NEW POTASSIUM BINDERS FOR THE TREATMENT OF HYPERKALEMIA: University of Michigan School of Medicine, Ann Arbor, Michigan, USA (BP); Director, ASH

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1 NEW POTASSIUM BINDERS FOR THE TREATMENT OF HYPERKALEMIA: CURRENT DATA AND OPPORTUNITIES FOR THE FUTURE Online Supplement Bertram Pitt, MD and George L. Bakris, MD University of Michigan School of Medicine, Ann Arbor, Michigan, USA (BP); Director, ASH Comprehensive Hypertension Center, The University of Chicago Medicine, Chicago, Illinois, USA (G.L.B.)

2 Online Supplement References 1. Mehdi UF, Adams-Huet B, Raskin P, Vega GL, Toto RD. Addition of angiotensin receptor blockade or mineralocorticoid antagonism to maximal angiotensin-converting enzyme inhibition in diabetic nephropathy. J Am Soc Nephrol. 2009;20: Uijtendaal EV, Zwart-van Rijkom JE, van Solinge WW, Egberts TC. Frequency of laboratory measurement and hyperkalaemia in hospitalised patients using serum potassium concentration increasing drugs. Eur J Clin Pharmacol. 2011;67: Reardon LC, Macpherson DS. in outpatients using angiotensin-converting enzyme inhibitors. How much should we worry? Arch Intern Med. 1998;158: Stevens MS, Dunlay RW. in hospitalized patients. Int Urol Nephrol. 2000;32: Jarman PR, Kehely AM, Mather HM. Hyperkalaemia in diabetes: prevalence and associations. Postgrad Med J. 1995;71: Sarafidis PA, Blacklock R, Wood E, Rumjon A, Simmonds S, Fletcher-Rogers J, Ariyanayagam R, Al-Yassin A, Sharpe C, Vinen K. Prevalence and factors associated with hyperkalemia in predialysis patients followed in a low-clearance clinic. Clin J Am Soc Nephrol. 2012;7: Einhorn LM, Zhan M, Hsu VD, Walker LD, Moen MF, Seliger SL, Weir MR, Fink JC. The frequency of hyperkalemia and its significance in chronic kidney disease. Arch Intern Med. 2009;169:

3 8. Harel Z, Gilbert C, Wald R, Bell C, Perl J, Juurlink D, Beyene J, Shah PS. The effect of combination treatment with aliskiren and blockers of the renin-angiotensin system on hyperkalaemia and acute kidney injury: systematic review and meta-analysis. BMJ. 2012;344:e Van Buren PN, Adams-Huet B, Nguyen M, Molina C, Toto RD. Potassium handling with dual renin-angiotensin system inhibition in diabetic nephropathy. Clin J Am Soc Nephrol. 2014;9: Khosla N, Kalaitzidis R, Bakris GL. Predictors of hyperkalemia risk following hypertension control with aldosterone blockade. Am J Nephrol. 2009;30: Miao Y, Dobre D, Heerspink HJ, Brenner BM, Cooper ME, Parving HH, Shahinfar S, Grobbee D, de ZD. Increased serum potassium affects renal outcomes: a post hoc analysis of the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trial. Diabetologia. 2011;54: Weinberg JM, Appel LJ, Bakris G, Gassman JJ, Greene T, Kendrick CA, Wang X, Lash J, Lewis JA, Pogue V, Thornley-Brown D, Phillips RA. Risk of hyperkalemia in nondiabetic patients with chronic kidney disease receiving antihypertensive therapy. Arch Intern Med. 2009;169:

4 Table S1. Literature-Reported s of Mehdi et al. 1 Prospective, Type 1 or 2 diabetes 80 6 meq/l 2/27 placebo University medical randomized, mellitus with SBP 10/26 losartan center in U.S. double-blind, >130 mmhg and 14/27 placebo UACR 300 mg/g spironolactone controlled trial of despite ACEI or ARB placebo, losartan for 3 months. 100 mg/day, or spironolactone 25 mg/day added to lisinopril mg/day Uijtendaal et al. 2 Cross-sectional Hospitalized and 9, meq/l 5.9% (1 PID) University hospital receiving 1 PID; 9.9% ( 2 PID)

5 in the Netherlands dialysis excluded In subset with egfr 80 ml/min egfr 50 ml/min: 18% 15.8% (1 PID) egfr ml/min 16.9% ( 2 PID) 23% In subset with egfr 50 ml/min diabetes: 14% 10.1% (1 PID) Diabetes 20% 12.8% ( 2 PID) RAASi 60% Reardon et al. 3 Case-control with 1, mmol/l 194 (11%) VA Medical Center hyperkalemia on Mean SCr 1.3 mg/dl Hypertension 88% Diabetes 45% 5

6 Heart failure 30% ACE-inhibitor 100% Stevens et al. 4 Case-control Dialysis excluded 1,060 >5.5 mmol/l 35 (3.3%) Tertiary teaching CrCl 37 ml/min hospital in US Diabetes 54% ACEI 46% Jarman et al. 5 Hospital diabetes Observational Diabetes 100% 1,764 >5 mmol/l 270 (15%) >5 mmol/l clinic Sarafidis et al. 6 Cross-sectional Pre-dialysis CKD 238 >5.0 meq/l 54.2% CKD clinic in Mean age 66 years tertiary university Hypertension 95% hospital, US Diabetes 45% egfr

7 ml/min/1.73 m 2 ACE-inhibitor or ARB 49.7% ACEI/ARB 10% MRA 1% Einhorn et al 7 Retrospective, Veterans with 1 245, meq/l 33,637/245,808 Veterans Health observational hospitalization, 174,935 no CKD (13.7%) Administration outpatient 70,873 CKD (Stage CKD and RAASi: measurement of SCr 3, 81.6%; Stage 4, 7.67 a and 1potassium 11.8%; Stage 5 No CKD and value 6.7%) RAASi: 2.30 a CKD and no RAASi: 8.22 a No CKD and no 7

8 RAASi: 1.77 a Harel et al 8 Systematic Varied by study; >5.5 meq/l RR for review hypertension, post- hyperkalemia: MI, ACS, heart aliskiren + ACEI failure, diabetes, or ARB vs. proteinuria monotherapy 1.58 Aliskiren + ACEI or (95% CI ) ARB vs. ACEI or ARB monotherapy Van Buren et al 9 Prospective, Diabetes, 80 6 meq/l 7.4% placebo University Medical randomized, hypertension, UACR 38.5% losartan Center double-blind >300 mg/g on 51.9% placebo Lisinopril spironolactone controlled trial of Mean SCr 1.4 mg/dl 8

9 losartan, spironolactone, or placebo on top of (placebo), 1.7 mg/dl (losartan), 1.8 mg/dl (spironolactone) lisinopril Khosla et al 10 Retrospective Hypertensive patients 46 >5.5 meq/l 8 (17.3%) Tertiary care, cohort study in whom university based spironolactone was hypertension added to achieve goal clinics blood pressure Diabetes: 87% ACEI or ARB: 100% egfr 57 ml/min/1.73 m 2 Miao et al 11 Post-hoc analysis Type 2 diabetes and 1,513 5 mmol/l 410 (30.6%) 9

10 of RENAAL nephropathy enrolled in the RENAAL trial Weinberg et al. 12 Retrospective Non diabetic African 1,053 >5.5 meq/l 51 patients with analysis of AASK Americans with hyperkalemic hypertensive CKD events egfr: 47 Event rates for ml/min/1.73 m 2 hyperkalemia: ACEI: 39% egfr 30 ml/min/m 2 : 6.87 b egfr >30 to 40: 2.75 b On RAASi: 2.45 b a Per 100 patient-months; b Per 100 patient-years AASK = African American Study of Kidney Disease and Hypertension; ACEI = angiotensin converting enzyme inhibitor; ACS = acute coronary syndrome; ARB = angiotensin receptor blocker; CKD = chronic kidney disease; egfr = estimated glomerular 10

11 filtration rate; MI = myocardial infarction; PID = potassium increasing drug; RAASi = renin angiotensin aldosterone system inhibitor; RENAAL = Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan trial; SBP = systolic blood pressure; SCr = serum creatinine; UACR = urine albumin-to-creatinine ratio; VA = Veterans Affairs 11

12 Table S2. Common Sources of Dietary Potassium Source Unit Measure Potassium (mg) per Unit Measure Molasses 1 cup (337 g) 4934 Pork loin backribs 1071 g 2870 Turkey breast (cooked) 863 g 2563 Cocoa powder (unsweetened) 86 g 2158 Canned soup, New England 1 can (519 g) 1749 Clam Chowder Baked russet potatoes 299 g 1644 Rotisserie cooked chicken 483 g 1463 Raisins 1 cup (165 g) 1361 Dry roasted pistachio nuts 1 cup (123 g) 1239 Avocado, raw 1 cup (pureed) (230 g) 1166 Canned pureed tomatoes 1 cup (250 g) 1098 Roasted almonds 1 cup (157 g) 1097 Roasted peanuts 1 cup (144 g) 1045 Salmon 108 g 1037 Lima beans, boiled 1 cup (170 g) 969 Sweet potato, baked 1 cup (200 g) 950 Great northern beans, canned 1 cup (262 g) 920 Tomato soup, canned 1 cup (148 g) 832 Vegetable juice, V8, canned 8 oz (243 g) 819

13 Table S2. Common Sources of Dietary Potassium (continued) Source Unit Measure Potassium (mg) per Unit Measure Bananas, raw 1 cup, mashed (225 g) 806 Black beans, cooked (boiled) 1 cup (185 g) 801 Refried beans, canned 1 cup (231 g) 795 Baked beans, canned 1 cup (253 g) 782 Pork chops, cooked 150 g 776 Cashews, dry roasted 1 cup (137 g) 774 Pinto beans, cooked (boiled) 1 cup (171 g) 746 Tomato sauce, canned 1 cup (245 g) 728 Beef ribeye, grilled 138 g 564 Kiwifruit 1 cup (180 g) 562 Fish, haddock, cooked 150 g 526 Orange juice 1 cup (248 g) 496 Milk (reduced fat 2%) 1 cup (246 g) 448 Yogurt, plain, low-fat 6 oz (170 g) 398 Chicken breast, grilled 3 oz (85 g) 357 Egg, whole, hard-boiled 1 cup (136 g) 171 Source: 13

Aggressive blood pressure reduction and renin angiotensin system blockade in chronic kidney disease: time for re-evaluation?

http://www.kidney-international.org & 2013 International Society of Nephrology Aggressive blood pressure reduction and renin angiotensin system blockade in chronic kidney disease: time for re-evaluation?