Abstract
Background and Aims
Chronic kidney disease – mineral and bone disorder (CKD-MBD) is a well-known syndrome in end stage renal disease. Vascular calcifications are one of its components. Renal transplantation seemed to halt the progression of vascular calcifications.
The aim of this study was to analyse the progression of vascular calcifications in a cohort of renal transplanted patients, and the associations of those with the old and new bone-derived hormones.
Method
We performed a prospective cohort study of a consecutive sample of de novo single renal transplanted patients in our unit. All patients were submitted to a bone biopsy and laboratorial evaluation at baseline (time 0) including measurements of calcium (Ca), phosphorus (Pi), magnesium (Mg), vitamin D (vitD), calcitonin, parathyroid hormone (PTH), bone alkaline phosphatase (bAP) and total alkaline phosphatase (tAP), alpha-klotho, fibroblast grow-factor 23 (FGF23) and sclerostin. Patients were followed for 12 months, after which performed a second bone biopsy and laboratorial evaluation (time 1). At inclusion, demographic, clinical and transplant-related data were collected, X-ray of the pelvis and hands (Adragão score) and echocardiographic findings were recorded. At the end of the study, echocardiogram, X-ray of pelvis and hands, bone densitometry and non-contrast cardiac CT (Agatston score) were performed. Immunosuppression included induction therapy followed by tacrolimus, mycophenolate mofetil and prednisolone. Continuous variables are presented as medians and categorical variables as frequencies. Associations between variables were performed using Wilcoxon rank sum 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. Mean age 50.1±12.7 years, 59 men (69.4%), 66 caucasian (77.6%), median BMI 25.1±3.4. 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.
The median baseline and 12 months Adragão score had no differences [1 (0 – 2)]. The median coronary artery calcium score was 48.5 (0 – 535) and median percentile was 80 (0 – 92.5). Valvular calcifications were present in 15 and 16 patients at baseline and after 1 year respectively, with no statistical difference between the two time points.
Coronary artery calcium scores were correlated with age (p<0.001), two time points Adragão score (p<0.001), presence of valvular calcification in time 1 evaluation (p=0.004), baseline calcium (p=0.02), baseline and 1-year sclerostin (p=0.01; p=0.04). Coronary artery calcium scores were higher in patients with highest values of FGF23 at baseline (p=0.04). Using a pairwise correlation, vitamin D levels (r=0.4, p=0.0004), iPTH (r=0.6, p<0.001) and total cholesterol levels (r=-0.3, p=0.01) were correlated with the score. Coronary calcium Percentile (adjusted for age, gender and race) was correlated with Adragão score in the two time points (p=0.0001; p=0.002), with presence of valvular calcifications in time 1 evaluation (p=0.02), baseline and 1-year calcium serum levels (p=0.004; p=0.02) and baseline sclerostin (p=0.01).
Conclusion
In conclusion, vascular calcifications stabilize after renal transplant. Adragão score, that is a less expensive exam than cardiac CT, can assess vascular calcifications in renal transplanted patients. Only calcium and sclerostin correlated with both Agatston scores and coronary calcium percentiles.
Deep learning for automated exclusion of cardiac CT examinations negative for coronary artery calcium