COVID-19-related collapsing glomerulopathy revealing a rare risk variant of APOL1: lessons for the clinical nephrologist

Excerpt

A 57-year-old patient of Congolese origin with a medical history of hypertension under triple therapy was referred to the emergency department due to significant deterioration in general condition, loss of 10 kg in one month, fever, anosmia and ageusia. He also reported a few episodes of non-bloody diarrhea and oliguria. Laboratory findings revealed severe acute kidney failure (serum creatinine at 30.3 mg/dL versus 0.8 mg/dL one month earlier, blood urea nitrogen at 536 mg/dL), hyperkaliemia at 7.4 mmol/L, and low bicarbonatemia at 13 mmol/L (Supplemental table). There was glomerular-range proteinuria with urinary protein-to-creatinine ratio (uPCR) at 1.2 g/g including 0.6 g/g of albuminuria and microscopic hematuria (41/mm³). Normocytic anemia was also noticed (10 g/dL), as was lymphopenia (300/mm³), marked inflammatory syndrome (C-reactive protein 2.5 mg/dL, fibrinogen 0.52 g/dL), and hypoalbuminemia (2.5 g/dL). Etiological assessment showed significant activation of the alternate complement pathway (low C3, normal C4), non-significant titer of anti-nuclear antibodies (1/80), and negative anti-neutrophil cytoplasmic, anti-glomerular basement membrane and anti-PLA2R antibodies. Biological findings also revealed polyclonal hypergammaglobulinemia, normal light chain ratio, and negative cryoglobulinemia. Testing for human immunodeficiency, hepatitis B/C viruses, and syphilis were negative, as were CMV, HHV6, HHV7 and Parvovirus B19 detection by PCR. Finally, nasal and tracheal PCR confirmed acute SARS-CoV-2 infection. The patient initially needed two dialysis sessions. He did not require any oxygen support nor specific treatment for COVID-19 infection. However, given the persisting kidney dysfunction one month later (serum creatinine 2.5 mg/dL and increased uPCR 4.9 g/g), a kidney biopsy was performed, revealing a collapsing variant of focal and segmental glomerulosclerosis (FSGS): histological examination was significant for diffuse hypertrophy and vacuolation of podocyte cytoplasm, diffuse interstitial lymphoplasmacytic infiltrate, and acute tubular necrosis associated with several microcystic tubular dilations (Fig. 1). There was no sign of cellular proliferation within the glomeruli. Immunofluorescence testing revealed mild peripheral and polytypic IgM and C3 deposits within the glomeruli. Electron microscopy did not reveal any foot process effacement, immune deposition, or endothelial tubulo-reticular inclusion. In this context, APOL1 genotyping was performed on a peripheral blood sample with respect to G0 wild type, G1 (rs73885319 and rs60910145) and G2 (rs71785313) SNPs by direct Sanger sequencing. This analysis revealed the rare APOL1 genotype G1^GM/G1^G+. Four months after admission, renal outcome was globally favorable with serum creatinine stabilization at 1.6 mg/dL and sequelae proteinuria at 1.6 g/g under ACE inhibitors. On a physical level, the patient fully recovered.

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