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New England Journal of Medicine 05/2013; 368(19):1844-5. · 53.30 Impact Factor
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ABSTRACT: BACKGROUND: Impaired kidney function is an established predictor of mortality after acute nonvariceal upper gastrointestinal bleeding (ANVUGIB); however, which factors are associated with mortality after ANVUGIB among patients undergoing dialysis is unknown. We examined the associations among demographic characteristics, dialysis-specific features, and comorbid conditions with short-term mortality after ANVUGIB among patients on dialysis. METHODS: Design: Retrospective cohort study. Setting: United States Renal Data System (USRDS), a nation-wide registry of patients with end-stage renal disease. Participants: All ANVUGIB episodes identified by validated algorithms in Medicare-covered patients between 2003 and 2007. Measurements: Demographic characteristics and comorbid conditions from 1 year of billing claims prior to each bleeding event. We used logistic regression extended with generalized estimating equations methods to model the associations among risk factors and 30-day mortality following ANVUGIB events. RESULTS: From 2003 to 2007, we identified 40,016 eligible patients with 50,497 episodes of ANVUGIB. Overall 30-day mortality was 10.7% (95% CI: 10.4-11.0). Older age, white race, longer dialysis vintage, peritoneal dialysis (vs. hemodialysis), and hospitalized (vs. outpatient) episodes were independently associated with a higher risk of 30-day mortality. Most but not all comorbid conditions were associated with death after ANVUGIB. The joint ability of all factors captured to discriminate mortality was modest (c=0.68). CONCLUSIONS: We identified a profile of risk factors for 30-day mortality after ANVUGIB among patients on dialysis that was distinct from what had been reported in non-dialysis populations. Specifically, peritoneal dialysis and more years since initiation of dialysis were independently associated with short-term death after ANVUGIB.
BMC Nephrology 04/2013; 14(1):97. · 2.18 Impact Factor
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ABSTRACT: OBJECTIVES: To evaluate the cost-effectiveness of statins for primary prevention of myocardial infarction (MI) and stroke in patients with chronic kidney disease (CKD). BACKGROUND: Patients with CKD have an elevated risk of MI and stroke. Although HMG Co-A reductase inhibitors ("statins") may prevent cardiovascular events in patients with non-dialysis-requiring CKD, adverse drug effects and competing risks could materially influence net effects and clinical decision-making. METHODS: We developed a decision-analytic model of CKD and cardiovascular disease (CVD) to determine the cost-effectiveness of low-cost generic statins for primary CVD prevention in men and women with hypertension and mild-to-moderate CKD. Outcomes included MI and stroke rates, discounted quality adjusted life years (QALYs) and lifetime costs (2010 USD), and incremental cost-effectiveness ratios. RESULTS: For 65 year-old men with moderate hypertension and mild-to-moderate CKD, statins reduced the combined rate of MI and stroke, yielded 0.10 QALYs, and increased costs by $1,800 ($18,000 per QALY gained). For patients with lower baseline cardiovascular risks, health and economic benefits were smaller; for 65 year-old women, statins yielded 0.06 QALYs and increased costs by $1,900 ($33,400 per QALY gained). Results were sensitive to rates of rhabdomyolysis and drug costs. Statins are less cost-effective when obtained at average retail prices, particularly in patients at lower CVD risk. CONCLUSIONS: While statins reduce absolute CVD risk in patients with CKD, increased risk of rhabdomyolysis, and competing risks associated with progressive CKD, partly offset these gains. Low-cost generic statins appear cost-effective for primary prevention of CVD in patients with mild-to-moderate CKD and hypertension.
Journal of the American College of Cardiology 03/2013; 61(12):1250-1258. · 14.16 Impact Factor
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Dick de Zeeuw,
Tadao Akizawa,
Rajiv Agarwal,
Paul Audhya,
George L Bakris,
Melanie Chin,
Melissa Krauth,
Hiddo J Lambers Heerspink,
Colin J Meyer,
John J McMurray,
Hans-Henrik Parving,
Pablo E Pergola,
Giuseppe Remuzzi,
Robert D Toto,
Nosratola D Vaziri,
Christoph Wanner,
David G Warnock,
Janet Wittes, Glenn M Chertow
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ABSTRACT: Background: Chronic kidney disease (CKD) associated with type 2 diabetes mellitus constitutes a global epidemic complicated by considerable renal and cardiovascular morbidity and mortality, despite the provision of inhibitors of the renin-angiotensin-aldosterone system (RAAS). Bardoxolone methyl, a synthetic triterpenoid that reduces oxidative stress and inflammation through Nrf2 activation and inhibition of NF-κB was previously shown to increase estimated glomerular filtration rate (eGFR) in patients with CKD associated with type 2 diabetes mellitus. To date, no antioxidant or anti-inflammatory therapy has proved successful at slowing the progression of CKD. Methods: Herein, we describe the design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes: the Occurrence of Renal Events (BEACON) trial, a multinational, multicenter, double-blind, randomized, placebo-controlled Phase 3 trial designed to determine whether long-term administration of bardoxolone methyl (on a background of standard therapy, including RAAS inhibitors) safely reduces renal and cardiac morbidity and mortality. Results: The primary composite endpoint is time-to-first occurrence of either end-stage renal disease or cardiovascular death. Secondary endpoints include the change in eGFR and time to occurrence of cardiovascular events. Conclusion: BEACON will be the first event-driven trial to evaluate the effect of an oral antioxidant and anti-inflammatory drug in advanced CKD.
American Journal of Nephrology 02/2013; 37(3):212-222. · 2.54 Impact Factor
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John T Daugirdas,
Tom Greene,
Michael V Rocco,
George A Kaysen,
Thomas A Depner,
Nathan W Levin, Glenn M Chertow,
Daniel B Ornt,
Jochen G Raimann,
Brett Larive,
Alan S Kliger
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ABSTRACT: Frequent hemodialysis can alter volume status, blood pressure, and the concentration of osmotically active solutes, each of which might affect residual kidney function (RKF). In the Frequent Hemodialysis Network Daily and Nocturnal Trials, we examined the effects of assignment to six compared with three-times-per-week hemodialysis on follow-up RKF. In both trials, baseline RKF was inversely correlated with number of years since onset of ESRD. In the Nocturnal Trial, 63 participants had non-zero RKF at baseline (mean urine volume 0.76 liter/day, urea clearance 2.3 ml/min, and creatinine clearance 4.7 ml/min). In those assigned to frequent nocturnal dialysis, these indices were all significantly lower at month 4 and were mostly so at month 12 compared with controls. In the frequent dialysis group, urine volume had declined to zero in 52% and 67% of patients at months 4 and 12, respectively, compared with 18% and 36% in controls. In the Daily Trial, 83 patients had non-zero RKF at baseline (mean urine volume 0.43 liter/day, urea clearance 1.2 ml/min, and creatinine clearance 2.7 ml/min). Here, treatment assignment did not significantly influence follow-up levels of the measured indices, although the range in baseline RKF was narrower, potentially limiting power to detect differences. Thus, frequent nocturnal hemodialysis appears to promote a more rapid loss of RKF, the mechanism of which remains to be determined. Whether RKF also declines with frequent daily treatment could not be determined.Kidney International advance online publication, 23 January 2013; doi:10.1038/ki.2012.457.
Kidney International 01/2013; · 6.61 Impact Factor
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ABSTRACT: BACKGROUND: Patients undergoing maintenance hemodialysis frequently exhibit poor mental health. We studied the effects of frequent in-center and nocturnal hemodialysis on depressive symptoms and self-reported mental health. STUDY DESIGN: 1-year randomized controlled clinical trials. SETTING & PARTICIPANTS: Hemodialysis centers in the United States and Canada. 332 patients were randomly assigned to frequent (6-times-weekly) compared with conventional (3-times-weekly) hemodialysis in the Frequent Hemodialysis Network (FHN) Daily (n = 245) and Nocturnal (n = 87) Trials. INTERVENTION: The Daily Trial was a trial of frequent (6-times-weekly) compared with conventional (3-times-weekly) in-center hemodialysis. The Nocturnal Trial assigned patients to either frequent nocturnal (6-times-weekly) hemodialysis or conventional (3-times-weekly) hemodialysis. OUTCOMES: Self-reported depressive symptoms and mental health. MEASUREMENTS: Beck Depression Inventory and the mental health composite score and emotional subscale of the RAND 36-Item Health Survey at baseline and 4 and 12 months. The mental health composite score is derived by summarizing these domains of the RAND 36-Item Health Survey: emotional, role emotional, energy/fatigue, and social functioning scales. RESULTS: In the Daily Trial, participants randomly assigned to frequent compared with conventional in-center hemodialysis showed no significant change over 12 months in adjusted mean Beck Depression Inventory score (-1.9 ± 0.7 vs -0.6 ± 0.7; P = 0.2), but experienced clinically significant improvements in adjusted mean mental health composite (3.7 ± 0.9 vs 0.2 ± 1.0; P = 0.007) and emotional subscale (5.2 ± 1.6 vs -0.3 ± 1.7; P = 0.01) scores. In the Nocturnal Trial, there were no significant changes in the same metrics in participants randomly assigned to nocturnal compared with conventional hemodialysis. LIMITATIONS: Trial interventions were not blinded. CONCLUSIONS: Frequent in-center hemodialysis, as compared with conventional in-center hemodialysis, improved self-reported general mental health. Changes in self-reported depressive symptoms were not statistically significant. We were unable to conclude whether nocturnal hemodialysis yielded similar effects.
American Journal of Kidney Diseases 01/2013; · 5.43 Impact Factor
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ABSTRACT: The development of acute kidney injury (AKI) after cardiac surgery is associated with significant mortality, morbidity, and cost. The last decade has seen major changes in the complexity of cardiac surgical candidates and in the number and type of cardiac surgical procedures being performed.
Using data from the Nationwide Inpatient Sample, we determined the annual rates of AKI, AKI requiring dialysis (AKI-D), and inpatient mortality after cardiac surgery in the United States in the years 1999 through 2008.
Inpatient mortality with AKI and AKI-D decreased from 27.9% and 45.9%, respectively, in 1999 to 12.8% and 35.3%, respectively, in 2008. Compared with 1999, the odds of AKI and AKI-D in 2008, adjusted for demographic and clinical factors, were 3.30 (95% confidence interval [CI]: 2.89 to 3.77) and 2.23 (95% CI: 1.78 to 2.80), respectively. Corresponding adjusted odds of death associated with AKI and AKI-D were 0.31 (95% CI: 0.26 to 0.36) and 0.47 (95% CI: 0.34 to 0.65.) Taken together, the attributable risks for death after cardiac surgery associated with AKI and AKI-D increased from 30% and 5%, respectively, in 1999 to 47% and 14%, respectively, in 2008.
In sum, despite improvements in individual patient outcomes over the decade 1999 to 2008, the population contribution of AKI and AKI-D to inpatient mortality after surgery increased over the same period.
The Annals of thoracic surgery 01/2013; 95(1):20-8. · 3.74 Impact Factor
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ABSTRACT: BACKGROUND AND OBJECTIVES: Despite high mortality and low levels of physical activity (PA) among patients starting dialysis, the link between low PA and mortality has not been carefully evaluated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Comprehensive Dialysis Study was a prospective cohort study that enrolled patients who started dialysis between June 2005 and June 2007 in a random sample of dialysis facilities in the United States. The Human Activity Profile (HAP) was administered to estimate PA among 1554 ambulatory enrolled patients in the Comprehensive Dialysis Study. Patients were followed until death or September 30, 2009, and the major outcome was all-cause mortality. RESULTS: The average age was 59.8 (14.2) years; 55% of participants were male, 28% were black, and 56% had diabetes mellitus. The majority (57.3%) had low fitness estimated from the HAP score. The median follow-up was 2.6 (interquartile range, 2.2-3.1) years. The association between PA and mortality was linear across the range of scores (1-94). After multivariable adjustment, lower adjusted activity score on the HAP was associated with higher mortality (hazard ratio, 1.30; 95% confidence interval, 1.23-1.39 per 10 points). Patients in the lowest level of fitness experienced a 3.5-fold (95% confidence interval, 2.54-4.89) increase in risk of death compared with those with average or above fitness. CONCLUSIONS: Low levels of PA are strongly associated with mortality among patients new to dialysis. Interventions aimed to preserve or enhance PA should be prospectively tested.
Clinical Journal of the American Society of Nephrology 11/2012; · 5.23 Impact Factor
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Circulation 10/2012; 126(16):1937-8. · 14.74 Impact Factor
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ABSTRACT: The lack of reliable human proxies for minor (ie, non-HLA) histocompatibility loci hampers the ability to leverage these factors toward improving transplant outcomes. Despite conflicting reports of the effect of donor-recipient sex mismatch on renal allografts, the association between acute rejection of renal allografts and the development of human alloantibodies to the male H-Y antigen suggested to us that donor-recipient sex mismatch deserved re-evaluation.
To evaluate whether the relationships between donor sex and allograft failure differed by recipient sex.
We studied recipients of deceased-donor (n = 125,369) and living-donor (n = 63,139) transplants in the United States Renal Data System. Using Cox proportional hazards models stratified by donor type, we estimated the association between donor-recipient sex mismatch and death-censored allograft failure with adjustment for known risk factors, with and without the use of multiple imputation methods to account for potential bias and/or loss of efficiency due to missing data.
The advantage afforded by male donor kidneys was more pronounced among male than among female recipients (8% vs 2% relative risk reduction; interaction P < 0.01). This difference is of the order of magnitude of several other risk factors affecting donor selection decisions.
Donor-recipient sex mismatch affects renal allograft survival in a direction consistent with immune responses to sexually determined minor histocompatibility antigens. Our study provides a paradigm for clinical detection of markers for minor histocompatibility loci.
Gender Medicine 08/2012; 9(5):335-347.e2. · 2.10 Impact Factor
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ABSTRACT: Symptoms of sleep and mood disturbances are common among patients on dialysis and are associated with significant decrements in survival and health-related quality of life. We used data from the Comprehensive Dialysis Study (CDS) to examine the association of self-reported physical activity with self-reported symptoms of insomnia, restless legs syndrome (RLS), and depression in patients new to dialysis. The CDS collected data on physical activity, functional status, and health-related quality of life from 1678 patients on either peritoneal (n = 169) or hemodialysis (n = 1509). The Human Activity Profile was used to measure self-reported physical activity. Symptoms were elicited in the following manner: insomnia using three questions designed to capture difficulty in initiating or maintaining sleep, RLS using three questions based on the National Institutes of Health workshop, and depression using the two-item Patient Health Questionnaire. We obtained data on symptoms of insomnia and depression for 1636, and on symptoms of RLS for 1622 (>98%) patients. Of these, 863 (53%) reported one of three insomnia symptoms as occurring at a persistent frequency. Symptoms of RLS and depression occurred in 477 (29%) and 451 (28%) of patients, respectively. The Adjusted Activity Score of the Human Activity Profile was inversely correlated with all three conditions in models adjusting for demographics, comorbid conditions, and laboratory variables. Sleep and mood disturbances were commonly reported in our large, diverse cohort of patients new to dialysis. Patients who reported lower levels of physical activity were more likely to report symptoms of insomnia, RLS, and depression.
Hemodialysis International 07/2012; · 1.54 Impact Factor
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Geoffrey A Block,
David C Wheeler,
Martha S Persky,
Bryan Kestenbaum,
Markus Ketteler,
David M Spiegel,
Matthew A Allison,
John Asplin,
Gerard Smits,
Andrew N Hoofnagle,
Laura Kooienga,
Ravi Thadhani,
Michael Mannstadt,
Myles Wolf, Glenn M Chertow
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ABSTRACT: Some propose using phosphate binders in the CKD population given the association between higher levels of phosphorus and mortality, but their safety and efficacy in this population are not well understood. Here, we aimed to determine the effects of phosphate binders on parameters of mineral metabolism and vascular calcification among patients with moderate to advanced CKD. We randomly assigned 148 patients with estimated GFR=20-45 ml/min per 1.73 m(2) to calcium acetate, lanthanum carbonate, sevelamer carbonate, or placebo. The primary endpoint was change in mean serum phosphorus from baseline to the average of months 3, 6, and 9. Serum phosphorus decreased from a baseline mean of 4.2 mg/dl in both active and placebo arms to 3.9 mg/dl with active therapy and 4.1 mg/dl with placebo (P=0.03). Phosphate binders, but not placebo, decreased mean 24-hour urine phosphorus by 22%. Median serum intact parathyroid hormone remained stable with active therapy and increased with placebo (P=0.002). Active therapy did not significantly affect plasma C-terminal fibroblast growth factor 23 levels. Active therapy did, however, significantly increase calcification of the coronary arteries and abdominal aorta (coronary: median increases of 18.1% versus 0.6%, P=0.05; abdominal aorta: median increases of 15.4% versus 3.4%, P=0.03). In conclusion, phosphate binders significantly lower serum and urinary phosphorus and attenuate progression of secondary hyperparathyroidism among patients with CKD who have normal or near-normal levels of serum phosphorus; however, they also promote the progression of vascular calcification. The safety and efficacy of phosphate binders in CKD remain uncertain.
Journal of the American Society of Nephrology 07/2012; 23(8):1407-15. · 9.66 Impact Factor
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ABSTRACT: In light of the recent trend toward earlier dialysis initiation and its association with mortality among patients with end-stage renal disease, we hypothesized that frailty is associated with higher estimated glomerular filtration rate (eGFR) at dialysis start and may confound the relation between earlier dialysis initiation and mortality.
We examined frailty among participants of the Comprehensive Dialysis Study (CDS), a special study of the US Renal Data System, which enrolled incident patients from September 1, 2005, through June 1, 2007. Patients were followed for vital status through September 30, 2009, and for time to first hospitalization through December 31, 2008. We used multivariate logistic regression to model the association of frailty with eGFR at dialysis start and proportional hazards regression to assess the outcomes of death or hospitalization.
Among 1576 CDS participants included, the prevalence of frailty was 73%. In multivariate analysis, higher eGFR at dialysis initiation was associated with higher odds of frailty (odds ratio [OR], 1.44 [95% CI, 1.23-1.68] per 5 mL/min/1.73 m(2); P < .001). Frailty was independently associated with mortality (hazard ratio [HR], 1.57 [95% CI, 1.25-1.97]; P < .001) and time to first hospitalization (HR, 1.26 [95% CI, 1.09-1.45]; P < .001). While higher eGFR at dialysis initiation was associated with mortality (HR, 1.12 [95% CI, 1.02-1.23] per 5 mL/min/1.73 m(2); P = .02), the association was no longer statistically significant after frailty was accounted for (HR, 1.08 [95% CI, 0.98-1.19] per 5 mL/min/1.73 m(2); P = .11).
Frailty is extremely common among patients starting dialysis in the United States and is associated with higher eGFR at dialysis initiation. Recognition of signs and symptoms of frailty by clinicians may prompt earlier initiation of dialysis and may explain, at least in part, the well-described association between eGFR at dialysis initiation and mortality.
Archives of internal medicine 06/2012; 172(14):1071-7. · 11.46 Impact Factor
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ABSTRACT: This study examined the associations between homelessness and clinical outcomes of CKD among adults from the urban healthcare safety net.
This retrospective cohort study examined 15,343 adults with CKD stages 3-5 who received ambulatory care during 1996-2005 from the Community Health Network of San Francisco. Main outcome measures were time to ESRD or death and frequency of emergency department visits and hospitalizations.
Overall, 858 persons (6%) with CKD stages 3-5 were homeless. Homeless adults were younger, were disproportionately male and uninsured, and suffered from far higher rates of depression and substance abuse compared with adults with stable housing (P<0.001 for all comparisons). Over a median follow-up of 2.8 years (interquartile range=1.4-6.1), homeless adults experienced significantly higher crude risk of ESRD or death (hazard ratio=1.82, 95% confidence interval=1.49-2.22) compared with housed adults. This elevated risk was attenuated but remained significantly higher (adjusted hazard ratio=1.28, 95% confidence interval=1.04-1.58) after controlling for differences in sociodemographics, comorbid conditions, and laboratory variables. Homeless adults were also far more likely to use acute care services (median [interquartile range] number of emergency department visits was 9 [4-20] versus 1 [0-4], P<0.001) than housed counterparts.
Homeless adults with CKD suffer from increased morbidity and mortality and use costly acute care services far more frequently than peers who are stably housed. These findings warrant additional inquiry into the unmet health needs of the homeless with CKD to provide appropriate and effective care to this disadvantaged group.
Clinical Journal of the American Society of Nephrology 06/2012; 7(7):1094-102. · 5.23 Impact Factor
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ABSTRACT: OBJECTIVE: Serum albumin and prealbumin concentrations are strongly associated with the risk of death in dialysis patients. Our study examined the association among demographic characteristics, body composition, comorbidities, dialysis modality and access, inflammation, and longitudinal measures of albumin and prealbumin concentrations in incident dialysis patients. DESIGN, SETTING, SUBJECTS, AND OUTCOME MEASURES: The Comprehensive Dialysis Study is a prospective cohort study of incident dialysis patients; in this report, we examined the data from 266 Nutrition substudy participants who donated serum. The independent variables of interest were baseline age, sex, race, Quetélet's (body mass) index, dialysis modality and access, diabetes, heart failure, atherosclerotic vascular disease, serum creatinine level, and longitudinal measures of C-reactive protein. The outcomes of interest (dependent variables) were longitudinal measures of albumin and prealbumin concentrations, recorded at study entry and thereafter every 3 months for 1 year. RESULTS: In multivariable mixed linear models, female sex, peritoneal dialysis, hemodialysis with a catheter, and higher C-reactive protein concentrations were associated with lower serum albumin concentrations, and serum albumin concentrations increased slightly over the year. In comparison, prealbumin concentrations did not significantly change over time; female sex, lower body mass index, diabetes, atherosclerotic vascular disease, and higher C-reactive protein concentrations were associated with lower prealbumin concentrations. Serum creatinine had a curvilinear relation with serum albumin and prealbumin. CONCLUSIONS: Serum albumin level increases early in the course of dialysis, whereas prealbumin level does not, and the predictors of serum concentrations differ at any given time. Further understanding of the mechanisms underlying differences between albumin and prealbumin kinetics in dialysis patients may lead to an improved approach to the management of protein-energy wasting.
Journal of Renal Nutrition 05/2012; · 1.57 Impact Factor
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ABSTRACT: Recent studies have focused on the association between dialysate sodium (Na(+) ) prescriptions and interdialytic weight gain (IDWG). We report on a case series of 13 patients undergoing conventional, thrice-weekly in-center hemodialysis with an individualized dialysate Na(+) prescription. Individualized dialysate Na(+) was achieved in all patients through a stepwise weekly reduction of the standard dialysate Na(+) prescription (140 mEq/L) by 2-3 mEq/L until reaching a Na(+) gradient of -2 mEq/L (dialysate Na(+) minus average plasma Na(+) over the preceding 3 months). Interdialytic weight gain, with and without indexing to dry weight (IDWG%), blood pressure, and the proportion of treatments with cramps, intradialytic hypotension (drop in systolic blood pressure >30 mmHg) and intradialytic hypotension requiring an intervention were reviewed. At the beginning of the observation period, the pre-hemodialysis (HD) plasma Na(+) concentration ranged from 130 to 141 mEq/L. When switched from the standard to the individualized dialysate Na(+) concentration, IDWG% decreased from 3.4% ± 1.6% to 2.5% ± 1.0% (P = 0.003) with no change in pre- or post-HD systolic or diastolic blood pressures (all P > 0.05). We found no significant change in the proportion of treatments with cramps (6% vs. 13%), intradialytic hypotension (62% vs. 65%), or intradialytic hypotension requiring an intervention (29% vs. 33%). Individualized reduction of dialysate Na(+) reduces IDWG% without significantly increasing the frequency of cramps or hypotension.
Hemodialysis International 05/2012; · 1.54 Impact Factor
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Glenn M Chertow,
Ricardo Correa-Rotter,
Geoffrey A Block,
Tilman B Drueke,
Jürgen Floege,
William G Goodman,
Charles A Herzog,
Yumi Kubo,
Gerard M London,
Kenneth W Mahaffey,
Thomas-Christian Mix,
Sharon M Moe,
David C Wheeler,
Patrick S Parfrey
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ABSTRACT: Secondary hyperparathyroidism (sHPT) and other abnormalities associated with chronic kidney disease-mineral bone disorder can contribute to dystrophic (including vascular) calcification. Dietary modification and variety of medications can be used to attenuate the severity of sHPT. However, it is unknown whether any of these approaches can reduce the high risks of death and cardiovascular disease in patients with end-stage renal disease.
The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) trial was designed to test the hypothesis that treatment with the calcimimetic agent cinacalcet compared with placebo (on a background of conventional therapy including phosphate binders +/- vitamin D sterols) reduces time to death or non-fatal cardiovascular events (specifically myocardial infarction, unstable angina, heart failure and peripheral arterial disease events) among patients on hemodialysis with sHPT. This report describes baseline characteristics of enrolled subjects with a focus on regional variation.
There were 3883 subjects randomized from 22 countries, including the USA, Canada, Australia, three Latin American nations, Russia and 15 European nations. The burden of overt cardiovascular disease at baseline was high (e.g. myocardial infarction 12.4%, heart failure 23.3%). The median plasma parathyroid hormone concentration at baseline was 692 pg/mL (10%, 90% range, 363-1694 pg/mL). At baseline, 87.2% of subjects were prescribed phosphate binders and 57.5% were prescribed activated vitamin D derivatives. Demographic data, comorbid conditions and baseline laboratory data varied significantly across regions.
EVOLVE enrolled 3883 subjects on hemodialysis with moderate to severe sHPT. Inclusion of subjects from multiple global regions with varying degrees of disease severity will enhance the external validity of the trial results.
Nephrology Dialysis Transplantation 04/2012; 27(7):2872-9. · 3.40 Impact Factor
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ABSTRACT: The Centers for Medicare and Medicaid Services (CMS) Medical Evidence Report (form CMS-2728) queries providers about the timing of the patient's first nephrologist consultation before initiation of dialysis. The monitoring of disease-specific goals in the Healthy People 2020 initiative will use information from this question, but the accuracy of the reported information is unknown. We defined a cohort of 80,509 patients aged ≥67 years who initiated dialysis between July 2005 and December 2008 with ≥2 years of uninterrupted Medicare coverage as their primary payer. The primary referent, determined from claims data, was the first observed outpatient nephrologist consultation; secondary analyses used the earliest nephrology consultation, whether inpatient or outpatient. We used linear regression models to assess the associations among the magnitude of discrepant reporting and patient characteristics and we tested for any temporal trends. When using the earliest recorded outpatient nephrology encounter, agreement between the two sources of ascertainment was 48.2%, and the κ statistic was 0.29 when we categorized the timing of the visit into four periods (never, <6, 6-12, and >12 months). When we dichotomized the timing of first predialysis nephrology care at >12 or ≤12 months, accuracy was 70% (κ=0.36), but it differed by patient characteristics and declined over time. In conclusion, we found substantial disagreement between information from the CMS Medical Evidence Report and Medicare physician claims on the timing of first predialysis nephrologist care. More-specific instructions may improve reporting and increase the utility of form CMS-2728 for research and public health surveillance.
Journal of the American Society of Nephrology 04/2012; 23(6):1078-85. · 9.66 Impact Factor
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ABSTRACT: The US National Institutes of Health (NIH) and Centers for Medicare and Medicaid Services (CMS) sponsored a randomized clinical trial comparing six versus three times per week in-center hemodialysis (the Frequent Hemodialysis Network [FHN] Daily Trial), to test the effects of frequent hemodialysis on an array of intermediate outcomes. Herein we report challenges to enrollment and randomization into the trial.
Screening and enrollment was tracked at all participating dialysis clinics and specific reasons for dropout after baseline assessment were recorded for all enrolled subjects. Reasons for consent refusal were recorded in a subset of (10 out of 65) sites.
The trial screened 6276 hemodialysis patients on three times weekly hemodialysis in 65 hemodialysis clinics, 3481 (55%) were considered eligible for enrollment, and 3124 (90%) were approached for consent; 378 (12%) consented and 245 were randomized (65% of those enrolled). Prospective subjects chose not to participate primarily because of the anticipated time required for three extra treatments per week and the difficulties in following the protocol.
Recruitment into the FHN Daily Trial proved challenging but the goal of 250 randomized subjects was almost met.
Journal of nephrology 04/2012; 25(3):302-9. · 1.65 Impact Factor
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ABSTRACT: The objective of this study was to determine the incidence of acute kidney injury (AKI) and its relation with mortality among hospitalized patients.
Analysis of hospital discharge and laboratory data from an urban academic medical center over a 1-year period. We included hospitalized adult patients receiving two or more serum creatinine (sCr) measurements. We excluded prisoners, psychiatry, labor and delivery, and transferred patients, 'bedded outpatients' as well as individuals with a history of kidney transplant or chronic dialysis. We defined AKI as (a) an increase in sCr of ≥0.3 mg/dl; (b) an increase in sCr to ≥150% of baseline, or (c) the initiation of dialysis in a patient with no known history of prior dialysis. We identified factors associated with AKI as well as the relationships between AKI and in-hospital mortality. RESUlTS: Among the 19,249 hospitalizations included in the analysis, the incidence of AKI was 22.7%. Older persons, Blacks, and patients with reduced baseline kidney function were more likely to develop AKI (all p < 0.001). Among AKI cases, the most common primary admitting diagnosis groups were circulatory diseases (25.4%) and infection (16.4%). After adjustment for age, sex, race, admitting sCr concentration, and the severity of illness index, AKI was independently associated with in-hospital mortality (adjusted odds ratio 4.43, 95% confidence interval 3.68-5.35).
AKI occurred in over 1 of 5 hospitalizations and was associated with a more than fourfold increased likelihood of death. These observations highlight the importance of AKI recognition as well as the association of AKI with mortality in hospitalized patients.
American Journal of Nephrology 04/2012; 35(4):349-55. · 2.54 Impact Factor
