Failed Tubule Recovery, AKI-CKD Transition, and Kidney Disease Progression

被引:572
作者
Venkatachalam, Manjeri A. [1 ]
Weinberg, Joel M. [2 ,3 ]
Kriz, Wilhelm [4 ]
Bidani, Anil K. [5 ,6 ]
机构
[1] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA
[2] Vet Affairs Ann Arbor Healthcare Syst, Dept Med, Ann Arbor, MI USA
[3] Univ Michigan, Med Ctr, Ann Arbor, MI USA
[4] Heidelberg Univ, Med Fak Mannheim, Abt Anat & Entwicklungsbiol Mannheim, Med Fak Mannheim, Baden Wurttemberg, Germany
[5] Loyola Univ, Dept Med, Maywood, IL 60153 USA
[6] Hines Vet Affairs Hosp, Maywood, IL USA
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2015年 / 26卷 / 08期
关键词
ACUTE-RENAL-FAILURE; PERICYTE-MYOFIBROBLAST TRANSITION; ISCHEMIA-REPERFUSION INJURY; GROWTH-FACTOR-BETA; INTERSTITIAL FIBROSIS; PROXIMAL TUBULE; MASS REDUCTION; EPITHELIAL-CELLS; PERITUBULAR CAPILLARIES; ENDOTHELIAL INJURY;
D O I
10.1681/ASN.2015010006
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
The transition of AKI to CKD has major clinical significance. As reviewed here, recent studies show that a subpopulation of dedifferentiated, proliferating tubules recovering from AKI undergo pathologic growth arrest, fail to redifferentiate, and become atrophic. These abnormal tubules exhibit persistent, unregulated, and progressively increasing profibrotic signaling along multiple pathways. Paracrine products derived therefrom perturb normal interactions between peritubular capillary endothelium and pericyte-like fibroblasts, leading to myofibroblast transformation, proliferation, and fibrosis as well as capillary disintegration and rarefaction. Although signals from injured endothelium and inflammatory/immune cells also contribute, tubule injury alone is sufficient to produce the interstitial pathology required for fibrosis. Localized hypoxia produced by microvascular pathology may also prevent tubule recovery. However, fibrosis is not intrinsically progressive, and microvascular pathology develops strictly around damaged tubules; thus, additional deterioration of kidney structure after the transition of AKI to CKD requires new acute injury or other mechanisms of progression. Indeed, experiments using an acute-on-chronic injury model suggest that additional loss of parenchyma caused by failed repair of AKI in kidneys with prior renal mass reduction triggers hemodynamically mediated processes that damage glomeruli to cause progression. Continued investigation of these pathologic mechanisms should reveal options for preventing renal disease progression after AKI.
引用
收藏
页码:1765 / 1776
页数:12
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