Advances in treatment of hyperkalemia in chronic kidney disease

Introduction: Hyperkalemia is a frequent electrolyte disorder associated with life-threatening cardiac arrhythmias and sudden death. Patients prone to hyperkalemia have chronic kidney disease (CKD) either alone or in conjunction with diabetes or heart failure (HF). Although agents inhibiting the renin–angiotensin–aldosterone–system (RAAS) are currently the first-line treatments toward cardio- and nephroprotection, their administration often leads to potassium elevation in such patients and results in high rates of treatment discontinuation. Areas covered: This article provides an overview of factors interfering with potassium homeostasis and discusses emerging potassium-lowering therapies for long-term management of hyperkalemia. Expert opinion: In recent randomized clinical studies, two new oral potassium-exchanging compounds, patiromer and sodium zirconium cyclosilicate, were shown to effectively normalize elevated serum potassium and chronically maintain potassium homeostasis in hyperkalemic patients treated with RAAS blockers. Both agents exhibit good tolerability and were not associated with serious adverse effects. Although additional research is required, these drugs are promising for lowering the risk of incident hyperkalemia associated with RAAS blockade use in people with diabetes or HF who have CKD. They also provide the opportunity to test whether patients who could not previously receive RAAS blockade may benefit from their cardio- and renoprotective effects.

[1]  M. Freeman,et al.  Effect of Patiromer on Serum Potassium Level in Patients With Hyperkalemia and Diabetic Kidney Disease: The AMETHYST-DN Randomized Clinical Trial. , 2015, JAMA.

[2]  Bhupinder Singh,et al.  New agents for hyperkalemia. , 2015, The New England journal of medicine.

[3]  T. Gomes,et al.  Trimethoprim–sulfamethoxazole and risk of sudden death among patients taking spironolactone , 2015, Canadian Medical Association Journal.

[4]  P. Lavin,et al.  Sodium zirconium cyclosilicate in hyperkalemia. , 2015, The New England journal of medicine.

[5]  G. Bakris,et al.  Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors. , 2015, The New England journal of medicine.

[6]  P. Lavin,et al.  Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia: the HARMONIZE randomized clinical trial. , 2014, JAMA.

[7]  C. Kovesdy Management of hyperkalaemia in chronic kidney disease , 2014, Nature Reviews Nephrology.

[8]  G. Bakris,et al.  Prediction and management of hyperkalemia across the spectrum of chronic kidney disease. , 2014, Seminars in nephrology.

[9]  L. Ruilope,et al.  Aggressive blood pressure reduction and renin-angiotensin system blockade in chronic kidney disease: time for re-evaluation? , 2014, Kidney international.

[10]  R. Agarwal,et al.  Chlorthalidone for Poorly Controlled Hypertension in Chronic Kidney Disease: An Interventional Pilot Study , 2014, American Journal of Nephrology.

[11]  P. Peduzzi,et al.  Combined angiotensin inhibition for the treatment of diabetic nephropathy. , 2013, The New England journal of medicine.

[12]  P. Welling Regulation of potassium channel trafficking in the distal nephron , 2013, Current opinion in nephrology and hypertension.

[13]  K. Gombert-Handoko,et al.  Evaluation of the concurrent use of potassium-influencing drugs as risk factors for the development of hyperkalemia , 2013, International Journal of Clinical Pharmacy.

[14]  P. Welling Regulation of renal potassium secretion: molecular mechanisms. , 2013, Seminars in nephrology.

[15]  Jeffrey Perl,et al.  Gastrointestinal adverse events with sodium polystyrene sulfonate (Kayexalate) use: a systematic review. , 2013, The American journal of medicine.

[16]  Nish Chaturvedi,et al.  Cardiorenal end points in a trial of aliskiren for type 2 diabetes. , 2012, The New England journal of medicine.

[17]  H. Heerspink,et al.  Management of hyperkalaemia consequent to mineralocorticoid-receptor antagonist therapy , 2012, Nature Reviews Nephrology.

[18]  T. Ng,et al.  Thiazide Diuretics as Chronic Antihypertensive Therapy in Patients with Severe Renal Disease—Is There a Role in the Absence of Diuresis? , 2012, The Annals of pharmacotherapy.

[19]  K. Abbott,et al.  Association of prescription of oral sodium polystyrene sulfonate with sorbitol in an inpatient setting with colonic necrosis: a retrospective cohort study. , 2012, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[20]  I. Piña,et al.  Mineralocorticoid receptor antagonists for heart failure with reduced ejection fraction: integrating evidence into clinical practice. , 2012, European heart journal.

[21]  P. Sarafidis,et al.  Prevalence and factors associated with hyperkalemia in predialysis patients followed in a low-clearance clinic. , 2012, Clinical journal of the American Society of Nephrology : CJASN.

[22]  M. Raebel Hyperkalemia associated with use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. , 2012, Cardiovascular therapeutics.

[23]  Subhash Banerjee,et al.  Predictors of hyperkalemia and death in patients with cardiac and renal disease. , 2012, The American journal of cardiology.

[24]  M. Epstein,et al.  Aldosterone blockade and the mineralocorticoid receptor in the management of chronic kidney disease: current concepts and emerging treatment paradigms. , 2012, Kidney international.

[25]  Mahboob Rahman,et al.  Metabolic Complications in Elderly Adults with Chronic Kidney Disease , 2012, Journal of the American Geriatrics Society.

[26]  Bertram Pitt,et al.  Evaluation of the efficacy and safety of RLY5016, a polymeric potassium binder, in a double-blind, placebo-controlled study in patients with chronic heart failure (the PEARL-HF) trial , 2011, European heart journal.

[27]  J. McMurray,et al.  Eplerenone in patients with systolic heart failure and mild symptoms. , 2011, The New England journal of medicine.

[28]  Arsh K Jain,et al.  Beta-blockers, trimethoprim-sulfamethoxazole, and the risk of hyperkalemia requiring hospitalization in the elderly: a nested case-control study. , 2010, Clinical journal of the American Society of Nephrology : CJASN.

[29]  R. Sterns,et al.  Ion-exchange resins for the treatment of hyperkalemia: are they safe and effective? , 2010, Journal of the American Society of Nephrology : JASN.

[30]  M. Rolfe,et al.  Potassium homeostasis and renin-angiotensin-aldosterone system inhibitors. , 2010, Clinical journal of the American Society of Nephrology : CJASN.

[31]  H. Bilo,et al.  eGFR and creatinine clearance in relation to metabolic changes in an unselected patient population. , 2009, European journal of internal medicine.

[32]  L. Appel,et al.  Risk of hyperkalemia in nondiabetic patients with chronic kidney disease receiving antihypertensive therapy. , 2009, Archives of internal medicine.

[33]  G. Bakris,et al.  Original Report: Patient-oriented, Translational Research Predictors of Hyperkalemia Risk following Hypertension Control with Aldosterone Blockade Nephrology American Journal Of , 2022 .

[34]  M. Zhan,et al.  The frequency of hyperkalemia and its significance in chronic kidney disease. , 2009, Archives of internal medicine.

[35]  S. Moss,et al.  Intestinal Necrosis due to Sodium Polystyrene Sulfonate (Kayexalate) in Sorbitol , 2009, Southern medical journal.

[36]  S. Yusuf,et al.  Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial , 2008, The Lancet.

[37]  S. Yusuf,et al.  Telmisartan, ramipril, or both in patients at high risk for vascular events. , 2008, The New England journal of medicine.

[38]  A. Kshirsagar,et al.  Change in proteinuria after adding aldosterone blockers to ACE inhibitors or angiotensin receptor blockers in CKD: a systematic review. , 2008, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[39]  F Boomsma,et al.  Beneficial impact of spironolactone on nephrotic range albuminuria in diabetic nephropathy. , 2006, Kidney international.

[40]  H. Parving,et al.  Beneficial effects of adding spironolactone to recommended antihypertensive treatment in diabetic nephropathy: a randomized, double-masked, cross-over study. , 2005, Diabetes care.

[41]  B. Palmer Managing hyperkalemia caused by inhibitors of the renin-angiotensin-aldosterone system. , 2004, The New England journal of medicine.

[42]  N. Hollenberg Aldosterone in the development and progression of renal injury. , 2004, Kidney international.

[43]  Bruce Kupelnick,et al.  K/DOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease , 2004 .

[44]  Tom Greene,et al.  Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. , 2002, JAMA.

[45]  E. Lewis,et al.  Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. , 2001, The New England journal of medicine.

[46]  G. Becker,et al.  Spironolactone in addition to ACE inhibition to reduce proteinuria in patients with chronic renal disease. , 2001, The New England journal of medicine.

[47]  B. Brenner,et al.  Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. , 2001, The New England journal of medicine.

[48]  N. Hollenberg ACE inhibition or angiotensin receptor blockade: impact on potassium in renal failure. , 2001, Current hypertension reports.

[49]  G. Bakris,et al.  ACE inhibition or angiotensin receptor blockade: impact on potassium in renal failure. VAL-K Study Group. , 2000, Kidney international.

[50]  M. Perazella,et al.  Drug-induced hyperkalemia: old culprits and new offenders. , 2000, The American journal of medicine.

[51]  B. Pitt,et al.  The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure , 2000 .

[52]  B. Pitt,et al.  The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. , 1999, The New England journal of medicine.

[53]  M. Marinella Trimethoprim-Induced Hyperkalemia: An Analysis of Reported Cases , 1999, Gerontology.

[54]  D. Batlle,et al.  A subdepressor low dose of ramipril lowers urinary protein excretion without increasing plasma potassium. , 1999, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[55]  A. Smally,et al.  Hyperkalemia and digoxin toxicity in a patient with kidney failure. , 1996, Annals of emergency medicine.

[56]  F. Locatelli,et al.  Effect of the Angiotensin-Converting–Enzyme Inhibitor Benazepril on the Progression of Chronic Renal Insufficiency , 1996 .

[57]  L. Fishman,et al.  Heparin-induced aldosterone suppression and hyperkalemia. , 1995, The American journal of medicine.

[58]  R. Bain,et al.  The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. , 1993, The New England journal of medicine.

[59]  W. Henrich,et al.  Implications of nonsteroidal anti-inflammatory drug therapy. , 1986, The American journal of medicine.

[60]  D. Simmons,et al.  Acid-base alterations and plasma potassium concentration. , 1959, The American journal of physiology.

[61]  Usrds NIH, U. . Renal Data System: Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States. , 2012 .

[62]  R. Garrick Addition of Angiotensin Receptor Blockade or Mineralocorticoid Antagonism to Maximal Angiotensin-Converting Enzyme Inhibition in Diabetic Nephropathy , 2010 .

[63]  Olivier Moranne,et al.  Timing of onset of CKD-related metabolic complications. , 2009, Journal of the American Society of Nephrology : JASN.

[64]  Y. Ubara,et al.  Analysis of factors causing hyperkalemia. , 2007, Internal medicine.

[65]  G. Bakris,et al.  Antihypertensive therapy in the presence of proteinuria. , 2007, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[66]  B. Jaber,et al.  Prevention of radiocontrast nephropathy with N-acetylcysteine in patients with chronic kidney disease: a meta-analysis of randomized, controlled trials. , 2004, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[67]  F. Locatelli,et al.  Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group. , 1996, The New England journal of medicine.

[68]  A Fournier,et al.  The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. , 1994, The New England journal of medicine.

[69]  R. DeFronzo,et al.  Hyperkalemia and hyporeninemic hypoaldosteronism. , 1980, Kidney international.