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. 2022 Oct 28;23(1):347.
doi: 10.1186/s12882-022-02967-5.

Polygenic association of glomerular filtration rate decline in world trade center responders

Farrukh M Koraishy  1 , Frank D Mann  2 , Monika A Waszczuk  3 , Pei-Fen Kuan  4 , Katherine Jonas  5 , Xiaohua Yang  6 , Anna Docherty  7 , Andrey Shabalin  7 , Sean Clouston  2 , Roman Kotov  5 , Benjamin Luft  6
Affiliations

Polygenic association of glomerular filtration rate decline in world trade center responders

Farrukh M Koraishy et al. BMC Nephrol. .

Abstract

Background: The factors associated with estimated glomerular filtrate rate (eGFR) decline in low risk adults remain relatively unknown. We hypothesized that a polygenic risk score (PRS) will be associated with eGFR decline.

Methods: We analyzed genetic data from 1,601 adult participants with European ancestry in the World Trade Center Health Program (baseline age 49.68 ± 8.79 years, 93% male, 23% hypertensive, 7% diabetic and 1% with cardiovascular disease) with ≥ three serial measures of serum creatinine. PRSs were calculated from an aggregation of single nucleotide polymorphisms (SNPs) from a recent, large-scale genome-wide association study (GWAS) of rapid eGFR decline. Generalized linear models were used to evaluate the association of PRS with renal outcomes: baseline eGFR and CKD stage, rate of change in eGFR, stable versus declining eGFR over a 3-5-year observation period. eGFR decline was defined in separate analyses as "clinical" (> -1.0 ml/min/1.73 m2/year) or "empirical" (lower most quartile of eGFR slopes).

Results: The mean baseline eGFR was ~ 86 ml/min/1.73 m2. Subjects with decline in eGFR were more likely to be diabetic. PRS was significantly associated with lower baseline eGFR (B = -0.96, p = 0.002), higher CKD stage (OR = 1.17, p = 0.010), decline in eGFR (OR = 1.14, p = 0.036) relative to stable eGFR, and the lower quartile of eGFR slopes (OR = 1.21, p = 0.008), after adjusting for established risk factors for CKD.

Conclusion: Common genetic variants are associated with eGFR decline in middle-aged adults with relatively low comorbidity burdens.

Keywords: Chronic kidney disease (CKD); Estimated glomerular filtration rate (eGFR); Polygenic risk score (PRS).

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Conflict of interest statement

The authors declare that they have no competing interests.

References

    1. Chronic Kidney Disease in the United States. Centers for Disease Control and Prevention. Chronic Kidney Disease Initiative Web site. https://www.cdc.gov/kidneydisease/publications-resources/ckd-national-fa.... Published 2021. Accessed2021.
    1. Turin TC, Coresh J, Tonelli M, et al. Short-term change in kidney function and risk of end-stage renal disease. Nephrol Dial Transplant. 2012;27(10):3835–43. - PubMed
    1. USRDS Annual Data Report 2017.
    1. Natali A, Boldrini B, Baldi S, et al. Impact of mild to moderate reductions of glomerular filtration rate on coronary artery disease severity. Nutr Metab Cardiovasc Dis. 2014;24(6):681–8. - PubMed
    1. Mohandas R, Segal M, Srinivas TR, et al. Mild renal dysfunction and long-term adverse outcomes in women with chest pain: results from the National Heart, Lung, and Blood Institute-sponsored Women’s Ischemia Syndrome Evaluation (WISE) Am Heart J. 2015;169(3):412–8. - PMC - PubMed

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