Advertisement

European Journal of Pediatrics

, Volume 173, Issue 2, pp 263–263 | Cite as

Renal tubular dysfunction in patients with molecular defects of the insulin receptor gene

  • Yuki Abe
  • Toru Watanabe
Correspondence

Keywords

Molecular Defect Potassium Excretion Renal Tubular Dysfunction Renal Pathway Receptor Insufficiency 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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 [3]. 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 [1]. 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) [2]. 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.

References

  1. 1.
    Abe Y, Sato T, Takagi M, Watanabe T, Nagayama Y, Hasegawa T, Abe T (2012) A case of Rabson-Mendenhall syndrome with a novel mutation in the tyrosine kinase domain of the insulin receptor gene complicated by medullary sponge kidney. J Pediatr Endocrinol Metab 25:587–590PubMedCrossRefGoogle Scholar
  2. 2.
    Cheng CJ, Huang CL (2011) Activation of PI3-kinase stimulates endocytosis of ROMK via Akt1/SGK1-dependent phosphorylation of WNK1. J Am Soc Nephrol 22:460–471PubMedCrossRefGoogle Scholar
  3. 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

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Department of PediatricsNiigata City General HospitalNiigataJapan

Personalised recommendations