelines for the prevention and treatment of PD-related infections are based on variable evidence. We describe practice patterns across facilities participating in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS).METHODS:PDOPPS, a prospective cohort study, enrolled nationally representative samples of PD patients in Australia/New Zealand (ANZ), Canada, Thailand, Japan, the UK and the USA. Data on PD-related infection prevention and treatment practices across facilities were obtained from a survey of medical directors'.RESULTS:A total of 170 centers, caring for >11 000 patients, were included. The proportion of facilities reporting antibiotic administration at the time of PD catheter insertion was lowest in the USA (63%) and highest in Canada and the UK (100%). Exit-site antimicrobial prophylaxis was variably used across countries, with Japan (4%) and Thailand (28%) having the lowest proportions. Exit-site mupirocin was the predominant exit-site prophylactic strategy in ANZ (56%), Canada (50%) and the UK (47%), while exit-site aminoglycosides were more common in the USA (72%). Empiric Gram-positive peritonitis treatment with vancomycin was most common in the UK (88%) and USA (83%) compared with 10-45% elsewhere. Empiric Gram-negative peritonitis treatment with aminoglycoside therapy was highest in ANZ (72%) and the UK (77%) compared with 10-45% elsewhere.CONCLUSIONS:Variation in PD-related infection prevention and treatment strategies exist across countries with limited uptake of ISPD guideline recommendations. Further work will aim to understand the impact these differences have on the wide variation in infection risk between facilities and other clinically relevant PD outcomes.

It is unclear whether warfarin is protective or harmful in patients with ESRD and atrial fibrillation. This state of equipoise raises the question of whether alternative anticoagulants may have a therapeutic role. We aimed to determine apixaban pharmacokinetics at steady state in patients on hemodialysis. Seven patients received apixaban 2.5 mg twice daily for 8 days. Blood samples were collected before and after apixaban administration on days 1 and 8 (nondialysis days). Significant accumulation of the drug was observed between days 1 and 8 with the 2.5-mg dose. The area under the concentration-time curve from 0 to 24 hours increased from 628 to 2054 ng h/ml (P<0.001). Trough levels increased from 45 to 132 ng/ml (P<0.001). On day 9, after a 2.5-mg dose, apixaban levels were monitored hourly during dialysis. Only 4% of the drug was removed. After a 5-day washout period, five patients received 5 mg apixaban twice daily for 8 days. The area under the concentration-time curve further increased to 6045 ng h/ml (P=0.03), and trough levels increased to 218 ng/ml (P=0.03), above the 90th percentile for the 5-mg dose in patients with preserved renal function. Apixaban 2.5 mg twice daily in patients on hemodialysis resulted in drug exposure comparable with that of the standard dose (5 mg twice daily) in patients with preserved renal function and might be a reasonable alternative to warfarin for stroke prevention in patients on dialysis. Apixaban 5 mg twice daily led to supratherapeutic levels in patients on hemodialysis and should be avoided.

Background: Acute kidney injury (AKI) is common in patients with nonvalvular atrial fibrillation (NVAF) taking oral anticoagulants (OAC), especially in those with underlying chronic kidney disease (CKD). However, little is known on the comparative risk of AKI with the use of different OAC, including the direct acting oral anticoagulants (DOACs).

Magnesium balance is infrequently discussed in the dialysis population, and the clinical consequences of derangements in magnesium homeostasis are incompletely understood. There is an association between hypomagnesemia and adverse outcomes including increases in cardiovascular disease and mortality, while elevated magnesium levels have also been linked with complications such as osteomalacia. In this review, we discuss the features of magnesium physiology relevant to dialysis patients and provide an updated summary of the literature linking magnesium derangements with bone disease, cardiovascular disease, sudden cardiac death, and mortality.

Cardiac troponin (cTn) is essential for the diagnosis of an acute coronary syndrome (ACS). However, in end-stage renal disease (ESRD) baseline cTn levels are often elevated, and it is unknown whether the hemodialysis (HD) procedure affects cTn levels. This leaves clinicians unsure of how to interpret cTn in HD patients with cardiac ischemia. We therefore sought to determine if plasma levels of high-sensitivity cardiac troponin T (hs-cTnT) vary during or after HD treatment. We prospectively enrolled 10 chronic HD patients who were admitted to our institution. All participants were receiving thrice weekly HD before admission and were medically stable. Those admitted for ACS or to critical care units were excluded. Baseline hs-cTnT was measured immediately before HD. For the subsequent 6 hours, hs-cTnT was measured every 2 hours and every 3 hours thereafter for a total collection period of 24 hours. A significant decline in mean hs-cTnT was noted with HD. During HD (2 hours after HD initiation), hs-cTnT decreased by 10.7% (confidence interval 5% to 17%). Immediately after HD (4 hours after HD initiation), a decline of 12% (confidence interval 5% to 19%) was observed. Thereafter hs-cTnT began to rise. Hs-cTnT levels returned to baseline by 11 hours after HD completion and remained stable for the reminder of the study. In conclusion, HD induces a short-lived negative bias in hs-cTnT. When measured for investigation of ACS, hs-cTnT concentration should be interpreted with respect to time of dialysis and specimen collection.

Adverse outcomes in peritoneal dialysis ( PD ), including PD related infections, the loss of residual kidney function ( RKF ), and longitudinal, deleterious changes in peritoneal membrane function continue to limit the long‐term success of PD therapy. The observation that these deleterious changes occur upon exposure to conventional glucose‐based PD solutions fuels the search for a more biocompatible PD solution. The development of a novel PD solution with a neutral pH , and lower in glucose degradation products ( GDP s) compared to its conventional predecessors has been labeled a “biocompatible” solution. While considerable evidence in support of these novel solutions’ biocompatibility has emerged from cell culture and animal studies, the clinical benefits as compared to conventional PD solutions are less clear. Neutral pH low GDP (NpHLGDP) PD solutions appear to be effective in reducing infusion pain, but their effects on other clinical endpoints including peritoneal membrane function, preservation of RKF , PD ‐related infections, and technique and patient survival are less clear. The literature is limited by studies characterized by relatively few patients, short follow‐up time, heterogeneity with regards to the novel PD solution type under study, and the different patient populations under study. Nonetheless, the search for a more biocompatible PD solution continues with emerging data on promising non glucose‐based solutions.

BACKGROUND:Early retraining of patients/caregivers at 3 months after peritoneal dialysis (PD) initiation is recommended to prevent peritonitis. We sought to better understand if the risk of peritonitis was highest early after the initiation of PD and if the risk varied by time on therapy and by organism.METHODS:Using the multicenter Canadian Baxter POET database, we studied 4,247 incident PD patients. Time on dialysis was divided into 3-month intervals over the first 2 years on PD, with 0 - 3 months serving as the reference period. After creating several organism categories (all organisms, coagulase-negative staphylococcus (CNS), Staphylococcus aureus, streptococcus, Gramnegative, culture-negative, and yeast), time to first peritonitis was analyzed by Kaplan-Meier analysis and using smooth hazard plots. The risk of peritonitis for each of these categories over time was then analyzed in a multivariable model after adjusting for potential confounding variables.RESULTS:The overall risk of peritonitis (all organisms) was greatest in the first 3 months on PD compared with all subsequent 3-month intervals (p = 0.001). Organism-specific analyses revealed an increased risk of culture-negative peritonitis in the first 3 months (p < 0.001) but no increased risk of CNS peritonitis or any of the other pre-specified organism categories.CONCLUSIONS:The overall risk of peritonitis was greatest in the first 3 months on PD and was largely driven by an increased risk of culture-negative peritonitis but not by CNS. Better understanding of this increased early peritonitis risk is warranted in order to develop strategies aimed at its prevention.

Background: Low-molecular weight heparins (LMWH) are not traditionally used to treat venous thromboembolism (VTE) among dialysis patients because their renal clearance may lead to less predictability in the degree of anticoagulation for a given dose. We determined the risk of major bleeding with LMWH compared with vitamin K antagonist (VKA) use in dialysis patients diagnosed with VTE in a real world setting. Methods: Using the linked administrative healthcare databases of the province of Quebec, Canada, we identified all patients with incident VTE between 2000 and 2009 and pre-existing dialysis status (hemodialysis or peritoneal dialysis). We included patients dispensed VKA or LMWH for the first time within 30 days of their VTE. Monotherapy was successive dispensation of LMWH in the absence of VKA, or vice versa. Combination therapy was LMWH and VKA on the same day. For each patient, we determined average daily dose and duration of continuous use. Patients were followed from VKA or LMWH initiation until a switch or discontinuation of anticoagulation, or major bleeding (emergency room visit or hospital admission for gastrointestinal bleeding or bleeding into a critical organ). Using a Cox proportional hazards model, we determined the incidence of major bleeding associated with LMWH monotherapy, compared with VKA monotherapy. The risk estimate was adjusted for deciles of a propensity score for LMWH use, which included comorbidities-, dialysis-, and VTE-related covariates, as well as calendar year. Results: In all, 647 dialysis patients with VTE were identified: 467 started VKA, 82 started LMWH, and 96 started both. Initiators of LMWH were 35 dalteparin, 26 tinzaparin, 19 enoxaparin, and 2 nadroparin. Median (interquartile range, IQR) daily doses were 12,500 (7,500-17,570) IU dalteparin, 16,080 (13,540-20,000) IU tinzaparin, 100 (70-120) mg enoxaparin, and 15,910 (15,200-16,625) IU nadroparin. Median (IQR) duration of LMWH monotherapy was 37 (22-87) days, and 132 (65-235) for VKA monotherapy. More than 90% of LMWH monotherapy was from 2004 and onwards, and 80% of LMWH users had cancer (Table). There were 22 major bleeding events (86% gastrointestinal), 20 in VKA and 2 in LMWH users. No fatal bleeding occurred. Compared with VKA monotherapy, LMWH monotherapy was not associated with major bleeding (adjusted HR, 1.21; 95% CI: 0.20-7.37). Conclusions: To our knowledge, this is the first population-based cohort reporting LMWH use in dialysis patients with VTE. We observed LMWH monotherapy mostly in cancer patients and from 2004 and onwards. This may reflect the evidence supporting improved effectiveness of LMWH compared with VKA for cancer-associated VTE. Further, daily doses of LMWH were generally halved. Overall, LMWH alone in dialysis patients was not associated with an increased major bleeding risk. If replicated, these findings indicate LMWH use is feasible in this clinical setting. Disclosures No relevant conflicts of interest to declare.