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Kidney Week

Abstract: SA-PO1105

Association between Plasma Alpha 1-Antitrypsin Levels and Kidney Failure in Patients with CKD

Session Information

Category: CKD (Non-Dialysis)

  • 2301 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

  • Créon, Antoine, Centre de Recherche en Epidemiologie et Sante des Populations, Villejuif, Île-de-France, France
  • Klein, Julie, INSERM 1297, Toulouse, France
  • Liabeuf, Sophie, Centre Hospitalier Universitaire Amiens-Picardie, Amiens, France
  • Lange, Celine, Centre de Recherche en Epidemiologie et Sante des Populations, Villejuif, France
  • Jacquelinet, Christian, Centre de Recherche en Epidemiologie et Sante des Populations, Villejuif, France
  • Schanstra, Joost, INSERM 1297, Toulouse, France
  • Alencar de Pinho, Natalia, Centre de Recherche en Epidemiologie et Sante des Populations, Villejuif, Île-de-France, France
  • Massy, Ziad, Centre de Recherche en Epidemiologie et Sante des Populations, Villejuif, Île-de-France, France

Group or Team Name

  • Centre for Research in Epidemiology and Population Health.
Background

Chronic kidney disease (CKD) is overrepresented in persons with alpha-1-antitrypsin (AAT) deficiency, and previous studies suggest that AAT may play a role in kidney fibrosis. This study assessed the relationship between plasma AAT and kidney failure (KF) in patients with CKD.

Methods

National, prospective cohort of 2263 patients with CKD stage 2-5. Baseline plasma AAT was measured centrally with ELISA (Bio-techne, DY1268, normal ranges from 0.9 g/l to 1.8 g/l). Cause-specific Cox models were used to estimate hazard ratios (HR) for KF, defined as initiation of kidney replacement therapy, adjusted for demographics, eGFR, albuminuria, albumin, hemoglobin, CRP, cardiovascular comorbidities, and use of RAAS, diuretics, MRAs, and corticosteroids.

Results

Patients had a mean age (±SD) of 66 years (±13) and 34% were females. The mean eGFR was 35 (±13) ml/min/1.73 m2 and median AAT (Q1-Q3) was 1.49 g/l (1.23-1.80). Over a median follow-up of 5.8 (5.4-6.3) years, 563 patients experienced KF. The relationship between AAT and KF followed a U-shaped pattern (figure 1). The adjusted HR (95% CI) of KF associated with a 0.5 g/l-lower baseline AAT relative to its median value was 1.33 (1.02 -1.73), while that for a 0.5 g/l-higher baseline AAT value was 1.45 (1.10-1.92).

Conclusion

A U-shaped relationship between plasma AAT and KF suggests a relative imbalance between systemic inflammation and anti-inflammatory AAT in patients with low baseline plasma AAT. Clinical studies are needed to clarify whether therapy with AAT, currently indicated only for the treatment of the severe forms of genetic AAT deficiency, may be helpful to correct AAT levels and potentially protect the risk of progression from CKD to KF.

Funding

  • Government Support – Non-U.S.