Management of Hyperkalemia in CKD patients

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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

2-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
2-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 2-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 2 -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 Dont: 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