PHAR 401

PHARMACOTHERAPY OF
CHRONIC KIDNEY DISEASE II

Alan Lau, Pharm.D.

Professor and Director, Clinical Pharmacy Education
University of Illinois at Chicago
College of Pharmacy

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Sodium

The capacity of CKD patients to regulate sodium excretion in steady

state is relatively well preserved, until late stages of renal failure.
The major defect is the inability to change the rate of sodium
excretion abruptly in response to abrupt changes in salt intake.
Oliguria in ESRD sodium retention

edema
circulatory overload
hypertension
congestive heart failure (CHF)

CHF (secondary to hypertension and increased aldosterone) may

also contribute to sodium retention

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Optimal sodium intake:

Sodium restriction is only needed in patients with

evidence of total body sodium excess (CHF, edema) and
those with marked hypertension.
Sodium intake can be determined by measuring the 24
hour urinary sodium excretion after 4-5 days of a given
diet. The desired amount of sodium intake is generally
close to the patient's upper limit of excretion rather than
the lower limit.
<2 grams of sodium (5 g sodium chloride)
May be adjusted according to sodium excretion of the patient.

FLUIDANDELECTROLYTEBALANCEINCKD
Optimal sodium intake:

Sodium restriction is only needed in patients with

evidence of total body sodium excess (CHF, edema) and
those with marked hypertension.
Sodium intake can be determined by measuring the 24
hour urinary sodium excretion after 4-5 days of a given
diet. The desired amount of sodium intake is generally
close to the patient's upper limit of excretion rather than
the lower limit.
<2 grams of sodium (5 g sodium chloride)
May be adjusted according to sodium excretion of the patient.

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Water

As renal failure progresses, a gradual narrowing in the

upper and lower limits of water excretion occurs.
Urinary tonicity becomes fixed and deviates little from
isotonicity
Excess water intake will result in water retention and
hyponatremia.
Rapid reduction of water intake will result in volume
depletion.
2 L/day is appropriate for most patients or
750-1000 cc + urine output.

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Potassium

Potassium balance

Renal excretion of potassium is impaired in renal failure. As the GFR

decreases, secretion of potassium by the colon increases to maintain
potassium balance.
The increased stool potassium is aldosterone-dependent and has been
associated with an increase in colonic mucosal (Na-K)-ATPase.
Similar adaptation for increased potassium excretion also occurs in
remaining nephrons.
Potential causes of hyperkalemia:

metabolic acidosis
catabolic states (infections, trauma, surgery, steroid treatment)
dietary indiscretion
salt substitutes
blood transfusion
sudden decrease in urine output

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Potassium

Drugs that may result in hyperkalemia:

+
+
+
+
+

+
+

Potassium content: penicillin

Prevent potassium cellular entry: B-adrenergic antagonists
Release of muscle potassium: succinylcholine, depolarizing muscle
relaxant
Reduce urinary potassium excretion: potassium-sparing diuretics
Inhibit angiotensin activity:
+
directly - ACE inhibitors
+
indirectly - PG synthetase inhibitors
decrease colonic potassium excretion: constipating agents
(Na-K)-ATPase inhibition to decrease potassium excretion: digoxin

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Potassium

Dietary intake
Restriction

of potassium intake is not necessary for most

patients until ESRD occurs (CrCl: <10-15 ml/min).
Reduced dietary intake is often recommended for patients
with marked oliguria and increased potassium load (such
as concurrent illness, catabolic states, and metabolic
acidosis.)

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Treatment of hyperkalemia

Urgency

Need to maintain a very narrow range of serum concentration

Goal: maintain serum concentration (pre-hemodialysis) of 4.5-5.5 mEq/L

Kayexalate resin (sodium polystyrene sulfonate)

15-20 gm in 20ml of 70% sorbitol PO qd-qid

30-60 gm of the drug may be mixed with 100ml of tap water to be given as
enema. The enema should be retained for at least 30 minutes.
A cation exchange resin which binds 1 meq of potassium per gram of resin
in exchange for sodium.
May be administered orally or rectally, which has a more rapid onset of
effect.
Adverse effects may include constipation and sodium overload when given
in large quantity
Should not be administered with citrus fruit juices.

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Treatment of hyperkalemia

Glucose and insulin

40-60 gm glucose + 20-30u insulin infused over 30-60 min.

(1 unit of regular insulin/2 gm of glucose)
effect seen in 10-20 min.

Albuterol

binds with 2-adrenoreceptor to activate adrenyl cyclase

has additive effect with glucose-insulin combination
inconsistent hypokalemic effect when used alone, should use with
other agents
may cause tachycardia, use cautiously with coronary artery disease
nebulization (20 mg dissolved in 4 ml saline, inhaled over 10 min.):
less tachycardia than IV, may require multiple doses
IV: faster onset (30 min. vs 90 min.)

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Treatment of hyperkalemia

Sodium bicarbonate

Calcium gluconate

50-100 mEq IV over 30-45 min.

slower onset
antagonizes deleterious and life threatening cardiac membrane
depolarizing effects of hyperkalemia
indicated when dangerous EKG abnormalities are present (heart block,
absent P waves, wide QRS, etc.)
may be given for K> 6.5mEq/L and peaked T waves
10 ml 10% Ca gluconate solution (4.5 mEq Ca) IV over 2-5 min.
rapid onset, effect may last 1-2 hours
requires EKG monitoring
contraindicated in hypercalcemia and high/toxic digoxin concentration

Dialysis

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Acid-base balance
Acid-base balance tends to remain normal until GFR < 50%.
Significant acidemia is unusual before GFR decreases to about
20% of normal.
Diarrhea, dehydration, sepsis, excessive catabolism, fever, or
administration of acid can result in a dramatic fall in arterial pH.

GFR

H+ excretion pH and HCO3 NH4+ excretion (mechanism used to excrete H+)

P04 excretion (mechanism used to excrete titratable acids)
retention of SO4 and other organic ions

calcium carbonate from bone is used to buffer H+

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Acid-base balance
H+ + HCO3-

Metabolic acidosis is characterized with a serum HCO3

concentration, a compensatory pCO2 and a modest
arterial pH
Symptoms: anorexia, nausea, lethargy

H2CO3

CO2 + H2O

Kussmaul's respiration (deep, sighing respiration) to increase CO2

excretion (compensatory alkalosis)

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Acid-base balance
Treatment of acidosis
May

be compensated by respiratory alkalosis in mild

acidosis
Sodium bicarbonate (IV, PO)
Sodium citrate and citric acid solution (Shohl's solution)
(BicitraR)
Monitor serum bicarbonate concentration to keep at or >
22 mmol/L

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Uric acid
Renal excretion of uric acid is impaired
Allopurinol may be indicated in certain patients with
hyperuricemia
Uricosuric agents are generally ineffective

Magnesium
Hypermagnesemia can result in reduced neuromuscular
activities
Avoid magnesium-containing medications (e.g. laxatives,
antacids)