High Serum Soluble α-Klotho Levels in Patients with Autosomal Dominant Polycystic Kidney Disease

Abstract

This study aims to determine fibroblast growth factor-23 and soluble α-Klotho levels in patients with autosomal dominant polycystic kidney disease. A total of 76 patients with autosomal dominant polycystic kidney disease and 32 healthy volunteers were included in the study. Serum fibroblast growth factor-23 and soluble α-Klotho levels were measured with ELISA kits. Parathyroid hormone, phosphate, calcium, creatinine, 25-hydroxyvitamin D3 levels, urinary protein to creatinine ratio and estimated glomerular filtration rate were also measured or calculated. Patients with autosomal dominant polycystic kidney disease had significantly higher serum parathyroid hormone (p<0.001), fibroblast growth factor-23 (p<0.001), soluble α-Klotho levels (p=0.001) and lower serum 25-hydroxyvitamin D3 levels (p<0.001) as compared with healthy volunteers. Serum fibroblast growth factor-23, soluble α-Klotho and 25-hydroxyvitamin D3 levels were similar in all five chronic kidney disease stages of autosomal dominant polycystic kidney disease (p>0.05). Fibroblast growth factor-23 (r=-0.251, p=0.034) and soluble α-Klotho levels (r=-0.251, p=0.034) were found to be negatively correlated with estimated glomerular filtration rate. This study shows increased fibroblast growth factor-23 levels in patients with autosomal dominant polycystic kidney disease which is in harmony with the general trend in patients with chronic kidney disease of other aetiologies, but, unlike them, also a significant increase in serum soluble α-Klotho levels in patients with autosomal dominant polycystic kidney disease suggesting an aberrant production or a decreased clearance of α-Klotho molecule. Considering the unique increases in erythropoietin levels due to erythropoietin production in renal cysts, we assume, patients with autosomal dominant polycystic kidney disease may potentially have different soluble α-Klotho production/clearance characteristics than the patients with other parenchymal renal diseases.

The Iron-Klotho-VDR Axis Is a Major Determinant of Proximal Convoluted Tubule Injury in Haptoglobin 2-2 Genotype Diabetic Nephropathy Patients and Mice

“…We further found out that in the Hp 2-2 genotype, α -klotho renal expression is gradually reduced with the progression in CKD stages, and this decrease is more prominent in the diabetic state. This association is in agreement with previous studies that have shown that renal α-klotho gene expression is regulated by pathophysiological conditions including hypertension, diabetes, and chronic renal failure in animal models and in humans [ 16 , 17 , 20 , 29 – 32 ].…”

“…Previous studies have indicated that renal α-klotho gene expression is regulated by pathophysiological conditions including long-term hypertension, oxidative stress, diabetes, and chronic renal failure in both animal models and humans [ 16 , 17 , 20 , 29 – 32 ]. Hence, we evaluated whether the increased renal iron deposits associated with the Hp 2-2 genotype also affect the α -klotho renal expression both in DN mice and patients.…”

Fibroblast growth factor 23 and α-Klotho serum concentration did not differ between children with autosomal dominant polycystic kidney disease and healthy controls

“…Most of the research states that the eGFR decrease is correlated with FGF-23 concentration increase in ADPKD and CKD patients in both adults [13][14][15][16] and children [8,[17][18][19][20][21]. The highest concentration of FGF-23 was found among patients with end-stage renal disease [19,22].…”

“…Klotho protein concentration increased as the eGFR increased, which was observed in the total cohort group. Information about Klotho protein fluctuations during CKD progression are disparate [13][14][15][16][17][18][19][26][27][28][29]. Most of the available research says that adult patients with ADPKD experience serum Klotho concentration decrease with the progression of CKD [13-15, 26, 27]; the same can also be observed in children [17][18][19].…”

“…On the other hand, Sari et al suggest autonomic Klotho protein production as the cause of its increased concentration during ADPKD. It could be connected with excessive tubule cell proliferation and cyst growth, and thus increased secretion of some substances [16]. A parallel situation has been suggested in which erythropoietin accumulates in renal cysts of patients suffering from ADPKD [31].…”