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(Hypertension. 2002;39:281.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Albuminuria in Hypertension Is Linked to Altered Lysosomal Activity and TGF-ß1 Expression

Leileata M. Russo; Tanya M. Osicka; Fabrice Bonnet; George Jerums; Wayne D. Comper

Department of Biochemistry and Molecular Biology, Monash University (L.M.R., W.D.C.), Clayton, Victoria, Australia; and Endocrine Unit and Department of Medicine, Austin and Repatriation Medical Centre, University of Melbourne (T.M.O., F.B., G.J.), Heidelberg, Victoria, Australia.

Correspondence to Wayne D. Comper, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia 3800. E-mail wayne.comper{at}med.monash.edu.au

Increased intraglomerular pressure is considered a major factor for increased albumin excretion in hypertension. However, other factors should also be considered because recent studies in both humans and rats have demonstrated that proteins undergoing filtration and renal passage are extensively modified by renal cell lysosomal processing; >95% of albumin is degraded to peptides that are not detected by routine immunochemical assays. Changes in postglomerular lysosomal processing may therefore be responsible for the increased intact albumin excreted in hypertension-related kidney disease. We hypothesize that transforming growth factor-ß, which is known to decrease lysosomal activity, may be upregulated in hypertension and may play a role in increased intact albumin excretion. The aims of this study were to determine the effect that hypertension has on (1) renal cell lysosomal processing of albumin and dextran sulfate, (2) glomerular permeability, and (3) renal transforming growth factor-ß₁ expression. Spontaneously hypertensive rats and Wistar-Kyoto rats were used at 8, 16, and 24 weeks. We demonstrate that albuminuria in hypertension is linked to an inhibition of lysosomal processing as determined by (1) size exclusion chromatography analysis of urinary [¹⁴C]albumin structural integrity and (2) ion exchange analysis of urinary [³H]dextran sulfate. This inhibition gives rise to an increased proportion of radioimmunoassay detectable (intact) albumin and intact dextran sulfate independent of changes in glomerular capillary wall permeability as determined by the fractional clearance of [³H]Ficolls of various radii. These changes may be correlated with increased renal transforming growth factor-ß₁ expression.

Key Words: albuminuria • lysosomal processing • glomerular permeability • dextran sulfate • transforming growth factors

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