Urinary Vitamin D Binding Protein: A Marker of Kidney Tubular Dysfunction in Patients at Risk for Type 2 Diabetes

Zhila Semnani-Azad; Windy Z N Wang; David E C Cole; Luke W Johnston; Betty Y L Wong; Lei Fu; Ravi Retnakaran; Stewart B Harris; Anthony J Hanley

doi:10.1210/jendso/bvae014

Urinary Vitamin D Binding Protein: A Marker of Kidney Tubular Dysfunction in Patients at Risk for Type 2 Diabetes

J Endocr Soc. 2024 Jan 31;8(3):bvae014. doi: 10.1210/jendso/bvae014. eCollection 2024 Jan 16.

Authors

Zhila Semnani-Azad^{1

2}, Windy Z N Wang², David E C Cole^{3

4

5

6}, Luke W Johnston⁷, Betty Y L Wong⁵, Lei Fu^{5

6}, Ravi Retnakaran^{8

9

10}, Stewart B Harris¹¹, Anthony J Hanley^{2

8

9

12}

Affiliations

¹ Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
² Department of Nutritional Sciences, University of Toronto, Toronto, ON M5S 1A8, Canada.
³ Department of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
⁴ Department of Pediatrics (Genetics), University of Toronto, Toronto, ON M5S 1A8, Canada.
⁵ Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada.
⁶ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
⁷ Department of Public Health, Aarhus University, Aarhus 8000, Denmark.
⁸ Division of Endocrinology and Metabolism, University of Toronto, Toronto, ON M5S 1A8, Canada.
⁹ Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada.
¹⁰ Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada.
¹¹ Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada.
¹² Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5S 1A8, Canada.

Abstract

Context: Recent studies have reported elevated urinary vitamin D binding protein (uVDBP) concentrations in patients with diabetic kidney disease, although the utility of uVDBP to predict deterioration of kidney function over time has not been examined.

Objective: Our objective was to assess the association of uVDBP with longitudinal changes in kidney function.

Methods: Adults at-risk for type 2 diabetes from the Prospective Metabolism and Islet Cell Evaluation (PROMISE) study had 3 assessments over 6 years (n = 727). Urinary albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were used as measures of kidney function. Measurements of uVDBP were performed with enzyme-linked immunosorbent assay and normalized to urine creatinine (uVDBP:cr). Generalized estimating equations (GEEs) evaluated longitudinal associations of uVDBP and uVDBP:cr with measures of kidney function, adjusting for covariates.

Results: Renal uVDBP loss increased with ACR severity at baseline. Individuals with normoalbuminuria, microalbuminuria, and macroalbuminuria had median log uVDBP:cr concentrations of 1.62 μg/mmol, 2.63 μg/mmol, and 2.48 μg/mmol, respectively, and ACR positively correlated with uVDBP concentrations (r = 0.37; P < .001). There was no significant association between uVDBP and eGFR at baseline. Adjusted longitudinal GEE models indicated that each SD increase both in baseline and longitudinal uVDBP:cr was significantly associated with higher ACR over 6 years (β = 30.67 and β = 32.91, respectively). Conversely, neither baseline nor longitudinal uVDBP:cr measures showed a significant association with changes in eGFR over time. These results suggest that loss of uVDBP:cr over time may be a useful marker for predicting renal tubular damage in individuals at risk for diabetes.

Keywords: diabetes; kidney function; longitudinal study; prediabetes; type 2; vitamin D binding protein.