The miniature pig possesses unmatched advantages as an animal model because of its high homology with humans. Our experiment aimed to build a chronic renal failure (CRF) model in pigs via laparoscopy.

Exogenous creatinine clearance rate was determined in 8 partially (approx 75%) nephrectomized dogs fed 2 concentrations of dietary sodium, beginning 9 weeks after partial nephrectomy was performed. In a double crossover design, dogs were then fed low-sodium diet (0.18% sodium on a dry-weight basis) or high-sodium diet (1.3% sodium on a dry-weight basis) in 2 sequences (L/H/L or H/L/H) for 3 consecutive 4-week observation periods. Glomerular filtration rate (GFR) was measured by exogenous creatinine clearance before and after partial nephrectomy, and every 2 weeks during the experimental diet periods. Initial mean +/- SD GFR (3.76 +/- 0.78 ml/min/kg of body weight) decreased precipitously after nephrectomy (1.25 +/- 0.45 ml/min/kg); however, during the postnephrectomy and experimental diet periods, GFR gradually increased in all dogs to nearly half the prenephrectomy values (1.87 +/- 0.22 ml/min/kg). Significant differences in GFR were not observed when dogs were fed the IM or the H/L/H sequence. Therefore, it was concluded that abrupt change from high dietary sodium (1.3%) to restricted dietary sodium (0.18%), or vice versa, does not cause deterioration of renal function in dogs with moderate renal impairment. However, caution should be used in extrapolating these findings to dogs with clinically evident (azotemia, isosthenuria) renal failure.

Renal mass was surgically reduced in 78 dogs by uninephrectomy or by combined renal infarction and uninephrectomy. Renal clearance of inulin and renal clearance of exogenous creatinine were determined simultaneously, and the creatinine to inulin clearance (C/I) ratio was calculated. Clearance procedures were performed 2 to 3 months after reduction of renal mass, and were repeated at intervals thereafter. Overall, the C/I ratio was 1.008 +/- 0.007 for 192 determinations, with a highly significant correlation (R2 = 0.994, P < 0.0001) between creatinine clearance and inulin clearance. There was no significant effect of gender of dogs, time after partial renal ablation, or dietary protein intake on C/I ratios. Degree of renal ablation did not affect C/I ratios. The results indicated that exogenous creatinine clearance is a valid measure of glomerular filtration rate in both male and female dogs with reduced renal mass.

Excretion of creatinine, sodium sulfanilate (SS), and phenolsulfonphthalein (PSP) was studied in healthy goats. In conscious goats, mean (+/- SEM) inulin clearance was 2.26 +/- 0.08 ml/min/kg of body weight. Endogenous creatinine clearance, 1.97 +/- 0.09 ml/min/kg, underestimated inulin clearance (P < 0.01), probably because of the presence of noncreatinine chromogens in caprine plasma. The estimated renal clearance of PSP was 6.88 +/- 0.39 ml/min/kg, whereas the estimated renal clearance of SS was 3.71 +/- 0.39 ml/min/kg. Both exceeded inulin clearance (P < 0.01), confirming renal tubular secretion of both compounds. In 6 anesthetized goats, exogenous creatinine clearance and SS clearance exceeded inulin clearance (P < 0.05). Results of stop-flow experiments documented secretion of creatinine and ss by the peoximal portion of the caprine nephron. Plasma half-life of PSP in uninephrectomized goats exceeded that in intact goats (20.2 +/- 1.5 min vs 11.9 +/- 0.7 min; P < 0.01). Similarly, plasma half-life of SS was greater in goats after uninephrectomy (58.2 +/- 6.2 min vs 30.4 1.2 min; p < 0.01).

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 period 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.

To determine the effects of long-term dietary protein restriction in cats with chronic renal failure (CRF), 4 healthy adult cats and 7 cats with surgically induced CRF were fed a high-protein (HP, 51.7% protein) diet and 4 healthy adult cats and 7 cats with surgically induced CRF were fed a low-protein (LP, 27.6% protein) diet for 1 year. Cats with induced CRF that were fed the LP diet had reduced serum urea nitrogen concentrations, despite lower glomerular filtration rates, compared with cats with CRF fed the HP diet. Despite five-sixths reduction in renal mass, reduced glomerular filtration rate, and azotemia, 13 of the 14 cats with induced CRF retained the ability to concentrate urine and produced urine with a specific gravity > 1.035. Cats fed the HP diet consumed significantly more calories than did cats fed the Lp diet, presumably because the HP diet was more palatable. As a result of the lower caloric intake in cats fed the LP diet, these cats were protein and calorie restricted, compared with cats fed the HP diet. Cats fed the HP diet weighed significantly more than did cats fed the LP diet. Mean hematocrit and mean serum albumin concentration ere significantly lower in control cats and in cats with CRF fed the LP diet, compared with control cats and cats with CRF fed the HP diet. Hypokalemia developed in 4 of 7 cats with CRF fed the HP diet (containing 0.3% potassium); hypokalemia did not develop in control cats fed the same diet or in cats with CRF fed the LP diet containing 0.4% potassium. Excessive kaliuresis, hypomagnesemia, and metabolic acidosis did not appear to contribute to the hypokalemia. Subsequent supplementation of the HP diet with potassium gluconate prevented hypokalemia in cats with CRF.

Effects of a protein meal (2.7 g of casein/kg of body weight) on glomerular filtration rate (GFR) and renal plasma flow (RPF) were assessed in dogs after 15/16 nephrectomy (n = 10), and were compared with observations in dogs with intact kidneys (n = 5). Increase in GFR and RPF was observed in both groups of dogs between 1.5 and 8 hours after protein ingestion. A maximal value for GFR was observed between 4 and 5 hours after protein ingestion in dogs of both groups. Enhancement of urinary protein excretion was evident in partially nephrectomized dogs after protein ingestion (P < 0.05), a result that was confirmed by 24-hour total urine collection from partially nephrectomized dogs fed a balanced ration. A qualitatively similar vasodilatory response was observed in partially nephrectomized dogs and in dogs with intact kidneys, and the mean maximal increase of GFR and RPF expressed as a percentage of baseline values in the latter dogs (47.0 +/- 8.1 and 43.6 +/- 10.3%, respectively) exceeded that observed in partially nephrectomized dogs (20.8 +/- 2.2 and 22.7 +/- 6.3%, respectively; P < 0.01). The incremental response of the kidneys to protein ingestion was directly related to the degree of renal function, as reflected in the linear regression relationship between the incremental increase in GFR and the baseline value for GFR (P < 0.01, R2 = 0.721).