David C. Mendelssohn

Left ventricular mass index increase in early renal disease: Impact of decline in hemoglobin

Cardiovascular disease occurs in patients with progressive renal disease both before and after the initiation of dialysis. Left ventricular hypertrophy (LVH) is an independent predictor of morbidity and mortality in dialysis populations and is common in the renal insufficiency population. LVH is associated with numerous modifiable risk factors, but little is known about LV growth (LVG) in mild-to-moderate renal insufficiency. This prospective multicenter Canadian cohort study identifies factors associated with LVG, measured using two-dimensional-targeted M-mode echocardiography. Eight centers enrolled 446 patients, 318 of whom had protocol-mandated clinical, laboratory, and echocardiographic measurements recorded. We report 246 patients with assessable echocardiograms at both baseline and 12 months with an overall prevalence of LVH of 36%. LV mass index (LVMI) increased significantly (>20% of baseline or >20 g/m2) from baseline to 12 months in 25% of the population. Other than baseline LVMI, no differences in baseline variables were noted between patients with and without LVG. However, there were significant differences in decline of Hgb level (-0.854 v -0.108 g/dL; P = 0.0001) and change in systolic blood pressure (+6.50 v -1.09 mm Hg; P = 0.03) between the groups with and without LVG. Multivariate analysis showed the independent contribution of decrease in Hgb level (odds ratio [OR], 1.32 for each 0.5-g/dL decrease; P = 0.004), increase in systolic blood pressure (OR, 1.11 for each 5-mm Hg increase; P = 0.01), and lower baseline LVMI (OR, 0.85 for each 10-g/m2; P = 0.011) in predicting LVG. Thus, after adjusting for baseline LVMI, Hgb level and systolic blood pressure remain independently important predictors of LVG. We defined the important modifiable risk factors. There remains a critical need to establish optimal therapeutic strategies and targets to improve clinical outcomes.

Effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease: an updated systematic review and meta-analysis.

BACKGROUND Phosphate binders (calcium-based and calcium-free) are recommended to lower serum phosphate and prevent hyperphosphataemia in patients with chronic kidney disease, but their effects on mortality and cardiovascular outcomes are unknown. We aimed to update our meta-analysis on the effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease. METHODS We did a systematic review of articles published in any language after Aug 1, 2008, up until Oct 22, 2012, by searching Medline, Embase, International Pharmaceutical Abstracts, Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature. We included all randomised and non-randomised trials that compared outcomes between patients with chronic kidney disease taking calcium-based phosphate binders with those taking non-calcium-based binders. Eligible studies, determined by consensus with predefined criteria, were reviewed, and data were extracted onto a standard form. We combined data from randomised trials to assess the primary outcome of all-cause mortality using the DerSimonian and Laird random effects model. FINDINGS Our search identified 847 reports, of which eight new studies (five randomised trials) met our inclusion criteria and were added to the ten (nine randomised trials) included in our previous meta-analysis. Analysis of the 11 randomised trials (4622 patients) that reported an outcome of mortality showed that patients assigned to non-calcium-based binders had a 22% reduction in all-cause mortality compared with those assigned to calcium-based phosphate binders (risk ratio 0·78, 95% CI 0·61-0·98). INTERPRETATION Non-calcium-based phosphate binders are associated with a decreased risk of all-cause mortality compared with calcium-based phosphate binders in patients with chronic kidney disease. Further studies are needed to identify causes of mortality and to assess whether mortality differs by type of non-calcium-based phosphate binder. FUNDING None.

Guidelines for the management of chronic kidney disease

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

Multidisciplinary Predialysis Programs: Quantification and Limitations of Their Impact on Patient Outcomes in Two Canadian Settings

A 1993 National Institutes of Health Consensus statement stressed the importance of early medical intervention in predialysis populations. Given the need for evidence-based practice, we report the outcomes of predialysis programs in two major Canadian cities. The purpose of this report was to determine whether the institution of a multidisciplinary predialysis program is of benefit to patients, and to analyze those factors that are important in actualizing those benefits. Data from two different studies is presented: (1) a prospective, nonrandomized cohort study comparing patients who were or were not exposed to an ongoing multidisciplinary predialysis team (St Pauls Hospital) and (2) a retrospective review of outcomes before and after the institution of a predialysis program (The Toronto Hospital). Although created independently in major academic centers in Canada, the programs both aimed to reduce urgent dialysis starts, improve preparedness for dialysis, and improve resource utilization. The Vancouver study was able to demonstrate significantly fewer urgent dialysis starts (13% v 35%; P < 0.05), more outpatient training (76% v 43%; P < 0.05), and less hospital days in the first month of dialysis (6.5 days v 13.5 days; P < 0.05). Cost savings of the program patients in 1993 are conservatively estimated to be

Predialysis psychoeducational intervention and coping styles influence time to dialysis in chronic kidney disease

173,000 (Canadian dollars) or over

Health-related Quality of Life in CKD Patients: Correlates and Evolution over Time

4,000 per patient. The Toronto study demonstrated success in predialysis access creation (86.3% of patients), but could not realize any benefit in terms of elective dialysis initiation due to well-documented hemodialysis resource constraints. We conclude that an approach to predialysis patients involving a multidisciplinary team can have a positive impact on quantitative outcomes, but essential elements for success include (1) early referral to a nephrology center, (2) adequate resources for dedicated predialysis program staff and infrastructure, and (3) available resources for patients with end-stage renal disease (ESRD) (dialysis stations). In times of economic constraints, objective data are necessary to justify resource-intensive proactive programs for patients with ESRD. Future studies should confirm and extend our observations so that optimum and cost-effective care for patients approaching ESRD is uniformly available.

Outcomes of percutaneous kidney biopsy, including those of solitary native kidneys

BACKGROUND Consensus endorses predialysis intervention before the onset of end-stage renal disease. In a previous study, predialysis psychoeducational intervention (PPI) extended time to dialysis therapy by a median of 6 months. We undertook to replicate and extend this finding by examining hypothesized mechanisms. METHODS We used an inception-cohort, prospective, randomized, controlled trial with follow-up to evaluate an intervention that included an interactive 1-on-1 slide-supported educational session, a printed summary (booklet), and supportive telephone calls once every 3 weeks. Participants were sampled from 15 Canadian (tertiary care) nephrology units and included 297 patients with progressive chronic kidney disease (CKD) expected to require renal replacement therapy (RRT) within 6 to 18 months. The main outcome was time to dialysis therapy (censored at 18 months if still awaiting RRT). RESULTS Time to dialysis therapy was significantly longer (median, 17.0 months) for the PPI group than the usual-care control group (median, 14.2 months; Coxs proportional hazards analysis, controlling for general nonrenal health, P < 0.001). Coping by avoidance of threat-related information (called blunting) was associated with shorter times to dialysis therapy (P < 0.032). A group x blunting interaction (P < 0.069) indicated: (1) time to dialysis therapy was shortened in the usual-care group, especially when patients coped by blunting; but (2) time to dialysis therapy was extended with PPI, even among patients who coped by blunting. Knowledge acquisition predicted time to dialysis therapy (r = 0.14; P < 0.013). Time to dialysis therapy was unrelated to depression or social support. CONCLUSION PPI extends time to dialysis therapy in patients with progressive CKD. The mechanism may involve the acquisition and implementation of illness-related knowledge. Routine follow-up also may be especially important when patients cope by avoiding threat-related information.

Modifiable Practices Associated with Sudden Death among Hemodialysis Patients in the Dialysis Outcomes and Practice Patterns Study

BACKGROUND AND OBJECTIVES Very few large-scale studies have investigated the determinants of health-related quality of life (HRQOL) in chronic kidney disease (CKD) patients not on dialysis or the evolution of HRQOL over time. DESIGN AND SETTING A prospective evaluation was undertaken of HRQOL in a cohort of 1186 CKD patients cared for in nephrology clinics in North America. Baseline and follow-up HRQOL were evaluated using the validated Kidney Disease Quality Of Life instrument. RESULTS Baseline measures of HRQOL were reduced in CKD patients in proportion to the severity grade of CKD. Physical functioning score declined progressively with more advanced stages of CKD and so did the score for role-physical. Female gender and the presence of diabetes and a history of cardiovascular co-morbidities were also associated with reduced HRQOL (physical composite score: male: 41.0 +/- 10.2; female: 37.7 +/- 10.8; P < 0.0001; diabetic: 37.3 +/- 10.6; nondiabetic: 41.6 +/- 10.2; P < 0.0001; history of congestive heart failure, yes: 35.4 +/- 9.7; no: 40.3 +/- 10.6; P < 0.0001; history of myocardial infarction, yes: 36.1 +/- 10.0; no: 40.2 +/- 10.6; P < 0.0001). Anemia and beta blocker usage were also associated with lower HRQOL scores. HRQOL measures declined over time in this population. The main correlates of change over time were age, albumin level and co-existent co-morbidities. CONCLUSIONS These observations highlight the profound impact CKD has on HRQOL and suggest potential areas that can be targeted for therapeutic intervention.

Health-related quality of life and hemoglobin levels in chronic kidney disease patients.

A solitary native kidney is generally considered to be an absolute contraindication to percutaneous biopsy. However, technical advances, such as real-time ultrasound guidance and automated core biopsy systems, provide an excellent safety profile with an extremely low risk of catastrophic complications and have caused some investigators to call for a reassessment of this contraindication. The overall results at our institution are reported. Of 544 consecutive native and allograft kidney biopsies conducted over 2.5 years, 482 were performed with an automated core biopsy system and 281 also used real-time ultrasound guidance. The overall complication rate was 5.3%. Transient gross hematuria was seen in 4.4% and hematoma was seen in 1.5%; no patient experienced loss of kidney function and there were no deaths. We recently have begun to perform percutaneous biopsy of solitary native kidneys in carefully selected patients. To date, nine such procedures have been attempted, with success in eight cases. One patient had transient gross hematuria; no other complications were noted. This encouraging preliminary experience suggests that otherwise uncomplicated adult patients with a solitary kidney might be considered for percutaneous biopsy. It now seems appropriate to prospectively evaluate percutaneous biopsy of solitary kidneys in a larger cohort of unselected patients.

Reimbursement of Dialysis: A Comparison of Seven Countries

BACKGROUND AND OBJECTIVES Sudden death is common in hemodialysis patients, but whether modifiable practices affect the risk of sudden death remains unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This study analyzed 37,765 participants in 12 countries in the Dialysis Outcomes and Practice Patterns Study to explore the association of the following practices with sudden death (due to cardiac arrhythmia, cardiac arrest, and/or hyperkalemia): treatment time [TT] <210 minutes, Kt/V <1.2, ultrafiltration volume >5.7% of postdialysis weight, low dialysate potassium [K(D) <3]), and prescription of Q wave/T wave interval-prolonging drugs. Cox regression was used to estimate effects on mortality, adjusting for potential confounders. An instrumental variable approach was used to further control for unmeasured patient-level confounding. RESULTS There were 9046 deaths, 26% of which were sudden (crude mortality rate, 15.3/100 patient-years; median follow-up, 1.59 years). Associations with sudden death included hazard ratios of 1.13 for short TT, 1.15 for large ultrafiltration volume, and 1.10 for low Kt/V. Compared with K(D) ≥3 mEq/L, the sudden death rate was higher for K(D) ≤1.5 and K(D)=2-2.5 mEq/L. The instrumental variable approach yielded generally consistent findings. The sudden death rate was elevated for patients taking amiodarone, but not other Q wave/T wave interval-prolonging drugs. CONCLUSIONS This study identified modifiable dialysis practices associated with higher risk of sudden death, including short TT, large ultrafiltration volume, and low K(D). Because K(D) <3 mEq/L is common and easy to change, K(D) tailoring may prevent some sudden deaths. This hypothesis merits testing in clinical trials.