Nickan Research Institute Immunopathologia Persa 2423-8015 11 2 2025 07 01 Clinical significance of APOL1-mediated renal disease e43770 e43770 10.34172/ipp.2025.43770 EN Paniz Pourpashang https://orcid.org/0000-0003-4469-086X Azadeh Khayyat https://orcid.org/0000-0002-1867-1609 Mohammad Ali Esmaeil pour https://orcid.org/0000-0002-0393-3928 Maryam Ghasemi https://orcid.org/0000-0003-1635-6880 Shiva Rouzbahani https://orcid.org/0000-0003-3083-3161 Journal Article 10.34172/ipp.2025.43770 2024 08 16 2025 01 10 APOL1-associated renal disease, also known as APOL1 renal risk variants or APOL1 nephropathy, represents a genetic kidney disorder associated with certain variants of the APOL1 gene. The APOL1 gene encodes a protein that plays a crucial role in the immune system’s response to trypanosome infection, the cause of African sleeping sickness. However, two distinct genetic variants of the APOL1 gene, known as G1 and G2, have been conclusively associated with an elevated risk of renal disease in individuals of African descent. Recent research has demonstrated that carrying two copies of either the G1 or G2 variant significantly increases the risk of progressive kidney diseases, such as focal segmental glomerulosclerosis (FSGS) and hypertensive kidney disease. APOL1-associated kidney disease typically presents with features of chronic kidney disease, including proteinuria, hematuria, hypertension, and declining kidney function. Furthermore, hypertension and diabetes serve as additional risk factors for kidney disease, and individuals with both conditions and APOL1 gene variants may further elevate their risk of developing renal disorders. Obesity and smoking also contribute to the risk of kidney disease, particularly in cases with APOL1 gene variants. Moreover, various medical conditions, including lupus, HIV, and sickle cell disease, can exacerbate the likelihood of kidney disease in individuals with APOL1 gene variants. These conditions could lead to end-stage renal disease (ESRD) necessitating treatments such as dialysis or kidney transplantation.