Alteraciones de la inmunidad innata, inflamación de bajo grado y progresión de la aterosclerosis subclínica en pacientes con enfermedad renal crónica y en trasplantados renales

Abstract

Introduction: Cardiovascular disease is prevalent in patients with chronic kidney disease (CKD) and kidney transplants and constitutes a main cause of death in these patients. The classical cardiovascular risk factors (i. e. hypertension and diabetes) are very prevalent but they do not explain the increase of cardiovascular risk and mortality. Moreover, non-traditional cardiovascular risk factors such as endothelial dysfunction, subclinical inflammation, mannose binding lectin alterations, are important in CKD and kidney transplants recipients. The presence and progression of subclinical atherosclerosis evaluated by carotid ultrasound, allows a better stratification of cardiovascular risk in general populations and populations at risk. Thus, the aim of this doctoral thesis is evaluate if kidney transplants modify the presence and progression of subclinical atherosclerosis independently of renal function. Material and methods: Two cohorts of patients with CKD and kidney transplants recipients with glomerular filtration rate (GFR-e) 60 ml/min/1. 73 m2 not on dialysis were included. In basal visit levels of ADMA, VEGF, ICAM-1, IL-6, TNFR2, MCP-1 and MBL were determined, number of endothelial progenitor cells and circulating endothelial cells were quantified. Ambulatory blood pressure monitoring (ABPM), ankle-brachial index, pulse wave velocity (PWV) and carotid ultrasound were performed at basal visit and 36 months of follow-up. At 18 months of follow up, a PWV and carotid ultrasound were recorded. In each visit, cardiovascular and renal events were registered. Results: Office BP was not different between transplants and CKD patients (139. 5±14. 3 vs. 135. 2±19. 3, P=1. 00, respectively). ABPM 24-hr systolic blood pressure (SBP) (133. 9±14. 3 vs. 126. 2±16. 1, P=0. 014), awake SBP (135. 6±15. 2 vs. 128. 7±16. 2, P=0. 042), and sleep SBP (131. 2±16. 2 vs. 120. 2±17. 9, P=0. 0014) were higher in renal transplants. When patients were classified according to BP patterns associated with highest cardiovascular risk, the proportion of patients with both nocturnal hypertension and non-dipper pattern was higher in transplants (68. 5% vs. 47. 4%,P=0. 03). In the multivariate regression analysis, transplantation was an independent predictor of 24-hr, awake, and sleep SBP. Log IL-6 (P=. 011), and total number of carotid plaques (P=. 013) were higher, while the percentage decline of SBP from day to night was lower in kidney transplant recipients (P=. 003). Independent predictors of 24-hour SBP were urinary protein/creatinine ratio and circulating monocytes (P=. 001), while Log IL-6, serum creatinine, and total number of carotid plaques (P=. 0001) were independent predictors of percentage decline of SBP from day to night. Conclusions: Office BP is similar in kidney transplants and CKD patients with similar renal function. On the contrary, hypertension is more severe in kidney transplants when evaluated with ABPM mainly as a result of increased sleep systolic BP. Thus, precise evaluation of hypertension in kidney transplants requires ABPM. Kidney transplants presents a higher levels of IL-6 and more subclinical atherosclerosis, and subclinical atherosclerosis and systemic inflammation are associated with hypertension after transplantation.

Date of Award	19 Sept 2017
Original language	Spanish
Awarding Institution	Vall d'Hebron University Hospital (HUVH)
Supervisor	Jaime Guardia Masso (Tutor) & Daniel Seron Micas (Director)