Cost-effectiveness Analysis of Vascular Access Referral Policies in CKD.

BACKGROUND: The optimal timing of vascular access referral for patients with chronic kidney disease who may need hemodialysis (HD) is a pressing question in nephrology. Current referral policies have not been rigorously compared with respect to costs and benefits and do not consider patient-specific factors such as age. STUDY DESIGN: Monte Carlo simulation model. SETTING & POPULATION: Patients with chronic kidney disease, referred to a multidisciplinary kidney clinic in a universal health care system. MODEL, PERSPECTIVE, & TIMEFRAME: Cost-effectiveness analysis, payer perspective, lifetime horizon. INTERVENTION: The following vascular access referral policies are considered: central venous catheter (CVC) only, arteriovenous fistula (AVF) or graft (AVG) referral upon HD initiation, AVF (or AVG) referral when HD is forecast to begin within 12 (or 3 for AVG) months, AVF (or AVG) referral when estimated glomerular filtration rate is <15 (or <10 for AVG) mL/min/1.73m2. OUTCOMES: Incremental cost-effectiveness ratios (ICERs, in 2014 US dollars per quality-adjusted life-year [QALY] gained). RESULTS: The ICER of AVF (AVG) referral within 12 (3) months of forecasted HD initiation, compared to using only a CVC, is ∼$105k/QALY ($101k/QALY) at a population level (HD costs included). Pre-HD AVF or AVG referral dominates delaying referral until HD initiation. The ICER of pre-HD referral increases with patient age. Results are most sensitive to erythropoietin costs, ongoing HD costs, and patients' utilities for HD. When ongoing HD costs are excluded from the analysis, pre-HD AVF dominates both pre-HD AVG and CVC-only policies. LIMITATIONS: Literature-based estimates for HD, AVF, and AVG utilities are limited. CONCLUSIONS: The cost-effectiveness of vascular access referral is largely driven by the annual costs of HD, erythropoietin costs, and access-specific utilities. Further research is needed in the field of dialysis-related quality of life to inform decision making regarding vascular access referral.

Successful Treatment of Hepatitis C with Simeprevir, Sofosbuvir, and Ribavirin in an HIV Coinfected Liver Transplant Patient with Advanced Chronic Kidney Disease.

Although major advances have occurred in treating patients with hepatitis C virus (HCV) with the development of new direct-acting antivirals (DAAs), treatment of liver transplant recipients with HCV, human immunodeficiency virus (HIV) coinfection, and renal disease is challenging due to the lack of efficacy and safety data in this population. We report a case of successful HCV therapy in a postliver transplant HIV coinfected patient, with stage 4 chronic kidney disease, using an all-oral regimen of simeprevir, sofosbuvir, and ribavirin. The 51-year-old male achieved SVR24, and no specific HIV-related or transplant-related adverse events were documented during the treatment period. The new DAAs show promise for HIV coinfected patients and those with severe to end-stage renal disease (ESRD); however, robust clinical trials or large cohort studies will need to be conducted to confirm the efficacy and safety of these newer agents in this setting.

Acute Kidney Injury With Tobramycin-Impregnated Bone Cement Spacers in Prosthetic Joint Infections.

BACKGROUND: Antibiotic-impregnated bone cement spacer (ACS) with tobramycin ± vancomycin is commonly used in a 2-stage replacement of infected prosthetic joints. This procedure has been associated with development of acute kidney injury (AKI). OBJECTIVE: To determine the incidence and risk factors for AKI after implantation of tobramycin-impregnated ACS. METHODS: This prospective, observational study evaluated 50 consecutive patients who received tobramycin ACS for first-stage revision of an infected hip or knee arthroplasty from August 2011 to February 2013. AKI was defined as 50% or greater rise in serum creatinine (SCr) from baseline within the first 7 postoperative days (PODs). RESULTS: The incidence of AKI was 20%, with median onset occurring at POD 2 (interquartile range [IQR] = 1-3); patients with AKI had a longer median duration of hospital stay (16 days, IQR = 12-17, vs 10 days, IQR = 8-10; P = 0.03). Serum tobramycin concentrations were significantly higher in the AKI group, peaking on POD 1 (median 1.9 vs 0.9 µg/mL, P = 0.01). Risk factors for nephrotoxicity identified by multivariate analysis were use of bone cement premanufactured with gentamicin (OR = 8.2; 95% CI = 1.1-60; P = 0.04), administration of blood transfusions intraoperatively (OR = 32.5; 95% CI = 2.3-454.3; P = 0.01) and nonsteroidal anti-inflammatory drugs postoperatively (OR = 23.0; 95% CI = 1.3-397.7; P = 0.03). CONCLUSIONS: Tobramycin ACS is associated with a high risk of AKI. Measures to minimize AKI risk in the perioperative period include early detection through close monitoring of SCr, avoiding use of premanufactured bone cement containing gentamicin, and avoiding potential nephrotoxins within the first 72 hours postoperatively.

Part versus whole: a randomized trial of central venous catheterization education.

Central venous catheterization (CVC) is a complex but commonly performed procedure. How best to teach this complex skill has not been clearly delineated. We conducted a randomized trial of the effects of two types of teaching of CVC on skill acquisition and retention. We randomly assigned novice internal medicine residents to learning CVC in-part or in-whole. The part-group was taught the first part of the procedure, followed by practice, followed by being taught the second and final portion of the procedure, and followed by practice. The whole-group was taught the procedure in its entirety, followed by practice. Teaching and practice time for both groups was otherwise held constant. Performances were assessed at baseline, post-training, and at 1 month. The primary outcome was skill retention at 1-month, rated by using a global rating scale and a 22-item checklist, and defined as the score increase between 1-month and baseline. Skill acquisition is defined as the score increase post-training and baseline. Raters were blinded to the participants' identity, group assignment, and time point. Participants in the part-task group outperformed the whole-task group in skill acquisition (2.2 ± 0.8 vs 1.3 ± 1.0; g = 1.01; p = 0.04) and in skill retention (1.5 ± 0.7 vs 0.5 ± 0.8; g = 1.39; p = 0.006) using the global rating scale. Scores rated by the checklist were not significantly different (52.0 ± 25.3 vs 43.5 ± 23.4; g = 0.33; p = 0.47 for skill acquisition; and 48.5 ± 34.9 vs 41.1 ± 20.4; g = 0.35; p = 0.44 for skill retention). For teaching ultrasound-guided CVC to novice learners, teaching in part is preferable than teaching in whole.

Timing of arteriovenous fistula creation in patients With CKD: a decision analysis.

BACKGROUND: The optimal time for arteriovenous fistula (AVF) referral is uncertain. Improving the timeliness of referral may reduce central venous catheter (CVC) use. STUDY DESIGN: Monte Carlo simulation model. SETTING & POPULATION: Patients with chronic kidney disease (CKD) followed up in a multidisciplinary clinic, overall and stratified by age. MODEL, PERSPECTIVE, & TIMEFRAME: Decision analysis, patient, patient's lifetime. INTERVENTION: AVF referral, using 1 of 2 strategies: refer when hemodialysis is anticipated to begin within a certain time frame or refer when estimated glomerular filtration rate (eGFR) drops below a certain threshold. OUTCOMES: A range of values for each strategy are compared to each other with respect to incident vascular access type (AVF or CVC), percentage of patients with an unnecessary AVF creation, and life expectancy after dialysis therapy initiation. RESULTS: A 15-month referral time frame gave 34% with incident CVCs, 14% with unnecessary AVFs, and a life expectancy of 1,751 days. Time frames of 12-18 months performed similarly. Referral at eGFR of 20 mL/min/1.73 m(2) gave 38% with incident CVCs, 20% with unnecessary AVFs, and life expectancy of 1,742 days. Using an eGFR threshold of 15 mL/min/1.73 m(2), 10% had an unnecessary AVF. Policy performance was affected by CKD progression rate and age. For fast progressors (ΔeGFR = -7mL/min/1.73 m(2) per year), referral at eGFR of 25 mL/min/1.73 m(2) achieved a similar incident CVC percentage (~40%) as referral at 15 mL/min/1.73 m(2) in slower progressors (ΔeGFR = -2.78 mL/min/1.73 m(2) per year). For patients aged 70-80 and 80-90 years, time frames of 15-18 months yielded 16%-22% with unnecessary AVFs (vs 9%-11% in 50- to 60-year-olds); an eGFR threshold strategy of 20 mL/min/1.73 m(2) yielded 24% unnecessary AVFs in 80- to 90-year-olds versus 16% in 50- to 60-year-olds. LIMITATIONS: Our model does not consider patients with nonlinear CKD progression or acute kidney injury. We did not include arteriovenous grafts or consider cost or quality of life. CONCLUSIONS: In general, AVF referral within about 12 months of the estimated time to dialysis performed best among time frame strategies, and referral at eGFR < 15-20 mL/min/1.73 m(2) performed best among threshold strategies. The timing of referral should also be guided by the individual rate of CKD progression. Elderly patients with CKD could be referred later to reduce the risk of creating an AVF that is never used.

Albuminuria post-liver transplant is a predictor of kidney disease progression and mortality.

BACKGROUND: Albuminuria is a marker of chronic kidney disease (CKD) associated with an increased risk of end-stage kidney disease (ESKD) and mortality in the general population, but it is uncertain whether the same association exists in liver transplant (LT) recipients. This study examined the association between albuminuria and kidney failure and mortality in LT recipients.METHODS: Retrospective cohort study of 294 adults who received a LT between January 1, 1989, and December 31, 2011, in British Columbia, Canada. Cox multivariable regression was used to determine the association between ACR and a primary combined outcome of mortality, doubling of serum creatinine, or ESKD; and a secondary outcome of a decrease in estimated glomerular filtration rate (eGFR) ≥30%. RESULTS: At baseline, mean eGFR was 67 (SD 20.9) mL/min/1.73 m2, and 10% had severe albuminuria (ACR >30 mg/mmol). The primary outcome occurred in 20.4% (60) of patients and was associated with ACR >30 mg/mmol (HR 2.77, 95% CI 1.28-6.04; P = 0.01). A decline in eGFR ≥30% occurred in 21.8% (64) of patients, and was associated with ACR >30 mg/mmol (HR 4.77, 95% CI 2.31-9.86; P < 0.0001). CONCLUSIONS: Severe albuminuria (ACR >30 mg/mmol) was associated with an increased risk of loss of kidney function and mortality after LT. Prospective studies are needed to determine if specific interventions directed at reducing albuminuria can improve long-term outcomes in LT recipients.

Comparing the use of global rating scale with checklists for the assessment of central venous catheterization skills using simulation.

The use of checklists is recommended for the assessment of competency in central venous catheterization (CVC) insertion. To explore the use of a global rating scale in the assessment of CVC skills, this study seeks to compare its use with two checklists, within the context of a formative examination using simulation. Video-recorded performances of CVC insertion by 34 first-year medical residents were reviewed by two independent, trained evaluators. Each evaluator used three assessment tools: a ten-item checklist, a 21-item checklist, and a nine-item global rating scale. Exploratory principal component analysis of the global rating scale revealed two factors, accounting for 84.1% of the variance: technical ability and safety. The two checklist scores correlated positively with the weighted factor score on technical ability (0.49 [95% CI 0.17-0.71] for the 10-item checklist; 0.43 [95% CI 0.10-0.67] for the 21-item checklist) and negatively with the weighted factor score on safety (-0.17 [95% CI -0.48-0.18] for the 10-item checklist; -0.13 [95% CI -0.45-0.22] for the 21-item checklist). A checklist score of <80% was strong indication of incompetence. However, a high checklist score did not preclude incompetence. Ratings using the global rating scale identified an additional 11 candidates (32%) who were deemed incompetent despite scoring >80% on both checklists. All these candidates committed serious errors. In conclusion, the practice of universal adoption of checklists as the preferred method of assessment of procedural skills should be questioned. The inclusion of global rating scales should be considered.

Proliferative glomerulonephritis with monoclonal IgG deposits secondary to chronic lymphocytic leukemia. Report of two cases.

Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a recently described entity that is only rarely associated with a hematological or lymphoproliferative malignancy. We describe the cases of two men with preexisting chronic lymphocytic leukemia (CLL) who developed endocapillary proliferative glomerulonephritis with nonorganized monoclonal IgG(1) deposits. One biopsy also showed CLL infiltration of the cortex. Both patients were treated with rituximab in addition to cyclophosphamide in one case and fludarabine in the other with significant improvement of their renal disease and CLL. This report provides additional evidence to support the use of rituximab in the therapy of CLL-associated PGNMID.

Dedication of a nurse to educating suboptimal haemodialysis starts improved transition to independent modalities of renal replacement therapy.

BACKGROUND: Haemodialysis (HD) initiation is unplanned in up to 50% of patients, mainly due to late diagnosis and/or late nephrology referral. In these patients, time does not permit the multidisciplinary predialysis care that is associated with increased independent renal replacement therapy (RRT) modality choice and better access to kidney transplantation. We established a Renal Triage Nurse (RTN) position to educate suboptimal HD starts and to facilitate transition to independent modalities of RRT. METHODS: Adult patients starting HD from 1 January 2005 to 31 December 2008 with < 180 days nephrology follow-up and surviving at least 180 days were included (suboptimal HD starts). The RTN educated suboptimal HD starts beginning in December 2006. Patients initiating RRT via the multidisciplinary predialysis clinic (MPC) were included for comparison. Multivariable logistic regression was used to determine the association between being seen by the RTN and achieving independent modalities of RRT. RESULTS: There were 176 patients: 78 suboptimal HD starts (38 of these were educated by the RTN) and 98 patients initiated RRT after a minimum 180-day follow-up at the MPC. Of the RTN patients, 27.8% switched to independent RRT modalities (peritoneal dialysis n = 7, home haemodialysis n = 1, transplant n = 2). RTN patients were more likely to live alone (33.3% versus 10.8%, P = 0.02) and to have cerebrovascular disease (25.0% versus 7.1%, P = 0.03); however, adjusting for these variables, suboptimal HD starts seen by the RTN were more likely to transition to independent RRT (OR 3.75, 95% CI 1.08-13.05) than those not seen. The proportion starting on an independent modality via the MPC was 39.8%. The RTN achieved a rate of independent RRT not statistically different to that observed in patients starting RRT via the MPC (OR 0.74, 95% CI 0.19-2.94 in multivariable analysis). CONCLUSIONS: Addition of the RTN to the HD care team facilitated transition to independent modalities of RRT in suboptimal HD starts. This standardized approach to the care of such patients should be considered in HD units where suboptimal HD starts are common.

Evaluation of Statin Use and Prescribing in Patients with Chronic Kidney Disease Not Receiving Treatment with Kidney Transplant or Dialysis.

BACKGROUND: Chronic kidney disease (CKD) is a risk factor for cardiovascular disease. The Kidney Disease Improving Global Outcomes 2013 guidelines and the Canadian Cardiovascular Society 2016 guidelines recommend statins for primary prevention of cardiovascular disease in CKD patients aged 50 years or older who are not receiving treatment with kidney transplant or dialysis. OBJECTIVES: To evaluate statin use for patients in the Vancouver General Hospital Kidney Care Clinic (VGH KCC) and to gain insight into the KCC nephrologists' practices and perspectives regarding the prescribing of statins for patients with CKD. METHODS: The study comprised 2 parts. Part 1 consisted of a cross-sectional study of all statin-eligible patients in the VGH KCC followed by a retrospective chart review. In the chart review, data were collected for 250 statin users and 250 non-users. Logistic regression analyses were performed to determine associations between demographic variables and statin use or non-use. Part 2 was an electronic survey of VGH KCC nephrologists. RESULTS: Of the 813 statin-eligible patients, 512 (63%) were taking a statin. Patients were approximately 5 times more likely to be receiving statin therapy when it was indicated for secondary versus primary prevention (adjusted odds ratio 4.64, 95% confidence interval 2.95-7.47). Eight of the 9 KCC nephrologists completed the survey, and 7 (87.5%) of these respondents indicated that they never or rarely prescribed statins themselves to KCC patients for primary prevention. However, the same number reported that they sometimes or often suggested statin initiation to family physicians. Three of the respondents indicated agreement with guideline recommendations, but many stated that the decision for statin initiation should be individualized to the patient. Strategies to improve statin prescribing rates that were endorsed by respondents included educating family physicians, creating preprinted orders and laboratory requisitions for statin initiation, providing educational materials about statins to patients, and implementing a protocol for KCC pharmacists to counsel patients about statins. CONCLUSIONS: Many statin-eligible VGH KCC patients were not receiving statin therapy, and most of the KCC nephrologists considered statin prescribing as a role for family physicians. Within the KCC, future directions will be to develop a standardized approach to identify patients who would benefit from statin therapy, and to implement strategies to improve statin prescribing rates in appropriate patients.

CONTEXTE: L'insuffisance rénale chronique (IRC) est un facteur de risque de maladie cardiovasculaire. Les directives du Kidney Disease Improving Global Outcomes de 2013 et celles de la Société canadienne de cardiologie de 2016 recommandent l'utilisation de statines comme mode de prévention principal des maladies cardiovasculaires par les patients âgés d'au moins 50 ans et souffrant d'IRC, qui ne reçoivent pas de traitement par greffe rénale ou dialyse. OBJECTIFS: Évaluer l'utilisation des statines pour les patients résidant au Vancouver General Hospital Kidney Care Clinic (VGH KCC) et améliorer la compréhension des pratiques et points de vue des néphrologues de la KCC concernant la prescription de statines aux patients souffrant d'une IRC. MÉTHODES: L'étude comportait deux parties. La première consistait en une étude transversale de tous les patients admis à recevoir des statines au VGH KCC, suivie d'un examen rétrospectif des dossiers. Les données destinées à cet examen ont été recueillies auprès de 250 utilisateurs de statines et de 250 non-utilisateurs. Les analyses de régression logistique ont permis de déterminer les associations entre les variables démographiques et l'utilisation (ou non) de statines. La deuxième partie consistait en une enquête menée électroniquement auprès des néphrologues du VGH KCC. RÉSULTATS: Des 813 patients admissibles à l'utilisation de statines, 512 (63 %) en prenaient déjà. Les patients avaient environ cinq fois plus de chances de recevoir un traitement par statines, lorsque celles-ci étaient indiquées pour la prévention secondaire ou primaire (rapport de cote révisé 4,64, 95 % intervalle de confiance 2,95 ­ 7,47). Huit des neuf néphrologues de la KCC ont participé à l'enquête et sept (87,5 %) d'entre eux ont indiqué qu'ils n'avaient jamais, ou rarement, prescrit de statines aux patients du KCC dans le cadre d'une intervention primaire. Cependant, le même nombre de répondants a indiqué avoir parfois ou souvent proposé aux médecins de famille de commencer un traitement aux statines. Trois répondants ont indiqué être d'accord avec les recommandations préconisées dans les directives, mais bon nombre des néphrologues interrogés ont signalé que la décision d'entreprendre un tel traitement devait être individualisée. Les stratégies visant à améliorer les taux de prescription de statines approuvées par les répondants comprenaient la sensibilisation des médecins de famille, la création d'ordonnances et de demandes d'analyse en laboratoire préimprimées pour entreprendre un traitement aux statines, l'offre aux patients de matériel de formation sur le sujet et la mise en place d'un protocole pour les pharmaciens de la KCC leur permettant de conseiller les patients. CONCLUSIONS: Beaucoup de patients admissibles à un traitement aux statines du VGH KCC ne le recevaient pas, et la plupart des néphrologues de la KCC considéraient que la prescription de ce type de traitement relevait des médecins de famille. Au sein de la KCC, les orientations futures consisteront à élaborer une approche standardisée pour identifier les patients qui tireraient profit d'une thérapie aux statines et à mettre en place des stratégies visant à améliorer les taux de prescription de statines aux patients concernés.

A prospective cohort study of predictors of upper extremity arteriovenous fistula maturation.

BACKGROUND: A substantial proportion of arteriovenous fistulas fail to function adequately for hemodialysis. Existing studies on arteriovenous fistula failure prediction assess patency rather than the more clinically relevant outcome of arteriovenous fistula function. We hypothesized that preoperative demographic and ultrasound characteristics, and postoperative assessment by an experienced vascular access nurse would predict which arteriovenous fistulas will not function adequately for hemodialysis. METHODS: Prospective cohort study of chronic kidney disease patients at a tertiary care center in Vancouver, Canada, with arteriovenous fistula creation between 2009 and 2013. Pre and postoperative clinical assessment and ultrasound blood vessel mapping were performed by an experienced vascular access nurse. The primary outcome was failure to achieve a fistula used successfully for hemodialysis (FUSH). RESULTS: Outcomes were assessed in 200 patients; 123 (61.5%) arteriovenous fistulas were radiocephalic. Overall, 26.5% of arteriovenous fistulas had FUSH failure (34.1% of lower arm vs 14.3% of upper arm, p = 0.002). Univariate predictors of FUSH failure included older age (p = 0.03), female sex (p = 0.05), smaller arterial diameter (p ⩽ 0.001), lower artery volume flow (p = 0.04), and smaller vein diameter (p = 0.01). In multivariable analysis, artery diameter (odds ratio: 0.44, 95% confidence interval: 0.28-0.68) most significantly predicted FUSH failure. Vascular access nurse assessment 6 weeks postoperatively correctly predicted outcome in 83.8% of FUSH and 65.0% of FUSH failure. CONCLUSION: Smaller artery diameter most strongly predicted FUSH failure. Early postoperative nursing assessment was more useful to predict FUSH than FUSH failure, and as such was insufficient in determining which arteriovenous fistulas should be abandoned as many predicted to fail could be salvaged with further intervention.

Incidental atherosclerotic renal artery stenosis diagnosed at cardiac catheterization: no difference in kidney function with or without stenting.

BACKGROUND: The long-term kidney function of patients with atherosclerotic renal artery stenosis (ARAS) diagnosed incidentally at the time of cardiac catheterization is not well described despite the increasingly common practice of assessing these vessels at the time of cardiac investigation. METHODS: This is a retrospective analysis of a cohort identified prospectively at the time of non-emergent coronary angiography. Those with >or=50% ARAS were managed medically and underwent stenting if recommended by their nephrologist and/or cardiologist. Longitudinal regression analysis was used to compare the annualized change in estimated glomerular filtration rate (GFR) in stented and unstented patients. Cox regression analysis was used to determine the predictors of a decline in GFR by >or=25%. RESULTS: Of 140 patients, 67 (48%) were stented, mostly for preservation of kidney function (70.1%) and/or resistant hypertension (53.7%). Median follow-up time was 943 days. Stented patients were younger, had higher systolic blood pressure and more severe ARAS. The adjusted rate of change in GFR was -1.49 (95% CI -2.33 to -0.65) ml/min/1.73 m(2)/year in the unstented group, and -1.48 (95% CI -2.34 to -0.62) ml/min/1.73 m(2)/year in the stented group (p = 0.99). A decline of GFR >or=25% occurred in 42 (30%) patients; no patient required dialysis. Only the presence of cereberovascular disease was associated with this outcome (hazard ratio 2.52, 95% CI 1.56-5.41). CONCLUSION: We were unable to demonstrate a benefit or harm of renal artery stenting for ARAS, thus further increasing the uncertainty of the significance of these lesions and how they are best managed.

Systematic review identified suboptimal reporting and use of race/ethnicity in general medical journals.

OBJECTIVE: Methods of reporting of race/ethnicity in biomedical journals are largely unknown. We aimed to systematically examine the reporting practice of race/ethnicity and socioeconomic status (SES) information in biomedical journals. STUDY DESIGN AND SETTING: All primary research articles that reported more than one racial/ethnic group, published between 1999 and 2003 in Annals of Internal Medicine, JAMA, The Lancet, and The New England Journal of Medicine (n=1,152) were reviewed for their use of race/ethnicity and SES variables. Interobserver reliability was assessed by independent abstraction of 10% of study sample. RESULTS: There were a total of 116 different terms used to describe various racial/ethnic groups. Assignment of race/ethnicity by self-report was stated in only 13% of papers; 52% of papers identifying race/ethnicity of study participants did not report any SES information. Overall, 16% of articles explicitly stated reasons for collecting information on race/ethnicity. CONCLUSION: Our results suggest that race/ethnicity information was suboptimally reported in general medical journals. Terminology used was highly variable. Method of establishing racial/ethnic categories, rationale for collecting race/ethnicity data, and SES information were underreported.

Randomized Controlled Trial for the Effect of Vitamin D Supplementation on Vascular Stiffness in CKD.

BACKGROUND AND OBJECTIVES: Vitamin D is implicated in vascular health in CKD. This study compared placebo, calcifediol, and calcitriol treatment with changes in vascular stiffness, BP, proteinuria, mineral metabolism parameters, C-reactive protein, and fibroblast growth factor 23 in patients with stable CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a double-blind, randomized controlled trial in out-patient CKD clinics in Vancouver, Canada, from February of 2011 to August of 2014, enrolling 119 patients with an eGFR of 15-45 ml/min per 1.73 m2. Change in pulse wave velocity (PWV) was measured after 6 months of treatment with a fixed dose of oral calcifediol (5000 IU 25-hydroxyvitamin D3), calcitriol (0.5 µg 1,25-dihydroxyvitamin D3), or placebo, thrice weekly. RESULTS: Eighty-seven participants were evaluated. Mean age was 66 years, 71% were men, 40% were diabetic, and mean baseline PWV was 11.5 m/s (SD=3.9 m/s). After 6 months, the PWV decreased in the calcifediol group (mean change, -1.1; 95% confidence interval [95% CI], -2.2 to 0.1 m/s), remained unchanged in the calcitriol group (mean change, 0.2; 95% CI, -0.9 to 1.4 m/s), and increased in the placebo group (mean change, 1.1; 95% CI, -0.1 to 2.2 m/s). The overall P value for between-arm changes was 0.03. Absolute PWV change was significantly different between groups (P=0.04): the combined vitamin D treatment group saw decreased PWV (mean change, -0.4; 95% CI, -1.2 to 0.4 m/s) whereas the placebo group saw increased PWV (mean change, +1.1; 95% CI, -0.1 to 2.2 m/s). The treatment group demonstrated significantly decreased serum parathyroid hormone (mean difference, -0.5; 95% CI, -0.7 to -0.3 ln[pg/ml]; P<0.001) and increased calcium (mean difference, 0.4; 95% CI, -0.1 to 0.7 mg/dl; P=0.02). In observational analysis, participants in the highest 25-hydroxyvitamin D tertile at trial end had significant decreases in PWV (mean change, -1.0; 95% CI, -2.0 to 0.0 m/s) compared with the middle and lowest tertiles (P<0.01). Side effects were minor and rare. CONCLUSIONS: Six months of supplemental vitamin D analogs at fixed doses may achieve a reduction of PWV in patients with advanced CKD. Because the treatment effect was attenuated when baseline PWV was included as a covariate, these findings should be replicated in larger populations and further studied.

Exploring mitochondrial nephrotoxicity as a potential mechanism of kidney dysfunction among HIV-infected patients on highly active antiretroviral therapy.

BACKGROUND: Tenofovir (TDF) exposure has been associated with renal dysfunction. Mitochondrial nephrotoxicity was investigated as an underlying mechanism. Given the interaction between TDF and didanosine (ddl), their concurrent use was also investigated. DESIGN: Relative kidney biopsy mitochondrial DNA (mtDNA) to nuclear DNA ratios were measured retrospectively. HIV+ individuals on TDF within 6 months preceeding the biopsy (HIV+/TDF+, n=21) were compared to HIV+ individuals who never received TDF (HIV+/TDF-, n=10) and to HIV uninfected controls (HIV-,n=22). Twelve of the HIV+/TDF+ individuals received concurrent ddl, 10 of those once at unadjusted ddl dosage. Tubular mitochondria morphology was also examined by electron microscopy. Statistical analyses were done on log-transformed mtDNA/nDNA, using non-parametric tests. RESULTS: Kidney mtDNA levels were different among the three groups (P=0.046). mtDNA ratios were lower in HIV+/TDF+ subjects (7.5 [2.0-12.1]) than in HIV- ones (14.3 [6.0-16.5], P=0.014), but not lower than HIV+/TDF- controls (6.4 [2.8-11.9], P=0.82). Among HIV+ subjects, there was a difference between TDF-, TDF+/ddl- and TDF+/ddl+ (P=0.005), with concurrent TDF/ddl use associated with lower mtDNA (2.1 [1.9-5.5], n=12) than TDF+/ddl- (13.8 [7.5-16.4], n=9, P=0.003). No TDF-/ddl+ biopsies were available. In regression analyses, only HIV infection (P=0.03), and TDF/ddl use (P=0.003) were associated with lower mtDNA. At the ultrastructural level, abnormal tubular mitochondria was more prevalent in HIV+/TDF+ biopsies than HIV+/TDF- and HIV- ones together (P<0.001) but not more so in TDF+/ddl+ biopsies than TDF+/ddl- ones (P=0.67). CONCLUSIONS: Renal dysfunction in this population may be mediated through mitochondrial nephrotoxicity that involves more than one drug and/or pathogenesis. Kidney mtDNA depletion was associated with HIV infection and concurrent TDF/ddl therapy but not TDF use alone, while kidney ultrastructural mitochondrial abnormalities were seen with TDF use. The interaction between TDF and ddl may be relevant in the kidney where both drugs are cleared. The clinical relevance of our findings needs to be evaluated given the current recommendation for reduced doses of ddl when used in conjunction with TDF.

The older living kidney donor: Part of the solution to the organ shortage.

BACKGROUND: Strategies to increase kidney transplantation are urgently needed. METHODS: We studied all (n = 73,073) first kidney-only transplant recipients in the United States between 1995 and 2003 to determine the incidence and outcomes of living donor transplantation as a function of donor age. Because 90% of living donors were <55 years, we defined older living donors as > or =55 years. Factors associated with transplantation from older living donors and the association of living donor age with allograft function and survival were determined. RESULTS: Recipients of older age, female gender, white race, and preemptive transplants had higher odds of older living donor transplantation. Older living donor transplantation was more likely from spousal donors rather than blood relatives, and more likely when a husband was the donor. The glomerular filtration rate (GFR) one year after transplantation decreased with increasing donor age (P < 0.001). Graft survival from living donors > or =55 years was 85% and 76% at three and five years (compared to 89% and 82% with living donors <55 years, and 82% and 73% with deceased donors <55 years). In a multivariate model, the risk of graft loss with living donors 55-64 years was similar to that with deceased donors <55 years, while recipients from living donors 65-69 years (HR = 1.3, 95% CI: 1.1-1.7) and >70 years (HR = 1.7, 95% CI: 1.1-2.6) had a higher relative risk of graft loss. CONCLUSIONS: Outcomes are excellent with living donors <65 years. Expanded use of older living donors may help meet the demand for transplantation.

Anemia and the heart in chronic kidney disease.

Cardiovascular disease is highly prevalent at all stages of chronic kidney disease (CKD) and is the leading cause of morbidity and mortality. Individuals with CKD commonly have multiple risk factors for the development of cardiovascular disease, including both traditional and nontraditional risk factors. Anemia is a nontraditional cardiovascular risk factor found in CKD that contributes to the development and progression of structural abnormalities of the heart, namely left ventricular hypertrophy and dilation. In addition, a deficiency of erythropoietin per se also may have important pathophysiologic consequences. In this review we summarize the evidence from observational studies showing an association between anemia and adverse cardiac outcomes at all stages of CKD. In addition, we provide an overview of the evidence accumulating from randomized controlled trials conducted in both nondialysis and dialysis CKD populations evaluating the effect of anemia correction on cardiac outcomes such as changes in left ventricular hypertrophy.

Notes From the Field: Direct Observation Versus Rating by Videos for the Assessment of Central Venous Catheterization Skills.

Blinded assessments of technical skills using video-recordings may offer more objective assessments than direct observations. This study seeks to compare these two modalities. Two trained assessors independently assessed 18 central venous catheterization performances by direct observation and video-recorded assessments using two tools. Although sound quality was deemed adequate in all videos, portions of the video for wire handling and drape handling were frequently out of view (n = 13, 72% for wire-handling; n = 17, 94% for drape-handling). There were no differences in summary global rating scores, checklist scores, or pass/fail decisions for either modality (p > 0.05). Inter-rater reliability was acceptable for both modalities. Of the 26 discrepancies identified between direct observation and video-recorded assessments, three discrepancies (12%) were due to inattention during video review, while one (4%) discrepancy was due to inattention during direct observation. In conclusion, although scores did not differ between the two assessment modalities, techniques of video-recording may significantly impact individual items of assessments.

Establishing a Canadian national clinical trials network for kidney disease: proceedings of a planning workshop.

Knowledge generation through randomized controlled trials (RCTs) is critical to advance the medical evidence base, inform decision-making, and improve care and outcomes. Unfortunately, nephrology has typically lagged behind other medical specialties in this regard. The establishment of formal clinical trial networks can facilitate the successful conduct of RCTs and has significantly increased the number of RCTs performed worldwide in other medical specialties. No such formal network of nephrology trialists exists in Canada. On April 24, 2014, the Canadian Kidney Knowledge Translation and Generation Network (CANN-NET) Clinical Trials Committee held a stakeholder engagement meeting to address this gap and improve the nephrology clinical trial landscape in Canada. The meeting was held in Vancouver in association with the 2014 Canadian Society of Nephrology Annual General Meeting and was co-sponsored by the Kidney Foundation of Canada and CANN-NET. Attendees included nephrologists from university- and non-university-affiliated nephrology practices, administrators, and representatives from the Kidney Foundation of Canada. Through structured presentations and facilitated group discussions, the group explored the extent to which nephrology trials are currently happening in Canada, barriers to leading or participating in larger investigator-initiated trials, and strategies to improve clinical trial output in nephrology in Canada. The themes and action items arising from this meeting are discussed.

La création d'un bagage de connaissances commun par la conduite d'essais cliniques est essentielle pour assurer l'avancement des notions de base en médecine, étayer la prise de décisions, améliorer les soins aux patients et assurer de meilleurs résultats cliniques. L'établissement d'un réseau officiel et reconnu de partage des connaissances issues d'essais cliniques peut en faciliter la conduite et assurer leur bon déroulement. La preuve en est faite par l'augmentation du nombre d'essais cliniques probants ayant été menés à travers le monde, dans d'autres disciplines médicales. Malheureusement, la néphrologie tire de l'arrière à cet égard par rapport aux autres spécialités, un tel réseau de partage n'existe pas dans le domaine au Canada. C'est dans ce contexte que le 24 avril 2014, le comité des essais cliniques de la « Canadian Kidney Knowledge Translation and Generation Network ¼ (CANN-NET) a tenu une assemblée générale afin de mobiliser les parties intéressées. On a voulu leur exposer cette lacune, tenter d'apporter des solutions et ultimement, faire progresser le bilan de la néphrologie en cette matière. La conférence, en collaboration avec l'assemblée générale annuelle de la Société canadienne de néphrologie, s'est tenue à Vancouver et était subventionnée conjointement par la Fondation canadienne du Rein et le CANN-NET. Parmi les participants, on comptait des néphrologues pratiquants associés ou non à un établissement universitaire ainsi que des administrateurs et des représentants de la Fondation canadienne du Rein. À l'aide de présentations structurées et de discussions de groupe, les participants ont pu observer l'état actuel des essais cliniques au pays, identifier les barrières entravant la participation à plus grande échelle à des essais entrepris sous l'initiative d'un chercheur, et discuter de stratégies pour améliorer les résultats d'essais cliniques en néphrologie au Canada. Le présent article fait état des thèmes abordés lors de cette assemblée et des mesures à prendre pour atteindre les objectifs fixés.