Mechanisms of Acute Kidney Injury–Chronic Kidney Disease Transition: Unraveling Maladaptive Repair and Therapeutic Opportunities
Acute kidney injury (AKI) causes damage to the renal epithelium, initiating a reparative process intended to restore renal function. Although effective repair can result in the complete recovery of kidney function, this process is frequently incomplete. In instances where repair is unsuccessful, the...
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MDPI AG
2025-05-01
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| author | Dongxue Xu Xiaoyu Zhang Jingjing Pang Yiming Li Zhiyong Peng |
| author_facet | Dongxue Xu Xiaoyu Zhang Jingjing Pang Yiming Li Zhiyong Peng |
| author_sort | Dongxue Xu |
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| description | Acute kidney injury (AKI) causes damage to the renal epithelium, initiating a reparative process intended to restore renal function. Although effective repair can result in the complete recovery of kidney function, this process is frequently incomplete. In instances where repair is unsuccessful, the kidney experiences maladaptive alterations that may progressively result in chronic kidney disease (CKD), a phenomenon referred to as failed repair. This condition is precipitated by hypotensive, septic, or toxic insults, which initiate a series of pathophysiological processes, including microcirculatory dysfunction, the activation of inflammatory responses, and the death of tubular epithelial cells. These events collectively compromise renal function and trigger a complex repair response. This review provides a comprehensive examination of the multifactorial mechanisms underlying the initiation and progression of AKI, the regenerative pathways facilitating structural recovery in severely damaged kidneys, and the critical transition from adaptive repair to maladaptive remodeling. Central to this transition are mechanisms such as epigenetic reprogramming, G2/M cell-cycle arrest, cellular senescence, mitochondrial dysfunction, metabolism reprogramming, and cell death, which collectively drive the progression of CKD. These mechanistic insights offer a robust foundation for the development of targeted therapeutic strategies aimed at enhancing adaptive renal repair. |
| format | Article |
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| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
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| series | Biomolecules |
| spelling | doaj-art-3fce6f83e1124830b339ee5fa1bcd0a92025-08-20T03:27:21ZengMDPI AGBiomolecules2218-273X2025-05-0115679410.3390/biom15060794Mechanisms of Acute Kidney Injury–Chronic Kidney Disease Transition: Unraveling Maladaptive Repair and Therapeutic OpportunitiesDongxue Xu0Xiaoyu Zhang1Jingjing Pang2Yiming Li3Zhiyong Peng4Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, ChinaDepartment of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, ChinaDepartment of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, ChinaDepartment of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, ChinaDepartment of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, ChinaAcute kidney injury (AKI) causes damage to the renal epithelium, initiating a reparative process intended to restore renal function. Although effective repair can result in the complete recovery of kidney function, this process is frequently incomplete. In instances where repair is unsuccessful, the kidney experiences maladaptive alterations that may progressively result in chronic kidney disease (CKD), a phenomenon referred to as failed repair. This condition is precipitated by hypotensive, septic, or toxic insults, which initiate a series of pathophysiological processes, including microcirculatory dysfunction, the activation of inflammatory responses, and the death of tubular epithelial cells. These events collectively compromise renal function and trigger a complex repair response. This review provides a comprehensive examination of the multifactorial mechanisms underlying the initiation and progression of AKI, the regenerative pathways facilitating structural recovery in severely damaged kidneys, and the critical transition from adaptive repair to maladaptive remodeling. Central to this transition are mechanisms such as epigenetic reprogramming, G2/M cell-cycle arrest, cellular senescence, mitochondrial dysfunction, metabolism reprogramming, and cell death, which collectively drive the progression of CKD. These mechanistic insights offer a robust foundation for the development of targeted therapeutic strategies aimed at enhancing adaptive renal repair.https://www.mdpi.com/2218-273X/15/6/794AKICKDtransition mechanismstargeted therapeuticmaladaptive repair |
| spellingShingle | Dongxue Xu Xiaoyu Zhang Jingjing Pang Yiming Li Zhiyong Peng Mechanisms of Acute Kidney Injury–Chronic Kidney Disease Transition: Unraveling Maladaptive Repair and Therapeutic Opportunities Biomolecules AKI CKD transition mechanisms targeted therapeutic maladaptive repair |
| title | Mechanisms of Acute Kidney Injury–Chronic Kidney Disease Transition: Unraveling Maladaptive Repair and Therapeutic Opportunities |
| title_full | Mechanisms of Acute Kidney Injury–Chronic Kidney Disease Transition: Unraveling Maladaptive Repair and Therapeutic Opportunities |
| title_fullStr | Mechanisms of Acute Kidney Injury–Chronic Kidney Disease Transition: Unraveling Maladaptive Repair and Therapeutic Opportunities |
| title_full_unstemmed | Mechanisms of Acute Kidney Injury–Chronic Kidney Disease Transition: Unraveling Maladaptive Repair and Therapeutic Opportunities |
| title_short | Mechanisms of Acute Kidney Injury–Chronic Kidney Disease Transition: Unraveling Maladaptive Repair and Therapeutic Opportunities |
| title_sort | mechanisms of acute kidney injury chronic kidney disease transition unraveling maladaptive repair and therapeutic opportunities |
| topic | AKI CKD transition mechanisms targeted therapeutic maladaptive repair |
| url | https://www.mdpi.com/2218-273X/15/6/794 |
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