Mechanisms of COVID-19-induced kidney injury and current pharmacotherapies.

The COVID-19 pandemic created a worldwide debilitating health crisis with the entire humanity suffering from the deleterious effects associated with the high infectivity and mortality rates. While significant evidence is currently available online and targets various aspects of the disease, both inflammatory and noninflammatory kidney manifestations secondary to COVID-19 infection are still largely underrepresented. In this review, we summarized current knowledge about COVID-19-related kidney manifestations, their pathologic mechanisms as well as various pharmacotherapies used to treat patients with COVID-19. We also shed light on the effect of these medications on kidney functions that can further enhance renal damage secondary to the illness.

Patient with H syndrome, cardiogenic shock, multiorgan infiltration, and digital ischemia.

BACKGROUND: H syndrome (HS) is a rare autoinflammatory disease caused by a mutation in the solute carrier family 29, member 3 (SCL29A3) gene. It has a variable clinical presentation and little phenotype-genotype correlation. The pathognomonic sign of HS is cutaneous hyperpigmentation located mainly in the inner thighs and often accompanied by other systemic manifestations. Improvement after tocilizumab treatment has been reported in a few patients with HS. We report the first patient with HS who presented cardiogenic shock, multiorgan infiltration, and digital ischemia. CASE PRESENTATION: 8-year-old boy born to consanguineous parents of Moroccan origin who was admitted to the intensive care unit during the Coronavirus Disease-2019 (COVID-19) pandemic with tachypnoea, tachycardia, and oliguria. Echocardiography showed dilated cardiomyopathy and severe systolic dysfunction compatible with cardiogenic shock. Additionally, he presented with multiple organ dysfunction syndrome. SARS-CoV-2 polymerase chain reaction (PCR) and antibody detection by chromatographic immunoassay were negative. A previously ordered gene panel for pre-existing sensorineural hearing loss showed a pathological mutation in the SCL29A3 gene compatible with H syndrome. Computed tomography scan revealed extensive alveolar infiltrates in the lungs and multiple poor defined hypodense lesions in liver, spleen, and kidneys; adenopathy; and cardiomegaly with left ventricle subendocardial nodules. Invasive mechanical ventilation, broad antibiotic and antifungal coverage showed no significant response. Therefore, Tocilizumab as compassionate use together with pulsed intravenous methylprednisolone was initiated. Improvement was impressive leading to normalization of inflammation markers, liver and kidney function, and stabilising heart function. Two weeks later, he was discharged and has been clinically well since then on two weekly administration of Tocilizumab. CONCLUSIONS: We report the most severe disease course produced by HS described so far in the literature. Our patient's manifestations included uncommon, new complications such as acute heart failure with severe systolic dysfunction, multi-organ cell infiltrate, and digital ischemia. Most of the clinical symptoms of our patient could have been explained by SARS-CoV-2, demonstrating the importance of a detailed differential diagnosis to ensure optimal treatment. Although the mechanism of autoinflammation of HS remains uncertain, the good response of our patient to Tocilizumab makes a case for the important role of IL-6 in this syndrome and for considering Tocilizumab as a first-line treatment, at least in severely affected patients.

Coronavirus disease 2019 and kidney injury.

PURPOSE OF REVIEW: In this paper, we seek to review coronavirus disease 2019 (COVID-19) associated kidney injury with a focus on what is known about pathophysiology. RECENT FINDINGS: Kidney injury is a common complication of SARS-CoV-2 infection and is associated with increased morbidity and mortality. Acute tubular necrosis and glomerular injury are two common findings. Direct viral effect, endothelial dysfunction, and podocyte and tubular epithelial injury have been described. COVID-19-related glomerular injury may also be associated with high-risk APOL1 genotype. SUMMARY: Data on COVID-19 renal involvement have suggested novel mechanisms of kidney injury that need to be further elucidated. More data are needed on renal involvement in milder disease, renal-specific therapeutic interventions, and long-term sequelae.

Kidney involvement in COVID-19 and its treatments.

The lungs are the most commonly affected organ by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the kidneys are also frequently affected. Infection with SARS-CoV-2 can not only cause new kidney damage but also increase the difficulty of treatment and care as well as mortality for people with underlying kidney diseases. Kidney involvement in SARS-CoV-2 infection mainly manifests as kidney tubular injury. Proteinuria is the main clinical sign. To reduce patient mortality, kidney complications should be given increased attention in the diagnosis and treatment of coronavirus disease 2019 (COVID-19). This study reviews the existing literature and discusses COVID-19 infection in combination with kidney diseases in terms of kidney damage, pathogenesis, and treatment to guide clinical anti-epidemic responses.

COVID-19 impact on the renal system: Pathophysiology and clinical outcomes.

Coronavirus disease (COVID-19) causes many deleterious effects throughout the body. Prior studies show that the incidence of acute kidney injury in COVID-19 patients could be as high as 25%. There are also autopsy reports showing evidence of viral tropism to the renal system. In this regard, COVID-19 can damage the kidneys and increase a patient's risk of requiring dialysis. Available evidence suggests that renal involvement in COVID-19 infection is not uncommon, and there has been an increased incidence of chronic kidney disease related to the pandemic. In this literature analysis, we address COVID-19 and its effects on the renal system, including the pathophysiologic mechanisms. We also address current studies on the causes of injury to the renal system, the cause of kidney failure, its effect on mortality, the impact on dialysis patients, and the impact on renal transplant patients. COVID-19 disease may have unique features in individuals on chronic dialysis and kidney transplant recipients, requiring increased vigilance in limiting viral transmission in perioperative, in-patient, and dialysis center settings.

Angiotensin-converting enzyme 2 and kidney diseases in the era of coronavirus disease 2019.

In the decades since the discovery of angiotensin-converting enzyme 2 (ACE2), its protective role in terms of antagonizing activation of the classical renin-angiotensin system (RAS) axis has been recognized in clinical and experimental studies on kidney and cardiovascular diseases. The effects of ACE inhibitor/angiotensin type 1 receptor blockers (ACEi/ARBs) on ACE2-angiotensin-(1-7) (Ang- (1-7))-Mas receptor (MasR) axis activation has encouraged the use of such blockers in patients with kidney and cardiovascular diseases, until the emergence of coronavirus disease 2019 (COVID-19). The previously unchallenged functions of the ACE2-Ang-(1-7)-MasR axis and ACEi/ARBs are being re-evaluated in the era of COVID-19; the hypothesis is that ACEi/ARBs may increase the risk of severe acute respiratory syndrome coronavirus 2 infection by upregulating the human ACE2 receptor expression level. In this review, we examine ACE2 molecular structure, function (as an enzyme of the RAS), and distribution. We explore the roles played by ACE2 in kidney, cardiovascular, and pulmonary diseases, highlighting studies that defined the benefits imparted when ACEi/ARBs activated the local ACE2- Ang-(1-7)-MasR axis. Finally, the question of whether ACEi/ARBs therapies should be stopped in COVID-19-infected patients will be reviewed by reference to the available evidence.

ACE2, the kidney and the emergence of COVID-19 two decades after ACE2 discovery.

Angiotensin-converting enzyme II (ACE2) is a homologue of angiotensin-converting enzyme discovered in 2000. From the initial discovery, it was recognized that the kidneys were organs very rich on ACE2. Subsequent studies demonstrated the precise localization of ACE2 within the kidney and the importance of this enzyme in the metabolism of Angiotensin II and the formation of Angiotensin 1-7. With the recognition early in 2020 of ACE2 being the main receptor of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), the interest in this protein has dramatically increased. In this review, we will focus on kidney ACE2; its localization, its alterations in hypertension, diabetes, the effect of ACE inhibitors and angiotensin type 1 receptor blockers (ARBs) on ACE2 and the potential use of ACE2 recombinant proteins therapeutically for kidney disease. We also describe the emerging kidney manifestations of COVID-19, namely the frequent development of acute kidney injury. The possibility that binding of SARS-CoV-2 to kidney ACE2 plays a role in the kidney manifestations is also briefly discussed.

First results of the "Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS)".

PURPOSE: Knowledge regarding patients' clinical condition at severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection is sparse. Data in the international, multicenter Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS) cohort study may enhance the understanding of COVID-19. METHODS: Sociodemographic and clinical characteristics of SARS-CoV-2-infected patients, enrolled in the LEOSS cohort study between March 16, 2020, and May 14, 2020, were analyzed. Associations between baseline characteristics and clinical stages at diagnosis (uncomplicated vs. complicated) were assessed using logistic regression models. RESULTS: We included 2155 patients, 59.7% (1,287/2,155) were male; the most common age category was 66-85 years (39.6%; 500/2,155). The primary COVID-19 diagnosis was made in 35.0% (755/2,155) during complicated clinical stages. A significant univariate association between age; sex; body mass index; smoking; diabetes; cardiovascular, pulmonary, neurological, and kidney diseases; ACE inhibitor therapy; statin intake and an increased risk for complicated clinical stages of COVID-19 at diagnosis was found. Multivariable analysis revealed that advanced age [46-65 years: adjusted odds ratio (aOR): 1.73, 95% CI 1.25-2.42, p = 0.001; 66-85 years: aOR 1.93, 95% CI 1.36-2.74, p < 0.001; > 85 years: aOR 2.38, 95% CI 1.49-3.81, p < 0.001 vs. individuals aged 26-45 years], male sex (aOR 1.23, 95% CI 1.01-1.50, p = 0.040), cardiovascular disease (aOR 1.37, 95% CI 1.09-1.72, p = 0.007), and diabetes (aOR 1.33, 95% CI 1.04-1.69, p = 0.023) were associated with complicated stages of COVID-19 at diagnosis. CONCLUSION: The LEOSS cohort identified age, cardiovascular disease, diabetes and male sex as risk factors for complicated disease stages at SARS-CoV-2 diagnosis, thus confirming previous data. Further data regarding outcomes of the natural course of COVID-19 and the influence of treatment are required.

SARS-CoV-2 pathophysiology and its clinical implications: An integrative overview of the pharmacotherapeutic management of COVID-19.

Common manifestations of COVID-19 are respiratory and can extend from mild symptoms to severe acute respiratory distress. The severity of the illness can also extend from mild disease to life-threatening acute respiratory distress syndrome (ARDS). SARS-CoV-2 infection can also affect the gastrointestinal tract, liver and pancreatic functions, leading to gastrointestinal symptoms. Moreover, SARS-CoV-2 can cause central and peripheral neurological manifestations, affect the cardiovascular system and promote renal dysfunction. Epidemiological data have indicated that cancer patients are at a higher risk of contracting the SARS-CoV-2 virus. Considering the multitude of clinical symptoms of COVID-19, the objective of the present review was to summarize their pathophysiology in previously healthy patients, as well as in those with comorbidities. The present review summarizes the current, though admittedly fluid knowledge on the pathophysiology and symptoms of COVID-19 infection. Although unclear issues still remain, the present study contributes to a more complete understanding of the disease, and may drive the direction of new research. The recognition of the severity of the clinical symptoms of COVID-19 is crucial for the specific therapeutic management of affected patients.

Preprint Servers in Kidney Disease Research: A Rapid Review.

Preprint servers, such as arXiv and bioRxiv, have disrupted the scientific communication landscape by providing rapid access to research before peer review. medRxiv was launched as a free online repository for preprints in the medical, clinical, and related health sciences in 2019. In this review, we present the uptake of preprint server use in nephrology and discuss specific considerations regarding preprint server use in medicine. Distribution of kidney-related research on preprint servers is rising at an exponential rate. Survey of nephrology journals identified that 15 of 17 (88%) are publishing original research accepted submissions that have been uploaded to preprint servers. After reviewing 52 clinically impactful trials in nephrology discussed in the online Nephrology Journal Club (NephJC), an average lag of 300 days was found between study completion and publication, indicating an opportunity for faster research dissemination. Rapid review of papers discussing benefits and risks of preprint server use from the researcher, publisher, or end user perspective identified 53 papers that met criteria. Potential benefits of biomedical preprint servers included rapid dissemination, improved transparency of the peer review process, greater visibility and recognition, and collaboration. However, these benefits come at the risk of rapid spread of results not yet subjected to the rigors of peer review. Preprint servers shift the burden of critical appraisal to the reader. Media may be especially at risk due to their focus on "late-breaking" information. Preprint servers have played an even larger role when late-breaking research results are of special interest, such as during the global coronavirus disease 2019 pandemic. Coronavirus disease 2019 has brought both the benefits and risks of preprint servers to the forefront. Given the prominent online presence of the nephrology community, it is poised to lead the medicine community in appropriate use of preprint servers.

Multisystem effects of COVID-19: a concise review for practitioners.

While COVID-19 has primarily been characterized by the respiratory impact of viral pneumonia, it affects every organ system and carries a high consequent risk of death in critically ill patients. Higher sequential organ failure assessment (SOFA) scores have been associated with increased mortality in patients critically ill patients with COVID-19. It is important that clinicians managing critically ill COVID-19 patients be aware of the multisystem impact of the disease so that care can be focused on the prevention of end-organ injuries to potentially improve clinical outcomes. We review the multisystem complications of COVID-19 and associated treatment strategies to improve the care of critically ill COVID-19 patients.

Association of hypertension, diabetes, stroke, cancer, kidney disease, and high-cholesterol with COVID-19 disease severity and fatality: A systematic review.

BACKGROUND AND AIMS: To undertake a review and critical appraisal of published/preprint reports that offer methods of determining the effects of hypertension, diabetes, stroke, cancer, kidney issues, and high-cholesterol on COVID-19 disease severity. METHODS: A search was conducted by two authors independently on the freely available COVID-19 Open Research Dataset (CORD-19). We developed an automated search engine to screen a total of 59,000 articles in a few seconds. Filtering of the articles was then undertaken using keywords and questions, e.g. "Effects of diabetes on COVID/normal coronavirus/SARS-CoV-2/nCoV/COVID-19 disease severity, mortality?". The search terms were repeated for all the comorbidities considered in this paper. Additional articles were retrieved by searching via Google Scholar and PubMed. FINDINGS: A total of 54 articles were considered for a full review. It was observed that diabetes, hypertension, and cholesterol levels possess an apparent relation to COVID-19 severity. Other comorbidities, such as cancer, kidney disease, and stroke, must be further evaluated to determine a strong relationship to the virus. CONCLUSION: Reports associating cancer, kidney disease, and stroke with COVID-19 should be carefully interpreted, not only because of the size of the samples, but also because patients could be old, have a history of smoking, or have any other clinical condition suggesting that these factors might be associated with the poor COVID-19 outcomes rather than the comorbidity itself. Further research regarding this relationship and its clinical management is warranted.

Biochemical biomarkers alterations in Coronavirus Disease 2019 (COVID-19).

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory disease, which can evolve into multi-organ failure (MOF), leading to death. Several biochemical alterations have been described in COVID-19 patients. To date, many biomarkers reflecting the main pathophysiological characteristics of the disease have been identified and associated with the risk of developing severe disease. Lymphopenia represents the hallmark of the disease, and it can be detected since the early stage of infection. Increased levels of several inflammatory biomarkers, including c-reactive protein, have been found in COVID-19 patients and associated with an increased risk of severe disease, which is characterised by the so-called "cytokine storm". Also, the increase of cardiac and liver dysfunction biomarkers has been associated with poor outcome. In this review, we provide an overview of the main biochemical characteristics of COVID-19 and the associated biomarkers alterations.