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Changing Protein Permeability with Nephron Loss; Evidence for a Human Remnant Nephron Effect

Lookup NU author(s): Dr Jamie Willows, Dr Ian Logan, Professor Neil SheerinORCiD, Dr Charlie Tomson, Dr Tim Ellam



This is the authors' accepted manuscript of an article that has been published in its final definitive form by S. Karger AG, 2019.

For re-use rights please refer to the publisher's terms and conditions.


Background If loss of functioning nephrons predisposes to glomerular barotrauma (a ‘remnant nephron’ effect) then glomerular permeability should increase as glomerular filtration rate (GFR) falls, as is observed in animal models of nephron loss. Methods Changes in protein permeability, defined as proteinuria or albuminuria per ml/min of GFR, were measured in the setting of nephron loss due to kidney donation (ALTOLD cohort) or progressive CKD (MDRD, AASK and CRIC studies).Results Following kidney donation renal albumin permeability increased by 31% from predonation levels (p<0.001). With progression of CKD a 50% loss of residual GFR was accompanied by increases in proteinuria per ml/min GFR of 1.8-, 2.1-, and 1.6-fold in the MDRD, AASK and CRIC cohorts respectively (p<0.001 for all), independent of systolic BP changes and ACE/ARB use. A 70% reduction in GFR was associated with permeability increases of 3.1-, 4.4-, and 2.6-fold in the same cohorts. Among MDRD participants with progression of nonglomerular primary disease, the top quartile of final protein permeability was 141mg/ml/min. This degree of permeability would have resulted in nephrotic range proteinuria had it been present at the baseline mean GFR of 40ml/min, implying the development of de novo glomerular pathology as GFR fell. In the absence of a fall in GFR there was no increase in permeability.Conclusion Nephron loss is accompanied by a measurable increase in albuminuria which can be explained by increased glomerular protein permeability, even in the absence of a primary glomerular disease. This is consistent with a remnant nephron effect in human CKD.

Publication metadata

Author(s): Willows W, Odudu A, Logan I, Sheerin NS, Tomson C, Ellam T

Publication type: Article

Publication status: Published

Journal: American Journal of Nephrology

Year: 2019

Volume: 50

Pages: 152-159

Online publication date: 03/07/2019

Acceptance date: 06/06/2019

Date deposited: 08/06/2019

ISSN (print): 0250-8095

ISSN (electronic): 1421-9670

Publisher: S. Karger AG


DOI: 10.1159/000501472


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