Información de la revista
Vol. 35. Núm. 1.Enero 2015
Páginas 1-124
Vol. 35. Núm. 1.Enero 2015
Páginas 1-124
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Relación entre los niveles séricos de catepsina D y la disfunción endotelial en pacientes con enfermedad renal crónica
Relation between serum cathepsin D levels and endothelial dysfunction in patients with chronic kidney disease
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11867
Nihal Ozkayara, Serhan Piskinpasaa, Fatma Akyela, Didem Turguta, Mesudiye Buluta, Turan Turhanb, Fatih Dedea
a Department of Nephrology, Ankara Numune Education and Research Hospital, Ankara, Turkey,
b Department of Biochemistry and Medical Chemistry, Ankara Numune Education and Research Hospital, Ankara, Turkey,
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Este estudio se llevó a cabo con el objetivo de investigar el papel de la catepsina D, un mediador inflamatorio y aterosclerótico de la disfunción endotelial en la enfermedad renal crónica. En él, se incluyó a 65 pacientes con enfermedad renal crónica en los estadios 2-4 (35 mujeres y 30 hombres con una media de edad de 55,8 ± 15,6 años). Se calcularon los niveles séricos de creatinina y catepsina D así como la tasa de filtrado glomerular (TFG) y se midió el porcentaje de dilatación mediada por flujo (DMF) de la arteria braquial mediante angiografía y ecografía doppler bidimensional en color y en escala de grises. Se consideró que una DMF de ≤6% era indicativa de disfunción endotelial. La TFG media, la mediana de los niveles de creatinina y la mediana de los niveles de catepsina D fueron, respectivamente, 40,2 ± 11,2 mL/min/1,73 m2; 1,7 mg/dL; y 819,75 ng/mL. La disfunción endotelial afectaba a 30 de los 65 pacientes (46,2%). Entre los grupos con y sin disfunción endotelial, se observó una diferencia significativa en los niveles de catepsina D (p = 0,001) y creatinina (p = 0,03) así como correlaciones significativas y negativas entre el porcentaje de DMF de la arteria braquial y los niveles de catepsina D (r = −0,359, p = 0,003) y creatinina (r = −0,304, p = 0,014). La catepsina D, que se asocia a la aterosclerosis, tiene un papel importante en el proceso de disfunción endotelial. Es fundamental que se realicen otros estudios que puedan determinar la función exacta de la catepsina D en la disfunción endotelial y su valor como herramienta de diagnóstico temprano y como diana del tratamiento de enfermedades cardiovasculares en pacientes con enfermedad renal crónica.

Palabras clave:
Catepsina D
Palabras clave:
Disfunción endotelial
Palabras clave:
Enfermedad renal crónica (ERC)
Palabras clave:
Dilatación mediada por flujo de la arteria braquial

We aimed to investigate the role of cathepsin D, an inflammatory and atherosclerotic mediator, in endothelial dysfunction in chronic kidney disease. The study included 65 patients with stage 2–4 chronic kidney disease (35 females, 30 males; mean age, 55.8±15.6 years). Serum creatinine and cathepsin D levels and glomerular filtration rates (GFRs) were determined, and brachial flow-mediated dilation (FMD) percentage was measured by two-dimensional gray scale and color flow Doppler and vascular imaging. FMD ≤6% was considered to indicate endothelial dysfunction. Mean GFR, median creatinine levels, and median cathepsin D levels were 40.2±11.2mL/min/1.73m2, 1.7mg/dL, and 819.75ng/mL, respectively. Endothelial dysfunction was present in 30 of the 65 patients (46.2%). There was a significant difference between groups with and without endothelial dysfunction in terms of cathepsin D (p=0.001) and creatinine (p=0.03) levels, and negative and significant correlations were found between brachial artery FMD% and cathepsin D (r=−0.359, p=0.003) and creatinine (r=−0.304, p=0.014) levels. Cathepsin D, which is known to be associated with atherosclerosis, may play a role in the process of endothelial dysfunction. Further studies are essential to determine the exact function of cathepsin D in endothelial dysfunction in chronic kidney disease and to determine its value as a tool for early diagnosis and target for treatment of cardiovascular diseases in patients with chronic kidney disease.

Keywords:
Cathepsin D
Keywords:
Endothelial dysfunction
Keywords:
Chronic kidney disease (CKD)
Keywords:
Brachial flow-mediated dilation
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Bibliografía
[1]
Banerjee D, Contreras G, Jaraba I, Carvalho D, Ortega L, Carvalho C, et al. Chronic kidney disease stages 3-5 and cardiovascular disease in the veterans affairs population. Int Urol Nephrol 2009;41:443-51. [Pubmed]
[2]
Schiffrin EL, Lipman ML, Mann JF. Chronic kidney disease: effects on the cardiovascular system. Circulation 2007;116:85-97. [Pubmed]
[3]
Alsagaff MY, Thaha M, Aminuddin M, Yogiarto RM, Yogiantoro M, Tomino Y. Asymmetric dimethylarginine: a novel cardiovascular risk factor in end-stage renal disease. J Int Med Res 2012;40:340-9. [Pubmed]
[4]
Olechnowicz-Tietz S, Gluba A, Paradowska A, Banach M, Rysz J. The risk of atherosclerosis in patients with chronic kidney disease. Int Urol Nephrol 2013;45:1605-12. [Pubmed]
[5]
Lishmanov A, Dorairajan S, Pak Y, Chaudhary K, Chockalingam A. Elevated serum parathyroid hormone is a cardiovascular risk factor in moderate chronic kidney disease. Int Urol Nephrol 2012;44:541-7. [Pubmed]
[6]
Mordi I, Tzemos N. Is reversal of endothelial dysfunction still an attractive target in modern cardiology? World J Cardiol 2014;6:824-35. [Pubmed]
[7]
Vogel RA. Measurement of endothelial function by brachial artery flow-mediated vasodilatation. Am J Cardiol 2001;88(2A):31E-34E. [Pubmed]
[8]
Shechter M, Shechter A, Koren-Morag N, Feinberg MS, Hiersch L. Usefulness of brachial artery flow-mediated dilation to predict long-term cardiovascular events in subjects without heart disease. Am J Cardiol 2014;113:162-7. [Pubmed]
[9]
Tarro Genta F, Eleuteri E, Temporelli PL, Comazzi F, Tidu M, Bouslenko Z, et al. Flow-mediated dilation normalization predicts outcome in chronic heart failure patients. J Card Fail 2013;19:260-7. [Pubmed]
[10]
Lee MJ, Han SH, Lee JE, Choi HY, Yoon CY, Kim EJ, et al. Endothelial dysfunction is associated with major adverse cardiovascular events in peritoneal dialysis patients. Medicine (Baltimore) 2014;93:e73.
[11]
Kocak H, Gumuslu S, Sahin E, Ceken K, Ermis C, Gocmen AY, et al. Relationship between carotid artery intima-media thickness and brachial artery flow-mediated dilation in peritoneal dialysis patients. Int Urol Nephrol 2009;41:409-16. [Pubmed]
[12]
Recio-Mayoral A, Banerjee D, Streather C, Kaski JC. Atherosclerosis. Endothelial dysfunction, inflammation and atherosclerosis in chronic kidney disease--a cross-sectional study of predialysis, dialysis and kidney-transplantation patients. Atherosclerosis 2011;216:446-51. [Pubmed]
[13]
Benes P, Vetvicka V, Fusek M. Cathepsin D¿many functions of one aspartic protease. Crit Rev Oncol Hematol 2008;68:12-28. [Pubmed]
[14]
Duran MC, Martin-Ventura JL, Mohammed S, Barderas MG, Blanco-Colio LM, Mas S, et al. Atorvastatin modulates the profile of proteins released by human atherosclerotic plaques. Eur J Pharmacol 2007;562:119-29. [Pubmed]
[15]
Barderas MG, Dardé VM, de la Cuesta F, Martin-Ventura JL, Blanco-Colio LM, Jiménez-Narcher J, et al. Proteomic analysis of circulating monocytes identifies cathepsin D as a potential novel plasma marker of acute coronary syndromes. Clin Med Cardiol 2008;2:191-200.
[16]
Liu J, Sukhova GK, Sun JS, Xu WH, Libby P, Shi GP. Lysosomal cysteine proteases in atherosclerosis. Arterioscler Thromb Vasc Biol 2004;24:1359-66. [Pubmed]
[17]
Lutgens SP, Cleutjens KB, Daemen MJ, Heeneman S. Cathepsin cysteine proteases in cardiovascular disease. Faseb J 2007;21:3029-41. [Pubmed]
[18]
Moallem SA, Nazemian F, Eliasi S, Alamdaran SA, Shamsara J, Mohammadpour AH. Correlation between cathepsin D serum concentration and carotid intima-media thickness in hemodialysis patients. Int Urol Nephrol 2011;43:841-8. [Pubmed]
[19]
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al.; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann Intern Med 2009;150:604-12. [Pubmed]
[20]
Weiner DE, Tighiouart H, Amin MG, Stark PC, MacLeod B, Griffith JL, et al. Chronic kidney disease as a risk factor for cardiovascular disease and all-cause mortality: a pooled analysis of community-based studies. J Am Soc Nephrol 2004;15:1307-15. [Pubmed]
[21]
McCullough PA, Steigerwalt S, Tolia K, Chen SC, Li S, Norris KC, et al.; KEEP Investigators. Cardiovascular disease in chronic kidney disease: data from the Kidney Early Evaluation Program (KEEP). Curr Diab Rep 2011;11:47-55.
[22]
Wright J, Hutchison A. Cardiovascular disease in patients with chronic kidney disease. Vasc Health Risk Manag 2009,5:713-22. [Pubmed]
[23]
Landmesser U, Hornig B, Drexler H. Endothelial function: a critical determinant in atherosclerosis? Circulation 2004;109(21 Suppl 1):II27-33. [Pubmed]
[24]
Santoro D, Bellinghieri G, Conti G, Pazzano D, Satta E, Costantino G, et al. Endothelial dysfunction in chronic renal failure. J Ren Nutr 2010;20(5 Suppl):S103-8. [Pubmed]
[25]
Bolton CH, Downs LG, Victory JG, Dwight JF, Tomson CR, Mackness MI, et al. Endothelial dysfunction in chronic renal failure: roles of lipoprotein oxidation and pro-inflammatory cytokines. Nephrol Dial Transplant 2001;16:1189-97. [Pubmed]
[26]
Rajendran P, Rengarajan T, Thangavel J, Nishigaki Y, Sakthisekaran D, Sethi G, et al. The vascular endothelium and human diseases. Int J Biol Sci 2013;9:1057-69. [Pubmed]
[27]
Ghiadoni L, Cupisti A, Huang Y, Mattei P, Cardinal H, Favilla S, et al. Endothelial dysfunction and oxidative stress in chronic renal failure. J Nephrol 2004;17:512-9. [Pubmed]
[28]
Benes P, Vetvicka V, Fusek M. Cathepsin D--many functions of one aspartic protease. Crit Rev Oncol Hematol 2008;68:12-28. [Pubmed]
[29]
Hakala JK, Oksjoki R, Laine P, Du H, Grabowski GA, Kovanen PT, et al. Lysosomal enzymes are released from cultured human macrophages, hydrolyze LDL in vitro, and are present extracellularly in human atherosclerotic lesions. Arterioscler Thromb Vasc Biol 2003;23:1430-6. [Pubmed]
[30]
Haidar B, Kiss RS, Sarov-Blat L, Brunet R, Harder C, McPherson R, et al. Cathepsin D, a lysosomal protease, regulates ABCA1-mediated lipid efflux. J Biol Chem 2006;281:39971-81. [Pubmed]
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