Management of Hyperkalemia in CKD patients

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Management of Hyperkalemia in CKD patients

• Dr

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Overview

• Introduction
• Hyperkalemia in CKD
• Incidence
• Significance
• Causes
• Management
• Summary and conclusions

3
Introduction

• CKD
• Common disease
• Affecting a growing number of population across
  globe
• May be associated with a variety of electrolyte
  disturbances
• Such as hyperkalemia

Arch Intern Med. 2009169(12)1156-1162
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Introduction

• CKD - Hyperkalemia
• Great concern to nephrologists because of
• Possible implications for patient safety related
  to the potential for associated adverse cardiac
  outcomes

Arch Intern Med. 2009169(12)1156-1162
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Hyperkalemia in CKD

• Hyperkalemia is usually defined as
• Plasma potassium (K ) gt 5.0 mEq/L, even though
  exact cut-off is arbitrary
• The incidence of hyperkalemia in hospitalized
  patients varies from
• 1.4 to 10 depending on the arbitrary level of
  potassium

Electrolyte Blood Pressure 2005 371-78.
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Hyperkalemia in CKD

• Hyperkalemia
• Prevalence in ESRD
• 5 to 10
• Contributes to 1.9 to 5 of deaths among
  patients with ESRD

ESRD End stage renal disease
Electrolyte Blood Pressure 2005 371-78.
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Hyperkalemia in CKD Incidence
Arch Intern Med. 2009169(12)1156-1162
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Hyperkalemia in CKD Significance

• CKD - Hyperkalemia
• One study determined the incidence of
  hyperkalemia in CKD and whether it is associated
  with excess mortality
• Results
• Of the 66 259 hyperkalemic events (3.2 of
  records), more occurred as inpatient events (n34
  937 52.7) than as outpatient events (n31 322
  47.3).
• The adjusted rate of hyperkalemia was higher in
  patients with CKD than in those without CKD among
  individuals treated with RAAS blockers (7.67 vs
  2.30 per 100 patient-months P.001) and those
  without RAAS blocker treatment (8.22 vs 1.77 per
  100 patient months P.001).

Arch Intern Med. 2009169(12)1156-1162
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Hyperkalemia in CKD Significance

• CKD Hyperkalemia
• Study results continued
• The adjusted odds ratio (OR) of death with a
  moderate (K, 5.5 and 6.0 mEq/L to convert to
  mmol/L, multiply by 1.0) and severe (K , 6.0
  mEq/L) hyperkalemic event was highest with no CKD
  (OR, 10.32 and 31.64, respectively) vs stage 3
  (OR, 5.35 and 19.52, respectively), stage 4 (OR,
  5.73 and 11.56, respectively), or stage 5 (OR,
  2.31 and 8.02, respectively) CKD, with all P.001
  vs normokalemia and no CKD.

Arch Intern Med. 2009169(12)1156-1162
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Hyperkalemia in CKD Significance

• CKD Hyperkalemia
• Study Conclusions
• The risk of hyperkalemia is increased with CKD,
  and its occurrence increases the odds of
  mortality within 1 day of the event
• These findings underscore the importance of this
  metabolic disturbance as a threat to patient
  safety in CKD

Arch Intern Med. 2009169(12)1156-1162
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Hyperkalemia in CKD Causes

• CKD hyperkalemia
• Causes
• An impaired GFR combined with a frequently high
  dietary K intake relative to residual renal
  function

Arch Intern Med. 2009169(12)1156-1162
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Hyperkalemia in CKD Causes
Pediatr Nephrol Published online 22 December 2010
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Hyperkalemia in CKD Causes

• If potassium intake is normal, CKD does not
  produce significant hyper- kalemia until the GFR
  is
• lt 5 ml/min

Electrolyte Blood Pressure 2005 371-78.
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Hyperkalemia in CKD Causes

• CKD hyperkalemia
• Causes
• Commonly observed extracellular shift of K
  caused by the metabolic acidosis of renal failure
  
• Under almost all conditions,
• Hyperkalemia not due to redistribution of
  potassium is related to impaired renal potassium
  excretion

Arch Intern Med. 2009169(12)1156-1162
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Hyperkalemia in CKD Causes

• CKD hyperkalemia
• Causes
• Most importantly, recommended treatment with
  renin angiotensin- aldosterone system (RAAS)
  blockers that inhibit renal K excretion

Arch Intern Med. 2009169(12)1156-1162
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Hyperkalemia in CKD Causes
Am J Kidney Dis 201056387-393.
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Hyperkalemia in CKD Causes
Pediatr Nephrol Published online 22 December 2010
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Hyperkalemia in CKD

• Preservation of normokalemia results from
• An adaptive increase in K excretion by remnant
  nephrons and increased bowel loss
• However, hyperkalemia may be an early feature of
  renal failure in patients with
• (hyperchloremic) metabolic acidosis and
  hyporeninemic hypoaldosteronism, which occur
  particularly in patients with
• Tubulointerstitial disease and diabetes mellitus

Electrolyte Blood Pressure 2005 371-78.
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Hyperkalemia in CKD

• Clinical management for hyperkalemia in patients
  with CKD requires
• Exclusion of pseudohyperkalemia,
• Assessmemt of the urgency for treatment, and
• Appropriate acute and chronic therapy

Electrolyte Blood Pressure 2005 371-78.
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Hyperkalemia in CKD

• Pseudohyperkalemia
• Important to avoid unnecessary treatment
• The most common cause of pseudohyperkalemia is
  hemolysis, which is usually
• Easily noted due to a pink tinge to the plasma
  resulting from release of hemoglobin from damaged
  red blood cells
• Alternatively, an excessively tight tourniquet
  surrounding an exercising extremity (e.g.,
  opening and closing a hand) can increase plasma
  K by gt 2 mEq/L)
• Excessive numbers of either leukocytes gt
  70,000/cm3, or platelets gt 1,000,000/cm3 also can
  lead to pseudohyperkalemia

Electrolyte Blood Pressure 2005 371-78.
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Hyperkalemia in CKD

• Pseudohyperkalemia
• When the serum K is gt0.3 mEq/L as compared with
  a simultaneous plasma K ,
• Pseudohyperkalemia should be diagnosed
• Plasma K can be measured by obtaining a
  heparinized blood specimen
• If pseudohyperkalemia exists,
• All further K levels should be measured using
  plasma

Electrolyte Blood Pressure 2005 371-78.
22
Hyperkalemia in CKD

• Clinical manifestations of hyperkalemia
• May be asymptomatic or life-threatening
• The main danger of hyperkalemia is a
• Cardiac arrhythmia
• ECGs
• Considered to be sensitive indicators of the
  presence of hyperkalemia
• ECG abnormalities consistent with hyperkalemia in
  the hospitalized hyperkalemia patients were
  observed in only 14 of episodes
• Serum K levels gt 8 mEq/L are almost invariably
  associated with ECG abnormalities
• However, minimal or atypical ECG changes have
  been observed in some cases of severe hyperkalemia

Electrolyte Blood Pressure 2005 371-78.
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Hyperkalemia in CKD

• Clinical manifestations of hyperkalemia
• Minor ECG abnormalities (tall-peaked T waves) may
  be the first indication of hyperkalaemia but
• By the time serious changes occur, the patient
  usually complains of muscle weakness,
  paresthesia, and lethargy
• Severe hyperkalemia
• Can cause bilateral flaccid paralysis of
  extremities, and weakness of repiratory muscles
• However unlike hypokalemia, complete paralysis is
  uncommon.

Electrolyte Blood Pressure 2005 371-78.
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Hyperkalemia in CKD Treatment

• Acute / emergency treatment of hyperkalemia
• Acute reduction of serum K is required at levels
  exceeding 7.0 mEq/L, because of the risk of
  cardiac arrest
• For acute therapy of hyperkalemia in an urgent
  situation, regardless of the underlying cause,
  following treatments have been recommended

Electrolyte Blood Pressure 2005 371-78.
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Hyperkalemia in CKD Treatment

• Acute / emergency treatment of hyperkalemia
• Emergency treatment should be started by the
  administration of calcium (10-30 mL of 10
  calcium gluconate over 10 min intravenously)
• Intravenous infusion of calcium is the most rapid
  and effective way to antagonize the myocardial
  toxic effects of hyperkalemia

Electrolyte Blood Pressure 2005 371-78.
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Hyperkalemia in CKD Treatment

• Acute / emergency treatment of hyperkalemia
• Furthermore, intravenous glucose (50 mL dextrose
  50 , preferably by central venous infusion)
  should be given followed by or combined with 10
  units of short-acting regular insulin, because
• Combined administration of glucose and insulin
  results in a greater decline in serum K levels
• Intravenous insulin rapidly stimulates uptake of
  K into cells, primarily the muscle and liver

Electrolyte Blood Pressure 2005 371-78.
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Hyperkalemia in CKD Treatment

• Acute / emergency treatment of hyperkalemia
• ß2-adrenergic agonists,
• which also induce cellular K uptake, are useful
  for the acute therapy of hyperkalemia
• A direct comparison between
• Intravenous (0.5 mg) and nebulized (10 mg)
  albuterol (salbutamol) in ESRD patients revealed
  a similar potassium-lowering

Electrolyte Blood Pressure 2005 371-78.
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Hyperkalemia in CKD Treatment

• Acute / emergency treatment of hyperkalemia
• However, 20-40 of ESRD patients are refractory
  to the K -lowering effect of albuterol and
• Not possible to predict non-responders
• Combined use of
• ß2-adrenergic agonists with glucose and insulin
• will maximize the reduction in serum K

Electrolyte Blood Pressure 2005 371-78.
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Hyperkalemia in CKD Treatment

• Acute / emergency treatment of hyperkalemia
• When especially used alone, bicarbonate is
  probably less effective than either ß2-agonist or
  insulin in the acute treatment of hyperkalemia
• Recent studies show conflicting evidences whether
  bicarbonate can act in a synergistic fashion with
  either insulin or ß2 -adrenergic agonists

Electrolyte Blood Pressure 2005 371-78.
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Hyperkalemia in CKD Treatment

• Acute / emergency treatment of hyperkalemia
• Dialysis should be considered the primary method
  of K removal when hyperkalemia is persistent or
  severe
• Hemodialysis is the most rapid method of K
  removal
• Removal rates of K can approximate 35 mEq/hr
  with a dialysate bath potassium concentration of
  1-2 mEq/L
• A glucose free dialysate is preferable to
  minimize a glucose-induced shift of K into cell,
  lessening the removal of K

Electrolyte Blood Pressure 2005 371-78.
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Hyperkalemia in CKD Treatment

• Acute / emergency treatment of hyperkalemia
• Peritoneal dialysis and chronic hemodiafiltration
  are effective in chronic hyperkalemia, but
• Do not remove K fast enough to be recommended
  for use in acute, severe hyperkalemia
• Although dialysis is the most rapid method
  available to treat most cases of hyperkalemia,
• other modes of treatment should not be delayed
  while waiting to institute dialysis

Electrolyte Blood Pressure 2005 371-78.
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Hyperkalemia in CKD Treatment

• Chronic treatment of hyperkalemia in CKD
• Important to determine underlying causes for
  hyperkalemia.
• One should find modifiable causes of hyperkalemia
  in CKD patients
• Common modifiable causes are
• Concomitant medications and
• Excessive dietary intake
• A careful history on the dietary habit and the
  medication is necessary

Electrolyte Blood Pressure 2005 371-78.
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Hyperkalemia in CKD Treatment

• Chronic treatment of hyperkalemia in CKD
• 3 general categories
• (1) to avoid or replace drugs that cause
  hyperkalemia
• (2) to prescribe a low-potassium diet and avoid
  constipation, and
• (3) to enhance potassium excretion by residual
  functioning nephrons or to remove it more
  efficiently by dialysis and/or by the
  gastrointestinal tract

Electrolyte Blood Pressure 2005 371-78.
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Hyperkalemia in CKD Treatment

• Chronic treatment of hyperkalemia in CKD
• Follow-up should be in 2 weeks if serum K gt5.1
  mEq/L for outpatients management of CKD
• If mild hyperkalemia develops after medications,
• Reduce the dose of medications that interfere K
  balance by 50 and
• Reassess the serum K every 5 to 7 days until
  serum K has returned to baseline
• If serum K does not return to baseline within 2
  to 4 weeks,
• Discontinue that medications and select an
  alternate medication

Electrolyte Blood Pressure 2005 371-78.
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Hyperkalemia in CKD Treatment

• Chronic treatment of hyperkalemia in CKD
• Target potassium intake of a low potassium diet
  is
• lt2 to 3 g/d (approximately 50 to 75 mEq/d)
• The DASH diet should not be routinely recommended
  to patients with CKD stage 3, 4 and 5 (GFRlt60
  mL/min/1.73 m2) because of its high content of
  fruits and vegetables
• Salt substitutes should not be recommended in CKD

Electrolyte Blood Pressure 2005 371-78.
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Hyperkalemia in CKD Treatment

• Chronic treatment of hyperkalemia in CKD
• Beside excess potassium dietary intake and
  constipation, it is also important to look for
  prolonged fasting
• Overnight fasting in preparation for surgery in
  dialysis patients may induce hyperkalemia due to
  a fall in the concentration of insulin
• This can be avoided by continuous infusion of 10
  glucose at 50 mL/h mixed with or without regular
  insulin

Electrolyte Blood Pressure 2005 371-78.
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Hyperkalemia in CKD Treatment

• Chronic treatment of hyperkalemia in CKD
• Promoting diuresis with a loop diuretic can
  control chronic, mild hyperkalemia

Electrolyte Blood Pressure 2005 371-78.
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Hyperkalemia in CKD Treatment

• Chronic treatment of hyperkalemia in CKD
• Thiazide and loop diuretics increase the delivery
  of sodium to the distal tubule, thereby
  increasing urinary potassium excretion
• This may be a useful side-effect in CKD,
  especially in patients treated with an ACE
  inhibitor or ARB
• However, most of thiazides are effective in
  kaliuresis in patients with GFR gt approx. 30
  mL/min/1.73 m2

Electrolyte Blood Pressure 2005 371-78.
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Hyperkalemia in CKD Treatment

• Chronic treatment of hyperkalemia in CKD
• An active component of licorice,
• Glycyrrhetinic acid might be considered as one of
  the therapeutic agents for chronically
  hyperkalemic patients on maintenance hemodialysis

Electrolyte Blood Pressure 2005 371-78.
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Hyperkalemia in CKD Treatment

• Either after acute hyperkalemia has been
  corrected or in chronic management of less severe
  hyperkalemia in CKD patients, the more slowly
  acting
• Cation exchange resin may be given orally or
  rectally (e.g. sodium/calcium polystyrene
  sulfonate 15-30 g, with an equal amount of
  sorbitol to prevent fecal impaction)
• Cation exchange resin may be given in order to
  prevent a further increase in serum K

Electrolyte Blood Pressure 2005 371-78.
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Potassium binding resins in hyperkalemia

• Hot topic in Nephrology
• Recent editorial
• Damned If You Do, Damned If You Dont Potassium
  Binding Resins in Hyperkalemia

CJASN ePress. Published on August 26, 2010
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Potassium binding resins in hyperkalemia

• SPS resins increase stool potassium excretion in
  normokalemic subjects, but proportionately more
  potassium excreted due to cathartics when the two
  are combined
• In hyperkalemic patients, oral SPS mixed in water
  significantly decreases serum potassium within 24
  hours

CJASN ePress. Published on August 26, 2010
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Potassium binding resins in hyperkalemia

• SPS/sorbitol-associated colonic necrosis is most
  commonly seen in patients
• who have received enemas in the setting of recent
  abdominal surgery, bowel injury, or intestinal
  dysfunction
• It is a rare event,
• on the order of 0.2 to 0.3, almost exclusively
  present in patients at risk

CJASN ePress. Published on August 26, 2010
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Potassium binding resins in hyperkalemia

• Authors concluded
• SPS ion-exchange resins are the only agents,
• other than dialysis and diuretics,
• Available to increase K excretion in
  hyperkalemia, and
• when used appropriately,
• they appear to be
• Clinically effective and reasonably safe

CJASN ePress. Published on August 26, 2010
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Summary Drugs for hyperkalemia
Pediatr Nephrol Published online 22 December 2010
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Hyperkalemia in CKD Treatment

• Either asymptomatic and mild hyperkalemia or
  chronic hyperkalemia in CKD patients is common

Electrolyte Blood Pressure 2005 371-78.
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Conclusions

• Hyperkalemia is common and life threatening
  complication of CKD
• The effective and rapid diagnosis and management
  of acute and chronic hyperkalemia is clinically
  relevant and can be life-saving
• In treatment of moderate to severe hyperkalemia,
  the combination of medications with different
  therapeutic approaches is usually effective, and
  often methods of blood purification can be
  avoided.

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Conclusions

• In patients with severe hyperkalemia and major
  ECG abnormalities, conservative efforts should be
  initiated immediately to stabilize the patient,
  but management should include rapid facilitation
  of renal replacement treatment

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Thank You!