Effect of indomethacin on glomerular permselectivity and hemodynamics in nephrotoxic serum nephritis

Neugarten, Joel; Kozin, Arthur; Cook, Karen
July 1989
Kidney International;Jul1989, Vol. 36 Issue 1, p51
Academic Journal
The present study was undertaken to determine the effects of prostaglandin synthesis inhibition on glomerular hemodynamics in nephrotoxic serum nephritis and to elucidate the mechanisms by which prostaglandin synthesis inhibition reduces proteinuria in nephritic rats. Dextran sieving studies were performed before and after intravenous administration of indomethacin to control rats and to nephritic rats with heavy proteinuria. Indomethacin did not significantly alter mean arterial pressure, glomerular filtration rote or proteinuria in control rats nor were significant changes in dextran sieving observed. By contrast, in nephritic rats indomethacin significantly reduced glomerular filtration rate (2.58 ± 0.50 vs. 1.39 ± 0.27 ml/min, P < 0.001), proteinuria (0.198 ± 0.079 vs. 0.048 ± 0.019 mg/min, P < 0.05) and filtration rate-corrected proteinuria (0.059 ± 0.033 vs. 0.031 ± 0.013 mg/ml GFR, P < 0.05). The fractional clearance of neutral dextrans with molecular radii exceeding 42 Å were elevated above control values in nephritic rats (P < 0.05). After administration of indomethacin, the fractional clearance of neutral dextrans uniformly declined toward control values and remained elevated only for molecular radii exceeding 54 Å. Assessment of glomerular hemodynamics in nephritic rats before and after indomethacin showed significant declines in single nephron filtration rate (31.5 ± 3.0 vs. 21.2 ± 2.5 nl/min, P < 0.02), glomerular plasma flow rate (99.5 ± 6.7 vs. 68.5 ± 7.8 nl/min, P < 0.05) and glomerular ultrafiltration coefficient (0.0430 ± 0.0033 vs. 0.0339 ± 0.0032 nl · sec-1, mm Hg-1 P < 0.05). Indomethacin did not significantly change these parameters in control rats. Utilizing a heteroporous mathematical model of the glomerular basement membrane, we calculated that the proportion of glomerular filtrate permeating the shunt pathway was elevated above control values in nephritis (0.33% vs. 0.17%), but declined to a value or 0.21% after administration of indomethacin. These data suggest that in nephrotoxic serum nephritis prostaglandin inhibition reduces proteinuria by reducing filtration rate and by improving glomerular size-selectivity via decreased utilization of the shunt pathway.


Related Articles

  • 392. Fish oil does not improve glomerular permselectivity of tubulointerstitial inflammation. Branten, A.J.W.; Klasen, I.S.; Wetzels, J.F.M. // Kidney;May/Jun2003, Vol. 12 Issue 3, p144 

    Objective: To test the hyhpothesis that fish oil supplementation would improve glomerular permselectivity or attenuate tubulointerstitial inflammation. Methodology: Excretion of both low- and high-molecularweight proteins and excretion of the chemokines monocyte chemoattractant protein-1 (MCP-1)...

  • Effects of angiotensin II receptor blockade on remnant glomerular permselectivity. Mayer, Gert; Lafayette, Richard A.; Oliver, James; Deen, William M.; Myers, Bryan D.; Meyer, Timothy W. // Kidney International;Feb1993, Vol. 43 Issue 2, p346 

    This study examined the mechanisms by which angio- tensin II (Ang II) receptor blockade improves glomerular barrier function in rats with reduced nephron number. Proteinuria was measured at four weeks after 5/6 renal ablation, and rats were then divided into a group which received the Ang II...

  • Proteinuria. Barratt, Martin // British Medical Journal (Clinical Research Edition);11/19/1983, Vol. 287 Issue 6404, p1489 

    Examines the presence of proteinuria in renal diseases. Distinction between normal and pathological proteinuria; Measurement of the index of glomerular permeability; Difference of proteinuria in renal tubular disease and glomerular disease.

  • Effect of indomethacin on glomerular permeability in the nephrotic syndrome. Tiggeler, Roland G. W. L.; Hulme, Barry; Wijdeveld, Paul G. A. B. // Kidney International;Sep1978, Vol. 16 Issue 3, p312 

    Examines the effect of nonsteroid anti-inflammatory drug indomethacin on glomerular permeability in the nephrotic syndrome. Possibility that the drug limits the pathologic process in the glomeruli; Mechanism of its effects on proteinuria; Role of indomethacin as mediators of intrarenal and...

  • Reversing glomerular hypertension stabilizes established glomerular injury. Meyer, Timothy W.; Anderson, Sharon; Rennke, Helmut G.; Brenner, Barry M. // Kidney International;Mar1987, Vol. 31 Issue 3, p752 

    Munich-Wistar rats were studied 18 weeks following 5⁄6 renal ablation. In untreated group 1 rats maintained on standard chow containing 24% protein, sustained systemic and glomerular hypertension were associated with increasing proteinuria and widespread glomerular injury. In group 2,...

  • Systemic and glomerular hypertension in progressive renal disease. Anderson, Sharon // Kidney International Supplement;Sep1988, Issue 25, p119 

    Reports on the systemic and glomerular hypertension in progressive renal disease. Insights provided into the complex and variable relationship between systemic and glomerular hypertension; Explanation of the variable renal responses to systemic hypertension and to antihypertensive therapy;...

  • Influence of converting enzyme inhibition on glomerular filtration rate and proteinuria. Rodicio, Josi L.; Alacazar, José M.; Ruilope, Luis M. // Kidney International;Oct1990, Vol. 38 Issue 4, p590 

    The article focuses on the influence of converting enzyme inhibition on glomerular filtration rate and proteinuria. The progression of chronic renal failure is facilitated by the presence of arterial hypertension. Proteinuria is a factor that indicates a poor prognosis for the progression of...

  • Elevated urinary excretion of the C5b-9 complex in membranous nephropathy. Schulze, Matthias; Donadio Jr., James V.; Pruchno, Charles J.; Baker, Patricia J.; Johnson, Richard J.; Stahl, Role A. K.; Watkins, Sandra; Martin, Donald C.; Wurzner, Reinhard; Gotze, Otto; Couser, William G. // Kidney International;Sep1991, Vol. 40 Issue 3, p533 

    ln experimental membranous nephropathy, antibody binding to glomerular epithelial cell membrane antigens results in complement activation and formation of complement C5b-9 membrane attack complexes in glomeruli. During active disease, the C5b-9 complexes are shed into hie urine. To test the...

  • Dysfunctions of cell biological mechanisms of visceral epithelial cell (podocytes) in glomerular diseases. Kerjaschki, Dontscho // Kidney International;Feb1994, Vol. 45 Issue 2, p300 

    Outlines a few examples of how some basic cell biological functions of podocytes can turn into focal points of glomerular disease. Podocyte shape-surface charge-proteinuria triangle; Cell membrane domains of podocytes; Adhesive properties of the basal cell membrane domain of podocytes; Slit...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics