A clinical approach to tubulopathies in children and young adults

Abstract

Kidney tubules are responsible for the preservation of fluid, electrolyte and acid-base homeostasis via passive and active mechanisms. These physiological processes can be disrupted by inherited or acquired aetiologies. The net result is a tubulopathy. It is important to make a prompt and accurate diagnosis of tubulopathies in children and young adults. This allows timely and appropriate management, including disease-specific therapies, and avoids complications such as growth failure. Tubulopathies can present with a variety of non-specific clinical features which can be diagnostically challenging. In this review, we build from this common anatomical and physiological understanding to present a tangible appreciation of tubulopathies as they are likely to be clinically encountered among affected children and young adults.

Keywords: Genetics; Hypokalaemia; Magnesium; Nephrocalcinosis; Rare disease; Salt-wasting; Tubulopathy.

Fig. 1

The nephron with associated segments

Fig. 2

Diagnostic flow chart for hypokalaemic metabolic acidosis

Fig. 3

Diagnostic flow chart for hypokalaemic metabolic alkalosis

Fig. 4

Thick ascending limb of the Loop of Henle with the NKCC2, ROMK, Barrtin subunit and CIC-Ka/b implicated Bartter syndrome. Also demonstrates paracellular reabsorption of sodium, magnesium and calcium via tight junction transmembrane proteins claudin 10, 16 and 19

Fig. 5

Distal convoluted tubule with the NCC implicated in Gitelman syndrome and KCNJ10 implicated in EAST syndrome. Decreased expression of TRPM6 postulated to be the cause of hypomagnesaemia in Gitelman syndrome