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526-P: Urine Tricarboxylic Acid Cycle Organic Anions and Progression of Diabetic Kidney Disease

Publication ,  Conference
LUNYERA, J; NGUYEN, M; DIAMANTIDIS, CJ; BOSWORTH, HB; PATEL, UD; DAVENPORT, CA; BAIN, JR; MUEHLBAUER, M; ILKAYEVA, O; SHAH, SH; SCIALLA, J
Published in: Diabetes
June 1, 2020

Background: Urine tricarboxylic acid (TCA) cycle organic anions (OAs) are elevated in diabetes and may be biomarkers for diabetic kidney disease (DKD) progression.Methods: We conducted an ancillary study to the Simultaneous Risk Factor Control Using Telehealth to Slow Progression of Diabetic Kidney Disease (STOP-DKD) Trial - a randomized trial of pharmacist-led medication and behavior management in 281 patients with early to moderate DKD at Duke from 2014-2015. In this study, we used linear mixed models to assess associations of 10 urine TCA cycle OAs with estimated glomerular filtration rate (eGFR) and eGFR decline. TCA cycle OAs were measured in 24h urine samples by targeted MS and modeled as: (1) the average of z-scores for each OAs; and (2) factor scores derived by principal component analysis (PCA). We extended follow-up for eGFR to mid-2019 using electronic health records.Results: Among 132 participants (50% men; 58% Black; mean age 64 years [SD 9]; median eGFR 72 ml/min/1.73m2 [IQR 59-89] and urine albumin-to-creatinine [UACR] 25 mg/g [IQR 9-81]), PCA identified 3 OA metabolite factors (F). Fumarate, malate, α-ketoglutarate, citrate, lactate, and pyruvate loaded positively on F1; succinate, pyruvate, and lactate loaded negatively on F2; and methylsuccinate, ethylmalonate, and methylmalonate loaded positively on F3. Over a median follow-up of 1 year [IQR 1.3], higher average OA z score, F1, and F3 were each strongly associated with higher baseline eGFR after adjustment for age, sex, race, and log(UACR) at baseline (all p<0.01). Higher F2, but not other scores, was associated with faster eGFR decline (p=0.05).Conclusion: Lower urine TCA cycle OAs, most notably a factor comprising lower succinate, pyruvate and lactate, are potential biomarkers for faster DKD progression.

Duke Scholars

Published In

Diabetes

DOI

EISSN

1939-327X

ISSN

0012-1797

Publication Date

June 1, 2020

Volume

69

Issue

Supplement_1

Publisher

American Diabetes Association

Related Subject Headings

  • Endocrinology & Metabolism
  • 32 Biomedical and clinical sciences
  • 11 Medical and Health Sciences
 

Citation

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LUNYERA, J., NGUYEN, M., DIAMANTIDIS, C. J., BOSWORTH, H. B., PATEL, U. D., DAVENPORT, C. A., … SCIALLA, J. (2020). 526-P: Urine Tricarboxylic Acid Cycle Organic Anions and Progression of Diabetic Kidney Disease. In Diabetes (Vol. 69). American Diabetes Association. https://doi.org/10.2337/db20-526-p
LUNYERA, J. O. S. E. P. H., M. A. G. G. I. E. NGUYEN, CLARISSA J. DIAMANTIDIS, HAYDEN B. BOSWORTH, UPTAL D. PATEL, CLEMONTINA A. DAVENPORT, JAMES R. BAIN, et al. “526-P: Urine Tricarboxylic Acid Cycle Organic Anions and Progression of Diabetic Kidney Disease.” In Diabetes, Vol. 69. American Diabetes Association, 2020. https://doi.org/10.2337/db20-526-p.
LUNYERA J, NGUYEN M, DIAMANTIDIS CJ, BOSWORTH HB, PATEL UD, DAVENPORT CA, et al. 526-P: Urine Tricarboxylic Acid Cycle Organic Anions and Progression of Diabetic Kidney Disease. In: Diabetes. American Diabetes Association; 2020.
LUNYERA, J. O. S. E. P. H., et al. “526-P: Urine Tricarboxylic Acid Cycle Organic Anions and Progression of Diabetic Kidney Disease.” Diabetes, vol. 69, no. Supplement_1, American Diabetes Association, 2020. Crossref, doi:10.2337/db20-526-p.
LUNYERA J, NGUYEN M, DIAMANTIDIS CJ, BOSWORTH HB, PATEL UD, DAVENPORT CA, BAIN JR, MUEHLBAUER M, ILKAYEVA O, SHAH SH, SCIALLA J. 526-P: Urine Tricarboxylic Acid Cycle Organic Anions and Progression of Diabetic Kidney Disease. Diabetes. American Diabetes Association; 2020.

Published In

Diabetes

DOI

EISSN

1939-327X

ISSN

0012-1797

Publication Date

June 1, 2020

Volume

69

Issue

Supplement_1

Publisher

American Diabetes Association

Related Subject Headings

  • Endocrinology & Metabolism
  • 32 Biomedical and clinical sciences
  • 11 Medical and Health Sciences