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Biomedical subjects

D R Finco

Publications and source records attributed to D R Finco.

At least 19 recordsLinked to original sources

Effects of dietary protein on glomerular mesangial area and basement membrane thickness in aged uninephrectomized dogs.

The primary objective of this study was to determine the effects of diets containing 18% or 34% protein on glomerular mesangial area (GMA) and basement membrane thickness (GBMT) in uninephrectomized aged dogs. A secondary objective was to determine the combined effects of aging and uninephrectomy on GMA and GBMT in dogs. Ten clinically healthy, pure-bred dogs were unilaterally nephrectomized at about 8 y of age. After 2 mo, 5 dogs were fed an 18% protein diet and 5 dogs were fed a 34% protein diet for 48 mo. At month 48, the dogs were euthanized and the remaining kidney was collected. Samples of kidney from both times of collection were used to measure GMA and GBMT using electron microscopy. The effects of diet on GMA and GBMT were analyzed (student's t-test) using necropsy/nephrectomy score ratios. The effects of time-nephrectomy were determined by comparing nephrectomy values for GMA and GBMT with necropsy values (paired t-test). Dogs fed 34% dietary protein did not have a significant increase in GMA and GBM thickness when compared to dogs fed the 18% protein diet. A significant increase in GMA and GBMT occurred with time-nephrectomy (P = 0.011 and 0.018, respectively). Although dietary protein intake was not a significant factor in causing structural changes to glomeruli in uninephrectomized aged dogs, the power to detect a difference was low. However, significant effects of aging and nephrectomy were detected despite the low power of the study. These results suggest that the increases in GMA and GBMT that occur over time are not markedly influenced by dietary protein intake. However, subtle protein effects cannot be eliminated as a possibility based on this study.

Aging↗

Effects of dietary polyunsaturated fatty acid supplementation in early renal insufficiency in dogs.

Dietary supplementation with polyunsaturated fatty acids (PUFAs) alters the course of experimental kidney disease in dogs. In particular, supplementation with omega-6 PUFAs hastens the decline of kidney function, and omega-3 PUFAs are renoprotective. We investigated the early stages of renal insufficiency to determine whether PUFA supplementation altered the magnitude of hypercholesterolemia or glomerular hemodynamics. Two months after 11/12 nephrectomy, dogs were randomly divided into three groups of 6 animals each. Each group of dogs was then 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 were rich in omega-3 PUFAs (menhaden fish oil, group FO), omega-6 PUFAs (safflower oil, group SO), or saturated fatty acids (beef tallow, group C). Early in renal insufficiency, before significant kidney damage, group FO had a lower (P<.05) serum cholesterol concentration and tended to have a lower urinary prostaglandin E2 (PGE2) and thromboxane A2 (TxA2) excretion than group C. In contrast, group SO had a higher mean glomerular capillary pressure (P<.05) and more glomerular enlargement (P<.05) and tended to have higher eicosanoid excretion rates than group C. These differences in lipid metabolism, glomerular hypertension and hypertrophy, and urinary eicosanoid metabolism could explain, in part, the beneficial effects of omega-3 PUFAs and the detrimental effects of omega-6 PUFAs when administered on a long-term basis in this model of renal insufficiency.

Animals↗

Soy protein increases glomerular filtration rate in dogs with normal or reduced renal function.

In mammals, protein ingestion increases the glomerular filtration rate (GFR), an effect which has been incriminated as a risk factor in progression of renal disease. Some studies suggest that a postprandial increase in GFR is absent or mild with vegetable proteins compared to animal proteins. The objective of this experiment was to determine whether vegetable (soy) protein had different effects than animal protein on GFR in dogs with normal or reduced renal function. A trial was conducted in which GFR was measured in four dogs with normal kidney function and seven dogs with reduced renal mass before and after administering protein. Normal dogs were fed four protein sources (casein, soy meal, soy flakes and purified soy protein). Dogs with reduced renal mass were fed three protein sources (casein, purified soy protein and pork liver). All proteins significantly (P < 0.05) increased the GFR in both groups except for casein (P = 0.066) in normal dogs. Proteins did not differ significantly in the magnitude of the increase in GFR that was induced. This study indicates that soy proteins in dogs have the same effect on GFR as animal-source proteins, which is contrary to reports of effects in humans.

Animal Feed↗

Effects of an extract of Serenoa repens on dogs with hyperplasia of the prostate gland.

OBJECTIVE: To determine effects of an extract of Serenoa repens on dogs with prostatic hyperplasia. ANIMALS: 20 mature male dogs with benign prostatic hyperplasia. PROCEDURE: Dogs were assigned to 3 comparable groups on the basis of prostatic volume per kg of body weight and degree of prostatic hyperplasia determined histologically. Dogs in 2 groups were treated for 91 days (8 received 500 mg, PO, q 8 h [1,500 mg/d], and 6 received 100 mg, PO, q 8 h [300 mg/d]). The control group of 6 dogs did not receive medication. Effects of treatment on prostatic volume, prostatic weight, prostatic histologic characteristics, radiographic and ultrasonographic assessment of prostatic size, results of CBC, serum biochemical analyses, and urinalysis, serum testosterone concentration, and semen characteristics were determined. At the termination of the study, all dogs were euthanatized, and necropsies were performed. Investigators conducting tests and interpreting results were not aware of treatment group of each dog. RESULTS: Treatment did not affect prostatic weight, prostatic volume, or prostatic histologic scores, libido, semen characteristics, radiographs of the caudal portion of the abdomen, prostatic ultrasonographs, or serum testosterone concentrations. Results of CBC, serum biochemical analyses or urinalysis, and body weights did not change during treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with an extract of S repens for 91 days did not significantly affect the prostate gland of dogs. Adverse effects were not evident. Although products containing extracts of S repens are widely advertised for men with prostatic hyperplasia, beneficial or harmful effects of this plant extract were not found in dogs with prostatic hyperplasia.

Animals↗

Beneficial effects of chronic administration of dietary omega-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.

Animals↗

Interventional nutrition for renal disease.

Interventional nutrition plays a central role in the management of renal diseases in veterinary medicine. Most of the clinically observable abnormalities produced by the disruption of renal function are influenced by dietary intake of calories, phosphorus, sodium, potassium, protein, or acid load. Further, the kidney is susceptible to self-perpetuating injury, an inherent property of this organ, and the extent of this injury can be modified by adjustments in dietary intake of phosphorus and polyunsaturated fatty acids. The response of each animal with renal insufficiency to the disease and to nutritional intervention varies dramatically, and individualized therapy is required; the only constant nutritional characteristic of renal insufficiency is inappetance and loss of body weight. Successful interventional nutrition must take all of these principles into account.

Acid-Base Equilibrium↗

Is there a role for dietary polyunsaturated fatty acid supplementation in canine renal disease?

Dogs with spontaneous renal diseases frequently develop progressive uremia. After partial nephrectomy, a similar pattern of progressively declining renal function develops. This pattern may be attributed in part to the development of glomerular hypertension in remnant canine nephrons. Changes in the composition of dietary polyunsaturated fatty acids (PUFA) modify glomerular hemodynamics in normal rats and affect the chronic course of renal disease in partially nephrectomized rats. Thus, dietary PUFA supplementation might alter progressive canine nephropathies. However, the response of dogs with renal insufficiency to dietary manipulations frequently differs substantially from that of laboratory rodents, and the effects of dietary PUFA composition have been poorly characterized in dogs with chronic renal disease. Here we address the hypothesis that dietary PUFA supplementation may delay the progression of chronic renal insufficiency in dogs. In particular, dogs ingesting diets supplemented with (n-6) PUFA exhibited severe glomerular hypertension associated with rapidly progressive renal failure. In contrast, dietary supplementation with (n-3) PUFA prevented deterioration of the glomerular filtration rate and preserved renal structure. The results of these model studies demonstrate that dietary PUFA supplementation may alter renal hemodynamics and the long-term course of renal injury in dogs. Clinical trials to address the potential benefits of dietary (n-3) PUFA supplementation in a variety of spontaneous renal diseases seem warranted.

Animals↗

Protein and calorie effects on progression of induced chronic renal failure in cats.

OBJECTIVE: To determine effects of dietary protein and calories on progression of induced chronic renal failure in cats. ANIMALS: 28 young adult female cats. PROCEDURE: Renal mass was reduced surgically, and glomerular filtration rate (GFR) was determined. Cats were alloted to 4 groups of 7 with similar mean GFR (1.52 to 1.55 ml/min/kg of body weight). Diets were formulated to provide: low protein and calorie (diet A), low protein and high calorie (diet B), high protein and low calorie (diet C), and high protein and calorie (diet D) intakes. Cats were fed their prescribed diet for 12 months, then blood and urine biochemical variables were measured, after which kidney specimens were examined microscopically. RESULTS: Protein intake by cats of groups C and D (9.0 g/d/kg) was substantially greater than that by cats of groups A and B (5.3 and 5.2 g/d/kg, respectively). Caloric intake by cats of groups B and D (73 and 71 calories/d/kg, respectively) was greater than that by cats of groups A and C (58 and 55 calories/d/kg, respectively). Renal glomerular lesions were mild and not affected by protein, calories or their interactions. Nonglomerular lesions, though mild, were significantly influenced by calorie intake, but not by protein or calorie-protein interactions. The GFR did not decrease in any group. Urine protein-to-creatinine ratio increased significantly in all groups after reduction of renal mass, but values from all groups remained within the reference range (0 to 0.3). CONCLUSIONS AND CLINICAL RELEVANCE: Diets replete in protein were not associated with increased severity of glomerular or nonglomerular renal lesions, increased proteinuria, or decreased GFR. Diets replete in calories were not associated with increased severity of glomerular lesions, but were associated with mild increase of nonglomerular lesions. Factors other than protein and calorie intake must be considered potential causes of progression of renal failure in cats. Results raise questions about the practice of restricting quantity of protein in the diet of cats with chronic renal failure, with the intention of ameliorating development of further renal damage.

Adipose Tissue↗

Evaluation of renal function in rhesus monkeys and comparison to beagle dogs following oral administration of the organic acid triclopyr (3,5,6-trichloro-2-pyridinyloxyacetic acid).

The current study evaluated the effects of triclopyr (3,5, 6-trichloro-2-pyridinyloxyacetic acid) on renal function following oral administration in the beagle dog and rhesus monkey. Male rhesus monkeys were orally administered triclopyr by gavage at a dose of 5 mg/kg/day, 7 days/week for 28 days, after which the dosage was increased to 20 mg/kg/day for 102 consecutive days. Groups of male dogs were administered either a single oral dose of 5 mg/kg triclopyr or were fed a diet spiked with triclopyr at a dose of 5 mg/kg/day for 47 consecutive days. The following functional and clinical chemistry parameters were evaluated: exogenous phenolsulfonphthalein (PSP) excretion, inulin and para-aminohippurate (PAH) clearance (monkeys only), endogenous serum creatinine, and blood urea nitrogen (BUN) at multiple time points during the study. Creatinine, BUN, and inulin clearance were within the normal range from both species following triclopyr administration which indicates that repeated administration of triclopyr in the dog and monkey had no effect on glomerular filtration rate (GFR). In monkeys, the percentage excretion of PSP and PAH appeared to increase following triclopyr administration (20 mg/kg/day), suggesting that these weak organic acids may be competing for the same plasma protein-binding site enhancing their clearance. More importantly, these data strongly suggest that triclopyr is not competing with PSP or PAH for the active secretory site within the monkey kidney proximal tubules. In contrast, PSP clearance studies in dogs clearly demonstrated that triclopyr administration (5 mg/kg) can significantly decrease the percentage PSP excretion even following a single dose administration. The decrease in percentage PSP was reversible and inversely related to the plasma triclopyr concentration. Overall, these data clearly indicate that triclopyr effectively competes with PSP for the active secretory site within the dog kidney proximal tubules. In contrast, the monkey was insensitive to the effects of triclopyr on the active secretory process even at doses fourfold higher (20 mg/kg/day) than the effective dose in the dog (5 mg/kg/day). These findings suggest that the effect observed on PSP and PAH excretion in the dog represent a physiological competition for excretion and not toxicity.

Administration, Oral↗

Pathophysiology and management of progressive renal disease.

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.

Animals↗

Effects of parathyroidectomy on induced renal failure in dogs.

OBJECTIVE: To determine the effects of parathyroid hormone (PTH) depletion on dogs with induced chronic renal failure. ANIMALS: 2 groups of 26 mixed-breed dogs of both sexes (13 were parathyroidectomized [PTX] and 13 had sham surgery). PROCEDURE: After surgical reduction of renal mass and PTX, dogs were selected for a 24-month period of study and monitored for clinical, hematologic, blood biochemical, and organ function status. On development of uremia or after 24 months, dogs were euthanatized, and tissues were examined. RESULTS: Higher survival rate and smaller decrement in renal function (glomerular filtration rate) were observed in PTX dogs, compared with those that had sham surgery, but values did not reach statistical significance. The PTX dogs remained hypocalcemic during the study and had lower serum Ca2+ X P product values. Regardless of parathyroid state, survivors and fatalities could be separated on the basis of serum Ca2+ X P product values. Parathyroidectomy did not prevent renal deposition of calcium, and renal lesions were poorly correlated with renal cortical calcium concentration. Abnormalities reported in dogs with renal failure, which were attributed to PTH (glucose intolerance, pulmonary hypertension), were not observed in PTX dogs or those that had sham surgery. CONCLUSIONS AND CLINICAL RELEVANCE: PTX had beneficial effects, but these were mediated via changes in mineral homeostasis rather than via direct effects of PTH. Results attributable to PTX were similar to those previously obtained by dietary restriction of phosphate intake.

Acidosis↗

Reliability of using random urine samples for "spot" determination of fractional excretion of electrolytes in cats.

OBJECTIVE: To determine whether the "spot" method of determining fractional excretion (FE) of electrolytes in cats is accurate. ANIMALS: 5 clinically normal young adult female cats. PROCEDURE: Cats were acclimated to metabolism cages, and 2 consecutive 72-hour collections of urine were made to determine FE of total calcium, potassium, total magnesium, sodium, and phosphorus by conventional methods, using endogenous creatinine clearance as an estimate of glomerular filtration rate. During collections, small samples of urine were obtained by cystocentesis at 8 AM, 3 PM, and 9 PM for determination of FE of the electrolytes by use of the "spot" method. RESULTS: Values from "spot" determinations were highly variable, compared with 72-hour values, with a high percentage falling outside the range of mean +/- 2 SD for 72-hour FE values. CONCLUSIONS AND CLINICAL RELEVANCE: The "spot" method for determining FE is not precise, and if used, caution and judgement should be exercised in interpretation of the results.

Animals↗

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.

Animals↗

Detrusor-sphincter dyssynergia.

Detrusor-sphincter dyssynergia refers to failure of the urethral sphincter to relax during detrusor contraction. The cause is a central nervous system lesion located between the brain stem micturition center and the sacral spinal cord. This is an extremely rare condition in cats. It may be confused with a failure of urethral relaxation due to local urethral causes such as inflammation or edema. This article reviews detrusor-sphincter dyssynergia to allow the reader to distinguish this rare condition from more common conditions that prevent bladder emptying.

Adrenergic alpha-Antagonists↗

Pathophysiology of urethral obstruction.

Obstructive uropathy refers to abnormalities in structure or function of the urinary tract caused by impairment of normal flow of urine, and the resulting local and systemic effects of that impairment. Clinic consequences of obstructive uropathy are associated with abnormalities in fluid balance, electrolyte metabolism, acid-base balance, and retention of metabolic wastes. These consequences are partly due to build up of intravesical, ureteral, and renal pressure, influx of leukocytes into renal parenchyma resulting in release of cytokines, and alterations in intravascular hemodynamics. This article discusses pathophysiologic mechanisms and consequences of obstructive uropathy in cats.

Animals↗

Evaluation of a single injection method, using iohexol, for estimating glomerular filtration rate in cats and dogs.

OBJECTIVE: To evaluate the utility of a method for estimating glomerular filtration rate (GFR) after single IV administration of iohexol. DESIGN: The plasma clearance of iodine (PCI), taken as the quotient of the administered dose of iodine (300 to 600 mg of l/kg of body weight) divided by the area under the plasma iodine concentration versus time curve determined by 4 methods (PCI1-PCI4). The results for PCI were compared with simultaneously obtained values for the urinary clearance of exogenously administered creatinine (CCr), a widely accepted method for the measurement of GFR in cats and dogs. ANIMALS: Cats and dogs that were renal intact (n = 5 cats; n = 1 dog) or had renal mass reduced by partial nephrectomy (n = 5 cats; n = 7 dogs). RESULTS: Values for PCI were closely related (R2 values ranged from 0.947 to 0.992; P < 0.0001 in all cases) to CCr. Despite this close correlation between CCr and PCI, the 95% confidence interval for the difference between PCI3 and CCr included values that exceeded 1.4 ml/min/kg, which represents 50% of the mean value for CCr in renal-intact cats. CONCLUSIONS: Determination of PCI provided a reliable estimate of GFR in cats and dogs of this study. However, differences between 1 of the methods (PCI3) and CCr are clinically important, emphasizing the need to use more than simple linear regression analysis and correlation coefficients when attempting to validate new measurement techniques. CLINICAL RELEVANCE: The determination of PCI provided a reliable estimate of GFR in cats and dogs of this study.

Animals↗

Use of plasma clearance of inulin for estimating glomerular filtration rate in cats.

OBJECTIVE: To evaluate utility of a method for estimating glomerular filtration rate after a single i.v. injection of inulin. ANIMALS: Cats that were renal intact (n = 3) or had renal mass reduced by partial nephrectomy (n = 6). PROCEDURE: Plasma clearance of inulin (PCln) was taken as the quotient of the administered dose of inulin (150 mg) divided by the area under the plasma inulin concentration versus time curve determined by 3 methods (PCln1-PCln3). Results for PCln were compared with simultaneously obtained values for urinary clearance of exogenous creatinine (CCr), an accepted method for the estimation of glomerular filtration rate (GFR) in cats. RESULTS: Values for PCln were closely related (R2 ranged from 0.951 to 0.972, P < 0.0001 in all instances) to CCr. However, PCln3 provided an estimate of GFR that consistently overestimated CCr. CONCLUSION: Determination of PCln by use of PCln1 and PCln2 provided a reliable estimate of GFR in cats of this study. CLINICAL RELEVANCE: Determination of PCln appears to provide a reliable estimate of GFR in cats with early-stage renal disease and no evidence of derangement of body fluid status. In particular, PCln2, which requires only 3 determinations of plasma inulin concentration, should be considered when an estimate of GFR is sought in a cat with suspected early-stage renal disease.

Animals↗

Relationship between plasma creatinine concentration and glomerular filtration rate in dogs.

Glomerula filtration rate (GFR), plasma creatinine concentration (CR), and plasma urea nitrogen concentration (BUN) were measured in 129 adult dogs with reduced renal mass. A preliminary examination of the relationship between CR and GFR was conducted, and the inverse model (GFR vs. 1/CR) was chosen for further evaluation. The slope of the regression of GFR on 1/CR which was computed from actual data was not statistically different from a theoretical regression line generated from the clearance equation. Evaluation of subsets of the population revealed no significant difference between male (n = 69) and female (n = 60) dogs on the slope of the regression equations. Diets differing in protein concentration (16% protein, n = 35: 21% protein, n = 75: 32% protein, n = 19) did not cause a significant difference in the slope of the regression equations. The regression equation and the confidence intervals generated in this study may be used to predict a probable range of GFR values from CR in individual dogs. Such values may be useful in adjusting drug dosages in dogs with renal disease. However, since the derived equation did not differ significantly from the theoretical inverse relationship between GFR and CR, it remains to be established whether the equation is advantageous.

Animals↗