COVID-19-associated nephritis: early warning for disease severity and complications?
Authors: Oliver Gross, Onnen Moerer, Manfred Weber, Tobias B Huber, Simone Scheithauer
Journal: The Lancet (2020)

Among patients with coronavirus disease 2019 (COVID-19), parameters for the prediction of the need for admission to intensive care units (ICUs) are urgently needed to enable appropriate resource allocation. Here we report that analysis of a urine sample on admission to hospital can be used to detect systemic capillary leak syndrome, which can be a predictor of fluid overload, respiratory failure, need for ICU admission, and death. At our medical centre (University Medical Center Göttingen, Göttingen, Germany), we identified abnormalities in the urine samples of patients with COVID-19 who became very sick within a few days. Three of these patients had coincidentally submitted urine samples in the few weeks before their infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These urine samples had been normal. However, on March 21, 2020, since becoming infected with SARS-CoV-2, the urine sample of one of these three patients was also positive for SARS-CoV-2 RNA. The urine samples of the other two patients have not been tested because of safety concerns. Some patients with COVID-19 were eventually admitted to the ICU. Before their admission to ICU, we detected low antithrombin III concentrations (26–62% [reference >70%]), severe hypalbuminaemia (serum albumin concentration of 1·4–1·9 mg/dL [reference 3·4–5·0 mg/dL]), and urine samples positive for blood, albumin, and leukocytes. Unlike patients in ICU, patients with COVID-19 receiving treatment for mild symptoms in the intermediate care unit had serum albumin concentrations above 2·0 mg/dL, and antithrombin concentrations were low but within normal limits. Patients with COVID-19 on the normal ward had the best serum albumin results (above 2·5 mg/dL) and normal urine. On the basis of these findings, we generated an algorithm for early detection of COVID-19-associated nephritis and to assess the risk of respiratory decompensation by capillary leak syndrome (figure). Can COVID-19 cause nephritis, and how might nephritis predict complications? SARS-CoV-2 uses the receptor ACE2 for cell entry, and podocytes express ACE2.1Harris RC Podocyte ACE2 protects against diabetic nephropathy.Kidney Int. 2012; 82: 255-256Summary Full Text Full Text PDF PubMed Scopus (16) Google Scholar Glomerular changes and nephritis-like histology have been described in postmortem samples from patients with COVID-19.2Su H Yang M Wan C et al.Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China.Kidney Int. 2020; (published online April 6.)DOI:10.1016/j.kint.2020.04.003Summary Full Text Full Text PDF PubMed Scopus (1274) Google Scholar Other zoonoses, such as some hantaviruses, cause nephrotic syndrome, which in turn induces cardiopulmonary syndrome.3Vaheri A Strandin T Hepojoki J et al.Uncovering the mysteries of hantavirus infections.Nat Rev Microbiol. 2013; 11: 539-550Crossref PubMed Scopus (359) Google Scholar, 4Llah ST Mir S Sharif S Khan S Mir MA Hantavirus induced cardiopulmonary syndrome: a public health concern.J Med Virol. 2018; 90: 1003-1009Crossref PubMed Scopus (22) Google Scholar Complications of nephrotic syndrome are known to be similar to capillary leak syndrome, and preventive therapies are available.5Noone DG Iijima K Parekh R Idiopathic nephrotic syndrome in children.Lancet. 2018; 392: 61-74Summary Full Text Full Text PDF PubMed Scopus (322) Google Scholar We recommend that patients with COVID-19 who have nephritis be carefully monitored for the following conditions: pulmonary interstitial oedema, due to severe fluid overload similar to nephrotic syndrome; immune incompetence, due to renal loss of immunoglobulins; circulatory insufficiency, due to hypalbuminaemia; poor drug response because of impaired plasma protein binding; and thromboembolic events due to antithrombin deficiency. In summary, the respiratory tract is the gateway for SARS-CoV-2 infection, but we postulate that COVID-19-associated nephritis, which can be easily screened for through a simple and inexpensive urine sample analysis, might help predict complications. This algorithm awaits further validation as a prediction tool. We have initiated a multicentre observational study (NCT04347824) in Germany to confirm our findings. If validated, we believe this tool could allow early anticipation of later need for ICU admission, improved allocation of patients for special therapies (eg, in clinical trials), and initiation of preventive strategies focused on capillary leak syndrome, including treatment that could save lives. The same screening methods could be used for the risk evaluation of outpatients. We declare no competing interests.