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Ratio of Urinary Proteins to Albumin Excretion Shifts Substantially during Progression of the Podocytopathy Alport Syndrome, and Spot Urine Is a Reliable Method to Detect These Pathologic Changes

The urinary albumin- and protein-to-creatinine ratios (UACR and UPCR, respectively) are key endpoints in most clinical trials assessing risk of progression of chronic kidney disease (CKD). For the first time, the current study compares the UACR versus the UPCR head-to-head at early stages of CKD, ta...

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Autores principales: Boeckhaus, Jan, Mohr, Lea, Dihazi, Hassan, Tönshoff, Burkhard, Weber, Lutz T., Pape, Lars, Latta, Kay, Fehrenbach, Henry, Lange-Sperandio, Baerbel, Kettwig, Matthias, Staude, Hagen, König, Sabine, John-Kroegel, Ulrike, Gellermann, Jutta, Hoppe, Bernd, Galiano, Matthias, Haffner, Dieter, Rhode, Heidrun, Gross, Oliver
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10177071/
https://www.ncbi.nlm.nih.gov/pubmed/37174733
http://dx.doi.org/10.3390/cells12091333
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author Boeckhaus, Jan
Mohr, Lea
Dihazi, Hassan
Tönshoff, Burkhard
Weber, Lutz T.
Pape, Lars
Latta, Kay
Fehrenbach, Henry
Lange-Sperandio, Baerbel
Kettwig, Matthias
Staude, Hagen
König, Sabine
John-Kroegel, Ulrike
Gellermann, Jutta
Hoppe, Bernd
Galiano, Matthias
Haffner, Dieter
Rhode, Heidrun
Gross, Oliver
author_facet Boeckhaus, Jan
Mohr, Lea
Dihazi, Hassan
Tönshoff, Burkhard
Weber, Lutz T.
Pape, Lars
Latta, Kay
Fehrenbach, Henry
Lange-Sperandio, Baerbel
Kettwig, Matthias
Staude, Hagen
König, Sabine
John-Kroegel, Ulrike
Gellermann, Jutta
Hoppe, Bernd
Galiano, Matthias
Haffner, Dieter
Rhode, Heidrun
Gross, Oliver
author_sort Boeckhaus, Jan
collection PubMed
description The urinary albumin- and protein-to-creatinine ratios (UACR and UPCR, respectively) are key endpoints in most clinical trials assessing risk of progression of chronic kidney disease (CKD). For the first time, the current study compares the UACR versus the UPCR head-to-head at early stages of CKD, taking use of the hereditary podocytopathy Alport syndrome (AS) as a model disease for any CKD. Urine samples originated from the prospective randomized, controlled EARLY PRO-TECT Alport trial (NCT01485978). Urine samples from 47 children with confirmed diagnoses of AS at very early stages of CKD were divided according to the current stage of AS: stage 0 (UACR < 30 mg/g), stage 1 (30–300 mg/g) or stage 2 (>300 mg/g). The range of estimated glomerular filtration rate was 75–187.6 mL/min. The mean age was 10.4 ± 4.5 years. In children at stage 0, proteinuria in spot urine, confirmed in 24 h urine, was almost ten times higher than albuminuria (106.4 ± 42.2 vs. 12.5 ± 9.7; p < 0.05); it was “only” about three times higher in stage 1 (328.5 ± 210.1 vs. 132.3 ± 80.5; p < 0.05) and almost equal in stage 2 (1481.9 ± 983.4 vs. 1109.7 ± 873.6; p = 0.36). In 17 children, UACRs and UPCRs were measured simultaneously in 24 h urine and spot urine in the same study visit. Interestingly, the UACR (and UPCR) in 24 h urine vs. in spot urine varied by less than 10% (266.8 ± 426.4 vs. 291.2 ± 530.2). In conclusion, our study provides the first evidence that in patients with normal glomerular filtration rate (GFR) and low amounts of albuminuria, especially in children with podocytopathies such as AS, measuring the UACR and UPCR in spot urine is a reliable and convenient alternative to 24 h urine collection. Our study advocates both the UACR and the UPCR as relevant diagnostic biomarkers in future clinical trials in children with glomerular diseases because the UPCR seems to be a very significant parameter at very early stages of podocytopathies. The German Federal Ministry of Education and Research funded this trial (01KG1104).
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spelling pubmed-101770712023-05-13 Ratio of Urinary Proteins to Albumin Excretion Shifts Substantially during Progression of the Podocytopathy Alport Syndrome, and Spot Urine Is a Reliable Method to Detect These Pathologic Changes Boeckhaus, Jan Mohr, Lea Dihazi, Hassan Tönshoff, Burkhard Weber, Lutz T. Pape, Lars Latta, Kay Fehrenbach, Henry Lange-Sperandio, Baerbel Kettwig, Matthias Staude, Hagen König, Sabine John-Kroegel, Ulrike Gellermann, Jutta Hoppe, Bernd Galiano, Matthias Haffner, Dieter Rhode, Heidrun Gross, Oliver Cells Article The urinary albumin- and protein-to-creatinine ratios (UACR and UPCR, respectively) are key endpoints in most clinical trials assessing risk of progression of chronic kidney disease (CKD). For the first time, the current study compares the UACR versus the UPCR head-to-head at early stages of CKD, taking use of the hereditary podocytopathy Alport syndrome (AS) as a model disease for any CKD. Urine samples originated from the prospective randomized, controlled EARLY PRO-TECT Alport trial (NCT01485978). Urine samples from 47 children with confirmed diagnoses of AS at very early stages of CKD were divided according to the current stage of AS: stage 0 (UACR < 30 mg/g), stage 1 (30–300 mg/g) or stage 2 (>300 mg/g). The range of estimated glomerular filtration rate was 75–187.6 mL/min. The mean age was 10.4 ± 4.5 years. In children at stage 0, proteinuria in spot urine, confirmed in 24 h urine, was almost ten times higher than albuminuria (106.4 ± 42.2 vs. 12.5 ± 9.7; p < 0.05); it was “only” about three times higher in stage 1 (328.5 ± 210.1 vs. 132.3 ± 80.5; p < 0.05) and almost equal in stage 2 (1481.9 ± 983.4 vs. 1109.7 ± 873.6; p = 0.36). In 17 children, UACRs and UPCRs were measured simultaneously in 24 h urine and spot urine in the same study visit. Interestingly, the UACR (and UPCR) in 24 h urine vs. in spot urine varied by less than 10% (266.8 ± 426.4 vs. 291.2 ± 530.2). In conclusion, our study provides the first evidence that in patients with normal glomerular filtration rate (GFR) and low amounts of albuminuria, especially in children with podocytopathies such as AS, measuring the UACR and UPCR in spot urine is a reliable and convenient alternative to 24 h urine collection. Our study advocates both the UACR and the UPCR as relevant diagnostic biomarkers in future clinical trials in children with glomerular diseases because the UPCR seems to be a very significant parameter at very early stages of podocytopathies. The German Federal Ministry of Education and Research funded this trial (01KG1104). MDPI 2023-05-07 /pmc/articles/PMC10177071/ /pubmed/37174733 http://dx.doi.org/10.3390/cells12091333 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Boeckhaus, Jan
Mohr, Lea
Dihazi, Hassan
Tönshoff, Burkhard
Weber, Lutz T.
Pape, Lars
Latta, Kay
Fehrenbach, Henry
Lange-Sperandio, Baerbel
Kettwig, Matthias
Staude, Hagen
König, Sabine
John-Kroegel, Ulrike
Gellermann, Jutta
Hoppe, Bernd
Galiano, Matthias
Haffner, Dieter
Rhode, Heidrun
Gross, Oliver
Ratio of Urinary Proteins to Albumin Excretion Shifts Substantially during Progression of the Podocytopathy Alport Syndrome, and Spot Urine Is a Reliable Method to Detect These Pathologic Changes
title Ratio of Urinary Proteins to Albumin Excretion Shifts Substantially during Progression of the Podocytopathy Alport Syndrome, and Spot Urine Is a Reliable Method to Detect These Pathologic Changes
title_full Ratio of Urinary Proteins to Albumin Excretion Shifts Substantially during Progression of the Podocytopathy Alport Syndrome, and Spot Urine Is a Reliable Method to Detect These Pathologic Changes
title_fullStr Ratio of Urinary Proteins to Albumin Excretion Shifts Substantially during Progression of the Podocytopathy Alport Syndrome, and Spot Urine Is a Reliable Method to Detect These Pathologic Changes
title_full_unstemmed Ratio of Urinary Proteins to Albumin Excretion Shifts Substantially during Progression of the Podocytopathy Alport Syndrome, and Spot Urine Is a Reliable Method to Detect These Pathologic Changes
title_short Ratio of Urinary Proteins to Albumin Excretion Shifts Substantially during Progression of the Podocytopathy Alport Syndrome, and Spot Urine Is a Reliable Method to Detect These Pathologic Changes
title_sort ratio of urinary proteins to albumin excretion shifts substantially during progression of the podocytopathy alport syndrome, and spot urine is a reliable method to detect these pathologic changes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10177071/
https://www.ncbi.nlm.nih.gov/pubmed/37174733
http://dx.doi.org/10.3390/cells12091333
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