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International medical graduates (IMGs) seeking licensure in Canada have been recruited to practise in medically underserviced areas, but retention of these physicians remains a concern. This study explored retention of IMG family physicians in Manitoba and its predictors.We used data from the University of Manitoba, provincial registries and Manitoba Health. Inclusion criteria were IMGs who completed University of Manitoba IMG training or assessment programs, and their return-of-service. Practice location, certification and licensure status were examined. We used logistic regression to consider the effects of a mentorship program, Manitoba residency at application, IMG program and years since program graduation on retention.A total of 197 IMGs met the inclusion criteria. Most IMGs (63.5%) remained in Manitoba, and 59.2% of this group practised outside of Winnipeg. Of those remaining in Manitoba, most (69.6%) held full provincial licensure and national certification. The regression model was significant (χLong-term retention of IMG physicians remains a concern. Potential interventions likely to increase retention, such as Manitoba residency at application and a focus on mentorship programs, should be further explored.Des diplômés de facultés de médecine étrangères (DFME) désireux d’obtenir un permis d’exercice au Canada ont été recrutés pour exercer en régions sous-desservies, mais la fidélisation de ces médecins demeure préoccupante. Cette étude a examiné la fidélisation des médecins de famille DFME au Manitoba et les facteurs permettant de la prédire.Nous avons utilisé des données de l’Université du Manitoba, des registres provinciaux et du ministère de la Santé du Manitoba. Pour être inclus dans l’étude, les DFME devaient avoir suivi une formation adaptée à leur situation à l’Université du Manitoba ou avoir participé à un programme d’évaluation à cette même université, et avoir conclu une entente de retour de service. Le lieu de pratique, la certification et le type de permis obtenu ont été relevés. Nous avons utilisé une régression logistique pour tenir compte de l’effet sur la fidélisation des éléments suivants : avoir participé à un programme de mentorat, habiter au Manitoba au moment de demander l’admission au programme, avoir participé à un programme destiné aux DFME et nombre d’années écoulées depuis l’obtention du diplôme associé à ce programme.En tout, 197 DFME répondaient aux critères d’inclusion. La plupart des DFME (63,5 %) sont restés au Manitoba et, de ce groupe, 59,2 % pratiquent à l’extérieur de Winnipeg. Parmi ceux qui sont restés au Manitoba, la plupart (69,6 %) détenaient un permis d’exercice sans restriction et une certification nationale. Le modèle de régression logistique a été significatif (χLa fidélisation à long terme des médecins DFME demeure préoccupante. Il faudrait explorer davantage des interventions axées sur les facteurs susceptibles d’améliorer la fidélisation, notamment le fait que les postulants habitent au Manitoba au moment de présenter leur demande et l’importance à accorder aux programmes de mentorat.

Introduction The fact that acute kidney injury (AKI) is associated with worse clinical outcomes forms the basis of most AKI prognostic scoring systems. However, early reversibility of renal dysfunction in acute illness is not considered in such systems. We sought to determine whether early (≤ 24 hours after shock documentation) reversibility of AKI was independently associated with in-hospital mortality in septic shock. Methods Patient information was derived from an international database of septic shock cases from 28 different institutions in Canada, the United States and Saudi Arabia. Data from a final cohort of 5443 patients admitted with septic shock between Jan 1996 and Dec 2009 was analyzed. The following 4 definitions were used in regards to AKI status: (1) reversible AKI = AKI of any RIFLE severity prevalent at shock diagnosis or incident at 6 hours post-diagnosis that reverses by 24 hours, (2) persistent AKI = AKI prevalent at shock diagnosis and persisting during the entire 24 hours post-shock diagnosis, (3) new AKI = AKI incident between 6 and 24 hours post-shock diagnosis, and (4) improved AKI = AKI prevalent at shock diagnosis or incident at 6 hours post followed by improvement of AKI severity across at least one RIFLE category over the first 24 hours. Cox proportional hazards were used to determine the association between AKI status and in-hospital mortality. Results During the first 24 hours, reversible AKI occurred in 13.0%, persistent AKI in 54.9%, new AKI in 11.7%, and no AKI in 22.4%. In adjusted analyses, reversible AKI was associated with improved survival (HR, 0.64; 95% CI, 0.53-0.77) compared to no AKI (referent), persistent AKI (HR, 0.99; 95% CI, 0.88-1.11), and new AKI (HR, 1.41; 95% CI, 1.22-1.62). Improved AKI occurred in 19.1% with improvement across any RIFLE category associated with a significant decrease in mortality (HR, 0.53; 95% CI, 0.45-0.63). More rapid antimicrobial administration, lower Acute Physiology and Chronic Health Evaluation II score, lower age, and a smaller number of failed organs (excluding renal) on the day of shock as well as community-acquired infection were independently associated with reversible AKI. Conclusion In septic shock, reversible AKI within the first 24 hours of admission confers a survival benefit compared to no, new, or persistent AKI. Prognostic AKI classification schemes should consider integration of early AKI reversibility into the scoring system.

Background Peritoneal dialysis (PD) for long-term management of diuretic resistant volume overload in heart failure (HF) may provide potential benefit with few adverse consequences. We examined the impact of PD on clinical status hospitalizations, and complications of therapy in severe end-stage HF. Methods A consecutive case series of 10 transplant ineligible patients receiving PD solely for HF volume management between 2007 and 2011 was evaluated with clinical data reviewed pre- and post-PD initiation. Results The mean ejection fraction (EF) pre-PD was 24.5 ± 6.0% with the majority of patients having NYHA class IIIB symptoms and moderate-severe right ventricular dysfunction. 9/10 patients were Stage 3 chronic kidney disease (CKD) or worse. After PD initiation, average weight loss was almost 7 kg (p = 0.016) with improvement in diuretic response, peripheral edema, and functional class. There was a significant decrease in re-hospitalization from an average of 3.2 ± 2.5 to 0.1 ± 0.3 admissions per patient (p = 0.007) and reduced average length of stay from 37 ± 36.7 to 0.78 ± 2.3 days (p = 0.019). Summary Objective criteriabased institution of PD for the treatment of diuretic refractory severe-end-stage HF was well tolerated and demonstrated favorable outcomes; these included improved clinical status, reduced hospitalizations and length of stay, with very few and easily treatable PDrelated complications. PD appears to be a viable option in refractory, end-stage congestive heart failure (CHF).

After heart surgery, acute kidney injury (AKI) confers substantial long-term risk of death and chronic kidney disease. We hypothesized that small changes in serum creatinine (SCr) levels measured within a few hours of exit from the operating room could help discriminate those at low versus high risk of AKI.Prospective cohort of 350 elective cardiac surgery patients (valve or coronary artery bypass grafting) recruited in Winnipeg, Canada. Baseline SCr level was obtained at the preoperative visit 2 weeks before surgery. The postoperative SCr level was drawn within 6 hours of completion of surgery and then daily while the patient was in the hospital.Immediate (ie,6 hours) postoperative SCr level change (ΔSCr), categorized as within 10% (reference), decrease10%, or increase10% relative to baseline.AKI, defined according to the new KDIGO (Kidney Disease: Improving Global Outcomes) consensus definition as an increase in SCr level0.3 mg/dL within 48 hours or1.5 times baseline within 1 week.We compared the C statistic of logistic models with and without inclusion of immediate postoperative ΔSCr.After surgery, 176 patients (52%) experienced a decrease10% in SCr level, 26 (7.4%) experienced an increase10%, and 143 had ΔSCr within ±10% of baseline. During hospitalization, 53 (14%) developed AKI. Bypass pump time, baseline estimated glomerular filtration rate, and European System for Cardiac Operative Risk Evaluation (euroSCORE) were associated with AKI in a parsimonious base logistic model. Added to the base model, immediate postoperative ΔSCr was associated strongly with subsequent AKI and significantly improved model discrimination over the base model (C statistic, 0.78 [95% CI, 0.71-0.85] vs 0.69 [95% CI, 0.62-0.77]; P0.001). A ≥10% SCr level decrease predicted significantly lower AKI risk (OR, 0.37; 95% CI, 0.18-0.76), whereas a ≥10% SCr level increase predicted significantly higher (OR, 6.38; 95% CI, 2.37-17.2) AKI risk compared with the reference category.We used a surrogate marker of AKI. External validation of our results is warranted.In elective cardiac surgery patients, measurement of immediate postoperative ΔSCr improves prediction of AKI.

Cardiovascular disease (CVD) is the leading cause of mortality in end-stage renal disease (ESRD), approximating a 10- to 20-fold higher risk of death in dialysis patients than in the general population. Despite this, dialysis patients often undergo fewer investigations, receive less invasive procedures, and are prescribed fewer medications compared with age-matched non-ESRD patients. A lack of randomized control trials for evidence-based treatment strategies in this population may explain some of these discrepancies, but there is concern that an attitude of "therapeutic nihilism" may be impacting on the medical care of these patients. In this review, we will explore CVD in the ESRD population. Specifically, we will try to address the following issues in patients with ESRD: (1) mechanisms of CVD, (2) cardiac evaluation and the role of coronary revascularization with percutaneous or coronary artery bypass procedures, and (3) cardiac pharmacotherapy use.

Background: The Aboriginal population in Canada experiences high rates of end-stage renal disease and need for dialytic therapies. Our objective was to examine rates of mortality, technique failure and peritonitis among adult aboriginal patients receiving peritoneal dialysis in the province of Manitoba. We also aimed to explore whether differences in these rates may be accounted for by location of residence (i.e., urban versus rural). Methods: We included all adult patients residing in the province of Manitoba who received peritoneal dialysis during the period from 1997–2007 ( n = 727). We extracted data from a local administrative database and from the Canadian Organ Replacement Registry and the Peritonitis Organism Exit-sites/Tunnel infections (POET) database. We used Cox and logistic regression models to determine the relationship between outcomes and Aboriginal ethnicity. We performed Kaplan–Meier analyses to examine the relationship between outcomes and urban (i.e., 50 km or less from the primary dialysis centre in Winnipeg) versus rural (i.e., more than 50 km from the centre) residency among patients who were aboriginal. Results: One hundred sixty-one Aboriginal and 566 non-Aboriginal patients were included in the analyses. Adjusted hazard ratios for mortality (HR 1.476, CI 1.073–2.030) and adjusted time to peritonitis (HR 1.785, CI 1.352–2.357) were significantly higher among Aboriginal patients than among non-Aboriginal patients. We found no significant differences in mortality, technique failure or peritonitis between urban- or rural-residing Aboriginal patients. Interpretation: Compared with non-Aboriginal patients receiving peritoneal dialysis, Aboriginal patients receiving peritoneal dialysis had higher mortality and faster time to peritonitis independent of comorbidities and demographic characteristics. This effect was not influenced by place of residence, whether rural or urban.

Background 2009 pandemic influenza A(H1N1) has led to a global increase in severe respiratory illness. Little is known about kidney outcomes and dialytic requirements in critically ill patients infected with pandemic H1N1. Study Design Prospective observational study. Setting & Participants 50 patients with pandemic H1N1 admitted to any of 7 intensive care units in Manitoba, Canada, were prospectively followed. Outcome & Measurements Outcomes were kidney injury and kidney failure defined using RIFLE (risk, injury, failure, loss, end-stage disease) criteria or need for dialysis therapy. Results The pandemic H1N1 group was composed of 50 critically ill patients with pandemic H1N1 with severe respiratory syndrome (47 confirmed cases, 3 probable). Kidney injury, kidney failure, and need for dialysis occurred in 66.7%, 66%, and 11% of patients, respectively. Mortality was 16%. Kidney failure was associated with increased death (OR, 11.29; 95% CI, 1.29-98.9), whereas the need for dialysis was associated with an increase in length of stay (RR, 2.38; 95% CI, 2.13-25.75). Limitations Small population studied from single Canadian province; thus, limited generalizability. Conclusions In critically ill patients with pandemic H1N1, kidney injury, kidney failure, and the need for dialysis are common and associated with an increase in mortality and length of intensive care unit stay.

Admission rates and outcomes of patients who have ESRD and are admitted to an intensive care unit (ICU) are not well defined. We conducted a historical cohort study using a prospective regional ICU database that captured all 11 adult ICUs in Winnipeg, Canada. Between 2000 and 2006, there were 34,965 total admissions to the ICU, 1173 (3.4%) of which were patients with ESRD. The main admission diagnoses among patients with ESRD were cardiac disease (31%), sepsis (15%), and arrest (10%). Compared with other patients in the ICU, those with ESRD were significantly younger but had more diabetes, peripheral arterial disease, and higher APACHE II (Acute Physiology and Chronic Health Evaluation II) scores; mean length of stay in the ICU was similar, however, between these two groups. Restricting the analysis to first admissions to the ICU, unadjusted in-hospital mortality was higher for patients with ESRD (16 versus 11%; P < 0.0001), but this difference did not persist after adjustment for baseline illness severity. In conclusion, although ESRD associates with increased mortality among patients who are admitted to the ICU, this effect is mostly a result of comorbidity.

New guidelines for the management of chronic kidney disease have been developed by the Canadian Society of Nephrology (Appendix 1 contains the full-text guidelines; available at [www.cmaj.ca/cgi/content/full/179/11/1154/DC1][1]). These guidelines describe key aspects of the management of chronic

cute kidney injury (AKI) is a serious andpotentially devastating complication inhospitalized patients. In the setting of cardiacsurgery with cardiopulmonary bypass (CPB),acute kidney failure requiring dialysis occurs inapproximately 1%-2% of patients and is associ-ated with a mortality in excess of 60%.

A young female with sickle cell disease was treated for biopsy-proven IgA nephropathy. Serum creatinine levels resolved to normal range, but a year later, she presented with oedema, hypertension and acute renal failure. A repeat renal biopsy showed acute-on-chronic thrombotic microangiopathy (TMA). We suggest that circulating microparticles could be a pathophysiological link between sickle cell disease and the development of renal TMA. This case emphasizes the importance of a further biopsy for acutely declining renal function, even when a definite diagnosis has been made from a previous biopsy.

Calcitonin gene-related peptide (CGRP) is a potent vasodilator that is suggested to act via ATP-sensitive K channels (KATP). In the present study, we examined the actions of CGRP on pressure- and angiotensin II-induced vasoconstriction, using the in vitro perfused hydronephrotic rat kidney. Elevated pressure (from 80 to 180 mmHg) and 0.1 nM angiotensin II elicited similar decreases in afferent diameter in this model. CGRP inhibited myogenic reactivity in a concentration-dependent manner, completely preventing pressure-induced constriction at 10 nM (95 ± 10% inhibition). These effects were partially attenuated by 10 μM glibenclamide (62 ± 16% inhibition, P = 0.025), indicating both KATP-dependent and -independent actions of CGRP. In contrast, 10 nM CGRP inhibited angiotensin II-induced vasoconstriction by only 54 ± 11%, and this action was not affected by glibenclamide (41 ± 11%, P = 0.31). CGRP also inhibited the efferent arteriolar response to angiotensin II in the absence and presence of glibenclamide. Pinacidil (1.0 μM), a KATP opener also preferentially inhibited pressure- vs. angiotensin II-induced vasoconstriction (97 ± 5 and 59 ± 13% inhibition, respectively; P = 0.034). We conclude that the renal vasodilatory mechanisms of CGRP are pleiotropic and involve both KATP-dependent and -independent pathways. The effectiveness of CGRP in opposing renal vasoconstriction and the role of KATP in this action appear to depend on the nature the underlying vasoconstriction. We suggest that this phenomenon reflects an inhibition of KATP activation by angiotensin II.

Background Serine hydrolases constitute a large enzyme family involved in a diversity of proteolytic and metabolic processes which are essential for many aspects of normal physiology. The roles of serine hydrolases in renal function are largely unknown and monitoring their activity may provide important insights into renal physiology. The goal of this study was to profile urinary serine hydrolases with activity-based protein profiling (ABPP) and to perform an in-depth compositional analysis. Methods Eighteen healthy individuals provided random, mid-stream urine samples. ABPP was performed by reacting urines (n = 18) with a rhodamine-tagged fluorophosphonate probe and visualizing on SDS-PAGE. Active serine hydrolases were isolated with affinity purification and identified on MS-MS. Enzyme activity was confirmed with substrate specific assays. A complementary 2D LC/MS-MS analysis was performed to evaluate the composition of serine hydrolases in urine. Results Enzyme activity was closely, but not exclusively, correlated with protein quantity. Affinity purification and MS/MS identified 13 active serine hydrolases. The epithelial sodium channel (ENaC) and calcium channel (TRPV5) regulators, tissue kallikrein and plasmin were identified in active forms, suggesting a potential role in regulating sodium and calcium reabsorption in a healthy human model. Complement C1r subcomponent-like protein, mannan binding lectin serine protease 2 and myeloblastin (proteinase 3) were also identified in active forms. The in-depth compositional analysis identified 62 serine hydrolases in urine independent of activity state. Conclusions This study identified luminal regulators of electrolyte homeostasis in an active state in the urine, which suggests tissue kallikrein and plasmin may be functionally relevant in healthy individuals. Additional serine hydrolases were identified in an active form that may contribute to regulating innate immunity of the urinary tract. Finally, the optimized ABPP technique in urine demonstrates its feasibility, reproducibility and potential applicability to profiling urinary enzyme activity in different renal physiological and pathophysiological conditions.

Abstract K + channel openers (PCOs), such as pinacidil, elicit vasodilation primarily by hyperpolarization-induced inhibition of L-type Ca 2+ channel activation. The physiological role of other mechanisms suggested to contribute to PCO-induced vasodilation is not well established. In the renal microcirculation, L-type Ca 2+ channels play a prominent role in vasoconstriction of the afferent arteriole (AA) but are absent or physiologically silent in the efferent arteriole (EA). Thus, L-type Ca 2+ channel–dependent and –independent mechanisms can readily be distinguished in this model. In the present study, we found that pinacidil potently inhibited Bay K 8644–induced AA vasoconstriction. Pinacidil also preferentially inhibited angiotensin II–induced AA vasoconstriction (approximately ninefold greater potency than EA). These results are consistent with an AA effect of pinacidil on L-type Ca 2+ channel activation. Unexpectedly, 10 μmol/L pinacidil inhibited AA and EA responses to similar extents (84±10% and 71±9%, respectively). In both AAs and EAs, glibenclamide restored normal reactivity, indicating an involvement of the ATP-sensitive K + channels. In the EA, however, pretreatment with diltiazem did not alter the effects of pinacidil. Nevertheless, 45 mmol/L KCl reversed the EA actions of pinacidil, indicating an essential requirement for a normal K + gradient. These findings suggest that the EA actions of pinacidil involve alterations in membrane potential but not changes in L-type Ca 2+ channel activity. Overall, our findings do support the premise that L-type Ca 2+ channel modulation is involved in PCO-induced vasodilation in the renal microcirculation. The EA actions of pinacidil, however, suggest important additional vasodilatory mechanisms that also involve ATP-sensitive K + channel–induced hyperpolarization but are independent of L-type Ca 2+ channel modulation.

Acute kidney injury (AKI) complicating cardiopulmonary bypass (CPB) results in increased morbidity and mortality. Urinary hepcidin-25 has been shown to be elevated in patients who do not develop AKI after CPB using semiquantitative mass spectrometry (SELDI TOF-MS). The goals of this study were to quantitatively validate these findings with ELISA and evaluate the diagnostic performance of hepcidin-25 for AKI.A nested, case-control analysis of urinary hepcidin-25 in AKI (n = 22) and non-AKI (n = 22) patients was conducted to validate the SELDI TOF-MS data at the following times: preoperatively; the start of CPB; 1 hour on CPB; on arrival to the intensive care unit; and postoperative days (POD) 1 and 3 to 5. The diagnostic performance of hepcidin-25 was then evaluated in the entire prospective observational cohort (n = 338) at POD 1. AKI was defined as Cr50% from baseline, within 72 hours postoperatively.Urinary hepcidin-25/Cr ratio was significantly elevated in all patients at POD 1 compared with baseline (P0.0005) and was also significantly elevated in non-AKI versus AKI patients at POD 1 (P0.0005). Increased log(10) hepcidin-25/Cr ratio was strongly associated with avoidance of AKI on univariate analysis. On multivariate analysis, the log(10) hepcidin-25/Cr ratio (P0.0001) was associated with avoidance of AKI with an area under the curve of 0.80, sensitivity 0.68, specificity 0.68, and negative predictive value 0.96.Elevated urinary hepcidin-25 on POD 1 is a strong predictor of avoidance of AKI beyond postoperative day 1.

End-stage renal disease (ESRD) patients admitted to the intensive care unit (ICU) have poor survival and high rates of readmission; however, little evidence exists on long-term outcomes. We set out to investigate the long-term (6 and 12 months) survival of ESRD patients admitted to the ICU and whether differential survival could be explained by dialysis modality and vascular access.We compared the admission characteristics, outcomes and readmission rates of 619 ESRD [95 peritoneal dialysis (PD), 334 hemodialysis with a catheter (HD CVC), 190 hemodialysis with an AV fistula (HD AVF)] patients admitted to 11 ICU's in Winnipeg, Manitoba, Canada. Parametric and nonparametric tests were used as appropriate to determine differences in baseline characteristics. Multivariable Cox and logistic regression was used to assess outcomes between the groups.The 6- and 12-month crude survival was 62 and 52%, respectively. In a univariate model, modality and vascular access were associated with an increased hazard ratio (HR) of death [PD HR 1.60 95% confidence interval (CI) 1.20-2.13, HD CVC HR 1.55 95% CI 1.25-1.93] compared to patients on HD with an AVF. In three different multivariate adjusted models, this association persisted with HRs for death of 1.63-1.75 for PD and 1.50-1.58 for HD CVC.Overall long-term survival of ESRD patients after admission to the ICU is poor. Being on PD or being dialyzed with a catheter was independently associated with an increased mortality.

Summary Background and objectives Elderly patients (>65 years old) are a rapidly growing demographic in the ESRD and intensive care unit (ICU) populations, yet the effect of ESRD status on critical illness in elderly patients remains unknown. Reliable estimates of prognosis would help to inform care and management of this frail and vulnerable population. Design, setting, participants, & measurements The effect of ESRD status on survival and readmission rates was examined in a retrospective cohort of 14,650 elderly patients (>65 years old) admitted to 11 ICUs in Winnipeg, Manitoba, Canada between 2000 and 2006. Logistic regression models were used to adjust odds of mortality and readmission to ICU for baseline case mix and illness severity. Results Elderly ESRD patients had twofold higher crude in-hospital mortality (22% versus 13%, P versus 2.7%, P = 0.001). After adjustment for illness severity alone or illness severity and case mix, the odds ratio for mortality decreased to 0.85 (95% CI: 0.57 to 1.25) and 0.82 (95% CI: 0.55 to 1.23), respectively. In contrast, ESRD status remained significantly associated with readmission to ICU after adjustment for other risk factors (OR 2.06 [95% CI: 1.32, 3.22]). Conclusions Illness severity on admission, rather than ESRD status per se , appears to be the main driver of in-hospital mortality in elderly patients. However, ESRD status is an independent risk factor for early and late readmission, suggesting that this population might benefit from alternative strategies for ICU discharge.

First Nations (FN) patients on peritoneal dialysis experience poor outcomes. Whether discrepancies exist regarding the microbiology, rate of infections, and outcomes between FN and non-FN peoples remains unknown. Design, setting, participants,measures: All adult peritoneal dialysis patients (n = 727) from 1997 to 2007 residing in Manitoba, Canada, were included. Parametric and nonparametric tests were used as necessary. Negative binomial regression was used to determine the relationship of rates of exit site infections (ESIs) and peritonitis between FN and non-FN peoples.A total of 161 FN and 566 non-FN subjects were included in the analyses. The unadjusted relative rates of peritonitis and ESIs in FN subjects were 132.7 and 86.0/100 patient-years compared with 87.8 and 78.2/100 patient-years in non-FN populations, respectively. FN subjects were more likely to have culture-negative peritonitis (36.5 versus 20.8%, P0.0001) and Staphylococcus ESIs (54.1 versus 32.9%, P0.0001). The crude and adjusted rates of peritonitis were higher in FN subjects for total episodes and culture-negative and gram-negative peritonitis. Catheter removal because of peritonitis was similar in both groups (42.9 versus 38.1% for FN and non-FN subjects, respectively; P = 0.261).FN patients experience higher rates of peritonitis and similar rates of ESIs compared with non-FN patients. Interventions to improve outcomes and prevent infections should specifically be targeted to the FN population.

Background. Observational and randomized controlled studies suggest that patients with stage 4 and 5 chronic kidney disease (CKD) derive morbidity and mortality benefit from being followed up in multidisciplinary, allied health clinics. It remains unclear how these clinics should be structured in order to optimize an efficient use of resources. The objectives of this study are (i) to describe ‘human’ resource utilization in an established ‘traditional’ multidisciplinary CKD clinic and (ii) to optimize efficiency and accountability of this multidisciplinary CKD clinic while maintaining or improving delivered quality of care. Methods. We conducted a prospective, cohort, intervention study in the multidisciplinary CKD clinics at a university-affiliated hospital in Winnipeg, Canada. There were 480 patients identified as requiring multidisciplinary care (68% male; 32% female; 64% Caucasian, 25% First Nations, 7% Asian; mean age 61), and the majority of these were in stages 4 and 5 CKD (80%). The aetiologies of CKD included diabetes (53%), hypertension (10%) and glomerulonephritis (GN) (19%). At baseline, process engineering analyses were conducted on resource use and workflows within the clinics. The intervention entailed clinic restructuring including changes to scheduling templates and documentation format as well as standardization of practitioner roles. Cross-sectional data to serve as surrogates for quality of care and efficiency were collected 1 year pre- and post-intervention. Results. Optimization of clinic structure did not significantly change the cycle times among nurses, dieticians and pharmacists, but nephrologists’ cycle time decreased from 13.8 min [interquartile range (IQR) 8–17] to 10.0 min (IQR 10–15) with P < 0.001. Patient throughput time decreased from 73 min (IQR 51–95) to 68.5 min (IQR 55–80). Compliance with established practice guidelines prior to clinic restructuring was 61% for BP (

A grid was developed to evaluate control of serum calcium, phosphate, and parathyroid hormone levels in hemodialysis patients, based on guideline recommendations (National Kidney Foundation Kidney Disease Outcomes Quality Initiative and Canadian Society of Nephrology), and its face validity was examined in a representative sample of Canadian patients. A retrospective chart review was undertaken in hemodialysis patients from 7 Canadian units. Patients >18 years, on hemodialysis for > or =12 months, and > or =3 parathyroid hormone levels measured > or =1 month apart were included. The grid classified mineral metabolism control as optimal, suboptimal, or poor (mean of 3 measurements). Medication use, hospitalization, and Emergency Department visits were evaluated in relation to grid occupancy. A second comparative analysis of grid occupancy was undertaken on prevalent hemodialysis cases in British Columbia in 2008. Data from 268 patients (mean age 62.3 years) were analyzed. Using National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines, 17.5%, 28.8%, and 53.7% of patients had optimal, suboptimal, and poor control, respectively, of all 3 parameters (calcium, phosphate, and parathyroid hormone). Using Canadian Society of Nephrology criteria, optimal, suboptimal, and poor control rates were 6.3%, 4.2%, and 89.5%, respectively. Poor control was a possible or a probable cause of hospitalization or Emergency Department attendance in 8 patients. Data from British Columbia in 2008 (n=1858) show optimal, suboptimal, and poor control rates of 15.8%, 24.5%, and 59.7%, respectively. Poor mineral metabolism control among Canadian hemodialysis patients is not showing improvement. The therapeutic grid is a valid tool and may help guide therapeutic decisions, quality control initiatives, and patient counseling. http://www.ukidney.com/bone-and-mineral-metabolism-resource.

Background Medication adherence in haemodialysis patients is often challenging due to a high pill burden, complex and dynamic medication regimens and limited patient self-interest in care. The purpose of this study was to investigate the time within target INR and safety profile of thrice weekly warfarin administration in haemodialysis patients with a clinical indication for anticoagulation and documented nonadherence to medications. Methods Thirty-seven patients from two haemodialysis units in Winnipeg, Manitoba, Canada, were recruited, and 17 patients were treated with thrice weekly warfarin and compared to 20 patients treated with daily warfarin therapy. The patients were followed for 1 year with weekly international normalized ratio (INR), dosage and adverse events recorded. The primary outcome was percentage of time with INR in target and sub ( 4)-therapeutic INR. Adverse events were recorded in the two groups. Results The thrice weekly group had a higher burden of comorbidity (Charlson comorbidity index of 6.35 +/- 1.77 versus 4.55 +/- 1.64, P = 0.003) compared to the daily dosage group. In the thrice weekly dosage group, time within target INR was higher (56.9 versus 49.3%, P = 0.008), and time with supra-therapeutic INR > 4 lower (2.7 versus 4.3%, P = 0.03). Total bleeding events (7 versus 6) and major bleeding events (3 versus 2 events) were similar between the two groups. Conclusion In this pilot study, thrice weekly warfarin appears to be a safe and feasible dosing strategy in a select patient population. A randomized controlled trial of thrice weekly warfarin is warranted.

Background The early evolution of acute kidney injury (AKI) in humans is difficult to study noninvasively. We hypothesized that urine proteomics could provide insight into the early pathophysiology of human AKI. Study Design A prospective nested case-control study (n = 250) compared serial urinary proteomes of 22 patients with AKI and 22 patients without AKI before, during, and after cardiopulmonary bypass surgery. Outcomes AKI was defined as a greater than 50% increase in serum creatinine level, and non-AKI, as less than 10% increase from baseline. Measurements Serum creatinine, urine protein-creatinine ratio, neutrophil gelatinase-associated lipocalin (NGAL), α 1 -microglobulin, interferon-inducible protein-10 (IP-10), monokine induced by interferon gamma (Mig), interferon-inducible T cell alpha chemoatractant (I-TAC), interleukin 6 (IL-6), IL-1β, and IL-10. Urine protein profiling by means of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Results SELDI-TOF-MS showed intraoperative tubular stress in both groups on arrival to the intensive care unit, evidenced by β 2 -microglobulinuria. Non-AKI proteomes returned toward baseline postoperatively. In contrast, AKI proteomes showed a second phase of tubular injury/stress with the reappearance of β 2 -microglobulin and multiple unidentified peaks (3 to 5 and 6 to 8 kDa) and the appearance of established tubular injury markers: urinary protein, α 1 -microglobulin, and NGAL. Furthermore, 2 novel peaks (2.43 and 2.78 kDa) were found to be dominant in postoperative non-AKI urine samples. The 2.78-kDa protein was identified as the active 25–amino acid form of hepcidin (hepcidin-25), a key regulator of iron homeostasis. Finally, an inflammatory component of reperfusion injury was evaluated by means of enzyme-linked immunosorbent assay analysis of candidate chemokines (IP-10, I-TAC, and Mig) and cytokines (IL-6, IL-1β, and IL-10). Of these, IP-10 was upregulated in patients with versus without AKI postoperatively. Limitations This is an observational study. SELDI-TOF-MS is a semiquantitative technique. Conclusions Evaluation of human AKI revealed early intraoperative tubular stress in all patients. A second phase of injury observed in patients with AKI may involve IP-10 recruitment of inflammatory cells. The enhancement of hepcidin-25 in patients without AKI may suggest a novel role for iron sequestration in modulating AKI.

Background: Vascular calcification is believed to have a crucial role in the excess cardiovascular mortality and morbidity in patients with end-stage renal disease (ESRD). Methods and Results: Recent evidence suggests that uremic vascular calcification is an active cell-mediated process resembling osteogenesis in bone, rather than passive precipitation of calcium and phosphorus in the setting of deranged mineral metabolism. To date, several bone-associated proteins (osteopontin, bone sialoprotein, alkaline phosphatase, and type I collagen) have been shown in histological sections of vessels obtained from patients with ESRD or calcific uremic arteriolopathy. In in vitro experiments, the addition of uremic serum upregulates osteopontin expression by cultured vascular smooth muscle cells (VSMCs). Conclusion: We are only beginning to understand the process by which VSMCs transform into osteoblast-like cells, although phosphorus may have a key role. Additional factors mediating or modulating the development of vascular calcification in patients with ESRD remain to be identified. Further understanding of the pathophysiological state of uremic vascular calcification is needed to design effective therapeutic strategies to intervene with this devastating condition in the ESRD population. Am J Kidney Dis 41(S1):S96-S99. © 2003 by the National Kidney Foundation, Inc.

In May, 2009, a 32-year-old man presented to our emergency department with dyspnoea, productive cough with limited haemoptysis, diff use myalgia, and malaise. The symptoms had started 24 h earlier; he denied fever or chills. He had end-stage renal disease secondary to focal segmental glomerular sclerosis and had fl uid overload because he had missed three of his last eight haemodialysis treatments. His vital signs were: blood pressure 162/94 mm Hg, respiratory rate 20 breaths per min, temperature 37·5°C, oxygen saturation 95% with supplemental oxygen. Physical examination showed signs of volume overload and bilateral coarse crackles in the lungs. Chest radiography at admission showed bilateral airspace opacifi cation and vascular redistribution (fi gure). He was treated with antibiotics and urgent haemodialysis, during which 6·1 L of fl uid was removed. An additional 5·1 L were removed during a second dialysis treatment, but respiratory status did not improve; the patient was intubated and mechanically ventilated on day 4. Although afebrile, given the lack of improvement in clinical status, on day 4 of admission our patient was placed in respiratory isolation and a 5 day course of oseltamivir was started. Bronchoscopy showed no endobronchial lesions or alveolar haemorrhage. Bronchoalveolar samples were positive for infl uenza H1N1 virus by PCR. ICU admission was later complicated by Escherichia coli nosocomial pneumonia and tracheostomy. As of September, 2009, the patient has been extubated and discharged from hospital. As of Sept 6, 2009, more than 277 600 laboratoryconfi rmed cases of pandemic H1N1 infl uenza A have been reported to WHO. Whether the presentation and clinical course of H1N1 infl uenza is similar in the dialysis population to the general population is currently unknown. Observations from this case (and another, not described here) suggest that presentation in dialysis patients may diff er; most H1N1 infl uenza cases meet the defi nition for infl uenza-like illness of fever plus cough or sore throat—this did not transpire in two of our dialysis patients. Uraemia-induced immune dysfunction might lead to this atypical presentation in dialysis patients. Worryingly, the diagnosis of infl uenza was not considered until our patient failed to respond to fl uid removal and antibiotics. Haemodialysis patients are close to one another during their dialysis treatment, increasing their exposure to transmission of respiratory infection. Fortunately, to date no known cases have been directly linked to our case. The current recommendations for treat ment of H1N1 infl uenza are oseltamivir or zanamivir. Because oseltamivir is eliminated by the kidneys, a reduced dose of 75 mg orally 3 times weekly after haemodialysis is recommended, although postdialysis dosing of 30 mg daily has been shown to achieve adequate clinical exposure to the active form of the drug in haemodialysis patients. These results were obtained in patients dialysed on a low-fl ux dialyser, therefore this dose may be insuffi cient when high-fl ux dialyzers are used because of greater drug clearance. Because our centre uses only high-fl ux dialysers, we administered the increased dose of 75 mg daily for 5 days. H1N1 infl uenza A is an important diff erential diagnosis in dialysis patients who are short of breath or febrile. Our case highlights the potential impact of infl uenza in this vulnerable population.

Infrared (IR) spectroscopy has previously been established as a means to accurately quantify several serum and urine metabolites, based upon spectroscopy of dry films. The same technique has also provided the basis to develop certain diagnostic tests, developed in the 'metabolomics' spirit. Here, we report on the further development of an integrated microfluidic-IR technology and technique, customized with the aim of dramatically extending the capabilities of IR spectroscopy in both analytical and diagnostic (metabolomic) applications. By exploiting the laminar fluid diffusion interface (LFDI), serum specimens are processed to yield product streams that are better suited for metabolic fingerprinting; metabolites are captured within the aqueous product stream, while proteins (which otherwise dominate the spectra of films dried from serum) are present in much reduced concentration. Spectroscopy of films dried from the aqueous stream then provides enhanced diagnostic and analytical sensitivity. The manuscript introduces an LFDI card design that is customized for integration with IR spectroscopy, and details the development of a quantitative assay for serum creatinine--based upon LFDI-processed serum samples--that is substantially more accurate (standard error of calibration, SEC = 43 micromol/L) than the corresponding assay based upon unprocessed serum specimens (SEC = 138 micromol/L). Preliminary results of diffusion modeling are reported, and the prospects for further optimization of the technique, guided by accurate modeling, are discussed.

Background. The purpose of the present study was to determine the natural history of coronary artery and aorta calcification by spiral computed tomography (CT) in patients who undergo a renal transplant and patients on haemodialysis. Methods. Two cohorts were evaluated for the natural history of vascular calcification: (i) 23 patients who underwent a baseline CT scan at the time of renal transplant and a repeat evaluation 15–20 months later; and (ii) 33 chronic kidney disease, stage 5 haemodialysis subjects who underwent a baseline CT scan, all followed for a minimum of 15 months, and 17 of whom underwent a second CT scan. Results. In the patients undergoing a renal transplant, there was no net change in CAC with time, suggesting stabilization of calcification. In the haemodialysis patients, the median CAC increased by 1.27±1.88 score/days, P ¼ 0.013. There was a trend towards increasing AoC score in both groups. All patients without calcification at baseline remained calcification free at follow-up. In the 15 months following baseline, the six dialysis patients who died had a significantly greater CAC score at baseline compared with the 24 patients who remained alive. Similarly, those patients who were hospitalized had a greater baseline CAC than patients who were not hospitalized. Conclusion. In this preliminary study, renal transplantation appears to slow down or arrest CAC, whereas CAC progresses in haemodialysis patients. In haemodialysis patients, CAC was greater in patients who died or were hospitalized compared with those who remained alive or were not hospitalized.