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Am J Physiol Renal Physiol. 2018 Nov 1;315(5):F1484-F1492. doi: 10.1152/ajprenal.00183.2018. Epub 2018 Aug 22.

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

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Chronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases , Phoenix, Arizona.
Division of Nephrology and Hypertension, University of Louisville , Louisville, Kentucky.
Department of Biochemistry and Molecular Genetics, University of Louisville , Louisville, Kentucky.
Division of Kidney, Urologic, and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases , Bethesda, Maryland.
Division of Nephrology, Ohio State University , Columbus, Ohio.
Department of Medicine, University of Louisville , Louisville, Kentucky.
Division of Renal Diseases and Hypertension, University of Minnesota , Minneapolis, Minnesota.


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.


biomarker; diabetic kidney disease; inositol pentakisphosphate 2-kinase; kidney morphometry

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