Apolipoprotein L1 nephropathies: 2017 in review

Area of Science:

• Nephrology
• Genetics
• Molecular Biology

Background:

• Apolipoprotein L1 (APOL1) gene variants are a significant risk factor for kidney disease, particularly in individuals of African descent.
• Research into APOL1's role in renal pathology has intensified, with numerous studies published annually.
• Understanding the mechanisms underlying APOL1-associated nephrotoxicity is crucial for developing effective treatments.

Purpose of the Study:

• To review and synthesize key findings from publications on APOL1 renal risk variants published in 2017.
• To highlight advancements in understanding the clinical and molecular aspects of APOL1 nephropathy.
• To identify emerging trends and knowledge gaps in APOL1 research.

Main Methods:

• Systematic review of 24 selected articles published in 2017 focusing on APOL1 renal risk variants.
• Inclusion of both clinical studies (kidney disease, transplantation, hypertension, cardiovascular disease, genetic diversity) and laboratory investigations.
• Analysis of studies examining APOL1 associations with cellular mechanisms like protein interactions, mitochondrial and endolysosomal dysfunction, and inflammasome activation.

Main Results:

• Clinical studies explored APOL1 variant associations with various kidney diseases, transplantation outcomes, hypertension, and cardiovascular conditions.
• Laboratory studies investigated APOL1's role in cellular processes, including interactions with specific proteins (v-SNAREs, uPAR), mitochondrial dysfunction, endolysosomal trafficking defects, and inflammasome activation.
• The 2017 literature demonstrated a deepening understanding of APOL1's complex role in renal toxicity.

Conclusions:

• The study of APOL1 renal risk variants remains a dynamic field with ongoing discoveries.
• While significant progress has been made, the precise pathways mediating APOL1 nephrotoxicity in humans require further elucidation.
• Defining the most relevant molecular targets is essential for future therapeutic interventions in APOL1-associated kidney diseases.