Prognostic Value of Urinary Biomarkers in Proteinuria Progression in IgA Nephropathy Patients Treated with Budesonide

<b><i>Background</i> & <i>Objectives</i>:</b> Targeted-release budesonide (TRB) is the first approved agent aimed at targeting the early pathogenetic cascade in IgA nephropathy (IgAN). <b><i>Materials and Methods</i>:</b> This prospecti...

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Main Authors: Christodoulos Keskinis, Eleni Moysidou, Stamatia Stai, Michalis Christodoulou, Georgios Lioulios, Sotirios-Spyridon Vamvakas, Maria Stella Trivyza, Panagiotis Pateinakis, Marios Papasotiriou, Maria Stangou
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Language:English
Published: MDPI AG 2025-04-01
Series:Medicina
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Online Access:https://www.mdpi.com/1648-9144/61/5/807
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author Christodoulos Keskinis
Eleni Moysidou
Stamatia Stai
Michalis Christodoulou
Georgios Lioulios
Sotirios-Spyridon Vamvakas
Maria Stella Trivyza
Panagiotis Pateinakis
Marios Papasotiriou
Maria Stangou
author_facet Christodoulos Keskinis
Eleni Moysidou
Stamatia Stai
Michalis Christodoulou
Georgios Lioulios
Sotirios-Spyridon Vamvakas
Maria Stella Trivyza
Panagiotis Pateinakis
Marios Papasotiriou
Maria Stangou
author_sort Christodoulos Keskinis
collection DOAJ
description <b><i>Background</i> & <i>Objectives</i>:</b> Targeted-release budesonide (TRB) is the first approved agent aimed at targeting the early pathogenetic cascade in IgA nephropathy (IgAN). <b><i>Materials and Methods</i>:</b> This prospective study included Caucasian IgAN patients diagnosed within the last 5 years, who had started a 10-month TRB treatment and were followed in the outpatient clinic. All participants had been on the maximal supportive care dose for at least the previous 6 months. Kidney function and proteinuria levels were recorded at the start of TRB treatment (T0) and at 3, 6, and 10 months (T3, T6, and T10, respectively), while urinary monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9) and clusterin (CLU) levels were measured at T0 and T3. <b><i>Results</i>:</b> In the cohort of all patients (mean age 53.24 ± 12.76 years, estimated glomerular filtration rate (eGFR 52.84 ± 25.93 mL/min/1.73 m<sup>2</sup>, proteinuria 2.84 ± 1.26 g/24 h), significant correlations were observed at T0 between MMP-9 and MCP-1 (r = 0.74, <i>p</i> = 0.004), MMP-9 and uCLU (r = 0.77, <i>p</i> = 0.002), and MCP-1 and uCLU (r = 0.65, <i>p</i> = 0.01). At T3, a significant correlation between MMP-9 and urinary CLU (uCLU) persisted (r = 0.71, <i>p</i> = 0.03). Higher MCP-1 (r = −0.560, <i>p</i> = 0.046) and MMP-9 (r = −0.330, <i>p</i> = 0.012) levels at T0 were associated with reduced proteinuria. Conversely, increased clusterin at T3 (r = 0.599, <i>p</i> = 0.031) was associated with worsening proteinuria. <b><i>Conclusions</i>:</b> The treatment response to TRB was heterogeneous, with recent diagnosis (RD) patients showing improved kidney function and proteinuria, while older diagnosis (OD) patients exhibited worsening biomarkers and declining kidney function. Therefore, early interventions are crucial in IgAN patients. Finally, the biomarkers studied can be used prognostically to monitor disease progression.
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spelling doaj-art-c21d7114b4d247aeb831b962fbdcadc22025-08-20T03:47:59ZengMDPI AGMedicina1010-660X1648-91442025-04-0161580710.3390/medicina61050807Prognostic Value of Urinary Biomarkers in Proteinuria Progression in IgA Nephropathy Patients Treated with BudesonideChristodoulos Keskinis0Eleni Moysidou1Stamatia Stai2Michalis Christodoulou3Georgios Lioulios4Sotirios-Spyridon Vamvakas5Maria Stella Trivyza6Panagiotis Pateinakis7Marios Papasotiriou8Maria Stangou9School of Medicine, Aristotle University of Thessaloniki (AUTH), 54642 Thessaloniki, GreeceSchool of Medicine, Aristotle University of Thessaloniki (AUTH), 54642 Thessaloniki, GreeceSchool of Medicine, Aristotle University of Thessaloniki (AUTH), 54642 Thessaloniki, GreeceSchool of Medicine, Aristotle University of Thessaloniki (AUTH), 54642 Thessaloniki, GreeceSchool of Medicine, Aristotle University of Thessaloniki (AUTH), 54642 Thessaloniki, GreeceDepartment of Nutritional Science and Dietetics, University of Peloponnese, 24100 Kalamata, GreeceDepartment of Nephrology and Renal Transplantation, University Hospital of Patras, 26504 Patras, GreeceDepartment of Nephrology, Papageorgiou Hospital, 56429 Thessaloniki, GreeceDepartment of Nephrology and Renal Transplantation, University Hospital of Patras, 26504 Patras, GreeceSchool of Medicine, Aristotle University of Thessaloniki (AUTH), 54642 Thessaloniki, Greece<b><i>Background</i> & <i>Objectives</i>:</b> Targeted-release budesonide (TRB) is the first approved agent aimed at targeting the early pathogenetic cascade in IgA nephropathy (IgAN). <b><i>Materials and Methods</i>:</b> This prospective study included Caucasian IgAN patients diagnosed within the last 5 years, who had started a 10-month TRB treatment and were followed in the outpatient clinic. All participants had been on the maximal supportive care dose for at least the previous 6 months. Kidney function and proteinuria levels were recorded at the start of TRB treatment (T0) and at 3, 6, and 10 months (T3, T6, and T10, respectively), while urinary monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9) and clusterin (CLU) levels were measured at T0 and T3. <b><i>Results</i>:</b> In the cohort of all patients (mean age 53.24 ± 12.76 years, estimated glomerular filtration rate (eGFR 52.84 ± 25.93 mL/min/1.73 m<sup>2</sup>, proteinuria 2.84 ± 1.26 g/24 h), significant correlations were observed at T0 between MMP-9 and MCP-1 (r = 0.74, <i>p</i> = 0.004), MMP-9 and uCLU (r = 0.77, <i>p</i> = 0.002), and MCP-1 and uCLU (r = 0.65, <i>p</i> = 0.01). At T3, a significant correlation between MMP-9 and urinary CLU (uCLU) persisted (r = 0.71, <i>p</i> = 0.03). Higher MCP-1 (r = −0.560, <i>p</i> = 0.046) and MMP-9 (r = −0.330, <i>p</i> = 0.012) levels at T0 were associated with reduced proteinuria. Conversely, increased clusterin at T3 (r = 0.599, <i>p</i> = 0.031) was associated with worsening proteinuria. <b><i>Conclusions</i>:</b> The treatment response to TRB was heterogeneous, with recent diagnosis (RD) patients showing improved kidney function and proteinuria, while older diagnosis (OD) patients exhibited worsening biomarkers and declining kidney function. Therefore, early interventions are crucial in IgAN patients. Finally, the biomarkers studied can be used prognostically to monitor disease progression.https://www.mdpi.com/1648-9144/61/5/807IgA nephropathytargeted-release budesonideurinary biomarkersMonocyte Chemotactic Protein-1 (MCP-1)Matrix MetalloProteinase-9 (MMP-9)clusterin (CLU)
spellingShingle Christodoulos Keskinis
Eleni Moysidou
Stamatia Stai
Michalis Christodoulou
Georgios Lioulios
Sotirios-Spyridon Vamvakas
Maria Stella Trivyza
Panagiotis Pateinakis
Marios Papasotiriou
Maria Stangou
Prognostic Value of Urinary Biomarkers in Proteinuria Progression in IgA Nephropathy Patients Treated with Budesonide
Medicina
IgA nephropathy
targeted-release budesonide
urinary biomarkers
Monocyte Chemotactic Protein-1 (MCP-1)
Matrix MetalloProteinase-9 (MMP-9)
clusterin (CLU)
title Prognostic Value of Urinary Biomarkers in Proteinuria Progression in IgA Nephropathy Patients Treated with Budesonide
title_full Prognostic Value of Urinary Biomarkers in Proteinuria Progression in IgA Nephropathy Patients Treated with Budesonide
title_fullStr Prognostic Value of Urinary Biomarkers in Proteinuria Progression in IgA Nephropathy Patients Treated with Budesonide
title_full_unstemmed Prognostic Value of Urinary Biomarkers in Proteinuria Progression in IgA Nephropathy Patients Treated with Budesonide
title_short Prognostic Value of Urinary Biomarkers in Proteinuria Progression in IgA Nephropathy Patients Treated with Budesonide
title_sort prognostic value of urinary biomarkers in proteinuria progression in iga nephropathy patients treated with budesonide
topic IgA nephropathy
targeted-release budesonide
urinary biomarkers
Monocyte Chemotactic Protein-1 (MCP-1)
Matrix MetalloProteinase-9 (MMP-9)
clusterin (CLU)
url https://www.mdpi.com/1648-9144/61/5/807
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