Early glomerular dysfunction in human renal allografts

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background. The long-term outcome of renal allografts is characterized by a progressive deterioration of renal function and graft loss. Our aim was to determine early glomerular functional abnormalities, before they become clinically apparent. Methods. Glomerular hemodynamics and dextran sieving were characterized in 21 well-functioning cadaveric renal allograft recipients [normal glomerular filtration rate (GFR) and albumin excretion rate (AER), who also had a kidney biopsy with normal or minimal histological changes] and in 15 uninephrectomized kidney donors. Both groups were one to three years after transplantation or uninephrectomy. Results. The GFR and renal plasma flow (RPF) were similar in both groups (62 ± 3 vs. 63 ± 4, and 343 ± 26 vs. 334 ± 21 mL/min/1.73 m2 for GFR and RPF, in cadaveric recipients vs. donors, respectively), the AER was normal in both groups, but the mean arterial pressure was higher in renal recipients (103 ± 3 vs. 94 ± 3 mm Hg in uninephrectomy controls, P < 0.05). Despite similar levels of overall glomerular function in the two groups, the dextran sieving curve was uniformly elevated in the renal allograft recipients versus uninephrectomy controls (P < 0.05 for dextrans 38 to 66 Å). Using a log-normal glomerular pore-size distribution model to analyze potential mechanisms, the elevation in the dextran sieving curve resulted from a shift in the distribution of glomerular filtering pores to a larger size (mean glomerular pore size 46 ± 2 vs. 43 ± 2 Å for uninephrectomy controls, P < 0.05), resulting in a larger fraction of filtrate volume permeating very large pores. By morphometric analysis, the thickness of the glomerular basement membrane was increased in kidney allograft as compared to 2-kidney biopsy controls (614 ± 33 vs. 427 ± 22 nm, respectively, P < 0.05). Conclusions. Even in "well functioning" renal allografts there is a glomerular dysfunction characterized by increased permeability to macromolecules resulting from a shift of the glomerular pores to a larger size. These changes could be mediated by ultrastructural alterations at the glomerular capillary or by alterations in intraglomerular hemodynamics. Early allograft dysfunction may contribute to the progressive renal insufficiency of renal allografts.

Original languageEnglish (US)
Pages (from-to)1938-1947
Number of pages10
JournalKidney International
Volume60
Issue number5
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

Fingerprint

Allografts
Kidney
Dextrans
Glomerular Filtration Rate
Renal Plasma Flow
Albumins
Hemodynamics
Biopsy
Glomerular Basement Membrane
Renal Insufficiency
Permeability
Arterial Pressure
Transplantation
Transplants

Keywords

  • Dextran sieving
  • Glomerular morphometry
  • Hemodynamics
  • Permselectivity
  • Transplantation
  • Uninephrectomy

ASJC Scopus subject areas

  • Nephrology

Cite this

Early glomerular dysfunction in human renal allografts. / Zayas Montalvo, Carlos F; Guasch, A.

In: Kidney International, Vol. 60, No. 5, 01.01.2001, p. 1938-1947.

Research output: Contribution to journalArticle

@article{1cdbbd406a464031946e48602b021bdc,
title = "Early glomerular dysfunction in human renal allografts",
abstract = "Background. The long-term outcome of renal allografts is characterized by a progressive deterioration of renal function and graft loss. Our aim was to determine early glomerular functional abnormalities, before they become clinically apparent. Methods. Glomerular hemodynamics and dextran sieving were characterized in 21 well-functioning cadaveric renal allograft recipients [normal glomerular filtration rate (GFR) and albumin excretion rate (AER), who also had a kidney biopsy with normal or minimal histological changes] and in 15 uninephrectomized kidney donors. Both groups were one to three years after transplantation or uninephrectomy. Results. The GFR and renal plasma flow (RPF) were similar in both groups (62 ± 3 vs. 63 ± 4, and 343 ± 26 vs. 334 ± 21 mL/min/1.73 m2 for GFR and RPF, in cadaveric recipients vs. donors, respectively), the AER was normal in both groups, but the mean arterial pressure was higher in renal recipients (103 ± 3 vs. 94 ± 3 mm Hg in uninephrectomy controls, P < 0.05). Despite similar levels of overall glomerular function in the two groups, the dextran sieving curve was uniformly elevated in the renal allograft recipients versus uninephrectomy controls (P < 0.05 for dextrans 38 to 66 {\AA}). Using a log-normal glomerular pore-size distribution model to analyze potential mechanisms, the elevation in the dextran sieving curve resulted from a shift in the distribution of glomerular filtering pores to a larger size (mean glomerular pore size 46 ± 2 vs. 43 ± 2 {\AA} for uninephrectomy controls, P < 0.05), resulting in a larger fraction of filtrate volume permeating very large pores. By morphometric analysis, the thickness of the glomerular basement membrane was increased in kidney allograft as compared to 2-kidney biopsy controls (614 ± 33 vs. 427 ± 22 nm, respectively, P < 0.05). Conclusions. Even in {"}well functioning{"} renal allografts there is a glomerular dysfunction characterized by increased permeability to macromolecules resulting from a shift of the glomerular pores to a larger size. These changes could be mediated by ultrastructural alterations at the glomerular capillary or by alterations in intraglomerular hemodynamics. Early allograft dysfunction may contribute to the progressive renal insufficiency of renal allografts.",
keywords = "Dextran sieving, Glomerular morphometry, Hemodynamics, Permselectivity, Transplantation, Uninephrectomy",
author = "{Zayas Montalvo}, {Carlos F} and A. Guasch",
year = "2001",
month = "1",
day = "1",
doi = "10.1046/j.1523-1755.2001.00005.x",
language = "English (US)",
volume = "60",
pages = "1938--1947",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - Early glomerular dysfunction in human renal allografts

AU - Zayas Montalvo, Carlos F

AU - Guasch, A.

PY - 2001/1/1

Y1 - 2001/1/1

N2 - Background. The long-term outcome of renal allografts is characterized by a progressive deterioration of renal function and graft loss. Our aim was to determine early glomerular functional abnormalities, before they become clinically apparent. Methods. Glomerular hemodynamics and dextran sieving were characterized in 21 well-functioning cadaveric renal allograft recipients [normal glomerular filtration rate (GFR) and albumin excretion rate (AER), who also had a kidney biopsy with normal or minimal histological changes] and in 15 uninephrectomized kidney donors. Both groups were one to three years after transplantation or uninephrectomy. Results. The GFR and renal plasma flow (RPF) were similar in both groups (62 ± 3 vs. 63 ± 4, and 343 ± 26 vs. 334 ± 21 mL/min/1.73 m2 for GFR and RPF, in cadaveric recipients vs. donors, respectively), the AER was normal in both groups, but the mean arterial pressure was higher in renal recipients (103 ± 3 vs. 94 ± 3 mm Hg in uninephrectomy controls, P < 0.05). Despite similar levels of overall glomerular function in the two groups, the dextran sieving curve was uniformly elevated in the renal allograft recipients versus uninephrectomy controls (P < 0.05 for dextrans 38 to 66 Å). Using a log-normal glomerular pore-size distribution model to analyze potential mechanisms, the elevation in the dextran sieving curve resulted from a shift in the distribution of glomerular filtering pores to a larger size (mean glomerular pore size 46 ± 2 vs. 43 ± 2 Å for uninephrectomy controls, P < 0.05), resulting in a larger fraction of filtrate volume permeating very large pores. By morphometric analysis, the thickness of the glomerular basement membrane was increased in kidney allograft as compared to 2-kidney biopsy controls (614 ± 33 vs. 427 ± 22 nm, respectively, P < 0.05). Conclusions. Even in "well functioning" renal allografts there is a glomerular dysfunction characterized by increased permeability to macromolecules resulting from a shift of the glomerular pores to a larger size. These changes could be mediated by ultrastructural alterations at the glomerular capillary or by alterations in intraglomerular hemodynamics. Early allograft dysfunction may contribute to the progressive renal insufficiency of renal allografts.

AB - Background. The long-term outcome of renal allografts is characterized by a progressive deterioration of renal function and graft loss. Our aim was to determine early glomerular functional abnormalities, before they become clinically apparent. Methods. Glomerular hemodynamics and dextran sieving were characterized in 21 well-functioning cadaveric renal allograft recipients [normal glomerular filtration rate (GFR) and albumin excretion rate (AER), who also had a kidney biopsy with normal or minimal histological changes] and in 15 uninephrectomized kidney donors. Both groups were one to three years after transplantation or uninephrectomy. Results. The GFR and renal plasma flow (RPF) were similar in both groups (62 ± 3 vs. 63 ± 4, and 343 ± 26 vs. 334 ± 21 mL/min/1.73 m2 for GFR and RPF, in cadaveric recipients vs. donors, respectively), the AER was normal in both groups, but the mean arterial pressure was higher in renal recipients (103 ± 3 vs. 94 ± 3 mm Hg in uninephrectomy controls, P < 0.05). Despite similar levels of overall glomerular function in the two groups, the dextran sieving curve was uniformly elevated in the renal allograft recipients versus uninephrectomy controls (P < 0.05 for dextrans 38 to 66 Å). Using a log-normal glomerular pore-size distribution model to analyze potential mechanisms, the elevation in the dextran sieving curve resulted from a shift in the distribution of glomerular filtering pores to a larger size (mean glomerular pore size 46 ± 2 vs. 43 ± 2 Å for uninephrectomy controls, P < 0.05), resulting in a larger fraction of filtrate volume permeating very large pores. By morphometric analysis, the thickness of the glomerular basement membrane was increased in kidney allograft as compared to 2-kidney biopsy controls (614 ± 33 vs. 427 ± 22 nm, respectively, P < 0.05). Conclusions. Even in "well functioning" renal allografts there is a glomerular dysfunction characterized by increased permeability to macromolecules resulting from a shift of the glomerular pores to a larger size. These changes could be mediated by ultrastructural alterations at the glomerular capillary or by alterations in intraglomerular hemodynamics. Early allograft dysfunction may contribute to the progressive renal insufficiency of renal allografts.

KW - Dextran sieving

KW - Glomerular morphometry

KW - Hemodynamics

KW - Permselectivity

KW - Transplantation

KW - Uninephrectomy

UR - http://www.scopus.com/inward/record.url?scp=0034783874&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034783874&partnerID=8YFLogxK

U2 - 10.1046/j.1523-1755.2001.00005.x

DO - 10.1046/j.1523-1755.2001.00005.x

M3 - Article

C2 - 11703613

AN - SCOPUS:0034783874

VL - 60

SP - 1938

EP - 1947

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 5

ER -