Brown S. A. et al. 1998
This study was conducted on 21 dogs of both sex body weight between 11 ± 0,7 kg, individually maintained. All dogs had a renal mass previously (2 months before) removed by nephrectomy of the right kidney and 7/8 infarction of the left kidney.
The dogs were divided into three groups of seven subjects each, 4 males and 3 females. Initially each dog was fed with a predetermined quantity of food based on an energy requirement of 132kcal / Kg. Subsequently, adequate quantities of food were added to maintain a stable body weight.
For two months after the reduction of the renal mass, all the dogs were fed the same maintenance food in order to allow the establishment of stable conditions of chronic renal insufficiency before this study.
The experimental diet contained 20,8% protein, 1,8% fat, 0,3% sodium, 0,8% potassium, 0,9% calcium and 0,4% phosphorus on a dry matter basis. Immediately before each meal a quantity of lipids equal to 15% of daily ration was added, therefore the final combination of the ration was 16,8% fat, 17,7% protein, 0,3% sodium, 0,7% potassium, 0,8% calcium and 0,4% phosphorus. Vitamin E, 5 IU per kilogram of body weight was also added to each ration.
The lipids were stored at -20 ° C until 12 hours before feeding and were kept at 4 ° C overnight before feeding; the two oils were stored in pre-weighed vials under nitrogen.
The lipid sources were the following:
- ω-3 PUFA (FO group), menhaden fish oil
- ω-6 PUFA (SO group), safflower oil
- saturated fatty acids (BT group), beef tallow
The fatty acid profile was as follows;
FO group
- 13,6% eicosapentaenoic acid
- 12,5% docosahexaenoic acid
- 1,2% linoleic acid
- 33,4% monounsaturated fatty acids
- 30,6% saturated fatty acids
SO group
- 77,7% linoleic acid
- 13,0% monounsaturated fatty acids
- 9,9% saturated fatty acids
BT group
- 4,3% linoleic acid
- 47,1% monounsaturated fatty acids
- 48,1% saturated fatty acids
Two months after nephrotomy, all subjects underwent blood tests to evaluate renal parameters (SCr, BUN, cholesterol, HDL-cholesterol, triglycerides, total protein, albumin, hematocrit, CCr and urine protein-to-creatinine ratio).
Thereafter checks were performed after fasting for 12-16 hour once a month. After the determinations performed at 20 months, the subjects were suppressed.
After the suppression, the remaining kidney tissue is removed from each dog.
The prevalence of glomerulosclerosis, tubular lesions, interstitial fibrosis, interstitial inflammatory and glomerular cell infiltrate and cellularity were assessed.
At the time of division into groups, there were no significant differences in the urine protein-to-creatinine ratio, CCr, SCr and BUN. During the dietary test the mean dietary intakes were not significantly different between groups. An average body weight gain of 4,0% was found during the 20-month diet study.
All three groups had a significant similar (p <0,05) increase in the urine protein-to-creatinine ratio at the start of the dietary trial compared to the mean prenephrectomy value of 0,11 ± 0,01.
Although the extent of proteinuria was similar in all three groups at the time of the start of the dietary trial it increased progressively in the SO and BT groups, and the mean overall value for these groups exceeded the corresponding value for the FO group.
During the dietary study, the average CCr was consistently higher in the FO group. Renal function progressively decreased in the SO group, and at 12 months the mean CCr for the SO group was significantly (p <0,05) lower than the CCr for either of the other groups. The final average value for CCr for the SO group (0,59 ± 0,12 ml / min / kg) recorded an average variation of -43% ± 16,9% from the initial value. The final value for the FO group (1,29 ± 0,18 ml / min / kg) was significantly higher than the SO and BT groups during the 20-month dietary test. As a result of these differences in the pattern of renal function evolution in the study, kidney disease was significantly accelerated in the SO group compared to the FO group. Two months of the study, the plasma cholesterol concentration was 236,1 ± 18,7 mg / dl in the SO group, 268,2 ± 18,5 in the BT group and 202,3 ± 23,2 in the FO group. Although this represented a trend for plasma cholesterol values (BT group> SO group> FO group), these differences were significant (p <0,05) only for the FO group compared to the BT group.
Plasma HDL-cholesterol was also significantly lower in the FO group. However, there was no change in any group in the relationship between HDL-cholesterol and total cholesterol.
There was a significant decrease in the plasma triglyceride concentration in the FO group.
In conclusion after the reduction of the renal mass, a progressive deterioration of renal function associated with proteinuria, hypercholesterolemia, morphologic evidence of glomerular and tubulointerstitial damage and a greater prevalence of end-stage renal failure in the group integrated with ω-6 PUFA has been described.
Dietary supplementation with BT was also associated with evidence of progressive decreases in renal function and structure. However, the rate of kidney function decay was slower in this group and fewer dogs achieved end-stage renal failure.
Progression to end-stage renal disease in this group was also associated with proteinuria, hypercholesterolaemia and morphologic evidence of glomerular and tubulointerstitial damage.
In contrast, dogs fed a diet supplemented with fish oil, a rich source of ω-3 PUFA, did not show progressive decreases in renal function and the final values for CCr and SCr actually reflected an increase in renal function during the 20 months test.
Furthermore, the conservation of renal function, the size of the glomerular and tubulointerstitial lesions have been drastically reduced, further demonstrating the renoprotective effect of dietary supplementation with ω-3 PUFA.