Elevated Urinary Level of Vitamin D Binding Protein as a Biomarker for Diabetic Nephropathy

Abstract

Diabetic nephropathy (DN) is one of the most common complications, which results in chronic kidney disease in diabetic patients. It is also one of the causes of increased cardiovascular mortality. However, a considerable amount of significant diabetic renal structural injury may occur in absolute clinical silence, which renders diagnosis difficult. Currently, routine kidney biopsy for DN is not permitted in clinical practice, as the procedure is invasive. Microalbuminuria is considered as the best available, non-invasive marker for DN risk, but certain studies have shown it to have inadequate specificity and sensitivity. Thus, additional studies are required, and feasible measures for the diagnosis of DN prior to advanced renal dysfunction are considered to be of clinical importance with public health implications. The aim of the present work was to assess urinary level of urinary vitamin D binding protein as a biomarker for diabetic nephropathy and to evaluate its clinical significance in diagnosis as well as assessment of disease activity. The vitamin D binding protein (DBP), originally known as the Group-specific component (Gc-globulin), is a 51–58kDa multifunctional serum glycoprotein synthesized in large quantities by hepatic parenchymal cells and secreted into the circulation as a monomeric mature peptide of 458 residues and three structural domains. In our study, recruited from the national institute of nephrology and urology in Cairo, following quantitative measurement of 45 urine sample with ELISA, Diabetic patients were categorized into two groups depending on their albumin /creatinine ratio and healthy control subjects. Patients with infection, collagen disease, decompensated heart failure, liver disease, oncogenic disease, type 1 DM and GFR less than 60 ml/min. were excluded from our study. All study population (diabetic patients and healthy control) were subjected to full history taken, clinical examination and laboratory investigation which include(parameters of kidney function, lipid profile, blood glucose profile, ESR, ACR and UVDBP). Our results showed that,eGFR was significantly decreased in diabetic patients with microalbuminuria compared to normoalbuminuria and significantly decreased in patients with normoalbuminuria compared to healthy control (p-value >0.01)(table 4). HBA1c was significantly increased in diabetic patients with microalbuminuria compared to normoalbuminuria and significantly increased in patients with normoalbuminuria compared to healthy control (p-value >0.01)(table 4). ACR was significantly increased in diabetic patients with microalbuminuria compared to normoalbuminuria and significantly increased in patients with normoalbuminuria compared to healthy control (p-value >0.01)(table 4). Urinary vitamin D binding protein (UVDBP) was significantly increased in diabetic patients with microalbuminuria compared to normoalbuminuria and significantly increased in patients with normoalbuminuria compared to healthy control (p-value >0.01)(table 5). UVDBP wascorrelated positively with age , DM duration, HBA1c,PPBS, GFR and ACR, while it correlated negatively with blood pressure, FBS, serum urea, serum creatinine,cholesterol, HDL, LDL, TGs and ESR(table 6). Multivariate linear regression analysis including age, DM duration,FBS, PPBS, HBA1c, creatinine, GFR, HDL,ESR and ACRshow thatACR level was independent predictor to VDBP level and vice versa(table 9).