Pediatr Nephrol (2011) 26:377–384 Excessive intake In patients with unimpaired renal function and intact other regulatory mechanisms, large amounts of potassium are needed to achieve hyperkalemia [11]. Whereas in patients with impaired renal function, especially when GFR is <15 ml/min, a slight increase in potassium intake can cause severe hyperkalemia. Impaired elimination of potassium 1) 2) Renal insufficiency acute or chronic: reduced GFR 2 (especially <15 ml/min/1.73 m ) with low urine flow (and therefore low sodium delivery to the distal tubule) lead to decreased renal excretion of potassium. Medications interfering with urinary potassium excretion (also see Table 2): of special clinical relevance are potassium-sparing diuretics (amiloride or spironolactone), cyclosporine, trimetoprim [12]. Non-steroidal anti-inflam- matory drugs (NSAIDs; ibuprofen, naproxen) and ACEI (angiotensin converting enzyme inhibitors) as well as angiotensin receptor inhibitors can cause a decrease in aldosterone and GFR and thereby lead to hyperkalemia [13]. Combined treatment with spironolactone and ACE inhibitors, especially in patients with renal impairment or heart failure, has to be monitored very carefully. Table 2 Drugs inducing hyperkalemia 379 3) Hypoaldosteronism may either be primary (e.g. M. Addison) or secondary (e.g. chronic renal failure), resulting in hyperkalemia accompanied by urinary salt wasting, leading to volume depletion and hypotension [14, 15]. A similar picture can be seen in patients with obstructive uropathy and renal tubular acidosis [16, 17]. 4) Pseudohypoaldosteronism (PHA) refers to a heteroge- neous group of disorders of electrolyte metabolism characterized by hyperkalemia, metabolic acidosis, and normal GRF [18]. PHA type I caused by autosomal dominant mutations in the human mineralocorticoid receptor (MR) gene is limited to the kidneys. PHA type I secondary to loss of function mutations of the ENaC not only affects the kidney but also the lungs, colon, and sweat and salivary glands. PHA-II (also known as Gordon’s syndrome) is a rare familial renal tubular defect caused by loss of function mutations in WNK1 or WNK4 [19]. Gordon’s syndrome is characterized by volume expansion, suppressed renin, and reduced mineralocorticoid-induced renal clearance of potassium leading to hypertension and hyperkalemia, and hyper- chloremic acidosis with normal glomerular filtration rate [20]. 5) Congenital adrenal hyperplasia (CAH): caused by mutation or deletion of any of the genes that code for enzymes involved in cortisol or aldosterone synthesis Drug Amiloride Spironolactone Cyclosporine, Tacrolimus Trimetoprim, Pentamidine NSAIDs ACE inhibitors, Angiotensin-II receptor antagonists Beta blockers Calcium channels blockers (Nifedipine, Amlodipine) Succinylcholine Digoxin Heparin Mannitol Mechanisms Blocking sodium channels of luminal membrane of principal cells Mineralocorticoid receptor antagonist (competing with aldosterone) Inhibition of adrenal aldosterone biosynthesis Inhibition of adrenal aldosterone biosynthesis Induction of chloride channel shunt Increasing potassium efflux from cells Blocking of sodium channels in the luminal membrane of principal cells Induction of hyporeninemic hypoaldosteronism through inhibiting renal prostaglandin synthesis Reduction in adrenal aldosterone biosynthesis through interrupting renin-aldosterone axis Reduction in effective glomerular filtration rate Inhibiting renin secretion Decrease in cellular potassium uptake Inhibition of adrenal aldosterone biosynthesis Reduction in aldosterone secretion Leakage of potassium out of cells through depolarization of cell membranes Inhibition of Na+/K+-ATPase Inhibition of adrenal aldosterone biosynthesis Decreasing number and affinity of angiotensin-II receptors “Solvent drag phenomena” whereby potassium shifts out of cells due to the body’s attempt to maintain isotonicity while undergoing a hypertonic infusion NSAIDs non-steroidal anti-inflammatory drugs