The Emerging Role of Innate Immunity in Chronic Kidney Diseases

Tang, Philip Chiu‐Tsun; Zhang, Yingying; Chan, Max Kam-Kwan; Lam, Winson Wing-Yin; Chung, Jeff Yat‐Fai; Kang, Wei; To, Ka‐Fai; Lan, Hui‐Yao; Tang, Patrick Ming‐Kuen

doi:10.3390/ijms21114018

Cited by 35 publications

(45 citation statements)

References 164 publications

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“…Binding of TNF-α to TNFR1 is reported to alter renal hemodynamics, reducing GFR and renal blood flow, while binding to TNFR2 signals for increased macrophage infiltration to the renal interstitium, ultimately leading to renal injury in the form of interstitial fibrosis and glomerulosclerosis [ 142 ]. This finding is in line with accumulating evidence that renal inflammation activates cells of the immune system, which plays a key role in pro-fibrotic mechanisms leading to ESRD [ 138 ].…”

Section: Middle Molecule Uremic Toxinssupporting

confidence: 88%

“…Mechanisms for the Progression of CKD CKD presents as a low grade, persistent, chronic inflammatory state. Research has focused on unravelling the complex role of innate and adaptive immunity in the sustained inflammatory milieu that ultimately leads to renal fibrosis and ESRD [138]. It has been documented that HD patients have elevated levels of TNF-α and IL-6, as they are not effectively cleared due to size restrictions of traditional dialytic membranes [139].…”

Section: Tumor Necrosis Factor Alphamentioning

confidence: 99%

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Uremic Toxins in the Progression of Chronic Kidney Disease and Cardiovascular Disease: Mechanisms and Therapeutic Targets

Lim

Sidor

Tonial

et al. 2021

Toxins

165

110

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Chronic kidney disease (CKD) is a progressive loss of renal function. The gradual decline in kidney function leads to an accumulation of toxins normally cleared by the kidneys, resulting in uremia. Uremic toxins are classified into three categories: free water-soluble low-molecular-weight solutes, protein-bound solutes, and middle molecules. CKD patients have increased risk of developing cardiovascular disease (CVD), due to an assortment of CKD-specific risk factors. The accumulation of uremic toxins in the circulation and in tissues is associated with the progression of CKD and its co-morbidities, including CVD. Although numerous uremic toxins have been identified to date and many of them are believed to play a role in the progression of CKD and CVD, very few toxins have been extensively studied. The pathophysiological mechanisms of uremic toxins must be investigated further for a better understanding of their roles in disease progression and to develop therapeutic interventions against uremic toxicity. This review discusses the renal and cardiovascular toxicity of uremic toxins indoxyl sulfate, p-cresyl sulfate, hippuric acid, TMAO, ADMA, TNF-α, and IL-6. A focus is also placed on potential therapeutic targets against uremic toxicity.

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Section: Middle Molecule Uremic Toxinssupporting

confidence: 88%

Section: Tumor Necrosis Factor Alphamentioning

confidence: 99%

Uremic Toxins in the Progression of Chronic Kidney Disease and Cardiovascular Disease: Mechanisms and Therapeutic Targets

Lim

Sidor

Tonial

et al. 2021

Toxins

165

110

View full text Add to dashboard Cite

show abstract

“…Decrease of the phagocytic capacity of macrophages impacts negatively the kidney function and produces a chronic inflammation status ( 40 ). Innate immunity keeps a crucial potential in many renal diseases ( 41 ).…”

Section: Introductionmentioning

confidence: 99%

Focus on the Gut–Kidney Axis in Health and Disease

et al. 2021

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The recent new developments in technology with culture-independent techniques including genome sequencing methodologies shed light on the identification of microbiota bacterial species and their role in health and disease. Microbiome is actually reported as an important predictive tool for evaluating characteristic shifts in case of disease. Our present review states the development of different renal diseases and pathologies linked to the intestinal dysbiosis, which impacts on host homeostasis. The gastrointestinal–kidney dialogue provides intriguing features in the pathogenesis of several renal diseases. Without any doubt, investigation of this interconnection consists one of the most cutting-edge areas of research with potential implications on our health.

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“…Although numerous studies have been published on CRF, effective drugs available for clinical treatment are very limited in supply [15,16]. Treatment of CRF by TCM has elicited positive results, however, and this approach has led to a diversi cation of treatment methods, broadening developmental prospects for therapy [17].…”

Section: Fig 9 Discussionmentioning

confidence: 99%

Preliminary study of the mechanism underlying how Jianshen Granules ameliorate renal failure in 5/6 nephrectomy model rats

Zhang²,

Kong³

et al. 2020

Preprint

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Background: Chronic renal failure (CRF) is a worldwide public health concern, and at present, there are limited treatment options available. Jianshen Granules, a traditional Chinese herbal medicine, have been used clinically in the treatment of renal diseases for a large number of years in the Air Force Medical Center of the Chinese People's Liberation Army (PLA), and have shown great efficacy. In the present study, both the effectiveness and the mechanism of action of Jianshen Granules to treat CRF were investigated. Methods: A rat model of CRF was established by 5/6 nephrectomy. Rats were administered with distilled water, Uremic Clearance Granules (UCGs), or Jianshen Granules. During the administration period, the physiological state of the rats was observed, and the biochemical parameters of interest were measured. The pathology of the kidney tissues were assessed using hematoxylin and eosin (H.E.), and Masson’s staining. In addition, the expression level of transforming growth factor‑β1 (TGF‑β1) was detected. Human kidney cells (HKC cells) were used to investigate the effects of Jianshen Granules on apoptosis induced by hydrogen peroxide (H2O2), whereas cell viability was assessed by Cell Counting Kit‑8 (CCK‑8) assay. The level of apoptosis, the mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) and Ca2 + levels were measured using a flow cytometry. Results: The results revealed that Jianshen Granules could reduce the levels of serum creatinine, blood urea nitrogen, alanine aminotransferase and aspartate aminotransferase, and the volume of urine in CRF rats. Renal histopathological examinations revealed that Jianshen Granules had an ameliorative effect on renal injury. In addition, Jianshen Granules led to a marked decrease in TGF‑β1 levels in CRF rats. Following treatment with Jianshen Granules, cell viability and the level of the MMP increased, whereas the levels of ROS and Ca2+ were reduced significantly. The increased level of TGF‑β1 was detected in the H2O2‑treated group, although this increase was attenuated by treatment with Jianshen Granules. Conclusion: Taken together, the results of the present study have shown that Jianshen Granules are able to ameliorate renal failure in CRF rats, and to inhibit apoptosis of HKC cells induced by H2O2 via downregulation of TGF‑β1.

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The Emerging Role of Innate Immunity in Chronic Kidney Diseases

Cited by 35 publications

References 164 publications

Uremic Toxins in the Progression of Chronic Kidney Disease and Cardiovascular Disease: Mechanisms and Therapeutic Targets

Uremic Toxins in the Progression of Chronic Kidney Disease and Cardiovascular Disease: Mechanisms and Therapeutic Targets

Focus on the Gut–Kidney Axis in Health and Disease

Preliminary study of the mechanism underlying how Jianshen Granules ameliorate renal failure in 5/6 nephrectomy model rats

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