The link between the fibroblast growth factor-23—klotho—vitamin D3 axis and the renin—angiotensin—aldosterone axis in the development and progression of obesity-related kidney disease

Abstract

Abstract Introduction and aim of the work Obesity is established as an important contributor of increased diabetes mellitus, hypertension and cardiovascular disease, all of which can promote chronic kidney disease (CKD). Recently, there is a growing appreciation that even in the absence of these risks, obesity itself significantly increases CKD and accelerates its progression. The aim of this work is to evaluate the link between Renin-Angiotensin-Aldosterone System (RAAS) and FGF23-Klotho-1,25D3 axis and their impact in obese and non-obese CKD patients. Patients and methods In a cross sectional randomized multi centers study, two hundred twenty six CKD patients stage III and IV (eGFR20–60 ml/min/m2) have enrolled in this study as follows: group I; 87 non diabetic CKD patients aged 20–40 years with body mass index (BMI) between 20–25 kgm/m2; group II; 130 non diabetic CKD patients aged 20–40 years with (BMI) >30 kgm/m2 and group III; 89 CKD patients aged >60 years. All patient have been tested for plasma leptinlevels, 1,25-dihydrocholicalciferole (1,25D3), plasmaparathormone (PTH) Serum calcium (Ca), serum phosphorus (PO4), and plasma FGF-23 , plasma renin activity (PRA), plasma angiotensinogen receptor 1 & 2 (AT1 & AT2) and plasma aldosterone (ALD) and pulse wave velocity (PWV). Results The eGFR was significantly reduced in the obese group II (eGFR = 37.7 ± 13.6) when compared with eGFR of the lean group I (eGFR = 49.3 ± 7.51) were P < 0.001, but not significant when compared with the old age group III (eGFR = 41.0 ± 13.47). The obese group II shows significant increase in the ALD/PRA ratio when compared with the lean group I and old age group III (43.23 ± 14.9) for group II vs 11.29 ± 4.1 for group I, P < 0.001 and 24.91 ± 12.1 for group III, P < 0.05 ). Regarding the FGF23-Klotho-vitD3 axis, its components of the obese group II (FGF23 259.55 ± 138.6 Ru/ml; PTH 77.63 ± X32.4 pg/ml; S.PO 4.74 ± 1.61 mg/dl) were significantly elevated when compared to the lean group I (FGF23 132.81 ± 126.1 Ru/ ml; PTH 59.18 ± 24.7 pg/ml; S.PO4 3.85 ± 0.92 mg/dl); the P values were <0.001, <0.01 and <0.05 respectively , while when compared with the old age group III (FGF23 179.33 ± 237.4 Ru/ml; PTH 70.94 ± 15.26 pg/ml; S.PO4 4.09 ± 0.42 mg/dl), values were of less significance. Plasma insulin levels were significantly high in the obese group II (insulin = 13.73 ± 2.38fg/l) than the lean group I (insulin = 5.59 ± 2.31 fg/l) and P < 0.001 and in group III p. insulin level was 10.7 ± 1.68 (P < 0.05). Conclusion Obesity per se is an independent risk factor in the development and progression of chronic kidney disease specially in young age patients.