[Show abstract][Hide abstract] ABSTRACT: Background and objectives:
Prior studies have shown that the APOL1 risk alleles are associated with a greater risk of HIV-associated nephropathy and FSGS among blacks who are HIV positive. We sought to determine whether the APOL1 high-risk genotype incrementally improved the prediction of these underlying lesions beyond conventional clinical factors.
Design, setting, participants, & measurements:
In a cross-sectional study, we analyzed data from 203 blacks who are HIV positive, underwent kidney biopsies between 1996 and 2011, and were genotyped for the APOL1 G1 and G2 alleles. Predictive logistic regression models with conventional clinical factors were compared with those that also included APOL1 genotype using receiver-operating curves and bootstrapping analyses with crossvalidation.
The addition of APOL1 genotype to HIV-related risk factors for kidney disease in a predictive model improved the prediction of non-HIV-associated nephropathy FSGS, specifically, increasing the c statistic from 0.65 to 0.74 (P=0.04). Although two risk alleles were significantly associated with higher odds of HIV-associated nephropathy, APOL1 genotype did not add incrementally to the prediction of this specific histopathology.
APOL1 genotype may provide additional diagnostic information to traditional clinical variables in predicting underlying FSGS spectrum lesions in blacks who are HIV positive. In contrast, although APOL1 risk genotype predicts HIV-associated nephropathy, it lacked a high c statistic sufficient for discrimination to eliminate the role of kidney biopsy in the clinical care of blacks who are HIV positive with nephrotic proteinuria or unexplained kidney disease.
Full-text · Article · Dec 2015 · Clinical Journal of the American Society of Nephrology
[Show abstract][Hide abstract] ABSTRACT: Hematuria is considered a sign of active renal disease in patients with small-vessel vasculitis. In patients who are in apparent clinical remission, presence of persistent or new-onset microscopic hematuria may reflect active vasculitis, damage, or other glomerular pathology.
We identified 74 patients from the Johns Hopkins Renal Pathology database between 1995 and 2009 with the diagnosis of pauciimmune glomerulonephritis (GN). Among them we identified 9 who were in clinical remission and underwent a renal biopsy for evaluation of persistent or new-onset hematuria.
Nine patients with small-vessel vasculitis, 8 antineutrophil cytoplasmic antibody (ANCA)-positive and 1 ANCA-negative, underwent a renal biopsy at variable time periods after remission of vasculitis (6 to 164 months) for persistent microscopic hematuria (n = 6) or new-onset microscopic hematuria (n = 3). All patients were in apparent clinical remission at the time of renal biopsy. Of the 3 patients presenting with new-onset hematuria, 2 had crescentic IgA nephropathy and 1 had healed crescentic pauciimmune GN. Of the 6 patients with persistent hematuria, 2 had arteriosclerosis, 2 had focal segmental glomerulosclerosis, and 2 had global and segmental glomerulosclerosis and healed crescentic GN, and none had active vasculitis.
Microscopic hematuria in patients with renal vasculitis otherwise in remission could represent chronic glomerular injury from prior episode of vasculitis or may represent new glomerular pathology. Renal biopsy should be considered in these patients to guide therapy.
No preview · Article · Jun 2012 · The Journal of Rheumatology
[Show abstract][Hide abstract] ABSTRACT: Recently, an association was found between nondiabetic kidney disease in African Americans and two independent sequence variants in the APOL1 gene, encoding apolipoprotein L1. In this study we determined the frequency of APOL1 risk variants in patients with biopsy-proven HIV-associated nephropathy (HIVAN) and distinctive pathological characteristics potentially driven by those risk variants. Among 76 patients with HIVAN, 60 were successfully genotyped for APOL1 G1 and G2 polymorphisms. In this cohort, 37 had two risk alleles, 18 were heterozygous, and 5 had neither risk variant. There were no differences in the pathological findings of HIVAN and the number of APOL1 risk alleles. Further, the progression to end-stage kidney disease or death did not differ by the number of risk alleles. Median renal survival was 9.3 months in patients with zero or one risk allele compared to 11.7 months in patients with two APOL1 risk alleles. Thus, our study suggests that although the majority of African-American patients with HIVAN have two APOL1 risk alleles other as yet unknown factors in the host, including genetic risk variants and environmental or viral factors, may influence the development of this disorder in those with zero or one APOL1 risk allele.
Full-text · Article · Apr 2012 · Kidney International
[Show abstract][Hide abstract] ABSTRACT: Fibrillary glomerulonephritis (GN) is an uncommon cause of rapidly progressive kidney failure. We report a case of rapidly progressive kidney failure with kidney biopsy showing crescentic GN on light microscopy and immunofluorescence showing linear/globular glomerular basement membrane (GBM) staining for immunoglobulin G and C3, consistent with anti-GBM disease. However, electron microscopy showed fibrillary deposits in the GBM, suggesting a diagnosis of fibrillary GN. As exemplified by this case, it is important to consider fibrillary GN in the differential diagnosis of crescentic GN with linear immunoglobulin G deposits within the GBM. Electron microscopy is crucial to make this diagnosis.
Full-text · Article · Mar 2012 · American Journal of Kidney Diseases
[Show abstract][Hide abstract] 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.
No preview · Article · Dec 2011 · Journal of the American Society of Nephrology
[Show abstract][Hide abstract] ABSTRACT: Kidney International aims to inform the renal researcher and practicing nephrologists on all aspects of renal research. Clinical and basic renal research, commentaries, The Renal Consult, Nephrology sans Frontieres, minireviews, reviews, Nephrology Images, Journal Club. Published weekly online and twice a month in print.
Full-text · Article · Apr 2011 · Kidney International