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소아청소년기 당뇨병성 신병증 (II) ; 병리 소견 및 병태생리를 중심으로

Diabetic Nephropathy in Childhood and Adolescence (II) ; Pathology and Pathophysiology

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키워드

주제분류소아과학

초록

당뇨병성 신병증은 최근 우리나라를 포함한 서구 사회에서는 만성 신부전의 가장 많은 원인 중 하나이며, 꾸준히 증가추세이다. 조직학적으로는, 사구체, 세뇨간질, 소동맥 등 신장의 주요 부위에 병변이 나타나는데, 특징적으로 사구체 기저막의 비후와 족세포의 변화와 함께 사구체 경화, 소동맥의 유리질 경화와 세뇨간질 부위에 섬유화 등이 나타난다. 당뇨병성 신병증은 혈역학적 인자들과 대사성 인자들 간의 복잡한 상호작용의 결과로 일어난다. 고혈당은 혈류역학적 요소로 고혈압과 함께 사구체내압의 증가와 혈관활성물질의 활성화에 함께, 비혈역학적 경로들, 예를 들면, 후기 당화합 최종생성물 생성, 세포 내 신호전달체계와 물질, 시토카인, 산화 스트레스 등 다양한 원인들을 활성화시킨다. 이러한 대사적, 혈류역학적인 인자들은 신장의 알부민 투과성을 증가시키고 세포 외 기질의 축적을 일으키며 결과적으로 증가된 단백뇨, 사구체경화와 세뇨관간질의 섬유화를 일으키게 된다.

Abstract

Diabetic nephropathy is a major cause of chronic renal failure in developing countries, and the prevalence rate has markedly increased during the past decade. Diabetic nephropathy shows various specific histological changes not only in the glomeruli but also in the tubulointerstitial region. In the early stage, the effacement of podocyte foot processes and thickened glomerular basement membrane (GBM) is noticed even at the stage of microalbuminuria. Nodular, diffuse, and exudative lesions, so-called diabetic glomerulosclerosis, are well known as glomerular lesions. Interstitial lesions also exhibit fibrosis, edema, and thickened tubular basement membrane. Diabetic nephropathy is considered to be multifactorial in origin with increasing evidence that one of the major pathways involved in the development and progression of diabetic nephropathy as a result of hyperglycemia. Hyperglycemia induces renal damage directly or through hemodynamic alterations, such as, glomerular hyperfiltration, shear stress, and microalbuminuria. Chronic hyperglycemia also induces nonhemodynamic dysregulations, such as, increased production of advanced glycosylation endproducts, oxidative stress, activation of signal pathway, and subsequent various cytokines. Those pathogenic mechanisms resulted in extracellular matrix deposition including mesangial expansion and GBM thickening, glomerular hypertrophy, inflammation, and proteinuria. In this review, recent opinions on the histopathologic changes and pathophysiologic mechanisms leading to initiation and progression of diabetic nephropathy will be introduced.

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