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Publications

Journal Article Ahead of print

PubMed: 42816442 DOI: 10.1093/joneph/aajag249

The Interplay Between Klotho, Aldosterone, and Vascular Damage in Chronic Kidney Disease: Insights from a Cross-Sectional Study.

J Nephrol

Authors: Lida Tartaglione, Silverio Rotondi, Marzia Pasquali, Adolfo Perrotta, Francesca Tinti, Antonella Zaccaria, Viviana Beatriz Quiñonez, Federico Andreetti, Valeria Fassino, Silvia Lai, Claudio Letizia, Luigi Petramala, Francesco Circosta, Gianluigi Zaza, Sandro Mazzaferro

Affiliations

  • Department of Internal Medicine and Medical Specialties, AOU Policlinico Umberto I, Roma.
  • Department of Translational and Precision Medicine, Nephrology Unit Polo Pontino, Sapienza University of Rome.
  • Department of Translational and Precision Medicine, Division of Nephrology, Sapienza University of Rome.
  • Department of Clinical and Molecular Medicine, Nephrology and Dialysis Unit, AOU S. Andrea, Sapienza University of Rome.
  • Department of experimental Medicine, AOU Policlinico Umberto I, Roma.
  • Department of Medical and Cardiovascular Sciences, "Sapienza" University of Rome, Rome, Italy.
  • Department of Translational and Precision Medicine, "Sapienza" University of Rome, Rome, Italy.
  • Dialysis Unit, American Hospital, Rome.

Abstract

BACKGROUND

Patients with chronic kidney disease (CKD) are at increased risk of vascular calcification and cardiovascular mortality. Reduced Klotho levels have been associated with vascular damage in CKD through both direct and indirect mechanisms. Klotho deficiency, a hallmark of CKD, has been suggested to contribute to the hyperaldosteronism observed in CKD. This study aimed to evaluate the relationship between serum Klotho (s-Klotho), aldosterone, and vascular damage in CKD.

METHODS

We studied 55 patients with CKD stages G1-5 (52.0, IQR: 39.0-63.0 y; 27 M/28 F; eGFR 53.1±31.7 ml/min). Vascular damage was assessed non-invasively using the cardio-ankle vascular index (CAVI), ankle-brachial index (ABI), and intima-media thickness (IMT). s-Klotho and aldosterone levels were measured. A control group of 38 age- and sex-matched hypertensive patients without CKD was used for comparison of vascular parameters.

RESULTS

CAVI values in CKD patients were pathological (8.4±1.2) but did not differ from controls. s-Klotho levels progressively declined across CKD stages (p for trend <0.001) and correlated positively with eGFR, while showing negative associations with age and vascular parameters (CAVI, ABI, and IMT). s-Klotho also correlated with aldosterone, whose levels were elevated only in advanced CKD (stages G4-5) and showed no association with vascular parameters. Multivariate analysis identified age as the only independent determinant of CAVI; s-Klotho emerged as an independent predictor only in models excluding age.

CONCLUSION

s-Klotho levels progressively decline in CKD and are associated with vascular damage, supporting an association between Klotho deficiency and vascular damage that appears independent of aldosterone.

MeSH

Kidney Diseases, Aldosterone, Cross-Sectional Studies, Ankle, Kidney, Nephrology, Kidney Transplantation