Treatment of X-linked hereditary nephritis in Samoyed dogs with angiotensin converting enzyme (ACE) inhibitor.
X-linked hereditary nephritis (HN) in Samoyed dogs is a model for human HN (Alport's syndrome). Angiotensin converting enzyme (ACE) inhibitors have been shown to slow the progression of renal disease in animal models and human patients. To determine the effect of ACE inhibitor treatment on X-linked HN in Samoyed dogs, a group of affected and a group of normal males were each randomly divided into two subgroups, which were either treated with an ACE inhibitor or left untreated. ACE inhibitor treatment caused significant increases (P < 0.05) in plasma renin activity in normal and affected dogs, confirming its effectiveness, but did not lower systemic blood pressure. Three of four affected treated dogs had improved weight gains and, overall, treated dogs survived 1.36 times longer than affected untreated dogs (P < 0.05). ACE inhibitor treatment of affected dogs significantly delayed (P < 0.05) the onset of an increase in serum creatinine concentration, tended to delay the decline of glomerular filtration rate and effective renal plasma flow (ERPF), significantly improved (P < 0.05) the ERPF at 110-154 days of age, and significantly slowed (P < 0.01) the rate of increase of proteinuria. Affected treated dogs showed a significant (P < 0.05) transient reduction in glomerular basement membrane splitting. Thus, ACE inhibitor treatment of Samoyed dogs with X-linked HN produced beneficial effects with respect to renal function, renal structure, and survival.
Grodecki
K M
KM
Department of Pathobiology, University of Guelph, Ontario, Canada.
Gains
M J
MJ
Baumal
R
R
Osmond
D H
DH
Cotter
B
B
Valli
V E
VE
Jacobs
R M
RM
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001485:Basement Membrane / Q000648:ultrastructure; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004285:Dogs; D004656:Enalapril / Q000627:therapeutic use*; D008040:Genetic Linkage / Q000235:genetics*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007677:Kidney Function Tests; D007678:Kidney Glomerulus / Q000648:ultrastructure; D008297:Male; D009394:Nephritis, Hereditary / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood; D014960:X Chromosome / Q000235:genetics*
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D003404:Creatinine; D012083:Renin