PMID- 14736954 OWN - NLM STAT- MEDLINE DCOM- 20041005 LR - 20190513 IS - 0931-0509 (Print) IS - 0931-0509 (Linking) VI - 19 IP - 2 DP - 2004 Feb TI - Renal processing of serum proteins in an albumin-deficient environment: an in vivo study of glomerulonephritis in the Nagase analbuminaemic rat. PG - 320-8 AB - BACKGROUND: Plasma albumin has been considered as important for governing glomerular permselectivity as well as being tubulotoxic in proteinuric states. The purpose of this study was to examine glomerular permselectivity and protein clearance of plasma albumin-deficient Nagase analbuminaemic rats (NAR) in normal and proteinuric states associated with puromycin aminonucleoside nephrosis (PAN) and anti-glomerular basement membrane glomerulonephritis (anti-GBM GN) and to compare the results with those of previous studies using Sprague-Dawley rats. METHODS: Glomerular permselectivity was measured using tritium-labelled polydisperse Ficoll. In vivo fractional clearance (FC) of albumin, transferrin and immunoglobulin G was measured to include both intact and degraded forms of filtered material. Endogenous protein clearance was analysed using two-dimensional electrophoresis in combination with matrix-assisted laser desorption ionization (MALDI) mass spectrometry. RESULTS: FCs of proteins and Ficoll in control NAR were similar to those found in Sprague-Dawley rats. Despite the lack of serum albumin in NAR, proteinuria and morphological changes observed were also similar to those found in Sprague-Dawley rats, with total protein excretion increasing 6-fold in PAN rats and 4-fold in anti-GBM GN rats with respect to controls. Two-dimensional electrophoresis in combination with MALDI mass spectrometry identified the major proteins being excreted as transferrin and a group of mildly acidic proteins in the MW range 40-50 kDa, namely antithrombin III, kininogen, alpha-1-antiproteinase, haemopexin and vitamin D-binding protein. CONCLUSIONS: Both diseases exhibited similar effects to those observed in Sprague-Dawley rats despite the lack of serum albumin, including inhibition of renal protein degradation. The net changes in protein FC, particularly in the range of radii of 36-55 A, could not be accounted for by changes in size selectivity as Ficoll FC was little affected by the disease states. This emphasizes the need to reassess the relative importance of changes in renal tubular handling vs changes in glomerular capillary barrier in proteinuric states. These studies also demonstrate that albumin is not a critical factor in governing glomerular permselectivity or proteinuria. FAU - Osicka, Tanya M AU - Osicka TM AD - Endocrine Unit, Austin & Repatriation Medical Centre, Department of Medicine, University of Melbourne, Heidelberg, Victoria, Australia. FAU - Strong, Kimberley J AU - Strong KJ FAU - Nikolic-Paterson, David J AU - Nikolic-Paterson DJ FAU - Atkins, Robert C AU - Atkins RC FAU - Jerums, George AU - Jerums G FAU - Comper, Wayne D AU - Comper WD LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Nephrol Dial Transplant JT - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JID - 8706402 RN - 0 (Blood Proteins) RN - 0 (Immunoglobulin G) RN - 0 (Transferrin) RN - EC 3.2.1.52 (Acetylglucosaminidase) SB - IM MH - Acetylglucosaminidase MH - Albuminuria/*diagnosis/etiology MH - Animals MH - Blood Protein Electrophoresis MH - Blood Proteins/*metabolism MH - Chromatography MH - Disease Models, Animal MH - Female MH - Glomerular Filtration Rate MH - Glomerulonephritis/complications/*pathology/*physiopathology MH - Immunoglobulin G/analysis MH - Male MH - Probability MH - Proteinuria/*diagnosis/etiology MH - Radioimmunoassay MH - Rats MH - Rats, Sprague-Dawley MH - Sensitivity and Specificity MH - Transferrin/metabolism EDAT- 2004/01/23 05:00 MHDA- 2004/10/06 09:00 CRDT- 2004/01/23 05:00 PHST- 2004/01/23 05:00 [pubmed] PHST- 2004/10/06 09:00 [medline] PHST- 2004/01/23 05:00 [entrez] AID - 10.1093/ndt/gfg226 [doi] PST - ppublish SO - Nephrol Dial Transplant. 2004 Feb;19(2):320-8. doi: 10.1093/ndt/gfg226.