Urinary Marinobufagenin Reflects the Severity of Renal Disease in Non-Advanced CKD: a Pilot Study

Abstract Background and Aims The identification of new biomolecules involved in the pathogenesis of chronic kidney disease (CKD) which may improve clinical understanding remains a research priority. Marinobufagenin (MBG) is an endogenous cardiotonic steroid endowed with natriuretic and vasoactive properties, which altered levels trigger fibrosis of various organs, including the kidney. The kidney plays a central role in regulating the systemic MBG balance through its urinary excretion (uMBG) but the impact of a reduced clearance due to CKD remains unknown. In this pilot study, we analyzed the clinical and diagnostic significance of uMBG in a cohort of CKD patients with mild-to-moderate CKD (stage 2-4) Method uMBG was measured in 108 CKD patients (mean age 71.6 ± 10 yrs, 70.4% male; mean eGFR 40.54 ± 17 mL/min/1.73 m2) together with a series of clinical, anthropometric, laboratory and instrumental parameters to identify clinical predictors in this cohort. Additionally, uMBG was measured in 25 healthy matched subjects. Results CKD patients displayed lower uMBG values as compared with controls (0.37 [IQR 0.25-0.45] vs. 0.64 [0.46-0.78] nmol/L; p = 0.004). Clinical, independent predictors of uMBG in our study cohort were eGFR (β = 0.248; p = 0.01), the use of statins (β=-0.326; p = 0.001), diabetes (β = 0.243; p = 0.009) and urinary sodium (β = 0.204; p = 0.01). At logistic regression analysis, higher uMBG levels were associated with a lower probability of having an eGFR ≤30 mL/min (OR 0.868; 95% CI 0.798-0.986; p = 0.03). At ROC analyses, uMBG displayed a good diagnostic capacity in identifying patients with more advanced CKD (AUC 0.675; 95% CI 0.578 to 0.762; p = 0.002; Fig. 1). Conclusion Conclusions: Overall, CKD patients display a reduced uMBG excretion which parallels the severity of renal clearance impairment. Sodium intake, diabetes and the assumption of statins may modulate such relationship. Additional studies are needed to confirm the diagnostic usefulness and biological meaning of measuring uMBG as a way to assess CKD severity.