hyperkalemia: epidemiology, pathophysiology, and … hyperkalemia.pdf · nephsap: 2007;6....

11/16/2015

1

Improving the Management of Hyperkalemia

Biff F. Palmer, M.D.Professor of Internal MedicineUniversity of Texas Southwestern Medical CenterDallas, Texas

Hyperkalemia: Epidemiology, Pathophysiology, and Clinical Consequences

11/16/2015

2

Distribution of Total Body K+

Muscle: 2,700 mEq

Liver: 250 mEq

Erythrocytes: 250 mEq

Bone: 300 mEq

Intracellular Fluid3,500 mEq (140-150 mEq/L)

Extracellular fluid70 mEq (3.5-5.5 mEq/L)

K+ Gradient Sets Cell Voltage

Regulation of K+ Homeostasis

ICF3,500 mEq

(140-150 mEq/L)

ECF70 mEq

(3.5-5.5 mEq/L)

Intake100 mEq

Renal excretion90 mEq

GI excretion10 mEq

Cell Shift

11/16/2015

3

Epidemiology of Hyperkalemia

• Incidence as high as 40%-55% in patients with CKD

• Even in specialized CKD clinics, the incidence is as high as 55%

Einhorn LM, et al. Arch Intern Med. 2009;169:1156-1162. Hayes J, et al. Nephron Clin Pract. 2012;120:c8-c16. Sarafidis PA, et al. Clin J Am Soc Nephrol. 2012;7:1234-1241.

Does the development of hyperkalemia have prognostic significance?

11/16/2015

4

Einhorn LM, et al. Arch Intern Med. 2009;169:1156-1162.

Serum Potassium (mEq/L)

1-day mortality rate 6-17 times higher in patients with K+

≥5.5 mEq/L than in those with K+

< 5.5 mEq/L

< 5.5 > 5.5 and < 6.0 > 6.0

Ratio compared to < 5.5 1.0 6.2 16.7

Mortality Rate Within 1 Day of a Hyperkalemia Event

1-D

ay M

ort

alit

y R

ate

Differential Diagnosis of Hyperkalemia

• Pseudohyperkalemia

• Excess K+ intake

• Cell shifts

• Impaired renal excretion

• Only cause of sustained hyperkalemia

11/16/2015

5

Seasonal Pseudohyperkalemia

Samples taken over 2 years from general practice, inpatient samples unaffected

Sinclair D, et al. J Clin Pathol. 2003;56:385-387.




11/16/2015

6

Excess Intake

• Salt substitutes

• Large amounts of juice

• Coconut juice (44.3 mmol/L)

• Orange juice (51-yo-man with K+ of 9 mEq/L, drank 2.5 L daily, 1,125 mEq/d for 3 wks)

• Noni juice

• River bed clay (100 mEq/100 g clay)

• Burnt match heads (cautopyreiophagia)

• Bananas:

– 15 yo with K+ of 6.1 mEq/L ingesting 20/d

Palmer BF, Sterns RH. Neph SAP. 2009;8. Sterns RH, Palmer BF. NephSAP: 2007;6.




• Cell shifts

• Impaired renal excretion

• Only cause of sustained hyperkalemia

11/16/2015

7

Impaired Renal K+ Excretion

• Primary decrease in mineralocorticoid activity

Renin

IMPAIRED RELEASEOF RENIN

NSAIDsBeta Blockers

Cyclosporine, TacrolimusDiabetesElderly

Angiotensin I Angiotensin II

Aldosterone

Na+

Na+

K+

K+LUMEN

Afferent Arteriole

Juxtaglomerularcells

AdrenalGland

Collecting Duct(principal cell)

Palmer BF. N Engl J Med .2004;351:585-592.

Primary Decrease in Mineralocorticoid Activity

11/16/2015

8

Change in PRA and Aldosterone with Na+ Restriction in Young vs Elderly

Plasma Renin Activity (ng/100 mL/3h) Plasma Aldosterone (ng/100 mL)

Na+ Intake (mEq/24h) Na+ Intake (mEq/24h)

Weidmann P, et al. Kidney Int. 1975;8:325-333.

K+ Infusion: Blunted Rise in Serum Aldosterone in Elderly vs Young

Ald

oste

rone

(pg

/mL)

Time (min)

KCl (0.05 mEq/kg wt over 45 minutes)

Mulkerrin E, et al. J Am Soc Nephrol. 1995.;6:1459-1462

Similar basal levels and increase in serum K+ during infusion

11/16/2015

9


Renin


NSAIDsBeta Blockers



ANGIOTENSIN-CONVERTING ENZYME

INHIBITORS

ANGIOTENSINRECEPTOR BLOCKERS

Aldosterone

Na+

Na+

K+

K+LUMEN

Afferent Arteriole


AdrenalGland


DIRECT RENININHIBITOR

Palmer BF. N Engl J Med. 2004;351:585-592.

Renin


NSAIDsBeta Blockers




INHIBITORS


Aldosterone

IMPAIREDALDOSTERONEMETABOLISM

Adrenal DiseaseHeparin

Ketoconazole

Na+

K+

K+LUMEN

Afferent Arteriole


AdrenalGland





Na+

11/16/2015

10

Renin


NSAIDsBeta Blockers




INHIBITORS


Aldosterone



Ketoconazole

Na+

K+

K+

ALDOSTERONERECEPTORBLOCKERS

SpironolactoneEplerenone

Drospirenone

LUMEN

Afferent Arteriole


AdrenalGland





Na+

Renin


NSAIDsBeta Blockers




INHIBITORS


Aldosterone



Ketoconazole

SODIUM CHANNELBLOCKERS

AmilorideTriamterene

TrimethoprimPentamidine

Na+

K+

K+

ALDOSTERONERECEPTORBLOCKERS

SpironolactoneEplerenone

Drospirenone

LUMEN

Afferent Arteriole


AdrenalGland





Na+

11/16/2015

11



• Primary decrease in distal Na+ delivery

Primary Decrease in Distal Na+

Delivery

• Oliguric acute renal failure

• Acute glomerulonephritis

11/16/2015

12



• Primary decrease in distal Na+ delivery

• Abnormal cortical collecting duct

Abnormal Collecting Duct

• Drugs

• Tubulointerstitial nephritis

• Urinary obstruction

11/16/2015

13

What are the clinical consequencesof hyperkalemia?

Clinical Consequences of Hyperkalemia

• Cardiac toxicity

11/16/2015

14

Poor Sensitivity and Specificity of ECG as Diagnostic Test for Hyperkalemia

• In 127 patients with serum K+ between 6-9.3 mEq/L, only 46% of ECGs noted to have changes1

• In 90 cases, only 24 noted to have characteristic T- wave changes as read by a cardiologist2

• Only 1/14 who presented with arrhythmias or arrest had strict criteria

Potassium quintiles by presence of strict criteria for ECG changes

1Acker CG, et al. Arch Intern Med. 1998;158:917-924. 2Montague BT, et al. Clin J Am Soc Nephrol. 2008;3:324-330.

Clinical Consequences of Hyperkalemia

• Cardiac toxicity

• Muscle weakness

• Impaired renal acidification

11/16/2015

15

Hyperkalemia

NH4+

Medullaryaccumulation

NH4+NH4

+

H+

NH3

NH3

H+

NH3

H+

H+

H+

H+

UpH = 5.0Net acid excretion reduced

Metabolic Acidosis in CKD

Metabolic Acidosis

Increased ammoniagenesis in remaining nephrons

Increased endothelinComplement activation

Tubulointerstitial renal disease

Chen W, Abramowitz MK. BMC Nephrol. 2014;15:55.

11/16/2015

16

Summary

• Hyperkalemia is common in CKD patients and in those with conditions that disrupt the renin-angiotensin-aldosterone system

• Hyperkalemic events are associated with worse outcomes– Cardiac events

– Muscle weakness

– Impaired acidification

• Strategies to limit development of hyperkalemia would be of clinical utility

Hyperkalemia Management: Current Challenges and Evolving Perspectives

11/16/2015

17

RAASi Promotes Kidney‐Saving and

Life‐Saving Benefits in Patients With CKD,

Heart Failure, or Diabetes Mellitus

CKD, chronic kidney disease; RAASi, renin-angiotensin-aldosterone system inhibitor.

RALES/EMPHASIS‐HF: MRAs Improved Survival in Patients With HF

HF, heart failure; MRAs, mineralocorticoid receptor antagonists.Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999;341(10):709-717.

11/16/2015

18

Hyperkalemia Is a Common Complication

in Patients With Heart Failure Receiving

Mineralocorticoid Receptor Antagonists

Hospitalizations for Hyperkalemia Spiked in Heart Failure Patients After Publication of RALES

Juurlink DN, Mamdani MM, Lee DS, Kopp A, Austin PC, Laupacis A, Redelmeier DA. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med. 2004;351(6):543-551.

Online releaseof RALES

Rate of hospital admission for hyperkalemia among patients recently hospitalized

for heart failure who were receiving ACEi

Rat

e o

f A

dm

issi

on

fo

r H

yper

kale

mia

(p

er 1

,000

pat

ien

ts)

Study Year

1994

10

12

14

8

6

4

2

0

1995 1996 1997 1998 1999 2000 2001

The yellow lines and 95% CIs beginning in 1999 represent the projected rates of hospital admissions for hyperkalemia.

11/16/2015

19

Hyperkalemia Is a Major Reason for Discontinuation of MRA• 134 HF patients followed in a Portuguese HF clinic

• Spironolactone use in patients with sCr ≤2.5 mg/dL and K+ ≤5 mEq/L

• 25% of patients withdrew from spironolactone therapy (19/76)

HF, heart failure; MRA, mineralocorticoid receptor antagonist; sCR, serum creatinineLopes RJ, et al. Clin Cardiol. 2008;31:509-513.

% of Patien

ts

*Severe hyperkalemia (≥6 mEq/L) occurred in 7 patients who withdrew from spironolactone therapy (9.2%).

Reason for spironolactone suspension (%)

Discontinuation of MRA

Entresto (LCZ696) is approved by FDA

• Combination of the ARB valsartan and neprilysin inhibitor

• Indicated to reduce the risk of cardiovascular death and hospitalization for heart failure patients with chronic heart failure (CHF) (NYHA class II-IV) and reduced ejection fraction

11/16/2015

20

Hyperkalemia Will Remain an Issue With LCZ‐696PARADIGM Heart Failure Study

•PARADIGM‐HF selected a population at low risk for hyperkalemia prior to randomization

–Excluded patients with eGFR <30 mL/min/1.73 m2

–Excluded patients with serum potassium level of more than 5.2 mmol/L at screening (or more than 5.4 mmol/L at randomization)

•Hyperkalemia rates remained high in all patients despite carefully selected population

–>5.5 mmol/L: 16.1% LCZ‐696 versus 17.3% ACEi (P = .15)

–>6.0 mmol/L: 4.3% LCZ‐696 versus 5.6% ACEi (P = .007)

eGFR, estimated glomerular filtration rate; HF, heart failure. McMurray J, et.al. N Engl J Med. 2014;371(11):993-1004.

Hyperkalemia versus RAASi: The Catch‐22 of Managing Diseases That Benefit From RAASi Therapy

Prescribe RAASi and

Accept Presence of

Hyperkalemia?

RAASi, renin-angiotensin-aldosterone system inhibitor.

Avoid/Discontinue

Proven RAASi

Therapies?

CATCH‐22

11/16/2015

21

Hyperkalemia Is a Leading Reason for Not Starting RAASiand the Major Reason for Discontinuation of RAASi in CKD

• 279 patients with CKD followed up for a mean of 22 months

• Baseline mean eGFR was 33.3 mL/min/1.73m2 and the serum K+ was 4.73 mEq/L

Yildrim T, et al. Ren Fail. 2012;34(9):1095-1099.

(80 patients) (51 patients)

% of Patients

CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; RAASi, renin-angiotensin-aldosterone system inhibitor.

Current Guidelines Tend to Lessen the Use of

Full Recommended Doses of Renin‐

Angiotensin‐Aldosterone System Inhibitors

Because of Concerns Related to Hyperkalemia

11/16/2015

22

Guidelines Recommend RAASi Modifications at Various Serum K+ Levels

Serum K+ Threshold Before Change in RAASi Guideline Recommendation

>6.0

>5.5

>5.0

ACA/AHA HFa:Maintain MRA 4.0‐5.0

ACC/AHA,a ESC HF,b K/DOQIf:Reduce dose of/stop ACEi/ARB, AA if >5.5

HFSA HFc: MRA not recommended >5.0

NICEe:Stop RAASi if >6.0

NICEe: don’t start RAASi if >5.0

KDIGO Guidelines do not provide

recommendationsd

K/DOQIf: don’t start RAASi if > 5.0

MRA, mineralocorticoid receptor antagonist; RAASi, renin-angiotensin-aldosterone inhibitor.a. Yancy CW, et al. J Am Coll Cardiol. 2013;62(16):e147-239. b. McMurray JJ, et al. Eur Heart J. 2012;33(14):1787-1847.c. Heart Failure Society of America, Lindenfeld J, et al. J Card Fail. 2010;16(6):e1-e194. d. KDIGO Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl. 2013;3(1). e. National Institute for Health and Care Excellence (NICE) [UK]. 2008. http://www.nice.org.uk/CG73. f. http://www.kidney.org/professionals/kdoqi/guidelines_bp/guide_11.htm#table131.

Serum K

+ (m

Eq/L)

Hyperkalemia Prevents Use of Guideline‐Recommended RAASi Therapy to Delay Progression to ESRD

Kidney Disease Outcomes Quality Initiative, Guideline 11: Use of ACEis and ARBs in CKD

• In general, highest tolerated doses of ACEior ARB (RAASi) are recommended

• If hyperkalemia develops, reduce dose of ACEi or ARB and/or discontinue the ACEior ARB

Optimal dose25%

Untreated/can’t tolerate

33%

Suboptimal dose42%

RAASi treatmentin CKD*

~90% of nephrologists: hyperkalemia is top concern with use of RAASi medication**

ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CKD, chronic kidney disease; ESRD, end-stage renal disease; RAASi, renin-angiotensin-aldosterone system inhibitor.

*Estimates based on data adapted from Treatment Algorithm Quantitative Study, June 2013, N = 386. **Primary market research, April 2012.

11/16/2015

23

Therapies To Treat Acute Hyperkalemia

aModified from Weisberg LS. Crit Care Med. 2008;36(12):3246-3251. bModified from Floege J, Johnson RJ, Feehally J, eds. Comprehensive Clinical Nephrology. St.Louis, MO: Mosby; 2010. cBallantyne F 3rd, Davis LD, Reynolds EW Jr. Am J Physiol. 1975;229(4):935-940.MOA, mechanism of action; CPS, calcium polystyrene sulfonate; SPS, sodium polystyrene sulfonate.

Calcium gluconate salt↓ threshold poten al of cardiac myocytesa

InsulinActivates the Na+/K+‐ATPase pumpa

β‐adrenoceptor agonists

Sodium bicarbonateAlkalinizes the urine, thereby enhancing urinary K+ excretiona

Loop diureticsEnhance urinary K+ excretionb

SPS/CPSEnhance K+ removal through the colonc

HemodialysisRemoval of K+ from blooda

Membrane Stabilizationa,b K+ Redistributiona,b K + Eliminationa,b

Sodium Polystyrene Sulfonate:Limited Data to Substantiate Efficacy

aSterns RH, Rojas M, Bernstein P, Chennupati S. J Am Soc Nephrol. 2010;21(5):733-735. bKayaxelate PI 2010. cKamel KS, Schreiber M. Nephrol Dial Transplant. 2012;27(12):4294-4297. dGruy-Kapral C, Emmett M, Santa Ana CA, Porter JL, Fordtran JS, Fine KD. J Am Soc Nephrol. 1998;9(10):1924-1930.FDA, US Food and Drug Administration; SPS, sodium polystyrene sulfonate.

“…no convincing evidence that SPS increases fecal K+ losses in experimental animals or humans and no evidence that adding sorbitol

to the resin increases its effectiveness...”a

FDA approved in 1958, before well‐controlled studies were requireda

• Indicated for the treatment of hyperkalemiab

There is concern that kayexalate may not be effective without osmoticallyactive amounts of sorbitolc,d

11/16/2015

24

WARNINGSIntestinal Necrosis

• Cases of intestinal necrosis, which may be fatal, and other serious gastrointestinal adverse events (bleeding, ischemic colitis, perforation) have been reported in association with kayexalate use

• The majority of these cases reported the concomitant use of sorbitol

• Risk factors for gastrointestinal adverse events were present in many of the cases, including prematurity, history of intestinal disease or surgery, hypovolemia, and renal insufficiency and failure

• Concomitant administration of sorbitol is not recommended

FDA Issued Warning on Sodium Polystyrene Sulfonate in September 2009

Kayexalate Prescribing Information. December 2010. www,fda.gov/Safety/MedWatch/SafetyInformation/ucm186845.htm. FDA, US Food and Drug Administration.

Necrosis (62%), Ulceration (48%), Perforation (9%), and SPS crystals (90%)a

Histopathology of SPS‐Related GI Injury

Hematoxylin and eosin stain (original magnification ×40)

SPS crystals within the ulcer and on the surfaceb

aHarel Z, Harel S, Shah PS, Wald R, Perl J, Bell CM. Am J Med. 2013;126(3):264.e9-24. bBomback AS, Woosley JT, Kshirsagar AV. Am J Emerg Med. 2009 Jul;27(6):753.e1-2.GI, gastointestinal; SPS, sodium polystyrene sulfonate.

Base of an ulcer that shows necrotic debrisreplacing the intestinal mucosab

11/16/2015

25

Patiromer (RLY5016) Is a Polymer That Binds Potassium in the Colon

• Patiromer is a nonabsorbed K+

binding polymer

• Patiromer binds K+ in colon

• Patiromer acts as a “sink” to increase colonic K+ excretion

Patiromer (RLY5016)

Buysse JM, et al. Future Cardiol. 20128:17-28.GFR, glomerular filtration rate; RAAS, renin-angiotensin-aldosterone system.

Hyperkalemia is most commonly caused by chronic kidney disease, or the use of RAAS blockade drugs that limit urinary K+ excretion and increase serum K+ level

Hyperkalemia

Patiromer in Patients With Kidney Disease and Hyperkalemia Receiving RAAS Inhibitors (OPAL‐HK)

• Patients with CKD on RAAS inhibitors (n = 243) with hyperkalemia (5.1‐6.5 mEq/L) were assigned to receive patiromer (4.2 or 8.4 g twice daily) for 4 weeks

• Eligible patients (n = 107) included those with baseline K+ of 5.5‐6.4 mEq/L in whom the K+ level decreased to 3.8‐5.0 mEq/L entered an 8‐week randomized withdrawal phase in which they were randomized to continue patiromer or switch to placebo.

Weir MR, et al. N Engl J Med. 2015;372:211-221.CKD, chronic kidney disease; RAAS, renin-angiotensin-aldosterone system.

11/16/2015

26

Patiromer Titrated Dose

Potassium 5.5 ‐ <6.5

Potassium 5.1 ‐ <5.5

Part ASingle‐Blind,Uncontrolled

n = 243

Part BRandomized Withdrawal,

Single‐Blind, Placebo‐Controlled

n = 107

4 Weeks

Part B PrimaryEndpoint:Between‐Group Difference in Serum Potassium at Week 4

Subjects with CKD andon RAAS inhibitors

Responders with Part A Baseline Potassium 5.5‐6.4

Patiromer +RAAS Inhibitor

Placebo +RAAS Inhibitor

8 Weeks

Part A Primary Endpoint:Change from Baseline in Mean Serum Potassium

Weir MR, et al. N Engl J Med. 2015;372:211-221.CKD, chronic kidney disease; RAAS, renin-angiotensin-aldosterone system.

Phase 3 Trial Design

Pivotal Phase 3 Trial – Part A Results

Weir MR, et al. N Engl J Med. 2015;372:211-221.

Baseline Week 4Week 2

Dose Group 1−0.65

DoseGroup 2−1.23

AllSubjects−1.01

P<0.001

Part A Primary Efficacy Endpoint:Mean Change from Baseline to Part A Week 4 (All Subjects)

Week 1 Week 3Day 2

P < .001

11/16/2015

27

* Or earlier time point if subject first had serum potassium <3.8 mEq/L or ≥5.5 mEq/L


Placebo Patiromer

Est

imat

ed M

edia

n C

han

ge

fro

m P

art

B

Bas

elin

e in

Ser

um

Po

tass

ium

(m

Eq

/L)

∆ = 0.72 mEq/L

P <0.001

Estimated Median Change from Part B Baseline 0.00 mEq/L0.72 mEq/L

Pivotal Phase 3 Trial – Part B ResultsPart B Primary Efficacy Endpoint: Difference Between Groups in the Median Change in Serum Potassium from Part B Baseline to Part B Week 4*

Pro

port

ion

With

Rec

urre

nt

Hyp

erka

lem

ia

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

AW4/BBL BW1 BW2 BW3 BW4 BW5 BW6 BW7 BW8

52 46 38 31 29 23 16 12 4

55 53 48 47 44 39 38 38 29

Study Week

Subjects without recurrent hyperkalemia at any time before, and at, the study visit and still on study drug

PlaceboPatiromer

Time to First Recurrent Hyperkalemia Event During Phase 3 Part B

Weeks 1-4* Recurrent Hyperkalemia = Serum

Potassium ≥5.5 mEq/L

Weeks 5-8 Recurrent Hyperkalemia = Serum

Potassium ≥5.1 mEq/L

* Part B Weeks 1-4 = Primary Efficacy Outcome Period


11/16/2015

28

Adverse Events During the Safety Follow‐up Period for That Phase


Adverse Events During the Randomized Withdrawal Phase and Through the Safety Follow‐up Period for That Phase

Adverse Event Patients(N = 52)

Patiromer(N = 55)

≥1 Adverse event 26 (50) 26 (47)

Headache 4 (8) 2 (4)

Supraventricular extrasystoles 1 (2) 2 (4)

Constipation 0 2 (4)

Diarrhea 0 2 (4)

Nausea 0 2 (4)

≥1 Serious adverse event 1 (2) 0

All data presented as n (%).

Responses to Patiromerwere sustained over 52 weeks (AMETHYST‐DN Randomized Clinical Trial)

J Am Med Assoc 2015;314(2):151‐161

11/16/2015

29

Patiromer (Veltassa) is approved by FDA and indicated for the treatment of hyperkalemia

Valtassa binds to many orally administered medications, which could decrease their absorption and reduce their effectiveness, administer other oral medications at least 6 hours before or 6 hours after Valtassa

FDA Safety Alert

FDA is requiring the Kayexalate manufacturer to conduct studies to investigate Kayexalate’s potential to bind to other medications administered by mouth

Prescribers and patients should consider separating Kayexalate dosing from other medications taken by mouth by at least 6 hours

11/16/2015

30

ZS‐9: A novel, selective K+ binder

ZS‐9 Properties

• Microporous zirconium silicate compound

• Insoluble, highly stable• 9.3x more K+ binding capacity than

Kayexalate® • >125x more selective for K+ than

Kayexalate®

HARMONIZE Trial

• Multicenter, randomized, double‐blind, placebo‐controlled trial evaluating zirconium cyclosilicate (ZS‐9) 3 times daily in an initial 48‐hour open label phase (n = 258)

• Patients (n = 237) achieving normokalemia (3.5‐5.0 mEq/L) were randomized to once‐daily ZS‐9, 5 g (n = 45), 10 g (n = 51) or 15 g (n = 56), or placebo (n = 85) daily for 28 days.

Kosiborod M, et al. JAMA. 2014;312(21):2223-2233.

11/16/2015

31

HARMONIZE Trial

Participants with comorbidity in open label phase:

Kosiborod M, et al. JAMA. 2014;312(21):2223-2233.CHF, congestive heart failure; DM, diabetes mellitus; RAASi, renin-angiotensin aldosterone inhibitor.

CHF 36.4%

DM 65.9%

RAASi 69.8%

Serum Potassium Levels During the Open‐Label Phase (48 hours)


11/16/2015

32

Serum Potassium Levels During the Open‐Label Phase (48 hours)


Serum Potassium Levels During the Randomized Phase (Days 8–29) According to Study Group


11/16/2015

33

Serum Potassium Levels During the Randomized Phase (Days 8–29) According to Study Group


Sodium Zirconium Cyclosilicate in Hyperkalemia

• Multicenter, two‐stage double blind trial

• Patients (n = 754) with hyperkalemia randomly assigned to receive ZS‐9 (1.25 g, 2.5 g, 5 g, or 10 g) or placebo 3 times daily for 48 hours.

• Patients achieving normokalemia (3.5–4.9 mEq/L) were randomly assigned to ZS‐9 or placebo once daily from days 3 through 11.

Packham DK, et al. N Engl J Med. 2015;372:222-231.

11/16/2015

34

Packham DK, et al. N Engl J Med. 2015;372:222-231.

Potassium Levels During the Study

Rev CV Med 16 140 2015

11/16/2015

35

Conclusion

• Hyperkalemia is an important clinical concern

• Rate of change of potassium level is the main concern

• Dietary factors are important

• Newer therapies may provide a safer, more consistent management strategy

hyperkalemia: epidemiology, pathophysiology, and … hyperkalemia.pdf · nephsap: 2007;6....

Documents