APOL1 Risk Variants Predict Histopathology and Progression to ESRD in HIV-Related Kidney Disease

Abstract

With earlier institution of antiretroviral therapy, kidney diseases other than HIV-associated nephropathy (HIVAN) predominate in HIV-infected persons. Outcomes for these diseases are typically worse among those infected with HIV, but the reasons for this are not clear. Here, we examined the role of APOL1 risk variants in predicting renal histopathology and progression to ESRD in 98 HIV-infected African Americans with non-HIVAN kidney disease on biopsy. We used survival analysis to determine time to ESRD associated with APOL1 genotype. Among the 29 patients with two APOL1 risk alleles, the majority (76%) had FSGS and 10% had hypertensive nephrosclerosis. In contrast, among the 54 patients with one APOL1 risk allele, 47% had immune-complex GN as the predominant lesion and only 23% had FSGS. Among the 25 patients with no APOL1 risk allele, 40% had immune-complex GN and 12% had FSGS. In 310 person-years of observation, 29 patients progressed to ESRD. In adjusted analyses, individuals with two APOL1 risk alleles had a nearly three-fold higher risk for ESRD compared with those with one or zero risk alleles (P=0.03). In summary, these data demonstrate an association between APOL1 variants and renal outcomes in non-HIVAN kidney disease, suggesting a possible use for APOL1 genotyping to help guide the care of HIV-infected patients.

APOL1 Risk Variants Are Strongly Associated with HIV-Associated Nephropathy in Black South Africans

“…Although the ORs in this study were higher for HIVAN and lower for FSGS compared with the ratios observed in African Americans, the differences were not statistically significant (P=0.56 and P=0.21 for FSGS and HIVAN, respectively). We also compared ORs for HIV-positive FSGS seen in this study with data from Fine et al 20 for African Americans with HIV-positive FSGS compared with a population control group from the study by Kopp et al 13 (OR, 24.5; 95% confidence interval [95% CI], 9.7 to 65.1); P=4.3310 214 ); the Woolf test gave a P value of 0.07.…”

“…12,13 In addition, other studies also demonstrated higher association of APOL1 risk alleles with FSGS. 20,27 It is possible that HIV infection is an incidental finding to primary FSGS in black South Africans, with FSGS being the commonest histology reported in children and adults worldwide. 28,29 However, others have suggested that FSGS may be part of the spectrum of histology in response to HIV infection.…”

African origins and chronic kidney disease susceptibility in the human immunodeficiency virus era

“…In the United States there has been a steady decline in the incidence of HIVAN with the introduction of HAART, in spite of stable frequencies of the risk variants [68] . Risk factors for progression to ESRD in HIVAN are severity of renal dysfunction, percentage of sclerotic glomeruli [25,69] , lack of viral suppression [26,70] , 2 APOL1 risk alleles [63,71] , while use of renin angiotensin system blockers were reported to be protective [25] . HIV-infected individuals with non-HIVAN pathology and two APOL1 risk alleles had an almost 3-fold risk of ESRD, in spite of effective ARTsuppression of viral load and use of renin-angiotensin aldosterone blockers; baseline kidney function was the strongest predictor of progression to ESRD in this study [71] .…”

“…Risk factors for progression to ESRD in HIVAN are severity of renal dysfunction, percentage of sclerotic glomeruli [25,69] , lack of viral suppression [26,70] , 2 APOL1 risk alleles [63,71] , while use of renin angiotensin system blockers were reported to be protective [25] . HIV-infected individuals with non-HIVAN pathology and two APOL1 risk alleles had an almost 3-fold risk of ESRD, in spite of effective ARTsuppression of viral load and use of renin-angiotensin aldosterone blockers; baseline kidney function was the strongest predictor of progression to ESRD in this study [71] . Investigators reviewing the African American study on Kidney Disease and Hypertension (AASK) and The Chronic Renal Insufficiency Cohort (CRIC) found that APOL1 risk variants in black patients were associated with higher rates of ESRD and progression of CKD [72] .…”

Neighborhood Socioeconomic Status, Race, and Mortality in Young Adult Dialysis Patients

“…1 The greater incidence of ESRD among blacks has been attributed to prevalent CKD risk factors (including hypertension, 2,3 diabetes, 4,5 and obesity 6 ), genetic predisposition, [7][8][9] low socioeconomic status (SES), [10][11][12] and inequalities in the access and quality of kidney disease care. 13,14 Despite the greater incidence of ESRD, numerous studies have shown that blacks experience paradoxically better survival on dialysis compared with whites.…”