Aiyoub Pezeshgi 1
, Muhammed Mubarak 2
, Arjang Djamali 3
, Leila Mostafavi 4
, Siamak Moghadam-Kia 5
, Niloufar Alimohammadi 6
, Payam Peymani 7
, Saharnaz Pezeshgi 8* 1
Department of internal Medicine and Zanjan Metabolic Disease Research Center, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran2
Department of Histopathology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan3
Division of Nephrology, Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA4
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA5
Division of Rheumatology and Clinical Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA6
Department of Medicine, New York University School of Medicine, New York, New York, USA7
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands8
School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Kidney is one of the most predominantly organs affected by coronavirus disease 2019 (COVID-19) after the respiratory and immune systems. Among the renal parenchymal components, the tubulointerstitial compartment is presumed to be the prime target of injury in COVID-19. The main mechanism of renal tubular damage by COVID-19 is considered to be indirect, i.e., cytokine-mediated injury. A proportion of infected individuals mount a strong inflammatory response to the virus by an exaggerated immune response of the body, namely cytokine storm. Sudden and massive release of cytokines may lead to serious systemic hyper-inflammation and renal tubular injury and inflammation resulting in acute renal failure. In addition, a number of cases of glomerulopathies, particularly collapsing glomerulopathy (CG) have been reported, predominantly in people of African ancestry, as a rare form of kidney involvement by SARS-CoV-2 that may originate from the background genetic susceptibility in this population complicated by the second hit of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, either directly or indirectly. It is noteworthy that renal injury in COVID-19 could be severe in individuals of African origin due to the aforementioned genetic susceptibility, especially the presence of high-risk apolipoprotein L1 (APOL1) genotypes. Although the exact mechanism of kidney injury by SARS-CoV-2 is as yet unknown, multiple mechanisms are likely involved in renal damage caused by this virus. This review was aimed to summarize the salient points of pathogenesis of kidney injury, particularly glomerular injury in COVID-19 disease in the light of published data. A clear understanding of these is imperative for the proper management of these cases. For this review, a search was made of Google Scholar, Web of Science, Scopus, EBSCO and PubMed for finding English language articles related to COVID-19, kidney injury and glomerulopathy. From the information given in finally selected papers, the key aspects regarding glomerular involvement in COVID-19 were drawn out and are presented in this descriptive review.
Implication for health policy/practice/research/medical education: Kidney injury is common in patients with coronavirus disease 2019 (COVID-19). Most of the cases are presumed to be due to tubular injury. However, cases of glomerulopathy, particularly collapsing glomerulopathy (CG), are being increasingly reported, predominantly in patients of African ancestry. Although the exact pathogenesis of CG in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still unsettled, accumulating evidence suggests this manifestation of kidney injury may be related to high risk APOL1 genetic susceptibility superimposed by a second hit by SARS-CoV-2, either directly or indirectly.
Please cite this paper as: Pezeshgi A, Mubarak M, Djamali A, Mostafavi L, Moghadam-Kia S, Alimohammadi N, Peymani P, Pezeshgi S. COVID19-associated glomerulopathy and high-risk APOL1 genotype; Basis for a two-hit mechanism of injury? A narrative review on recent findings. J Nephropathol. 2021;10(2):e11. DOI: 10.34172/jnp.2021.11.