สำนักราชบัณฑิตยสภา

The Journal of the Royal Institute of Thailand Vol. 27 No. 1 Jan.-Mar. 2002 “√Õπÿ ¡Ÿ ≈‡ √’ º‘ ¥ª√°µ‘ À≈Õ¥‡≈◊ Õ¥‰µÀ¥µ— « ·≈–°“√∑”≈“¬‰µ ÒˆÙ Abstract Hemodynamic Maladjustment in Progression of Renal Disease Narisa Futrakul, Piyaratana Tosukhowong, Yuvadee Valyapongpichit, Numdee Tipprukmas, Sathis Sirisuigh, Pridavan Chaisuriya, Suthiluk Patumraj, Prasit Futrakul* *Fellow, the Academy of Science, the Royal Institute, Thailand Although the pathogenetic mechanism of renal disease progression remains enigmatic, there is accumulative evidence to imply that microvascular injury in the renal circulation is likely to deter- mine nephronal damage, namely glomerulosclerosis and tubulointerstitial fibrosis. In this regard, maladjustment of the glomerular microcirculation secondary to glomerular endothelial cell dysfunc- tion is believed to be the trigger of such injury. An enhanced release of vasoconstrictors such as angiotensin II, endothelin and thromboxane A2 due to glomerular endothelial dysfunction induces a preferential vasoconstriction of the efferent arteriole by which it raises not only intraglomerular pressure but also an exaggeratedly reduced peritubular capillary flow, which supplies the tubulo- interstitial compartment. The increased intraglomerular pressure in the presence of increased intrarenal resistance, if persisting long enough, would induce intraglomerular injury with subse- quent development of glomerulosclerosis, whereas a sustained reduction in peritubular capillary flowwould induce injury to the tubulointerstitial structure, with subsequent development of tubulo- interstitial fibrosis. It is perceived that there is an inverse relationship between renal perfusion and nephronal injury: the lower the reduction in renal perfusion, the greater the intensity of glomerulo- sclerosis and tubulointerstitial fibrosis. This also implies that there is a progressive reduction in renal perfusion as the disease severity progresses. The progressive reduction in renal perfusion uniquely observed in chronic renal disease sug- gests that there may be certain toxic factor(s) in the circulation that are capable of inducing a sponta- neous endothelial cell injury. In this regard, an in vitro study indeed indicates that sera from chronic renal patients can induce endothelial cell cytotoxicity. Further study to identify such factor(s) ren- ders a supportive view that an oxidant - antioxidant imbalance is likely, at least in part, to be respon- sible for spontaneous glomerular endothelial cytotoxicity. A correction of both hemodynamic mal- adjustment and oxidant - antioxidant imbalance is capable of not only of retarding the renal disease progression but also of improving renal function. Key words : oxidant, anti-oxidant, hemodynamic maladjustment, endothetial cytotoxicity