Our understanding of COVID-19-associated kidney dysfunction continues to evolve rapidly. In brief, more than one-third of hospitalized patients with COVID-19 develop AKI, and the most common kidney pathology finding in patients who die from COVID-19 and undergo autopsy is acute tubular injury; a minority have focal fibrin thrombi. In addition to tubular injury, kidney biopsy case series have revealed diverse injury patterns which can be loosely generalized into podocytopathies, thrombotic microangiopathy (TMA)/acute endothelial injury, and sequelae of immune activation.
COVID-19-associated kidney injury is highlighted in the following case. The patient is a 44-year-old Hispanic man with a history of obesity, hypertension, and atrial fibrillation who presented with mild upper respiratory symptoms and a syncopal episode. He was found to be hypertensive (155/108 mm Hg), have an intracranial hemorrhage involving the basal ganglia, acute kidney injury (AKI) with a creatinine of 6.7 mg/dL, and nephrotic range proteinuria (11.4 g/g on uPCR); he tested positive for SARS-CoV-2 infection. The patient was discharged after stroke management, and experienced only minimal COVID-19 symptoms which resolved. However, creatinine remained elevated in the outpatient setting, peaking at 12 mg/dL four weeks after initially testing positive for COVID-19. Dialysis was initiated and a kidney biopsy was performed.
Kidney biopsy demonstrated collapsing glomerulopathy with ultrastructural features of acute endothelial injury, as well as acute tubular injury. Immunofluorescence studies were negative for immune deposits. Electron microscopy revealed acute endothelial injury, with loss of endothelial cell fenestrations and subendothelial space expansion due to accumulation of electron-lucent material. There was widespread podocyte foot process effacement, as is seen in podocytopathies and collapsing glomerulopathy. The patient remained on dialysis. He tested positive for homozygous APOL1 high-risk alleles, despite the very low prevalence of these in the Hispanic population (case and images provided courtesy of Dr. Shreeram Akilesh, see more images from this case published in AJKD).
This case highlights a few key features of COVID-19-related kidney dysfunction which have been shown in other studies. First, significant renal injury may occur even in the setting of mild respiratory symptoms. Second, there is a strong association between the development of collapsing glomerulopathy in the setting of COVID-19 and APOL1 high-risk allele carriers, which parallels that seen in HIV-infected patients. Third, acute endothelial injury may be seen, with or without systemic features of TMA. Finally, acute tubular injury is relatively common.
African American and Hispanic patients are disproportionately affected by certain COVID-19-related kidney diseases. In patients with COVID-19 and kidney dysfunction requiring biopsy, podocytopathies were common and usually manifest as collapsing glomerulopathy and associated with high-risk APOL1 genotypes. TMA and acute endothelial injury have been described, particularly in the setting of additional underlying diseases; endothelial dysfunction may represent an important mechanism of SARS-CoV-2 associated organ injury. A variety of immune-mediated glomerular diseases have been documented, including immune complex deposition, anti-glomerular basement membrane disease, and pauci-immune crescentic glomerulonephritis. Transplant patients who get COVID-19 have increased incidence of rejection. Most studies have shown no definitive direct coronavirus infection in the kidney. Systemic cytokine-mediated effects, immune responses, and hemodynamic issues appear to be key drivers of kidney injury in patients with COVID-19.
– Post prepared by Nicole Andeen, AJKDBlog Contributor
Title: Multicenter Clinicopathologic Correlation of Kidney Biopsies Performed in COVID-19 Patients Presenting With Acute Kidney Injury or Proteinuria
Authors: S. Akilesh, C.C. Nast, M. Yamashita, K. Henriksen, V. Charu, M.L. Troxell, N. Kambham, E. Bracamonte, D. Houghton, N.I. Ahmed, C.C. Chong, B. Thajudeen, S. Rehman
F. Khoury, J.E. Zuckerman, J. Gitomer, P.C. Raguram, S. Mujeeb, U. Schwarze, M.B. Shannon, I. De Castro, C.E. Alpers, R.F. Nicosia, N.K. Andeen, and Kelly D. Smith
In the face of the unprecedented public health crisis posed by the current pandemic, this special collection gathers COVID-19–related publications from the NKF family of journals. All articles in the collection are freely available.