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TRANSLATIONAL PHYSIOLOGY

Loss of size selectivity of the glomerular filtration barrier in rats following laparotomy and muscle trauma

Department of Nephrology, University Hospital of Lund, Lund, Sweden

Submitted 5 May 2009 ; accepted in final form 1 July 2009

Posttraumatic microalbuminuria may be caused by either charge- or size-selective alterations in the glomerular filtration barrier, or both, and/or to a reduction in proximal tubular protein reabsorption. This study was performed to elucidate the pathophysiology of the increases in glomerular permeability occurring in rats exposed to a laparotomy or to a laparotomy and muscle trauma. In anesthetized Wistar rats (250–280 g), the left ureter was cannulated for urine collection, while simultaneously blood access was achieved. Rats were exposed to trauma by a laparotomy (L; n = 8), or by a combination of L and muscle trauma (MT; L+MT) induced by topical blunt injury of the abdominal muscles bilaterally. After L, muscles were crushed using hemostatic forceps at either 2 x 2 sites ("small" MT; n = 9), or at 2 x 5 sites ("large" MT; n = 9). Sham groups (n = 16), not exposed to a laparotomy, were used as controls. The glomerular sieving coefficients () to polydisperse FITC-Ficoll-70/400 (molecular radius 13–80 Å) were determined at 5 or 60 min after L and L+MT, respectively, from plasma and urine samples, and analyzed by high-performance size-exclusion chromatography. A tissue-uptake technique was used to assess for ¹²⁵I-labeled serum albumin. L, with or without MT, increased for Ficoll_55–80Å and albumin rapidly and markedly. -Ficoll_70Å thus increased approximately threefold, and for albumin significantly, for all trauma groups. According to the "two-pore model" of glomerular permeability, these changes mainly reflect an increase in the number of large pores in the glomerular filter without any primary changes in the charge-selective properties of the filter.

microalbuminuria; glomerular sieving coefficients; albumin; Ficoll; capillary permeability