Clinically normal dogs were evaluated in states of dehydration, euhydration, and after fluid administration to determine effects of hydration state on renal clearance values. Endogenous creatinine, exogenous creatinine, and [(14)C]inulin clearances, were determined to measure glomerular filtration rate (GFR); in some experiments p-aminohippurate clearance was determined to measure renal plasma flow. Dehydration caused significant (P < 0.05) decrease in clearance values, compared with euhydration, and clearance values during euhydration were significantly (P < 0.05) less than values obtained after a single gavage with water (30 ml/kg of body weight). Sustained administration of 3 fluid regimens was evaluated for effects on clearance values (treatment A = 30 ml of lactated Ringer's solution/kg/h; treatment B = 30 ml of water/kg by gavage hourly; treatment C = 10 ml of glucose:lactated Ringer's solution/ kg/h). All regimens of fluid therapy caused significant P < 0.05), progressive increases in GFR, but treatment C resulted in the most stable GFR values. Increases in clearance values were associated with positive fluid balance; the rate of fluid administration was greater than the rate of urine formation. Data from 285 GFR determinations on 85 dogs were evaluated retrospectively. For each determination, three 20-minute urine collections were made beginning 40 minutes after 30 mi of water/kg was given by gavage. Values between collections were significantly (P < 0.05) different, but varied by < 3%. Comparison of methods for measurement of GFR indicated that endogenous creatinine clearance and [14)C]inulin clearance were highly correlated (R(2) = 0.82), but mean clearance values were markedly different (mean +/- SEM, 28.70 +/- 0.01 and 37.07 +/- 1.29 ml/min, respectively). Exogenous creatinine clearance and [(14)C]inulin clearance were highly correlated (R(2) = 0.95), and mean values were 40.54 +/- 0.70 and 41.02 +/- 0.70 ml/min respectively. We conclude that: state of hydration has a marked effect on GFR; rate of fluid administration that exceeds rate of urine production results in progressive increases in GFR; a single water gavage of 30 ml/kg gives stable GFR values for three 20-minute collection periods, may avoid subclinical states of dehydration, and facilitates accurate urine collections; and endogenous creatinine clearance, as conducted in this study, does not accurately measure GFR.

Nine adult female sheep were each surgically fitted with an Ivan and Johnston reentrant cannula in the cranial part of the duodenum just distal to the pylorus. By diversion (loss) of abomasal outflow, this model has been shown to consistently induce hypochloremic, hypokalemic metabolic alkalosis, accompanied by hyponatremia and dehydration. Each sheep was subjected to 3 treatment trials, each preceded by a 24-hour prediversion period, and a diversion period during which a syndrome of hypochloremia (68 +/- 2 mEq/L), hypokalemia, hyponatremia, and metabolic alkalosis was induced. Development of this syndrome was attributable to losses of large amounts of acid and electrolytes in the abomasal effluent. Mean total electrolyte contents of the effluent were: Cl-, 650 +/- 27 mEq; Na+, 388 +/- 23 mEq; and K+, 123 +/- 12 mEq, with total volume loss ranging from 3.6 to 10.0 L of gastric contents and pH ranging from 3 to 5. Decreases in plasma electrolyte concentrations also can be attributed to decreased intake, because anorexia developed shortly after the onset of diversion. Electrolyte losses in urine during diversion were minimal for Cl-(mean +/- SEM, 12.0 +/- 5.1 mEq), but were greater for Na+ (124.2 +/- 14.5 mEq) and K+ (185.1 +/- 31.2 mEq). Treatments consisted of 0.9% NaCl (300 mosm/ L), 3.6% NaCl (1,200 mosm/L, and 7.2% NaCl (2,400 mosm/L) administered over a 2-hour period, with the administered volume determined by the estimated total extracellular fluid Cl- deficit. Significant difference was not found among treatments, with all solutions resulting in return of clinicopathologic and physical variables to prediversion values within 12 hours of treatment. We concluded that rapid iv replacement of Cl-, with small volumes of hypertonic saline solution, is safe and effective for correction of experimentally induced hypochloremic, hypokalemic, metabolic alkalosis in sheep.

We determined whether administration of cisplatin in hypertonic saline solution would prevent significant decrease in renal function, as measured by exogenous creatinine clearance, in healthy dogs. A single dose of cisplatin (70 mg/m2 of body surface) was mixed in 3% saline solution and was infused IV (6.5 ml/kg of body weight) over a 20-minute period to 6 healthy dogs. Exogenous creatinine clearance was determined prior to treatment of dogs with cisplatin and again on days 3 and 21 after administration of cisplatin. All 6 dogs vomited at least once within 12 hours of treatment with cisplatin; however, clinically important changes in appetite, body weight, or hydration status were not apparent during the 21-day study. Although mean values for exogenous creatinine clearance decreased from baseline on days 3 and 21, changes were not significantly different. Renal histologic lesions included mild, chronic, lymphoplasmacytic interstitial nephritis in 5 dogs, and presumably, were unrelated to treatment with cisplatin. Mild renal tubular atrophy (n = 2) and tubular necrosis (n = 1) may have developed secondary to treatment with cisplatin. Results of this study indicated that administration of a single dose of cisplatin in 3% saline solution to healthy dogs was not associated with significant decrease in glomerular filtration rate. This is a convenient protocol for administering cisplatin; however, additional study is required before it can be recommended for clinical patients, especially those with preexisting renal disease or those receiving multiple doses of cisplatin.

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.

Pharmacokinetic variables of phenolsulfonphthalein (PSP) were determined in sheep after rapid IV injection and IV infusion to steady state. In Suffolk wethers, an average of < 75% of an IV administered dose was eliminated in urine, indicating that measures of systemic clearance overestimate renal clearance in this species. Furthermore, PSP elimination from plasma was more rapid in Suffolk than Rambouillet wethers and, in Suffolk ewes, systemic clearance decreased from mean +/- SD 7.8 +/- 0.3 ml/min/kg of body weight to 4.7 +/- 1.1 ml/min/kg at steady-state plasma concentration of 2.4 +/- 0.3 and 151.3 +/- 31.8 micrograms/ml, respectively. These observations indicate that, similar to that in other species, systemic clearance of PSP in sheep is concentration-dependent and that significant differences may exist between breeds.

To investigate the determinants of glomerular ultrafiltration, renal micropuncture studies were performed in 9 cats. Mean single nephron glomerular filtration rate (SNGFR), directly measured in outer cortical nephrons, was 29.4 +/- 3.0 nl/min. This was similar to the estimated value for SNGFR (31.3 +/- 4.6 nl/min) obtained by dividing left kidney total glomerular filtration rate (1.41 +/- 0.12 ml/min/kg of body weight) by left glomerular count (175,200 +/- 13,600 glomeruli/kidney). In micropuncture studies performed at mean renal perfusion pressure of 101.3 +/-1.0 mm of Hg, the glomerular capillary hydrostatic pressure was 58.0 +/- 1.4 mm of Hg. The glomerular transcapillary hydrostatic pressure gradient (40.0 +/- 1.8 mm of Hg) exceeded colloid osmotic pressure at the efferent end of the glomerular capillaries (28.4 +/- 2.1 mm of Hg) in all cats studied, indicating existence of positive effective filtration pressure throughout the glomerular capillary bed. These results indicate that glomerular capillary pressure is sufficiently high to prevent forces from reaching filtration pressure equilibrium in feline outer cortical nephrons. Thus, the value of SNGFR in feline nephrons depends on the glomerular transcapillary hydrostatic pressure gradient and the glomerular ultrafiltration coefficient.