Chapter 046. Sodium and Water (Part 18) pdf

Chapter 046. Sodium and Water
(Part 18)

Algorithm depicting clinical approach to hyperkalemia. NSAID,
nonsteroidal anti-inflammatory drug; ACE, angiotensin-converting enzyme; RTA,
renal tubular acidosis; TTKG, transtubular K
+
concentration gradient.
The appropriate renal response to hyperkalemia is to excrete at least 200
mmol of K
+
daily. In most cases, diminished renal K
+
loss is due to impaired K
+

secretion, which can be assessed by measuring the transtubular K
+
concentration
gradient (TTKG). A TTKG <10 implies a decreased driving force for K
+
secretion
due to either hypoaldosteronism or resistance to the renal effects of
mineralocorticoid. This can be determined by evaluating the kaliuretic response to
administration of mineralocorticoid (e.g., 9α-fludrocortisone). Primary adrenal
insufficiency can be differentiated from hyporeninemic hypoaldosteronism by
examining the renin-aldosterone axis. Renin and aldosterone levels should be
measured in the supine and upright positions following 3 days of Na
+
restriction
(Na

+
intake <10 mmol/d) in combination with a loop diuretic to induce mild
volume contraction. Aldosterone-resistant hyperkalemia can result from the
various causes of impaired distal Na
+
reabsorption or from a Cl
–
shunt. The former
leads to salt wasting, ECF volume contraction, and high renin and aldosterone
levels. In contrast, enhanced distal Cl
–
reabsorption is associated with volume
expansion and suppressed renin and aldosterone secretion. As mentioned above,
hypoaldosteronism seldom causes severe hyperkalemia in the absence of increased
dietary K
+
intake, renal insufficiency, transcellular K
+
shifts, or antikaliuretic
drugs.
Hyperkalemia: Treatment
The approach to therapy depends on the degree of hyperkalemia as
determined by the plasma K
+
concentration, associated muscular weakness, and
changes on the electrocardiogram. Potentially fatal hyperkalemia rarely occurs
unless the plasma K
+
concentration exceeds 7.5 mmol/L and is usually associated
with profound weakness and absent P waves, QRS widening, or ventricular

arrhythmias on the electrocardiogram.
Severe hyperkalemia requires emergent treatment directed at minimizing
membrane depolarization, shifting K
+
into cells, and promoting K
+
loss. In
addition, exogenous K
+
intake and antikaliuretic drugs should be discontinued.
Administration of calcium gluconate decreases membrane excitability. The usual
dose is 10 mL of a 10% solution infused over 2–3 min. The effect begins within
minutes but is short-lived (30–60 min), and the dose can be repeated if no change
in the electrocardiogram is seen after 5–10 min. Insulin causes K
+
to shift into
cells by mechanisms described previously and will temporarily lower the plasma
K
+
concentration. Although glucose alone will stimulate insulin release from
normal pancreatic βcells, a more rapid response generally occurs when exogenous
insulin is administered (with glucose to prevent hypoglycemia). A commonly
recommended combination is 10–20 units of regular insulin and 25–50 g of
glucose. Obviously, hyperglycemic patients should not be given glucose. If
effective, the plasma K
+
concentration will fall by 0.5–1.5 mmol/L in 15–30 min,
and the effect will last for several hours. Alkali therapy with intravenous NaHCO
3

can also shift K
+
into cells. This is safest when administered as an isotonic solution
of 3 ampules per liter (134 mmol/L NaHCO
3
) and ideally should be reserved for
severe hyperkalemia associated with metabolic acidosis. Patients with end-stage
renal disease seldom respond to this intervention and may not tolerate the Na
+
load
and resultant volume expansion. When administered parenterally or in nebulized
form, β
2
-adrenergic agonists promote cellular uptake of K
+
(see above). The onset
of action is 30 min, lowering the plasma K
+
concentration by 0.5 to 1.5 mmol/L,
and the effect lasts 2–4 h.
Removal of K
+
can be achieved using diuretics, cation-exchange resin, or
dialysis. Loop and thiazide diuretics, often in combination, may enhance K
+

excretion if renal function is adequate. Sodium polystyrene sulfonate is a cation-
exchange resin that promotes the exchange of Na
+
for K

+
in the gastrointestinal
tract. Each gram binds 1 mmol of K
+
and releases 2–3 mmol of Na
+
. When given
by mouth, the usual dose is 25–50 g mixed with 100 mL of 20% sorbitol to
prevent constipation. This will generally lower the plasma K
+
concentration by
0.5–1.0 mmol/L within 1–2 h and last for 4–6 h. Sodium polystyrene sulfonate can
also be administered as a retention enema consisting of 50 g of resin and 50 mL of
70% sorbitol mixed in 150 mL of tap water. The sorbitol should be omitted from
the enema in postoperative patients due to the increased incidence of sorbitol-
induced colonic necrosis, especially following renal transplantation. The most
rapid and effective way of lowering the plasma K
+
concentration is hemodialysis.
This should be reserved for patients with renal failure and those with severe life-
threatening hyperkalemia unresponsive to more conservative measures. Peritoneal
dialysis also removes K
+
but is only 15–20% as effective as hemodialysis. Finally,
the underlying cause of the hyperkalemia should be treated. This may involve
dietary modification, correction of metabolic acidosis, cautious volume expansion,
and administration of exogenous mineralocorticoid.
Further Readings
Adrogue
HJ, Madias NE: Hypernatremia. N Engl J Med 342:1493, 2000

[PMID: 10816188]
———: Hyponatremia. N Engl J Med 342:1581, 2000
Berl T, Verbalis J: Pathophysiology of water metabolism, in
Brenner &
Rector's The Kidney, 7th ed, BM Brenner (ed). Philadelphia, Saunders, 2004
Cohn JN et al: New guidelines for potassium replacement in clinical
practice: A contemporary review by the National Council on Potassium in Clinical
Practice. Arch Intern Med 160:2429, 2000 [PMID: 10979053]
Goldszmidt MA, Iliescu EA: DDA
VP to prevent rapid correction in
hyponatremia. Clin Nephrol 53:226, 2000 [PMID: 10749304]
Greenberg A, Verbalis JG: Vasopressin receptor antagonists. Kidney Int
69:2124, 2006 [PMID: 16672911]
Gross P: Treatment of severe hyponatremia. Kidney Int 60:24
17, 2001
[PMID: 11737620]
Harrigan MR: Cerebral salt wasting syndrome. Crit Care Clin 17:125, 2001
[PMID: 11219225]
Mount DB: Disorders of potassium balance, in
Brenner & Rector's The
Kidney, 7th ed, BM Brenner (ed). Philadelphia, Saunders, 2004
Nielsen S et al: Aquaporins in the kidney: From molecules to medicine.
Physiol Rev 82:205, 2002 [PMID: 11773613]
Warnock DG: Genetic forms of renal potassium and magnesium wasting.
Am J Med 112:235, 2002 [PMID: 11893352]
Bibliography
Arieff AI: Treatmen
t of hyponatremic encephalopathy with antagonists to
antidiuretic hormone. J Lab Clin Med 138:8, 2001 [PMID: 11433222]
Charytan D, Goldfarb DS: Indications for hospitalization of patients with

hyperkalemia. Arch Intern Med 160:1605, 2000 [PMID: 10847253]
DeFronzo RA, Smith JD: Clinical disorders of hyperkalemia, in
Clinical
Disorders of Fluid and Electrolyte Metabolism
, 5th ed, RG Narins (ed). New
York, McGraw-Hill, 1994
Field MJ et al: Regulation of renal potassium metabolism, in
Clinical
Disorders of Fluid and Electrolyte Metabolism
, 5th ed, RG Narins (ed). New
York, McGraw-Hill, 1994
McKenna K, Thompson C: Osmoregulation in clinical disorders of thirst
appreciation. Clin Endocrinol 49:139, 1998 [PMID: 9828896]
Sands JM, Bichet DG: Nephrogenic di
abetes insipidus. Ann Intern Med
144:186, 2006 [PMID: 16461963]
Schrier RW: Body water homeostasis: Clinical disorders of urinary dilution
and concentration. J Am Soc Nephrol 17:1820, 2006 [PMID: 16738014]