Early glomerular dysfunction in human renal allografts

C. F. Zayas, A. Guasch

Research output: Contribution to journalArticle

10 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Nephrology

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