Effective renal plasma flow (ERPF) was evaluated, using the measurement of p-aminohippurate clearance (CLPAH) and quantitative renal scintigraphy (QRS) with 99mTc-mercaptoacetyltriglycine (99mTc-MAG3). The CLPAH and QRS determinations were made in 6 dogs: 2 determinations for each dog before, and 1 determination after induction of renal failure by administration of amphotericin B. Least-squares regression analysis was used to derive an equation to estimate ERPF from QRS data. The results indicated that QRS, using 99mTc-MAG3, correlated reasonably well (r = 0.82, P < 0.001) with ERPF determined from the CLPAH value. The right kidney contributed 53.3% of global ERPF (P = 0.002). Hepatobiliary excretion of 99mTc-MAG3 was variable within each dog. There was not a consistent pattern with respect to time or renal function. All dogs had nausea or emesis, or both, after IV administration of 99mTc-MAG3. The QRS method with 99mTc-MAG3 provides an adequate means to estimate ERPF in healthy dogs and dogs with renal failure.

Four diets were formulated to contain: 16% protein and 0.4% phosphorus-diet 1; 16% protein and 1.4% phosphorus-diet 2; 32% protein and 0.4% phosphorus-diet 3; and 32% protein and 1.4% phosphorus-diet 4. Forty-eight dogs were fed diet 1 for 3 months after surgical reduction of renal mass, then were allotted to 4 groups of 12 dogs each, with equal mean values for glomerular filtration rate (GFR). Dog of groups 1-4 were fed diets 1-4, respectively, for 24 months. Data collected from the dogs during and at termination of the study were analyzed statistically for effects of dietary protein, phosphorus (P), time, and interactions between these factors. During the 24 months of study, 24 dogs developed uremia and were euthanatized for necropsy. Necropsy also was performed on the remaining 24 dogs after they were euthanatized at the end of the study. Dog survival was significantly enhanced by 0.4% P diets (vs 1.4% P diets), but survival was not significantly influenced by amount of dietary protein. The 0.4% P diets (vs 1.4% P diets) significantly increased the period that GFR remained stable before it decreased, but dietary protein did not have significant effect. Significant blood biochemical changes attributed to P, protein, and time were identified during the study. Terminally, plasma parathyroid hormone concentration was significantly increased from prediet values in all groups of dogs. Urine protein excretion was not significantly affected by dietary amount of either protein or P, when measured by either timed urine collection or urine protein-to-creatinine ratio. A tendency was seen for increased protein excretion with passage of time. Histologic and mineral analyses of kidneys removed at necropsy revealed some significant difference attributable to diet, but differences were more marked when diet was ignored, and the 24 surviving dogs were compared with the 24 that developed uremia. Overall, amount of dietary P was more important than amount of dietary protein for preventing adverse responses. However, because renal damage specifically attributable to either dietary component was not obvious, it is possible that the effects of P were manifested by extrarenal mechanisms.

The influence of induced chronic renal failure on 24-hour urinary excretion and fractional excretion of sodium and potassium was studied in cats. Induction of chronic renal failure significantly increased fractional excretion of potassium (P < 0.0001) and sodium (P < 0.05); however, 24-hour urinary excretion of sodium and potassium decreased slightly following induction of chronic renal failure. Fractional excretion and 24-hour urinary excretion of sodium and potassium were compared by linear regression in clinically normal cats, cats with chronic renal failure, and clinically normal and affected cats combined. In clinically normal cats, linear regression revealed only moderate correlation between fractional excretion and 24-hour urinary excretion for sodium and potassium. Linear regression of these same relationships in cats with chronic renal failure, and in clinically normal cats and cats with chronic renal failure combined, indicated low correlation. Fractional excretions of sodium and potassium were not reliable indicators of 24-hour urinary excretion of these electrolytes in cats with chronic renal failure or unknown glomerular filtration rate. Fractional excretion of potassium and sodium correlated only moderately with urinary excretion in clinically normal cats.

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).

Twenty-four dogs with induced, severe chronic renal failure were allotted to 2 groups of 12 each. Group-A dogs were fed a 0.4% phosphorus (P)/0.6% calcium, 32% protein diet, and group-B dogs were fed a 1.4% P/1.9% calcium, 32% protein diet. Dogs were studied over 24 months to determine clinical status, survival, blood biochemical alterations, glomerular filtration rate (GFR), urinary excretion of P and protein, renal morphologic changes, and renal tissue concentrations of calcium, P, and magnesium. Group-A dogs developed statistically significant differences from group-B dogs in several blood biochemical values (PCV and total solids, calcium, P, potassium, sodium, chloride, total CO2 (TCO2), anion gap, and parathyroid hormone concentrations) and in urinary P excretion. Mean (+/- SEM) GFR values in group-A and group-B dogs were nearly identical when diets were initiated (group A = 0.73 +/- 0.05 ml/min/kg of body weight; group B = 0.72 +/- 0.08 ml/min/kg), but significantly (P = 0.0346) lower GFR developed in group-B than in group-A dogs over time. At 24 months, GFR in survivors was 0.83 +/- 0.08 and 0.63 +/- 0.15 ml/min/kg for dogs of groups A and B, respectively. Other measurements favored the hypothesis that P/calcium restriction was beneficial, but values failed to reach statistical significance. Survival was greater at 24 months in group-A than in group-B (7 vs 5) dogs, and renal tissue concentrations of calcium and P were higher in group-B than in group-A dogs. Differences were not detected between groups in urinary excretion of protein and in the type or severity of renal lesions. We conclude that P/calcium restriction at 32% protein intake is beneficial to dogs with chronic renal failure, but that the degree of restriction imposed in group-A dogs of this study did not prevent development of abnormalities. Factors other than dietary P/calcium intake may have a role in progression of renal failure to uremia.

The function of atrial natriuretic peptide (ANP) is claimed to be control of salt and water homeostasis, and thus, the hormone may be involved in the pathogenesis of certain diseases with impaired volume regulation. We, therefore, studied plasma ANP concentration in dogs with chronic renal failure, congestive heart failure, and hyperadrenocorticism. Dogs with chronic renal failure had twofold higher plasma ANP concentration (16.2 +/- 5.8 fmol/ml), compared with healthy dogs (8.3 +/- 3.5 fmol/ml). An even more distinct increase (sixfold) of plasma ANP concentration was found in dogs with congestive heart failure (52.9 +/- 29.7 fmol/ml). In contrast, dogs with hyperadrenocorticism did not have high ANP plasma concentration (5.5 +/- 2.0 fmol/ml). High-performance liquid chromatographic analysis of plasma from dogs with congestive heart failure indicated that, in addition to the normal circulating form of ANP (99-126), the unprocessed precursor ANP (1-126) is detectable in the circulation. These qualitative and quantitative alterations of plasma ANP concentration in dogs further suggest involvement of this peptide in the development and/or maintenance of diseases associated with impaired volume regulation.

Serum from dogs with surgically induced renal impairment was incorporated into the medium for erythroid bone marrow cultures. A significant correlation was found between serum activities of erythropoietin and numbers of erythroid colony-forming units grown in culture. Serum creatinine concentrations had no correlation, and serum parathyroid hormone activities had a negative correlation with numbers of erythroid colony-forming units that was below the level of significance. Purified 1-84 parathyroid hormone added to bone marrow cultures was found to be stimulatory to erythroid colony-forming unit growth in higher concentrations, but decreased the number of burst-forming units. Unmeasured substances in the canine serum appeared to have a greater effect on the canine erythroid bone marrow cultures than did creatinine or parathyroid hormone values.

Objective-To determine and compare the ratio of uracil (U) to dihydrouracil (UH2) concentrations in plasma as an indicator of dihydropyrimidine dehydrogenase activity in clinically normal dogs and dogs with neoplasia or renal insufficiency. Animals-101 client-and shelter-owned dogs. Procedures-Study dogs included 74 clinically normal dogs, 17 dogs with neoplasia, and 10 dogs with renal insufficiency. For each dog, a blood sample was collected into an EDTA-containing tube; plasma U and UH2 concentrations were determined via UV high-performance liquid chromatography, and the U:UH2 concentration ratio was calculated. Data were compared among dogs grouped on the basis of sex, clinical group assignment, reproductive status (sexually intact, spayed, or castrated), and age. Results-Mean +/- SEM U:UH2 concentration ratio for all dogs was 1.55 +/- 0.08 (median, 1.38; range, 0.4 to 7.14). In 14 (13.9%) dogs, the U:UH2 concentration ratio was considered abnormal (ie, > 2). Overall, mean ratio for sexually intact dogs was significantly higher than that for neutered dogs; a similar difference was apparent among males but not females. Dogs with ratios > 2 and dogs with ratios less than 2 did not differ significantly with regard to sex, clinical group, reproductive status, or age. Conclusions and Clinical Relevance-Determination of the U:UH2 concentration ratio was easy to perform. Ratios were variable among dogs, possibly suggesting differences in dihydropyrimidine dehydrogenase activity. However, studies correlating U:UH2 concentration ratio and fluoropyrimidine antimetabolite drug tolerability are required to further evaluate the test's validity and its appropriate use in dogs.

Feline serum samples (n = 434) were classified as hypercalcemic, normocalcemic, or hypocalcemic based on both total calcium (tCa) and ionized calcium (iCa) concentrations. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive diagnostic likelihood ratio (PDLR), and negative diagnostic likelihood ratio (NDLR) were calculated for prediction of hypercalcemia and hypocalcemia in all samples, in hypoalbuminemic cats, and in those with chronic renal failure (CRF) as compared with cats that had other conditions. Diagnostic discordance in prediction of iCa using tCa was 40%. Sensitivity of tCa in prediction of ionized hypercalcemia was low and specificity was high. The PDLR for prediction of ionized hypercalcemia or hypocalcemia was low in all cats, especially in those with CRF. Due to the high level of diagnostic discordance, tCa should not be used to predict iCa concentration. Concentration of iCa should be measured directly when accurate assessment of calcium status is needed.