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Single-Nephron GFR in Different Glomerular Basement Membrane Stages of Membranous Nephropathy
KEY POINTS: The first study that estimated single-nephron GFR (SNGFR) in patients with membranous nephropathy (MN). Associations of SNGFR with MN staging by electron microscopy and clinicopathologic findings were cross-sectionally investigated. This study illustrates a role for disease-specific GBM...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Society of Nephrology
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10371379/ https://www.ncbi.nlm.nih.gov/pubmed/37166967 http://dx.doi.org/10.34067/KID.0000000000000142 |
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author | Okabayashi, Yusuke Tsuboi, Nobuo Marumoto, Hirokazu Sasaki, Takaya Haruhara, Kotaro Kanzaki, Go Koike, Kentaro Ueda, Hiroyuki Shimizu, Akira Puelles, Victor G. D'Agati, Vivette Yokoo, Takashi |
author_facet | Okabayashi, Yusuke Tsuboi, Nobuo Marumoto, Hirokazu Sasaki, Takaya Haruhara, Kotaro Kanzaki, Go Koike, Kentaro Ueda, Hiroyuki Shimizu, Akira Puelles, Victor G. D'Agati, Vivette Yokoo, Takashi |
author_sort | Okabayashi, Yusuke |
collection | PubMed |
description | KEY POINTS: The first study that estimated single-nephron GFR (SNGFR) in patients with membranous nephropathy (MN). Associations of SNGFR with MN staging by electron microscopy and clinicopathologic findings were cross-sectionally investigated. This study illustrates a role for disease-specific GBM structural lesions as determinants of SNGFR in patients with MN. BACKGROUND: Alterations in single-nephron dynamics have been demonstrated in animal models of membranous nephropathy (MN). This study applied a recently developed technique to estimate single-nephron parameters in human MN. METHODS: Single-nephron GFR (SNGFR) and single-nephron urinary protein excretion (SNUPE) were calculated by dividing total GFR and UPE by the total estimated number of nonglobally sclerotic glomeruli (NSG). The NSG number per kidney was estimated using cortical volume assessment and biopsy-based stereology. MN staging by electron microscopy was performed using Ehrenreich-Churg (EC) criteria. Single-nephron parameters were analyzed in relation to clinicopathological factors known to associate with disease outcomes. RESULTS: The study included 109 patients with MN (mean age 65 years; 73% male; eGFR 62 ml/min, 36% on renin-angiotensin-aldosterone system inhibitors prebiopsy). EC stages were I, 19%; II, 49%; III, 26%; and IV, 6%. There was no difference in glomerular volume among EC stage groups. With advancing EC stage, SNGFR and SNUPE decreased from mean 56–42 nl/min and 5.1–3.8 µg/d, respectively. In multivariable models, EC stage was associated with SNGFR even after adjustment for key clinicopathological factors, such as reduced GFR, serum albumin, UPE, segmental glomerulosclerosis, chronic tubulointerstitial damage, and prebiopsy use of renin-angiotensin-aldosterone system inhibitors. By contrast, EC stage was not associated with glomerular volume and SNUPE after multivariable adjustment. CONCLUSIONS: These results provide the first clinical evidence of alterations in single-nephron dynamics with advancing EC stage of human MN and support a role for disease-specific glomerular basement membrane structural lesions as determinants of SNGFR. |
format | Online Article Text |
id | pubmed-10371379 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society of Nephrology |
record_format | MEDLINE/PubMed |
spelling | pubmed-103713792023-08-03 Single-Nephron GFR in Different Glomerular Basement Membrane Stages of Membranous Nephropathy Okabayashi, Yusuke Tsuboi, Nobuo Marumoto, Hirokazu Sasaki, Takaya Haruhara, Kotaro Kanzaki, Go Koike, Kentaro Ueda, Hiroyuki Shimizu, Akira Puelles, Victor G. D'Agati, Vivette Yokoo, Takashi Kidney360 Original Investigation KEY POINTS: The first study that estimated single-nephron GFR (SNGFR) in patients with membranous nephropathy (MN). Associations of SNGFR with MN staging by electron microscopy and clinicopathologic findings were cross-sectionally investigated. This study illustrates a role for disease-specific GBM structural lesions as determinants of SNGFR in patients with MN. BACKGROUND: Alterations in single-nephron dynamics have been demonstrated in animal models of membranous nephropathy (MN). This study applied a recently developed technique to estimate single-nephron parameters in human MN. METHODS: Single-nephron GFR (SNGFR) and single-nephron urinary protein excretion (SNUPE) were calculated by dividing total GFR and UPE by the total estimated number of nonglobally sclerotic glomeruli (NSG). The NSG number per kidney was estimated using cortical volume assessment and biopsy-based stereology. MN staging by electron microscopy was performed using Ehrenreich-Churg (EC) criteria. Single-nephron parameters were analyzed in relation to clinicopathological factors known to associate with disease outcomes. RESULTS: The study included 109 patients with MN (mean age 65 years; 73% male; eGFR 62 ml/min, 36% on renin-angiotensin-aldosterone system inhibitors prebiopsy). EC stages were I, 19%; II, 49%; III, 26%; and IV, 6%. There was no difference in glomerular volume among EC stage groups. With advancing EC stage, SNGFR and SNUPE decreased from mean 56–42 nl/min and 5.1–3.8 µg/d, respectively. In multivariable models, EC stage was associated with SNGFR even after adjustment for key clinicopathological factors, such as reduced GFR, serum albumin, UPE, segmental glomerulosclerosis, chronic tubulointerstitial damage, and prebiopsy use of renin-angiotensin-aldosterone system inhibitors. By contrast, EC stage was not associated with glomerular volume and SNUPE after multivariable adjustment. CONCLUSIONS: These results provide the first clinical evidence of alterations in single-nephron dynamics with advancing EC stage of human MN and support a role for disease-specific glomerular basement membrane structural lesions as determinants of SNGFR. American Society of Nephrology 2023-05-10 /pmc/articles/PMC10371379/ /pubmed/37166967 http://dx.doi.org/10.34067/KID.0000000000000142 Text en Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
spellingShingle | Original Investigation Okabayashi, Yusuke Tsuboi, Nobuo Marumoto, Hirokazu Sasaki, Takaya Haruhara, Kotaro Kanzaki, Go Koike, Kentaro Ueda, Hiroyuki Shimizu, Akira Puelles, Victor G. D'Agati, Vivette Yokoo, Takashi Single-Nephron GFR in Different Glomerular Basement Membrane Stages of Membranous Nephropathy |
title | Single-Nephron GFR in Different Glomerular Basement Membrane Stages of Membranous Nephropathy |
title_full | Single-Nephron GFR in Different Glomerular Basement Membrane Stages of Membranous Nephropathy |
title_fullStr | Single-Nephron GFR in Different Glomerular Basement Membrane Stages of Membranous Nephropathy |
title_full_unstemmed | Single-Nephron GFR in Different Glomerular Basement Membrane Stages of Membranous Nephropathy |
title_short | Single-Nephron GFR in Different Glomerular Basement Membrane Stages of Membranous Nephropathy |
title_sort | single-nephron gfr in different glomerular basement membrane stages of membranous nephropathy |
topic | Original Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10371379/ https://www.ncbi.nlm.nih.gov/pubmed/37166967 http://dx.doi.org/10.34067/KID.0000000000000142 |
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