NDT Advance Access originally published online on April 21, 2004
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Nephrol Dial Transplant (2004) 19: 1724-1731
Nephrol Dial Transplant Vol. 19 No. 7 © ERA-EDTA 2004; all rights reserved
Original Article
Increased glomerular albumin permeability in old spontaneously hypertensive rats
1 Department of Nephrology and 2 Department of Medicine, Lund University Hospital, Sweden and3 Department of Physiology, University of Bergen, Bergen, Norway
Correspondence and offprint requests to: Omran Bakoush, MD, Department of Nephrology, Lund University Hospital, S-221 85 Lund, Sweden. Email: Omran.Bakoush{at}skane.se
Background. Severe long-standing hypertension is associated with an increased urinary protein excretion.
Methods. To investigate the mechanisms of this proteinuria, we measured the glomerular clearances and calculated the glomerular sieving coefficients (
) for neutral albumin (o-alb) and for native albumin (alb) in spontaneously hypertensive rats (SHR) at the ages of 3, 9 and 14 months, in comparison with age-matched normal control Wistar rats (NCR). The hypothesis was that increases in the glomerular permeability of both negatively charged and neutral albumin would indicate a preferential size-selective dysfunction of the glomerular capillary wall (GCW), while an increased permeability to negatively charged albumin, as compared with neutral albumin, predominantly would indicate a charge-selectivity dysfunction of the GCW. A tissue (renal) uptake technique together with urinary sampling was used to assess . The glomerular filtration rate was assessed using the plasma to urine clearance of 51Cr-EDTA.
Results. The alb in SHR increased 2.6 times at 14 months of age as compared with at 3 months, while there was no significant change of alb in NCR with age. Furthermore, the increased alb in old SHR correlated significantly with an increase in o-alb (r = 0.86, P<0.001), suggesting that albuminuria in old SHR primarily results from an increased number of rather unselective (‘large’) pores in the glomerular filter.
Conclusions. In old age, but not at a young age, hypertensive rats develop proteinuria as a result of dysfunction of the glomerular capillary filter, affecting primarily its size-selectivity. The changes are functionally compatible with the appearance in the glomerular barrier of an increased number of more unselective pores.
Keywords: albuminuria; charge-selectivity; glomerular capillary wall; hypertension; macromolecular transport
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