Abstract
Background and Aims
Changes in dietary phosphorus regulate serum FGF-23, parathyroid hormone, 1,25(OH)(2)D and Klotho concentrations . Cardiovascular disease (CVD) is the principal killer of patients with chronic kidney disease and hyperphosphetemia is a potent risk factor it. Of many causative factors for CVD in CKD, dietary interventions involving restriction of dietary phosphorous intake can help reduce onset of CVD at early stages of CKD with other corrective measures. Muscle wasting is a consequence of uremic syndrome which alters body composition. The aim of the study was to study effect of dietary phosphorous restriction on FGF-23, iPTH, Klotho, 1,25(OH)(2)D and body composition in chronic kidney disease patients.
Method
This is a longitudinal study with 12 months intervention, approved by Ethics Committee of the institute. A total 132 subjects were recruited (66 healthy controls, 66 CKD patient. of 66 patients 33 were in CKD stage 1 and 33 in stage 2. GFR was calculated with the help of MDRD formula. Biochemical parameters of subjects were evaluated at baseline, 6 and 12 months along with the anthropometric measurements (body weight, height, mid upper arm circumference (MUAC), and skin folds). Three days dietary recall was taken to evaluate energy, protein and phosphorous intake. CKD patients whose dietary phosphorous intake was more than 1000 mg/day, were given intense dietary counseling and prescribed dietary modifications by restricting dietary phosphorous between 800-1000 mg/day.
Results
The mean age of controls and patients was 37.01±9.62 and 38.27±12.06 and eGFR of 136.94±11.77 and 83.69±17.37 respectively. One way ANOVA showed significant difference among controls and the study groups in hemoglobin (p<0.001), s albumin (p<0.001), FGF-23 (p<0.001), klotho (p<0.001), urinary protein (p<0.001) and Nephron Index (p<0.001).The mean energy intake (p = 0.001) and dietary phosphorous intake (p<0.001) of the CKD patients decreased significantly with the decline in the renal function along with the anthropometric measures i.e. BMI (p = 0.041),WHR (p = 0.015) and all four skin folds (p<0.001). On applying Pearson’s correlation, eGFR correlated negatively with urinary protein (-0.739, 0.000), FGF-23 (-0.679, 0.000) and serum phosphorous (-0.697, 0.000) and positively with klotho (0.872, 0.000). FGF-23 correlated negatively with klotho (-0.742, 0.000). Dietary phosphorous was found to be positively correlated with urinary protein (0.496, 0.000), serum phosphorous (0.680, 0.000) and FGF-23 (0.573, 0.000) and negatively with Klotho (-0.602, 0.000). Nephron index revealed a positive correlation with eGFR (0.529, 0.000). Urinary protein correlated negatively with klotho (-0.810, 0.000). A multiple linear regression was run to predict eGFR from anthropometric variables such as BMI, WHR, MUAC, skin folds thickness and handgrip strength. All anthropometric variables predicted decline in eGFR (p<0.05, R2 =0.223). At 6 and 12 months; repeated ANOVAs analysis showed a statistically significant difference in serum creatinine (p=0.000), serum phosphorous (p=0.000), FGF-23(p=0.000) and klotho (p=0.000).
Conclusion
Elevated levels of FGF-23 and decreased Klotho levels, with the moderate decline in renal function improved with the restricted phosphorous diet at 6 and 12 months emphasizing the importance of phosphorus restriction at an early stage.
Disorders in the System of Mineral and Bone Metabolism Regulators—FGF-23, Klotho and Sclerostin—in Chronic Kidney Disease: Clinical Significance and Possibilities for Correction