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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
KDIGO
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
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
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
KDIGO
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
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
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
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
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
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
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
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