ปีที่ ๓๒ ฉบับที่ ๓ กรกฎาคม-กันยายน ๒๕๕๐

«“√ “√ √“™∫— ≥±‘ µ¬ ∂“π π√‘ “ øŸ µ√–°Ÿ ≈ ·≈–§≥– 569 ªï ∑’Ë ÛÚ ©∫— ∫∑’Ë Û °.§.-°.¬. Úıı Abstract Vascular Repair in Chronic Kidney Disease Narisa Futrakul Department of Physiology, King Chulalongkorn Memorial Hospital Monnipha Sila-asna Institute of Research and Development of Science and Technology, Mahidol University Prasit Futrakul Visith Sitprija Fellow of the Academy of Science, The Royal Institute, Thailand Anond Bunjaratavej Associate Fellow of the Academy of Science, The Royal Institute, Thailand Much evidence renders support that renal microvascular disease is the crucial deter- minant of tubulointerstitial fibrosis and renal disease progression. Renal microvascular disease in chronic kidney disease represents an imbalance in vascular homeostasis due to enhanced vascular injury and a defective vascular repair. Vascular injury is due to enhanced activity of circulating toxins such as oxidative stress and immunocirculatory imbalance, which induces glomerular endothelial injury. Glomerular endothelial injury is an insidious, continuously progressive and subclinical, which is substantiated by enhanced circulatory endothelial cell enumeration, and endothelial cell cytotoxicity tests. In addition to glomerular endothelial injury, a dysfunctioning glomerular endothelium can be attested by intrarenal hemodynamic study, which reveals a preferential constriction of the efferent arteriole so called the hemodynamic maladjustment. Such constriction induces a sustained and progressive reduction in peritubular capillary flow, chronic ischemic injury to the tubulointerstitium, and eventually tubulointerstitial fibrosis. Vascular repair is impaired in chronic kidney disease. Multiple defects are encountered namely defective vascular endothelial growth factor, defective endothelial progenitor cell, and impaired nitric oxide production. Impaired endothelial progenitor cell in conjunction with impaired nitric oxide production, culminate in default angiogenesis. Taken together, enhanced vascular injury in the presence of defective vascular repair induces a sustained and progressive renal microvascular disease which has continuously damaged the nephronal structure. Under the present practice associated with delayed diagnosis and inappropriate therapy with conventional strategy, the hemodynamic maladjustment is inappropriately corrected, and ineffectively prevents the renal disprogression towards end-stage renal disease. Key words : vascular homeostasis, oxidative stress, endothelial progenitor cell, hemodynamic maladjustment, VEGF Ò. Futrakul N, Butthep P, Patumraj S, Siriviriyakul S, Futrakul P. Microvascu- lar disease and endothelial dysfunction inchronic kidney diseases : Therapeutic implication. Clin Hemorheol Microcirc 2006; 34: 265-371. ÒÒ. Futrakul N, Sila-asna M, Futrakul P. A default angiogenesis in chronic kid- ney disease. Clin Hemorheol Microcirc (in press). ÒÚ. Futrakul N, Chaivatanarat T, Futrakul P, et al. Peritubular capillary flow determines tubulointerstitial disease in idiopathic nephrotic syndrome. Ren Fail 2000; 22: 329-335.