State-of-the-art strategies for the prevention of progression of glomerular disease to renal insufficiency

In this review, we present recent developments i n t h e p a t h o l o g y o f p r o g r e s s i v e glomerulosclerosis. Insights are based on evidence provided predominantly by us. We also describe a novel approach for studying local blockades of the renin-angiotensin system (RAS) and the cyclooxygenase-dependent pathway, with the objective to ameliorate progressive glomerulosclerosis. This method involves an in vivo imaging system using confocal laser scan microscopy. Introduction The r ena l g lomeru lus , an a r t e r i a l microvasculature system, has been studied extensively, not only because it is a representative unit of physiological ultrafiltration but also in order to understand the mechanisms behind glomerular diseases, particularly progressive glomerulosclerosis, which can lead to “renal death.” The number of patients with chronic renal insufficiency who need hemodialysis or renal transplantation has been on the rise everywhere [1]. In 2003, of more than one million patients worldwide, 320,000 were in the United States of America and were receiving maintenance dialysis [2]. In Japan, the corresponding number of such patients was 275,000 patients. The annual costs for maintenance dialysis were calculated to be more than 1.2 billion yen in 2007 [3]. It has been suggested that glomerular hemodynamic changes or glomerular growth responses may trigger the development of glomerulosclerosis, irrespective of etiology [4,5]. However, the cellular and molecular mechanisms behind progressive glomerulosclerosis remain unclear. The ultimate aim for any nephrologist is to prevent the progression of glomerulosclerosis to renal insufficiency, and the regression of sclerotic lesions in progressive, chronic glomerular diseases, such as diabetic nephropathy and IgA nephritis [6]. A n i m a l m o d e l s f o r c l a r i f y i n g t h e pathophysiological mechanisms underlying the progression of glomerular disease to renal insufficiency We often use the rat as an experimental model, due to its suitability for pathophysiological or pharmacological research. Certain experimental rat models mimic irreversible human glomerulosclerosis. Of these, the 5/6 ablation State-of-the-art strategies for the prevention of progression of glomerular disease to renal insufficiency Takashi Oite, Tomizo Ohyama, Kikuo Ikegami, Takao Asai Department of Clinical Engineering and Medical Technology, Faculty of Medical Technology, Niigata University of Health and Welfare, Niigata, Japan