Flaviu Bob1, Adalbert Schiller1, Romulus Timar2, Daniel Lighezan3, Oana Schiller4, Bogdan Timar5, Cristiana Georgeta Bujor6, Mircea Munteanu7, Florica Gadalean1, Adelina Mihaescu1, Iulia Grosu1, Andreea Hategan7, Lazar Chisavu1, Agneta-Maria Pusztai8, Adrian Covic9. 1. Nephrology Department, University of Medicine and Pharmacy "Victor Babes", Timisoara, Romania. 2. Diabetes and Metabolic Diseases Department, University of Medicine and Pharmacy "Victor Babes", Timisoara, Romania. Electronic address: rtimar@yahoo.com. 3. Internal Medicine 1 Department, University of Medicine and Pharmacy "Victor Babes", Timisoara, Romania. 4. BBraun Avitum Dialysis Center, Timisoara, Romania. 5. Medical Informatics and Biostatistics Department, University of Medicine and Pharmacy "Victor Babes", Timisoara, Romania. 6. Biochemistry Department, University of Medicine and Pharmacy "Victor Babes", Timisoara, Romania. 7. Diabetes and Metabolic Diseases Department, University of Medicine and Pharmacy "Victor Babes", Timisoara, Romania. 8. Anatomy Department, University of Medicine and Pharmacy "Victor Babes", Timisoara, Romania. 9. Nephrology Department, Dialysis and Renal Transplant Center, "Dr. C.I. Parhon" University Hospital, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania.
Abstract
BACKGROUND: Klotho is found in two forms: a transmembrane form and a soluble form (s-Klotho). In order to be excreted, s-Klotho, that is too large to be filtered, will probably reach the proximal convoluted tubule by a transcytosis process. The aim of our study was to show the relationship between the levels of s-Klotho and tubular injury in patients with diabetic kidney disease (DKD), using as tubular injury marker the kidney injury molecule-1 (KIM-1). METHODS: Our study included 63 DKD patients (stages 1-5, mean eGFR 65.15±32.45ml/min) with a mean age 58.13±12 years. In all patients we determined serum levels of: KIM-1 and s-Klotho using ELISA, urinary albumin/creatinine ratio (UACR) and reduction in the estimated glomerular filtration rate (eGFR) per year. RESULTS: We found a strong statistically significant correlation of s-Klotho with the rate of reduction of eGFR/year (r=0.714, p=0.0004) and with the tubular injury marker KIM-1 (r=0.758, p=0.005) and strong correlations of UACR with the rate of reduction of eGFR/year (r=0.53, p<0.01), KIM-1 (r=0.49, p<0.05) and s-Klotho (r=0.52, p<0.01). CONCLUSION: Despite previous published data, that shows a decrease of s-Klotho in chronic kidney disease, in our study the rapid annual decline of kidney function but not the level of eGFR was associated with increased s-Klotho. A possible explanation could be a more severe proximal tubule injury that could lead to a reduction of tubular excretion of s-Klotho as suggested by the correlation of s-Klotho levels with the serum levels of KIM-1.
BACKGROUND:Klotho is found in two forms: a transmembrane form and a soluble form (s-Klotho). In order to be excreted, s-Klotho, that is too large to be filtered, will probably reach the proximal convoluted tubule by a transcytosis process. The aim of our study was to show the relationship between the levels of s-Klotho and tubular injury in patients with diabetic kidney disease (DKD), using as tubular injury marker the kidney injury molecule-1 (KIM-1). METHODS: Our study included 63 DKD patients (stages 1-5, mean eGFR 65.15±32.45ml/min) with a mean age 58.13±12 years. In all patients we determined serum levels of: KIM-1 and s-Klotho using ELISA, urinary albumin/creatinine ratio (UACR) and reduction in the estimated glomerular filtration rate (eGFR) per year. RESULTS: We found a strong statistically significant correlation of s-Klotho with the rate of reduction of eGFR/year (r=0.714, p=0.0004) and with the tubular injury marker KIM-1 (r=0.758, p=0.005) and strong correlations of UACR with the rate of reduction of eGFR/year (r=0.53, p<0.01), KIM-1 (r=0.49, p<0.05) and s-Klotho (r=0.52, p<0.01). CONCLUSION: Despite previous published data, that shows a decrease of s-Klotho in chronic kidney disease, in our study the rapid annual decline of kidney function but not the level of eGFR was associated with increased s-Klotho. A possible explanation could be a more severe proximal tubule injury that could lead to a reduction of tubular excretion of s-Klotho as suggested by the correlation of s-Klotho levels with the serum levels of KIM-1.
Authors: Orlando M Gutiérrez; Michael G Shlipak; Ronit Katz; Sushrut S Waikar; Jason H Greenberg; Sarah J Schrauben; Steven Coca; Chirag R Parikh; Ramachandran S Vasan; Harold I Feldman; Paul L Kimmel; Mary Cushman; Joseph V Bonventre; Mark J Sarnak; Joachim H Ix Journal: Am J Kidney Dis Date: 2021-11-06 Impact factor: 11.072
Authors: Dana Dlouha; Milan Blaha; Eva Rohlova; Jaroslav A Hubacek; Vera Lanska; Jakub Visek; Vladimir Blaha Journal: Genes (Basel) Date: 2021-10-12 Impact factor: 4.096