3. A special case of COVID-19-associated nephropathy in people of African ancestry
Genetic variants of apolipoprotein L1 (APOL1), which greatly increases the risk of kidney diseases, are found only in people of African descent (Genovese et al., 2010). The APOL1 alleles became common in Sub-Saharan Africa due to protection conferred by these alleles against the pathogen that causes African sleeping sickness (trypanosomiasis). Studies in recent times suggest that black people living in Sub-Saharan Africa have high predisposition to kidney disease as do African Americans, and that these two groups (African Americans and Black Africans) have common genetic susceptibilities. Two APOL1 susceptibility gene variants (G1 and G2) are linked with hypertension-associated CKD, collapsing focal segmental glomerulosclerosis and HIV-associated nephropathy (Kopp et al., 2011; Tayo et al., 2013; Ulasi et al., 2013). The APOL1 kidney risk variants encode circulating APOL1, which functions as a trypanolytic factor capable of killing the trypanosome parasites in the human serum (Genovese et al., 2010). These APOL1 risk variants developed some 10,000 years ago in Sub-Saharan Africa where trypanosomiasis was endemic. Thus, APOL1 gene is an innate immunity gene common in people of African ancestry.
Recent studies suggest that people with high/low renal risk alleles for APOL1, who are COVID-19-positive, may have a high risk of developing renal failure, proteinuria and hematuria. There are six case reports of collapsing glomerulopathy among COVID-19 patients of African ancestry, with severe AKI and nephrotic range proteinuria, two of whom carried APOL1 renal risk genotypes (Kissling et al., 2020; Larsen et al., 2020; Mohamed et al., 2020; Peleg et al., 2020). APOL1 coding variants have been associated with collapsing glomerulopathy among individuals with untreated HIV infection or undergoing interferon treatment. There is a high frequency of APOL1 risk genotypes among African Americans (~13%) and West Africans (~25%), with lower frequencies found in East and South Africans (Genovese et al., 2010; Dummer et al., 2015; Kasembeli et al., 2015). Collapsing glomerulopathy has been described in 24 cases of COVID-19 infection; 23 out of the 24 (95.8%) cases were Africans or African American and 1 was Indian, 18 patients had APOL1 gene variants (12 were G1:G1 and 6 were G1:G2) (Ng et al., 2020a). This suggests that one of the major risk factors for AKI in patients with COVID-19 infection is black race (Hirsch et al., 2020). Individuals with high renal risk alleles for APOL1 who have COVID-19 infection may be at increased risk of developing AKI, proteinuria and hematuria and consequent chronic kidney disease. A likely mechanism may be upregulation of APOL1 mediated by cytokines resulting from the SARS CoV-2 infection. This hypothesis requires investigation. In addition, innate immune response to SARS CoV-2 infection can drive the APOL1 kidney disease in patients with APOL1 high risk genotypes. The later argument is based a case series of collapsing glomerulopathy linked to interferon therapy (Nichols et al., 2015).