key: cord-1028780-vj64tu4d authors: Mihalopoulos, Meredith; Dogra, Navneet; Mohamed, Nihal; Badani, Ketan; Kyprianou, Natasha title: COVID-19 and Kidney Disease: Molecular Determinants and Clinical Implications in Renal Cancer date: 2020-06-09 journal: Eur Urol Focus DOI: 10.1016/j.euf.2020.06.002 sha: b02b56197b5339b56e247b09ede87e2cd91d692f doc_id: 1028780 cord_uid: vj64tu4d CONTEXT: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic that erupted in December 2019 has affected more than a million people from over 200 countries, claiming over 70 000 lives (by April 7, 2020). As the viral infection is driven by increased angiotensin-converting enzyme-2 (ACE2) expression, with the kidney exhibiting the highest expression, it is crucial to gain insights into the mechanisms underlying renal cell carcinoma (RCC) and coronavirus disease 2019 (COVID-19). OBJECTIVE: This study considers up-to-date information on the biological determinants shared by COVID-19 and renal disease, and aims to provide evidence-based recommendations for the clinical management of RCC patients with COVID-19. EVIDENCE ACQUISITION: A literature search was performed using all sources (MEDLINE, EMBASE, ScienceDirect, Cochrane Libraries, and Web of Science). As of March 31, 2020, the Center for Disease Control reported that of the adults hospitalized for COVID-19 with underlying conditions in the USA, 74.8% had chronic renal disease. EVIDENCE SYNTHESIS: Evidence is discussed from epidemiological studies on SARS-CoV-2 pandemic and molecular studies on the role of kidney in facilitating routes for SARS-CoV-2 entry, leading to increased virulence of SARS-CoV-2 and clinical manifestation of symptoms in RCC. CONCLUSIONS: This analysis will advance our understanding of (1) the molecular signatures shared by RCC and COVID-19 and (2) the clinical implications of overlapping signaling pathways in the therapeutic management of RCC and COVID-19 patients. PATIENT SUMMARY: Amid the coronavirus disease 2019 (COVID-19) pandemic, patients diagnosed with renal cell carcinoma and infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may receive complimentary treatment modalities to enhance therapeutic response. particular, ACE2 expression is higher in the kidneys than in 119 any other organ, with potentially 100 times higher expres- Docking and host cell entry of SARs-CoV-2 occur via virion-associated "spike protein" recognition and binding with the ACE2 receptor (1). Receptor recognition and ACE2 activation are assisted by transmembrane protein TMPRSS2 (2) , which leads to endocytosis of virions (3) and early endosome formation (4), and ultimately responsible for the release of viral RNA into the cytoplasm of host cells causing virulence. ACE2 = angiotensin-converting enzyme-2; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; TMPRSS2 = type-II transmembrane serine protease 2. had chronic renal failure [5] . Surgical patient triage Depending on local transmission patterns and hospital needs, lower-risk kidney tumors should be postponed, while larger and aggressive tumors should be treated as the risk of progression must be weighed against the risks of COVID-19. All patients planning to undergo surgery for kidney cancer should be tested prior to surgery, depending on local community access to testing. If the patient is COVID-19 positive, every effort should be made to delay surgery until full recovery of the patient and viral shedding risk is reduced. Operating room personnel Limit personnel in the operating room during surgery, allowing only essential personnel, and limit traffic in and out of rooms. PPE PPE is mandatory and should include N-95 masks to mitigate transmission risk. Operating room risk reduction Efforts should be made to reduce transmission during intubation and extubation, with only ESSENTIAL personnel present during these times. In addition, surgical transmission via surgical plume should be reduced by lowering cautery settings, application time, and total duration of tissue desiccation. Special considerations for minimally invasive surgery During minimally invasive surgery, CO 2 pressure should be maintained as low as safely possible, and gas leak or release from ports during surgery should be minimized. Every effort should be made to suction any residual CO 2 at the end of procedure prior to tumor extraction. A closed insufflation system should be used to reduce escape of CO 2 into the OR. Filters vary in size; the smallest filter available should be implemented to the suction system. COVID-19 = coronavirus disease 2019; OR = operating room; PPE = personal protective equipment. the virus (Fig. 3) . 378 and miR-451 as RCC biomarkers [69] . MERS, and sepsis [38, 73] . CRRT is also being used in current patients are discussed below [75] . blocking protease activity and inhibiting viral entry into the 501 cell (Fig. 2) . Endosome-lysosomal protease inhibitors such 502 as E64d or chlorpromazine, a clathrin-mediated endocyto-503 sis inhibitor, can also block endocytosis directly [80] . scope of such a development [75] . Understanding of COVID-19 based on 582 current evidence Emerging coronaviruses: genome structure replication, and pathogenesis Should COVID-19 concern nephrol-586 ogists? 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