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      Randomized, Double-Blind, Placebo-Controlled Trial of Spironolactone for Hypokalemia in Continuous Ambulatory Peritoneal Dialysis Patients : Spironolactone for Hypokalemic CAPD Patients

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          Most cited references 14

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          Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study.

          The Randomized Aldactone Evaluation Study (RALES) demonstrated that spironolactone significantly improves outcomes in patients with severe heart failure. Use of angiotensin-converting-enzyme (ACE) inhibitors is also indicated in these patients. However, life-threatening hyperkalemia can occur when these drugs are used together. We conducted a population-based time-series analysis to examine trends in the rate of spironolactone prescriptions and the rate of hospitalization for hyperkalemia in ambulatory patients before and after the publication of RALES. We linked prescription-claims data and hospital-admission records for more than 1.3 million adults 66 years of age or older in Ontario, Canada, for the period from 1994 through 2001. Among patients treated with ACE inhibitors who had recently been hospitalized for heart failure, the spironolactone-prescription rate was 34 per 1000 patients in 1994, and it increased immediately after the publication of RALES, to 149 per 1000 patients by late 2001 (P<0.001). The rate of hospitalization for hyperkalemia rose from 2.4 per 1000 patients in 1994 to 11.0 per 1000 patients in 2001 (P<0.001), and the associated mortality rose from 0.3 per 1000 to 2.0 per 1000 patients (P<0.001). As compared with expected numbers of events, there were 560 (95 percent confidence interval, 285 to 754) additional hyperkalemia-related hospitalizations and 73 (95 percent confidence interval, 27 to 120) additional hospital deaths during 2001 among older patients with heart failure who were treated with ACE inhibitors in Ontario. Publication of RALES was not associated with significant decreases in the rates of readmission for heart failure or death from all causes. The publication of RALES was associated with abrupt increases in the rate of prescriptions for spironolactone and in hyperkalemia-associated morbidity and mortality. Closer laboratory monitoring and more judicious use of spironolactone may reduce the occurrence of this complication. Copyright 2004 Massachusetts Medical Society
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            Charlson comorbidity index as a predictor of outcomes in incident peritoneal dialysis patients.

            A previous study at our center used the Charlson Comorbidity Index (CCI) (an index of comorbidity that includes age) to predict outcomes in a mixed group of incident and prevalent dialysis patients. The purpose of this study was to examine the usefulness of the CCI as a predictor in incident peritoneal dialysis (PD) patients and to examine whether it was a better predictor than simply the number of comorbid conditions or other known predictors, such as age, albumin level, diabetes, and cardiovascular disease. Since 1990, we have collected prospectively comorbidity data at the start of PD. All patients with known comorbidity and serum albumin and who did not have a prior history of hemodialysis or transplant were included (n = 268). Time at risk began at day 1 of PD training. Cox proportional hazards best subset selection was used to screen models to predict patient survival. Candidate models were analyzed further for proportionality and other model assumptions. Univariate analysis showed that significant predictors of mortality were CCI (chi-square = 43.3, P < 0.0001), age (chi-square = 23.7, P < 0.0001), cardiac disease (chi-square = 19.9, P <0.0001), number of comorbid conditions (chi-square = 15.6, P < 0.0001), serum albumin at the start of dialysis (chi-square = 15.3, P = 0.0001), and diabetes (chi-square = 4, P < 0.05). In multivariate analysis, CCI alone was the best predictor. The addition of serum albumin did not improve the model significantly (chi-square = 51.86 versus 49.34). For every increase of 1 in the CCI score, the relative risk of death was 1.54 (95% confidence interval, 1.36 to 1.74). CCI alone scored at the start of PD is a strong predictor of patient survival in incident end-stage renal disease patients on PD. This simple-to-calculate index would be useful to adjust for confounding in future studies and in the adjustment of case mix if Medicare moves to a capitated payment system.
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              Enhanced large intestinal potassium permeability in end-stage renal disease.

              The capacity of the colon for potassium (K+) secretion increases in end-stage renal disease (ESRD), to the extent that it makes a substantial contribution to K+ homeostasis. This colonic K+ adaptive response may reflect enhanced active K+ secretion, and be associated with an increase in apical membrane K+ permeability. In this study, this hypothesis was tested in patients with normal renal function or ESRD, by evaluating the effect of barium ions (a K+ channel inhibitor) on rectal K+ secretion using a rectal dialysis technique, and the expression of high conductance (BK) K+ channel protein in colonic mucosa by immunohistochemistry. Under basal conditions, rectal K+ secretion was almost threefold greater (p < 0.02) in ESRD patients (n = 8) than in patients with normal renal function (n = 10). Intraluminal barium (5 mmol/l) decreased K+ secretion in the ESRD patients by 45% (p < 0.05), but had no effect on K+ transport in patients with normal renal function. Immunostaining using a specific antibody to the BK channel alpha-subunit revealed greater (p < 0.001) levels of BK channel protein expression in surface colonocytes and crypt cells in ESRD patients (n = 9) than in patients with normal renal function (n = 9), in whom low levels of expression were mainly restricted to surface colonocytes. In conclusion, these results suggest that enhanced colonic K+ secretion in ESRD involves an increase in the apical K+ permeability of the large intestinal epithelium, which most likely reflects increased expression of apical BK channels. 2005 Pathological Society of Great Britain and Ireland
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                Author and article information

                Journal
                Therapeutic Apheresis and Dialysis
                Ther Apher Dial
                Wiley
                17449979
                February 2015
                February 2015
                September 04 2014
                : 19
                : 1
                : 81-86
                Affiliations
                [1 ]Facutly of Medicine; Burapha University; Mueng Chonburi Thailand
                [2 ]Internal Medicine Department; Chonburi Hospital; Mueng Chonburi Thailand
                Article
                10.1111/1744-9987.12219
                © 2014
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