Urine inositol pentakisphosphate 2-kinase and changes in kidney structure in early diabetic kidney disease in type 1 diabetes

Helen C. Looker, Michael L. Merchant, Madhavi J. Rane, Robert G. Nelson, Paul L. Kimmel, Brad H. Rovin, Jon B. Klein, Michael Mauer

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2 Scopus citations


We examined the association of urine inositol 1,3,4,5,6-pentakisphosphate 2-kinase (IPP2K) with the presence and progression of diabetic kidney disease (DKD) lesions. Urine IPP2K was measured at baseline by quantitative liquid chromatography-mass spectrometry in 215 participants from the Renin-Angiotensin System Study who had type 1 diabetes and were normoalbuminuric and normotensive with normal or increased glomerular filtration rate (GFR). Urine IPP2K was detectable in 166 participants. Participants with IPP2K below the limit of quantification (LOQ) were assigned concentrations of LOQ/√2. All concentrations were then standardized to urine creatinine (Cr) concentration. Kidney morphometric data were available from biopsies at baseline and after 5 yr. Relationships of IPP2K/Cr with morphometric variables were assessed by linear regression after adjustment for age, sex, diabetes duration, hemoglobin A1c, mean arterial pressure, treatment assignment, and, for longitudinal analyses, baseline structure. Baseline mean age was 29.7 yr, mean diabetes duration 11.2 yr, median albumin excretion rate 5.0 μg/min, and mean iohexol GFR 129 ml min-1 1.73m-2. Higher IPP2K/Cr was associated with higher baseline peripheral glomerular total filtration surface density [Sv(PGBM/ glom), tertile 3 vs. tertile 1 β = 0.527, P = 0.011] and with greater preservation of Sv(PGBM/glom) after 5 yr (tertile 3 vs. tertile 1 β = 0.317, P = 0.013). Smaller increases in mesangial fractional volume (tertile 3 vs. tertile 1 β = -0.578, P = 0.018) were observed after 5 yr in men with higher urine IPP2K/Cr concentrations. Higher urine IPP2K/Cr is associated with less severe kidney lesions at baseline and with preservation of kidney structure over 5 yr in individuals with type 1 diabetes and no clinical evidence of DKD at baseline.

Original languageEnglish (US)
Pages (from-to)F1484-F1492
JournalAmerican Journal of Physiology - Renal Physiology
Issue number5
StatePublished - Nov 2018

Bibliographical note

Funding Information:
This work was supported by the Chronic Kidney Disease Biomarker Consortium funded by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) U01 DK-85649, U01 DK-085673, U01 DK-085660, U01 DK-085688, U01 DK-085651, U01 DK-085689, and R01 DK-091584, and by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases.

Publisher Copyright:
© 2018 American Physiological Society. All rights reserved.


  • Biomarker
  • Diabetic kidney disease
  • Inositol pentakisphosphate 2-kinase
  • Kidney morphometry


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