Glomerular size-selective barrier dysfunction in nephrotoxic serum nephritis

P. A. Alfino, Joel Neugarten, R. G. Schacht, L. D. Dworkin, D. S. Baldwin

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

We have previously reported amelioration of heavy proteinuria, vascular sclerosis and glomerular structural damage by antihypertensive therapy in nephrotoxic serum nephritis (NSN). In the present study, we examine glomerular permselectivity in this hypertensive form of NSN and the effect of hypertension treatment on size-selective barrier function. Mean arterial pressure was maintained at normotensive levels (mean 123 ± 3 mm Hg) with a combination of hydralazine, hydrochlorthiazide and reserpine in 7 nephritic rats, while 10 untreated rats remained hypertensive (mean 165 ± 4 mm Hg). At six weeks, glomerular filtration rate was reduced in untreated rats (mean 0.54 ml/min) but was preserved in those rendered normotensive (mean 1.71 ml/min, P < 0.02). Twenty-four-hour urinary protein excretion, mean 371 ± 74 mg in hypertensive nephritic rats, was markedly reduced in rats on the antihypertensive regimen to a mean of 120 ± 17 mg (P < 0.02), as was 24-hour urinary gamma-globulin excretion (mean 35 ± 9 mg in untreated vs. 16 ± 2 mg in treated). Fractional clearances of tritiated polydisperse neutral dextrans were significantly enhanced for molecular radii exceeding 50 angstroms in hypertensive animals, indicative of a loss of glomerular size permselectivity. Rats on antihypertensive therapy did not develop such a size selective defect. Thus, hypertensive rats with nephrotoxic serum nephritis develop 'gaps' in the glomerular basement membrane which allow the excretion of large molecular weight neutral dextrans and gamma-globulin. This defect in glomerular permselectivity can be averted with antihypertensive therapy.

Original languageEnglish (US)
Pages (from-to)151-155
Number of pages5
JournalKidney International
Volume34
Issue number2
StatePublished - 1988
Externally publishedYes

Fingerprint

Nephritis
Antihypertensive Agents
Serum
gamma-Globulins
Dextrans
Kidney
Hydralazine
Glomerular Basement Membrane
Arteriosclerosis
Reserpine
Glomerular Filtration Rate
Proteinuria
Arterial Pressure
Therapeutics
Molecular Weight
Hypertension
Proteins

ASJC Scopus subject areas

  • Nephrology

Cite this

Alfino, P. A., Neugarten, J., Schacht, R. G., Dworkin, L. D., & Baldwin, D. S. (1988). Glomerular size-selective barrier dysfunction in nephrotoxic serum nephritis. Kidney International, 34(2), 151-155.

Glomerular size-selective barrier dysfunction in nephrotoxic serum nephritis. / Alfino, P. A.; Neugarten, Joel; Schacht, R. G.; Dworkin, L. D.; Baldwin, D. S.

In: Kidney International, Vol. 34, No. 2, 1988, p. 151-155.

Research output: Contribution to journalArticle

Alfino, PA, Neugarten, J, Schacht, RG, Dworkin, LD & Baldwin, DS 1988, 'Glomerular size-selective barrier dysfunction in nephrotoxic serum nephritis', Kidney International, vol. 34, no. 2, pp. 151-155.
Alfino, P. A. ; Neugarten, Joel ; Schacht, R. G. ; Dworkin, L. D. ; Baldwin, D. S. / Glomerular size-selective barrier dysfunction in nephrotoxic serum nephritis. In: Kidney International. 1988 ; Vol. 34, No. 2. pp. 151-155.
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