Dietary modification reduces splitting of glomerular basement membranes and delays death due to renal failure in canine X-linked hereditary nephritis.
Affected male (AM) Samoyed dogs with X-linked hereditary nephritis (HN) demonstrate splitting of all of their glomerular basement membranes (GBM) and rapidly develop renal failure within the first year of life, features reminiscent of those seen in male patients with X-linked HN. In contrast, carrier female (CF) dogs with X-linked HN show only isolated foci of splitting of GBM, and renal failure is never seen at such an early age. In the present study, we assessed whether a diet designed for dogs in renal failure could modify the changes seen in GBM of AM and CF dogs and improve the clinical outcome in the AM dogs. Beginning at 35 days of age, one group of dogs (unaffected, AM, and CF) was fed a regular diet, while a second group was fed a modified diet (i.e., restricted in protein, lipid, calcium, and phosphorus). AM dogs fed the modified diet showed less of a reduction in glomerular filtration rate than AM dogs fed the regular diet, indicative of a delay in the onset and a decrease in the severity of renal damage. Nevertheless, all of the AM dogs eventually died of renal failure regardless of diet. However, the onset and progression of renal failure were delayed and the severity of splitting of GBM was reduced in the AM dogs fed the modified diet; these dogs lived 53% longer than AM dogs fed the regular diet. CF dogs fed the modified diet also showed a reduced severity of splitting of GBM. In addition, when two CF dogs on the modified diet were switched to the regular diet, splitting of their GBM increased, indicating that continual administration of the modified diet was required to maintain the reduced rate of splitting. These studies indicate that dietary modification is beneficial in canine X-linked HN, and suggest that similar benefits (i.e., reduction in severity of splitting of GBM and delay in development of renal failure) might be observed in patients with HN who are treated with an appropriately modified diet.
Valli
V E
VE
Department of Pathology, Hospital for Sick Children, Guelph, Ontario.
Baumal
R
R
Thorner
P
P
Jacobs
R
R
Marrano
P
P
Davies
C
C
Qizilbash
B
B
Clarke
H
H
D000818:Animals; D001485:Basement Membrane / Q000473:pathology; D003404:Creatinine / Q000097:blood; D004044:Dietary Proteins / Q000009:adverse effects; D004283:Dog Diseases / Q000178:diet therapy*; D004285:Dogs; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000473:pathology / Q000662:veterinary*; D007678:Kidney Glomerulus / Q000473:pathology; D008136:Longevity; D008854:Microscopy, Electron; D009393:Nephritis / Q000235:genetics / Q000473:pathology / Q000662:veterinary*; D014960:X Chromosome
D004044:Dietary Proteins; D003404:Creatinine