Management of Hyperkalaemia - KDIGO · 2019-10-01 · Mango (1 cheek) 5 Nectarine 9 Peach 7 Grapes 6 Mashed potato 10 Hot chips (sml) 12 Juice (250mL) 10 Milkshake (250mL) 10 Ice-coffee

Management of Hyperkalaemia:

Prof Simon D Roger MD FRACP Director, Renal Research, Dept of Nephrology

Gosford, Australia

More Than Just Avoiding Bananas

KDIGO

Today's talk…… n  Who is at risk? Incidence and recurrence n  Hyperkalemia and mortality n  Impact of hyperkalemia on healthcare resource utilization, hospital visits

and emergency department visits n  Treatment options

n  What about the foods? n  Sub-optimal RAASi and MRA therapy due to fear of hyperkalemia n  What is on the horizon to lower potassium?

n  Unmet needs in hyperkalemic CKD patients: How would you manage the patient?

KDIGO

aAmong patients prescribed add-on MRA treatment CKD, chronic kidney disease; HF, heart failure; MRA, mineralocorticoid receptor antagonist

Hyperkalaemia is prevalent in specific patient populations, such as CKD and heart failure and those prescribed key drug classes

CKD (frequency 40–50%)29

Chronic heart failure (frequency up to 50%)62

Resistant hypertension (frequency up to

20%a)70,71

Diabetes mellitus (frequency up to

15%)69

↑K+ KDIGO

High potassium risk increases with CKD severity

CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; high K, hyperkalaemia Einhorn LM, et al. Arch Intern Med 2009;169:1156–1162

No CKD (reference) CKD stage 3 CKD stage 4 CKD stage 5

1.00

2.24

5.91

11.00

Odds ratio of K+ ≥5.5 mEq/L 14

12

10

8

6

4

2

0

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CV, cardiovascular; high K, hyperkalaemia; HypoK, hypokalaemia; MACE, major adverse cardiovascular events 1. Luo J, et al. Clin J Am Soc Nephrol 2016;11:90–100; 2. McMahon GM, et al. Intensive Care Med 2012;38:1834–1842; 3. Hayes J, et al. Nephron Clin Pract 2012;120:c8–c16; 4. An JN, et al. Crit Care 2012;16:R225; 5. Goyal A, et al. JAMA 2012;307:157–164

•  As serum K+ levels deviate from normal levels, rates of morbidity (including MACE) and mortality increase1–5

High potassium is associated with increased morbidity and mortality

Hypokalaemia Hyperkalemia

Potassium

NORMAL 5.0 mEq/L 3.5 mEq/L

HypoK high K

K+

NORMOKALAEMIA

Morbidity and mortality

Morbidity and mortality

KDIGO

Recent studies confirm high serum K+ levels are associated with increased risk of mortality and MACE in CKD

CKD, chronic kidney disease; CPRD, Clinical Practice Research Datalink; HES, hospital episode statistics; IRR, incident risk ratio; MACE, major adverse cardiovascular events Adapted from Qin L, et al. Presented at ERA-EDTA, Madrid; 3rd–6th June 2017; Oral presentation MO067

K+ levels and risk of mortality

Adj

uste

d IR

R

2.5

2.0

1.5

1.0

0.5

0.0

2.07

1.26

1.02 1.02

1.29

2.23

1.00

Serum K+ (mEq/L)

K+ levels and risk of MACE

Adj

uste

d IR

R

Serum K+ (mEq/L)

2.0

1.8

1.6

1.4

1.2

1.0

0.8

0.6

0.4

0.2

0.0

1.40

1.09 1.01 1.01

1.00

1.17

1.31

2.4

2.2

KDIGO

Today's talk…… n  Who is at risk? Incidence and recurrence n  Hyperkalemia and mortality n  Impact of hyperkalemia on healthcare resource utilization, hospital

visits and emergency department visits n  Treatment options



KDIGO

CKD patients with a hyperkalemic event are at higher risk of hospitalisation

CKD, chronic kidney disease; Adapted from Thomsen RW, et al. Presented at ERA-EDTA, Madrid, 3rd–6th June 2017; Oral presentation MO066

•  CKD patients with hyperkalemia were at higher risk of acute hospitalisation after an hyperkalemic event compared with the control group without hyperkalemia

•  The risk for the comparison cohort remained relatively unchanged over the same time period

Risk ratio: 1.72

After vs before risk ratio (95% CI): 1.72 (1.69, 1.74)

Risk of acute hospitalisation

% o

f pat

ient

s at

risk

of a

cute

hos

pita

lisat

ion

Patients with a hyperkalemic event Time-matched comparison cohort without a hyperkalemic event

100

80

60

40

0

20

6 months before a hyperkalemic event

6 months after hyperkalemic event

KDIGO

Many patients with CKD have recurrent hyperkalemic episodes, with successively shorter time between the episodes

CKD, chronic kidney disease; Adapted from Thomsen RW, et al. Presented at ERA-EDTA, Madrid, 3rd–6th June 2017; Oral presentation MO066

20.1%

27.5%

52.1%

First hyperkalemic event

24.5%

43.0%

32.6%

Second hyperkalemic event

18.3%

57.1%

24.7%

Third hyperkalemic event

15.9%

64.0%

20.1%

Fourth hyperkalemic event

No further hyperkalemic episode during follow-up

New hyperkalemic episode during follow-up

Dead without any hyperkalemic event

0.64 yrs 0.49 yrs 0.40 yrs

KDIGO

Rates of adverse outcomes increase with severity of hyperkalemia

CPRD, Clinical Practice Research Datalink; HES, hospital episode statistics; hyperkalemia, hyperkalaemia Horne L, et al. Presented at ERA-EDTA, Madrid; 3rd–6th June 2017; Poster presentation MP380

2.51 3.83

12.57

6.54 7.36

14.61 13.86 15.53

28.93

0.00

7.00

14.00

21.00

28.00

35.00

K 5.0 to <5.5 K 5.5 to <6.0 K >6.0

Inci

denc

e ra

te p

er 1

00 p

atie

nt y

ears

K+ level (mEq/L)

All-cause mortality CKD progression All-cause hospitalisation

K+ 5.0 to ≤5.5 K+ >5.5 to ≤6.0

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Fitch K, et al. Presented at the AMCP 2016; 19th–22nd April 2016; San Francisco, CA, USA; E62

Hyperkalemia is associated with higher healthcare costs

$5645

$1035

0

1000

2000

3000

4000

5000

6000

HiK patients Total Medicare population

Average monthly cost per US Medicare patient/member

Ave

rage

mon

thly

cos

t ($)

Hyperkalemic patients Total Medicare population

KDIGO

Recent data suggest that severity of hyperkalemia was associated with increasing use of healthcare resources

aCalculated among patients who had experienced ≥1 healthcare resource utilisation; healthcare resource utilisation was evaluated after an initial HiK event CPRD, Clinical Practice Research Datalink; HES, hospital episode statistics; HiK, hyperkalaemia Qin L, et al. Presented at ERA-EDTA, Madrid; 3rd–6th June 2017; Poster presentation SP321

0

2

4

6

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340 360

Mea

na n

umbe

r of h

ealth

care

re

sour

ce u

tilis

atio

ns

Days

K 5.0 to <5.5 K >5.5 to <6.0 K >6.0

Hospitalisations

KDIGO

Recent data suggest that severity of hyperkalemia was associated with increasing use of healthcare resources

aCalculated among patients who had experienced ≥1 healthcare resource utilisation; healthcare resource utilisation was evaluated after an initial hyperkalemia event CPRD, Clinical Practice Research Datalink; HES, hospital episode statistics; hyperkalemia, hyperkalaemia Qin L, et al. Presented at ERA-EDTA, Madrid; 3rd–6th June 2017; Poster presentation SP321

0

2

4

6

8

10

12

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340 360

Mea

na n

umbe

r of h

ealth

care

re

sour

ce u

tilis

atio

ns

Days

K 5.0 to <5.5 K >5.5 to <6.0 K >6.0

Outpatient visits

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How would you manage this patient? n  K 6.2 mEq/L n  Creatinine 220umol/L n  eGFR 22 ml/min/1.73m2

n  Frusemide (furosemide) n  Spironolactone

n  ACE-I (or ARB), say ramipril 10mg/day

n  And 7 other medications, including statin, blood thinners, oral hypoglycemics and anti-depressants

KDIGO

Dietary measures

n  Restrict their intake of high-potassium foods (>250 mg (6mmol) per 100 g)

n  Maintain a low-potassium diet (potassium intake of ≤3 g per day)

KDIGO

Which food has the highest potassium content per usual serve?

1)  Banana 2)  Tomato (3 slices) 3)  Hot chips (small) 4)  Iced-coffee (250mL) 5)  Beans (1/2 cup)

KDIGO

mmol potassiumBanana 9Mandarin 3Orange 5Tomato (3 slices) 3Mango (1 cheek) 5Nectarine 9Peach 7Grapes 6Mashed potato 10Hot chips (sml) 12Juice (250mL) 10Milkshake (250mL) 10Ice-coffee (250mL) 10Crisps (small packet) 15Apple 4Pear 4Strawberries 5Watermelon 6Carrot (1/2 cup) 4Beans (1/2 cup) 1Zucchini (1/2 cup) 4

Potassium: 1mmol = 39mg

KDIGO

mmol potassiumBanana 9Mandarin 3Orange 5Tomato (3 slices) 3Mango (1 cheek) 5Nectarine 9Peach 7Grapes 6Mashed potato 10Hot chips (sml) 12Juice (250mL) 10Milkshake (250mL) 10Ice-coffee (250mL) 10Crisps (small packet) 15Apple 4Pear 4Strawberries 5Watermelon 6Carrot (1/2 cup) 4Beans (1/2 cup) 1Zucchini (1/2 cup) 4

KDIGO

Lowering Potassium Levels

n  It’s not all about bananas… n  Anyone can lower a patient’s potassium, the

dietitian’s role, is to assess a patient’s diet and negotiate changes while: n  meeting patients preferences, n  keeping the diet healthy n  maintaining safe potassium levels

n  The hospital low potassium diets are very limiting

KDIGO

Lowering Potassium Levels

n  Soaking veg removes a small amount of extra potassium

n  Boil vegetables where possible (approximately 15% reduction)

n  Avoid Lite Salt/salt substitutes: why?

KDIGO

Asian fruits and their potassium content Item Grams K (mg/mmol) Level

Sugarcane 208 44/1.1 LowLychee, peeled, raw 100 150/3.8 LowPapaya 100 140/3.6 LowDragonfruit 100 59/1.5 LowDurian 100 54/1.4 LowGuava, Hawaiian, raw 100 150/3.8 LowLongan, raw 100 248/6.4 ModerateCoconut, fresh,mature fruit, flesh 100 305/7.8 HighCoconute, fresh, young or immature, flesh 100 138/3.5 LowCoconut, fresh, young or immature, water or juice 100ml 186/6.4 Moderate

KDIGO

VegetablesFuzzymelon/hairycucumber 100 147/3.8 LowWintermelon,raw 100 78/2.0 LowSpongegourd/Loofah,angledgourd 100 75/1.9 LowGourd,bitter,raw 100 116/3.0 LowChoko,peeled,raw 100 88/2.3 LowCabbage,bokchoy,raw(chinesecabbage) 80 208/5.3 Moderate

ChoySum 80 272/7.0 HighBroccoli,Raw(GaiLan/Chinesebroccoli) 100 226/5.8 ModerateChineselettuce/Pekinesecabbage 80 200/5 ModerateWatercress,raw 35 199.50/5.1 ModerateAmaranth,sprouted 35 214/5.5 ModerateCabbage,mustard,raw(Chinesemustard) 80 360/9 High

Asian Vegetables and their K content KDIGO

Sprout, bean, raw 35 45/1.2 LowLeaf lettuce "Yao-Mak"/Romaine lettuce 35 86/2.2 LowSpinach, water, raw 35 13/0.3 LowSeaweed, dried, hai tai (for soup) 100 3524/90 High

Seaweed, dried, agar agar 100 1125/29 High

Goji berries 100 810/21 HighSeaweed, kelp, raw 100 89/2.3 LowLotus root, raw 100 243/6.2 ModerateTaro/Yam, raw, peeled 100 300/7.7 High

Water chestnut, Chinese, raw 35 204/5.2 ModerateMushroom, shitake, raw 100 170/4.4 LowMushroom, enoki, raw 100 359/9.2 HighFungus, white, dried 100 159/4.0 Low

Asian Vegetables and their K content

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KDIGO

When do you get concerned about potassium?

n  Are you cardiology or nephrology? n  Acute or chronic? n  Background CKD

5.5 vs 6.0 mEq/L

KDIGO

Reduce the ACE-I/ARB

n  Problematic n  Pre 2013: Combination ACE-I and ARBs n  Post 2014: ACE-I or ARB with

spironolactone n  2015: restore the combination therapy:

And what about spironolactone?

Palmer SC et al. Lancet 2015; 385: 2047–56

KDIGO

Natriuretic response to loop diuretics is reduced in patients with kidney disease and other disorders

CKD, chorinc kidney disease; HF, heart failure; PD, pharmacodynamic; PK, pharmacokinetic Brater DC, Semin Nephrol 2011;31:483–494; 2. Zuber K et al. Clinician Reviews 2011;21:50–53

Healthy Edmatous disorders

Severe renal insufficiency

Na+

exc

retio

n ra

te

(mEq

/min

)

3.0

2.0

1.0

Heart failure, cirrhosis, and nephrotic syndrome

Na+

exc

retio

n ra

te

(mEq

/min

)

3.0

2.0

1.0

•  Because of the pharmacokinetic consequences associated with CKD, much higher doses of loop diuretics are needed in this patient population

•  In patients with heart failure, there is more proximal Na+ reabsorption in the nephron. This means very little Na+ is delivered to the distal tubule, which renders the loop diuretic less effective

Dose of furosemide

KDIGO

Recent retrospective data in CKD patients confirm that high K+ levels are associated with RAASi discontinuation

*Reference group. CI, confidence interval; CKD, chronic kidney disease; CPRD, Clinical Practice Research Datalink; eGFR, estimated glomerular filtration rate; HES, hospital episode statistics; RAASi, renin–angiotensin–aldosterone system inhibitor Adapted from Qin L, et al. Presented at ERA-EDTA, Madrid; 3rd–6th June 2017; Poster presentation MP373

eGFR 46–60 mL/min/1.73 m2

Adj

uste

d IR

R ±

95%

CI

5

4

3

2

1

0

Serum K+ (mEq/L)

Overall CKD cohort

Adj

uste

d IR

R ±

95%

CI

5

4

3

2

1

0

eGFR <30 mL/min/1.73 m2

eGFR 30–45 mL/min/1.73 m2

Serum K+ (mEq/L)

RAASi discontinuations RAASi discontinuations

KDIGO

aIn those receiving maximum doses of RAASi therapy; for the remaining events, the data period following an event was not sufficient to determine subsequent RAASi dose level. high K, hyperkalaemia; RAASi, renin–angiotensin–aldosterone system inhibitor Adapted from Epstein M, et al. Am J Manag Care 2015;21(Suppl 11):S212–S220

Down-titration or discontinuation of RAASi therapy is common following a high K eventa

Mild high K (K+ 5.1–5.4 mEq/L)

23,556 events

52

41

16 21 22

26

0

10

20

30

40

50

60

Moderate-to-severe high K (K+ ≥5.5 mEq/L)

11,608 events

Maintained maximum dose Down-titrated dose Discontinued

high

K e

vent

s (%

)

38% 47%

KDIGO

Sub-optimal or Discontinuation of RAAS Inhibitor is Associated with Adverse Outcomes or Mortality

HK, hyperkalaemia; RAASi, renin–angiotensin–aldosterone system inhibitor Epstein M, et al. Am J Manag Care 2015;21(Suppl 11):S212–S220

Retrospective study of 205,108 patients from the Humedica database on a RASSi

KDIGO

KDIGO

Time to K ≥5.5 mmol/L

KDIGO

Change in Systolic BP

KDIGO

Are We Optimally Managing Patients With High Potassium?

Change RAASi?

Treat high K?

Do nothing?

KDIGO

Hyperkalemia vs RAASi: The Catch-22 of managing diseases that benefit from RAASi therapy

n  RAASi, renin–angiotensin–aldosterone system inhibitor

CATCH-22

Prescribe RAASi and accept presence of

hyperkalemia?

Avoid/discontinue proven RAASi

therapies? KDIGO

Current Treatment Options for Hyperkalemia are Limited

KDIGO

What tastes like liquid concrete?

KDIGO

Median Sodium Polystyrene Sulfonate Treatment Duration was 7 days

90

80

70

60

50

40

30

20

10

0 0 10 20 30 40 50 60 70 80 90

Days since the initiations of SPS

Perc

ent

ag

e w

ho s

taye

d

on

SPS

(%)

100

Betts K, et al. Presented at ASN Kidney Week 2016; 15th–20th November 2016; Chicago, IL, USA; FR-PO786

KDIGO

Sodium Polystyrene Sulfonate

• Uncertain efficacy – no rigorous clinical trials, <7days • Poorly tolerated • Risks of intestinal toxicity (colonic necrosis) • Cost

SPS – FDA warning 2009

KDIGO

Two New Drugs On The Scene…..

•  ZS009/ sodium zirconium cyclosilicate (Lokelma)

• Patiromir (Valtessa) KDIGO

Two New Drugs On The Scene…..

•  ZS009/ sodium zirconium cyclosilicate (Lokelma)

• Patiromir (Valtessa)

They both work!

KDIGO

Synthetic Polymer Consisting Of Nonabsorbable Spherical Beads

KDIGO

CI, confidence interval; HK, hyperkalaemia; K+, potassium.

Weir MR, et al. N Engl J Med. 2015;372(3):211–21.

Baseline

Me

an

se

rum

K+

(mEq

/L)

Day 3 Week 1 Week 2 Week 3 Week 4

5.8

5.6

5.4

5.2

5.0

4.8

4.6

4.4

4.2

0

Overall Mild HK Moderate-to-severe HK

Treatment with Patiromer was Associated with a Reduction from Baseline in

Elevated Serum K+ Levels

KDIGO

0.72

0.0 0.0

0.2

0.4

0.6

0.8

1.0

Placebo Patiromer

OPAL-HK Part B: EFFICACY CONTINUED Treatment with Patiromer Maintained Serum K+ Control More

Effectively than Placebo Over the 8 Week Extension Phase

*Or earlier time point if subject first had serum K+ <3.8 mEq/L or ≥5.5 mEq/L. CI, confidence interval; K+, potassium. Weir MR, et al. N Engl J Med. 2015;372(3):211–21.

Part B primary efficacy endpoint: difference between groups in the median change in serum K+ from Part B baseline to Part B Week 4*

∆ = 0.72 mEq/L P<0.001

Change from baseline = 0.72 mEq/L Change from baseline = 0.00 mEq/L

Estim

ate

d m

ed

ian

ch

an

ge

fro

m

Part

B b

ase

line

in s

eru

m K

+ (

mEq

/L)

KDIGO

OPAL-HK Serum Aldosterone Decreased in Parallel with K+ During Initial

4-week Treatment Phase

The observed mean values were measured in a central laboratory.

Missing central laboratory serum K+ values were imputed from a local laboratory. K+, potassium; SE, standard error.

Weir M, et al. Kidney Int. 2016;90(3):696–704.

Me

an

(±SE

) se

rum

ald

ost

ero

ne

(ng

/dL)

M

ea

n (±SE) serum

K+ (m

Eq/L)

Study Visit

12.8

Baseline Day 3 Week 1 Week 2 Week 3 Week 4

12.4

12.0

11.6

11.2

10.8

10.4

10.0

9.6

9.2

8.8

8.4

5.8

5.6

5.4

5.2

5.0

4.8

4.6

4.4

4.2

4.0

Aldosterone K+

No. at risk Aldosterone

K+

243 243

215 217

236 237

224 228

218 221

219 219

KDIGO

OPAL-HK PART B Effect on Systolic Blood Pressure of Continuing vs Discontinuing Patiromer

(Placebo)

1. Weir M, et al. Kidney Int. 2016;90:696–704; 2. Weir MR, et al. N Engl J Med. 2015;372(3):211–21.

120

122

124

126

128

130

132

134

136

138

140

Start of randomised withdrawal Week 4 Week 8

Systolic blood pressure (mmHg)

*P=0.0001 vs start of randomised withdrawal

In the withdrawal phase, mean changes (LS mean) in SBP were significantly reduced by –6.70 mmHg (P<0.0001) in the Patiromer group

KDIGO

K+

Average Binding-Site Width: 3 Å

Sodium Zirconium Cyclosilicate (SZC/ZS-9) Crystal Structure

Stavros F, et al. PLoS One. 2014;9:e114686.

•  Inorganic crystalline zirconium silicate compound

•  Not a polymer

•  Insoluble, highly stable, and does not expand in water

•  Not systemically absorbed

•  High affinity for K+

•  Exchanges Na+ and H+ for K+

KDIGO

SZC Binds K+ Throughout the GI Tract*

SZC = sodium zirconium cyclosilicate.

Stavros F, et al. PLoS One. 2014;9:e114686.

•  Based on in vitro data, SZC may begin working immediately in the small intestine to preferentially capture K+

•  K+ is exchanged for sodium and hydrogen

H+

Na+

H+

Na+

SZC SZC

K+ K+

K+ K+

K+ K+

SZC

K+ K+

K+ Na+

SZC

Mg2+

H+ K+

Na+ K+

SZC

Na+ Na+

K+ H+

SZC

K+ K+

K+ K+

K+ K+

Large Intestine/Exit Small Intestine

K+K+

K+ K+

K+K+

K+ K+

K+ Na+

K+

K+Ca2+

Mg2+

H+

K+

K+Ca2+

Mg2+

Na+

K+

Ca2+Mg2+

K+ K+ Ca2+

K+

K+K+ K+

K+

Mg2+

K+

K+K+

Na+KDIGO

ZS-003: Sodium Zirconium Cyclosilicate

in Hyperkalemia

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

KDIGO

4.4

4.6

4.8

5.0

5.2

5.4

Initial Phase: Exponential Rate of Change in Serum K+ Over 48 Hours*

*Although the rate of decline is actually a curve, during the 48-hour time frame of interest, it appears linear as presented here; †p<0.05. SZC = sodium zirconium cyclosilicate. Packham DK, et al. Article and supplementary material. N Engl J Med. 2015;372:222-231.

Primary Efficacy Endpoint Se

rum

K+

(mEq

/L)

Time (hours) Dose

1 2 4 8 14 24 28 32 38 44 48 0

†

†

†

Placebo (n=158)

SZC 10 g (n=143)

SZC 2.5 g (n=141)

SZC 1.25 g (n=154)

SZC 5 g (n=157)

Within 48 hours, normokalemia was achieved in 98% of patients who received the 10 g dose

KDIGO

Rapid potassium decrease within 4 hours after the first 10g dose of SZC in patients with severe hyperkalemia

Kosiborod M, Peacock WF, Packham DK. Sodium zirconium cyclosilicate for urgent therapy of severe hyperkalemia. N Engl J Med 2015;372:1577-8.

KDIGO

Sodium Zirconium Cyclosilicate in Individuals With Hyperkalaemia:

A 12-Month Phase 3 Study

B Spinowitz et al. CJASN 2019: 4 (6) 798-809;

KDIGO

Sodium Zirconium Cyclosilicate in Individuals With Hyperkalemia: Impact on Bicarbonate

B Spinowitz et al. CJASN 2019: 4 (6) 798-809

KDIGO

Sodium Zirconium Cyclosilicate in Individuals With Hyperkalemia: Impact on urea

S Roger personal communication 2019

-1 .5

-1 .0

-0 .5

0 .0

0 .5

1 .0

1 .5

Mea

n c

han

ge

seru

m u

rea

+ 9

5% C

I (m

mo

l/L)

S e ru m u re a a t in it ia l p h a s e b a s e lin e (m m o l/L ) 1 2 .7 1 2 .7 1 2 .0 1 2 .9 1 2 .4

0 .34

– 0 .10p = 0 .1 4 5

0 .45p = 0 .7 1 5

– 0 .39p = 0 .0 1 1

– 0 .55p < 0 .0 0 1

A

B

KDIGO

Key Characteristics of Old and New K+-Binding Agents

FDA, US Food and Drug Administration; GI, gastrointestinal; MOA, mechanism of action; SPS, sodium polystyrene sulphonate; SZC, sodium zirconium cyclosilicate

1.Garimella PS, et al. Am J Kidney Dis 2016;67:545–547; 2. Weir MR, et al. N Engl J Med 2015;372:211–221; 3. Kosiborod M, et al. JAMA 2014;312:2223–2233; 4. Bushinsky DA, et al. Kidney Int 2015;88:1427–1433; Sanofi-Avents. Kayexalate Prescribing information 2009; 6. Patiromer Prescribing Information 2016; 7 AstraZeneca. Sodium Zirconium Cyclosilicate Summary of Product Characteristics 2018;; 8. Lepage L, et al. Clin J Am Soc Nephrol 2015;10:2136–2142; 9. Bakris GL, et al. JAMA 2015;314:151–161; 10. Packham DK, et al. N Engl J Med 2015;372:222–231

Sodium Polystyrene Sulphonate Patiromer Sodium Zirconium Cyclosilicate

Onset of action Unknown (generally hours to days) 7 hours after first dose4 1 hour following the first dose3

Safety / Tolerability Associated with: •  Safety and tolerability concerns8

•  Electrolyte disturbances

•  Hypomagnesaemia9 •  GI side effects, e.g.

mild-to-moderate constipation

•  Mild-to-moderate GI effects10 •  Oedema

!

Time to Normokalemia Unconfirmed Within 1 week2 Within 24 hours for 84%

of patients3

Drug–drug Interactions

With antacids, laxatives, digitalis, sorbitol, lithium, and thyroxine5

FDA: Must be taken 3 hours apart from other oral drugs6

Should be given 2 hours apart from oral medication with gastric pH-dependent bioavailability7

MOA1 Nonspecific cation binding in exchange for sodium

Patiromer is a polymer exchange resin

Selective K+ binding in exchange for sodium and hydrogen

Location of K+ Binding Colon Predominantly distal colon Likely entire GI tract

KDIGO





KDIGO

How would you manage the patient? n  2015:

n  Dietary restriction n  Reduce the dose of RAASi n  Correct the metabolic acidosis n  Increase diuretics n  Maybe regular SPS

(resonium)/or fludrocortisone

KDIGO

How would you manage the patient? n  2015

n  Dietary restriction n  Reduce the dose of RAASi n  Correct the metabolic acidosis n  Increase diuretics n  Maybe regular SPS

(resonium)/or fludrocortisone

n  2019 n  Maintain the diet n  Maintain the maximum/optimal

dose of RAASi n  Maintain the diuretics n  Start one of the newer potassium

lowering binders

KDIGO





KDIGO

Documents

Management of Hyperkalaemia - KDIGO · 2019-10-01 · Mango (1 cheek) 5 Nectarine 9 Peach 7 Grapes 6 Mashed potato 10 Hot chips (sml) 12 Juice (250mL) 10 Milkshake (250mL) 10 Ice-coffee