Topic Discussion: Hyperkalemia in Bartter Syndrome

Bartter syndrome is an autosomal recessive disorder characterized by renal salt wasting, hypokalemic metabolic alkalosis, and normotensive hyperreninemic hyperaldosteronism. Five variants of Bartter syndrome have been identified depending on the affected protein in the thick ascending limb of the loop of Henle:

·        Type 1: Inactivating gene mutation that encodes the  Na+-K+-2Cl- contransporter (NKCC2)

·        Type 2: Inactivating gene mutation that encodes the apical  K+ channel (ROMK)

·        Type 3: Inactivating gene mutation that encodes the  basolateral Cl- channel (ClCNKB)

·        Type 4: Inactivating gene mutation that encodes a basolateral accessory Cl- channel subunit Barttin (BSND)

·        Type 5: Inactivating gene mutation that encodes the  basolateral Calcium sensing receptor (CASR)

Apical ROMK ensures functioning of the NKCC2 cotransporter by recycling potassium back into the renal tubular lumen so hypokalemia in patients with defects in ROMK (Bartter's type II) is relatively mild compared with that in the other forms of Bartter's syndrome.

The mechanism of hypokalemia in Bartter syndrome is thought to be increased distal potassium secretion in the CCD caused by increased distal Na+ delivery in the setting of high aldosterone levels and also by activation of the flow-mediated K+ channels (Maxi-K or BK channels).

However, it has been recognized that Type 2 Bartter syndrome can sometimes course with hyperkalemia. The reason for this can be found in the developmental aspects of potassium secretion. Satlin et al have shown that CCDs isolated from newborn rabbits and studied by in vitro microperfusion show no net K+ secretion until after the third week of postnatal life; net K+ secretory rates increase to adult levels by 6 weeks of age. The role of the maxi-K channels appears to assume great importance in regulating K+ homeostasis under conditions where ROMK K+ secretion is limited like in Type 2 Bartter syndrome. Maxi-K channels are not consistently detected in the CCD until the 4th week of life. This is worsened by the fact that children with type 2 Bartter syndrome are usually born prematurely.

Although patients with type 2 Bartter syndrome may exhibit severe hyperkalemia during the first few days of life, the hyperkalemia is usually transitory. In fact, these patients typically exhibit modest hypokalemia beyond the neonatal period probably due to maturation and presence of Maxi-K channels after the 4^th week.

Hyperkalemia during neonatal period has also been described in type I pseudohypoaldosteronism (type I PHA). However, in type I PHA hyperkalemia is sustained beyond the neonatal period and is associated with metabolic acidosis

Post by

Dr. Helbert Rondon