Native and transplant kidney histopathological manifestations in association with COVID-19 infection: A systematic review

Abstract

BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can result in clinically significant multi-system disease including involvement in the kidney. The underlying histopathological processes were unknown at the start of the pandemic. As case reports and series have been published describing the underlying renal histopathology from kidney biopsies, we have started to gain an insight into the renal manifestations of this novel disease. AIM To provide an overview of the current literature on the renal histopathological features and mechanistic insights described in association with coronavirus disease 2019 (COVID-19) infection. METHODS A systematic review was performed by conducting a literature search in the following websites-‘PubMed’, ‘Web of Science’, ‘Embase’ and ‘Medline-ProQuest’ with the following search terms-“COVID-19 AND kidney biopsy”, “COVID-19 AND renal biopsy”, “SARS-CoV-2 AND kidney biopsy” and “SARS-CoV-2 AND renal biopsy”. We have included published data up until February 15, 2021, which includes kidney biopsies (native, transplant and postmortem) from patients with COVID-19. Data on clinical presentation, histopathological features, management and outcome was extracted from the reported studies. RESULTS The total number of biopsies reported on here is 288, of which 189 are postmortem, 84 native and 15 transplants. The results are varied and show underlying pathologies ranging from collapsing glomerulopathy and acute tubular injury (ATI) to anti-nuclear cytoplasmic antibody associated vasculitis and pigment nephropathy. There was variation in the specific treatment used for the various renal conditions, which included steroids, hydroxychloroquine, eculizumab, convalescent plasma, rituximab, anakinra, cyclophosphamide and renal replacement therapy, amongst others. The pathological process which occurs in the kidney following COVID-19 infection and leads to the described biopsy findings has been hypothesized in some conditions but not others (for example, sepsis related hypoperfusion for ATI). It is important to note that this represents a very small minority of the total number of cases of COVID-19 related kidney disease, and as such there may be inherent selection bias in the results described. Further work will be required to determine the pathogenetic link, if any, between COVID-19 and the other renal pathologies. CONCLUSION This report has clinical relevance as certain renal pathologies have specific management, with the implication that kidney biopsy in the setting of renal disease and COVID-19 should be an early consideration, dependent upon the clinical presentation.

Collapsing Glomerulonephritis in a Kidney Transplant Recipient after mRNA SARS-CoV-2 Vaccination

“…During the last year, CG has been defined as the most frequent histopathological diagnosis for COVID-19 patients with acute renal failure or proteinuria [1], giving birth to the term COVID-19 associated nephropathy (COVAN). It has also been described in kidney grafts [2,3,15]. One of the possible mechanisms for this kidney damage is the direct toxicity of the virus since autopsy studies have shown its presence in the kidneys [16].…”

“…Both de novo glomerulonephritis and relapses have been reported. Among them, focal segmental glomerulosclerosis (FSGS) has been highlighted, specifically the collapsing glomerulonephritis (CG) variant [1][2][3]. Likewise, administration of the vaccine to the population has revealed cases of glomerulonephritis.…”

Intrinsic Kidney Pathology Following COVID-19 Infection in Children and Adolescents: A Systematic Review

“…CG has previously been reported to associate with multiple infections and inflammatory conditions, namely HIV and systemic lupus erythematous [ 43 ]. Previous reviews evaluating COVID-19 induced glomerular disease in adults suggest CG to be amongst the most prevalent histopathological presentations [ 3 , 44 ]. The pathogenesis of CG is currently believed to be a multifactorial process associated with both direct viral invasion of glomerular structures and cytokine release [ 45 , 46 ].…”

“…The coronavirus disease (COVID-19) that began in 2019 has spiraled into a global pandemic, continuing up to this day, since the identification of the first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) case in Wuhan, China, in December 2019 [ 1 , 2 ]. Whilst data relating to the epidemiology, pathophysiology, risk factors and prognosis of adults with kidney histopathology following acute COVID-19 infection are becoming more well-established, there remains a sizable knowledge gap in our understanding of intrinsic pathological kidney manifestations in children following acute COVID-19 infection [ 3 ]. This is likely explained by the fact that children and adolescents only form about 1–2% of all COVID-19 cases reported globally [ 4 ].…”

COVID-19 and Kidney Transplantation: Epidemiology, Histopathological Presentation, Clinical Presentation and Outcomes, and Therapeutic Strategies

“…Several authors observing KTx patients affected by COVID-19 infections [20][21][22][23][24][25][26][27][28][29][30] have described different aspects. The authors are still debating whether the lesions are to be ascribed directly to the virus or if the virus acts indirectly.…”