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Polycystic Kidney Disease and Renal Fibrosis

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Renal Fibrosis: Mechanisms and Therapies

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1165))

Abstract

Polycystic kidney disease (PKD) is a common genetic disorder characterized by formations of numerous cysts in kidneys and most caused by PKD1 or PKD2 mutations in autosomal dominant polycystic kidney disease (ADPKD). The interstitial inflammation and fibrosis is one of the major pathological changes in polycystic kidney tissues with an accumulation of inflammatory cells, chemokines, and cytokines. The immune response is observed across different stages and occurs prior to or coincident with cyst formation in ADPKD. Evidence for inflammation as an important contributor to cyst growth and fibrosis includes increased interstitial macrophages, upregulated expressions of pro-inflammatory cytokines, activated complement system, and activated pathways including NF-κB and JAK-STAT signaling in polycystic kidney tissues. Inflammatory cells are responsible for overproduction of several pro-fibrotic growth factors which promote renal fibrosis in ADPKD. These growth factors trigger epithelial mesenchymal transition and myofibroblast/fibrocyte activation, which stimulate the expansion of extracellular matrix (ECM) including collagen I, III, IV, V, and fibronectin, leading to renal fibrosis and reduced renal function. Besides, there are imbalanced ECM turnover regulators which lead to the increased ECM production and inadequate degradation in polycystic kidney tissues. Several fibrosis associated signaling pathways, such as TGFβ-SMAD, Wnt, and periostin–integrin-linked kinase are also activated in polycystic kidney tissues. Although the effective anti-fibrotic treatments are limited at the present time, slowing the cyst expansion and fibrosis development is very important for prolonging life span and improving the palliative care of ADPKD patients. The inhibition of pro-fibrotic cytokines involved in fibrosis might be a new therapeutic strategy for ADPKD in the future.

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  1. Division of Nephrology, Kidney Institute of PLA, Changzheng Hospital, Second Military Medical University, Shanghai, China

    Cheng Xue & Chang-Lin Mei

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  1. Cheng Xue
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  1. Zhongda Hospital, Southeast University School of Medicine, Southeast University, Nanjing, Jiangsu, China

    Bi-Cheng Liu

  2. Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, Hong Kong

    Hui-Yao Lan

  3. Zhongda Hospital, Southeast University School of Medicine, Southeast University, Nanjing, Jiangsu, China

    Lin-Li Lv

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Xue, C., Mei, CL. (2019). Polycystic Kidney Disease and Renal Fibrosis. In: Liu, BC., Lan, HY., Lv, LL. (eds) Renal Fibrosis: Mechanisms and Therapies. Advances in Experimental Medicine and Biology, vol 1165. Springer, Singapore. https://doi.org/10.1007/978-981-13-8871-2_5

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