Very low urinary marinobufagenin excretion reflects a high risk of disease progression in non-advanced CKD
BackgroundChronic 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...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-02-01
|
| Series: | Frontiers in Physiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2025.1527805/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832548284389916672 |
|---|---|
| author | Davide Bolignano Davide Bolignano Marta Greco Marta Greco Loredana Tripodi Mario D’Agostino Paola Cianfrone Roberta Misiti Roberta Misiti Sara Pugliese Mariateresa Zicarelli Michela Musolino Michela Musolino Daniela Patrizia Foti Daniela Patrizia Foti Michele Andreucci Michele Andreucci Giuseppe Coppolino Giuseppe Coppolino |
| author_facet | Davide Bolignano Davide Bolignano Marta Greco Marta Greco Loredana Tripodi Mario D’Agostino Paola Cianfrone Roberta Misiti Roberta Misiti Sara Pugliese Mariateresa Zicarelli Michela Musolino Michela Musolino Daniela Patrizia Foti Daniela Patrizia Foti Michele Andreucci Michele Andreucci Giuseppe Coppolino Giuseppe Coppolino |
| author_sort | Davide Bolignano |
| collection | DOAJ |
| description | BackgroundChronic 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.MethodsAfter 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.ResultsDuring 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 24 h-proteinuria.ConclusionIn 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. |
| format | Article |
| id | doaj-art-a59e1070130447228044a99ec793e74e |
| institution | Kabale University |
| issn | 1664-042X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj-art-a59e1070130447228044a99ec793e74e2025-02-03T06:33:29ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2025-02-011610.3389/fphys.2025.15278051527805Very low urinary marinobufagenin excretion reflects a high risk of disease progression in non-advanced CKDDavide Bolignano0Davide Bolignano1Marta Greco2Marta Greco3Loredana Tripodi4Mario D’Agostino5Paola Cianfrone6Roberta Misiti7Roberta Misiti8Sara Pugliese9Mariateresa Zicarelli10Michela Musolino11Michela Musolino12Daniela Patrizia Foti13Daniela Patrizia Foti14Michele Andreucci15Michele Andreucci16Giuseppe Coppolino17Giuseppe Coppolino18Nephrology and Dialysis Unit, Magna-Graecia University Hospital, Catanzaro, ItalyDepartment of Medical and Surgical Sciences, Magna-Graecia University, Catanzaro, ItalyClinical Pathology Lab, Magna-Graecia University Hospital, Catanzaro, ItalyDepartment of Health Sciences, Magna-Graecia University, Catanzaro, ItalyNephrology and Dialysis Unit, Magna-Graecia University Hospital, Catanzaro, ItalyNephrology and Dialysis Unit, Magna-Graecia University Hospital, Catanzaro, ItalyNephrology and Dialysis Unit, Magna-Graecia University Hospital, Catanzaro, ItalyClinical Pathology Lab, Magna-Graecia University Hospital, Catanzaro, ItalyDepartment of Health Sciences, Magna-Graecia University, Catanzaro, ItalyNephrology and Dialysis Unit, Magna-Graecia University Hospital, Catanzaro, ItalyDepartment of Health Sciences, Magna-Graecia University, Catanzaro, ItalyNephrology and Dialysis Unit, Magna-Graecia University Hospital, Catanzaro, ItalyDepartment of Health Sciences, Magna-Graecia University, Catanzaro, ItalyClinical Pathology Lab, Magna-Graecia University Hospital, Catanzaro, ItalyDepartment of Experimental and Clinical Medicine, Magna-Graecia University, Catanzaro, ItalyNephrology and Dialysis Unit, Magna-Graecia University Hospital, Catanzaro, ItalyDepartment of Health Sciences, Magna-Graecia University, Catanzaro, ItalyNephrology and Dialysis Unit, Magna-Graecia University Hospital, Catanzaro, ItalyDepartment of Health Sciences, Magna-Graecia University, Catanzaro, ItalyBackgroundChronic 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.MethodsAfter 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.ResultsDuring 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 24 h-proteinuria.ConclusionIn 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.https://www.frontiersin.org/articles/10.3389/fphys.2025.1527805/fullchronic kidney diseaseCKD progressionbiomarkermarinobufageninrenal failure |
| spellingShingle | Davide Bolignano Davide Bolignano Marta Greco Marta Greco Loredana Tripodi Mario D’Agostino Paola Cianfrone Roberta Misiti Roberta Misiti Sara Pugliese Mariateresa Zicarelli Michela Musolino Michela Musolino Daniela Patrizia Foti Daniela Patrizia Foti Michele Andreucci Michele Andreucci Giuseppe Coppolino Giuseppe Coppolino Very low urinary marinobufagenin excretion reflects a high risk of disease progression in non-advanced CKD Frontiers in Physiology chronic kidney disease CKD progression biomarker marinobufagenin renal failure |
| title | Very low urinary marinobufagenin excretion reflects a high risk of disease progression in non-advanced CKD |
| title_full | Very low urinary marinobufagenin excretion reflects a high risk of disease progression in non-advanced CKD |
| title_fullStr | Very low urinary marinobufagenin excretion reflects a high risk of disease progression in non-advanced CKD |
| title_full_unstemmed | Very low urinary marinobufagenin excretion reflects a high risk of disease progression in non-advanced CKD |
| title_short | Very low urinary marinobufagenin excretion reflects a high risk of disease progression in non-advanced CKD |
| title_sort | very low urinary marinobufagenin excretion reflects a high risk of disease progression in non advanced ckd |
| topic | chronic kidney disease CKD progression biomarker marinobufagenin renal failure |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2025.1527805/full |
| work_keys_str_mv | AT davidebolignano verylowurinarymarinobufageninexcretionreflectsahighriskofdiseaseprogressioninnonadvancedckd AT davidebolignano verylowurinarymarinobufageninexcretionreflectsahighriskofdiseaseprogressioninnonadvancedckd AT martagreco verylowurinarymarinobufageninexcretionreflectsahighriskofdiseaseprogressioninnonadvancedckd AT martagreco verylowurinarymarinobufageninexcretionreflectsahighriskofdiseaseprogressioninnonadvancedckd AT loredanatripodi verylowurinarymarinobufageninexcretionreflectsahighriskofdiseaseprogressioninnonadvancedckd AT mariodagostino verylowurinarymarinobufageninexcretionreflectsahighriskofdiseaseprogressioninnonadvancedckd AT paolacianfrone verylowurinarymarinobufageninexcretionreflectsahighriskofdiseaseprogressioninnonadvancedckd AT robertamisiti verylowurinarymarinobufageninexcretionreflectsahighriskofdiseaseprogressioninnonadvancedckd AT robertamisiti verylowurinarymarinobufageninexcretionreflectsahighriskofdiseaseprogressioninnonadvancedckd AT sarapugliese verylowurinarymarinobufageninexcretionreflectsahighriskofdiseaseprogressioninnonadvancedckd AT mariateresazicarelli verylowurinarymarinobufageninexcretionreflectsahighriskofdiseaseprogressioninnonadvancedckd AT michelamusolino verylowurinarymarinobufageninexcretionreflectsahighriskofdiseaseprogressioninnonadvancedckd AT michelamusolino verylowurinarymarinobufageninexcretionreflectsahighriskofdiseaseprogressioninnonadvancedckd AT danielapatriziafoti verylowurinarymarinobufageninexcretionreflectsahighriskofdiseaseprogressioninnonadvancedckd AT danielapatriziafoti verylowurinarymarinobufageninexcretionreflectsahighriskofdiseaseprogressioninnonadvancedckd AT micheleandreucci verylowurinarymarinobufageninexcretionreflectsahighriskofdiseaseprogressioninnonadvancedckd AT micheleandreucci verylowurinarymarinobufageninexcretionreflectsahighriskofdiseaseprogressioninnonadvancedckd AT giuseppecoppolino verylowurinarymarinobufageninexcretionreflectsahighriskofdiseaseprogressioninnonadvancedckd AT giuseppecoppolino verylowurinarymarinobufageninexcretionreflectsahighriskofdiseaseprogressioninnonadvancedckd |