New paper adds evidence for role of myo-inositol transport in kidney disease

posted in: Interesting papers

A new paper by Peggy Sekula from Anna Köttgen’s team adds evidence for a role of myo-inositol in kidney disorders.

In this month’s issue of the Journal of the American Society of Nephrology (JASN), the authors report A Metabolome-Wide Association Study of Kidney Function and Disease in the General Population. They applied a nontargeted metabolomics approach to quantify 493 small molecules in human serumof 1735 participants in the KORA F4 study, followed by replication in 1164 individuals in the TwinsUK registry. After correction for multiple testing, 54 replicated metabolites significantly associated with eGFRcr, and six of these showed pairwise correlation (r≥0.50) with established kidney function measures: C-mannosyltryptophan, pseudouridine, N-acetylalanine, erythronate, myo-inositol, and N-acetylcarnosine.

It is now interesting to link these findings to previous reports that already relate myo-inositol to kidney function:

Raffler et al. [PLoS Genetics, 2015] reported a genome-wide association study with metabolomics (mGWAS) in urine. They found increased levels of myo-inositol in urine associated with a variant of SNP rs17702912 at the SLC5A11 locus, whereas an mGWAS in blood reported decreased levels for the same genetic variant [Nature, 2011]. SLC5A11 is a sodium-dependent cotransporter of myo-inositol.

For this locus, Raffler et al. additionally investigated whether the effects seen in blood and urine are directly coupled. To this end, they made use of myo-inositol levels in blood serum samples of the same KORA F4 participants. The ratio between the urinary myo-inositol and the serum myo-inositol levels shows an increase in association strength to the lead SNP in SLC5A11 (rs17702912) by seven orders of magnitude in comparison to the association of urinary myo-inositol alone (Purine < 1.95×10−24, Pblood < 1.50×10−4, Pratio < 2.43×10−31).

Earlier this year, Suhre et al. reported Urine Metabolite Profiles Predictive of Human Kidney Allograft Status (also published in JASN). In Table 1 of this paper, myo-inositol was reported to be increased (1.73×10−3) in urine from patients with acute cellular rejection (ACR) compared to urine from patients with protocol biopsies (controls).

This might indicate less effective re-absorption of myo-inositol in the kidneys of carriers of the effect allele of rs17702912. Chronic kidney disease and kidney rejection appear to have a similar effect on re-absorption of myo-inositol. One may thus speculate about a potential interaction between the genetic variant and the severity and onset of kidney disorders.