Changing Protein Permeability with Nephron Loss: Evidence for a Human Remnant Nephron Effect.
Adult
Aged
Animals
Disease Progression
Female
Glomerular Filtration Rate
/ physiology
Humans
Living Donors
Male
Middle Aged
Nephrectomy
/ adverse effects
Nephrons
/ metabolism
Permeability
Prospective Studies
Proteinuria
/ etiology
Renal Insufficiency, Chronic
/ complications
Risk Factors
Serum Albumin, Human
/ metabolism
Tissue and Organ Procurement
Chronic kidney disease
Glomerular filtration rate
Glomerulus
Hypertension
Proteinuria
Remnant nephron
Journal
American journal of nephrology
ISSN: 1421-9670
Titre abrégé: Am J Nephrol
Pays: Switzerland
ID NLM: 8109361
Informations de publication
Date de publication:
2019
2019
Historique:
received:
16
04
2019
accepted:
06
06
2019
pubmed:
4
7
2019
medline:
1
9
2020
entrez:
4
7
2019
Statut:
ppublish
Résumé
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. Changes in net renal protein permeability, defined as proteinuria or albuminuria per mL/min of GFR, were measured in the setting of nephron loss due to kidney donation (Assessing Long Term Outcomes in Living Kidney Donors cohort) or progressive chronic kidney disease (CKD; Modification of Diet in Renal Disease [MDRD], African American Study of Kidney Disease [AASK], and Chronic Renal insufficiency Cohort [CRIC] studies). 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 changes in systolic blood pressure and ACEi/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 75th percentile of final permeability was 141 mg/24 h proteinuria per mL/min GFR. This degree of permeability would have resulted in nephrotic range proteinuria had it been present at the baseline mean GFR of 40 mL/min, implying the development of de novo glomerular pathology as GFR fell. Increasing permeability also accompanied CKD progression in participants with nephrotic syndrome at baseline. Consequently, these participants had little improvement in 24 h proteinuria or serum albumin, despite substantial loss of functioning nephron mass across which the protein leak occurred. In the absence of a fall in GFR, there was no increase in permeability in any cohort. Nephron loss is accompanied by an increase in renal protein permeability, even in the absence of a primary glomerular disease. This is consistent with a remnant nephron effect in human CKD.
Sections du résumé
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 net renal protein permeability, defined as proteinuria or albuminuria per mL/min of GFR, were measured in the setting of nephron loss due to kidney donation (Assessing Long Term Outcomes in Living Kidney Donors cohort) or progressive chronic kidney disease (CKD; Modification of Diet in Renal Disease [MDRD], African American Study of Kidney Disease [AASK], and Chronic Renal insufficiency Cohort [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 changes in systolic blood pressure and ACEi/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 75th percentile of final permeability was 141 mg/24 h proteinuria per mL/min GFR. This degree of permeability would have resulted in nephrotic range proteinuria had it been present at the baseline mean GFR of 40 mL/min, implying the development of de novo glomerular pathology as GFR fell. Increasing permeability also accompanied CKD progression in participants with nephrotic syndrome at baseline. Consequently, these participants had little improvement in 24 h proteinuria or serum albumin, despite substantial loss of functioning nephron mass across which the protein leak occurred. In the absence of a fall in GFR, there was no increase in permeability in any cohort.
CONCLUSION
Nephron loss is accompanied by an increase in renal protein permeability, even in the absence of a primary glomerular disease. This is consistent with a remnant nephron effect in human CKD.
Identifiants
pubmed: 31269482
pii: 000501472
doi: 10.1159/000501472
doi:
Substances chimiques
Serum Albumin, Human
ZIF514RVZR
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
152-159Informations de copyright
© 2019 S. Karger AG, Basel.