The spectrum of kidney biopsies in hospitalized patients with COVID-19, acute kidney injury and/or proteinuria

Abstract

We report a multicentric retrospective case series of patients with COVID-19 who developed acute kidney injury and/or proteinuria and underwent a kidney biopsy in the Paris and its metropolitan area. Forty-seven patients (80.9% men) with COVID-19 who underwent a kidney biopsy between March 08 and May 19, 2020 were included. Median age was 63 years IQR [52–69]. Comorbidities included hypertension (66.0%), diabetes mellitus (27.7%), obesity (27.7%), history of chronic kidney (25.5%), cardiac (38.6%) and respiratory (27.3%) diseases. Initial symptoms were fever (85.1%), cough (63.8%), shortness of breath (55.3%), and diarrhea (23.4%). Almost all patients developed acute kidney injury (97.9%) and 63.8% required renal replacement therapy. Kidney biopsy showed two main histopathological patterns, including acute tubular injury in 20 (42.6%) patients, and glomerular injury consisting of collapsing glomerulopathy and focal segmental glomerulosclerosis in 17 (36.2%) patients. Two (4.3%) patients had acute vascular nephropathy, while eight (17%) had alternative diagnosis most likely unrelated to COVID-19. Acute tubular injury occurred almost invariably in the setting of severe forms of COVID-19, whereas patients with glomerular injury had various profiles of COVID-19 severity and collapsing glomerulopathy was only observed in patients harboring a combination of APOL1 risk variants. At last follow-up, 16 of the 30 patients who initially required dialysis were still on dialysis, and 9 died. The present study describes the spectrum of kidney lesions in patients with COVID-19. While acute tubular injury is correlated with COVID-19 severity, the pattern of glomerular injury is intimately associated with the expression of APOL1 risk variants.

Pathophysiology of COVID-19-associated acute kidney injury

“…Virus detection (using immunohistochemistry for SARS-CoV-2 nucleocapsid and RNA in situ hybridization) were negative in patient samples on which it was performed. Another series from France demonstrated tubular injury in the most severely ill cohort whereas glomerular pathology was restricted to the non-ICU patients 34 . Of note, most biopsies were performed several weeks after the onset of COVID-19 symptoms, and most have failed to show notable SARS-CoV-2 infection of the kidney.…”

“…In addition, these clinical data should be integrated with pathological findings from analyses of kidney biopsy samples 29 – 33 to gain greater insights into the pathophysiology of COVID-19 AKI. Evidence from a study of biopsy data from 47 patients in France demonstrated that kidney injury seen in cases with the most severe respiratory disease in the ICU is predominantly tubular (66.7%); by contrast, collapsing glomerulopathy and focal segmental glomerulosclerosis were not seen in critically ill patients but were observed in 70.6% of cases not in the ICU 34 . More than two coexisting comorbidities were seen in over 60% of cases and the occurrence of collapsing glomerulopathy correlated highly with the expression of high-risk APOL1 genotypes.…”

“…Collapsing glomerulopathy has been reported in several patients with COVID-19 (Supplementary Table 1 ). This entity has been described as COVID-19-associated nephropathy (COVAN), and seems to occur mostly in patients with non-severe respiratory symptoms of COVID-19 and isolated AKI or in those presenting with glomerular proteinuria 30 , 32 , 34 . Of note, collapsing glomerulopathy has previously been described in the context of other viral infections, including HIV parvovirus B19, cytomegalovirus and Epstein–Barr virus infections.…”

Acute Kidney Injuries of otherwise normal kidneys have different characteristics in different stages of COVID-19

“…Kidney biopsies may give some clues. Direct virulence of SARS-CoV-2 may be responsible for kidney involvement with acute tubular injury and podocytopathies [21,22,23]. In a report of kidney biopsies in COVID-19 patients, podocytopathies and tubulo-interstitial diseases were main ndings while immune mediated glomerular diseases were also found [24].…”

Case Report: Adult Post-COVID-19 Multisystem Inflammatory Syndrome and Thrombotic Microangiopathy

“…Kidney involvement is frequent in COVID-19, as more than 40% of cases have abnormal proteinuria at hospital admission (16,17). Scarce histological data are available, showing in most cases ATN, collapsing glomerulopathy or TMA in patients with acute COVID-19 infection (18)(19)(20)(21)(22). AKI is also common during MIS-C, ranging from 10% to 60% of the cases (6, 23, 24) while it was described in four adults in a case series of 20 MIS-A with cardiac involvement (12).…”