Case Presentation: Collapsing glomerulopathy, a variant of focal segmental glomerulosclerosis (FSGS), is characterized by segmental and global collapse of the glomerular capillaries marked by significant hypertrophy and hyperplasia of podocytes causing severe tubulointerstitial disease. (1) There has been an emergence of these cases among African American patients with COVID-19, especially those with the apolipoprotein L1 (APOL1) allele. This new entity is termed COVID-associated glomerulonephropathy (COVAN) and is becoming increasingly prevalent in areas where the APOL1 allele is endemic. Here we present a case of a 52 y/o African American female with past medical history of atrial fibrillation, hypertension, and morbid obesity who presented with a chief complaint of cough, fever, fatigue, and shortness of breath for one week. The patient was unvaccinated and found to have COVID-19. Upon admission, the patient did not require any oxygen and so was not started on any treatment for the virus. She was also diagnosed with an acute kidney injury (AKI) with a creatinine of 2.25 (baseline 1.09) and blood urea nitrogen at 44. Pre-renal etiology was suspected and intravenous fluids were given without improvement. The patient’s fractional excretion of sodium (FeNa) was <1% and urinalysis showed significant proteinuria. Renal ultrasound was ordered to rule out obstruction and nephrology was consulted as renal function deteriorated quickly. C3 and C4, protein/creatinine ratio, ANCA, and SPEC were ordered per nephrology recommendations and were unremarkable. Renal ultrasound showed no signs of obstruction and intravenous fluids were discontinued due to lack of benefit. With concern for COVID-associated nephropathy (COVAN), the patient was presented in nephrology conference and ultimately found to be positive for the APOL1 allele. Nephrology did not recommend biopsy or steroids, but because her respiratory status worsened, she was treated with steroids. Renal function subsequently improved from peak of creatinine of 4.3 to 2.26 on discharge.

Discussion: Here we present a case of a patient with renal injury in the setting of COVID pneumonia who was also found to be positive for the APOL1 allele. Approximately 14% of the African American population is homozygous for the APOL1 G1 or G2 alleles, providing a partial explanation for the increased burden of kidney failure in the African American population. (1) Several other viruses have been associated with collapsed glomerulonephropathy, notably HIV, CMV, Parvovirus and EBV. (2) The pathology lies in the activation of interferon pathways. The APOL1 risk allele is activated by the interferon-chemokine pathway. Once activated, it induces macrophages to engulf glomerular epithelial cells, disrupts mitochondrial homeostasis and ultimately leads to glomerular epithelial cell death. (1) AKI is not uncommon in COVID-19 patients, with some studies suggesting nearly 45% of ICU patients having AKI, many of which end up requiring kidney replacement therapy and therefore are at an increased risk of mortality. (2)

Conclusions: As cases of COVID-19 persist, COVAN should be suspected as a differential diagnosis in patients with AKI. The relationship between COVID-19 and collapsing glomerulonephropathy in the setting of APOL1 gene carriers can have important geographical and public health implications. Resources should be directed towards investigating the early use of anti-inflammatory agents in at-risk patients to counter the risk of kidney injury and improve overall mortality.