Wayne A. Crowell

Beneficial effects of chronic administration of dietary ω-3 polyunsaturated fatty acids in dogs with renal insufficiency

Dietary supplementation with polyunsaturated fatty acids (PUFA) alters the course of experimental renal disease in rats. However, chronic renal disease in other laboratory animals and in human beings frequently responds differently to experimental manipulations. We investigated the effects of variations in dietary PUFA composition on the chronic course of induced renal disease in dogs. Two months after 15/16 nephrectomy, dogs were randomly divided into three groups of seven animals each. For the next 20 months, each group of dogs was fed a low-fat basal diet supplemented with one of three sources of lipid to achieve a final concentration of 15% added fat. Fat sources provided omega-3 PUFA (menhaden fish oil, group FO), omega-6 PUFA (safflower oil, group SO), or saturated fatty acids (beef tallow, group BT). Throughout the dietary trial, the magnitude of proteinuria and the plasma concentrations of creatinine, cholesterol, and triglyceride were lower in group FO. The mean overall glomerular filtration rate was 0.89+/-0.18 ml/min per kilogram of body weight in group SO, a value that was significantly less (p < 0.05) than the corresponding values for groups BT and FO (1.21+/-0.18 and 1.43+/-0.20 ml/min/kg, respectively). Renal interstitial fibrosis also was significantly elevated in group SO. The extents of mesangial matrix expansion, glomerulosclerosis, and renal interstitial cellular infiltrate were similar in groups BT and SO, but lower (p < 0.05) in group FO. We conclude that supplementation with omega-6 PUFA enhanced renal injury; supplementation with omega-3 PUFA was renoprotective.

Pathophysiology and management of progressive renaldisease

Recently, the hypothesis that all renal diseases are inherently progressive and self-perpetuating has focused attention on adaptive changes in renal structure and function that occur whenever renal function is reduced. These glomerular adaptations to renal disease include increases in filtration rate, capillary pressure and size, and are referred to as glomerular hyperfiltration, glomerular hypertension and glomerular hypertrophy, respectively. Extrarenal changes, such as dietary phosphate excess, systemic hypertension, hyperlipidaemia, acidosis and hyperparathyroidism occur in animals with renal disease and may be contributors to progression of renal disease. Emphasis in the management of companion animals with renal disease has shifted to identifying, understanding and controlling those processes that play a role in the progression from early to end-stage renal failure. Advances made by veterinary nephrologists in the past 15 years permit resolution of old controversies, formulation of new hypotheses and discussion of unresolved issues about the nature of progressive renal disease in dogs and cats.

Does modifying dietary lipids influence the progression of renal failure

Recent studies have identified important effects of dietary fatty acid composition in animals with chronic renal disease, particularly in dogs. The theoretic basis for these effects provides a rationale for the use of diets enriched with omega-3 (but not omega-6) polyunsaturated fatty acids. A therapeutic trial with a diet enriched with omega-3 polyunsaturated fatty acids should be considered as a maneuver designed to slow the rate of progression of chronic renal disease in dogs.

Lesions in dogs following renal transplantation and immunosuppression.

Renal allografts were transplanted into 20 dogs (12 beagles, eight mongrels) following a prescribed protocol for pre-transplantation blood transfusions and kidney exchange. Immunosuppressive therapy (azathioprine and prednisone) was modified as needed for each dog. Seven of the beagle dogs survived for 1 year and were then euthanized; all other dogs died or were euthanized prior to 1 year post-transplantation. Graft rejection and renal failure were the greatest causes of mortality. Renal lesions which contributed to the death of some animals included renal vein thrombosis, nephrosis, and pyelonephritis. Inflammation of the lower respiratory tract (bronchitis, pneumonia, and pleuritis) was a contributory cause of death in some dogs. Cystitis and ureteritis occurred in almost half of the dogs. Prostatitis was seen in six of the 16 male dogs. Adrenal cortical atrophy, parathyroid gland hyperplasia, and bone marrow hypocellularity were seen in a majority of the dogs which survived 1 year.

Induction of chronic bacterial prostatitis in the dog.

Three methods of creating chronic bacterial prostatitis in dogs were evaluated. Injection of Escherichia coli into the prostatic or caudal vesicle artery after the prostate was pierced with a 22-gauge needle caused prostatic infection in 4 of 5 dogs. The infection persisted up to 28 days. Direct injection of E. coli into the prostate gland resulted in infection in 5 of 6 dogs which persisted up to 42 days. Injection of E. coli into the prostatic urethra after occlusion of the bladder neck caused infection in 2 of 8 dogs not subjected to piercing of the prostate gland and in 5 of 7 dogs subjected to prostate gland trauma. Infection persisted up to 28 days. Although all 3 methods resulted in persistent, chronic bacterial prostatitis, direct injection of bacteria into the prostate gland was technically the easiest to perform and resulted in the lowest incidence of concomitant infections of the rest of the urinary tract. Positive urine cultures for E. coli were found in all dogs at some time after infection. Positive urine and bladder tissue cultures were also found at necropsy in some dogs.

Early Renal Disease in BHE/cdb Rats Is Less in Rats Fed Beef Tallow Than in Rats Fed Menhaden Oil

Abstract The effects of feeding a 1% corn oil-9% menhaden oil or beef tallow diet on the early phase of diabetic nephropathy in BHE/cdb rats was studied. The diet groups were subdivided into rats with or without impaired glucose tolerance. Those fed menhaden oil had renal hypertrophy, mild albuminuria, decreased creatinine clearance, increased urea clearance, and more severe lesion scores than rats fed beef tallow. No differences in glomerular filtration rate, Na+,K+-ATPase activity, sorbitol dehydrogenase, or inositol 1,4,5-phosphate were observed. Beef tallow-fed rats had higher serum triglyceride levels and renal cholesterol levels. Renal and hepatic fatty acid profiles reflected the fatty acid profile of the dietary fat. These results suggest that beef tallow conferred a protective effect on the renal tissues of these diabetes-prone rats.