Kidney Biopsy Findings in Patients with COVID-19

Abstract

BackgroundCoronavirus disease 2019 (COVID-19) is thought to cause kidney injury by a variety of mechanisms. To date, pathologic analyses have been limited to patient reports and autopsy series.MethodsWe evaluated biopsy samples of native and allograft kidneys from patients with COVID-19 at a single center in New York City between March and June of 2020. We also used immunohistochemistry, in situ hybridization, and electron microscopy to examine this tissue for presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).ResultsThe study group included 17 patients with COVID-19 (12 men, 12 black; median age of 54 years). Sixteen patients had comorbidities, including hypertension, obesity, diabetes, malignancy, or a kidney or heart allograft. Nine patients developed COVID-19 pneumonia. Fifteen patients (88%) presented with AKI; nine had nephrotic-range proteinuria. Among 14 patients with a native kidney biopsy, 5 were diagnosed with collapsing glomerulopathy, 1 was diagnosed with minimal change disease, 2 were diagnosed with membranous glomerulopathy, 1 was diagnosed with crescentic transformation of lupus nephritis, 1 was diagnosed with anti-GBM nephritis, and 4 were diagnosed with isolated acute tubular injury. The three allograft specimens showed grade 2A acute T cell–mediated rejection, cortical infarction, or acute tubular injury. Genotyping of three patients with collapsing glomerulopathy and the patient with minimal change disease revealed that all four patients had APOL1 high-risk gene variants. We found no definitive evidence of SARS-CoV-2 in kidney cells. Biopsy diagnosis informed treatment and prognosis in all patients.ConclusionsPatients with COVID-19 develop a wide spectrum of glomerular and tubular diseases. Our findings provide evidence against direct viral infection of the kidneys as the major pathomechanism for COVID-19–related kidney injury and implicate cytokine-mediated effects and heightened adaptive immune responses.

Acute Kidney Injury in COVID-19: Another Challenge for Nephrology

“…Another finding is that some patients demonstrated collapsing focal segmental glomerulosclerosis. This pathology may be primarily limited to African American patients, and in some cases, genetic testing demonstrated the presence of APOL1 high-risk genotypes [3]. Less commonly reported findings include pigmented casts consistent with rhabdomyolysis, immune-mediated glomerular nephritis, and thrombotic microangiopathy.…”

Zebrafish studies on the vaccine candidate to COVID-19, the Spike protein: Production of antibody and adverse reaction

“…The response to SARS-CoV-2 in humans appears to be hemophagocytic lymphohistiocytosis (HLH), characterized by immune hyperactivation that occurs when Natural Killer cells and cytotoxic T lymphocytes do not eliminate activated macrophages, leading to excessive production of pro-inflammatory cytokines 43 . These pro-inflammatory cytokines could be associated with a major pathomechanism in kidney damage causing nephrotic proteinuria, collapsing glomerulopathy, membranous glomerulopathy, nephritis, and acute tubular injury 44 . Although some data suggest the incidence of Acute Kidney Injury (AKI) by SARS-CoV-2 to be low 45,46 , other studies indicate that AKI is one of the significantly more common complications in patients who died of COVID-19, pointed out as a marker of multiple organ dysfunction and severe disease 46–48 .…”

COVID-19–Associated Acute Kidney Injury

“…Although Cheng et al (1) observed high-sensitivity C-reactive protein levels to be elevated in most patients with AKI, definitive proof of the frequently invoked "cytokine storm" and its relative contribution to the majority of patients with AKI have been recently questioned. The infrequency of interstitial inflammation seen with the tubular injury subphenotype does not eliminate a potential contribution from systemic inflammation on local or regional hemodynamics (7). However, blood IL-6 levels in patients with COVID-19 have been observed to be lower compared with data from patients participating in previous National Heart, Lung and Blood Institute Acute Respiratory Distress Syndrome Network (ARDSNet) trials (8).…”