Abstract
BackgroundVitamin-D-binding protein (VDBP) is a low molecular weight protein that is filtered through the glomerulus as a 25-(OH) vitamin D 3/VDBP complex. In the normal kidney VDBP is reabsorbed and catabolized by proximal tubule epithelial cells reducing the urinary excretion to trace amounts. Acute tubular injury is expected to result in urinary VDBP loss. The purpose of our study was to explore the potential role of urinary VDBP as a biomarker of an acute renal damage.MethodWe included 314 patients with diabetes mellitus or mild renal impairment undergoing coronary angiography and collected blood and urine before and 24 hours after the CM application. Patients were followed for 90 days for the composite endpoint major adverse renal events (MARE: need for dialysis, doubling of serum creatinine after 90 days, unplanned emergency rehospitalization or death).ResultsIncreased urine VDBP concentration 24 hours after contrast media exposure was predictive for dialysis need (no dialysis: 113.06 ± 299.61ng/ml, n = 303; need for dialysis: 613.07 ± 700.45 ng/ml, n = 11, Mean ± SD, p<0.001), death (no death during follow-up: 121.41 ± 324.45 ng/ml, n = 306; death during follow-up: 522.01 ± 521.86 ng/ml, n = 8; Mean ± SD, p<0.003) and MARE (no MARE: 112.08 ± 302.00ng/ml, n = 298; MARE: 506.16 ± 624.61 ng/ml, n = 16, Mean ± SD, p<0.001) during the follow-up of 90 days after contrast media exposure. Correction of urine VDBP concentrations for creatinine excretion confirmed its predictive value and was consistent with increased levels of urinary Kidney Injury Molecule-1 (KIM-1) and baseline plasma creatinine in patients with above mentioned complications. The impact of urinary VDBP and KIM-1 on MARE was independent of known CIN risk factors such as anemia, preexisting renal failure, preexisting heart failure, and diabetes.ConclusionsUrinary VDBP is a promising novel biomarker of major contrast induced nephropathy-associated events 90 days after contrast media exposure.
Highlights
Acute kidney injury (AKI) is a severe condition associated with a mortality of up to to 70% [1,2,3,4,5] and prolonged hospitalitation increasing the costs of treatment [6].Biomarkers that can predict the disease progression or development of life threatening complications may help to better understand the disease pathways and to prevent complications
Increased urine Vitamin-D-binding protein (VDBP) concentration 24 hours after contrast media exposure was predictive for dialysis need, death and major adverse renal events (MARE) during the follow-up of 90 days after contrast media
Vitamin-D-binding protein (VDBP) is a low molecular weight protein that is filtered through the glomerulus as a 25-(OH) vitamin D 3/VDBP complex and is uptaken by megalin receptors in the brush border of proximal tubule cells
Summary
Acute kidney injury (AKI) is a severe condition associated with a mortality of up to to 70% [1,2,3,4,5] and prolonged hospitalitation increasing the costs of treatment [6].Biomarkers that can predict the disease progression or development of life threatening complications may help to better understand the disease pathways and to prevent complications. During AKI, increased urinary excretion of different molecules may be caused by either increased tubular secretion or impaired proximal tubular reabsorption [7,8,9] Some biomarkers such as liver-type fatty acid-binding protein (L-FABP) and neutrophil gelatinase-associated lipocalin (NGAL) are secreted by normal tubular cells into the urine, increased amounts of those biomarkers in plasma of AKI patients [10] may increase their urinary concentration, causing misinterpretation. Vitamin-D-binding protein (VDBP) is a low molecular weight protein that is filtered through the glomerulus as a 25-(OH) vitamin D 3/VDBP complex and is uptaken by megalin receptors in the brush border of proximal tubule cells. VDBP is reabsorbed by megalin mediated endocytosis and catabolized by proximal tubule epithelial cells reducing the urinary excretion to trace amounts [9]. In the normal kidney VDBP is reabsorbed and catabolized by proximal tubule epithelial cells reducing the urinary excretion to trace amounts. The purpose of our study was to explore the potential role of urinary VDBP as a biomarker of an acute renal damage.
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