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).