Association Between APOL1 Genotype and Need for Kidney Replacement Therapy in Patients Without Diabetes: Does Age Matter?

Wei, Jianqin; Johansen, Kirsten L.; McCulloch, Charles E.; Lipkowitz, Michael S.; Weir, Matthew R.; Lin, Feng; Campese, Vito M.; Ku, Elaine

doi:10.1053/j.ajkd.2019.08.017

Cited by 2 publications

(4 citation statements)

References 11 publications

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“…We found no evidence that age modified the associations of APOL1 genotype status with incident ESRD. These findings are in contrast with a recent study by Wei et al in AASK who reported a threshold age of 54 years, below which the APOL1 high‐risk genotypes were associated with a nearly 3‐fold higher HR of kidney replacement therapy and above which the APOL1 high‐risk genotypes were not associated with risk of kidney replacement therapy 27 . Importantly, participants of AASK consisted of African Americans with hypertension‐attributed CKD with baseline 123 I‐iothalamate GFR of 20 to 65 mL/min, 27‐29 whereas our study population was derived from a community‐based general population cohort with approximately 2% having a baseline eGFR below 60 mL/min/1.73 m 2 13,16 …”

Section: Discussioncontrasting

confidence: 99%

“…These findings are in contrast with a recent study by Wei et al in AASK who reported a threshold age of 54 years, below which the APOL1 high-risk genotypes were associated with a nearly 3-fold higher HR of kidney replacement therapy and above which the APOL1 high-risk genotypes were not associated with risk of kidney replacement therapy. 27 Importantly, participants of AASK consisted of African Americans with hypertension-attributed CKD with baseline 123 I-iothalamate GFR of 20 to 65 mL/min, [27][28][29] whereas our study population was derived from a community-based general population cohort with approximately 2% having a baseline eGFR below 60 mL/min/1.73 m 2 . 13,16 Our study shows that, even in older age, racial disparities in health outcomes continue to exist, and that many of these disparities, particularly in hospitalizations and all-cause mortality, are, in part, explained by social determinants of health.…”

Section: Discussionmentioning

confidence: 99%

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Race, APOL1 Risk Variants, and Clinical Outcomes among Older Adults: The ARIC Study

Chen

Coresh

Ballew

et al. 2020

J American Geriatrics Society

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BACKGROUND/OBJECTIVES: APOL1 high-risk genotypes confer an increased risk for kidney disease, but their clinical significance among older adults remains unclear. We aimed to determine whether APOL1 genotype status (high risk = 2 risk alleles; low risk = 0-1 risk alleles) and selfreported race (Black; White) are associated with number of hospitalizations, incident chronic kidney disease (CKD), endstage renal disease (ESRD), and mortality among older adults participating in a community-based cohort study. DESIGN: Observational longitudinal cohort study. SETTING: The Atherosclerosis Risk in Communities (ARIC) study. PARTICIPANTS: Community-dwelling older adults (mean age = 75.8 years; range = 66-90 years). RESULTS: Among 5,564 ARIC participants (78.2% White, 19.1% APOL1 low-risk Black, and 2.7% APOL1 high-risk Black), the proportion with creatinine and cystatin C-based estimated glomerular filtration rate (eGFR CrCys ) below 60 mL/min/1.73 m 2 at baseline was 40.6%, 34.8%, and 43.2%, respectively. Over a mean follow-up of 5.1 years, APOL1 high-risk Blacks had a 2.67-fold higher risk for ESRD compared with low-risk Blacks (95% confidence interval [CI] = 1.05-6.79) in models adjusted for age and sex. This association was no longer significant upon further adjustment for baseline eGFR CrCys and albuminuria (hazard ratio [HR] = 1.08; 95% CI = .39-2.96). Rate of hospitalizations and risks of mortality and incident CKD did not differ significantly by APOL1 genotype status. Compared with Whites, Blacks had 1.85-fold and 3.45-fold higher risks for incident CKD and ESRD, respectively, in models adjusted for age, sex, eGFR CrCys , and albuminuria. These associations persisted after additional adjustments for clinical/socioeconomic factors and APOL1 genotype (incident CKD: HR = 1.38; 95% CI = 1.06-1.81; ESRD: HR = 3.20; 95% CI = 1.16-8.86). CONCLUSION: Among older Black adults, APOL1 highrisk genotypes were associated with lower kidney function and therefore higher risk of ESRD. Racial disparities in incident kidney disease persisted in older age and were not fully explained by APOL1.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Race, APOL1 Risk Variants, and Clinical Outcomes among Older Adults: The ARIC Study

Chen

Coresh

Ballew

et al. 2020

J American Geriatrics Society

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“…This result is in disagreement with the study by kanji et al [30]. Moreover, this result was in agreement with the study by Wei et al that has demonstrated younger African American study of kidney disease and Hypertension (AASK) participants with high-risk genotype had the greatest KRT risk [34]. Genetic factors such as sickle cell trait have been investigated mostly among African Americans like of APOL1 genetic factors.…”

Section: оригінальні наукові роботиcontrasting

confidence: 48%

“…These studies revealed that genetic variants of APOL1 and non-muscle myosin heavy chain IIA (MHY9) in sickle cell disease (SCD) cause the progression of CKD to ESRD. The mean survival of patients with ESRD and SCD (sickle cell nephropathy) is estimated to be 4 years, even with dialytic treatment [34]. In the study by Masekoameng et al, they have not found a significant association between APOL1 and CKD in SCT patients, indicating that there is no evi-dence that SCT influences the relationship between APOL1 and CKD [35].…”

Section: оригінальні наукові роботиmentioning

confidence: 99%

The effect of APOL1 risk variants on emergent outcomes in kidney disorders: A meta-analysis of individual participant data

Amiri

2020

Ukr. J. Nephrol. and Dial.

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Abstract. Kidney diseases associated with APOL1 polymorphisms are human immunodeficiency virus-associated nephropathy, idiopathic focal segmental glomerulosclerosis, hypertension-attributed chronic kidney disease, lupus nephritis and sickle cell nephropathy. This research aimed to investigate the risk of genetic variants on disease contribution. Methods. In this individual participant data meta-analysis, eighteen patients with kidney dysfunction and at risk of APOL1 genotype were investigated. Clinical features, laboratory data at initial presentation, management and outcomes were collected. The paper has written based on searching PubMed Central and Google Scholar to identify potentially relevant articles. Median, percentage, mean ± standard deviation (SD), two-tailed t and chi-square tests were used for statistical analyses. Moreover, relative risk, odds ratio for statistical analyses were used. Results: The average age of patients at the time of diagnosis in APOL1-associated kidney disorders was 41.09 ± 20.63 years (ranging from 8 years to 70 years). Relative risk for kidney failure and persistent hemodialysis therapy in APOL1-associated nephropathy patients with renal risk variants (RRVs) were assessed 1.13 and odds ratio of 1.5 with 95% CI of 0.08-26.86 and the value of 0.0764 by chi-square test but there was no significant statistical result in this research (p-value of 0.782). The relative risk for patients of allograft failure with RRVs was assessed 1,0 odds ratio of 1,0 95% CI of 0.06-15.99 and p-value of 0.81. Conclusion: The present study revealed the risk and odds of APOL1 gene effect on the onset of kidney failure with replacement therapy in patients at risk of APOL1 genotype but results were not significant statistically. Future clinical research is required for investigating APOL1 gene effect on non-African ancestry.

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Association Between APOL1 Genotype and Need for Kidney Replacement Therapy in Patients Without Diabetes: Does Age Matter?

Abstract: Figure 1. Kaplan-Meier curves for cumulative KRT incidence among persons younger versus older than 54 years of age.

Cited by 2 publications

References 11 publications

Race, APOL1 Risk Variants, and Clinical Outcomes among Older Adults: The ARIC Study

Race, APOL1 Risk Variants, and Clinical Outcomes among Older Adults: The ARIC Study

The effect of APOL1 risk variants on emergent outcomes in kidney disorders: A meta-analysis of individual participant data

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