Soluble serum Klotho in diabetic nephropathy: Relationship to VEGF-A |
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| Authors: | Ina Maria Kacso Cosmina Ioana Bondor Gabriel Kacso |
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| Institution: | 1. University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj Napoca, Department of Nephrology, Romania;2. University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj Napoca, Department of Informatics and Biostatistics, Romania;3. University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj Napoca, Department of Oncology, Romania;1. Department of Internal Medicine, Seoul St. Mary''s Hospital, Seoul, South Korea;2. Daejeon St. Mary''s Hospital, Seoul, South Korea;3. Transplantation Research Center, Seoul St. Mary''s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea;4. Department of Internal Medicine, Chungnam National University Hospital, Daejeon, South Korea;1. Department of Transplantation Medicine, Nephrology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland;2. Department and Clinic of General and Transplantation Surgery, Medical University of Warsaw, Warsaw, Poland;1. School of Medicine, Yangzhou University, Yangzhou, 225001, Jiangsu, PR China;2. The Huangkui Research Institute of Suzhong Pharmaceutical Co, Ltd, Taizhou, 225500, Jiangsu, PR China;3. Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225001, PR China;4. Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, 225001, PR China;5. Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Yangzhou, 225001, PR China;1. Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Tenerife, España;2. Servicio de Análisis Clínicos, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Tenerife, España;3. Servicio de Nefrología, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Tenerife, España;4. GEENDIAB (Grupo Español de Estudio de la Nefropatía Diabética) |
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| Abstract: | ObjectivesBoth kidney expression and soluble serum Klotho are influenced by chronic kidney disease (CKD) and diabetes. Serum Klotho is a yet poorly explored biomarker. We describe, for the first time to our knowledge, serum Klotho in diabetic patients with CKD and its relationship to vascular endothelial growth factor A (VEGF-A).Design and methodsWe included 43 controls and 146 diabetic patients with different stages of CKD. Laboratory evaluation, urinary albumin/creatinine ratio (UACR), Klotho (ELISA), VEGF-A (ELISA) were performed.ResultsKlotho was 0.40(0.10–1.30) ng/mL in diabetic patients without CKD and 0.80(0.30–1.30) ng/mL in controls, p = 0.20; VEGF-A was higher in diabetic patients 73.85(57.32–119.00) pg/mL than in controls 43.20(30.1–65.9) pg/mL, p < 0.0001. Klotho increased with CKD stage: 0.2(0.10–0.40) ng/mL in CKD 1/2, 0.60(0.20–1.1) ng/mL in CKD 3/4 and 1.45(0.425–2.90) ng/mL in dialysis patients, p < 0.0001; it also increased with decreasing glomerular filtration rate (GFR). Klotho was lower in albuminuric (UACR > 30 mg/g) patients 0.20(0.10–0.70) ng/mL than in normoalbuminuric (UACR < 30 mg/g) ones 0.50(0.20–1.30) ng/mL, p = 0.03; lowest Klotho was found in microalbuminuric (UACR 30–300 mg/g) patients, p = 0.07. VEGF was lower in microalbuminuric patients but was not influenced by GFR. In diabetic patients but not in controls, Klotho correlated to VEGF-A (r = 0.29, p = 0.0003); in multiple regression VEGF-A was the only significant predictor of Klotho: b = 0.27, 95%CI (0.01–0.04), p = 0.001.ConclusionsIn diabetic patients, Klotho is decreased in early CKD and increases thereafter, paralleling reduced GFR. VEGF-A is higher in diabetic patients than in controls. Both Klotho and VEGF-A are decreased in the presence of microalbuminuria. In diabetes, Klotho strongly correlates to VEGF-A. |
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