APOL1 Nephropathy: From Genetics to Clinical Applications

Abstract

Rates of many types of severe kidney disease are much higher in Black individuals than most other ethnic groups. Much of this disparity can now be attributed to genetic variants in the apoL1 (APOL1) gene found only in individuals with recent African ancestry. These variants greatly increase rates of hypertension-associated ESKD, FSGS, HIV-associated nephropathy, and other forms of nondiabetic kidney disease. We discuss the population genetics of APOL1 risk variants and the clinical spectrum of APOL1 nephropathy. We then consider clinical issues that arise for the practicing nephrologist caring for the patient who may have APOL1 kidney disease.

Risk factors for symptomatic Avascular Necrosis (AVN) in a multi-ethnic Systemic Lupus Erythematosus (SLE) cohort

“…It is one of six members of the APOL gene family on human chromosome located on chromosome 22q12.3. It has an innate immune function which regulates intracellular death and APOL1 gene is associated with an excess risk of chronic and end stage kidney disease [32], as well as atherosclerotic disease in SLE [33]. Meanwhile, Multidrug-resistant transporter-1 (MDR1) gene is located on human chromosome 7 band q21.1.…”

Pandemics and pathology: a reflection on influenza, HIV/AIDS and SARS (COVID-19) pandemic infections

“… a However, review highlighted confusion and delays around managing peripartum women with respiratory distress with known or possible COVID-19. 19 …”

Genetic susceptibility of hypertension‐induced kidney disease

“…APOL1 variants‐related hypertensive kidney injury may involve alterations in podocyte function. Although the underlying mechanisms remain to be determined, APOL1 variants may create pores in cell membranes and injure podocyte function much the same as it lysis trypanosomes (Friedman & Pollak, 2020). Foot process effacement and glomerulosclerosis have been found in transgenic mice that contain podocyte‐specific Apol risk alleles, which may be due to alterations in endosomal trafficking and autophagy in podocytes (Beckerman et al., 2017; Kopp et al., 2011; Madhavan et al., 2011).…”

“…Chr.22 (22q12) Human (GWAS) Podocyte and glomerular function Friedman & Pollak, 2020;Foster et al, 2013;Genovese, Friedman, et al, 2010;Hayek et al, 2017;Parsa et al, 2013 APOL1 transgenic mice…”