Chapter 046. Sodium and Water (Part 18) pdf

NSAID, nonsteroidal anti-inflammatory drug; ACE, angiotensin-converting enzyme; RTA, renal tubular acidosis; TTKG, transtubular K+ concentration gradient.. The appropriate renal respons

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 NaHCO3

can also shift K+ into cells This is safest when administered as an isotonic solution

of 3 ampules per liter (134 mmol/L NaHCO3) 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, β2-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 cation-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: DDAVP 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 60:2417, 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: Treatment 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 diabetes 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]