scholarly journals Lymphocytes: Versatile Participants in Acute Kidney Injury and Progression to Chronic Kidney Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Chujin Cao ◽  
Ying Yao ◽  
Rui Zeng
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Renal Injury ◽  
Renal Fibrosis ◽  
Kidney Injury ◽  
Renal Parenchyma ◽  
Health Concern ◽  
High Morbidity ◽  
Parenchyma Cells

Background: Acute kidney injury (AKI) remains a major global public health concern due to its high morbidity and mortality. The progression from AKI to chronic kidney disease (CKD) makes it a scientific problem to be solved. However, it is with lack of effective treatments.Summary: Both innate and adaptive immune systems participate in the inflammatory process during AKI, and excessive or dysregulated immune responses play a pathogenic role in renal fibrosis, which is an important hallmark of CKD. Studies on the pathogenesis of AKI and CKD have clarified that renal injury induces the production of various chemokines by renal parenchyma cells or resident immune cells, which recruits multiple-subtype lymphocytes in circulation. Some infiltrated lymphocytes exacerbate injury by proinflammatory cytokine production, cytotoxicity, and interaction with renal resident cells, which constructs the inflammatory environment and induces further injury, even death of renal parenchyma cells. Others promote tissue repair by producing protective cytokines. In this review, we outline the diversity of these lymphocytes and their mechanisms to regulate the whole pathogenic stages of AKI and CKD; discuss the chronological responses and the plasticity of lymphocytes related to AKI and CKD progression; and introduce the potential therapies targeting lymphocytes of AKI and CKD, including the interventions of chemokines, cytokines, and lymphocyte frequency regulation in vivo, adaptive transfer of ex-expanded lymphocytes, and the treatments of gut microbiota or metabolite regulations based on gut-kidney axis.Key Message: In the process of AKI and CKD, T helper (Th) cells, innate, and innate-like lymphocytes exert mainly pathogenic roles, while double-negative T (DNT) cells and regulatory T cells (Tregs) are confirmed to be protective. Understanding the mechanisms by which lymphocytes mediate renal injury and renal fibrosis is necessary to promote the development of specific therapeutic strategies to protect from AKI and prevent the progression of CKD.

scholarly journals PGC1α in the kidney

2018 ◽  
Vol 314 (1) ◽  
pp. F1-F8 ◽  
Author(s):  
Matthew R. Lynch ◽  
Mei T. Tran ◽  
Samir M. Parikh
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Renal Fibrosis ◽  
Diabetic Kidney Disease ◽  
Kidney Injury ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Relationship ◽  
Prime Target

Acute kidney injury (AKI) arising from diverse etiologies is characterized by mitochondrial dysfunction. The peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC1α), a master regulator of mitochondrial biogenesis, has been shown to be protective in AKI. Interestingly, reduction of PGC1α has also been implicated in the development of diabetic kidney disease and renal fibrosis. The beneficial renal effects of PGC1α make it a prime target for therapeutics aimed at ameliorating AKI, forms of chronic kidney disease (CKD), and their intersection. This review summarizes the current literature on the relationship between renal health and PGC1α and proposes areas of future interest.

scholarly journals Acute kidney injury pathology and pathophysiology: a retrospective review

2020 ◽  
Author(s):  
Joseph P Gaut ◽  
Helen Liapis
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Renal Function ◽  
Kidney Disease ◽  
Renal Biopsy ◽  
Retrospective Review ◽  
Patient Management ◽  
Kidney Injury ◽  
High Morbidity ◽  
Underlying Pathology

Abstract Acute kidney injury (AKI) is the clinical term used for decline or loss of renal function. It is associated with chronic kidney disease (CKD) and high morbidity and mortality. However, not all causes of AKI lead to severe consequences and some are reversible. The underlying pathology can be a guide for treatment and assessment of prognosis. The Kidney Disease: Improving Global Outcomes guidelines recommend that the cause of AKI should be identified if possible. Renal biopsy can distinguish specific AKI entities and assist in patient management. This review aims to show the pathology of AKI, including glomerular and tubular diseases.

scholarly journals Inhibition of PTEN Activity Aggravates Post Renal Fibrosis in Mice with Ischemia Reperfusion-Induced Acute Kidney Injury

2017 ◽  
Vol 43 (5) ◽  
pp. 1841-1854 ◽  
Author(s):  
Jun Zhou ◽  
Jiying  Zhong ◽  
Sen  Lin ◽  
Zhenxing Huang ◽  
Hongtao Chen ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Renal Fibrosis ◽  
Smooth Muscle Actin ◽  
Ischemia Reperfusion ◽  
Specific Inhibitor ◽  
Kidney Injury ◽  
Control Group ◽  
Kidney Fibrosis

Background: Renal fibrosis is a common pathophysiological feature of chronic kidney disease. Acute kidney injury (AKI) is defined as an independent causal factor of chronic kidney disease, with a pathological representation of post renal fibrosis. However, the etiopathogenesis underlying post renal fibrosis induced by AKI is not completely understood. Methods: BALB/c mice were treated with bpv or vehicle controls and were, respectively, the ischemia reperfusion (IR) model group and control group. All of the animals had blood taken from the orbital venous plexus at 24 hours after IR. Six mice in each group were randomly chosen and euthanized 7 days after IR treatment, and the remaining six mice in each group were euthanized 14 days after IR treatment. We examined the effect on post kidney fibrosis of inhibiting PTEN activity in mice in an IR induced AKI experimental model. Results: Compared with vehicle mice, bpv-(PTEN specific inhibitor) treated mice accumulated more bone marrow-derived fibroblasts and myofibroblasts in the kidneys. Inhibition of PTEN activity increased the expression of α-smooth muscle actin and extracellular matrix proteins and post kidney fibrosis. Furthermore, inhibition of PTEN activity resulted in more inflammatory cytokines in the kidneys of mice subjected to IR-induced renal fibrosis. Moreover, inhibition of PTEN activity up-regulated PI3K protein expression and Akt phosphorylation. Conclusions: Our study demonstrated that PTEN played an important role in post renal fibrosis in mice with ischemia reperfusion-induced AKI. These results indicated that the PTEN/PI3K/Akt signaling pathway may serve as a novel therapeutic target for AKI-induced chronic kidney disease.

scholarly journals P0547THE DELETION OF AKT1 ATTENUATES RENAL FIBROSIS AND TUBULAR EPITHELIAL-MESENCHYMAL TRANSITION DURING ACUTE KIDNEY INJURY TO CHRONIC KIDNEY DISEASE PROGRESSION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Byung Min Ye ◽  
Il Young Kim ◽  
Min Jeong Kim ◽  
Soo Bong Lee ◽  
Dong Won Lee ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Renal Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Kidney Injury ◽  
Wild Type ◽  
Ckd Progression ◽  
Mesenchymal Transition ◽  
Tgf Β1

Abstract Background and Aims Acute kidney injury (AKI) is an underestimated, yet important risk factor for the development of chronic kidney disease (CKD), which is characterized by the tubulointerstitial fibrosis and tubular epithelial-mesenchymal transition (EMT). Akt has been reported to be involved in renal fibrosis and EMT. Thus, we investigated the role of Akt1, one of the three Akt isoforms, in the murine model of AKI to CKD progression. Method We subjected the wild type and Akt1−/− mice to unilateral ischemia-reperfusion injury (UIRI). UIRI was induced by clamping the left renal artery for 30 min followed by reperfusion. After 6 weeks of UIRI, the renal fibrosis and EMT were assessed by histology, immunohistochemistry, and western blot. Results After 6 weeks after UIRI, we found that Akt1, not Akt2 or Akt3, was activated in UIRI-kidney. The tubulointerstitial fibrosis was significantly alleviated in Akt1−/− mice compared with the wild type (WT) mice. Besides, the deletion of Akt1 decreased the expression of the vimentin and α-SMA and increased the expression of E-cadherin, indicating the suppression of tubular EMT. However, there was no difference in the activity of TGF-β1/Smad signalling, which is the potent inducer of renal fibrosis and EMT, between WT mice and Akt1−/− mice. The deletion of Akt1 also increased the GSK-3β activity and decreased the expression of β-catenin, Snail, and twist1. Conclusion Our findings demonstrate that the deletion of Akt1 attenuates the renal fibrosis and tubular EMT independently of TGF-β1/Smad signalling during the AKI to CKD progression. Akt1 may be the therapeutic target against the AKI to CKD progression.

scholarly journals Role of SIK1 in the transition of acute kidney injury into chronic kidney disease

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jinxiu Hu ◽  
Jiao Qiao ◽  
Qun Yu ◽  
Bing Liu ◽  
Junhui Zhen ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Transcription Factor ◽  
Kidney Disease ◽  
Kidney Injury ◽  
High Morbidity ◽  
Mesenchymal Transition ◽  
Immunohistochemistry Staining ◽  
Hk2 Cells

Abstract Background Acute kidney injury (AKI), with a high morbidity and mortality, is recognized as a risk factor for chronic kidney disease (CKD). AKI-CKD transition has been regarded as one of the most pressing unmet needs in renal diseases. Recently, studies have showed that salt inducible kinase 1 (SIK1) plays a role in epithelial-mesenchymal transition (EMT) and inflammation, which are the hallmarks of AKI-CKD transition. However, whether SIK1 is involved in AKI-CKD transition and by what mechanism it regulates AKI-CKD transition remains unknown. Methods We firstly detected the expression of SIK1 in kidney tissues of AKI patients and AKI mice by immunohistochemistry staining, and then we established Aristolochic acid (AA)-induced AKI-CKD transition model in C57BL/6 mice and HK2 cells. Subsequently, we performed immunohistochemistry staining, ELISA, real-time PCR, Western blot, immunofluorescence staining and Transwell assay to explore the role and underlying mechanism of SIK1 on AKI-CKD transition. Results The expression of SIK1 was down-regulated in AKI patients, AKI mice, AA-induced AKI-CKD transition mice, and HK2 cells. Functional analysis revealed that overexpression of SIK1 alleviated AA-induced AKI-CKD transition and HK2 cells injury in vivo and in vitro. Mechanistically, we demonstrated that SIK1 mediated AA-induced AKI-CKD transition by regulating WNT/β-catenin signaling, the canonical pathway involved in EMT, inflammation and renal fibrosis. In addition, we discovered that inhibition of WNT/β-catenin pathway and its downstream transcription factor Twist1 ameliorated HK2 cells injury, delaying the progression of AKI-CKD transition. Conclusions Our study demonstrated, for the first time, a protective role of SIK1 in AKI-CKD transition by regulating WNT/β-catenin signaling pathway and its downstream transcription factor Twist1, which will provide novel insights into the prevention and treatment AKI-CKD transition in the future.

scholarly journals Epigenetic Modification Drives Acute Kidney Injury-to-Chronic Kidney Disease Progression

Nephron ◽  
2021 ◽  
pp. 1-11
Author(s):  
Zhenzhen Li ◽  
Ningning Li
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Structural Damage ◽  
Epigenetic Modification ◽  
Kidney Injury ◽  
Epigenetic Modifications ◽  
High Morbidity ◽  
Inflammatory Factor

Acute kidney injury (AKI) is a common clinical critical disease. Due to its high morbidity, increasing risk of complications, high mortality rate, and high medical costs, it has become a global concern for human health problems. Initially, researchers believed that kidneys have a strong ability to regenerate and repair, but studies over the past 20 years have found that kidneys damaged by AKI are often incomplete or even unable to repair. Even when serum creatinine returns to baseline levels, renal structural damage persists for a long time, leading to the development of chronic kidney disease (CKD). The mechanism of AKI-to-CKD transition has not been fully elucidated. As an important regulator of gene expression, epigenetic modifications, such as histone modification, DNA methylation, and noncoding RNAs, may play an important role in this process. Alterations in epigenetic modification are induced by hypoxia, thus promoting the expression of inflammatory factor-related genes and collagen secretion. This review elaborated the role of epigenetic modifications in AKI-to-CKD progression, the diagnostic value of epigenetic modifications biomarkers in AKI chronic outcome, and the potential role of targeting epigenetic modifications in the prevention and treatment of AKI to CKD, in order to provide ideas for the subsequent establishment of targeted therapeutic strategies to prevent the progression of renal tubular-interstitial fibrosis.

scholarly journals MicroRNA-874-3p/ADAM (A Disintegrin and Metalloprotease) 19 Mediates Macrophage Activation and Renal Fibrosis After Acute Kidney Injury

Hypertension ◽  
2021 ◽  
Vol 77 (5) ◽  
pp. 1613-1626
Author(s):  
Junni Wang ◽  
Wanyun Nie ◽  
Xishao Xie ◽  
Mengqiu Bai ◽  
Yanhong Ma ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Renal Fibrosis ◽  
Kidney Injury ◽  
Macrophage Infiltration ◽  
Luciferase Reporter ◽  
Type I ◽  
Ccl2 Level ◽  
Chronic Model

Inflammation and maladaptive repair play a crucial role in the development of chronic kidney disease and hypertension after acute kidney injury. To study the mechanisms involved in acute kidney injury-to-chronic kidney disease transition, we established a chronic renal fibrosis mouse model that was triggered by an initial ischemia/reperfusion–induced acute kidney injury (acute-chronic model). Downregulation of microRNA-874-3p during renal fibrosis was identified by a genome-wide RNA-sequencing and was further confirmed in cell-based assays, mouse models, and human samples. Overexpression of microRNA-874-3p in the kidneys markedly alleviated renal fibrosis, accompanied with decreased infiltrated macrophages and expression of α-smooth muscle actin, type I collagen, fibronectin, CCL (C-C motif chemokine ligand) 2, and ADAM (A Disintegrin and Metalloprotease) 19. ADAM19 is a target gene of microRNA-874-3p as shown by luciferase reporter assays and was upregulated in the acute-chronic model. Overexpression of ADAM19 directly induced the expression of fibrotic genes, CCL2, and macrophage infiltration in vivo. Depletion of macrophages using clodronate liposomes ameliorated the fibrogenic effects of ADAM19. Overexpression of ADAM19 also induced accumulation of the Notch1 intracellular domain, an upstream regulator of CCL2 expression, whereas Notch1 pathway antagonist N-(N-[3,5-difluorophenacetyl]-L-alanyl)-S-phenylglycine t-butyl ester reduced CCL2 level in ADAM19-overexpressed cells. Collectively, microRNA-874-3p/ADAM19 mediates renal fibrosis after acute kidney injury by increasing macrophage infiltration via the Notch1/CCL2 pathway.

scholarly journals Non-steroidal anti-inflammatory drugs induced acute kidney injury: incidence, clinical presentation, management and outcomes of patients at Tertiary Hospital based longitudinal study in Mymensingh, Bangladesh

2018 ◽  
Vol 7 (2) ◽  
pp. 9-16
Author(s):  
Shamima Sattar ◽  
Mahmud Javed Hasan ◽  
Nitai Chandra Ray ◽  
ASM Ruhul Quddus
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Longitudinal Study ◽  
Kidney Disease ◽  
Renal Injury ◽  
Kidney Injury ◽  
Complete Recovery ◽  
Injury Incidence ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed in primary care for their analgesic and anti-inflammatory effects. Twelve percent of individuals currently report taking a NSAID daily. Renal injury caused by these agents can present in various forms, resulting from either acute or chronic use. Historically approximately five percent of patients initiated on NSAIDs experience a kidney-related adverse event. Drug-induced renal injury accounts for twenty percent of episodes of acute kidney injury (AKI). Patients requiring renal replacement therapy (RRT) have experienced an increased length of stay with associated healthcare costs per incident. The adverse effects of NSAIDs contribute to a significant economic burden, both to the patient and to the healthcare system.This study of NSAIDs induced AKI was carried out to highlight this issue. To find out the incidence, risk factors, diagnostic approach, clinical course, management and outcome of patients, this longitudinal study was carried out at Nephrology Department in Community Based Medical College Hospital Bangladesh from July 2015 to June 2016.Total 65 patients of NSAIDs induced AKI were included in this study. Any patient having pre existing renal pathology or chronic kidney disease was excluded from the study. Mean age of the patient was 36±7.12 yrs. Forty nine patients (74.38%) took NSAIDs at their own and 16 patients (24.61%) were prescribed by physician. Fifty six patients (86.15%) took NSAIDs because of musculoskeletal pain. Dehydration due to physical exertion (29.23%) gastroenteritis (16.92%) and nil per os (NPO) (6.15%)were the common predisposing factors. Common symptoms were swelling of the body (36.9%) headache (26.15%) fatigue (21.53%) and vomiting (13.84%) Oedema was the most common sign (36.9%) Blood urea and serum creatinine were raised in all patients. Treatment includes drug withdrawal (100%), fluid resuscitation (83.07%) fluid restriction (13.85%) short course of steroid (15.38%) and haemodialysis (10.76%) . Fifty one patients (78.46%) had complete recovery within two weeks of therapy whereas ten patients (15.38%) required more than two weeks to one month for complete recovery. Three patients (4.61%) developed chronic kidney disease (CKD). NSAIDs induced AKI carries a good prognosis with early diagnosis and proper management and it can be prevented by limiting the availability of over the counter drugs and creating awareness both in physicians and patients. These medications should be prescribed for the shortest duration, the lowest effective dose, and with careful surveillance to monitor nephrotoxicity precisely. NSAIDs should be used with special caution in elderly patients. CBMJ 2018 July: Vol. 07 No. 02 P: 09-16

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