Nodular lesions and mesangiolysis in diabetic nephropathy
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REVIEW ARTICLE
Nodular lesions and mesangiolysis in diabetic nephropathy Takashi Wada • Miho Shimizu • Hitoshi Yokoyama Yasunori Iwata • Yoshio Sakai • Shuichi Kaneko • Kengo Furuichi
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Received: 7 May 2012 / Accepted: 1 October 2012 Ó Japanese Society of Nephrology 2012
Abstract Diabetic nephropathy is a leading cause of end-stage renal failure all over the world. Advanced human diabetic nephropathy is characterized by the presence of specific lesions including nodular lesions, doughnut lesions, and exudative lesions. Thus far, animal models precisely mimicking advanced human diabetic nephropathy, especially nodular lesions, remain to be fully established. Animal models with spontaneous diabetic kidney diseases or with inducible kidney lesions may be useful for investigating the pathogenesis of diabetic nephropathy. Based on pathological features, we previously reported that diabetic glomerular nodular-like lesions were formed during the reconstruction process of mesangiolysis. Recently, we established nodular-like lesions resembling those seen in advanced human diabetic nephropathy through vascular Presented at the 41st Western Regional Meeting of the Japanese Society of Nephrology. T. Wada (&) M. Shimizu Y. Iwata K. Furuichi Division of Nephrology, Kanazawa University Hospital, 13-1 Takara-machi, Kanazawa 920-8641, Japan e-mail: [email protected] T. Wada Y. Iwata Y. Sakai Department of Laboratory Medicine, Kanazawa University, Kanazawa, Japan M. Shimizu S. Kaneko K. Furuichi Department of Disease Control and Homeostasis, Kanazawa University, Kanazawa, Japan H. Yokoyama Division of Nephrology, Kanazawa Medical University, Uchinada, Japan K. Furuichi Division of Blood Purification, Kanazawa University Hospital, Kanazawa, Japan
endothelial injury and mesangiolysis by administration of monocrotaline. Here, in this review, we discuss diabetic nodular lesions and its animal models resembling human diabetic kidney lesions, with our hypothesis that endothelial cell injury and mesangiolysis might be required for nodular lesions. Keywords Diabetic nephropathy Nodular lesion Mesangiolysis Glomerulosclerosis Extracellular matrix Matrix metalloproteinase
Introduction The number of patients with chronic kidney disease (CKD) on dialysis due to diabetic nephropathy is increasing worldwide. In Japan, the annual incidence of starting dialysis due to diabetic nephropathy has been in first place since 1998, indicating diabetic nephropathy as one of the most important causes of end-stage kidney disease. In clinical settings, insights for functional–pathological relationships in diabetic nephropathy are required for better prognosis. Generally speaking, it appears that in patients with type 2 diabetes, kidney structural changes are more heterogenous and diabetic glomerulopathy lesions are less severe than in type 1 diabetes patients with similar urine albumin levels [1]. The presence of persistent albuminuria is the hallmark of clinical diagnosis of diabetic nephropathy [1, 2]. However, some type 2 dia
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