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      Management of hyperkalaemia in chronic kidney disease

      Nature Reviews Nephrology

      Springer Science and Business Media LLC

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          Abstract

          Hyperkalaemia is common in patients with chronic kidney disease (CKD), in part because of the effects of kidney dysfunction on potassium homeostasis and in part because of the cluster of comorbidities (and their associated treatments) that occur in patients with CKD. Owing to its electrophysiological effects, severe hyperkalaemia represents a medical emergency that usually requires prompt intervention, whereas the prevention of hazardous hyperkalaemic episodes in at-risk patients requires measures aimed at the long-term normalization of potassium homeostasis. The options for effective and safe medical interventions to restore chronic potassium balance are few, and long-term management of hyperkalaemia is primarily limited to the correction of modifiable exacerbating factors. This situation can result in a difficult trade-off in patients with CKD, because drugs that are beneficial to these patients (for example, renin-angiotensin-aldosterone-system antagonists) are often the most prominent cause of their hyperkalaemia. Maintaining the use of these beneficial medications while implementing various strategies to control potassium balance is desirable; however, discontinuation rates remain high. The emergence of new medications that specifically target hyperkalaemia could lead to a therapeutic paradigm shift, emphasizing preventive management over ad hoc treatment of incidentally discovered elevations in serum potassium levels.

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          Most cited references 94

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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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            Death risk in hemodialysis patients: the predictive value of commonly measured variables and an evaluation of death rate differences between facilities.

            Logistic regression analysis was applied to a sample of more than 12,000 hemodialysis patients to evaluate the association of various patient descriptors, treatment time (hours/treatment), and various laboratory tests with the probability of death. Advancing age, white race, and diabetes were all associated with a significantly increased risk of death. Short dialysis times were also associated with high death risk before adjustment for the value of laboratory tests. Of the laboratory variables, low serum albumin less than 40 g/L (less than 4.0 g/dL) was most highly associated with death probability. About two thirds of patients had low albumin. These findings suggest that inadequate nutrition may be an important contributing factor to the mortality suffered by hemodialysis patients. The relative risk profiles for other laboratory tests are presented. Among these, low serum creatinine, not high, was associated with high death risk. Both serum albumin concentration and creatinine were directly correlated with treatment time so that high values for both substances were associated with long treatment times. The data suggest that physicians may select patients with high creatinine for more intense dialysis exposure and patients with low creatinine for less intense treatment. In a separate analysis, observed death rates were compared with rates expected on the basis of case mix for these 237 facilities. The data suggest substantial volatility of observed/expected ratios when facility size is small. Nonetheless, a minority of facilities (less than or equal to 2%) may have higher rates than expected when compared with the pool of all patients in this sample. The effect of various laboratory variables on mortality is substantial, while relatively few facilities have observed death rates that exceed their expected values. Therefore, we suggest that strategies designed to improve the overall mortality statistic for dialysis patients in the United States would be better directed toward improving the quality of care for all patients, particularly high-risk patients, within their usual treatment settings rather than trying to identify facilities with high death rate for possible regulatory intervention.
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              Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial.

              The cardiovascular risk associated with early renal insufficiency is unknown. Clinicians are often reluctant to use angiotensin-converting enzyme inhibitors in patients with renal insufficiency. To determine whether mild renal insufficiency increases cardiovascular risk and whether ramipril decreases that risk. Post hoc analysis. The Heart Outcomes and Prevention Evaluation (HOPE) study, a randomized, double-blind, multinational trial involving 267 study centers. 980 patients with mild renal insufficiency (serum creatinine concentration >/= 124 micromol/L [>/=1.4 mg/dL]) and 8307 patients with normal renal function (serum creatinine concentration 0.2 for the difference). In patients who had preexisting vascular disease or diabetes combined with an additional cardiovascular risk factor, mild renal insufficiency significantly increased the risk for subsequent cardiovascular events. Ramipril reduced cardiovascular risk without increasing adverse effects.
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                Author and article information

                Journal
                Nature Reviews Nephrology
                Nat Rev Nephrol
                Springer Science and Business Media LLC
                1759-5061
                1759-507X
                November 2014
                September 16 2014
                November 2014
                : 10
                : 11
                : 653-662
                Article
                10.1038/nrneph.2014.168
                25223988
                © 2014

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