Association Between APOL1 Genotype and Need for Kidney Replacement Therapy in Patients Without Diabetes: Does Age Matter?
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ABSTRACT:
SUBMITTER: Wei J
PROVIDER: S-EPMC7652210 | biostudies-literature | 2020 Feb
REPOSITORIES: biostudies-literature
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Association Between APOL1 Genotype and Need for Kidney Replacement Therapy in Patients Without Diabetes: Does Age Matter?
Wei Jenny J Johansen Kirsten L KL McCulloch Charles E CE Lipkowitz Michael M Weir Matthew M Lin Feng F Campese Vito M VM Smogorzewski Miroslaw M Ku Elaine E
American journal of kidney diseases : the official journal of the National Kidney Foundation 20191216 2
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Project description:ObjectiveWe sought to evaluate the cardiovascular impact of coding variants in the apolipoprotein L1 gene APOL1 that protect against trypanosome infection but have been associated with kidney disease among African Americans.Approach and resultsAs part of the Cardiovascular Health Study, a population-based cohort of Americans aged ≥65 years, we genotyped APOL1 polymorphisms rs73885319 and rs71785153 and examined kidney function, subclinical atherosclerosis, and incident cardiovascular disease and death over 13 years of follow-up among 91 African Americans with 2 risk alleles, 707 other African Americans, and 4964 white participants. The high-risk genotype with 2 risk alleles was associated with 2-fold higher levels of albuminuria and lower ankle-brachial indices but similar carotid intima-media thickness among African Americans. Median survival among high-risk African Americans was 9.9 years (95% confidence interval [CI], 8.7-11.9), compared with 13.6 years (95% CI, 12.5-14.3) among other African Americans and 13.3 years (95% CI, 13.0-13.6) among whites (P=0.03). The high-risk genotype was also associated with increased risk for incident myocardial infarction (adjusted hazard ratio 1.8; 95% CI, 1.1-3.0) and mortality (adjusted hazard ratio 1.3; 95% CI 1.0-1.7). Albuminuria and risk for myocardial infarction and mortality were nearly identical between African Americans with 0 to 1 risk alleles and whites.ConclusionsAPOL1 genotype is associated with albuminuria, subclinical atherosclerosis, incident myocardial infarction, and mortality in older African Americans. African Americans without 2 risk alleles do not differ significantly in risk of myocardial infarction or mortality from whites. APOL1 trypanolytic variants may account for a substantial proportion of the excess risk of chronic disease in African Americans.
| S-EPMC4732891 | biostudies-literature
Project description:Two apolipoprotein L1 gene (APOL1) renal-risk variants in donors and African American (AA) recipient race are associated with worse allograft survival in deceased-donor kidney transplantation (DDKT) from AA donors. To detect other factors impacting allograft survival from deceased AA kidney donors, APOL1 renal-risk variants were genotyped in additional AA kidney donors.The APOL1 genotypes were linked to outcomes in 478 newly analyzed DDKTs in the Scientific Registry of Transplant Recipients. Multivariate analyses accounting for recipient age, sex, race, panel-reactive antibody level, HLA match, cold ischemia time, donor age, and expanded criteria donation were performed. These 478 transplantations and 675 DDKTs from a prior report were jointly analyzed.Fully adjusted analyses limited to the new 478 DDKTs replicated shorter renal allograft survival in recipients of APOL1 2-renal-risk-variant kidneys (hazard ratio [HR], 2.00; P = 0.03). Combined analysis of 1153 DDKTs from AA donors revealed donor APOL1 high-risk genotype (HR, 2.05; P = 3 × 10), older donor age (HR, 1.18; P = 0.05), and younger recipient age (HR, 0.70; P = 0.001) adversely impacted allograft survival. Although prolonged allograft survival was seen in many recipients of APOL1 2-renal-risk-variant kidneys, follow-up serum creatinine concentrations were higher than that in recipients of 0/1 APOL1 renal-risk-variant kidneys. A competing risk analysis revealed that APOL1 impacted renal allograft survival, but not recipient survival. Interactions between donor age and APOL1 genotype on renal allograft survival were nonsignificant.Shorter renal allograft survival is reproducibly observed after DDKT from APOL1 2-renal-risk-variant donors. Younger recipient age and older donor age have independent adverse effects on renal allograft survival.
| S-EPMC4684443 | biostudies-literature
Project description:BackgroundAPOL1 genotype is associated with advanced kidney disease in African Americans, but the pathogenic mechanisms are unclear. Here, associations of APOL1 genotype with urine biomarkers of glomerular and tubular injury and kidney function decline were evaluated.Study designObservational study.Setting & participants431 human immunodeficiency virus (HIV)-infected African American women enrolled in Women's Interagency HIV Study (WIHS).PredictorAPOL1 genotype.OutcomesAlbumin-creatinine ratio (ACR), 4 tubular injury biomarkers (interleukin 18 [IL-18], kidney injury molecule 1 [KIM-1], neutrophil gelatinase-associated lipocalin [NGAL], and α1-microglobulin [A1M]), and kidney function estimated using the CKD-EPI cystatin C equation.MeasurementsParticipants were genotyped for APOL1 single-nucleotide polymorphisms rs73885319 (G1 allele) and rs71785313 (G2 allele). Urine biomarkers were measured using stored samples from 1999-2000. Cystatin C was measured using serum collected at baseline and 4- and 8-year follow-ups.ResultsAt baseline, ACRs were higher among 47 women with 2 APOL1 risk alleles versus 384 women with 0/1 risk allele (median, 24 vs 11mg/g; P<0.001). Compared with women with 0/1 risk allele, women with 2 risk alleles had 104% higher ACRs (95% CI, 29-223mg/g) and 2-fold greater risk of ACR>30 (95% CI, 1.17-3.44) mg/g after multivariable adjustment. APOL1 genotype showed little association with urine IL-18:Cr ratio, KIM-1:Cr ratio, and NGAL:Cr ratio (estimates of -5% [95% CI, -24% to 18%], -20% [95% CI, -36% to -1%], and 10% [95% CI, -26% to 64%], respectively) or detectable urine A1M (prevalence ratio, 1.13; 95% CI, 0.65-1.97) in adjusted analyses. Compared with women with 0/1 allele, women with 2 risk alleles had faster eGFR decline, by 1.2 (95% CI, 0.2 to 2.2) mL/min/1.73m(2) per year, and 1.7- and 3.4-fold greater rates of incident chronic kidney disease (95% CI, 1.1 to 2.5) and 10% annual eGFR decline (95% CI, 1.7 to 6.7), respectively, with minimal attenuation after adjustment for glomerular and tubular injury biomarker levels.LimitationsResults may not be generalizable to men.ConclusionsAmong HIV-infected African American women, APOL1-associated kidney injury appears to localize to the glomerulus, rather than the tubules.
| S-EPMC4615696 | biostudies-literature
Project description:Since the implementation of the model for end-stage liver disease (MELD) scoring system in 2002, the liver transplantation (LT) society has observed a substantial increase in the number of recipients with renal dysfunction. Intraoperative renal replacement therapy (ioRRT) has emerged as one of the solutions available to manage high-MELD score recipients; however, its usefulness has not yet been proven. To date, we have experienced five cases of simultaneous liver and kidney transplantation (SLKT). Recipients of SLKT tend to have a lower pre-transplant kidney function and the longer operation time mandates a larger amount of fluid than LT alone. Hence, anesthetic care is more prone to be challenged by hyperkalemia, metabolic acidosis, and volume overload, making ioRRT a theoretically valuable intervention. However, in all five cases, recipients were managed without ioRRT, resulting in excellent graft and patient survival. As such, in this case series, we discuss current issues about ioRRT and SLKT.
| S-EPMC5548951 | biostudies-other
Project description:BackgroundQuantifying the number and proportion of people with kidney failure (KF) who receive conservative kidney management is vital for health care system benchmarking and planning. It is not easy to ascertain this value precisely at the population level, but we can approximate it using information from different data sources to estimate the proportion of patients with advanced kidney disease who die without receiving dialysis or a transplant and should receive conservative kidney management.ObjectiveTo approximate the proportion of people with KF in Ontario, Canada, who die without receiving kidney replacement therapy.DesignA review of unpublished provincial renal agency reports of 3 retrospective population-based cohorts combined with clinical interpretation.PatientsThe 3 cohorts of people were: 1. those who died between January 1, 2013 and December 31, 2017, with an estimated glomerular filtration rate (eGFR) <10 mL/min/1.73 m2 and no evidence of receiving kidney replacement therapy; 2. those who initiated outpatient maintenance dialysis or received a preemptive transplant in the same period; and 3. those with a sustained low eGFR ≤ 10 mL/min/1.73 m2 between April 1, 2015 and March 31, 2018, and were followed for 1 year to determine if they started dialysis. In this last cohort, patients whose kidney function improved (evidence of an eGFR > 10 mL/min/1.73 m2) or who received a transplant during follow-up were excluded from the analysis.Measurements and methodsThe 3 cohorts were derived at ICES and used linked health care databases for the province of Ontario, Canada. In 2016, Ontario had a population of about 14 million people. Two nephrologists reviewed the data to provide the clinical approximation.ResultsThere were 1891 individuals with KF who died without kidney replacement (the no KRT cohort). The median (25th, 75th percentile) eGFR prior to death was 7 (5, 8) mL/min/1.73 m2. During the same period, 13 511 individuals started dialysis or received a preemptive kidney transplant (the KRT cohort). There were 7259 individuals in the low eGFR cohort; over the following year, 66% started dialysis, 20% died without dialysis, and 14% were alive without starting dialysis. The clinical approximation is that between 13 and 16% of people with KF die without receiving kidney replacement therapy.LimitationsThe data reports lacked certain information to inform the clinical approximation. There was no information on the conversations health professionals had with people about kidney replacement therapy, any decisions made about receiving conservative care, or the circumstances that preceded death without kidney replacement therapy.ConclusionsAfter reviewing data from the 3 cohorts, we clinically approximate that 1 in 6 people with KF in Ontario, Canada, die without receiving dialysis and should receive conservative kidney management.
| S-EPMC11909665 | biostudies-literature
Project description:BackgroundDespite evidence of an association between variants at the apolipoprotein L1 gene (APOL1) locus and a spectrum of related kidney diseases, underlying biological mechanisms remain unknown. An earlier preliminary study published by our group showed that an APOL1 variant (rs73885319) modified the association between high-density lipoprotein cholesterol (HDLC) and estimated glomerular filtration rate (eGFR) in African Americans. To further understand this relationship, we evaluated the interaction in two additional large cohorts of African Americans for a total of 3,592 unrelated individuals from the Howard University Family Study (HUFS), the Natural History of APOL1-Associated Nephropathy Study (NHAAN), and the Atherosclerosis Risk in Communities Study (ARIC). The association between HDLC and eGFR was determined using linear mixed models, and the interaction between rs73885319 genotype and HDLC was evaluated using a multiplicative term.ResultsAmong individuals homozygous for the risk genotype, a strong inverse HDLC-eGFR association was observed, with a positive association in others (p for the interaction of the rs73885319 × HDLC =0.0001). The interaction was similar in HUFS and NHAAN, and attenuated in ARIC. Given that ARIC participants were older, we investigated an age effect; age was a significant modifier of the observed interaction. When older individuals were excluded, the interaction in ARIC was similar to that in the other studies.ConclusionsBased on these findings, it is clear that the relationship between HDLC and eGFR is strongly influenced by the APOL1 rs73885319 kidney risk genotype. Moreover, the degree to which this variant modifies the association may depend on the age of the individual. More detailed physiological studies are warranted to understand how rs73885319 may affect the relationship between HDLC and eGFR in individuals with and without disease and across the lifespan.
| S-EPMC4448293 | biostudies-literature
Project description:Background and objectivesPrior 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, & measurementsIn 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.ResultsThe 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.ConclusionsAPOL1 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.
| S-EPMC4741048 | biostudies-literature
Project description: Not available
| S-EPMC10775300 | biostudies-literature
Project description:Apolipoprotein L-1 (APOL1) gene variants are associated with end-stage renal disease in African Americans (AAs). Here we investigate the impact of recipient APOL1 gene distributions on kidney allograft outcomes. We conducted a retrospective analysis of 119 AA kidney transplant recipients, and found that 58 (48.7%) carried two APOL1 kidney disease risk variants. Contrary to the association seen in native kidney disease, there is no difference in allograft survival at 5-year posttransplant for recipients with high-risk APOL1 genotypes. Thus, we were able to conclude that APOL1 genotypes do not increase risk of allograft loss after kidney transplantations, and carrying 2 APOL1 risk alleles should not be an impediment to transplantation.
| S-EPMC3387301 | biostudies-literature