Management of Type 2 Diabetic Kidney Disease in 2022: A Narrative Review for Specialists and Primary Care.

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.

Justification: L'insuffisance rénale est présente chez près de la moitié des patients canadiens atteints de diabète de type 2 (DT2). Il s'agit également de la première manifestation cardiorénale la plus fréquente du DT2. Bien qu'il existe des lignes directrices claires pour son dépistage, des occasions de diagnostiquer l'insuffisance rénale sont manquées, ce qui fait en sorte que de nombreux Canadiens ne reçoivent pas les meilleurs traitements disponibles. Cette préoccupation a pris de l'importance puisque de récents essais cliniques ont démontré des améliorations dans les paramètres rénaux et cardiovasculaires (CV) avec la prise de finérénone, un antagoniste non stéroïdien des récepteurs minéralocorticoïdes (nsMRA), et d'inhibiteurs du cotransporteur de glucose de sodium 2 (SGLT2). L'objectif de cet article est de fournir une revue narrative des données probantes actuelles appuyant cette nouvelle norme de soins pour le traitement de l'insuffisance rénale diabétique (IRD), ainsi que des points de pratique. Sources de l'information: Un groupe d'experts composé de cliniciens canadiens, dont neuf néphrologues, un endocrinologue et un prestataire de soins primaires, a été formé. Les auteurs de cette revue ont utilisé des lignes directrices et des essais cliniques publiés comme sources; ceux-ci ont été choisis sur la base d'une évaluation de leur pertinence pour les questions auxquelles ils avaient répondu. Méthodologie: Les panélistes se sont réunis virtuellement pour discuter de potentielles questions à répondre dans le cadre de cette revue, et se sont entendus sur dix questions clés. Deux membres du panel se sont portés volontaires pour être co-responsables et rédiger les résumés et les points de pratique pour chacune des questions identifiées. Ces derniers ont été distribués par courriel à l'ensemble des auteurs. Après deux tours de vote en ligne, une deuxième réunion virtuelle et la correspondance électronique qui a suivi, les auteurs sont parvenus à un consensus sur le contenu de la revue narrative, y compris sur tous les points de pratique. Principaux résultats: Il est essentiel que l'IRD soit diagnostiquée le plus tôt possible afin de prévenir de façon optimale la progression de la maladie et les complications qui y sont associées. On devrait procéder au dépistage systématique de l'IRD chez les patients diabétiques par l'évaluation de l'albumine urinaire ET de la fonction rénale. Les décisions relatives au traitement devraient être individualisées en fonction des risques et des avantages pour le patient, de ses besoins et préférences, de l'accès aux médicaments et des coûts, ainsi que du degré nécessaire de réduction de la glycémie. Les patients atteints d'IRD devraient être traités pour atteindre les cibles d'A1c et de pression artérielle. Le blocage du SRAA et le traitement avec des inhibiteurs du SGLT2 sont également des composantes clés de la norme de soins visant à réduire le risque d'événements rénaux et CV pour ces patients. La finérénone devrait également être envisagée pour réduire encore davantage les risques d'événements CV et de progression vers l'IRC. L'éducation des patients diabétiques auxquels on prescrit des inhibiteurs du SGLT2 et/ou de la finérénone est un élément important du traitement. Limites: Aucun processus officiel de directives n'a été utilisé. Les points de pratique ne sont pas notés et ne sont pas destinés à être considérés comme ayant le poids d'une directive de pratique clinique ou d'une déclaration de consensus officielle. Cependant, la plupart des points de pratique sont bien alignés avec les lignes directrices actuelles de pratique clinique.

Peritoneal Fluid Analysis in Peritoneal Dialysis-Associated Peritonitis.

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?

Establishing a Core Outcome Measure for Peritoneal Dialysis-related Peritonitis: A Standardized Outcomes in Nephrology-Peritoneal Dialysis Consensus Workshop Report.

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 minimizing 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 peritonitis 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.

Variation in Peritoneal Dialysis-Related Peritonitis Outcomes in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS).

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.

Peritoneal Dialysis-Related Infection Rates and Outcomes: Results From the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS).

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.

Variation of High-Sensitivity Troponin T Results in Patients Undergoing Continuous Renal Replacement Therapy.

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.

CONTEXTE: Les troponines cardiaques constituent le biomarqueur de choix pour diagnostiquer les lésions myocardiques. L'hémodialyse, qui provoque un léger et significatif déclin des troponines cardiaques à haute sensibilité (hs-cTnT), complique leur interprétation chez les patients atteints d'insuffisance rénale terminale. Cette observation suggère que la thérapie de remplacement rénal continue (TRRC) pourrait modifier similairement les taux de troponines cardiaques et affecter leur interprétation lorsqu'une ischémie cardiaque est examinée. OBJECTIF: Nous souhaitions évaluer l'effet dans le temps d'une TRRC sur les taux de hs-cTnT chez des patients sans lésions myocardiques actives. TYPE D'ÉTUDE: Une étude observationnelle prospective. CADRE: Un hôpital de soins tertiaires de Montréal (Québec). SUJETS: Un groupe de dix patients gravement malades, souffrant d'insuffisance rénale aiguë (IRA) et suivant une TRRC. Les patients hospitalisés aux soins intensifs cardiaques ou atteints d'un syndrome coronarien aigu ont été exclus. La prescription d'une TRRC était laissée à la discrétion du médecin intensiviste traitant et des doses relativement élevées ont été administrées au cours de l'étude. MESURES: Les taux de hs-cTnT ont été mesurés conjointement aux prélèvements sanguins de routine requis pour une TRRC; soit avant son initiation, dans les six heures suivantes, puis aux six heures environ par la suite. MÉTHODOLOGIE: Les variations des taux de hs-cTnT, de créatinine et d'albumine ont été colligées pour la durée de la TRRC. La variation moyenne des concentrations d'analytes sériques par rapport aux valeurs initiales et les intervalles de confiance à 95 % ont été déterminés pour des périodes de temps précises. Des tests t couplés ont été employés pour établir la signification statistique des résultats. RÉSULTATS: Chez les patients examinés, l'IRA était principalement due à une nécrose tubulaire aiguë causée par un choc septique ou hémorragique. Le taux moyen de hs-cTnT a chuté de 42 % dans les 5 à 10 heures suivant l'initiation de la TRRC par rapport aux valeurs observées pré-TRRC. Les taux ont ensuite plafonné pour la durée de la TRRC. LIMITES: Il s'agit d'une étude monocentrique applicable uniquement aux mesures de hs-cTnT. CONCLUSION: Cette étude démontre une baisse significative des hs-cTnT dans les 5 à 10 heures suivant l'initiation d'une TRRC. Ce résultat suggère que l'interprétation des variations observées dans les taux de troponines cardiaques au cours d'une TRRC devrait tenir compte du moment où l'échantillon est prélevé par rapport à son initiation.

Regional variation in the treatment and prevention of peritoneal dialysis-related infections in the Peritoneal Dialysis Outcomes and Practice Patterns Study.

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.

Effect of Hemodialysis on Levels of High-Sensitivity Cardiac Troponin T.

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.

Clinical aspects of magnesium physiology in patients on dialysis.

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.

Apixaban Pharmacokinetics at Steady State in Hemodialysis Patients.

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.

"Biocompatible" Neutral pH Low-GDP Peritoneal Dialysis Solutions: Much Ado About Nothing?

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 (GDPs) 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.

Does the risk of peritoneal dialysis-associated peritonitis vary by time on treatment?

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.

Vascular Access Type and Patient and Technique Survival in Home Hemodialysis Patients: The Canadian Organ Replacement Register.

BACKGROUND: While central venous catheter (CVC) use has expanded home hemodialysis (HHD) eligibility to many patients who may be unable to self-cannulate an arteriovenous (AV) access, the association between CVC use and mortality has not been directly examined among HHD patients. STUDY DESIGN: Registry-based retrospective observational cohort study. SETTING & PARTICIPANTS: Incident HHD patients in The Canadian Organ Replacement Register who had information for vascular access type (CVC vs AV access) within the first year of HHD therapy initiation. PREDICTOR: Use of a CVC versus an AV access (AV fistula or graft) within the first year of HHD therapy initiation. OUTCOME: The composite of all-cause mortality and technique failure (long-term transfer to an alternate dialysis modality). A Cox proportional hazards model was used to evaluate the adjusted composite outcome and each outcome separately. RESULTS: 1,869 patients initiated HHD therapy in Canada in 1996 to 2012, of whom 1,217 had an access type recorded within the first year of HHD therapy initiation. Compared to CVC use (n=523) and during a median follow-up of 513 and 427 days for AV access and CVC patients, respectively, AV access use (n=694) was associated with lower risk for the composite event of death and technique failure (490 events; adjusted HR, 0.78; 95% CI, 0.64-0.94) and lower adjusted all-cause mortality (129 deaths; adjusted HR, 0.63; 95% CI, 0.43-0.91); the risk for technique failure was nominally lower, but this result was not statistically significant (361 events; adjusted HR, 0.84; 95% CI, 0.67-1.05). Results were robust to sensitivity analyses and after missing data imputation. LIMITATIONS: Missing information for vascular access type (n=659[35% of patients]) and lack of information for longitudinal changes in vascular access type. CONCLUSIONS: Compared to CVC use, AV access use was associated with superior survival. Minimizing CVC use and maximizing AV access use while addressing barriers to their placement and self-cannulation may improve HHD outcomes.

The relationship between proton pump inhibitor use and serum magnesium concentration among hemodialysis patients: a cross-sectional study.

BACKGROUND: Observational data suggest that serum magnesium (Mg) concentration is inversely related to vascular calcification and hyperparathyroidism among patients with end-stage renal disease (ESRD). In recent years, there have been several case reports of hypomagnesemia due to use of proton-pump inhibitors (PPI), with the hypomagnesemia attributed to inappropriate gastrointestinal (GI) Mg loss. We hypothesized that the tendency to GI Mg loss is more common than is currently reported. Since patients with ESRD have little to no renal Mg loss to affect serum Mg concentration, dialysis patients are an interesting population in whom to study the relationship between PPI use and serum Mg levels. METHODS: Using a single-center cross-sectional design, we studied 155 prevalent hemodialysis (HD) patients. Serum Mg concentration for each patient was determined based on the mean of 3 consecutive serum Mg levels drawn at 6 week intervals. PPI use at the time of the blood tests was documented. The relationship between PPI use and Mg concentration was determined in unadjusted analyses, as well as after adjustment for age, gender, race, cause of ESRD, diabetes, time on HD and dialysate Mg concentration. RESULTS: 55 % of patients were on PPIs at the time of the study. The majority of patients (62 %) used a dialysate Mg (in mmol/L) of 0.5, and the remainder (38 %) used a dialysate Mg of 0.375. Serum Mg levels were significantly lower among PPI users vs. non-users (0.93 vs. 1.02 mmol/L, p < 0.001). This finding persisted after stratifying for dialysate Mg concentration, and after multivariable adjustment (p < 0.001). In addition, more PPI users vs. non-users had a Mg level < 1 mmol/L (79 % vs. 43 %) and a Mg level < 0.8 mmol/L (16 % vs. 4 %). There was a non-significant trend toward increased time on PPI being associated with lower serum Mg levels (p = 0.067). CONCLUSION: Among HD patients, PPI users have lower serum Mg levels as compared with non-users. Further research is required to determine whether the magnitude of change in Mg levels among PPI users is associated with adverse outcomes.

The impact of transfer from hemodialysis on peritoneal dialysis technique survival.

BACKGROUND: A significant proportion of peritoneal dialysis (PD) patients receive an initial period of hemodialysis (HD) before transitioning to PD ("PD-switch"). We sought to better understand the risks of PD technique failure (TF) and mortality for those patients compared with patients starting with PD as their first dialysis modality ("PD-first"). METHODS: Using Canadian Organ Replacement Register data, we compared the risk of PD TF between PD-first and PD-switch patients within the first year after HD initiation. In a secondary analysis, the PD-switch patients were stratified into three groups based on timing of the switch from initial HD to PD as follows: 0 - 90 days, 91 - 180 days, and 181 - 365 days. Each group was compared with PD-first patients for risk of PD TF and death. RESULTS: Between 2001 and 2010, 9404 patients initiated PD as their first renal replacement therapy, and 3757 switched from HD to PD. After multivariable adjustment, the risk of PD TF was higher among PD-switch patients than among PD-first patients [adjusted hazard ratio (AHR): 1.37; 95% confidence interval (CI): 1.26 to 1.49], particularly within the first year after the switch from HD to PD (AHR: 1.51; 95% CI: 1.36 to 1.68). There was no association between time on HD within the first year and subsequent risk of PD TF. For all the stratified PD-switch groups, death rates were higher than those for PD-first patients. CONCLUSIONS: Compared with patients who start renal replacement therapy with PD, those who transfer from HD to PD within the first year on dialysis experience higher rates of PD TF and death, with the highest risk being observed in the initial year after the switch to PD.

Tramadol for noncancer pain and the risk of hyponatremia.

BACKGROUND: Case reports have signaled a possible association between tramadol, a weak opioid analgesic, and hyponatremia. The objective of this study was to determine whether the use of tramadol is associated with an increased risk of hyponatremia, when compared with codeine. METHODS: Using the UK Clinical Practice Research Datalink and Hospital Episodes Statistics database, a population-based cohort of 332,880 patients initiating tramadol or codeine was assembled from 1998 through 2012. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of hospitalization for hyponatremia associated with the use of tramadol, compared with codeine, in the first 30 days after initiation. A similar analysis was conducted within a highly restricted sub-cohort, which additionally excluded patients with any serum sodium level abnormality in the year before cohort entry. All models were adjusted for propensity score quintiles. RESULTS: The incidence rates of hospitalization for hyponatremia were 4.6 (95% CI, 2.4-8.0) and 1.9 (95% CI, 1.4-2.5) per 10,000 person-months for tramadol and codeine users, respectively. In the adjusted model, the use of tramadol was associated with a 2-fold increased risk of hospitalization for hyponatremia, compared with codeine (adjusted HR 2.05; 95% CI, 1.08-3.86). In the highly restricted sub-cohort, the use of tramadol was associated with an over 3-fold increased risk of hospitalization for hyponatremia, compared with codeine (adjusted HR 3.54; 95% CI, 1.32-9.54). CONCLUSIONS: In this first population-based study, the use of tramadol was associated with an increased risk of hyponatremia requiring hospitalization.