HYPERKALAEMIA IN CKD PATIENTS

Patients with CKD are at high risk of developing hyperkalaemia1,2

Although patients with hyperkalaemia are typically asymptomatic, the condition can become life-threatening if left untreated.3

Grey body figure with kidneys highlighted
Grey body figure with kidneys highlighted
Green clipboard icon
Green clipboard icon

To increase the chance of early diagnosis and treatment, it’s important to be able to identify patients at high risk of developing hyperkalaemia.3

High-risk patients include individuals with:

  • CKD (non-dialysis)1,2
  • CKD with dialysis1,2
  • CKD or HF and undergoing optimisation with RAASi therapy1,3-6

In addition, there are other patient groups at high risk of hyperkalaemia, including those with resistant hypertension and diabetic nephropathy.3

Learn more about hyperkalaemia with expert nephrologist Dr David Goldsmith

  1. Nilsson E, et al. ERA-EDTA, Madrid, 2017. Poster presentation SP313. 
  2. Kovesdy, CP. Nat. Rev. Nephrol. 2014; 10: 653–662. 
  3. Renal Association Clinical Practice Guidelines 2014. Treatment of Acute Hyperkalemia in Adults. 
  4. Vardeny O, et al. Circ Heart Fail. 2014; 7: 573-579.
  5. Chomicki J, Klem P & Marrs J. J Am Soc Hypertens. 2014; 8: e30–e31.
  6. National Kidney Foundation. 2014. Clinical update on hyperkalemia.

HYPERKALAEMIA IN CKD PATIENTS

Mechanism of CKD that could lead to hyperkalaemia

With impaired kidney function, the amount of potassium excreted through the urine becomes compromised and decreases. This could be due to a decreased function of nephrons, which results in reduced glomerular filtration rate (GFR). As GFR decreases, the body’s ability to maintain potassium homeostasis becomes diminished, which increases the risk of hyperkalaemia.1,2

Schematic to show potassium filtration cycle in the nephron of the kidney
Schematic to show potassium filtration cycle in the nephron of the kidney

Adapted from Palmer BF. N Engl J Med. 2004; 351: 585-92.3

  1. Schnaper HW. Pediatr Nephrol. 2014;29: 1-17.
  2. Korgaonkar S et al. Clin J Am Nephrol. 2010;5:762-769.
  3. Palmer BF. N Engl J Med. 2004; 351: 585-92.

HYPERKALAEMIA IN CKD PATIENTS

Individuals with CKD have a higher incidence rate of hyperkalaemia compared to individuals without CKD1

In an observational study in Sweden, 55% of stage 4 CKD patients developed hyperkalaemia within 3 years.1

CKD was >1.5-fold more common in patients with an incident hyperkalaemia event of K+ >6.0 mmol/L, relative to patients with K+ 5.0–≤5.5 and K >5.5–≤6.0.*2 

ADJUSTED
OR 5.6

Patients with stage 4
CKD were associated
with a higher
hyperkalaemia risk**1

The higher risk of hyperkalaemia observed among patients with CKD demonstrates the importance of renal function monitoring and decreased kidney function in hyperkalaemia.2 

Bar graph to show the three-year incidence proportion of hyperkalaemia
Bar graph to show the three-year incidence proportion of hyperkalaemia

G1-2: eGFR≥60; G3: eGFR 60-30; G4+: eGFR<30 mL/min/1.73m2

Adapted from Nilsson et al.2017.1

OR odds ratio

*Based on a retrospective population-based risk factor analysis in the UK.

**Based on a multivariable logistic regression analysis in an observational study in Sweden. Reference group: patients with eGFR ≥60 ml/min/1.73m2

References:

  1. Nilsson E, et al. ERA-EDTA, Madrid, 2017. Poster presentation SP313.
  2. Horne L, et al. ERA-EDTA, Madrid, 2017. Poster presentation MP370.

HYPERKALAEMIA IN CKD PATIENTS

Hyperkalaemia >5.5mEq/L is associated with increased risk of hospitalisation*1 and mortality**2

Real-world evidence shows that serum K+ levels <3.5 and ≥5.5 mEq/L are associated with greater risks of major adverse cardiac events (MACE).1 Hyperkalaemia predisposes to cardiac arrhythmias and increases the risk of cardiac events.1 

*Compared to matched cohorts without hyperkalaemia

**Compared to a normokalaemia range K+≥3.5-5 mEq/L

References:

  1. Thomsen et al. Nephrol Dial Transplant; 2017: 1–10.(suppl.)
  2. Qin L, et al. ERA-EDTA, Madrid, 2017. Poster presentation MO067.

HYPERKALAEMIA IN CKD PATIENTS

Hyperkalaemia in CKD can be a recurrent problem and frequency increases with each episode1

Many CKD patients have recurrent hyperkalaemia episodes, with successively shorter time between the episodes.1

Recent real-world evidence studies, analysing healthcare databases in Denmark and the UK, have shown that hyperkalaemia is associated with poor clinical outcomes including:1,2

Green potassium symbol icon
Green potassium symbol icon

RECURRENT HYPERKALAEMIA1

Green hospital bed icon
Green hospital bed icon

ACUTE HOSPITALISATIONS1

Green head icon
Green head icon

MORTALITY1,2

Green heart icon
Green heart icon

MAJOR ADVERSE
CARDIOVASCULAR EVENTS (MACE)2

Many CKD patients have recurrent hyperkalaemia episodes, with successively shorter time between the episodes1

Graph to show the distribution of RAASi dose levels in patients with CKD (stage 3-4)
Graph to show the distribution of RAASi dose levels in patients with CKD (stage 3-4)

Dead without any HK event

New HK episode during follow up

No further HK episode during follow up

Time in years represents median time to next hyperkalaemic event and does not represent time to death

Adapted from Thomsen et al. 2017.1

Hyperkalaemia is associated with an increased risk of hospitalisation*1

In a matched cohort analysis in Denmark, there was an increased risk of hospitalisation in:**1

  • CKD patients with hyperkalaemia vs. matched cohort without hyperkalaemia
  • In the 6 months following the initial hyperkalaemia event compared to the 6 months before

Bar graph to show the increased risk of acute hospitalization following an initial hyperkalaemia
Bar graph to show the increased risk of acute hospitalization following an initial hyperkalaemia

Adapted from Thomsen et al. 2017.1

Hyperkalaemia can become life threatening
if untreated2,3

In a US matched cohort study lasting 52 months, CKD patients with serum K+ ≥6 mEq/L were 3x more likely to die than patients with normokalaemia.3

*after versus before hyperkalaemia event relative risk

**CKD comparisons without hyperkalaemia individually matched to CKD patients with hyperkalaemia on gender, age, time since CKD diagnosis, CKD stage (eGFR category), CCI score category, presence of hyperkalaemia-associated conditions and presence or absence of hyperkalaemia-associated drug use.

References:

  1. Thomsen RW et al. Nephrol Dial Transplant. 2017: 1–10. [Epub ahead of print]
  2. Qin L, et al. ERA-EDTA, Madrid, 2017. Poster presentation MO067.
  3. Luo J et al. Clin J Am Soc Nephrol. 2016; 11: 90-100.

HYPERKALAEMIA IN CKD PATIENTS

Suboptimal RAASi treatment is common in CKD, and is associated with increased morbidity and mortality*1

Hyperkalaemia contributes to the under utilisation of RAASi therapy in CKD.1

  • Down-regulation of RAASi therapy is a common strategy in the chronic management of hyperkalaemia but studies show that sub-maximum doses or discontinuation can cause poor outcomes.1
  • In a large observational US study, 58% CKD (stage 3-4) patients** were on sub-maximum doses of RAASi.1

Graph to show the distribution of RAASi dose levels in patients with CKD (stage 3-4)
Graph to show the distribution of RAASi dose levels in patients with CKD (stage 3-4)

Maximum dose

Submaximum dose

Discontinued

Adapted from Epstein et al. 2015.1

Suboptimal RAASi treatment is common in CKD, and is associated with increased morbidity and mortality*1

Patients on sub maximum or discontinued RAASi are at 2x higher risk of death**1

Control of serum potassium levels in
hyperkalaemia may allow for ongoing
RAASi therapy in high-risk patients2

In real-world analysis in the UK, there were an estimated 53,587 RAASi discontinuations in 704,830 patient-years of follow up.2 (crude rate = 0.076 discontinuations per patient-year)2

RAASi, renin-angiotensin-aldosterone inhibitors

*Compared to optimal RAASi treatment

**Electronic health records of 205,108 patients. Diabetes mellitus was not excluded from this comorbidity group.

References:

  1. Epstein M et al. Am J Manag Care 2015; 21: S212-S220.
  2. Qin L, et al. ERA-EDTA, Madrid, 2017. Poster presentation MP373

HYPERKALAEMIA IN CKD PATIENTS

Hyperkalaemia has a substantial economic burden on the healthcare system1

 

Cohort analysis of CKD patients with hyperkalaemia in Denmark1

For 6 months before vs. 6 months after an index hyperkalaemia event, patients had: 

MEAN HOSPITAL DAYS (acute)

3.73 | 6.25
VS

(P<0.05)

MEAN HOSPITAL DAYS (non-acute)

1.11 | 2.03
VS

(P<0.05)

MEAN OUTPATIENT CARE VISITS

1.43 | 1.56
VS

(P<0.05)

Substantial increase in healthcare resource utilisation in the 6 months after index hyperkalaemia event compared with the 6 months before1 

As the costs of hospital admission constitute the largest healthcare cost component, the economic burden associated with hyperkalaemia for healthcare systems and societies is expected to be high.1 

  1. Thomsen R et al. ERA-EDTA, Madrid, 2017. Poster presentation SP318.

HYPERKALAEMIA IN CKD PATIENTS

There is a need for additional treatment options for hyperkalaemia1

The goal of long-term control of serum potassium is to prevent recurrence of hyperkalaemia1

 

Critical care management of hyperkalaemia

Many hyperkalaemia patients are treated in the acute setting, where the main goal is to restore normal membrane potential and prevent cardiac arrhythmia.1 

Protect the heart:2

  • Intravenous calcium salts 

Shift potassium into cells:2

  • Sodium bicarbonate
  • Insulin/glucose
  • β2 agonists

Remove excess potassium from the body:2

  • Diuretics
  • Cation exchange resin (mild-moderate hyperkalaemia)
  • Dialysis

 

Long-term management of hyperkalaemia

Hyperkalaemia is episodic and may represent a chronic problem for patients with CKD. Ongoing monitoring and long-term maintenance therapy may be necessary to avoid further risk of recurrent hyperkalaemia.3,4

Historically, there have been a number of therapeutic options available, both pharmacological and non-pharmacological. Whilst they are associated with some benefits, treatment options are still limited. 

PHARMACOLOGICAL THERAPIES

Cation exchange resins

  • Cases of intestinal injury have been reported in association with calcium polystyrene sulfonate (CPS) and sodium polystyrene sulfonate (SPS)5-8
  • Lack of clinical data to support use beyond 7 days of treatment9-12
  • Intestinal intolerance has been reported in association with CPS and SPS, including nausea, vomiting, gastric irritation, constipation and diarrhoea5-8

Patiromer

  • Indicated in the treatment of hyperkalaemia, but should not replace emergency treatment for life-threatening hyperkalaemia13

NON-PHARMACOLOGICAL THERAPIES

Low potassium diet

  • Doesn’t tackle the underlying cause of hyperkalaemia and has limited effectiveness and variable patient compliance14,15

OTHER OPTIONS

Renin-angiotensin-aldosterone system inhibition (RAASi) dose reduction

  • RAASi is beneficial for the preservation of cardio-renal function, and dose reduction is associated with an increased risk of mortality*16,17

*Compared to patients on maximum doses of RAASi

References:

  1. National Kidney Foundation, 2014. Clinical Update on Hyperkalaemia.
  2. Renal Association Clinical Practice Guidelines 2014. Treatment of Acute Hyperkalemia in Adults.
  3. Einhorn LM et al. Arch Intern Med. 2009; 169: 1156-62.
  4. Sarwar CMS et al. J Am Coll Cardiol. 2016; 68: 1575-89.
  5. Sanofi-Aventis. Calcium resonium® Summary of Product Characteristics.
  6. Sanofi-Aventis. Resonium A® Summary of Product Characteristics.
  7. Sanofi-Aventis. Calcium resonium® Prescribing information.
  8. Sanofi-Aventis. Kayexalate® Prescribing information.
  9. Lepage L et al. Clin J Am Soc Nephrol. 2015;10:2136-42.
  10. Nasir K & Ahmad A. J Ayub Coll Abbottabad. 2014; 26:455-8.
  11. Gruy-Kapral C et al. J Am Soc Nephrol. 1998;9:1924-30.
  12. Emmett M et al. Gastroenterol. 1995 Mar;108:752-60.
  13. Vifor Pharma. Veltessa (patiromer) summary of product characteristics.
  14. Packham DK & Kosiborod M. Am J Cardiovasc Drugs. 2016;16:19-31.
  15. Sanghavis S et al. Semin Dial. 2013;26:597-603.
  16. Epstein M et al. Am J Manag Care 2015; 21: S212-S220.
  17. Maggioni AP et al. Eur J Heart Fail. 2013;15:1173-84.

HYPERKALAEMIA IN CKD PATIENTS

Summary

Patients with CKD are at high risk of developing hyperkalaemia1,2 

Hyperkalaemia >5.5mEq/L is associated with an increased risk of hospitalisation*3 and mortality**4

Hyperkalaemia in CKD can be a recurrent problem and frequency increases with each episode3 

Suboptimal RAASi treatment is common in CKD, and is associated with increased morbidity and mortality†5,6 

There is a need for additional treatment options for the management of hyperkalaemia7 

*Compared to matched cohorts without hyperkalaemia

**Compared to a normokalaemia range K+≥3.5-5 mEq/L

†Compared to optimal RAASi treatment

References:

  1. Nilsson E, et al. ERA-EDTA, Madrid, 2017. Poster presentation SP313.
  2. Kovesdy, CP. Nat. Rev. Nephrol. 2014; 10: 653–662.
  3. Thomsen et al. Nephrol Dial Transplant; 2017: 1–10.[Epub ahead of print]
  4. Qin L, et al. ERA-EDTA, Madrid, 2017. Poster presentation MO067.
  5. Epstein M et al. Am J Manag Care 2015; 21: S212-S220.
  6. Sadjadi SA et al. Ther Clin Risk Manag. 2009; 5(3): 547-552.
  7. National Kidney Foundation, 2014. Clinical Update on Hyperkalaemia.