380 results. Approximately 90% of cases of CAH are due to 21-hydroxylase deficiency [21]. The particular phenotype and degree of hyperkalemia depends on the sex of the individual, the location of the block in synthesis, and the severity of the genetic deletion or mutation. 6) Congestive heart failure: reduced renal function and treatment with drugs interfering with renal potassium excretion often lead to hyperkalemia [14, 22]. 7) Constipation: enteral elimination of potassium can be decreased and therefore lead to hyperkalemia, which again might lead to reduced bowel movements. Patients with bowel emptying problems secondary to myelodysplasia or VACTERL-association are at special risk. Increased shift of potassium from intra to extracellular space 1) Acidosis: Mineral acidosis is more likely to cause a shift of potassium from intracellular space into extra- cellular space than organic acidosis. 2) Diabetes mellitus: reduced insulin levels lead to accumulation of potassium in the extracellular space [23]. 3) Acute increase in osmolality secondary to hyperglyce- mia or mannitol infusion causes potassium to exit from cells [24]. 4) Acute cell-tissue breakdown: if extensive cell damage occurs, intracellular potassium is released into extra- cellular space. This can be the case in patients with rhabdomyolysis, tumorlyis, hemolysis, or after massive transfusion. 5) Drugs (also see Table 2): digoxin and beta-blockers (especially non-selective ones) inhibit the basolateral Na+/K+-ATPase [25]. Succinylcholine, especially when given to patients with burn injuries, immobilization, or inflammation [26]. 6) Hyperkalemic periodic paralysis: rare condition with mutations of the muscular sodium channel, resulting in paralytic episodes associated with elevated K+ levels [27]. Diagnosis of hyperkalemia Hyperkalemia can be classified according to serum potas- sium into mild (5.5–6.5 mmol/l), moderate (6.5–7.5 mmol/ l) and severe (>7.5 mmol/l) hyperkalemia. Hyperkalemia is rarely associated with symptoms, occasionally patients complain of palpitations, nausea, muscle pain, or paresthesia. However, moderate and Pediatr Nephrol (2011) 26:377–384 especially severe hyperkalemia can lead to disturbances of cardiac rhythm, which can be fatal [28, 29]. Electro- cardiography (ECG) monitoring is mandatory in patients with serum potassium >6.5 mmol/l. ECG changes may present as non-specific repolarization abnormalities, “peaked” T-waves, and QRS widening as well as depression of ST-segment. Examination and investigations should be systematic and always include assessment of cardiac function, kidneys, and urinary tract as well as hydration status and neurological evaluation. Laboratory workup should be comprehensive, especially if the underlying cause is unknown (Table 3). Figure 1 gives a diagnostic algorithm based on GFR and aldosterone levels. Pseudohyperkalemia If elevated serum potassium is found in an asymptomatic patient with no apparent cause, factitious hyperkalemia should be considered. This results from leakage of potassium from the intracellular space during or after blood sampling. In these cases, elevation of serum potassium concentration does not reflect the level of serum potassium in vivo and no treatment is needed. Especially in pediatrics, mechanical hemolysis can occur during difficult blood draws, and even more in samples with lymphocytosis or thrombocytosis. Especially when capillary samples are taken, excess alcohol on the skin should be avoided, as it is the primary cause of the hemolysis in this process. Correction factors have been discussed, but blood usually has to be drawn again [30]. Management of hyperkalemia Therapeutic strategies should be individualized, taking into account the degree and the cause of hyperkalemia. Management should not only rely on ECG changes but be guided by the clinical scenario and serial potassium measurements [29, 31]. Treatment has to be more aggres- sive the higher and the faster the rise of the potassium level, and the greater the evidence of toxicity (ECG changes). Most medical therapies for hyperkalemia provide only transitory improvement by shifting K+ into intracellular space without actually eliminating potassium. These thera- peutic measures often are sufficient in acute hyperkalemia in patients without significant renal impairment, where an increase in renal potassium excretion can be achieved. In patients with moderate to severe hyperkalemia (>6.5 mmol/l), especially those with renal impairment, all therapeutic strategies including renal replacement therapy may be necessary [32].