Abstract
Background and Aims
Successful renal transplant restores many physiologic abnormalities, including improvement of chronic kidney disease-mineral and bone disorder (CKD-MBD) syndrome, and modifications of bone-related molecules in disease and health can help to understand pathophysiology of this syndrome.
The aim of this study was to analyse the evolution of some of the new CKD-MBD players [alpha-klotho, fibroblast grow factor (FGF) 23, sclerostin] pre and post transplantation and the associations between those and the usual markers of the CKD-MBD disease [parathyroid hormone (PTH), bone alkaline phosphatase (bAP), calcitonin, vitamin D (vitD), phosphorus (Pi), Calcium (Ca) and Magnesium (Mg)] pre and post transplant. We also looked at the differences between values in the two time-points (delta).
Method
We performed a prospective cohort study of a consecutive sample of de novo single renal transplanted patients in our unit. At inclusion, demographic, clinical and transplant-related data were collected, X-ray of the pelvis and hands (for Adragão score) and echocardiographic findings were recorded. All patients were submitted to a bone biopsy and laboratorial evaluation at baseline (time 0). Patients were followed for 12 months (time 1), after which performed laboratorial evaluation, a second bone biopsy, echocardiogram, X-ray of pelvis and hands, bone densitometry and non-contrast cardiac CT (Agatston score). Continuous variables are presented as medians and categorical variables as frequencies. Associations between variables were performed using Wilcoxon matched-pairs test and Spearman correlation test. STATA software was used and p < 0.05 was considered statistically significant.
Results
We recruited 85 patients from 1st October 2015 to 1st March 2018. At the end of 12 months, 6 patients refuse to perform the 2nd evaluation, 5 had primary non-function of the kidney graft, 1 had no sample on bone biopsy in time 0 and 4 patients died. We performed a 2nd evaluation in 69 patients and included those in this study.
Mean age 50.2±12.4 years, 48 men, 53 caucasian (78.8%), median BMI 24.5 (22.7 – 27.8), median dialysis vintage 55 (42 – 84). We observe a significant reduction on phosphorus (delta: -1.1 mg/dl), magnesium (delta: -0.5 mg/dl), PTH (delta: -297.7 pg/ml), Calcitonin (delta: -0.9 ng/L), sclerostin (delta: -1.1 ng/ml), bone alkaline phosphatase (delta: -11.5 U/L) and FGF23 (delta: -1656.5 RU/ml). Both calcium (delta: 0.7 mg/dl) and alpha-klotho (delta: 265.7 pg/ml) serum levels increase, with no significant changes in vitamin D levels.
With restoring renal health (time 1) and comparing with time 0, PTH maintain the negative correlation with sclerostin (p=0.02) and the positive correlation with FGF23 (p=0.0002) as in time 0; modify the correlation with Pi, becoming a negative correlation instead of positive (p=0.001) and gain new correlations with Ca (p=0.001) and vitamin D levels (p=0.03). Also, PTH correlated with the delta FGF23 (rho=-0.4, p=0.003) and sclerostin correlated with delta PTH (p=0.01). FGF23 didn’t associate with delta PTH, neither PTH associated with delta sclerostin. FGF23 didn’t reveal statistical association with Pi or Ca levels after transplant, contrasting with positive associations in pre transplant (p=0.002, p<0.0001). On the contrary, sclerostin developed a new correlation with Pi (p=0.0004) and a negative correlation with Ca (p=0.01). We didn’t find correlations between these molecules and alpha-klotho.
Conclusion
In conclusion, it seems that sclerostin influences PTH levels and that PTH is the stimulus for the increase or decrease of FGF23 serum levels (as we found a positive association between those two molecules in both time-points and a negative association between PTH and the difference of FGF23 pre and post transplant). Levels of Ca and Pi seemed to be directly influenced by the level of PTH in post transplant, and those minerals seemed to be key factors for sclerostin secretion.
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