Kidney damage in Covid-19: clinical and morphological manifestations of renal pathology in 220 patients died from Covid-19

Kidney damage is common in patients with severe forms of COVID-19 and associated with poor prognosis. The causes and nature of kidney damage at COVID-19 have not yet been determined. The study aimed to investigate the incidence, causes and nature of kidney damage in patients with COVID-19. The data obtained from 220 patients, died from COVID-19 between April 20 and May 20, 2020. At the time of hospitalization, 55 (25%) patients had features of chronic kidney disease (CKD). Acute kidney injury (AKI) developed in 135 patients (61%), its frequency did not differ significantly depending on the baseline renal function (67% vs 61% in patients with CKD and with initially normal function, respectively). The only significant predictor of AKI development was the duration of mechanical ventilation (6.1 vs 1.7 days). The number of patients receiving mechanical ventilation or ECMO for 5 or more days was 43% vs 10% for AKI and normal renal function, respectively. Pathologic examination revealed preexisting renal pathology in 76 patients (43%), including 34 out of 55 (62%) patients who had a decrease in glomerular filtration rate (GFR) at the time of hospitalization, and in 40 out of 165 (24%) patients who had normal kidney function at admission (P<0.01). The most common pathological feature responsible for kidney injury in the vast majority of cases was acute tubular necrosis. In some cases, tubular damage was associated with isometric vacuolization of the tubular epithelium. Most patients had also prominent capillaries and venular congestion with erythrocyte aggregates obstructing the lumen of peritubular and glomerular capillaries. Six patients with AKI (5.2%) had morphological features of thrombotic microangiopathy, accompanied by clinical manifestations (anemia, thrombocytopenia, increased LDH). Conclusion: acute kidney injury is a common complication of severe forms of coronavirus infection. The duration of mechanical ventilation is a significant predictor of its development. Thrombotic microangiopathy may be one of the rare causes of kidney damage in COVID-19.

COVID-19, острое повреждение почек, почечная патология, тромботическая микроангиопатия, COVID-19, acute kidney injury, renal pathology, thrombotic microangiopathy

1. Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395:565-574.

2. Tan W, Zhao X, Ma X, Wang W, Niu P, Xu W, et al. A novel coronavirus genome identified in a cluster of pneumonia cases-Wuhan, China 2019- 2020. China CDCWeekly.2020;2(4):61-2.

3. Guarner J. Three Emerging Coronaviruses in Two DecadesThe Story of SARS, MERS, and Now COVID-19. American Journal of Clinical Pathology. 2020.

4. Gorbalenya AE. Severe acute respiratory syndrome related coronavirus-The species and its viruses, a statement of the Coronavirus Study Group. BioRxiv. 2020.

5. Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. The Lancet. 2020;395(10223):470-3

6. Leisman D, Deutschman C and Legrand M Facing COVID-19 in the ICU: vascular dysfunction, thrombosis, and dysregulated inflammation Intensive Care Med. 2020 Apr 28: 1-4. doi: 10.1007/s00134-020-06059-6 [Epub ahead of print]

7. Chang J.C. Acute Respiratory Distress Syndrome as an Organ Phenotype of Vascular Microthrombotic Disease: Based on Hemostatic Theory and Endothelial Molecular Pathogenesis Clinical and Applied Thrombosis/Hemostasis Volume 25: 1-20

8. Sun K, Chen J, Viboud C. Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population-level observational study. The LancetDigital Health. 2020.

9. Wu C. et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern. Med. https://doi.org/10.1001/jamainternmed.2020.0994 (2020).

10. Liang W,GuanW, Chen R,WangW, Li J, Xu K, et al. Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. The Lancet Oncology. 2020;21(3):335-7.

11. Yan Deng, Wei Liu, Kui Liu et al. Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 (COVID-19) in Wuhan, China: a retrospective study. Chinese Medical Journal, Publish Ahead of Print DOI: 10.1097/CM9.0000000000000824

12. Wang L, Li X, Chen H, Yan S, Li D, Li Y, Gong Z: Coronavirus Disease 19 Infection Does Not Result in Acute Kidney Injury: An Analysis of 116 Hospitalized Patients from Wuhan, China. Am J Nephrol 2020;51:343-348. doi: 10.1159/000507471

13. Guan, W.-j. et al. Clinical characteristics of coronavirus disease 2019 in China. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa2002032 (2020).

14. Huang, C., Wang, Y., Li, X. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395: 497-506

15. Diao B, Wang C, Wang R, et al.: Human Kidney is a Target for Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection. In medRxiv, 2020

16. Cheng Y, Luo R, Wang K et al. Kidney disease is associated with in-hospital death of patients with COVID-19 Kidney International (2020) 97, 829-838; https://doi.org/10.1016/j.kint.2020.03.005

17. Panitchote, A., Mehkri, O., Hastings, A. et al. Factors associated with acute kidney injury in acute respiratory distress syndrome. Ann. Intensive Care 9, 74 (2019). https://doi.org/10.1186/s13613-019-0552-5

18. Joannidis M, Forni LG, Klein SJ, et al. Lung-kidney interactions in critically ill patients: consensus report of the Acute Disease Quality Initiative (ADQI) 21 Workgroup. Intensive Care Med. 2020;46(4):654-672. doi:10.1007/s00134-019-05869-7

19. Hirsch J S. Ng J H., Rosset D W al. Acute kidney injury in patients hospitalized with COVID-19 Kidney International, (2020), doi: https://doi.org/10.1016/j.kint.2020.05.006.

20. Ronco, C., Reis, T. Kidney involvement in COVID-19 and rationale for extracorporeal therapies. Nat Rev Nephrol 16, 308-310 (2020). https://doi.org/10.1038/s41581-020-0284-7

21. Патологическая анатомия covid-19 - атлас под общей редакцией О.В.Зайратьянца, Москва 2020

22. Su H, Yang M, Wan C, et al. Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China [published online ahead of print, 2020 Apr 9]. Kidney Int. 2020;S0085-2538(20)30369-0. doi:10.1016/j.kint.2020.04.003

23. Farkash, E.A., Wilson, A.M., and Jentzen, J.M. Ultrastructural Evidence for Direct Renal Infection with SARS-CoV-2. J Am Soc Nephrol. 2020;

24. Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395(10234):1417-1418. doi:10.1016/S0140-6736(20)30937-5

25. Kudose S, Batal I, Santoriello D et al. Kidney Biopsy Findings in Patients with COVID-19 Vol. 31, Issue 8 August 2020. doi:https://doi.org/10.1681/ASN.2020060802

26. Noris M, Benigni A, Remuzzi G, The case of Complement activation in COVID-19 multiorgan impact Kidney International DOI: 10.1016/j.kint.2020.05.013

27. Wilk, C.M. Coronaviruses hijack the complement system. Nat Rev Immunol 20, 350 (2020). https://doi.org/10.1038/s41577-020-0314-5

28. Gao, T. et al. Highly pathogenic coronavirus N protein aggravates lung injury by MASP-2-mediated complement over-activation. Preprint at medRxiv https://doi.org/10.1101/2020.03.29.20041962 (2020)

29. Gralinski, L.E., Sheahan, T.P., Morrison, T.E. et al. Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis. mBio. 2018; 9

30. Chang JC. Acute Respiratory Distress Syndrome as an Organ Phenotype of Vascular Microthrombotic Disease: Based on Hemostatic Theory and Endothelial Molecular Pathogenesis. Clin Appl Thromb Hemost. 2019;25:1076029619887437. doi:10.1177/1076029619887437

31. Magro, C., Mulvey, J.J., Berlin, D. et al. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases. Transl Res. 2020

32. Jhaveri, K. D., Meir, L. R., Flores Chang, B. S., Parikh, R., Wanchoo, R., Barilla-LaBarca, M. L., Bijol, V., & Hajizadeh, N. (2020). Thrombotic microangiopathy in a patient with COVID-19. Kidney international, S0085-2538(20)30629-3. Advance online publication. https://doi.org/10.1016/j.kint.2020.05.025

33. Emami A, Javanmardi F, Pirbonyeh N, Akbari A. Prevalence of Underlying Diseases in Hospitalized Patients with COVID-19: a Systematic Review and Meta-Analysis. Arch Acad EmergMede. 2020; 8(1): e35.

34. Hill NR, Fatoba ST, Oke JL, et al. Global Prevalence of Chronic Kidney Disease - A Systematic Review and Meta-Analysis. PLoS One. 2016;11(7):e0158765. Published 2016 Jul 6. doi:10.1371/journal.pone.0158765

35. Henry B.M, Lippi G. Chronic kidney disease is associated with severe coronavirus disease 2019 (COVID-19) infection. International Urology and Nephrology https://doi.org/10.1007/s11255-020-02451-9

36. Li X, Wang L, Yan S, Yang F, Xiang L, Zhu J, Shen B, Gong Z, Clinical characteristics of 25 death cases with COVID-19: a retrospective review of medical records in a single medical center, Wuhan, China, International Journal of Infectious Diseases (2020), doi:https://doi.org/10.1016/j.ijid.2020.03.053

37. Ciceri F, Beretta L, Scandroglio AM, et al. Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS): an atypical acute respiratory distress syndrome working hypothesis. Critical Care and Resuscitation: Journal of the Australasian Academy of Critical Care Medicine. 2020 Apr;22(2):95-97.