A High-Risk Variant of the ApoL1 Gene Correlates with Increased Interstitial Fibrosis and Tubular Atrophy among African Americans with Arterionephrosclerosis
Huma Fatima, Laura P Peterson, Haichun Yang, Agnes B Fogo. University of Alabama at Birmingham, Birmingham, AL; Vanderbilt University Medical Center, Nashville, TN
Background: Previously we found that blood pressure levels and proteinuria did not account for morphological lesions in arterionephrosclerosis attributed to hypertension, suggesting other factors may play a role. Recently a variant of the ApoL1 gene that is commonly seen in African Americans (AA) but very rare in Caucasians (C) was implicated in hypertension-attributable end stage kidney disease. In normal kidney, ApoL1 is expressed in podocyte, proximal tubular epithelia and arteriolar endothelium. In kidney disease, the localization and expression level of ApoL1 change. However, the mechanism of this increased disease risk and correlation with histopathologic changes in the kidney are unknown.
Design: All clinical renal biopsies with a histological diagnosis of arterionephrosclerosis 1988-1999 were identified. Excluding insufficient biopsy samples, 46 biopsy samples were analyzed for the presence of the high risk ApoL1 gene variant. We then compared genotype results with pathological lesions, serum creatinine and proteinuria.
Results: Our population included 13 C (5 male/8 female) and 33 AA patients (25 male/8 female), on average 54.4 ± 14.8 yrs. Amongst AA patients, 12 had 0 risk alleles, 12 had 1 risk alleles and 9 had 2 risk alleles. The 13 C patients all had 0 risk alleles. Amongst patients with 0 risk alleles, C and AA had similar clinical and morphology features. Serum creatinine, proteinuria, total global glomerulosclerosis (GS) or types of GS (obsolescent, solidified or disappearing), segmental GS, mesangial expansion, periglomerular fibrosis, arterial and arteriolar injury did not differ in AA with or without risk alleles. However, there was more severe tubular atrophy in those AA with 2 risk alleles than those with 0 risk alleles (37.2 ± 25.0 vs. 13.3 ± 14.7%, p<0.05). Similarly, interstitial fibrosis was more severe in AA with 2 risk alleles than those with 0 risk alleles (43.9 ± 27.7 vs. 17.1 ± 17.8%, p<0.05).
Conclusions: Homozygosity for a high-risk variant of ApoL1 in patients with arterionephrosclerosis correlates with the extent of interstitial fibrosis and tubular atrophy in biopsy specimens, but is not correlated with glomerular, arterial or arteriolar injury.
Category: Kidney (does not include tumors)
Tuesday, March 5, 2013 8:15 AM
Proffered Papers: Section H, Tuesday Morning