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      Management of hyperkalemia in patients with kidney disease: a position paper endorsed by the Italian Society of Nephrology

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          Abstract

          Hyperkalemia (HK) is the most common electrolyte disturbance observed in patients with kidney disease, particularly in those in whom diabetes and heart failure are present or are on treatment with renin–angiotensin–aldosterone system inhibitors (RAASIs). HK is recognised as a major risk of potentially life threatening cardiac arrhythmic complications. When an acute reduction of renal function manifests, both in patients with chronic kidney disease (CKD) and in those with previously normal renal function, HK is the main indication for the execution of urgent medical treatment and the recourse to extracorporeal replacement therapies. In patients with end-stage renal disease, the presence of HK not responsive to medical therapy is an indication at the beginning of chronic renal replacement therapy. HK can also be associated indirectly with the progression of CKD, because the finding of high potassium values leads to withdrawal of treatment with RAASIs, which constitute the first choice nephro-protective treatment. It is therefore essential to identify patients at risk of developing HK, and to implement therapeutic interventions aimed at preventing and treating this dangerous complication of kidney disease. Current strategies aimed at the prevention and treatment of HK are still unsatisfactory, as evidenced by the relatively high prevalence of HK also in patients under stable nephrology care, and even in the ideal setting of randomized clinical trials where optimal treatment and monitoring are mandatory. This position paper will review the main therapeutic interventions to be implemented for the prevention, detection and treatment of HK in patients with CKD on conservative care, in those on dialysis, in patients in whom renal disease is associated with diabetes, heart failure, resistant hypertension and who are on treatment with RAASIs, and finally in those presenting with severe acute HK.

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          Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association

          Resistant hypertension (RH) is defined as above-goal elevated blood pressure (BP) in a patient despite the concurrent use of 3 antihypertensive drug classes, commonly including a long-acting calcium channel blocker, a blocker of the renin-angiotensin system (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker), and a diuretic. The antihypertensive drugs should be administered at maximum or maximally tolerated daily doses. RH also includes patients whose BP achieves target values on ≥4 antihypertensive medications. The diagnosis of RH requires assurance of antihypertensive medication adherence and exclusion of the "white-coat effect" (office BP above goal but out-of-office BP at or below target). The importance of RH is underscored by the associated risk of adverse outcomes compared with non-RH. This article is an updated American Heart Association scientific statement on the detection, evaluation, and management of RH. Once antihypertensive medication adherence is confirmed and out-of-office BP recordings exclude a white-coat effect, evaluation includes identification of contributing lifestyle issues, detection of drugs interfering with antihypertensive medication effectiveness, screening for secondary hypertension, and assessment of target organ damage. Management of RH includes maximization of lifestyle interventions, use of long-acting thiazide-like diuretics (chlorthalidone or indapamide), addition of a mineralocorticoid receptor antagonist (spironolactone or eplerenone), and, if BP remains elevated, stepwise addition of antihypertensive drugs with complementary mechanisms of action to lower BP. If BP remains uncontrolled, referral to a hypertension specialist is advised.
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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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              Effect of Finerenone on Albuminuria in Patients With Diabetic Nephropathy: A Randomized Clinical Trial.

              Steroidal mineralocorticoid receptor antagonists, when added to a renin-angiotensin system blocker, further reduce proteinuria in patients with chronic kidney disease but may be underused because of a high risk of adverse events.
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                Author and article information

                Contributors
                +39 0586614383 , stefano2.bianchi@uslnordovest.toscana.it
                f.aucella@operapadrepio.it
                luca.denicola@unicampania.it
                simonetta.genovesi@unimib.it
                ernesto.paoletti@hsanmartino.it
                giuregolisti@gmail.com
                Journal
                J Nephrol
                J. Nephrol
                Journal of Nephrology
                Springer International Publishing (Cham )
                1121-8428
                1724-6059
                22 May 2019
                22 May 2019
                2019
                : 32
                : 4
                : 499-516
                Affiliations
                [1 ]Nephrology and Dialysis Unit, Department of Internal Medicine, Azienda ASL Toscana Nord Ovest, Livorno, Italy
                [2 ]ISNI 0000 0004 1757 9135, GRID grid.413503.0, Nephrology and Dialysis Unit, , IRCCS “Casa Sollievo della Sofferenza” Scientific Institute for Research and Health Care, ; San Giovanni Rotondo, Italy
                [3 ]Division of Nephrology, University of Campania, Naples, Italy
                [4 ]ISNI 0000 0004 1757 2822, GRID grid.4708.b, Department of Medicine and Surgery, , University of Milano - Bicocca San Gerardo Hospital, Nephrology Unit, ; Monza, Italy
                [5 ]ISNI 0000 0001 2151 3065, GRID grid.5606.5, Nephrology, Dialysis and Transplantation, , University of Genoa and Policlinico, ; San Martino Genoa, Italy
                [6 ]ISNI 0000 0004 1758 0937, GRID grid.10383.39, Acute and Chronic Renal Failure Unit, Department of Medicine and Surgery, , University of Parma, ; Parma, Italy
                Author information
                http://orcid.org/0000-0003-3981-6325
                Article
                617
                10.1007/s40620-019-00617-y
                6588653
                31119681
                a266cfe1-7dee-4ffe-b8ed-52829292c705
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 10 March 2019
                : 5 May 2019
                Categories
                Position papers and Guidelines
                Custom metadata
                © Italian Society of Nephrology 2019

                hyperkalemia,chronic kidney disease,acute kidney injury,renin–angiotensin–aldosterone inhibitors

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