Effects of aging and dietary protein intake on uninephrectomized geriatric dogs

Delmar R. Finco From the Department of Physiology and Pharmacology (Finco, S. Brown, Barsanti) and Department of Pathology (Crowell, C Brown), College of Veterinary Medicine, The University of Georgia, Athens, GA 30602, and The Iams Co, Lewisburg, OH 45338 (Carey, Hirakawa).

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Scott Alan Brawn From the Department of Physiology and Pharmacology (Finco, S. Brown, Barsanti) and Department of Pathology (Crowell, C Brown), College of Veterinary Medicine, The University of Georgia, Athens, GA 30602, and The Iams Co, Lewisburg, OH 45338 (Carey, Hirakawa).

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Wayne A. Crowell From the Department of Physiology and Pharmacology (Finco, S. Brown, Barsanti) and Department of Pathology (Crowell, C Brown), College of Veterinary Medicine, The University of Georgia, Athens, GA 30602, and The Iams Co, Lewisburg, OH 45338 (Carey, Hirakawa).

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Cathy A. Brown From the Department of Physiology and Pharmacology (Finco, S. Brown, Barsanti) and Department of Pathology (Crowell, C Brown), College of Veterinary Medicine, The University of Georgia, Athens, GA 30602, and The Iams Co, Lewisburg, OH 45338 (Carey, Hirakawa).

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Jeanne A. Barsanti From the Department of Physiology and Pharmacology (Finco, S. Brown, Barsanti) and Department of Pathology (Crowell, C Brown), College of Veterinary Medicine, The University of Georgia, Athens, GA 30602, and The Iams Co, Lewisburg, OH 45338 (Carey, Hirakawa).

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Daniel P. Carey From the Department of Physiology and Pharmacology (Finco, S. Brown, Barsanti) and Department of Pathology (Crowell, C Brown), College of Veterinary Medicine, The University of Georgia, Athens, GA 30602, and The Iams Co, Lewisburg, OH 45338 (Carey, Hirakawa).

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Diane A. Hirakawa From the Department of Physiology and Pharmacology (Finco, S. Brown, Barsanti) and Department of Pathology (Crowell, C Brown), College of Veterinary Medicine, The University of Georgia, Athens, GA 30602, and The Iams Co, Lewisburg, OH 45338 (Carey, Hirakawa).

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Summary

Thirty-one clinically normal Cocker Spaniels, Miniature Schnauzers, and Doberman Pinschers (28 female, 3 male) 7 to 8 years old were uninephrectomized (month −2) to increase the risk of renal damage associated with reduction of renal mass. Two diets, differing principally in protein concentration, were used to test the hypothesis that high dietary protein intake causes renal damage in aging dogs.

For 2 months after uninephrectomy, all dogs were fed diet A (18% protein). After glomerular filtration rate (gfr) was measured (month 0), 16 dogs were assigned to group A and were fed diet A for an additional 48 months. The other 15 dogs were assigned to group B, and were fed diet B (34% protein) for the subsequent 48 months. At 6-month intervals, GFR and urine protein-to-creatinine ratio (UP/C) were determined. At 48 months, terminal studies were done, survivors were euthanatized, and tissues were examined.

Of 16 dogs in group A, 10 survived, compared with 13 of 15 in group B. Among survivors, a significant difference in GFR was not found between groups A and B, and decrease in GFR was not evident with time in either group. At 48 months, oral administration of casein caused minor acute effects on GFR and renal plasma flow in dogs of groups A and B.

The UP/C values increased significantly (P = 0.001) from baseline values, but the increase was not progressive. The UP/C values were not affected by diet. Some dogs in both groups developed UP/C > 1.0.

Morphologic studies performed on kidneys removed at -2 months (nephrectomy) and at 48 months (necropsy) revealed increased kidney weight in both groups at month 48, compared with month −2 (P = 0.003); at month 48, kidney weight change was significantly (P = 0.004) greater in group-B than in group-A dogs. Increased glomerular area at month 48, compared with month −2, was significantly (P = 0.000) related to time, but not to diet.

Significant (P = 0.000) increase in glomerular mesangial matrix, interstitial fibrosis (P = 0.001), cell infiltration (P = 0.000), and lesions of the renal pelvis (P = 0.04) was observed between month −2 and month 48. Time, representing combined effects of uninephrectomy and aging, was the major factor responsible for the morphologic changes. Diet effects were significance (P = 0.008) for cell infiltration, but did not reach significance for mesangial matrix accumulation, fibrosis, or pelvic lesions. Kidney mineral analysis revealed no renal mineralization in either group between −2 and 48 months.

Results indicated that GFR did not decrease with time during the geriatric peroid studied, but severity of renal lesions was increased. Effects of time and uninephrectomy, although not separable, were more important than those of dietary protein intake on progression of renal lesions.

Summary

Thirty-one clinically normal Cocker Spaniels, Miniature Schnauzers, and Doberman Pinschers (28 female, 3 male) 7 to 8 years old were uninephrectomized (month −2) to increase the risk of renal damage associated with reduction of renal mass. Two diets, differing principally in protein concentration, were used to test the hypothesis that high dietary protein intake causes renal damage in aging dogs.

For 2 months after uninephrectomy, all dogs were fed diet A (18% protein). After glomerular filtration rate (gfr) was measured (month 0), 16 dogs were assigned to group A and were fed diet A for an additional 48 months. The other 15 dogs were assigned to group B, and were fed diet B (34% protein) for the subsequent 48 months. At 6-month intervals, GFR and urine protein-to-creatinine ratio (UP/C) were determined. At 48 months, terminal studies were done, survivors were euthanatized, and tissues were examined.

Of 16 dogs in group A, 10 survived, compared with 13 of 15 in group B. Among survivors, a significant difference in GFR was not found between groups A and B, and decrease in GFR was not evident with time in either group. At 48 months, oral administration of casein caused minor acute effects on GFR and renal plasma flow in dogs of groups A and B.

The UP/C values increased significantly (P = 0.001) from baseline values, but the increase was not progressive. The UP/C values were not affected by diet. Some dogs in both groups developed UP/C > 1.0.

Morphologic studies performed on kidneys removed at -2 months (nephrectomy) and at 48 months (necropsy) revealed increased kidney weight in both groups at month 48, compared with month −2 (P = 0.003); at month 48, kidney weight change was significantly (P = 0.004) greater in group-B than in group-A dogs. Increased glomerular area at month 48, compared with month −2, was significantly (P = 0.000) related to time, but not to diet.

Significant (P = 0.000) increase in glomerular mesangial matrix, interstitial fibrosis (P = 0.001), cell infiltration (P = 0.000), and lesions of the renal pelvis (P = 0.04) was observed between month −2 and month 48. Time, representing combined effects of uninephrectomy and aging, was the major factor responsible for the morphologic changes. Diet effects were significance (P = 0.008) for cell infiltration, but did not reach significance for mesangial matrix accumulation, fibrosis, or pelvic lesions. Kidney mineral analysis revealed no renal mineralization in either group between −2 and 48 months.

Results indicated that GFR did not decrease with time during the geriatric peroid studied, but severity of renal lesions was increased. Effects of time and uninephrectomy, although not separable, were more important than those of dietary protein intake on progression of renal lesions.

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