Mitochondrial DNA-Mediated Inflammation in Acute Kidney Injury and Chronic Kidney Disease

The integrity and function of mitochondria are essential for normal kidney physiology. Mitochondrial DNA (mtDNA) has been widely a concern in recent years because its abnormalities may result in disruption of aerobic respiration, cellular dysfunction, and even cell death. Particularly, aberrant mtDNA copy number (mtDNA-CN) is associated with the development of acute kidney injury and chronic kidney disease, and urinary mtDNA-CN shows the potential to be a promising indicator for clinical diagnosis and evaluation of kidney function. Several lines of evidence suggest that mtDNA may also trigger innate immunity, leading to kidney inflammation and fibrosis. In mechanism, mtDNA can be released into the cytoplasm under cell stress and recognized by multiple DNA-sensing mechanisms, including Toll-like receptor 9 (TLR9), cytosolic cGAS-stimulator of interferon genes (STING) signaling, and inflammasome activation, which then mediate downstream inflammatory cascades. In this review, we summarize the characteristics of these mtDNA-sensing pathways mediating inflammatory responses and their role in the pathogenesis of acute kidney injury, nondiabetic chronic kidney disease, and diabetic kidney disease. In addition, we highlight targeting of mtDNA-mediated inflammatory pathways as a novel therapeutic target for these kidney diseases.

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Stem cell-based treatment of kidney diseases

Experimental Biology and Medicine ◽

10.1177/1535370220915901 ◽

2020 ◽

Vol 245 (10) ◽

pp. 902-910

Author(s):

Binbin Pan ◽

Guoping Fan

Keyword(s):

Chronic Kidney Disease ◽

Stem Cells ◽

Acute Kidney Injury ◽

Stem Cell ◽

Kidney Disease ◽

Cell Therapy ◽

Kidney Diseases ◽

Kidney Injury ◽

Great Promise ◽

Kidney Organoids

Kidney dysfunction, including chronic kidney disease and acute kidney injury, is a globally prevalent health problem. However, treatment regimens are still lacking, especially for conditions involving kidney fibrosis. Stem cells hold great promise in the treatment of chronic kidney disease and acute kidney injury, but success has been hampered by insufficient incorporation of the stem cells in the injured kidney. Thus, new approaches for the restoration of kidney function after acute or chronic injury have been explored. Recently, kidney organoids have emerged as a useful tool in the treatment of kidney diseases. In this review, we discuss the mechanisms and approaches of cell therapy in acute kidney injury and chronic kidney disease, including diabetic kidney disease and lupus nephritis. We also summarize the potential applications of kidney organoids in the treatment of kidney diseases. Impact statement Stem cells hold great promise in regenerative medicine. Pluripotent stem cells have been differentiated into kidney organoids to understand human kidney development and to dissect renal disease mechanisms. Meanwhile, recent studies have explored the treatment of kidney diseases using a variety of cells, including mesenchymal stem cells and renal derivatives. This mini-review discusses the diverse mechanisms underlying current renal disease treatment via stem cell therapy. We postulate that clinical applications of stem cell therapy for kidney diseases can be readily achieved in the near future.

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PROTON PUMP INHIBITORS AND THE RISK OF CHRONIC KIDNEY DISEASES: A CRITICAL REVIEW

International Journal of Current Pharmaceutical Research ◽

10.22159/ijcpr.2020v12i5.39783 ◽

2020 ◽

pp. 11-14

Author(s):

SHAREEF J. ◽

SRIDHAR S. B. ◽

SHARIFF A.

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Kidney Disease ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

End Stage Renal Disease ◽

Kidney Diseases ◽

Kidney Injury ◽

Stage Renal Disease ◽

End Stage

Proton pump inhibitors (PPIs) are most widely used medications for acid related gastrointestinal disorders. Accessible evidence based studies suggest that the increased use of PPI is linked to a greater risk of developing kidney diseases. This review aims to determine the association of kidney disease with the use of proton pump inhibitor with various study designs. PubMed, Scopus and Google Scholar databases as well as a reference list of relevant articles were systematically searched for studies by using the following search terms; ‘proton pump inhibitors’, ‘acute kidney injury’, ‘chronic kidney disease’ and ‘end stage renal disease’. Both observational and randomized controlled trials (RCTs) exploring the association of PPI use with kidney disease were eligible for inclusion. A total of 8 articles, including 9 studies (n = 794,349 participants) were identified and included in the review. Majority of the studies showed a higher risk of kidney outcomes in patients taking PPIs, with effect higher of acute kidney injury (4-to 6-fold) compared with chronic kidney disease and end stage renal disease (1.5-to 2.5-fold). However, the studies suggest that the strength of evidence is weak and could not prove causation. The risk increased considerably with the use of high dose of PPIs and prolonged duration of exposure necessitates the monitoring of renal function. Exercising vigilance in PPI use and cessation of proton pump inhibitor when there is no clear indication may be a reasonable approach to reduce the population burden of kidney diseases.

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Malignancy-associated kidney disease

Progress in Health Sciences ◽

10.5604/01.3001.0009.5255 ◽

2016 ◽

Vol 6 (1) ◽

pp. 0-0

Author(s):

K Kozłowska ◽

J. Małyszko

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Nephrotic Syndrome ◽

Renal Replacement Therapy ◽

Kidney Disease ◽

Replacement Therapy ◽

Tubulointerstitial Nephritis ◽

Kidney Diseases ◽

Kidney Injury ◽

Electrolyte Abnormalities

Malignancy or its treatment affect kidney in several ways. The most common are acute kidney injury and chronic kidney disease. Other form of kidney diseases can also be present such as nephrotic syndrome, tubulointerstitial nephritis, thrombotic microangipathy etc. In addition, electrolyte abnormalities such as hypercalcemia, hyponatremia and hypernatremia, hypokalemia and hyperkalemia, and hypomagnesemia. are observed. Treatment of malignancy associated kidney disease is usually symptomatic. Cessation of the offending agent or other supportive measures if needed i.e. renal replacement therapy are also implemented.

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The Kynurenine Pathway in Acute Kidney Injury and Chronic Kidney Disease

American Journal of Nephrology ◽

10.1159/000519811 ◽

2021 ◽

pp. 1-17

Author(s):

Hai Ning Wee ◽

Jian-Jun Liu ◽

Jianhong Ching ◽

Jean-Paul Kovalik ◽

Su Chi Lim

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Kidney Disease ◽

Animal Models ◽

Kidney Diseases ◽

Kidney Injury ◽

Kynurenine Pathway ◽

T Cell Subsets ◽

Renal Diseases ◽

Tryptophan Degradation

Background: The kynurenine pathway (KP) is the major catabolic pathway for tryptophan degradation. The KP plays an important role as the sole de novo nicotinamide adenine dinucleotide (NAD+) biosynthetic pathway in normal human physiology and functions as a counter-regulatory mechanism to mitigate immune responses during inflammation. Although the KP has been implicated in a variety of disorders including Huntington’s disease, seizures, cardiovascular disease, and osteoporosis, its role in renal diseases is seldom discussed. Summary: This review summarizes the roles of the KP and its metabolites in acute kidney injury (AKI) and chronic kidney disease (CKD) based on current literature evidence. Metabolomics studies demonstrated that the KP metabolites were significantly altered in patients and animal models with AKI or CKD. The diagnostic and prognostic values of the KP metabolites in AKI and CKD were highlighted in cross-sectional and longitudinal human observational studies. The biological impact of the KP on the pathophysiology of AKI and CKD has been studied in experimental models of different etiologies. In particular, the activation of the KP was found to confer protection in animal models of glomerulonephritis, and its immunomodulatory mechanism may involve the regulation of T cell subsets such as Th17 and regulatory T cells. Manipulation of the KP to increase NAD+ production or diversion toward specific KP metabolites was also found to be beneficial in animal models of AKI. Key Messages: KP metabolites are reported to be dysregulated in human observational and animal experimental studies of AKI and CKD. In AKI, the magnitude and direction of changes in the KP depend on the etiology of the damage. In CKD, KP metabolites are altered with the onset and progression of CKD all the way to advanced stages of the disease, including uremia and its related vascular complications. The activation of the KP and diversion to specific sub-branches are currently being explored as therapeutic strategies in these diseases, especially with regards to the immunomodulatory effects of certain KP metabolites. Further elucidation of the KP may hold promise for the development of biomarkers and targeted therapies for these kidney diseases.

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The Cross-Link between Ferroptosis and Kidney Diseases

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/6654887 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Jingyu Wang ◽

Yi Liu ◽

Yaqing Wang ◽

Li Sun

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Cell Death ◽

Kidney Disease ◽

Metabolic Disorders ◽

Kidney Diseases ◽

Kidney Injury ◽

Cross Link ◽

Social Wealth

Acute and chronic kidney injuries result from structural dysfunction and metabolic disorders of the kidney in various etiologies, which significantly affect human survival and social wealth. Nephropathies are often accompanied by various forms of cell death and complex microenvironments. In recent decades, the study of kidney diseases and the traditional forms of cell death have improved. Nontraditional forms of cell death, represented by ferroptosis and necroptosis, have been discovered in the field of kidney diseases, which have reshuffled the role of traditional cell death in nephropathies. Although interactions between ferroptosis and acute kidney injury (AKI) have been continuously explored, studies on ferroptosis and chronic kidney disease (CKD) remain limited. Here, we have reviewed the therapeutic significance of ferroptosis in AKI and anticipated the curative potential of ferroptosis for CKD in the hope of providing insights into ferroptosis and CKD.

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Exogenous Wnt1 Prevents Acute Kidney Injury and Its Subsequent Progression to Chronic Kidney Disease

Frontiers in Physiology ◽

10.3389/fphys.2021.745816 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xue Hong ◽

Yanni Zhou ◽

Dedong Wang ◽

Fuping Lyu ◽

Tianjun Guan ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Kidney Disease ◽

Inflammatory Responses ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Blood Biochemical

Studies suggest that Wnt/β-catenin agonists are beneficial in the treatment of acute kidney injury (AKI); however, it remains elusive about its role in the prevention of AKI and its progression to chronic kidney disease (CKD). In this study, renal Wnt/β-catenin signaling was either activated by overexpression of exogenous Wnt1 or inhibited by administration with ICG-001, a small molecule inhibitor of β-catenin signaling, before mice were subjected to ischemia/reperfusion injury (IRI) to induce AKI and subsequent CKD. Our results showed that in vivo expression of exogenous Wnt1 before IR protected mice against AKI, and impeded the progression of AKI to CKD in mice, as evidenced by both blood biochemical and kidney histological analyses. In contrast, pre-treatment of ICG-001 before IR had no effect on renal Wnt/β-catenin signaling or the progression of AKI to CKD. Mechanistically, in vivo expression of exogenous Wnt1 before IR suppressed the expression of proapoptotic proteins in AKI mice, and reduced inflammatory responses in both AKI and CKD mice. Additionally, exogenous Wnt1 inhibited apoptosis of tubular cells induced by hypoxia-reoxygenation (H/R) treatment in vitro. To conclude, the present study provides evidences to support the preventive effect of Wnt/β-catenin activation on IR-related AKI and its subsequent progression to CKD.

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Defining AKD: The Spectrum of AKI, AKD, and CKD

Nephron ◽

10.1159/000516647 ◽

2021 ◽

pp. 1-4

Author(s):

Andrew S. Levey

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Kidney Disease ◽

Kidney Diseases ◽

Kidney Injury ◽

Consensus Conference ◽

Clinical Presentations ◽

Kdigo Guidelines

Kidney Disease Improving Global Outcomes (KDIGO) guidelines address the definition, classification, and management of acute kidney injury (AKI) and chronic kidney disease (CKD). In practice, some clinical presentations of acute kidney diseases and disorders (AKD) do not meet the criteria for AKI or CKD. In principle, these presentations may be caused by the same diseases that cause AKI or CKD, which could be detected, evaluated, and treated before they evolve to AKI or CKD. In 2020, KDIGO convened a consensus conference to review recent evidence on the epidemiology of AKD and harmonize the definition and classification of AKD to be consistent with KDIGO definitions and classifications of AKI and CKD.

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Inflammasomes in the Pathophysiology of Kidney Diseases

Kidney Diseases ◽

10.1159/000438843 ◽

2015 ◽

Vol 1 (3) ◽

pp. 187-193 ◽

Cited By ~ 14

Author(s):

Humaira Masood ◽

Ruochen Che ◽

Aihua Zhang

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Kidney Disease ◽

Nlrp3 Inflammasome ◽

Epithelial Mesenchymal Transition ◽

Kidney Diseases ◽

Kidney Injury ◽

Mesenchymal Transition ◽

Proinflammatory Mediators ◽

Underlying Mechanisms

Background: The inflammasome is a complex of proteins in the cytoplasm that consists of three main components: a sensor protein (receptor), an adapter protein and caspase-1. Inflammasomes are the critical components of innate immunity and have been gradually recognized as a critical mediator in various autoimmune diseases; also, their role in chronic kidney disease and acute kidney injury has been gradually accepted. Summary: Inflammasomes triggered by infectious or sterile injuries transfer proinflammatory mediators into mature ones through innate danger-signaling platforms. Information on inflammasomes in kidney disease will help to uncover the underlying mechanisms of nephropathy and provide novel therapeutic targets in the future. Key Messages: The inflammasomes can be activated by a series of exogenous and endogenous stimuli, including pathogen-and danger-associated molecular patterns released from or caused by damaged cells. The NACHT, LRR and PYD domain-containing protein 3 (NLRP3) in the kidney exerts its effect not only by the ‘canonical' pathway of IL-1β and IL-18 secretion but also by ‘noncanonical' pathways, such as tumor growth factor-β signaling, epithelial-mesenchymal transition and fibrosis. In both clinical and experimental data, the NLRP3 inflammasome was reported to be involved in the pathogenesis of chronic kidney disease and acute kidney injury. However, the underlying mechanisms are not fully understood. Therapies targeting the activation of the NLRP3 inflammasome or blocking its downstream effectors appear attractive for the pursuit of neuropathy treatments.

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