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Health state utilities (HSU) data collected in real-world evidence studies are at risk of bias. Although numerous guidance documents are available, practical advice to avoid bias in HSU studies is limited. Thus, the objective of this article was to develop a concise toolbox intended for investigators seeking to collect HSU in a real-world setting. The proposed toolbox builds on existing guidance and provides practical steps to help investigators perform good quality research. The toolbox aims at increasing the credibility of HSU data for future reimbursement decision making.

Introduction Diabetic nephropathy is the leading cause of kidney failure. Clinical practice guidelines recommend prescribing renin–angiotensin aldosterone system inhibitors (RAASi) to prevent diabetic nephropathy at any stage. We conducted this systematic review and meta-analysis to compare the effects of RAASi with placebo and other antihypertensive agents in adults with diabetes on continuous and binary kidney outcomes to provide a comprehensive review of the class effect of RAASi on several subgroups. Methods A systematic electronic search to identify randomized clinical trials of a duration of ≥ 12 months that recruited ≥ 50 adult participants with type 1 or 2 diabetes with any stage of chronic kidney disease and proteinuria was conducted in MEDLINE, CINAHL, EMBASE, and Cochrane library with no language restriction. Studies were screened against the inclusion and exclusion criteria by two reviewers independently. Results In this meta-analysis, evidence was drawn from 26,551 patients with diabetes from 46 studies. Our analysis shows that RAASi were better than placebo in reducing SrCr (the raw mean difference [RMD] = -13.4 μmol/L; 95%CI: -16.78; -10.01) and albuminuria levels (standardized mean difference [SMD] = -1; 95%CI: -1.57, -0.44, I2 = 96%). When compared to other active treatments, RAASi did not reduce SrCr (RMD = 0.03 μmol/L; 95%CI: -6.4, 6.10, I2 = 76%), caused a non-significant reduction of GFR levels (RMD = -1.21 mL/min; 95%CI: -4.52, 2.09, I2 = 86%), and resulted in modest reduction of albuminuria levels (SMD = -0.55; 95%CI: -0.95, -0.16, I2 = 90%). RAASi were superior to placebo in reducing the risks of kidney failure (OR = 0.74; 95%CI: 0.56, 0.97) and doubling of serum creatinine levels (SrCr; OR = 0.71; 95%CI: 0.55, 0.91), but not in promoting the regression of albuminuria (OR = 3.00; 95%CI: 0.96, 9.37). RAASi, however, were not superior to other antihypertensives in reducing the risks of these outcomes. Patients with type 2 diabetes, macroalbuminuria and longer duration of diabetes had less risk of developing kidney failure in placebo-controlled trials, while longer duration of diabetes, normal kidney function, and hypertension increased the probability of achieving regression of albuminuria in active-controlled trials. Conclusion While our findings revealed the non-superiority of RAASi over other antihypertensives and portrayed a class effect on several subgroups of study participants, it raised a challenging question on whether RAASi deserve their place as first-line therapy in managing diabetic nephropathy.

Renin-angiotensin system inhibitors (RASi) are not re-initiated for almost a quarter of patients who suffered acute kidney injury 6 months after discharge. This discontinuation might be partly explained by the nephrotoxicity of these medications, yet they remain of benefit, especially for patients with heart failure.To determine the factors deemed by clinicians to influence RASi re-initiation and set threshold values for important safety parameters.Three-round modified online Delphi survey.The study was conducted in Quebec, Canada.Twenty clinicians from nephrology, intensive care medicine, and internal medicine.The factors' importance was rated on 4-point Likert-type scale, ranging from "not important" to "very important" by the panelists.We conducted a brief literature review to uncover possible influencing factors followed by a 3-round modified Delphi survey to establish a consensus on the importance of these factors.We recruited 20 clinicians (7 nephrologists, 3 internists, and 10 intensive care physicians). We created a list of 25 factors, 15 of which met consensus. Eleven of these factors, including serum creatinine, glomerular filtration rate, and acute kidney injury (AKI) stage, were deemed as important while 4, such as responsibility ambiguity and absence of feedback, were deemed as not important. The majority of the 10 factors which did not meet consensus were related to the clinical setting, such as a pharmacist follow-up and the required time to ensure optimal RASi re-initiation.Quebec clinicians' agreement might not reflect the opinion of the rest of Canada. The survey measures clinicians' belief rather than their actual practice.Renin-angiotensin system inhibitors re-initiation is a rather complex concept which encompasses several factors. Our research uncovered some of these factors which may be used to develop guidelines on optimal RASi re-initiation.Six mois après avoir reçu leur congé de l’hôpital, près du quart des patients ayant vécu un épisode d’insuffisance rénale aiguë n’ont toujours pas réamorcé les inhibiteurs du système rénine-angiotensine (iSRA). Cette interruption pourrait s’expliquer en partie par la néphrotoxicité de ces médicaments, bien qu’ils soient bénéfiques, particulièrement pour les patients souffrant d’insuffisance cardiaque.Déterminer les facteurs jugés par les cliniciens comme exerçant une influence sur la reprise des iSRA et définir des valeurs de seuil pour les paramètres de sécurité considérés comme importants.Une version modifiée de l’enquête Delphi menée en ligne, en trois étapes.Étude menée au Québec (Canada).20 cliniciens en néphrologie, en médecine de soins intensifs ou en médecine interne.L’importance des facteurs a été évaluée par les panélistes sur une échelle de type Likert à quatre points allant de « pas important » à « très important ».Nous avons procédé à une brève revue de la littérature pour repérer les possibles facteurs influençant la reprise des iSRA. Une enquête Delphi modifiée a ensuite été menée en trois étapes afin d’établir un consensus sur l’importance de ces facteurs.Nous avons recruté 20 cliniciens (7 néphrologues, 3 internistes et 10 intensivistes). Nous avons créé une liste de 25 facteurs, dont 15 faisaient consensus. De ceux-ci, 11 ont été jugés importants, notamment la créatinine sérique, le débit de filtration glomérulaire et le stade de l’insuffisance rénale aigüe (IRA); alors que 4, notamment l’ambiguïté de la responsabilité et l’absence de rétroaction, ont été jugés non importants. La majorité des 10 facteurs qui ne faisaient pas consensus étaient liés au milieu clinique, notamment le suivi du pharmacien et le temps nécessaire pour assurer une reprise optimale des iSRA.L’accord des cliniciens du Québec pourrait ne pas refléter l’opinion des cliniciens du reste du Canada. L’enquête mesure les croyances des cliniciens plutôt que leur pratique réelle.La reprise des iSRA est un concept assez complexe qui englobe plusieurs facteurs. Notre recherche a révélé certains facteurs qui peuvent être utilisés pour élaborer des lignes directrices sur la reprise optimale des iSRA après un épisode d’insuffisance rénale aigüe.

Laparoscopic sleeve gastrectomy induces weight loss via the creation of a restrictive gastric tube for early satiety and is associated with an accelerated gastric transit time. A prospective, single-dose pharmacokinetic study was performed, prior to and after laparoscopic sleeve gastrectomy, for tacrolimus, extended-release tacrolimus, mycophenolate mofetil, and enteric-coated mycophenolate sodium. The study included 12 morbidly obese patients in chronic renal failure. The median decrease in body mass index was 8.8 kg/m2 with an excess body weight loss of 54.9%. The AUC24 of all drugs were increased after laparoscopic sleeve gastrectomy by 46%, 55%, 77%, and 74%, respectively. The maximum concentrations were increased for tacrolimus, extended-release tacrolimus, and mycophenolate mofetil by 43%, 46%, and 65%. The apparent total clearances were decreased for tacrolimus, mycophenolate mofetil, and enteric-coated mycophenolate sodium by 36%, 57%, and 38%. Laparoscopic sleeve gastrectomy can be associated with significant changes in pharmacokinetics of the drugs evaluated. The mechanism is likely decreased apparent drug clearance due to an increased drug exposure (from a more distal site of intestinal absorption with decreased intestinal metabolism), or decreased clearance (liver metabolism). Adapting the monitoring of immunosuppression will be important to avoid overdosing and potential side effects.

Residual renal function and diuresis preservation are associated with improved volume control and lower mortality in peritoneal dialysis (PD). Loop diuretics are used to maintain diuresis, although their optimal dosage remains unclear. This study aimed to compare the pharmacodynamics of a 250-mg and a 500-mg dose of oral furosemide in PD patients. 12 patients with a diuresis > 100 mL per day were randomized in a crossover pattern to successively receive an oral dose of 250 mg and 500 mg of furosemide. Twelve-hour natriuresis and diuresis were measured before and after each furosemide dose. Fractional excretion of sodium (FENa) and absolute sodium excretion increased after each dose, although these rises were not statistically significantly different (5.8% (250 mg) vs. 6.9% (500 mg), p = 0.57 for FENa and 42.6 mmol/12h (250 mg) vs. 70.8 mmol/12h (500 mg), p = 0.07 for absolute sodium excretion). Urinary volume was significantly increased after the 500-mg dose, whilst the difference did not reach statistical significance after the 250-mg dose. Furthermore, the higher dose was associated with a greater increase in diuresis than the lower dose (226 mL (250 mg) vs. 522 mL (500 mg), p = 0.04). Furosemide could be used at oral single doses reaching 500 mg in PD patients requiring greater volume control.

BACKGROUND Type 2 diabetes mellitus (T2DM) imposes a substantial burden owing to its increasing prevalence and life-threatening complications. In patients who do not achieve glycemic targets with oral antidiabetic drugs, the initiation of insulin is recommended. However, a serious concern regarding insulin is drug-induced hypoglycemia. Hypoglycemia is known to affect quality of life and the use of health care resources. However, health economics and outcomes research (HEOR) data for economic modelling are limited, particularly regarding utility values and productivity losses. OBJECTIVE This real-world prospective study aims to assess the impact of hypoglycemia on productivity and utility in insulin-treated adults with T2DM from Ontario and Quebec, Canada. METHODS This noninterventional, multicenter, 3-month prospective study will recruit patients from 4 medical clinics and 2 endocrinology or diabetes clinics. Patients will be identified using appointment lists and enrolled through consecutive sampling during routinely scheduled consultations. To be eligible, patients must be aged ≥18 years, diagnosed with T2DM, and treated with insulin. Utility and productivity will be measured using the EQ-5D-5L questionnaire and Institute for Medical Technology Assessment Productivity Cost Questionnaire, respectively. Questionnaires will be completed 4, 8, and 12 weeks after recruitment. Generalized estimating equation models will be used to investigate productivity losses and utility decrements associated with incident hypoglycemic events while controlling for individual patient characteristics. A total of 500 patients will be enrolled to ensure the precision of HEOR estimates. RESULTS This study is designed to fill a gap in the Canadian evidence on the impact of hypoglycemia on HEOR outcomes. More specifically, it will generate productivity and utility inputs for the economic modeling of T2DM. CONCLUSIONS Insulin therapy is expensive, and hypoglycemia is a significant component of economic evaluation. Robust HEOR data may help health technology assessment agencies in future reimbursement decision-making. INTERNATIONAL REGISTERED REPORT PRR1-10.2196/35461

Background Type 2 diabetes mellitus (T2DM) imposes a substantial burden owing to its increasing prevalence and life-threatening complications. In patients who do not achieve glycemic targets with oral antidiabetic drugs, the initiation of insulin is recommended. However, a serious concern regarding insulin is drug-induced hypoglycemia. Hypoglycemia is known to affect quality of life and the use of health care resources. However, health economics and outcomes research (HEOR) data for economic modelling are limited, particularly regarding utility values and productivity losses. Objective This real-world prospective study aims to assess the impact of hypoglycemia on productivity and utility in insulin-treated adults with T2DM from Ontario and Quebec, Canada. Methods This noninterventional, multicenter, 3-month prospective study will recruit patients from 4 medical clinics and 2 endocrinology or diabetes clinics. Patients will be identified using appointment lists and enrolled through consecutive sampling during routinely scheduled consultations. To be eligible, patients must be aged ≥18 years, diagnosed with T2DM, and treated with insulin. Utility and productivity will be measured using the EQ-5D-5L questionnaire and Institute for Medical Technology Assessment Productivity Cost Questionnaire, respectively. Questionnaires will be completed 4, 8, and 12 weeks after recruitment. Generalized estimating equation models will be used to investigate productivity losses and utility decrements associated with incident hypoglycemic events while controlling for individual patient characteristics. A total of 500 patients will be enrolled to ensure the precision of HEOR estimates. Results This study is designed to fill a gap in the Canadian evidence on the impact of hypoglycemia on HEOR outcomes. More specifically, it will generate productivity and utility inputs for the economic modeling of T2DM. Conclusions Insulin therapy is expensive, and hypoglycemia is a significant component of economic evaluation. Robust HEOR data may help health technology assessment agencies in future reimbursement decision-making. International Registered Report Identifier (IRRID) PRR1-10.2196/35461

Background Estimating glomerular filtration rate (GFR) in acute kidney injury (AKI) is challenging, with limited data comparing estimated and gold standard methods to assess GFR. The objective of our study was to assess the performance of the kinetic estimated GFR (KeGFR) and Jelliffe equations to estimate GFR in AKI, using a radioisotopic method (technetium-diethylenetriaminepentaacetic acid) as a reference measure. Methods We conducted a prospective multicenter observational study in hospitalized patients with AKI. We computed the Jelliffe and KeGFR equations to estimate GFR and compared these estimations to measured GFR (mGFR) by a radioisotopic method. The performances were assessed by correlation, Bland–Altman plots and smoothed and linear regressions. We conducted stratified analyses by age and chronic kidney disease (CKD). Results The study included 119 patients with AKI, mostly from the intensive care unit (63%) and with Stage 1 AKI (71%). The eGFR obtained from the Jelliffe and KeGFR equations showed a good correlation with mGFR (r = 0.73 and 0.68, respectively). The median eGFR by the Jelliffe and KeGFR equations was less than the median mGFR, indicating that these equations underestimated the mGFR. On Bland–Altman plots, the Jelliffe and KeGFR equations displayed a considerable lack of agreement with mGFR, with limits of agreement >40 mL/min/1.73 m2. Both equations performed better in CKD and the KeGFR performed better in older patients. Results were similar across AKI stages. Conclusions In our study, the Jelliffe and KeGFR equations had good correlations with mGFR; however, they had wide limits of agreement. Further studies are needed to optimize the prediction of mGFR with estimatation equations.

To evaluate the impact of concomitant use of conventional synthetic DMARDs (csCMARD) on adherence, switching and dose of biologic disease modifying antirheumatic drugs (bDMARD) in rheumatoid arthritis (RA) patients treated with bDMARDs.This was a population-based cohort study conducted in five provinces of Canada (Alberta, Manitoba, Ontario, Quebec, and Saskatchewan), and one American database (IBM® MarketScan® Databases). Adult RA patients entered the study after a 3-month initiation period of bDMARDs between 1 January 2007, and 30 March 2014. Concomitant csDMARD exposure was compared to non-csDMARD exposure on the following outcomes: discontinuation of bDMARD therapy, switching of bDMARDs, and percent change in dose of bDMARD compared to initial dose. The effect of the time-varying changes in csDMARD exposure was analyzed using marginal structural models. Dose change was analyzed using linear regression. Results from each participating site were combined using likelihood ratio meta-analysis.The study population comprised 20,221 new users of bDMARDs: adalimumab (7609), etanercept (9809), abatacept (1024), infliximab (1779). Concomitant use of csDMARD therapy was not significantly associated with reduced discontinuation of bDMARD treatment (hazard ratio 0.90, 95% intrinsic confidence interval 0.79 to 1.02) or reduced switching of bDMARDs (hazard ratio 0.95, 95% intrinsic confidence interval 0.80 to 1.11), but was associated with a small increase in bDMARD dose compared to the mean dose over the first three months of treatment (mean percentage change in dose +0.56% mg/day, 95% intrinsic confidence interval +0.14% to +0.97%).In this large study of RA patients using bDMARDs in Canada and the United States, we found no clear evidence that patients who received concomitant csDMARD therapy were less likely to discontinue, switch or increase their dose of bDMARD.

Supplemental material, sj-pdf-1-cjk-10.1177_2054358120987061 for Pharmacokinetics of Tobramycin Administered at the Beginning of Intermittent Hemodialysis Session (ESRD Study) by Marjolaine Giroux, Nicolas Bouchard, Anik Henderson, Lesly Lam, Van Anh Sylvie Tran, Denis Projean, Jean-François Tessier, Laurence Lepage, Paul Gavra, Georges Ouellet, Michel Vallée and Jean-Philippe Lafrance in Canadian Journal of Kidney Health and Disease

BACKGROUND: Kidney failure is associated with a high burden of morbidity and mortality. Previous studies have raised the possibility that arteriovenous fistula (AVF) creation may attenuate eGFR decline. This study aimed to compare eGFR decline in predialysis patients with an AVF, matched to patients oriented toward peritoneal dialysis (PD). METHODS: Predialysis patients with an AVF and those oriented toward PD were retrospectively matched using a propensity score. Time zero was defined as the “AVF creation date” for the AVF group and the “date when eGFR was closest to the matched patient’s eGFR at AVF creation” for the PD group. Crude and predicted eGFR decline in AVF and PD groups were compared before and after time zero using mixed-effect linear regressions. RESULTS: In total, 61 pairs were matched. Crude annual eGFR decline before AVF creation/time zero was −4.1 ml/min per m(2) per year in the AVF group versus −5.3 ml/min per m(2) per year in the PD group (P=0.75) and after time zero, −2.5 ml/min per m(2) per year in the AVF group versus −4.5 ml/min per m(2) per year in the PD group (P=0.02). The predicted annual decline decreased from −5.1 ml/min per m(2) per year in the AVF group before AVF creation to −2.8 ml/min per m(2) per year after (P

Supplemental material, Supplemental_File for Agreement Between Administrative Database and Medical Chart Review for the Prediction of Chronic Kidney Disease G category by Louise Roy, Michael Zappitelli, Brian White-Guay, Jean-Philippe Lafrance, Marc Dorais and Sylvie Perreault in Canadian Journal of Kidney Health and Disease

OBJECTIVES: (1) To evaluate the association between acute kidney injury (AKI) in the PICU and long-term mortality and (2) to determine the extent to which adding the urine output (UO)–defined AKI alters the association. METHODS: A 2-center retrospective cohort study of children (≤18 years old) admitted to the PICU between 2003 and 2005 for noncardiac surgery, with follow-up until 2010. Patients with end stage renal disease, no provincial health insurance number, who died during hospitalization, or could not be linked to administrative data were excluded. One hospitalization per patient was included. AKI was defined by using serum creatinine criteria and/or UO criteria. Mortality was ascertained by using administrative data. Cox regression analysis was performed to evaluate the association between AKI and long-term mortality. RESULTS: The study population included 2041 patients (55.7% male, mean admission age 6.5 ± 5.8 years). Of 2041 hospital survivors, 9 (0.4%) died within 30 days, 51 (2.5%) died within 1 year, and 118 (5.8%) died within 5 to 7 years postdischarge. AKI was independently associated with 5- to 7-year mortality (adjusted hazard ratio [95% confidence interval]: 3.10 [1.46–6.57] and 3.38 [1.63–7.02], respectively). Including UO did not strengthen the association. CONCLUSIONS: AKI is associated with 5- to 7-year mortality. Because this is an observational study we cannot determine if AKI is causative of mortality or of the pathophysiology. However, patients with AKI represent a high-risk group. It is reasonable that these patients be considered for targeted follow-up until future researchers better elucidate these relationships

Background and objectives Little is known about the long-term burden of AKI in the pediatric intensive care unit. We aim to evaluate if pediatric AKI is associated with higher health service use post–hospital discharge. Design, setting, participants, & measurements This is a retrospective cohort study of children (≤18 years old) admitted to two tertiary centers in Montreal, Canada. Only the first admission per patient was included. AKI was defined in two ways: serum creatinine alone or serum creatinine and/or urine output. The outcomes were 30-day, 1-year, and 5-year hospitalizations, emergency room visits, and physician visits per person-time using provincial administrative data. Univariable and multivariable Poisson regression were used to evaluate AKI associations with outcomes. Results A total of 2041 children were included (56% male, mean admission age 6.5±5.8 years); 299 of 1575 (19%) developed AKI defined using serum creatinine alone, and when urine output was included in the AKI definition 355 of 1622 (22%) children developed AKI. AKI defined using serum creatinine alone and AKI defined using serum creatinine and urine output were both associated with higher 1- and 5-year hospitalization risk (AKI by serum creatinine alone adjusted relative risk, 1.42; 95% confidence interval, 1.12 to 1.82; and 1.80; 1.54 to 2.11, respectively [similar when urine output was included]) and higher 5-year physician visits (adjusted relative risk, 1.26; 95% confidence interval, 1.14 to 1.39). AKI was not associated with emergency room use after adjustments. Conclusions AKI is independently associated with higher hospitalizations and physician visits postdischarge.

Background Arteriovenous fistula (AVF) is the vascular access of choice for patients on hemodialysis. Recent evidence suggests that AVF creation may slow estimated glomerular filtration rate (eGFR) decline. The study objective was to assess the impact of the AVF creation on eGFR decline, after controlling for key confounding factors. Methods This retrospective cohort study included adult patients followed in a single-center predialysis clinic between 1999 and 2016. Patients with a patent AVF were followed up to 2 years pre- and post-AVF creation. Estimated GFR trajectory was reported using linear mixed models adjusted for demographic characteristics, comorbidities and use of renin-angiotensin-aldosterone blockade. Results A total of 146 patients were studied with a median age 68.7 (60.5–75.4) years and a median eGFR at time of AVF creation of 12.8 (11.3–13.9) mL/min/1.73m2. The crude annual eGFR decline rates were − 3.60 ± 4.00 mL/min/1.73 m2 pre- and − 2.28 ± 3.56 mL/min/1.73 m2 post-AVF, resulting in a mean difference of 1.28 mL/min/1.73 m2 (95% CI 0.49, 2.07). In a mixed effect linear regression model, monthly eGFR decline was − 0.63 (95% CI -0.81, − 0.46; p 2/month. The period after AVF creation was associated with a relatively higher eGFR (β 0.94, 95% CI 0.61–1.26, p Conclusions In this cohort, AVF creation was associated with a significant reduction of eGFR decline. Further prospective studies are needed to confirm this association.

To develop a pediatric-specific hypertension algorithm using administrative data and use it to evaluate the association between acute kidney injury (AKI) in the intensive care unit (ICU) and hypertension diagnosis 5 years post-discharge. Two-center retrospective cohort study of children (≤ 18 years old) admitted to the pediatric ICU in Montreal, Canada, between 2003 and 2005 and followed until 2010. Patients with a valid healthcare number and without end-stage renal disease were included. Patients who could not be merged with the provincial database, did not survive admission, underwent cardiac surgery, had pre-existing renal disease associated with hypertension or a prior diagnosis of hypertension were excluded. AKI defined using the Kidney Disease: Improving Global Outcomes (KDIGO) definition. Using diagnostic codes and medications from administrative data, novel pediatric-specific hypertension definitions were designed. Both the evaluation of the prevalence of hypertension diagnosis and the association between AKI and hypertension occurred. Nineteen hundred and seventy eight patients were included (median age at admission [interquartile range] 4.3 years [1.1–11.8], 44% female, 325 (16.4%) developed AKI). Of these patients, 130 (7%) had a hypertension diagnosis 5 years after discharge. Patients with AKI had a higher prevalence of hypertension diagnosis [non-AKI: 84/1653 (5.1%) vs. AKI: 46/325 (14.2%), p

Additional file 1: Table S1. Baseline characteristics excluding patients with stable kidney function. Table S2. Estimated glomerular filtration rate at end of follow-up excluding patients with stable kidney function. Table S3. Determinants of the eGFR excluding patients with stable kidney disease- Adjusted mixed effect linear regression. Table S4. Determinants of the eGFR excluding patients with a change in RAAS blockade use - Adjusted mixed effect linear regression. Figure S1. Annual eGFR decline pre- and post-AVF creation over different observational periods.

Supplemental material, Supplementary_material_DArienzo_et_al_Revision_2_Clean for A Validation Study of Administrative Health Care Data to Detect Acute Kidney Injury in the Pediatric Intensive Care Unit by David D’Arienzo, Erin Hessey, Rami Ali, Sylvie Perreault, Susan Samuel, Louise Roy, Jacques Lacroix, Philippe Jouvet, Genevieve Morissette, Marc Dorais, Jean-Philippe Lafrance, Veronique Phan, Michael Pizzi, Rahul Chanchlani and Michael Zappitelli in Canadian Journal of Kidney Health and Disease

The optimal vitamin D3 therapy for the treatment of secondary hyperparathyroidism (SHPT) in chronic hemodialysis patients is still controversial. Recent studies suggest that uremia in end-stage renal disease is associated with enzymatic hepatic dysfunction altering 25-hydroxylation of vitamin D3. The goal of our study was to compare the efficacy of calcitriol, the fully hydroxylated active form of vitamin D3, to alfacalcidol which needs 25-hydroxylation to be effective, for the treatment of SHPT in chronic hemodialysis patients. We retrospectively reviewed 45 chronic hemodialysis patients who were switched from oral alfacalcidol to oral calcitriol for the treatment of SHPT. Parathyroid hormone (PTH), serum calcium and serum phosphorus levels were compared pre- and post-conversion using paired Student’s t tests. The mean dose of active vitamin D3 decreased from 3.50 mcg/week at baseline to 2.86 mcg (P

Supplemental material, Supplementary_table_1 for Association Between Low-Molecular-Weight Heparin and Risk of Bleeding Among Hemodialysis Patients: A Retrospective Cohort Study by Hind H. Lazrak, Emilie René, Naoual Elftouh and Jean-Philippe Lafrance in Canadian Journal of Kidney Health and Disease

Supplemental material, Appendices_(1) for Hospitalizations in Dialysis Patients in Canada: A National Cohort Study by Amber O. Molnar, Louise Moist, Scott Klarenbach, Jean-Philippe Lafrance, S. Joseph Kim, Karthik Tennankore, Jeffrey Perl, Joanne Kappel, Michael Terner, Jagbir Gill, and Manish M. Sood in Canadian Journal of Kidney Health and Disease

Hyperphosphatemia and metabolic acidosis are frequently encountered in advanced chronic kidney disease (CKD) patients. Correction of metabolic acidosis in patients with advanced CKD leads to a decrease in the progression of renal impairment and improves nutritional outcomes. Lanthanum carbonate is used for control of hyperphosphatemia. This study evaluated the effect of lanthanum carbonate on metabolic acidosis in CKD IV-V patients and in patients on dialysis.Retrospective data of patients in whom lanthanum carbonate therapy was initiated were collected from 2009 to 2013 in a single dialysis center. Of the 79 patients in whom lanthanum carbonate was introduced, 51 patients were included in the analysis. Of the 51 patients, 39 patients received chronic hemodialysis, two patients received peritoneal dialysis therapy, and 10 patients had stage IV-V CKD not on dialysis. The primary outcome was the serum bicarbonate change after the introduction of lanthanum carbonate.There was a significant increase in mean serum bicarbonate concentration of 2.79 mmol/L (p ≤ 0.001) compared to baseline. The increase remained in the CKD IV-V patients (2.50 mmol/L, p = 0.005) and in the patients on dialysis (2.81 mmol/L, p0.001). Serum bicarbonate remained higher (p0.05) than baseline up to 6 months after lanthanum carbonate introduction.In this study, lanthanum carbonate introduction increased serum bicarbonate concentration in a small sample of CKD IV-V patients and in patients on dialysis. Further studies are needed to confirm this effect and investigate whether the correction of metabolic acidosis by using lanthanum carbonate in CKD IV-V patients can improve clinical outcomes.

Background and objectives Peritoneal dialysis (PD) is associated with an increased risk of infection-related hospitalization (IRH) compared with hemodialysis. The objective of this study was to compare mortality and overall readmission after an IRH between PD and hemodialysis. Design, setting, participants, & measurements This propensity score–matched retrospective cohort study assessed patients undergoing long-term dialysis patients, derived from the Canadian Organ Replacement Register and Regie de l’assurance maladie du Quebec, who had at least one IRH between January 2001 and December 2007. Patients were followed until death, kidney transplantation, or end of the study period. To estimate the probability of receiving PD versus hemodialysis, propensity scores were obtained using multivariable logistic regression. Mortality and overall readmission risks after the initial IRH were compared using a Cox survival model. Results A total of 354 pairs of patients who had at least one IRH were matched for propensity score. During follow-up (median, 1.25 years), 138 hemodialysis patients (24.7/100 patient-years; 95% confidence interval [95% CI], 20.7 to 29.1) and 130 PD patients (21.2/100 patient-years; 95% CI, 17.7 to 25.1) died; 265 hemodialysis patients (144.6/100 patient-years; 95% CI, 127.7 to 163.1) and 299 PD patients (173.2/100 patient-years; 95% CI, 154.1 to 194.0) were readmitted for any cause; and 121 hemodialysis patients (29.7/100 patient-years; 95% CI, 24.7 to 35.5) and 168 PD patients (44.7/100 patient-years; 95% CI, 38.2 to 52.0) were readmitted for an infection. Compared with hemodialysis, PD was not associated with a different mortality risk after an IRH (hazard ratio [HR], 0.87; 95% CI, 0.69 to 1.11). PD was associated with a higher risk of infection-related overall readmission compared with hemodialysis (HR, 1.44; 95% CI, 1.14 to 1.81), but not with the risk of all-cause overall readmission (HR, 1.15; 95% CI, 0.98 to 1.36). Conclusions PD was not associated with higher mortality or all-cause overall readmission following an IRH compared with hemodialysis, but PD patients were at higher risk of infection-related overall readmission after IRH. IRHs are associated with significant mortality and overall readmissions. Evaluation of strategies to reduce infections in both hemodialysis and PD recipients are needed to improve patient care and outcomes.

Background Low molecular weight heparins (LMWH) have been extensively studied and became the treatment of choice for several indications including pulmonary embolism. While their efficacy in hemodialysis is considered similar to unfractionated heparin (UFH), their safety remains controversial mainly due to a risk of bioaccumulation in patients with renal impairment. The aim of this systematic review was to evaluate the safety of LMWH when compared to UFH for extracorporeal circuit (ECC) anticoagulation. Methods We used Pubmed, Embase, Cochrane central register of controlled trials, Trip database and NICE to retrieve relevant studies with no language restriction. We looked for controlled experimental trials comparing LMWH to UFH for ECC anticoagulation among end-stage renal disease patients undergoing chronic hemodialysis. Studies were kept if they reported at least one of the following outcomes: bleeding, lipid profile, cardiovascular events, osteoporosis or heparin-induced thrombocytopenia. Two independent reviewers conducted studies selection, quality assessment and data extraction with discrepancies solved by a third reviewer. Relative risk and 95% CI was calculated for dichotomous outcomes and mean weighted difference (MWD) with 95% CI was used to pool continuous variables. Results Seventeen studies were selected as part of the systematic. The relative risk for total bleeding was 0.76 (95% CI 0.26–2.22). The WMD calculated for total cholesterol was −28.70 mg/dl (95% CI -51.43 to −5.98), a WMD for triglycerides of −55.57 mg/dl (95% CI -94.49 to −16.66) was estimated, and finally LDL-cholesterol had a WMD of −14.88 mg/dl (95% CI -36.27 to 6.51). Conclusions LMWH showed to be at least as safe as UFH for ECC anticoagulation in chronic hemodialysis. The limited number of studies reporting on osteoporosis and HIT does not allow any conclusion for these outcomes. Larger studies are needed to evaluate properly the safety of LMWH in chronic hemodialysis. Electronic supplementary material The online version of this article (doi:10.1186/s12882-017-0596-4) contains supplementary material, which is available to authorized users.

Supplementary material providing the meta-analysis results for cholesterol (Table S1.) and triglycerides (Tables S2.), OPG/RANKL ratios (Table S3.), sensitivity analysis results (Table S4.) and funnel plots for publication bias. (PDF 177 kb)

Literature search strategies for Pubmed, Embase and Cochrane as used in this study are detailed in this document. (PDF 16 kb)

BACKGROUND After cardiovascular disease, infection is the second leading reason for admission to hospital among patients receiving long-term dialysis. We examined whether duration of dialysis treatment influences the rate of infection-related admission to hospital. METHODS Using provincial administrative databases for Quebec, we built a retrospective cohort of all adults receiving long-term dialysis (hemodialysis or peritoneal dialysis) between 2001 and 2007. We evaluated rates of infection-related admission to hospital according to length of time on dialysis. RESULTS A cohort of 9822 patients (mean age 66.3 [standard deviation ± 14.7] yr; 39.7% female) were followed for a median of 2.1 (range 1.0-3.9) years. Between 2001 and 2007, infection-related hospital admissions remained stable (from 0.20 to 0.19 per person-year; p = 0.7). All-cause hospital admission rates decreased by 22.9% (from 1.53 to 1.18 per person-year; p

Background Patients suffering from chronic kidney disease are at greater risk of developing infection than the normal population, and infections are the second cause of mortality after cardiovascular complications in this population. Some reports suggest that the intake of active vitamin D might be beneficial to prevent infections. Therefore, we aimed to determine if the oral intake of vitamin D receptor activator (VDRA) is associated with a lower risk of infection-related hospitalization (IRH) among incident chronic hemodialysis patients. Methods We conducted a nested case–control study in a cohort of 4933 patients initiating chronic hemodialysis between 1 January 2001 and 31 December 2007 in Quebec, Canada, using administrative databases. We identified cases of hospital admission indicating an infection as main diagnosis on the hospital's discharge sheet. Up to 10 controls were randomly selected for each case. Association between oral VDRA use and risk of IRH was estimated using conditional logistic regression. Results We identified 1136 cases of IRH and 10 396 controls during the study period. The intake of VDRA was not associated with the risk of being hospitalized due to an infection (odds ratio [OR], 1.07; 95% confidence interval [CI], 0.95–1.20). Using the prior 6-month cumulative dose of VDRA, we also found that a cumulative VDRA dose of less than 45 mcg (OR, 1.05; 95%CI, 0.92–1.19) or greater than 45 mcg (OR, 1.15; 95%CI, 0.96–1.36) was not associated with the IRH risk. Conclusions The oral intake of VDRA was not associated with the risk of IRH in incident hemodialysis patients. Copyright © 2014 John Wiley & Sons, Ltd.

Hyperkalemia is frequent, but occurs mostly in patients with chronic kidney disease and is often the cause of discontinuation or omission of renin-angiotensin-aldosterone system inhibitors in patients with diabetes, chronic kidney disease and heart failure.Without much evidence in the literature on its efficacy, sodium polystyrene sulfonate is being used frequently in the clinical setting to treat hyperkalemia. In the last few years, two new promising agents have been developed to treat hyperkalemia - patiromer and sodium zirconium cyclosilicate 9 (ZS-9). Both patiromer and ZS-9 have been shown to decrease potassium in patients with hyperkalemia and then to maintain normokalemia. Gastrointestinal adverse events were more frequent with patiromer, and edema occurred in patients using high doses of ZS-9, possibly due to its high sodium content.Although patiromer and ZS-9 are very promising in terms of safety and efficacy, many questions remain, mostly in terms of selection of patients, long-term effects and costs.

Background Clinical practice guidelines for appropriate nonsteroidal anti-inflammatory drug (NSAID) utilisation focus on preventing NSAID-related gastrointestinal (GI), cardiovascular (CV), congestive heart failure (CHF) and renal adverse events. We compared concordance of NSAID prescriptions with clinical practice guideline recommendations in Quebec, pre and post rofecoxib withdrawal from market. Methods Data were obtained from the Quebec Health Insurance Agency (RAMQ). All prescriptions for celecoxib and traditional NSAIDs (tNSAIDs) dispensed to patients ≥50 years of age were evaluated for concordance with clinical practice guidelines. Prescriptions were stratified by time period (pre and post rofecoxib withdrawal) and, GI, CV, CHF and renal risk factors at the dispensing date. Gastro-protective agent (GPA) co-prescriptions were also evaluated. Results We assessed 1,966,793 celecoxib and 1,743,481 tNSAIDs prescriptions. Of celecoxib prescriptions, 87.2% and 86.5% were appropriate in the post- and pre-periods, respectively, compared to 72.6% and 70.1% of tNSAIDs prescriptions, respectively. In logistic regression, ‘appropriateness’ of celecoxib prescriptions increased with age, rheumatoid arthritis and osteoarthritis (OA), and was higher in the post- versus pre-period (odds ratio 1.22, 95% confidence interval 1.18–1.26); it was lower in women and in patients with higher income. ‘Appropriateness’ of tNSAID prescriptions decreased in the post-period (0.92, 0.89–0.95), was lower in older persons and those with OA, and higher in women and in higher income patients. Of tNSAID prescriptions that should have received a GPA co-prescription, only 45.6% did. Conclusion Concordance with guideline recommendations increased for celecoxib and decreased for tNSAIDs after rofecoxib withdrawal; GPA co-prescription with tNSAIDs remained suboptimal. Copyright © 2012 John Wiley & Sons, Ltd.

OBJECTIVE To evaluate temporal trends in rates of initial lower extremity amputation (ILEA) among patients with diabetes in the Veterans Health Administration (VHA). RESEARCH DESIGN AND METHODS Retrospective administrative data analysis of VHA clinic users with diabetes in fiscal years (FY) 2000 to 2004 (1 October 1999–30 September 2004). We calculated annual age– and sex–standardized rates of initial major, minor, and total amputations for the overall population and for various racial/ethnic groups (African Americans, Hispanics, and whites). Trends in ILEA risk were evaluated with and without adjustment for demographic characteristics and other potential risk factors, including presence of microvascular and macrovascular diseases, and antiglycemic treatment. RESULTS Study populations of VHA patients with diabetes and without prior amputations ranged from 405,580 in FY 2000 to 739,377 in FY 2004. Age- and sex-standardized ILEA rates decreased by 34% (7.08/1,000 patients in FY 2000 to 4.65/1,000 patients in FY 2005) during the 5-year period. Minor and major amputation rates decreased by 33% (4.59 to 3.06/1,000) and 36% (2.49 to 1.59/1,000), respectively. Of major amputations, below-knee rates decreased from 1.08 to 0.87/1,000 (−19%), and above-knee decreased from 1.41 to 0.72/1,000 (−49%). Similar trends were seen for all racial groups. ILEA risk decreased by 28% (odds ratio 0.72 [95% CI 0.68–0.75]) when FY 2004 was compared with FY 2000 in the model, adjusting for demographic characteristics. This risk decrease was 22% in the model adjusting for all independent variables (odds ratio 0.78 [95% CI 0.74–0.82]). CONCLUSIONS Downward 5-year trends in ILEA rates were observed for all amputation levels and among all racial groups, even after adjustment for risk differences over time.

Background Existing acute kidney injury (AKI) definitions are not well adapted for database studies, leading to a great variety of methods used in research. Variations in time before hospitalization used to assess baseline kidney function when identifying episodes of AKI may lead to different case samples and mortality risks in database studies, but the magnitude of these effects is not known. Study Design A retrospective cohort study. Settings & Participants 1,126,636 veterans hospitalized at least once within the US Department of Veterans Affairs health care system between 2000 and 2005. Predictor AKI was defined by comparing (using ratio [≥1.5] or difference [increase of 0.3-0.5 mg/dL]) the highest serum creatinine level during hospitalization with the lowest level during 4 different baseline assessment periods (in-hospital only and 3, 6, or 12 months preadmission). Outcomes & Measurements In-hospital mortality risk was estimated using multivariable logistic regression models. Results Using the ratio definition, the cumulative incidence of AKI ranged from 12.5% (in-hospital only) to 18.3% (12 months preadmission). Newly added cases had milder AKI and lower mortality risk. The discriminative power increased slightly (C statistic increased from 0.846 to 0.855; P = 0.001) by extending the baseline period to at least 3 months. Both the ratio and difference definitions did not perform well in patients with chronic kidney disease stages 4 and 5. Limitations Possibility of residual confounding and under-representation of women (4.5%). Conclusions Many additional AKI cases may be identified by extending the baseline assessment period; however, added cases may be less severe with lower mortality risk. The relative strengths of these biases and combined effects of reducing misclassification (identification of more AKI cases) and increasing risk dilution (identifying milder cases) may vary across populations. Consensus regarding how baseline kidney function should be determined in database studies should be reached.

Background. Whilst chronic kidney disease (CKD) has been identified as a risk factor for the development of acute kidney injury (AKI), little has been published about the incidence and outcomes of those acute injuries on chronic stable kidney disease and even less in a referred cohort of CKD patients followed up by nephrologists. Methods. We followed up 6862 patients registered as CKD in British Columbia, Canada for a median time of 19.4 months after they achieved an estimated glomerular filtration rate (eGFR) value ≤30 mL/min/1.73 m 2 . AKI was defined as a decrease in eGFR of ≥25% compared to a moving baseline eGFR within 25 days. Results. Of the CKD patients, 44.9% had at least one AKI episode. Crude incidence rate for a first AKI event was 34.8 per 100 person-years. Older age [adjusted relative risks (RR) = 0.93 by 10 years, 95% confidence intervals (CI) = 0.90, 0.95] was associated with a lower risk of AKI. Of the patients, 15.3% died before dialysis and 18.1% initiated dialysis. AKI was associated with both a higher risk of death (adjusted RR = 2.32, 95% CI = 2.04, 2.64) and an increased risk of dialysis (adjusted RR = 2.33, 95% CI = 2.07, 2.61). Conclusions. In a referred CKD population, AKI was a frequent event and associated with higher risks of dialysis and mortality. The incidence of AKI appears to be less with older age in this population. Quantification of AKI incidence and its risk factors in different populations is important for clinicians and planners, so that appropriate identification, prevention and treatment strategies can be tested.

Acute kidney injury (AKI) associates with higher in-hospital mortality, but whether it also associates with increased long-term mortality is unknown, particularly after accounting for residual kidney function after hospital discharge. We retrospectively analyzed data from US veteran patients who survived at least 90 d after discharge from a hospitalization. We identified AKI events not requiring dialysis from laboratory data and classified them according to the ratio of the highest creatinine during the hospitalization to the lowest creatinine measured between 90 d before hospitalization and the date of discharge. We estimated mortality risks using multivariable Cox regression models adjusting for demographics, comorbidities, medication use, primary diagnosis of admission, length of stay, mechanical ventilation, and postdischarge estimated GFR (residual kidney function). Among the 864,933 hospitalized patients in the study cohort, we identified 82,711 hospitalizations of patients with AKI. In the study population of patients who survived at least 90 d after discharge, 17.4% died during follow-up (AKI 29.8%, without AKI 16.1%). The adjusted mortality risk associated with AKI was 1.41 (95% confidence interval [CI] 1.39 to 1.43) and increased with increasing AKI stage: 1.36 (95% CI 1.34 to 1.38), 1.46 (95% CI 1.42 to 1.50), and 1.59 (95% CI 1.54 to 1.65; P < 0.001 for trend). In conclusion, AKI that does not require dialysis associates with increased long-term mortality risk, independent of residual kidney function, for patients who survive 90 d after discharge. Long-term mortality risk is highest among the most severe cases of AKI.

Hospitalizations of chronic dialysis patients have not been previously studied at a national level in Canada. Understanding the scope and variables associated with hospitalizations will inform measures for improvement.To describe the risk of all-cause and infection-related hospitalizations in patients on dialysis.Retrospective cohort study using health care administrative databases.Provinces and territories across Canada (excluding Manitoba and Quebec).Incident chronic dialysis patients with a dialysis start date between January 1, 2005, and March 31, 2014. Patients with a prior history of kidney transplantation were excluded.Patient characteristics were recorded at baseline. Dialysis modality was treated as a time-varying covariate. The primary outcomes of interest were all-cause and dialysis-specific infection-related hospitalizations.Crude rates for all-cause hospitalization and infection-related hospitalization were determined per patient year (PPY) at 7 and 30 days, and at 3, 6, and 12 months postdialysis initiation. A stratified, gamma-distributed frailty model was used to assess repeat hospital admissions and to determine the inter-recurrence dependence of hospitalizations within individuals, as well as the hazard ratio (HR) attributed to each covariate of interest.A total of 38 369 incident chronic dialysis patients were included: 38 088 adults and 281 pediatric patients (age less than 18 years). There were 112 374 hospitalizations, of which 11.5% were infection-related hospitalizations. The all-cause hospitalization rate was similar for all adult age groups (age 65 years and older: 1.40, 1.35, and 1.18 admissions PPY at 7 days, 30 days, and 6 months, respectively). The all-cause hospitalization rate was higher for pediatric patients (1.67, 2.48, and 2.47 admissions PPY at 7 days, 30 days, and 6 months, respectively; adjusted HR: 2.73, 95% confidence interval [CI]: 2.37-3.15, referent age group: 45-64 years). Within the first 7 days after dialysis initiation, patients on peritoneal dialysis had a higher risk of all-cause hospitalization (HR: 1.27, 95% CI: 1.07-1.50) and infection-related hospitalization (HR: 2.05, 95% CI: 1.19-3.55) compared with patients on hemodialysis. Beyond 7 days, the risk did not differ significantly by dialysis modality. Female sex and Indigenous race were significant risk factors for all-cause hospitalization.The cohort had too few home hemodialysis patients to examine this subgroup. The outcome of infection-related hospitalization was determined using diagnostic codes. Dialysis patients from Manitoba and Quebec were not included.In Canada, the rates of hospitalization were not influenced by dialysis modality beyond the initial 7-day period following dialysis initiation; however, the rate of hospitalization in pediatric patients was higher than in adults at every time frame examined.Le taux d’hospitalisation des patients dialysés n’avait jamais fait l’objet d’une étude pancanadienne. Une connaissance approfondie de la portée et des variables associées aux hospitalisations orientera les mesures d’amélioration.L’étude visait à mieux évaluer les risques d’hospitalisations des patients dialysés; toutes causes confondues ou liées spécifiquement à une infection.Il s’agit d’une étude de cohorte rétrospective fondée sur des bases de données administratives en santé.L’étude couvrait les provinces et territoires du Canada à l’exception du Québec et du Manitoba.L’étude a porté sur tous les patients dialysés à vie dont le traitement avait commencé entre le 1er janvier 2005 et le 31 mars 2014. Les patients ayant reçu une greffe rénale ont été exclus.Les caractéristiques initiales des patients ont été consignées, et la modalité de dialyse a été traitée comme une co-variable sujette à changement dans le temps. La principale issue d’intérêt était une hospitalisation due à une infection directement liée à la dialyse, ou une hospitalisation toutes causes confondues.Les taux bruts d’hospitalisations toutes causes confondues (global) et d’hospitalisations liées à une infection ont été calculés en années-patients (HAP) à différents moments suivant le début de la dialyse (7 jours, 30 jours, 3 mois, 6 mois et 12 mois). Un modèle stratifié de fragilité à distribution gamma a été employé pour i) répertorier les hospitalisations répétées; ii) déterminer l’interrécurrence et le lien de dépendance entre les hospitalisations pour chaque patient; et iii) établir le rapport de risque (RR) attribué à chaque covariable d’intérêt.En tout, 38 369 patients dialysés, soit 38 088 adultes et 281 patients mineurs (moins de 18 ans) ont été inclus dans l’étude. Au cours de la période étudiée, on a répertorié 112 374 hospitalisations, dont 11,5 % étaient dues à une infection en lien direct avec la dialyse. Le taux d’hospitalisations global était similaire pour tous les groupes d’âge chez les patients adultes. Par exemple, chez les patients âgés de 65 ans et plus, ce taux se situait respectivement à 1,40 HAP, à 1,35 HAP et à 1,18 HAP lorsque calculé 7 jours, 30 jours et 6 mois après l’initiation de la dialyse. Lorsque comparé au groupe des 45-64 ans, le taux d’hospitalisations global s’est avéré plus élevé chez les patients pédiatriques (1,67 HAP à 7 jours, 2,48 HAP à 30 jours et 2,47 HAP à 6 mois) post-initiation de la dialyse (RR: 2,73; IC 95 %: 2,37-3,15). Dans les 7 jours suivant l’initiation du traitement, les patients traités par dialyse péritonéale présentaient un risque plus élevé d’hospitalisation toutes causes confondues (RR: 1,27; IC 95 %: 1,07-1,50) ou d’hospitalisation liée à une infection (RR: 2,05; IC 95 %: 1,19-3,55) que les patients hémodialysés. Par contre, cet écart entre les modalités de dialyse n’était plus observable au-delà des sept premiers jours. Enfin, le fait d’être autochtone ou de sexe féminin s’avérait un facteur de risque d’hospitalisation significatif (toutes causes confondues).Plusieurs facteurs limitent la portée des résultats: i) la cohorte comptait trop peu de patients hémodialysés à domicile pour permettre une analyse de ce sous-groupe; ii) les hospitalisations relatives à une infection ont été établies à l’aide de codes diagnostiques; et iii) les patients dialysés résidant au Québec et au Manitoba étaient exclus de l’étude.Au Canada, au-delà des sept jours suivant l’initiation de la dialyse, la modalité employée n’a plus d’influence sur les taux d’hospitalisations. Cependant, à tous les moments post-initiation mesurés, les taux d’hospitalisations se sont avérés plus élevés chez les patients pédiatriques que chez les adultes.

Purpose Use of non-steroidal anti-inflammatory drugs (NSAID) is associated with risk of acute kidney injury (AKI). Risk of AKI may vary with selectivity of the NSAID, but this has not been studied in a large cohort where AKI was assessed directly from laboratory data. The objective was to compare AKI risk between selective and non-selective NSAIDs using a laboratory-based definition of AKI. Methods We conducted a retrospective nested case-control study in the U.S. Department of Veterans Affairs health care system. From a cohort of 1 459 271 new NSAID users, we identified 22 824 cases of AKI (97% male; mean age: 63 years), and 336 734 matched controls between 2000 and 2006. AKI was defined as a creatinine increase of greater than 50%. Results We found higher risk of AKI in new users of any single NSAID (adjusted odds ratio = 1.82; 95%CI: 1.68, 1.98) compared to non-users without recent use. The risk of AKI varied among different NSAIDs with risk generally increasing with decrease in selectivity: rofecoxib (0.95; 0.64, 1.42), celecoxib (0.96; 0.63, 1.47), meloxicam (1.13; 0.63, 2.05), etodolac (1.31; 1.08, 1.59), diclofenac (1.11; 0.84, 1.48), piroxicam (1.53; 1.05, 2.23), salsalate (1.51; 1.22, 1.87), sulindac (1.61; 1.12, 2.30), ibuprofen (2.25, 2.04, 2.49), naproxen (1.72; 1.52, 1.95), high dose aspirin (3.64; 2.46, 5.37), indomethacin (1.94; 1.56, 2.42), keterolac (2.07; 1.78, 2.41). Those using multiple NSAIDs appeared to have higher risk (2.90; 2.62, 3.22). Conclusions This study provides evidence that risk of AKI may be lower with more selective agents than with naproxen or other non-selective NSAIDs. Copyright © 2009 John Wiley & Sons, Ltd.

Calcidiol insufficiency is highly prevalent in chronic kidney disease (CKD) and osteoporotic patients. We assessed and compared calcidiol levels in these two groups from the same geographical area to differentiate environmental factors from characteristics related to CKD.We measured calcidiol levels in 160 predialysis (group 1) and 53 osteoporotic (group 2) patients from a single center. Calcidiol insufficiency was defined as a level between 37.5 and 75 nmol/l and calcidiol deficiency was defined as a level below 37.5 nmol/l.In group 1, mean glomerular filtration rate (GFR), calcidiol, and parathyroid hormone (PTH) levels were 18.3 +/- 4.7 ml/min, 38.7 +/- 15.1 nmol/l, and 21.9 +/- 19.1 pmol/l. Calcidiol insufficiency and deficiency were present in 98.7% of patients. There was an inverse correlation between calcidiol and PTH levels (r = -0.25; P = 0.001). In group 2, mean GFR, calcidiol levels, and PTH levels were 68.6 +/- 17.6 ml/min, 73.8 +/- 27.1 nmol/l, and 4.23 +/- 1.83 pmol/l, respectively. Calcidiol insufficiency and deficiency were present in 50.9% of patients. There was an inverse correlation between calcidiol and PTH levels (r =-0.44; P = 0.02).In our predialysis population, calcidiol insufficiency and deficiency are present in almost every patient, being more common than previously reported. It is also more frequent than in a similar osteoporotic population, suggesting a cause unrelated to environmental factors. Interestingly, there is a significant inverse correlation between calcidiol and parathyroid levels in both populations. Further studies are needed to enable understanding of the mechanisms underlying calcidiol insufficiency.

Background Vascular access-related infections and septicemia are the main causes of infections among hemodialysis patients, the majority of them caused by Staphylococcus species. Acetylsalicylic acid (ASA) has recently been reported with a probable antistaphylococcal activity. This study aimed to evaluate the effect of ASA on the risk of dialysis-related infection and septicemia among incident chronic hemodialysis patients. Methods In a nested case–control study, we identified 449 cases of vascular access-related infections and septicemia, and 4156 controls between 2001 and 2007 from our incident chronic hemodialysis patients’ cohort. Cases were defined as patients hospitalized with a main diagnosis of vascular access-related infection or septicemia on the discharge sheet (ICD-9 codes). Up to ten controls per case were selected by incidence density sampling and matched to cases on age, sex and follow-up time. ASA exposure was measured at the admission and categorized as: no use, low dose (80–324 mg/d), high dose (≥325 mg/d). Odds ratios (OR) for infections were estimated using multivariable conditional logistic regression analysis, adjusting for potential confounders. Results Compared to no use, neither dose of ASA was associated with a decreased risk of infection: low dose (OR 1.03, 95 % CI 0.82-1.28) and high dose (OR 1.30, 95 % CI 0.96-1.75). However, diabetes (OR = 1.32, 95 % CI = 1.07–1.62) and anticoagulant use (OR = 1.62, 95 % CI = 1.30–2.02) were associated with a higher risk. Conclusion Among hemodialysis patients, ASA use was not associated with a reduced risk of hospitalizations for dialysis-related infections or septicemia. However, ASA may remain beneficial for its cardiovascular indications.

Background and objectives Hyperkalemia affects up to 10% of patients with CKD. Sodium polystyrene sulfonate has long been prescribed for this condition, although evidence is lacking on its efficacy for the treatment of mild hyperkalemia over several days. This study aimed to evaluate the efficacy of sodium polystyrene sulfonate in the treatment of mild hyperkalemia. Design, setting, participants, & measurements In total, 33 outpatients with CKD and mild hyperkalemia (5.0–5.9 mEq/L) in a single teaching hospital were included in this double–blind randomized clinical trial. We randomly assigned these patients to receive either placebo or sodium polystyrene sulfonate of 30 g orally one time per day for 7 days. The primary outcome was the comparison between study groups of the mean difference of serum potassium levels between the day after the last dose of treatment and baseline. Results The mean duration of treatment was 6.9 days. Sodium polystyrene sulfonate was superior to placebo in the reduction of serum potassium levels (mean difference between groups, −1.04 mEq/L; 95% confidence interval, −1.37 to −0.71). A higher proportion of patients in the sodium polystyrene sulfonate group attained normokalemia at the end of their treatment compared with those in the placebo group, but the difference did not reach statistical significance (73% versus 38%; P=0.07). There was a trend toward higher rates of electrolytic disturbances and an increase in gastrointestinal side effects in the group receiving sodium polystyrene sulfonate. Conclusions Sodium polystyrene sulfonate was superior to placebo in reducing serum potassium over 7 days in patients with mild hyperkalemia and CKD.

Background It is unknown whether variability of estimated Glomerular Filtration Rate (eGFR) is a risk factor for dialysis or death in patients with chronic kidney disease (CKD). This study aimed to evaluate variability of estimated Glomerular Filtration Rate (eGFR) as a risk factor for dialysis or death to facilitate optimum care among high risk patients. Methods A longitudinal retrospective cohort study of 70,598 Veterans Health Administration veteran patients with diabetes and CKD (stage 3–4) in 2000 with up to 5 years of follow-up. VHA and Medicare files were linked to derive study variables. We used Cox proportional hazards models to evaluate association between time to initial dialysis/death and key independent variables: time-varying eGFR variability (measured by standard deviation (SD)) and eGFR means and slopes while adjusting for prior hospitalizations, and comorbidities. Results There were 76.7% older than 65 years, 97.5% men, and 81.9% Whites. Patients were largely in early stage 3 (61.2%), followed by late stage 3 (28.9%), and stage 4 (9.9%); 29.1%, 46.8%, and 73.3%, respectively, died or had dialysis during the follow-up. eGFR SDs (median: 5.8, 5.1, and 4.0 ml/min/1.73 m2 ) and means (median: 54.1, 41.0, 27.2 ml/min/1.73 m2) from all two-year moving intervals decreased as CKD advanced; eGFR variability (relative to the mean) increased when CKD progressed (median coefficient of variation: 10.9, 12.8, and 15.4). Cox regressions revealed that one unit increase in a patient’s standard deviation of eGFRs from prior two years was significantly associated with about 7% increase in risk of dialysis/death in the current year, similarly in all three CKD stages. This was after adjusting for concurrent means and slopes of eGFRs, demographics, prior hospitalization, and comorbidities. For example, the hazard of dialysis/death increased by 7.2% (hazard ratio:1.072; 95% CI = 1.067, 1.080) in early stage 3. Conclusion eGFR variability was independently associated with elevated risk of dialysis/death even after controlling for eGFR means and slopes. Electronic supplementary material The online version of this article (doi:10.1186/s12882-015-0025-5) contains supplementary material, which is available to authorized users.

Several laboratory parameters can be altered in advanced renal failure. Results may be difficult to interpret and may become misleading and unreliable in such a context. On the other hand, some of the alterations may reflect real abnormalities. Thus sufficient knowledge and careful judgment are required by the clinician. We reviewed different publications related to biochemical anomalies in renal failure and report some of the main findings. The sections are divided as follows: cardiovascular risk factors and markers, inflammation markers, pancreatic and liver function tests, hormones, bone turnover indices and parathyroid hormone assays, tumor markers, carbohydrate metabolism indicators, and others. The information provided should be useful to clinicians involved in the care of renal failure patients.

quality improvement tool. Psychooncology 2012 46. Holland J, Watson M, Dunn J. The IPOS new International Standard of Quality Cancer Care: integrating the psychosocial domain into routine care. Psychooncology 2012, doi:10.1002/ pon.3116 [Epub ahead of print]. 47. Bultz BD, Groff SL, Fitch M et al. Implementing screening for distress, the 6th vital sign: a Canadian strategy for changing practice. Psychooncology 2011; 20: 463–469

Tacrolimus extended-release formulation has been approved for use in Canada since October 2008. In initial studies, efficacy and safety profile were demonstrated as similar for both formulations (twice-daily tacrolimus and extended-release formula tacrolimus). To validate the safety and efficacy of extended-release formula tacrolimus, we conducted a prospective observational study.At our institution, between January 2009 and January 2010, the switch from tacrolimus to extended-release formula tacrolimus was done in 130 stable kidney recipients. Clinical data were accessed at baseline (data before conversion), 1 to 2 weeks, 1 month, 3 months, 6 months, 12 months, and 24 months after conversion.One hundred thirty renal transplant recipients were included in the current study. During the observation period, we saw no acute rejection and no change in graft function (mean serum creatinine levels remained stable). However, compared with baseline, mean tacrolimus trough levels were significantly reduced at 1 to 2 weeks, at 1 month, 6 months, 12 months, and at 24 months after conversion. Regarding the safety profile, no significant changes were noted in blood glucose, potassium, and magnesium. Approximately 35% of recipients preferred the extended-release formula tacrolimus to twice-daily tacrolimus.Conversion from twice-daily tacrolimus to extended-release once-daily tacrolimus appears to be safe and convenient up to 2 years after conversion in some recipients.

This study examined clinical problem-solving processes in the context of a telemedical consultation, in order to verify to what extent the technological environment preserves the characteristics of medical reasoning that are known to occur in more traditional clinical settings. This study also provided an opportunity for examining certain fundamental aspects of medical reasoning about complex cases. Within a case-study design, we used a theoretical framework and qualitative methods originating from cognitive science. Expert physicians used reasoning strategies commensurate with the complexity of the case. The technological context of the telemedical consultation did not overly contrive the interaction, allowing them to use real-time problem-solving processes characterizing medical reasoning in naturalistic settings. The results also suggest that high levels of expertise in the presence of very complex cases may elicit a particular configuration of problem-solving processes, associating certain reasoning patterns that are usually related to non-expert problem-solving with others that are typical of expertise. We believe that the evaluation of image transmission and diagnostic performance in telemedicine, as well as the determination of its indications and technological configurations, may benefit from taking into account, with the help of cognitive methodologies, the interacting problem-solving modalities that may be encountered in this context.