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Nephrol Dial Transplant (1999) 14: 1898-1903
© 1999 European Renal Association-European Dialysis and Transplant Association

In vivo microvascular clearance of albumin in renal and extrarenal tissues in puromycin aminonucleoside (PAN) induced nephrotic syndrome

Björn W. Öqvist, Anna Rippe, Jan Tencer and Bengt Rippe

Department of Nephrology, University Hospital of Lund, Sweden

Correspondence and offprint requests to: Björn Öqvist, Department of Nephrology, University Hospital of Lund, S-221 85 Lund, Sweden.

Background. The nephrotic syndrome is characterized by generalized oedema considered to be due to the fall in serum albumin and to sodium retention. The aim of the present study was to investigate whether a generalized disturbance in vascular integrity contributes to the oedema formation.

Methods. We used the PAN-(puromycin aminonucleoside) nephritis model in order to induce the nephrotic syndrome in female Wistar rats. Eight rats were given PAN, 15 mg/100 g body weight, intraperitoneally 10 days prior to the study, whereas 21 rats served as controls. Albumin clearance to tissues was measured using a dual isotope technique. Repeated blood samples as well as samples from various muscles, kidney, liver, lung, heart, abdominal wall and from ascites fluid were taken to determine radioactivity and tissue dry-to-wet weights. Clearance of albumin (Clalb) from plasma to interstitium was calculated from the (linear) increment in `plasma equivalent tissue albumin space' as a function of time, corrected for intravascular volume and oedema. The plasma and urine concentrations of albumin were determined in a parallel study by single radial diffusion using monospecific rabbit anti-rat antiserum in seven PAN animals and 13 controls.

Results. A marked fall in dry-to-wet weight ratios together with pronounced proteinuria, oedema and ascites were found in the PAN animals. Haematocrit decreased from 45% (32–51) to 30% (28–38) and serum albumin from 22.0 g/l (16.3–25.2) to 4.94 g/l (3.20–6.72) in control and PAN animals, respectively. However, Clalb apparently remained unchanged in the PAN animals in comparison to controls in most tissues examined. Thus, in these in vivo experiments there was no direct evidence of an increased extravasation of albumin in extrarenal tissues.

Conclusions. There was no strong support for the contention that a generalized disturbance of capillary integrity outside the renal vasculature would contribute to the oedema formation in the PAN nephrotic syndrome.


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