Assessment of compensatory renal function and [125I]iothalamate clearance in sheep

Compensatory renal function and sodium [125I]iothalamate clearance were studied in 4 adult Merino ewes. Renal clearances of inulin (CIN), iothalamate (CIOT), and p-aminohippurate (CPAH) were used to measure renal function before and 7 and 170 days after 50% and 75% reductions in renal mass. Renal mass reduction to 50% of normal was achieved by ligation of the right renal artery, and to 25% of normal by ligating the right renal artery and branches of the left renal artery. Renal function (CIN and CPAH) after 50% renal mass reduction was 78% of normal on postligation day (PLD) 7 and 64% of normal on PLD 170. This decrease in renal function between PLD 7 and 170 was significant (P less than 0.05). Renal function (CIN and CPAH) after 75% renal mass reduction was 55% of normal on PLD 7 and 48% on PLD 170; however, this decrease in renal function between PLD 7 and 170 was not significant. Results indicated that, shortly after 50% renal mass reduction by renal arterial ligation, renal function in ewes was greater than that previously reported after unilateral nephrectomy and that a further decrease in renal function developed within 6 months after ligation. The mean CIOT in healthy ewes was 2.46 ml/min/kg of body weight. In healthy ewes and in ewes after renal mass reduction, regression of the simultaneous CIOT and CIN was CIOT = 0.276 + 1.05 CIN. The CIOT was higher than the corresponding CIN, and remained significantly (P less than 0.01) and consistently higher. Therefore, iothalamate can be used to estimate glomerular filtration rate in sheep, although a correction factor is required.     

THE EFFECTS OF A UNILATERAL ULTRASOUND-GUIDED RENAL BIOPSY ON RENAL FUNCTION IN HEALTHY SEDATED CATS

Complications of renal biopsies are well documented except for the change in renal function after a biopsy. Eighteen healthy, adult cats were divided into two groups (n = 9 cats/group). For the measurement of global and split renal function, Group 1 used the renal uptake of 99mTc-DTPA and Group 2 used the renal uptake of 99mTc-MAG3. Scintigraphic data were collected on days (-4), (-3), 0, 1, 2, and 4 post renal biopsy. Using ultrasound guidance, biopsies were taken from the right renal cortex on dO, before acquiring scintigraphic images. P - values less than 0.10 were considered significant due to the limited number of observations. The only statistically significant change (p = 0.08) in global renal function detected was by day following a unilateral renal biopsy. Cats imaged using 99mTc-MAG3 had discernible liver activity. A unilateral, ultrasound guided renal biopsy has minimal effect on renal function in normal, healthy sedated cats.     

Drugs and renal function

This article considers the interactions between drugs and renal function, first, the adverse effects of nephrotoxic drugs and the changes in drug response associated with renal failure. It then discusses drugs intended to alter urinary sodium excretion (diuretics) and urinary pH as well as drugs which alter renal concentrating and diluting capacity. In each case emphasis is placed on the relationship between the drug effects and normal renal mechanisms. Reasons for the special vulnerability of the kidney to the toxic effects of drugs (e.g. antibiotics) are discussed and the practical problems of adjustment of drug dosage according to renal function are indicated. Finally, consideration is given to drugs, notably oral sorbents, which can partially substitute for renal function and might therefore eventually prove ideal for the management of advanced renal failure in small animals.     

Acid-base balance of cats with chronic renal failure: effect of deterioration in renal function

In a previous cross-sectional study of feline chronic renal failure (CRF), metabolic acidosis was identified in 52.6 per cent of animals with severe renal failure (plasma creatinine concentration >400 micromol/litre). The aim of this longitudinal study was to determine whether metabolic acidosis preceded or accompanied a deterioration in renal function in cats with CRF. Data were analysed from 55 cats with CRF that had been followed longitudinally for at least four months. Twenty-one cases showed deterioration in renal function over the period of the study, as evidenced by significant rises in their plasma creatinine concentrations and decreases in bodyweight. In five of the 21 cases, acidaemia accompanied the deterioration in renal function. Only one of these cats had evidence of metabolic acidosis before renal function deterioration. One other case developed metabolic acidosis without a rise in plasma creatinine concentration. These data suggest that biochemical evidence of metabolic acidosis does not generally occur until late in the course of feline CRF.     

Laboratory diagnosis and characterization of renal disease in horses

Laboratory evaluation of renal function in horses has advanced dramatically in the last 10 years largely as a result of the interest generated by the creative approach to diagnostic indices taken by Brobst, Traver, Coffman, and others. Some methods of assessing renal function discussed here are clearly outside the scope of a practice environment but are available in referral hospitals for use in difficult or unusual cases. Other methods described, such as calculation of fractional excretions and urine to serum creatinine ratios, are accessible and readily interpreted by the veterinary practitioner. These diagnostic methods should help in the early identification of renal disease in horses and therefore should allow veterinarians the option to treat renal disease before renal failure is advanced. In addition, practitioners may be able to offer more informed prognoses after a more complete evaluation of renal function.     

Radiographic kidney measurements in captive cheetahs (Acinonyx jubatus).

The prevalence of chronic renal disease is substantial among captive cheetahs (Acinonyx jubatus). The purpose of this study was to determine kidney measurements from radiographs of captive cheetahs (n = 15) with normal renal function. The ratio of kidney length to length of the body of the second lumbar vertebrae has been established for domestic cats with normal renal function. The mean ratio of renal length to length of the second lumbar vertebra was 1.81 +/- 0.14 in cheetahs. This baseline data may allow an objective evaluation of radiographic kidney size in cheetahs. However, evaluation of a small number of cheetahs with confirmed renal failure resulted in a similar ratio.     

RENAL TRANSIT TIME OF 99mTc-DIETHYLENETRIAMINEPENTACETIC ACID (DTPA) IN NORMAL DOGS

The transit time of 99mTc-DTPA in the kidneys is an indicator of renal function that has been used in humans for the diagnosis of renal obstruction, renal artery stenosis, and rejection of renal transplants. Its use, however, has not been reported in the dog. 99mTc-DTPA scintigraphy was performed in 8 normal dogs and the time of peak was calculated as the time between the injection and the maximum renal uptake. Deconvolution analysis was performed to estimate the renal retention function using 3 different techniques, i.e. the matrix method, the fast Fourier transform (FFT) method, and the constrained least square method. The parenchymal and whole kidney mean transit times were calculated from the deconvolved renogram using alternatively the thorax and the aorta as the input function. Average mean transit times ranged from 137 to 184 seconds. Parenchymal mean transit time was significantly shorter than whole kidney mean transit time (P<0.03). Mean transit time calculated with the thorax as the input function was significantly longer than mean transit time calculated with the aorta (P<0.001). No differences were observed between mean transit time calculated with the matrix, FFT and constrained least square methods.     

Preliminary study of urinary excretion of liver-type fatty acid-binding protein in a cat model of chronic kidney disease

Urinary liver-type fatty acid-binding protein (uL-FABP) is a clinically useful biomarker for monitoring chronic kidney disease (CKD) in humans. However, long-term monitoring of uL-FABP in CKD cats has not been reported. The objective of this preliminary study was to investigate whether the urinary excretion of L-FABP could predict the deterioration of renal function in 2 CKD model cats. Urinary liver-type fatty acid-binding protein (uL-FABP) increased before standard renal biomarkers, including serum creatinine, blood urea nitrogen, and symmetric dimethylarginine, in 1 cat with deteriorating renal function, but remained low and relatively stable in another cat with stable renal function. Our results suggest that uL-FABP is a potential clinical biomarker for predicting the progression of CKD in cats, as it is in humans.     

Effects of acepromazine on renal function in anesthetized dogs

OBJECTIVE: To investigate the effects of IM administration of acepromazine on indices of relative renal blood flow and glomerular filtration rate (GFR) by means of scintigraphy, as well as the effects on physiologic, hematologic, and serum biochemical variables in anesthetized dogs, compared with effects of administration of saline. ANIMAL: 6 healthy Beagles. PROCEDURE: Acepromazine (0.1 mg/kg) or physiologic saline (0.9 NaCI) solution was administered IM 30 minutes prior to induction of anesthesia with thiopentone; anesthesia was maintained with inspired isoflurane for 2.25 hours. Blood gases and circulatory and ventilatory variables were monitored. Renal function was evaluated by scintigraphic measurements of GFR and relative renal blood flow and analyses of serum and urine. Statistical analyses used ANOVA or Friedman ANOVA. RESULTS: Values of relative renal blood flow and GFR remained high despite low blood pressures. After administration of acepromazine, mean +/- SD arterial blood pressure was 66 +/- 8 mm Hg during anesthesia; this value was below the threshold (80 mm Hg) for renal autoregulation of GFR. In comparison, mean arterial blood pressure after administration of saline was significantly higher (87 +/- 13 mm Hg). However, between treatments, there were no significant differences in GFR, relative renal blood flow, or other indices of renal function. CONCLUSIONS AND CLINICAL RELEVANCE: Measurements of renal function and blood flow in dogs during anesthesia with thiopentone and isoflurane did not differ significantly between treatments, which suggested that acepromazine protects renal function despite inducing reduction in blood pressure, compared with effects of administration of saline.     

An updated review: Laboratory investigation of equine renal disease

A variety of laboratory tests are available to assist the clinician in the assessment of kidney health and function. The majority of widely used tests are indicative of altered renal function, not becoming abnormal until function is significantly compromised. These include serum urea and creatinine concentrations, serum electrolyte concentrations, urine specific gravity (USG), fractional electrolyte excretion ratios and symmetric dimethylarginine (SDMA) concentrations. Some of these parameters may also be affected by nonrenal disease. The results of a further group of tests can indicate renal damage, but do not reflect renal function. These include urine tubular enzyme concentrations, urine protein concentrations, urine neutrophil gelatinase-associated lipocalin (NGAL) concentrations and cytological abnormalities.     

Progression of chronic renal disease in the dog

Progressive loss of nephron function may be caused by persistence of factors that initiated renal disease. However, newer studies suggest that nephron damage is self-perpetuating once renal mass is reduced to some critical level. Original theories on mechanisms of self-perpetuated nephron injury focused on intraglomerular hypertension and glomerular hypertrophy, but several other factors have now been incriminated, including tubulointerstitial responses, proteinuria, and oxidative stress. Studies of dogs with surgically reduced renal mass (remnant kidney model of chronic renal disease) have allowed investigation of the self-progression theory in this species. Use of this model eliminates pre-existing renal disease as a confounding factor. Data from these studies indicate that self-perpetuated renal injury is initiated when mild azotemia is induced (plasma creatinine concentration = 2 to 4 mg/dL). Thus, with naturally occurring renal disease(s), it is likely that self-perpetuated nephron damage is occurring before or at the time when most cases of chronic renal disease are diagnosed. In dogs with remnant kidneys, loss of renal function often occurs at a linear rate over time, but non-linear patterns are common as well. The reciprocal of plasma creatinine concentration, which has been used to monitor rate of progression, is only a fair marker of renal function when compared to GFR. Thus, clinical results from creatinine measurements on cases of naturally occurring disease should not be interpreted too stringently. In remnant kidney dogs, the magnitude of proteinuria (UPC ratio) was not predictive of the rate in decline of GFR, casting doubt on importance of proteinuria in causing progression of renal disease. However, progressive increases in UPC may be a marker of an accelerated rate of renal injury. Self-perpetuation of renal injury in dogs could be the sole mechanism by which naturally occurring renal diseases progress. When more information is available on the rate of progression of naturally occurring diseases, it may become apparent whether factors initially inciting renal damage have an additive effect on rate of progression.     

Diagnosis of renal agenesis in a beagle.

A case of right renal agenesis in a beagle, of interest because of the age of the dog at the time of diagnosis, is described. Physical, haematological, biochemical and urinary examinations, including measurement of endogenous creatinine clearance, were performed to assess renal function. Survey radiography, excretory urography, ultrasonography, computed tomography and nuclear magnetic resonance examinations were also used to confirm the absence of a kidney. The effect of kidney agenesis on renal function, evaluated on the basis of endogenous creatinine clearance, is discussed together with the benefits of the various imaging techniques to enable in vivo detection of renal abnormalities.     

RENAL NUCLEAR MEDICINE: A REVIEW

Renal nuclear medicine is used to evaluate renal function and morphology. Renal scintigraphy is the best imaging modality for evaluation of functional parameters such as glomerular filtration rate and effective renal plasma flow. The commonly used renal radiopharmaceuticals are reviewed. Both imaging and non-imaging techniques are presented. Specific applications of renal nuclear medicine are discussed.     

Quantitative renal scintigraphy in domestic pigeons (Columba livia domestica) exposed to toxic doses of gentamicin

OBJECTIVE: To standardize techniques for renal scintigraphy in birds, to use scintigraphy to assess gentamicin nephrotoxicosis in birds, to compare nuclear medicine assessments with histologic assessment of gentamicin nephrotoxicosis and serum uric acid concentrations, and to determine the radiopharmaceutical that best quantifies avian renal function. ANIMALS: 12 domestic pigeons (Columba livia domestica). PROCEDURE: Serum uric acid concentrations were determined for all birds. Renal scintigraphy techniques that used technetium-m99 (99mTc)-dimercaptosuccinic acid (DMSA; 4 hours after injection) and 99mTc-diethylenetriamine pentaacetic acid (DTPA; 15-minute dynamic study) were evaluated in all birds. Renal biopsy specimens were collected following baseline scans. Number and size of renal tubule granules positive for periodic acid-Schiff stain were scored for severity (scale of 0 to 4). Nephrotoxicosis was induced by administration of gentamicin. Serum uric acid concentrations were measured, and 99mTc-DMSA and 99mTc-DTPA scans were repeated after gentamicin administration. Birds were euthanatized, and complete necropsies were performed. RESULTS: Standard avian renal scintigraphy techniques were developed for 99mTc-DMSA and 99mTc-DTPA. Decreased renal radiopharmaceutical uptake for 99mTc-DMSA and 99mTc-DTPA indicated nephrotoxicosis. Cloacal accumulation of 99mTc-DTPA was significantly decreased after administration of gentamicin. Histologic grading of renal tissue before and after gentamicin administration confirmed nephrotoxicosis. Inconsistent serum uric acid concentrations could not be used to assess nephrotoxicosis. CONCLUSIONS AND CLINICAL RELEVANCE: Renal nuclear scintigraphy is a useful, noninvasive means to determine renal function in birds. Although 99mTc-DMSA may prove useful in the evaluation of renal morphology, Tc-DTPA is the radiopharmaceutical agent of choice for the assessment of renal function in avian species.     

Ascites, renal abnormalities, and electrolyte and acid-base disorders associated with liver disease

Ascites and renal dysfunction are often associated with decreased liver function and reflect the complex abnormalities of water, protein, electrolyte, and acid-base metabolism that may complicate severe liver disease. This article discusses the pathophysiology and management of ascites, polydipsia and polyuria, decreased renal function, and acid-base and electrolyte alterations that can complicate liver disease.     

Attenuation of ischemia-reperfusion injury by ascorbic acid in the canine renal transplantation

This study examined the effects of ascorbic acid on the attenuation of an ischemia-reperfusion (I/R) injury after a canine renal transplantation. Eight beagle dogs were subjected to a renal auto-transplantation followed by the administration of ascorbic acid (treatment group) and the same amount of vehicle (physiological saline, control group). Blood samples were collected from these dogs to perform the kidney function tests and the invasive blood pressure was measured in the renal artery at pre- and post- anastomosis. The antioxidant enzymes of level 72 h after the transplant were measured. The kidneys were taken for a histopathology evaluation at day 21. The kidney function tests showed a significant difference between the control and treatment group. The invasive blood pressure in the renal artery was similar in the groups. The activity of the antioxidant enzymes in the blood plasma was significant lower in the control group than in the treatment group. The histopathology findings revealed the treatment group to have less damage than the control group. The results of this study suggest that ascorbic acid alone might play a role in attenuating I/R injury and assist in the recovery of the renal function in a renal transplantation model.     

Pharmacokinetics of warfarin in rabbits during short-term and long-term uraemia

Warfarin was administered intravenously twice at an interval of six months to rabbits with surgically-induced impairment of renal function and to control animals. Pharmacokinetic analysis showed that the elimination rate of warfarin was significantly decreased in the uraemic group after 2 weeks duration of uraemia and was even further decreased at the second examination 6 months later. No significant changes in the volumes of distribution were found. Renal function tests indicated stable renal function between the two examinations.     

Effect of short-term treatment with meloxicam and pimobendan on the renal function in healthy beagle dogs

The aim of the study was to investigate the renal function in clinically normal dogs receiving meloxicam and pimobendan alone or in combination. Ten adult female beagle dogs were administered the treatment for 7 days in a randomized crossover trial (control/meloxicam/pimobendan/meloxicam and pimobendan). Renal function was assessed by blood urea, creatinine, sodium, potassium and chloride concentrations and by glomerular filtration rate, measured by means of renal scintigraphy [renal uptake of ^99mTc-diethylenetriaminepentacetic acid (DTPA)] and plasma clearance of ^99mTc-DTPA. As compared with the control group, renal uptake and plasma clearance of ^99mTc-DTPA were not significantly modified after a 7-day period of treatment with meloxicam or pimobendan alone, or meloxicam and pimobendan in combination. Furthermore, urea, creatinine, sodium, potassium and chloride levels in the serum of the dogs during the 7-day period treatment were not significantly modified in relation to the treatments. It was therefore concluded that meloxicam and pimobendan alone or in combination did not alter renal function in healthy dogs.     

Effect of nephrotomy on renal function and morphology in normal cats

OBJECTIVE: To assess effects over 12 weeks of bisection nephrotomy on renal function, size, and morphology in cats. STUDY DESIGN: Controlled, randomized, blinded experiment. SAMPLE POPULATION: Ten adult female cats. METHODS: Glomerular filtration rate (GFR), determined by quantitative renal scintigraphy using (99m)Technetium-diethylenetriamine-pentaacetic acid, urinalysis, urine culture, and ultrasonographic measurement of renal size were performed preoperatively. Left or right nephrotomy (5 cats/group) was performed. Total and individual kidney GFRs were determined at 2, 28, and 84 days, ultrasonographic measurements at 28 and 86 days, and ultrasound-guided biopsy at 86 days. RESULTS: No significant differences in mean GFR and kidney size of operated versus unoperated kidneys were observed. Individual GFR and renal size of all except 1 cat remained within normal limits. Two cats had evidence of transient ureteral obstruction in the immediate postoperative period. No significant, generalized histologic abnormalities were observed. CONCLUSIONS: Bisection nephrotomy in normal cats does not adversely affect renal function or morphology during the initial 12 weeks. CLINICAL RELEVANCE: Bisection nephrotomy can be safely performed in normal feline kidneys without causing a significant deleterious effect on renal function. Studies in cats with pre-existing renal insufficiency are needed to ensure adverse effects would not occur in clinical cases where this surgical procedure is warranted.     

Effect of tepoxalin on renal function in healthy dogs receiving an angiotensin-converting enzyme inhibitor

The objective of this study was to investigate renal function in clinically normal dogs receiving tepoxalin, a nonsteroidal inflammatory drug, either in association with or without an angiotensin-converting enzyme inhibitor (ACEI). Ten adult female Beagle dogs were used in the three phases of the study. The dogs were administered the drugs once daily for 7 days (experiment 1: placebo/tepoxalin/tepoxalin and benazepril; experiment 2: enalapril/tepoxalin and enalapril) or for 28 days (experiment 3: tepoxalin and benazepril together). Renal function was assessed by measurement of glomerular filtration rate (GFR) by renal scintigraphy [(renal uptake of 99mTc-diethylenetriaminepentacetic acid (DTPA)] and plasma clearance of 99mTc-DTPA. Compared with the placebo group, renal uptake and plasma clearance of 99mTc-DTPA were not significantly modified after a 7-day period of treatment with tepoxalin or enalapril alone, tepoxalin and benazepril or tepoxalin and enalapril together. No significant change was obtained in GFR after a 28-day period of dosing with tepoxalin and benazepril together. Therefore, it was concluded that tepoxalin did not alter renal function in healthy Beagle dogs receiving ACEI.