Very low urinary Marinobufagenin (uMBG) excretion reflects a high risk of disease progression in nonadvanced CKD

Davide Bolignano ^* Marta Greco Loredana Tripodi Mario D'Agostino Paola Cianfrone Roberta Misiti Sara Pugliese Mariateresa Zicarelli Michela Musolino Daniela Patrizia Foti Michele Andreucci Giuseppe Coppolino

• Magna Græcia University, Catanzaro, Italy

Background: Chronic kidney disease (CKD) has now reached pandemic proportions but risk prediction towards end-stage kidney disease (ESKD) remains challenging. Kidney fibrosis is a key determinant in the transition from CKD to ESKD. In this prospective study, we investigated the prognostic significance of urinary Marinobufagenin (uMBG), a cardiotonic steroid with acknowledged pro-fibrotic activity, for stratifying the risk of CKD progression in individuals with non-advanced renal disease. Methods: After baseline uMBG measurements, 108 CKD patients (eGFR 40.54±17 mL/min/1.73 m²) were prospectively followed up to 24 months. The study (renal) endpoint was a composite of serum creatinine doubling, eGFR decline >25% from baseline values, or ESKD requiring chronic renal replacement therapy. Results: During follow-up (mean 21 months), 32.4% of patients had progressive CKD. These individuals displayed almost halved baseline uMBG excretion as compared to others (p<0.0001). At ROC analysis uMBG showed a remarkable diagnostic capacity on CKD progression (AUC 0.898) and patients with uMBG ≤310 pmol/L (Best ROC-derived cut-off) had a significantly faster progression to the endpoint (Log-rank 57.9; p<0.0001). Restricted cubic splines fitting logistic and Cox-regression analyses revealed that the risk association between uMBG and CKD progression was best described by a curvilinear, inverse J-shaped trend, the highest risk associated with very low uMBG levels. This trend remained unaffected by adjustment for age, baseline eGFR, and 24hproteinuria.In individuals with non-advanced CKD, very low urinary excretion of MBG reflects a more sustained risk of CKD progression over time. Validation studies are needed to generalize these findings in larger heterogeneous cohorts.