Renal tubular dysfunction in patients with molecular defects of the insulin receptor gene
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KeywordsMolecular Defect Potassium Excretion Renal Tubular Dysfunction Renal Pathway Receptor Insufficiency
To the editor,
We read with interest on a case of Donohue syndrome with renal tubular dysfunction (RTD) and a mutation in the insulin receptor gene (INSR) written by Hovnik et al. that was published recently in your journal . The authors showed that although recombinant human insulin-like growth factor I (rh-IGF-I) therapy improved RTD, it did not improve the anabolic status of their patient.
We recently reported on a case of Rabson–Mendenhall syndrome with INSR mutations and RTD . Although the patient underwent rh-IGF-I therapy at the age of 4 months, his physical constitution continued to deteriorate, and RTD did not resolve.
The therapeutic effect of rh-IGF-I varies between cases. We suggest that rh-IGF-I may have had an inadequate effect in the patient of the study of Hovnik et al. because anabolic status did not improve.
Chin et al. showed that activation of phosphatidylinositol-3-kinase (PI3K) stimulated endocytosis of the renal outer medullary potassium channel (ROMK) . Insulin and IGF-I can activate PI3K and therefore may inhibit renal potassium excretion by reducing the abundance of ROMK. However, our patient showed sustained RTD after administration of rh-IGF-I, probably due to a poor response to rh-IGF-I. The patient in the study of Hovnik et al. appeared to be in a similar situation to our patient, because rh-IGF-I therapy did not improve their anabolic status. Therefore, recovery of RTD in their patient could not be fully explained by the effect of rh-IGF-I.
In our patient, RTD resolved spontaneously at the age of 18 months. The recovery of renal tubular function in Hovnik’s patient may have depended partially on rh-IGF-I treatment, although this may not have been the only mechanism. Some renal pathways other than the system mediated by IGF-I develop during infancy and may play a specific role in renal tubular function in patients with insulin receptor insufficiency.
- 3.Hovnik T, Bratanič N, Podkrajšek KT, Kovač J, Paro D, Podnar T, Bratina N, Battelino T (2013) Severe progressive obstructive cardiomyopathy and renal tubular dysfunction in Donohue syndrome with decreased insulin receptor autophosphorylation due to a novel INSR mutation. Eur J Pediatr 172:1125–1129PubMedCrossRefGoogle Scholar