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


Molecular Defect Potassium Excretion Renal Tubular Dysfunction Renal Pathway Receptor Insufficiency 
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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.


  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

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