Download Hyperkalemia in CKD

Management of
Hyperkalemia in CKD
patients
Dr
Overview
Introduction
 Hyperkalemia in CKD

Incidence
 Significance
 Causes
 Management


Summary and conclusions
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. 2009;169(12):1156-1162
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. 2009;169(12):1156-1162
Hyperkalemia in CKD

Hyperkalemia is usually defined as
Plasma potassium (K+ ) > 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; 3:71-78.
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; 3:71-78.
Hyperkalemia in CKD: Incidence
Arch Intern Med. 2009;169(12):1156-1162
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 (n=34 937 [52.7%])
than as outpatient events (n=31 322 [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. 2009;169(12):1156-1162
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. 2009;169(12):1156-1162
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. 2009;169(12):1156-1162
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. 2009;169(12):1156-1162
Hyperkalemia in CKD: Causes
Pediatr Nephrol Published online 22 December 2010
Hyperkalemia in CKD: Causes

If potassium intake is normal, CKD
does not produce significant hyperkalemia until the GFR is

< 5 ml/min
Electrolyte & Blood Pressure 2005; 3:71-78.
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. 2009;169(12):1156-1162
Hyperkalemia in CKD: Causes

CKD – hyperkalemia:

Causes
• Most importantly, recommended
treatment with renin angiotensinaldosterone system (RAAS) blockers that
inhibit renal K+ excretion
Arch Intern Med. 2009;169(12):1156-1162
Hyperkalemia in CKD: Causes
Am J Kidney Dis 2010;56:387-393.
Hyperkalemia in CKD: Causes
Pediatr Nephrol Published online 22 December 2010
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; 3:71-78.
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; 3:71-78.
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 > 2
mEq/L)
• Excessive numbers of either leukocytes >
70,000/cm3, or platelets > 1,000,000/cm3 also can
lead to pseudohyperkalemia
Electrolyte & Blood Pressure 2005; 3:71-78.
Hyperkalemia in CKD

Pseudohyperkalemia

When the serum K+ is >0.3 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; 3:71-78.
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 > 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; 3:71-78.
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; 3:71-78.
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; 3:71-78.
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; 3:71-78.
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; 3:71-78.
Hyperkalemia in CKD: Treatment

Acute / emergency treatment of
hyperkalemia

β2-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; 3:71-78.
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
• β2-adrenergic agonists with glucose and
insulin
• will maximize the reduction in serum K+
Electrolyte & Blood Pressure 2005; 3:71-78.
Hyperkalemia in CKD: Treatment

Acute / emergency treatment of
hyperkalemia


When especially used alone, bicarbonate is
probably less effective than either β2-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 β2 -adrenergic
agonists
Electrolyte & Blood Pressure 2005; 3:71-78.
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; 3:71-78.
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; 3:71-78.
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; 3:71-78.
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; 3:71-78.
Hyperkalemia in CKD: Treatment



Chronic treatment of hyperkalemia in CKD
Follow-up should be in 2 weeks if serum K+ >5.1
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; 3:71-78.
Hyperkalemia in CKD: Treatment


Chronic treatment of hyperkalemia in CKD
Target potassium intake of a “low potassium
diet” is

<2 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 (GFR<60
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; 3:71-78.
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; 3:71-78.
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; 3:71-78.
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 > approx. 30
mL/min/1.73 m2
Electrolyte & Blood Pressure 2005; 3:71-78.
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; 3:71-78.
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; 3:71-78.
Potassium binding resins in
hyperkalemia
Hot topic in Nephrology
 Recent editorial
 Damned If You Do, Damned If You
Don’t: Potassium Binding Resins in
Hyperkalemia

CJASN ePress. Published on August 26, 2010
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
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
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
Summary: Drugs for hyperkalemia
Pediatr Nephrol Published online 22 December 2010
Hyperkalemia in CKD: Treatment

Either asymptomatic and mild hyperkalemia
or chronic hyperkalemia in CKD patients is
common
Electrolyte & Blood Pressure 2005; 3:71-78.
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.
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