Paul Komenda

Intensive Hemodialysis Associates with Improved Survival Compared with Conventional Hemodialysis

Patients undergoing conventional maintenance hemodialysis typically receive three sessions per week, each lasting 2.5-5.5 hours. Recently, the use of more intensive hemodialysis (>5.5 hours, three to seven times per week) has increased, but the effects of these regimens on survival are uncertain. We conducted a retrospective cohort study to examine whether intensive hemodialysis associates with better survival than conventional hemodialysis. We identified 420 patients in the International Quotidian Dialysis Registry who received intensive home hemodialysis in France, the United States, and Canada between January 2000 and August 2010. We matched 338 of these patients to 1388 patients in the Dialysis Outcomes and Practice Patterns Study who received in-center conventional hemodialysis during the same time period by country, ESRD duration, and propensity score. The intensive hemodialysis group received a mean (SD) 4.8 (1.1) sessions per week with a mean treatment time of 7.4 (0.87) hours per session; the conventional group received three sessions per week with a mean treatment time of 3.9 (0.32) hours per session. During 3008 patient-years of follow-up, 45 (13%) of 338 patients receiving intensive hemodialysis died compared with 293 (21%) of 1388 patients receiving conventional hemodialysis (6.1 versus 10.5 deaths per 100 person-years; hazard ratio, 0.55 [95% confidence interval, 0.34-0.87]). The strength and direction of the observed association between intensive hemodialysis and improved survival were consistent across all prespecified subgroups and sensitivity analyses. In conclusion, there is a strong association between intensive home hemodialysis and improved survival, but whether this relationship is causal remains unknown.

Non-invasive endothelial function testing and the risk of adverse outcomes: a systematic review and meta-analysis

OBJECTIVES We performed a systematic review and meta-analysis to understand the role of flow-mediated dilatation (FMD) of the brachial artery (BA) and peripheral arterial tonometry (PAT) in predicting adverse events, including cardiovascular (CV) events and all-cause mortality. BACKGROUND FMD of the BA and PAT are non-invasive measures of endothelial function. Impairment of endothelial function is associated with increased CV events. While FMD is the more widely used and studied technique, PAT offers several advantages. The purpose of this systematic review and meta-analysis is to determine whether brachial FMD and PAT are independent risk factors for future CV events and mortality. METHODS Multiple electronic databases were searched for articles relating FMD or PAT to CV events. Data were extracted on study characteristics, study quality, and study outcomes. Relative risks (RRs) from individual studies were combined and a pooled multivariate RR was calculated. RESULTS Thirty-six studies for FMD were included in the systematic review, of which 32 studies consisting of 15, 191 individuals were meta-analysed. The pooled RR of CV events and all-cause mortality per 1% increase in brachial FMD, adjusting for potential confounders, was 0.90 (0.88-0.92). In contrast, only three studies evaluated the prognostic value of PAT for CV events, and the pooled RR per 0.1 increase in reactive hyperaemia index was 0.85 (0.78-0.93). CONCLUSION Brachial FMD and PAT are independent predictors of CV events and all-cause mortality. Further research to evaluate the prognostic utility of PAT is necessary to compare it with FMD as a non-invasive endothelial function test in clinical practice.

Patient and Technique Survival among a Canadian Multicenter Nocturnal Home Hemodialysis Cohort

BACKGROUND AND OBJECTIVES As a result of improved clinical and quality-of-life outcomes compared with conventional hemodialysis, interest in nocturnal home hemodialysis (NHD) has steadily increased in the past decade; however, little is known about the flow of patients through NHD programs or about patient-specific predictors of mortality or technique failure associated with this modality. This study addressed this gap in knowledge. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This study included 247 NHD patients of the Canadian Slow Long nightly ExtEnded dialysis Programs (CAN-SLEEP) cohort from 1994 through 2006 inclusive. The association between program- and patient-specific variables and risk for adverse outcomes was determined using uni- and multivariable Cox regression. RESULTS A total of 14.6% of the cohort experienced death or technique failure. Unadjusted 1- and 5-year adverse event-free survival was 95.2 and 80.1%, respectively. Significant predictors of a composite of mortality and technique failure included advanced age (P < 0.001), diabetes (P < 0.001), central venous catheter use (P = 0.01), and inability to perform NHD independently (P = 0.009) and were adjusted for center effect. Weekly frequency of NHD was not predictive. Age and diabetes remained significant with multivariable analysis (hazard ratio 1.07 and 2.64, respectively). Unadjusted 1- and 5-year technique survival was 97.9 and 95.2%, respectively. Only age was a significant predictor of technique failure. CONCLUSIONS NHD is associated with excellent adverse event-free survival. This study underscores the importance of modality-specific predictors in the success of home hemodialysis, as well as favorable baseline characteristics such as younger age and the absence of diabetes.

Major bleeding events and risk stratification of antithrombotic agents in hemodialysis: Results from the DOPPS

Benefits and risks of antithrombotic agents remain unclear in the hemodialysis population. To help clarify this we determined variation in antithrombotic agent use, rates of major bleeding events, and factors predictive of stroke and bleeding in 48,144 patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases I-IV. Antithrombotic agents including oral anticoagulants (OACs), aspirin (ASA), and anti-platelet agents (APAs) were recorded along with comorbidities at study entry, and clinical events including hospitalization due to bleeding were then collected every 4 months. There was wide variation in OAC (0.3-18%), APA (3-25%), and ASA use (8-36%), and major bleeding rates (0.05-0.22 events/year) among countries. All-cause mortality, cardiovascular mortality, and bleeding events requiring hospitalization were elevated in patients prescribed OACs across adjusted models. The CHADS2 score predicted the risk of stroke in atrial fibrillation patients. Gastrointestinal bleeding in the past 12 months was highly predictive of major bleeding events; for patients with previous gastrointestinal bleeding, the rate of bleeding exceeded the rate of stroke by at least twofold across all categories of CHADS2 score, including patients at high stroke risk. Appropriate risk stratification and a cautious approach should be considered before OAC use in the dialysis population.

Serum Creatinine Measurement Immediately After Cardiac Surgery and Prediction of Acute Kidney Injury

BACKGROUND 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. STUDY DESIGN 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. PREDICTOR Immediate (ie, <6 hours) postoperative SCr level change (ΔSCr), categorized as within 10% (reference), decrease >10%, or increase >10% relative to baseline. OUTCOME AKI, defined according to the new KDIGO (Kidney Disease: Improving Global Outcomes) consensus definition as an increase in SCr level >0.3 mg/dL within 48 hours or >1.5 times baseline within 1 week. MEASUREMENTS We compared the C statistic of logistic models with and without inclusion of immediate postoperative ΔSCr. RESULTS After surgery, 176 patients (52%) experienced a decrease >10% in SCr level, 26 (7.4%) experienced an increase >10%, 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]; P < 0.001). 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. LIMITATIONS We used a surrogate marker of AKI. External validation of our results is warranted. CONCLUSION In elective cardiac surgery patients, measurement of immediate postoperative ΔSCr improves prediction of AKI.

Canadian Society of Nephrology Commentary on the KDIGO Clinical Practice Guideline for CKD Evaluation and Management

We congratulate the KDIGO (Kidney Disease: Improving Global Outcomes) work group on their comprehensive work in a broad subject area and agreed with many of the recommendations in their clinical practice guideline on the evaluation and management of chronic kidney disease. We concur with the KDIGO definitions and classification of kidney disease and welcome the addition of albuminuria categories at all levels of glomerular filtration rate (GFR), the terminology of G categories rather than stages to describe level of GFR, the division of former stage 3 into new G categories 3a and 3b, and the addition of the underlying diagnosis. We agree with the use of the heat map to illustrate the relative contributions of low GFR and albuminuria to cardiovascular and renal risk, though we thought that the highest risk category was too broad, including as it does people at disparate levels of risk. We add an albuminuria category A4 for nephrotic-range proteinuria and D and T categories for patients on dialysis or with a functioning renal transplant. We recommend target blood pressure of 140/90mm Hg regardless of diabetes or proteinuria, and against the combination of angiotensin receptor blockers with angiotensin-converting enzyme inhibitors. We recommend against routine protein restriction. We concur on individualization of hemoglobin A1c targets. We do not agree with routine restriction of sodium intake to <2g/d, instead suggesting reduction of sodium intake in those with high intake (>3.3g/d). We suggest screening for anemia only when GFR is <30mL/min/1.73m(2). We recognize the absence of evidence on appropriate phosphate targets and methods of achieving them and do not agree with suggestions in this area. In drug dosing, we agree with the recommendation of using absolute clearance (ie, milliliters per minute), calculated from the patients estimated GFR (which is normalized to 1.73m(2)) and the patients actual anthropomorphic body surface area. We agree with referral to a nephrologist when GFR is <30mL/min/1.73m(2) (and for many other scenarios), but suggest urine albumin-creatinine ratio > 60mg/mmol or proteinuria with protein excretion > 1g/d as the referral threshold for proteinuria.

An economic assessment model for in-center, conventional home, and more frequent home hemodialysis

More intensive and/or frequent hemodialysis may provide clinical benefits to patients with end-stage renal disease; however, these dialysis treatments are more convenient to the patients if provided in their homes. Here we created a standardized model, based on a systematic review of available costing literature, to determine the economic viability of providing hemodialysis in the home that arrays costs and common approaches for assessing direct medical and nonmedical costs. Our model was based on data from Australia, Canada, and the United Kingdom. The first year start-up costs for all hemodialysis modalities were higher than in subsequent years with modeled costs for conventional home hemodialysis lower than in-center hemodialysis in subsequent years. Modeled costs for frequent home hemodialysis was higher than both in-center and conventional home hemodialysis in the United Kingdom, but lower than in-center hemodialysis and higher than conventional home hemodialysis in Australia and Canada in subsequent years. The higher costs of frequent compared to conventional home hemodialysis were because of higher consumable usage due to dialysis frequency. Thus, our findings reinforce the conclusions of previous studies showing that home-based conventional and more frequent hemodialysis may provide clinical benefit at reasonable costs.

Association of frailty and physical function in patients with non-dialysis CKD: a systematic review

BackgroundFrailty is a condition characterized by a decline in physical function and functional capacity. Common symptoms of frailty, such as weakness and exhaustion, are prevalent in patients with chronic kidney disease (CKD). The increased vulnerability of frail patients with coexisting CKD may place them at a heightened risk of encountering additional health complications. The purpose of this systematic review was to explore the link between frailty, CKD and clinical outcomes.MethodsWe searched for cross sectional and prospective studies in the general population and in the CKD population indexed in EMBASE, Pubmed, Web of Science, CINAHL, Cochrane and Ageline examining the association between frailty and CKD and those relating frailty in patients with CKD to clinical outcomes.ResultsWe screened 5,066 abstracts and retrieved 108 studies for full text review. We identified 7 studies associating frailty or physical function to CKD. From the 7 studies, we identified only two studies that related frailty in patients with CKD to a clinical outcome. CKD was consistently associated with increasing frailty or reduced physical function [odds ratios (OR) 1.30 to 3.12]. In patients with CKD, frailty was associated with a greater than two-fold higher risk of dialysis and/or death [OR from 2.0 to 5.88].ConclusionsCKD is associated with a higher risk of frailty or diminished physical function. Furthermore, the presence of frailty in patients with CKD may lead to a higher risk of mortality. Further research must be conducted to understand the mechanisms of frailty in CKD and to confirm its association with clinical outcomes.

Outcomes of Chronic Dialysis Patients Admitted to the Intensive Care Unit

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.

Regional Implementation of Creatinine Measurement Standardization

Because patients may receive care at multiple locations within a geographic area, serum creatinine measurements must be standardized across laboratories to enable comparisons of reported estimated glomerular filtration rate (eGFR). The results of a successful creatinine standardization program designed to minimize the contribution of laboratory error to the reporting of eGFR are reported; 107 laboratories, which tested creatinine on 124 analyzers from six different manufacturers, voluntarily participated. Each laboratory received a correction factor to apply to its creatinine measurements to standardize them to the isotope dilution mass spectrometry reference method. The adjusted values were then used to calculate eGFR using the Modification of Diet in Renal Disease (MDRD) equation. The standardization program reduced the average total error in the measurement of creatinine from 23.9 to 8.7% and the average analytical bias from 16.5 to 2.7%. Implementing this program on a larger scale could reduce the rate of incorrect classification of stage 3 chronic kidney disease by 84%.