Indirect effects of severe acute respiratory syndrome coronavirus 2 on the kidney in coronavirus disease patients

Abstract Among patients hospitalized for novel coronavirus disease (COVID-19), between 10 and 14% develop an acute kidney injury and around half display marked proteinuria and haematuria. Post-mortem analyses of COVID-19 kidney tissue suggest that renal tubular cells and podocytes are affected. Here we report two cases of collapsing glomerulopathy and tubulointerstitial lesions in living COVID-19 patients. Despite our use of sensitive reverse transcription polymerase chain reaction techniques in this study, we failed to detect the virus in blood, urine and kidney tissues. Our observations suggest that these kidney lesions are probably not due to direct infection of the kidney by severe acute respiratory syndrome coronavirus 2.

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Faculty Opinions recommendation of Sestrin-2 and BNIP3 regulate autophagy and mitophagy in renal tubular cells in acute kidney injury.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718012810.793481005 ◽

2013 ◽

Author(s):

Kenneth Hallows ◽

Mohammad Al-bataineh

Keyword(s):

Acute Kidney Injury ◽

Kidney Injury ◽

Tubular Cells ◽

Renal Tubular Cells ◽

Renal Tubular

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Extracellular vesicles as immune mediators in response to kidney injury

AJP Renal Physiology ◽

10.1152/ajprenal.00336.2017 ◽

2018 ◽

Vol 314 (1) ◽

pp. F9-F21 ◽

Cited By ~ 4

Author(s):

Eva Feigerlová ◽

Shyue-Fang Battaglia-Hsu ◽

Thierry Hauet ◽

Jean-Louis Guéant

Keyword(s):

Extracellular Vesicles ◽

Therapeutic Potential ◽

Kidney Tissue ◽

Kidney Injury ◽

Renal Tissue ◽

Bioactive Molecules ◽

Renal Diseases ◽

Cytokine Signaling ◽

Renal Tubular ◽

Tissue Recovery

Important progress has been made on cytokine signaling in response to kidney injury in the past decade, especially cytokine signaling mediated by extracellular vesicles (EVs). For example, EVs released by injured renal tubular epithelial cells (TECs) can regulate intercellular communications and influence tissue recovery via both regulating the expression and transferring cytokines, growth factors, as well as other bioactive molecules at the site of injury. The effects of EVs on kidney tissue seem to vary depending on the sources of EVs; however, the literature data are often inconsistent. For example, in rodents EVs derived from mesenchymal stem cells (MSC-EVs) and endothelial progenitor cells (EPC-EVs) can have both beneficial and harmful effects on injured renal tissue. Caution is thus needed in the interpretation of these data as contradictory findings on EVs may not only be related to the origin of EVs, they can also be caused by the different methods used for EV isolation and the physiological and pathological states of the tissues/cells under which they were obtained. Here, we review and discuss our current understanding related to the immunomodulatory function of EVs in renal tubular repair in the hope of encouraging further investigations on mechanisms related to their antiinflammatory and reparative role to better define the therapeutic potential of EVs in renal diseases.

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ACE2 Expression in Kidney and Testis May Cause Kidney and Testis Damage After 2019-nCoV Infection

10.1101/2020.02.12.20022418 ◽

2020 ◽

Cited By ~ 82

Author(s):

Caibin Fan ◽

Kai Li ◽

Yanhong Ding ◽

Wei Lu ◽

Jianqing Wang

Keyword(s):

Renal Function ◽

Young Patients ◽

Clinical Work ◽

Testicular Tissue ◽

Kidney Damage ◽

Function Evaluation ◽

Renal Tubular Cells ◽

Renal Tubular ◽

Novel Coronavirus ◽

Potential Pathogenicity

AbstractIn December 2019 and January 2020, novel coronavirus (2019-nCoV) - infected pneumonia (NCIP) occurred in Wuhan, and has already posed a serious threat to public health. ACE2 (Angiotensin Converting Enzyme 2) has been shown to be one of the major receptors that mediate the entry of 2019-nCoV into human cells, which also happens in severe acute respiratory syndrome coronavirus (SARS). Several researches have indicated that some patients have abnormal renal function or even kidney damage in addition to injury in respiratory system, and the related mechanism is unknown. This arouses our interest in whether coronavirus infection will affect the urinary and male reproductive systems. Here in this study, we used the online datasets to analyze ACE2 expression in different human organs. The results indicate that ACE2 highly expresses in renal tubular cells, Leydig cells and cells in seminiferous ducts in testis. Therefore, virus might directly bind to such ACE2 positive cells and damage the kidney and testicular tissue of patients. Our results indicate that renal function evaluation and special care should be performed in 2019-nCoV patients during clinical work, because of the kidney damage caused by virus and antiviral drugs with certain renal toxicity. In addition, due to the potential pathogenicity of the virus to testicular tissues, clinicians should pay attention to the risk of testicular lesions in patients during hospitalization and later clinical follow-up, especially the assessment and appropriate intervention in young patients’ fertility.

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Immunopathogenesis of Acute Kidney Injury

Toxicologic Pathology ◽

10.1177/0192623318799976 ◽

2018 ◽

Vol 46 (8) ◽

pp. 930-943 ◽

Cited By ~ 11

Author(s):

Zaher A. Radi

Keyword(s):

Acute Kidney Injury ◽

T Cells ◽

Kidney Tissue ◽

Kidney Injury ◽

Drug Induced ◽

Inflammatory Damage ◽

Anti Inflammatory ◽

Renal Tubular ◽

Molecular Patterns ◽

Damage Associated Molecular Patterns

Pathophysiologically, the classification of acute kidney injury (AKI) can be divided into three categories: (1) prerenal, (2) intrinsic, and (3) postrenal. Emerging evidence supports the involvement of renal tubular epithelial cells and the innate and adaptive arms of the immune system in the pathogenesis of intrinsic AKI. Pro-inflammatory damage-associated molecular patterns, pathogen-associated molecular patterns, hypoxia inducible factors, toll-like receptors, complement system, oxidative stress, adhesion molecules, cell death, resident renal dendritic cells, neutrophils, T and B lymphocytes, macrophages, natural killer T cells, cytokines, and secreted chemokines contribute to the immunopathogenesis of AKI. However, other immune cells and pathways such as M2 macrophages, regulatory T cells, progranulin, and autophagy exhibit anti-inflammatory properties and facilitate kidney tissue repair after AKI. Thus, therapies for AKI include agents such as anti-inflammatory (e.g., recombinant alkaline phosphatase), antioxidants (iron chelators), and apoptosis inhibitors. In preclinical toxicity studies, drug-induced kidney injury can be seen after exposure to a nephrotoxicant test article due to immune mechanisms and dysregulation of innate, and/or adaptive cellular immunity. The focus of this review will be on intrinsic AKI, as it relates to the immune and renal systems cross talks focusing on the cellular and pathophysiologic mechanisms of AKI.

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Urinary TCP1-eta: A Cortical Damage Marker for the Pathophysiological Diagnosis and Prognosis of Acute Kidney Injury

Toxicological Sciences ◽

10.1093/toxsci/kfz242 ◽

2019 ◽

Vol 174 (1) ◽

pp. 3-15 ◽

Cited By ~ 3

Author(s):

Sandra M Sancho-Martínez ◽

Fernando Sánchez-Juanes ◽

Víctor Blanco-Gozalo ◽

Miguel Fontecha-Barriuso ◽

Laura Prieto-García ◽

...

Keyword(s):

Acute Kidney Injury ◽

Kidney Injury ◽

Cortical Damage ◽

Renal Tubular Cells ◽

Tubular Necrosis ◽

Diagnosis And Prognosis ◽

A Cell ◽

Renal Tubular ◽

Dextran Solution

Abstract Acute kidney injury (AKI) is a serious syndrome with increasing incidence and health consequences, and high mortality rate among critically ill patients. Acute kidney injury lacks a unified definition, has ambiguous semantic boundaries, and relies on defective diagnosis. This, in part, is due to the absence of biomarkers substratifying AKI patients into pathophysiological categories based on which prognosis can be assigned and clinical treatment differentiated. For instance, AKI involving acute tubular necrosis (ATN) is expected to have a worse prognosis than prerenal, purely hemodynamic AKI. However, no biomarker has been unambiguously associated with tubular cell death or is able to provide etiological distinction. We used a cell-based system to identify TCP1-eta in the culture medium as a noninvasive marker of damaged renal tubular cells. In rat models of AKI, TCP1-eta was increased in the urine co-relating with renal cortical tubule damage. When kidneys from ATN rats were perfused in situ with Krebs-dextran solution, a portion of the urinary TCP1-eta protein content excreted into urine disappeared, and another portion remained within the urine. These results indicated that TCP1-eta was secreted by tubule cells and was not fully reabsorbed by the damaged tubules, both effects contributing to the increased urinary excretion. Urinary TCP1-eta is found in many etiologically heterogeneous AKI patients, and is statistically higher in patients partially recovered from severe AKI. In conclusion, urinary TCP1-eta poses a potential, substratifying biomarker of renal cortical damage associated with bad prognosis.

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Effects of Severe Acute Respiratory Syndrome Coronavirus 2 Infection on Pregnant Women and Their Infants

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2020-0232-sa ◽

2020 ◽

Vol 144 (10) ◽

pp. 1217-1222 ◽

Cited By ~ 11

Author(s):

Hui Yang ◽

Bin Hu ◽

Sudong Zhan ◽

Li-ye Yang ◽

Guoping Xiong

Keyword(s):

Computed Tomography ◽

Severe Acute Respiratory Syndrome ◽

Pregnant Women ◽

Perinatal Death ◽

Severe Pneumonia ◽

Neonatal Morbidity ◽

Late Pregnancy ◽

Chest Computed Tomography ◽

Polymerase Chain ◽

Novel Coronavirus

Context.— The pandemic of a novel coronavirus, termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has created an unprecedented global health burden. Objective.— To investigate the effect of the SARS-CoV-2 infection on maternal, fetal, and neonatal morbidity and other poor obstetrical outcomes. Design.— All suspected cases of pregnant women with coronavirus disease 2019 (COVID-19) admitted into one center in Wuhan from January 20 to March 19, 2020, were included. Detailed clinical data of those pregnancies with COVID-19 were retrospectively collected and analyzed. Results.— Twenty-seven pregnant women (4 early pregnancies included) with laboratory or clinically confirmed SARS-CoV-2 infection and 24 neonates born to the 23 women in late pregnancy were analyzed. On admission, 46.2% (13 of 27) of the patients had symptoms, including fever (11 of 27), cough (9 of 27), and vomiting (1 of 27). Decreased total lymphocytes count was observed in 81.5% (22 of 27) of patients. Twenty-six patients showed typical viral pneumonia by chest computed tomography scan, whereas 1 patient confirmed with COVID-19 infection showed no abnormality on chest computed tomography. One mother developed severe pneumonia 3 days after her delivery. No maternal or perinatal death occurred. Moreover, 1 early preterm newborn born to a mother with the complication of premature rupture of fetal membranes, highly suspected to have SARS-CoV-2 infection, was SARS-CoV-2 negative after repeated real-time reverse transcriptase polymerase chain reaction testing. Statistical differences were observed between the groups of women in early and late pregnancy with COVID-19 in the occurrence of lymphopenia and thrombocytopenia. Conclusions.— No major complications were reported among the studied cohort, though 1 serious case and 1 perinatal infection were observed. Much effort should be made to reduce the pathogenic effect of COVID-19 infection in pregnancies.

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Acute Kidney Injury in SARS-CoV-2 Infection: Direct Effect of Virus on Kidney Proximal Tubule Cells

International Journal of Molecular Sciences ◽

10.3390/ijms21093275 ◽

2020 ◽

Vol 21 (9) ◽

pp. 3275 ◽

Cited By ~ 10

Author(s):

Manoocher Soleimani

Keyword(s):

Acute Kidney Injury ◽

Severe Acute Respiratory Syndrome ◽

Proximal Tubule ◽

Rna Viruses ◽

Kidney Injury ◽

The Novel ◽

Proximal Tubule Cells ◽

Severe Respiratory Infection ◽

Tubule Cells ◽

Novel Coronavirus

Coronaviruses (CoVs), including Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and the novel coronavirus disease-2 (SARS-CoV-2) are a group of enveloped RNA viruses that cause a severe respiratory infection which is associated with a high mortality [...]

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Fibrinogen β–derived Bβ15-42 peptide protects against kidney ischemia/ reperfusion injury

Blood ◽

10.1182/blood-2011-02-338061 ◽

2011 ◽

Vol 118 (7) ◽

pp. 1934-1942 ◽

Cited By ~ 33

Author(s):

Aparna Krishnamoorthy ◽

Amrendra Kumar Ajay ◽

Dana Hoffmann ◽

Tae-Min Kim ◽

Victoria Ramirez ◽

...

Keyword(s):

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

High Sensitivity ◽

Kidney Damage ◽

Therapeutic Interventions ◽

Mrna Levels ◽

Renal Tubular Cells ◽

Renal Tubular ◽

Injury And Repair

AbstractIschemia/reperfusion (I/R) injury in the kidney is a major cause of acute kidney injury (AKI) in humans and is associated with significantly high mortality. To identify genes that modulate kidney injury and repair, we conducted genome-wide expression analysis in the rat kidneys after I/R and found that the mRNA levels of fibrinogen (Fg)α, Fgβ, and Fgγ chains significantly increase in the kidney and remain elevated throughout the regeneration process. Cellular characterization of Fgα and Fgγ chain immunoreactive proteins shows a predominant expression in renal tubular cells and the localization of immunoreactive Fgβ chain protein is primarily in the renal interstitium in healthy and regenerating kidney. We also show that urinary excretion of Fg is massively increased after kidney damage and is capable of distinguishing human patients with acute or chronic kidney injury (n = 25) from healthy volunteers (n = 25) with high sensitivity and specificity (area under the receiver operating characteristic of 0.98). Furthermore, we demonstrate that Fgβ-derived Bβ15-42 peptide administration protects mice from I/R-induced kidney injury by aiding in epithelial cell proliferation and tissue repair. Given that kidney regeneration is a major determinant of outcome for patients with kidney damage, these results provide new opportunities for the use of Fg in diagnosis, prevention, and therapeutic interventions in kidney disease.

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Acute kidney injury in the cancer patient

10.1093/med/9780199592548.003.0251 ◽

2015 ◽

Author(s):

Gilbert W. Moeckel ◽

Veena Manjunath ◽

Mark A. Perazella

Keyword(s):

Acute Kidney Injury ◽

Cancer Patients ◽

Clinical Presentation ◽

Kidney Tissue ◽

Hospital Setting ◽

Kidney Injury ◽

Direct Effects ◽

Significant Morbidity ◽

Adequate Treatment ◽

Kidney Lesions

Acute kidney injury in cancer patients is a complicated clinical condition associated with significant morbidity and mortality, especially in the hospital setting. Cancer patients may develop a variety of different kidney lesions that impair not only immediate survival but also limit the adequate treatment of the underlying malignant process. This poses a significant challenge for clinicians.The mechanisms that lead to acute kidney injury in cancer patients are similar to those seen in non-cancer patients. Moreover, significant morbidity is seen in association with chemotherapy, as well as through direct effects of the cancer on the kidney (i.e. obstruction, infiltrate).This chapter reviews the clinical presentation of the most common malignancies that affect the kidney, discusses their pathologic manifestations in kidney tissue, and reviews options for the clinical management of cancer patients with acute kidney injury.

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