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      Acute Kidney Injury in COVID-19 Pandemic

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          Abstract

          Dear Editor, We read with great interest the recent article by Perico et al. [1] on COVID-19 and kidney involvement. The authors reported that acute kidney injury (AKI) is one of most common comorbidities of COVID-19 [2]. However, previous reports showed that viruses of the Coronaviridae family differently affected the kidney: AKI was present in only 6% of patients with SARS coronavirus (SARS-CoV) infection [1], in 75% of patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection [3], and in 25% of patients with SARS-CoV2 infection [4]. In all cases, AKI was identified as a fatal complication. The different rates of renal involvement were independent of coronavirus renal tropism, since SARS-CoV and Sars-CoV2, and MERS-CoV receptors (ACE2 and DPP-4, respectively) are equally expressed in renal epithelium [5]. In particular, MERS-CoV showed a direct cytopathic effect on renal epithelial cells [4]. In contrast, SARS-CoV was associated with acute tubular necrosis without signs of glomerulopathy [1], and without in vitro cytopathic effect on renal epithelial cells; renal impairment was likely due to specific pathogenic conditions, including cytokine release syndrome, rather than active viral replication in the kidney, and was related to multi-organ failure [3]. Interestingly, subjects infected with SARS-CoV2 seem to be affected by AKI more frequently than subjects infected with SARS-CoV (25%) [2], despite the same human receptors (ACE2). Perhaps an increased affinity of SARS-CoV2 for ACE2 could explain its higher renal tropism [5]. A recent study showed that SARS-COV2 antigens accumulated in kidney tubules, suggesting that it is able to directly affect kidney cells. These data are consistent with the high prevalence (40%) of kidney injury, such as proteinuria and haematuria, at hospital admission of COVID-19 patients [2]. Therefore, given the role of AKI as a fatal comorbidity for COVID-19, and the frequent presence of renal signs in the early phase of the infection, we recommend early monitoring of renal involvement in these patients. Disclosure Statement The authors have no conflicts of interest to declare.

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          Most cited references9

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          Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus

          The recent emergence of Wuhan coronavirus (2019-nCoV) puts the world on alert. 2019-nCoV is reminiscent of the SARS-CoV outbreak in 2002 to 2003. Our decade-long structural studies on the receptor recognition by SARS-CoV have identified key interactions between SARS-CoV spike protein and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. One of the goals of SARS-CoV research was to build an atomic-level iterative framework of virus-receptor interactions to facilitate epidemic surveillance, predict species-specific receptor usage, and identify potential animal hosts and animal models of viruses. Based on the sequence of 2019-nCoV spike protein, we apply this predictive framework to provide novel insights into the receptor usage and likely host range of 2019-nCoV. This study provides a robust test of this reiterative framework, providing the basic, translational, and public health research communities with predictive insights that may help study and battle this novel 2019-nCoV.
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            Acute renal impairment in coronavirus-associated severe acute respiratory syndrome

            Acute renal impairment in coronavirus-associated severe acute respiratory syndrome. Background Severe acute respiratory syndrome (SARS) is a newly emerged infection from a novel coronavirus (SARS-CoV). Apart from fever and respiratory complications, acute renal impairment has been observed in some patients with SARS. Herein, we describe the clinical, pathologic, and laboratory features of the acute renal impairment complicating this new viral infection. Methods We conducted a retrospective analysis of the plasma creatinine concentration and other clinical parameters of the 536 SARS patients with normal plasma creatinine at first clinical presentation, admitted to two regional hospitals following a major outbreak in Hong Kong in March 2003. Kidney tissues from seven other patients with postmortem examinations were studied by light microscopy and electron microscopy. Results Among these 536 patients with SARS, 36 (6.7%) developed acute renal impairment occurring at a median duration of 20 days (range 5–48 days) after the onset of viral infection despite a normal plasma creatinine level at first clinical presentation. The acute renal impairment reflected the different prerenal and renal factors that exerted renal insult occurring in the context of multiorgan failure. Eventually, 33 SARS patients (91.7%) with acute renal impairment died. The mortality rate was significantly higher among patients with SARS and acute renal impairment compared with those with SARS and no renal impairment (91.7% vs. 8.8%) (P < 0.0001). Renal tissues revealed predominantly acute tubular necrosis with no evidence of glomerular pathology. The adjusted relative risk of mortality associated with the development of acute renal impairment was 4.057 (P < 0.001). By multivariate analysis, acute respiratory distress syndrome and age were the most significant independent risk factors predicting the development of acute renal impairment in SARS. Conclusion Acute renal impairment is uncommon in SARS but carries a high mortality. The acute renal impairment is likely to be related to multi-organ failure rather than the kidney tropism of the virus. The development of acute renal impairment is an important negative prognostic indicator for survival with SARS.
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              In-vitro renal epithelial cell infection reveals a viral kidney tropism as a potential mechanism for acute renal failure during Middle East Respiratory Syndrome (MERS) Coronavirus infection

              Background The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes symptoms similar to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), yet involving an additional component of acute renal failure (ARF) according to several published case reports. Impairment of the kidney is not typically seen in Coronavirus infections. The role of kidney infection in MERS is not understood. Findings A systematic review of communicated and peer-reviewed case reports revealed differences in descriptions of kidney involvement in MERS versus SARS patients. In particular, ARF in MERS patients occurred considerably earlier after a median time to onset of 11 days (SD ±2,0 days) as opposed to 20 days for SARS, according to the literature. In-situ histological staining of the respective cellular receptors for MERS- and SARS-Coronavirus showed highly similar staining patterns with a focus of a receptor-specific signal in kidney epithelial cells. Comparative infection experiments with SARS- and MERS-CoV in primary human kidney cells versus primary human bronchial epithelial cells showed cytopathogenic infection only in kidney cells, and only if infected with MERS-CoV. Kidney epithelial cells produced almost 1000-fold more infectious MERS-CoV progeny than bronchial epithelial cells, while only a small difference was seen between cell types when infected with SARS-CoV. Conclusion Epidemiological studies should analyze kidney impairment and its characteristics in MERS-CoV. Virus replication in the kidney with potential shedding in urine might constitute a way of transmission, and could explain untraceable transmission chains leading to new cases. Individual patients might benefit from early induction of renoprotective treatment.
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                Author and article information

                Journal
                Nephron Clin Pract
                Nephron Clin Pract
                NEF
                Nephron. Clinical Practice
                S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH-4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.com )
                1660-8151
                1660-2110
                19 May 2020
                : 1-2
                Affiliations
                [1 ] aDepartment of Public Health, Chair of Nephrology “Federico II”, University of Naples, Naples, Italy
                [2 ] bDepartment of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples “Federico II”, Naples, Italy
                [3 ] cInstitute for Biomedical Research and Innovation, National Research Council of Italy, Palermo, Italy
                Author notes
                *Dr. Ivana Capuano, Department of Public Health, Chair of Nephrology “Federico II”, University of Naples, Via Sergio Pansini, 5, IT–80131 Naples (Italy), ivanacapuano@ 123456libero.it
                Article
                nef-0001
                10.1159/000508381
                7270059
                32428921
                53400638-4cd8-4b77-be2b-653c0dc90aaa
                Copyright © 2020 by S. Karger AG, Basel

                This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

                History
                : 6 April 2020
                : 30 April 2020
                Page count
                References: 5, Pages: 2
                Categories
                Clinical Practice: Letter to the Editor

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