Association of Diabetic Kidney Disease Markers and Urinary Beta-CrossLaps in Type 2 Diabetes

Abstract

Introduction: Diabetic Kidney Disease (DKD) is a chronic complication in Type 2 diabetes. The Chronic Kidney Disease (CKD273) peptide classifier has been found to predict development of DKD even before microalbuminuria develops. Seventy four percent of peptides in the CKD273 classifier are Collagen degradation fragments. The Beta-CrossLaps (β-CTx) Enzyme Llinked Immunosorbent Assay (ELISA) assay detects the specific collagen degradation product, C terminal telopeptide of Type 1 collagen. In light of the Capillary Electrophoresis/Mass Spectrometry (CE-MS) findings, linking collagen degradation fragments excretion to early detection of DKD, the significance of urinary β-CTx levels as a DKD biomarker needs to be evaluated. Aim: To study the urinary excretion of β-CTx in type 2 diabetes patients and to evaluate its relation to microalbuminuria status and estimated Glomerular Filtration Rate (eGFR) of the patients. Materials and Methods: This descriptive cross-sectional study was undertaken at a tertiary care hospital, with enrollment of 82 type 2 diabetes patients from the diabetes Out Patient Department (OPD). Participants were divided into groups based on their Urinary Albumin Creatinine Ratio (UACR) and eGFR levels. The study participants were tested for Urinary β-CTx level, UACR and eGFR. Mean or median was calculated for the parameters with normal and non-normal distribution, respectively. All statistical testing was performed on online calculators available at the site; https://www.socscistatistics.com/. Results: The median urinary β-CTx level observed was 100.6 ng/ mmol of creatinine. Among the 82 participants, 15 participants had urinary β-CTx level 15 pg/mL, the sensitivity of the kit. Among the remaining 67 participants, the minimum Urinary BetaCrossLaps: Creatinine ratio observed was 2.6 ng/mmol and the maximum value observed was 2071 ng/mmol (i.e., 2.1 μg/mmol). The median urinary β-CTx level was highest (100.6 ng/mmol creatinine) in the patient group with eGFR in the normal range. The urinary β-CTx level was found to decline with decline in eGFR, with median urinary β-CTx 65.5 ng/mmol creatinine in the patient group with mildly decreased eGFR and 7.2 ng/mmol creatinine in the patient group with moderately decreased eGFR. Conclusion: The Urinary β-CTx concentration in type 2 Diabetes patients is dispersed over a wide range. The Urinary β-CTx concentration correlates with the eGFR of the patient and is not influenced by age, gender or duration of diabetes. This parameter is a potential early DKD biomarker

Keywords

• collagen degradation products
• diabetic nephropathy
• urinary biomarker