Dataset Information

COVID-19-Associated Glomerular Disease.

ABSTRACT:

Background

Studies have documented AKI with high-grade proteinuria in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In some patients, biopsies have revealed collapsing glomerulopathy, a distinct form of glomerular injury that has been associated with other viruses, including HIV. Previous patient reports have described patients of African ancestry who developed nephrotic-range proteinuria and AKI early in the course of disease.

Methods

In this patient series, we identified six patients with coronavirus disease 2019 (COVID-19), AKI, and nephrotic-range proteinuria. COVID-19 was diagnosed by a positive nasopharyngeal swab RT-PCR for SARS-CoV-2 infection. We examined biopsy specimens from one transplanted kidney and five native kidneys. Three of the six patients underwent genetic analysis of APOL1, the gene encoding the APOL1 protein, from DNA extracted from peripheral blood. In addition, we purified genomic DNA from paraffin-embedded tissue and performed APOL1 genotype analysis of one of the native biopsies and the donor kidney graft.

Results

All six patients were of recent African ancestry. They developed COVID-19-associated AKI with podocytopathy, collapsing glomerulopathy, or both. Patients exhibited generally mild respiratory symptoms, and no patient required ventilator support. Genetic testing performed in three patients confirmed high-risk APOL1 genotypes. One APOL1 high-risk patient developed collapsing glomerulopathy in the engrafted kidney, which was transplanted from a donor who carried a low-risk APOL1 genotype; this contradicts current models of APOL1-mediated kidney injury, and suggests that intrinsic renal expression of APOL1 may not be the driver of nephrotoxicity and specifically, of podocyte injury.

Conclusions

Glomerular disease presenting as proteinuria with or without AKI is an important presentation of COVID-19 infection and may be associated with a high-risk APOL1 genotype.

SUBMITTER: Shetty AA

PROVIDER: S-EPMC7894674 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: There is still no consensus about the coronavirus disease 2019 (COVID-19) vaccine-associated glomerular disease (CVAGD). Given the large number of vaccinations administered and the variations in glomerulopathy observed across different countries and regional environments, CVAGD remains an important area of concern. Aim of study: We aimed to elucidate the findings of CVAGD within a Taiwanese cohort using biopsy data. Additionally, we endeavored to clarify the presentation of CVAGD. Methods: We collected data from patients who underwent renal biopsy from June 2021 to October 2022 at Taichung Veterans General Hospital. Two independent nephrologists meticulously reviewed the charts to exclude cases unrelated to vaccination. Results: Initially, a total of 286 patients underwent renal biopsy at our institute. Ultimately, we identified 14 patients with highly suspected CVAGD. All 14 patients exhibited proteinuria and hematuria. The urinary protein-to-creatinine ratio was elevated (median of 2012.1 mg/g; interquartile range (IQR) 25%-IQR 75%: 941.85-3884.1 mg/g) with a median serum creatinine level of 1.71 mg/dL (0.79-5.35). The majority of CVAGD cases were diagnosed as immunoglobulin A (IgA) nephropathy (n = 5, 35.7%), followed by antineutrophil cytoplasmic antibody (ANCA)-related rapidly progressive glomerulonephritis (RPGN) (n = 4, 28.6%). There were only three cases of minimal change disease each: one case of focal segmental glomerulosclerosis, one of membranous glomerulonephritis, and one of lupus nephritis. The culprit of COVID-19 vaccinations was 35.7% (n = 5) of Oxford-AstraZeneca (ChAdOx1-S), 42.9% (n = 6) of Moderna, and 21.4% (n = 3) of BNT162b2. Most patients experienced improvements in renal function. Only two cases of P-ANCA RPGN and one case of IgA nephropathy did not recover. Eighty percent of IgA nephropathy cases had favorable outcomes, but none of the patients with P-ANCA RPGN achieved full recovery. Conclusions: IgA nephropathy and ANCA-related RPGN were the most common CVAGD, and all types of COVID-19 vaccines posed a risk for CVAGD. However, further studies are required to confirm causality.

Project description:Background The novel coronavirus disease (COVID-19), also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an evolving pandemic with significant mortality. Information about the impact of infection on glomerular disease patients in particular has been lacking. Understanding the virus's effect in glomerular disease is constantly changing. This review article summarizes the data published thus far on COVID-19 and its manifestations in pre-existing and de novo glomerular disease. Summary While patients with glomerular disease may be at higher risk of severe COVID-19 due to their immunosuppressed status, some data suggest that a low amount of immunosuppression may be helpful in mitigating the systemic inflammatory response which is associated with high mortality rates in COVID-19. There have been a few case reports on COVID-19 causing glomerular disease relapse in patients. Multiple mechanisms have been proposed for kidney injury, proteinuria, and hematuria in the setting of COVID-19. More commonly, these are caused by direct tubular injury due to hemodynamic instability and hypoxic injury. However, the cytokine storm induced by COVID-19 may trigger common post-viral glomerular disease such as IgA nephropathy, anti-GBM, and ANCA vasculitis that have also been described in COVID-19 patients. Collapsing glomerulopathy, a hallmark of HIV-associated nephropathy, is being reported SARS-CoV-2 cases, particularly in patients with high-risk APOL1 alleles. Direct viral invasion of glomerular structures is hypothesized to cause a podocytopathy due to virus's affinity to ACE2, but evidence for this remains under study. Key Messages Infection with SARS-CoV-2 may cause glomerular disease in certain patients. The mechanism of de novo glomerular disease in the setting of COVID-19 is under study. The management of patients with existing glomerular disease poses unique challenges, especially with regard to immunosuppression management. Further studies are needed to inform clinician decisions about the management of these patients during the COVID-19 pandemic.