The developed scar tissue in the infected kidneys may suggest a possible impact on kidney outcomes in the long term.
The fact that the coronavirus can result in severe damage in the human body is known, and also that kidneys can get infected. But what exactly happens in the kidney as a result of the infection remains elusive until now.
In this study, published in Cell Stem Cell, researchers investigated the kidney tissue of COVID-19 patients admitted to the Intensive Care Unit. They found scarring of the tissue as compared to ICU patients with a non-COVID-19 lung infection and a control group.
Next, the researchers questioned what exactly the cause was of the kidney damage. Could this be a direct effect of the virus, independent of systemic inflammation?
To investigate this, the researchers cultured mini kidneys, called organoids, in the lab. The kidney organoids are developed from stem cells and contain many different kidney cells, except for immune cells.
The kidney organoids were infected with SARS-CoV-2 and the researchers investigated the direct effect of the virus on the kidney cells, independent of potential secondary effects caused by immune cells or other systemic effects.
The results of this study indicate that the recent finding of another USA based large cohort study that reported kidney functional decline in over 90,000 COVID-19 survivors (Bowe et al, JASN) might be due to direct effects of the SARS-CoV2 virus on the kidney causing scar formation.
Researcher Jitske Jansen (Radboudumc) said, “In our study, we thoroughly investigated the causal damaging effects of the coronavirus in the kidneys. The infected kidney organoids show that the virus directly causes cell damage, independent of the immune system. With this work, we found a piece of the puzzle showing the deleterious effects the virus can have in the body.”
Researcher Katharina Reimer (RWTH Aachen Uniklinik) noted, “Kidney fibrosis, or scarring, is a serious long-term consequence that can occur virtually after any injury to the kidney and correlates with kidney function.
Long-term follow-up studies will provide further insights into kidney-related pathologies caused by SARS-CoV-2.”
To compare coronavirus disease 2019 (COVID-19) acute kidney injury (AKI) to sepsis-AKI (S-AKI). The morphology and transcriptomic and proteomic characteristics of autopsy kidneys were analyzed.
The spectrum of COVID-19 renal pathology included macrophage-dominant microvascular inflammation (glomerulitis and peritubular capillaritis), vascular dysfunction (peritubular capillary congestion and endothelial injury), and tubular injury with ultrastructural evidence of mitochondrial damage.
Investigation of the spatial architecture using a novel imaging mass cytometry revealed enrichment of CD3+CD4+ T cells in close proximity to antigen-presenting cells, and macrophage-enriched glomerular and interstitial infiltrates, suggesting an innate and adaptive immune tissue response.
Coronavirus disease 2019 AKI and S-AKI, as compared to nonseptic AKI, had an enrichment of transcriptional pathways involved in inflammation (apoptosis, autophagy, major histocompatibility complex class I and II, and type 1 T helper cell differentiation). Proteomic pathway analysis showed that COVID-19 AKI and to a lesser extent S-AKI were enriched in necroptosis and sirtuin-signaling pathways, both involved in regulatory response to inflammation. Upregulation of the ceramide-signaling pathway and downregulation of oxidative phosphorylation in COVID-19 AKI were noted.
This data highlights the similarities between S-AKI and COVID-19 AKI and suggests that mitochondrial dysfunction may play a pivotal role in COVID-19 AKI. This data may allow the development of novel diagnostic and therapeutic targets.
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), and is associated with acute kidney injury (AKI) in more than one-third of hospitalized patients.1
The AKI is often moderate to severe, and is an independent risk factor for in-hospital mortality.2,3 Acute tubular injury is considered the pathological hallmark of COVID-19 kidney disease as shown in both native and autopsy renal studies.4, 5, 6 Microthrombi, described in heart and lungs,7, 8, 9, 10, 11 is infrequently reported in kidneys.5,12 Similarly, although severe COVID-19 is associated with a systemic inflammatory response and inflammation in both lungs and heart, little is known about the immune response in the kidneys.
Direct viral toxicity, hemodynamic instability, cytokine storm, and immune-mediated injury have all been proposed as likely causes of renal injury in COVID-19.5,13,14 Recent studies have drawn similarities between sepsis-associated AKI (S-AKI) and COVID-19–related kidney injury.15,16 To date, reports evaluating the renal pathology in COVID-19 have largely focused on light microscopy and ultrastructural studies; molecular studies have been limited.
Herein, we present a series of COVID-19 patients who underwent postmortem examination with emphasis on renal pathology findings. Our study sought to describe the pathological spectrum of COVID-19–associated renal injury, and to characterize the molecular profile of COVID-19–associated AKI as compared with S-AKI and nonsepsis-related AKI (NS-AKI) to elucidate similarities and differences in underlying pathophysiology.
reference link : https://www.mayoclinicproceedings.org/article/S0025-6196(21)00510-3/fulltext
More information: Jitske Jansen et al, SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids, Cell Stem Cell (2021). DOI: 10.1016/j.stem.2021.12.010