Abstract Background and Aims Patients with CKD show high cardiovascular complication rates. There are classical cardiovascular risk factors, such as obesity, dyslipidemia, and diabetes; however, other cardiovascular disease risk factors are associated with mineral metabolism disorders (phosphorus, hyperparathyroidism, etc.) typically appear in CKD. Due to their pleiotropic effects, vitamin D analogs, such as cholecalciferol, calcitriol, or paricalcitol, have proven effective in controlling bone mineral disease secondary to CKD and cardiovascular pathologies. On the other hand, visceral adiposity has been shown as a risk factor in the general population and in patients with CKD. Specifically, the fat deposited in regions such as the epicardium generates a complex autocrine and paracrine hormonal mechanism that has been associated with cardiovascular complications. Although it has not been widely evaluated, the adipose tissue surrounding the kidneys (perirenal fat [PRF]) could provide additional information of interest in the CKD population. The aim of the study is to assess the relationship between cardiovascular disease, PRF, and the effect of therapeutic interventions for bone and mineral metabolism in patients with CKD. Method This prospective observational and cross-sectional study was designed to evaluate the usage of vitamin D analogs in patients with CKD, focusing on cardiovascular history and PRF accumulation. All the patients were evaluated at the outpatient clinic in Consuelo Hospital in Valencia Spain (January-November 2022). Eighty-three patients with different grades of CKD (G1A1 to G5A3 not on dialysis) were included and follow-up for 24 months. All the patient's data from electronic medical and analytical records were entered into a protocol sheet. The patients that meet the inclusion criteria (eGFR ≤90 or>15 ml/min/1.73 m2; age ≥18 years at the time of signing informed consent, and a life expectancy higher than 1 year) were eligible to participate in the study. As exclusion criteria, patients with an active inflammatory process such as infection, active cancer, or other inflammatory states were excluded beyond those mentioned in inclusion. Patients with an AKI, ADPKD, or CKD requiring RRT were also excluded. Patients were discriminated according to their history of cardiovascular disease (coronary artery disease, stroke, and peripheral vascular disease) and the use of Vitamin D analogs (Cholecalciferol, Calcitriol, and Paricalcitol). The thickness of the PRF was measured in centimeters (cm) through a B-mode ultrasound with a 3.5-MHz convex transductor (Alpinion®; Alpinion Medical Systems, Korea). Patients underwent a bilateral renal ultrasound, and the kidneys were measured anteroposteriorly, transversally, and longitudinally. PRF was measured in the distal third between the cortex and the hepatic border and/or spleen. Results The mean age of the patients was 58.3 ± 16 years. Patients with a cardiovascular disease history showed significantly higher levels of urea (62.0 vs 45.2 mg/dl, p < 0.05), uric acid (5.5 vs 4.3 mg/dl; p < 0.03), intact parathyroid hormone (iPTH) (186.2 vs 65.2 pcg/dl; p0.05) and decreased eGFR (53.55 vs 89.00 ml/min/1.73 mts2). The mean PRF thickness (0.99 vs 0.80 cm; SD ± 0.30; p0.05) was also observed to be elevated with respect to the group who had no previous cardiovascular events (Fig. 1). Moreover, this group showers higher levels (1.2 vs 7.1; p < 0.005) of CRP. Those patients on oral treatment with Paricalcitol (1 mcg/day) had lesser PRF accumulation than those treated with Cholecalciferol (1000 IU/day) or Calcitriol (0.5 mcg/day) (p < 0.05) (Fig. 2). It was not adjusted for confounding factors such as weight, height, or BMI. Conclusion These results show a close relationship between the presence of cardiovascular disease history and a higher accumulation of PRF. The mechanisms by which paricalcitol could influence the decrease in PRF are so far unknown, however, some studies have shown an association between PTH elevation and obesity. Finally, achieving a decrease in the latter could reduce visceral adipose tissue, thus reducing the cardiovascular risk in CKD-affected patients.
Read full abstract