Efeito da espironolactona na progressão da calcificação coronariana de pacientes com doença renal crônica em hemodiálise
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Data
2018-03-29
Autores
Gueiros, Jose Edevanilson de Barros [UNIFESP]
Orientadores
Carvalho, Aluizio Barbosa de [UNIFESP]
Tipo
Tese de doutorado
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Introdução: A patogênese da calcificação vascular (CV) na doença renal crônica é complexa e multifatorial. A aldosterona, através de sua ação no receptor mineralocorticoide, vem sendo reconhecida como um fator envolvido em vias osteoindutivas da CV. Estudos clínicos e experimentais têm demostrado que o uso da espironolactona está relacionado à prevenção da progressão da CV. Objetivo: Avaliar o efeito da espironolactona na progressão da calcificação coronariana (CCo) de pacientes em hemodiálise. Métodos: Pacientes com escore de cálcio coronariano (ECC) ≥ 30UA, avaliado por tomografia computadorizada de múltiplos detectores, foram randomizados em dois grupos: Grupo tratamento (Grupo GT, n=22) correspondendo aos pacientes que receberam espironolactona e Grupo controle (Grupo GC, n=23), aqueles que não sofreram intervenção medicamentosa e nem receberam placebo. O desfecho principal foi mudança percentual do ECC (progressão relativa), ao final do período de seguimento, que foi de 1 ano. Os pacientes foram avaliados mensalmente, através de consultas e coleta de exames laboratoriais. Ao final do estudo, foi realizada nova tomografia computadorizada, a fim de avaliar a progressão da CCo. Foram considerados progressores os pacientes com progressão relativa > 15% e não progressores aqueles ≤ 15%. Uma análise comparativa entre os pacientes que progrediram a CCo (Grupo PG) e os que não progrediram (Grupo NP) foi realizada. Resultados: Foram analisados dados de 35 pacientes que completaram o período de seguimento, sendo 18 no Grupo GT e 17 no Grupo GC. A progressão relativa do ECC foi semelhante em ambos os grupos, sendo de 21,5% e 27% nos grupos GT e GC, respectivamente. A grande maioria dos pacientes progrediram a CC, 61,1% no grupo GT e 70,6% no Grupo GC. Com relação aos exames laboratoriais, ao final do seguimento, observou-se um aumento do paratormônio intacto (p=0,035) e uma diminuição da esclerostina (p=0,002) no grupo GT. Entre os grupos, também ao final do estudo, a fosfatase alcalina total foi menor no Grupo GT quando comparado ao Grupo GC (p=0,002). O tratamento com espironolactona determinou um aumento da lipoproteína de alta densidade (HDL) no Grupo GT (p=0,007). No início do estudo, pacientes dos grupos PG e NP se diferenciaram pelo ECC, que foi menor no Grupo PG (p=0,002). No seguimento, os pacientes do grupo PG apresentaram maiores níveis de fósforo do que o grupo NP (p=0,016). O uso da espironolactona não determinou aumento na frequência de efeitos colaterais. Conclusões: O uso espironolactona não atenuou a progressão da CCo em pacientes submetidos à hemodiálise. O uso da espironolactona se mostrou seguro na população estudada. A hiperfosfatemia desempenha papel importante na progressão da CCo.
Introduction: The pathogenesis of vascular calcification (CV) in chronic kidney disease is complex and multifactorial. Aldosterone, through its action on the mineralocorticoid receptor, has been recognized as a factor involved in osteoinductive pathways of CV. Clinical and experimental studies have shown that the use of spironolactone is related to the prevention of CV progression. Objective: To evaluate the effect of spironolactone on the progression of coronary calcification (CC) in hemodialysis patients. Methods: Patients with a coronary calcium score (CCS) > 30 AU, evaluated by multiple-detector computed tomography, were randomized into two groups: treatment group (GT group, n=22) corresponding to patients receiving spironolactone and control group (GC group, n = 23), those who did not undergo drug intervention and did not receive placebo. The main outcome was a percentage change in CCS (relative progression), at the end of the follow-up period, which was one year. The patients were evaluated monthly, through consultations and collection of laboratory tests. At the end of the study, a new computer tomography was performed in order to evaluate the progression of CC. Patients with a relative progression rate> 15% were considered progressive and those not progressive were> 15%. A comparative analysis between the patients who progressed to the CC (group PG) and those who did not progress (group NP) was performed. Results: Data from 35 patients who completed the follow-up period were analyzed, being 18 in the GT group and 17 in the CG group. The relative progression of CCS was similar in both groups, being 21.5% and 27% in the GT and GC groups, respectively. The majority of the patients progressed to the CC, 61.1% in the GT group and 70.6% in the CG group. At the end of the follow-up, there was an increase in intact parathyroid hormone (p = 0.035) and a decrease in sclerostin (p = 0.002) in the GT group. Among the groups, also at the end of the study, total alkaline phosphatase was lower in the GT Group when compared to the GC Group (p = 0.002). Treatment with spironolactone determined an increase in high-density lipoprotein in the GT Group (p = 0.007). At the beginning of the study, patients in the PG and NP groups were differentiated by the CCS, which was lower in the PG group (p = 0.002). In the follow-up, patients in the PG group had higher levels of phosphorus than the NP group (p = 0.016). The use of spironolactone did not increase the frequency of side effects. Conclusions: The use of spironolactone did not attenuate the progression of the CC in patients undergoing hemodialysis. The use of spironolactone was safe in the study population. Hyperphosphatemia plays an important role in the progression of CC.
Introduction: The pathogenesis of vascular calcification (CV) in chronic kidney disease is complex and multifactorial. Aldosterone, through its action on the mineralocorticoid receptor, has been recognized as a factor involved in osteoinductive pathways of CV. Clinical and experimental studies have shown that the use of spironolactone is related to the prevention of CV progression. Objective: To evaluate the effect of spironolactone on the progression of coronary calcification (CC) in hemodialysis patients. Methods: Patients with a coronary calcium score (CCS) > 30 AU, evaluated by multiple-detector computed tomography, were randomized into two groups: treatment group (GT group, n=22) corresponding to patients receiving spironolactone and control group (GC group, n = 23), those who did not undergo drug intervention and did not receive placebo. The main outcome was a percentage change in CCS (relative progression), at the end of the follow-up period, which was one year. The patients were evaluated monthly, through consultations and collection of laboratory tests. At the end of the study, a new computer tomography was performed in order to evaluate the progression of CC. Patients with a relative progression rate> 15% were considered progressive and those not progressive were> 15%. A comparative analysis between the patients who progressed to the CC (group PG) and those who did not progress (group NP) was performed. Results: Data from 35 patients who completed the follow-up period were analyzed, being 18 in the GT group and 17 in the CG group. The relative progression of CCS was similar in both groups, being 21.5% and 27% in the GT and GC groups, respectively. The majority of the patients progressed to the CC, 61.1% in the GT group and 70.6% in the CG group. At the end of the follow-up, there was an increase in intact parathyroid hormone (p = 0.035) and a decrease in sclerostin (p = 0.002) in the GT group. Among the groups, also at the end of the study, total alkaline phosphatase was lower in the GT Group when compared to the GC Group (p = 0.002). Treatment with spironolactone determined an increase in high-density lipoprotein in the GT Group (p = 0.007). At the beginning of the study, patients in the PG and NP groups were differentiated by the CCS, which was lower in the PG group (p = 0.002). In the follow-up, patients in the PG group had higher levels of phosphorus than the NP group (p = 0.016). The use of spironolactone did not increase the frequency of side effects. Conclusions: The use of spironolactone did not attenuate the progression of the CC in patients undergoing hemodialysis. The use of spironolactone was safe in the study population. Hyperphosphatemia plays an important role in the progression of CC.