Obesity-related glomerulopathy in the presence of APOL1 risk alleles

R, Imbert; Seng, Nang San Hti Lar; Stokes, Michael B.; Jim, Belinda

doi:10.1136/bcr-2022-249624

Cited by 4 publications

(3 citation statements)

References 31 publications

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“…Observational studies show that carriers of APOL1 risk variants develop more frequently essential hypertension [81] and obesity [82] compared to noncarriers, suggesting that individuals with an APOL1 high-risk genotype may endure more severe insulin resistance. Accordingly, clinical and histopathological manifestations of insulin resistance in the kidney are remarkably similar to the clinical phenotype associated with APOL1 risk variants, namely albuminuria, CKD, faster CKD progression, glomerulomegaly, FSGS, and arterionephrosclerosis [106]. In addition, plasma APOL1 levels are increased in patients with more pronounced insulin resistance compared to those who are more insulin-sensitive [19,84].…”

Section: Introductionmentioning

confidence: 79%

“…First, essential hypertension [81] and obesity [82] occur more frequently in subjects with an APOL1 high-risk genotype compared to low-risk subjects, suggesting that carriers of APOL1 risk variants may experience more severe insulin resistance than noncarriers. Second, the kidney phenotype associated with mutated APOL1 and the kidney consequences of insulin resistance are strikingly similar (albuminuria, CKD, faster CKD progression, glomerulomegaly, FSGS, and arterionephrosclerosis) [106]. Third, patients with increased plasma APOL1 levels show more pronounced insulin resistance than those with lower circulating APOL1 [19,84].…”

Section: Relationship Between Insulin Resistance and Apol1mentioning

confidence: 99%

“…Biallelic carriage of APOL1 risk variants is associated with kidney manifestations of insulin resistance, such as albuminuria, CKD, glomerulomegaly, FSGS (in the setting of glomerular hyperfiltration), and arterionephrosclerosis (the pathological correlate of hypertension-associated nephropathy) [47,106]. As mentioned, several studies, including the Dallas Heart Study, the AASK, the CRIC, the SPRINT, the MESA, and the MVP, show very consistently that carriers of two copies of the APOL1 risk variants have a higher prevalence of albuminuria and greater values of albuminuria when compared to individuals with one or zero risk variants in varied African American population groups [4,10,35,36,87].…”

Section: The Kidney Phenotype Associated With the Apol1 High-risk Gen...mentioning

confidence: 99%

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Harboring apolipoprotein L1 (APOL1) variants coded by the G1 or G2 alleles of the APOL1 gene increases the risk for collapsing glomerulopathy, focal segmental glomerulosclerosis, albuminuria, chronic kidney disease, and accelerated kidney function decline towards end-stage kidney disease. However, most subjects carrying APOL1 variants do not develop the kidney phenotype unless a second clinical condition adds to the genotype, indicating that modifying factors modulate the genotype–phenotype correlation. Subjects with an APOL1 high-risk genotype are more likely to develop essential hypertension or obesity, suggesting that carriers of APOL1 risk variants experience more pronounced insulin resistance compared to noncarriers. Likewise, arterionephrosclerosis (the pathological correlate of hypertension-associated nephropathy) and glomerulomegaly take place among carriers of APOL1 risk variants, and these pathological changes are also present in conditions associated with insulin resistance, such as essential hypertension, aging, and diabetes. Insulin resistance may contribute to the clinical features associated with the APOL1 high-risk genotype. Unlike carriers of wild-type APOL1, bearers of APOL1 variants show impaired formation of lipid droplets, which may contribute to inducing insulin resistance. Nascent lipid droplets normally detach from the endoplasmic reticulum into the cytoplasm, although the proteins that enable this process remain to be fully defined. Wild-type APOL1 is located in the lipid droplet, whereas mutated APOL1 remains sited at the endoplasmic reticulum, suggesting that normal APOL1 may participate in lipid droplet biogenesis. The defective formation of lipid droplets is associated with insulin resistance, which in turn may modulate the clinical phenotype present in carriers of APOL1 risk variants.

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