RAS inhibition modulates kynurenine levels in a CKD population with and without type 2 diabetes mellitus

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Valeria Cernaro 1, Saverio Loddo 2, Vincenzo Macaione 2, Valentina Teresa Ferlazzo 2, Rosalia Maria Cigala 3, Francesco Crea 3, Concetta De Stefano 3, Antonina Rita Rosalia Genovese 4, Guido Gembillo 4, Davide Bolignano 5, Domenico Santoro 4, Roberto Vita 6, Michele Buemi 4, Salvatore Benvenga 6 7 8

Main idea: These findings may contribute to explain the well-known beneficial effects of RAS inhibition in CKD population, especially considering that kynurenine is emerging as a potential new biomarker of CKD.

Abstract

Kynurenine pathway of tryptophan metabolism is involved in the pathophysiology of chronic kidney disease (CKD) and diabetes mellitus. Renin-angiotensin system inhibitors (RASis) are recommended in these patients to decrease proteinuria, slow CKD progression and reduce cardiovascular risk. Whether these drugs influence kyn Laurenine levels in humans is unknown. We evaluated serum tryptophile in patients suffering from CKD with or without type 2 diabetes Mellitus, their correlations with markers of reduced kidney function, and their relationship with RAS-inhibiting therapy. Kynuranine levels were significantly lower in the group under RASis compared to the untreated group (1.56± 0.79 vs 2.16± 1.51 mu/mol/l) in this group. The link with proteinuria was directly related to both proteinuria and albuminuria.

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