Reliability of the MDRD method for estimating glomerular filtration rate in relation to gender, body mass index and extracellular fluid volume.

BACKGROUND: The accuracy of estimating glomerular filtration rate from plasma creatinine (eGFR) has been questioned but it is unclear how much covert error in several reference methods that have been used has contributed to this perceived inaccuracy. The aim of the study was to evaluate eGFR in comparison with a second 'gold standard' to test the performance of the primary gold standard and to examine the influence of patient demographics (age, body mass index (BMI), extracellular fluid volume (ECV) and gender). DESIGN: Non-fasting multisample GFR and ECV were measured in 80 subjects simultaneously and independently with Cr-51-EDTA (GFR(EDTA)) and iohexol (GFR(iohexol)). Percentage bias and imprecision in the prediction of, and disagreement with, GFR(EDTA) were compared between eGFR and GFR(iohexol). Another simplified method for measuring GFR, the slope-only method ((SO)GFR), was also evaluated against multisample GFR (measured with the opposing indicator). Accuracies were assessed in all subjects and across age, BMI and ECV boundaries of 65 y, 29 kg m(-2) and 14 L. RESULTS: eGFR was less precise than GFR(iohexol) (imprecisions of 22.3% and 12.9%; P < 0.01). The precision of (SO)GFR was intermediate between eGFR and GFR(iohexol). Both GFR(iohexol) and eGFR were less precise in the elderly, the obese and men, but minimally influenced by ECV. (SO)GFR was minimally influenced by subject demographics. CONCLUSION: Although eGFR does not predict GFR (based on a primary gold standard) as accurately as a second gold standard, a significant component of its poor performance is the result of inaccuracy in the primary gold standard. (SO)GFR measured with Cr-51-EDTA is superior to eGFR.

Glomerular filtration rate estimated by 3-sample plasma clearance of iohexol in 118 healthy dogs.

BACKGROUND: Glomerular filtration rate (GFR) decreases in the aging human kidney, but limited data exist in dogs. HYPOTHESIS: There is an effect of age and body size on estimated GFR in healthy dogs. ANIMALS: One hundred and eighteen healthy dogs of various breeds, ages, and body weights presenting to 3 referral centers. METHODS: GFR was estimated in clinically healthy dogs between 1 and 14 years of age. GFR was estimated from the plasma clearance of iohexol, by a compartmental model and an empirical correction formula, normalized to body weight in kilograms or liters of extracellular fluid volume (ECFV). For data analysis, dogs were divided into body weight quartiles 1.8-12.4, 13.2-25.5, 25.7-31.6, and 32.0-70.3 kg. RESULTS: In the complete data set, there was no trend toward lower estimated GFR/kg or GFR/ECFV with increasing age. GFR decreased with age in dogs in the smallest weight quartile only. A significant negative linear relationship was detected between body weight and estimated GFR/kg and GFR/ECFV. Reference ranges in different weight quartiles were 1.54-4.25, 1.29-3.50, 0.95-3.36, and 1.12-3.39 mL/min/kg, respectively. Standardization to ECFV rather than kilogram body weight did not produce substantial changes in the relationships between GFR estimates and age or weight. CONCLUSIONS AND CLINICAL IMPORTANCE: Interpretation of GFR results for early diagnosis of renal failure should take into account the weight and the age of the patient for small dogs.

Why has oral rehydration for calves and children diverged: direct vs. indirect criteria of efficacy.

Oral rehydration therapy (ORT) for acute diarrhoea has advanced in contrary directions in humans and animals; the unresolved question is whether this reflects species differences or a divergence in scientific outlook. This review suggests that the explanation lies in the fact that developments in veterinary ORT have the advantage of utilising more reliable criteria than those available from human patients. The dilemma for human ORT is that the validity of systematic reviews and meta-analyses are undermined when the underlying data only reflect crucial variables indirectly and unreliably. It is therefore possible that the approaches currently used to treat calves, which are radically different from those used by paediatricians, could potentially benefit children and the necessary additional research should be initiated. At a time when the value of animal models of human disease is frequently questioned, the benefits of being able to utilise disease models in the target species for clinical research deserve to be emphasised.

Comparative clinical science: The medicine of the future.

This review explores the emergence of Comparative Medicine in the late 19th Century as 'the medicine of the future', its failure to realise these expectations during the 20th century as it became increasingly equated with laboratory animal models of human disease, and explains why there is now an unprecedented opportunity for this latent potential to be fully realised. Comparative medicine no longer rests on apparent similarities between disease mechanisms in different species but on the rapidly maturing ability to relate these similarities to a remarkably rich shared genetic heritage. In the United Kingdom, the creation of the new Medical Research Council Comparative Clinical Science Panel, once securely funded, will provide the infrastructure and strategic focus to foster comparative clinical research, encouraging collaboration between veterinary and human medicine and between investigators in institutes and in practice. This will generate the necessary evidence base for veterinary practice, raise the standard of veterinary research, broaden the horizons of human medicine and create real opportunities for veterinary surgeons to reconcile research with practice. The review explores the broad scope of the science which will flourish in this new environment and examines specific areas in greater depth as examples, notably multifactorial disease such as hypertension and diarrhoea, also aspects of comparative endocrinology and oncology, with emphasis on the growing power conferred by comparative molecular genetics.

The Shipman reports: lessons and warnings.

The reports from the Shipman inquiry will lead to changes in the way the medical profession is regulated. Bob Michell fears that the veterinary profession will be affected, too.

Changes of sodium appetite during the estrous cycle of sheep.

The relative preference for sodium solutions and water was observed during a succession of estrous cycles in housed sheep. The luteal phase of the cycle was associated with statistically significant rises of sodium preference compared with the 6 days following estrus. These reflected changes in the intake both of sodium and water. The similar pattern with both bicarbonate and chloride suggests that it is the acceptability of the sodium which changes. The results are discussed in relation to sodium appetite and electrolyte homeostasis. The possible significance of any similar changes during the menstrual cycle is considered.

Sodium preference in sheep excreting sodium predominantly in urine or faeces.

On moderate sodium intakes (0.5 mmol/kg/day approx.) sheep are readily divided into those that are predominantly urinary or faecal excretors of sodium (U or F sheep). Water turnover and obligatory sodium loss are lower in F sheep. In view of these differences, sodium preference was examined in U and F sheep offered water and sodium bicarbonate solutions (40 or 300 mmol/l). The F sheep took significantly more of the bicarbonate solutions and, therefore, had sodium intakes that were 51% higher on the lower concentration, 94% higher on the higher concentration. Thus, F sheep not only conserve sodium more readily when it is scarce, they select it more readily when it is available.

Relationship between blood pressure and stress-prone temperament in dogs.

As part of an assessment of stress during the training of guide dogs for the blind, blood pressures have been monitored in their main breeds. For this article a population of 227 Labradors, between 9 and 24 months of age, had indirect arterial blood pressures measured and means taken of five readings. They were ranked according to their pressures. Prior to the measurements, their character was independently assessed as "stress-prone" or "non-stress-prone" by their highly experienced and trained handlers. The pressure data distribution of stress-prone animals in the ranking was analysed; they were significantly more likely to be found at the high end of the blood pressure range for that population.

Salt appetite during pregnancy in sheep.

Sodium preference was examined in three groups of sheep which had all sustained two consecutive pregnancies and lactations on either adequate sodium intakes (group C) or low sodium diets (B and C). Group B received a potassium supplement as well as a low sodium diet during the present experiment. No convincing or sustained increase in sodium preference resulted from the reduction in body sodium caused by pregnancy and lactation in group B or C, whether the sodium solutions offered were 40 or 300 mmol/l. In a second experiment, sodium preference (sodium bicarbonate, 40 mmol/l) was studied throughout pregnancy in sheep on low or adequate sodium diets, also non-pregnant controls on low sodium diets. Again, pregnancy on a low sodium intake failed to intensify salt appetite except for a transient (but significant) peak around d90, close to the peak of aldosterone secretion; a similar increase in preference occurred on the adequate sodium diet. However, salt appetite failed to intensify during the period of peak sodium demand (the last third of pregnancy) whereas renal and faecal sodium conservation are appropriately increased.

Comparison of cortisol concentrations in saliva and plasma of dogs.

It is increasingly important to have simple, non-invasive indicators of stress in animals. Studies in various species have shown that concentrations of cortisol in saliva relate closely to plasma levels of the free hormone; the aim of the present procedure was to show a similar correlation in the dog. Baseline blood and saliva samples were collected concurrently from six male beagles. Synthetic adrenocorticotrophic hormone was given and further samples were collected at 0.25, 0.5, one, two and 2.5 hours later. The results indicated a statistically significant correlation between the levels of cortisol in blood and saliva. Concentrations in saliva were between 5 and 10 per cent of those in plasma at each collection time. To demonstrate a response to a more natural stimulus, saliva samples were taken from a dog during exposure to a known stressor for that individual. The results showed a marked, delayed increase from baseline which was maintained for at least 0.5 hours after stressing.

Evaluation of iohexol as a marker for the clinical measurement of glomerular filtration rate in dogs.

The contrast medium iohexol can be used as a marker for the measurement of glomerular filtration rate. It has the advantages of sample stability and the availability of a simple, automated (though expensive) analyser. The clearance of iohexol was compared with the clearance of Tc-DTPA in 24 dogs with known or suspected renal impairment. The results were comparable but fractionally lower with iohexol. The correction factors developed for human beings were found to be satisfactory in the dogs, thus validating the software routines used in the automated analyser with the canine samples.

Effect of oestrogen and progesterone on sodium, potassium and water balance in sheep.

The effects of oestrogen and progesterone, injected alone or during successive periods, were studied in mature ovariectomised ewes on sodium intakes ranging from 1 to 4 mmol kg-1 d-1. Progesterone had no effect on fluid and electrolyte balance. Oestrogen (17 beta oestradiol) inhibited drinking but had little effect on water excretion whereas it reduced both food intake and urinary potassium concentration. Since the resulting changes in potassium intake and excretion were very similar, oestrogen had little net effect on potassium balance; neither change lasted beyond the treatment period. Oestrogen had a biphasic effect on urinary and faecal sodium excretion, an initial enhancement of salt loss being followed by sodium retention. Faecal sodium retention and the biphasic effect on renal sodium excretion were independent of changes in food intake. These observations are discussed in relation to the pattern of change of electrolyte balance during the reproductive cycle and the influence of changes in food intake and factors affecting sodium preference. The fact that a variety of responses is involved in a coordinated change of sodium balance is emphasised and its possible importance is considered.

Longitudinal studies of reproducibility and variability of indirect (oscillometric) blood pressure measurements in dogs: evidence for tracking.

To be clinically reliable, blood pressure readings taken in quiet surroundings with good technique from healthy, unstressed subjects accustomed to the procedure, should be reasonably constant between occasions. Apart from changes attributable to age or stress, sustained rises suggest hypertension. Yet it is increasingly realised that arterial pressure shows great short-term lability. Despite this, 'tracking' occurs in groups of humans, i.e. when ranked by blood pressure they tend to maintain their rank order. This paper examines month-on-month variability of arterial pressure, measured by non-invasive oscillometry (Dinamap) in both pet dogs and kennel populations. 'Tracking' occurred and there was also evidence of 'white coat' effects. Heart rate was more variable than arterial pressure and should not be used to reject pressure readings unless changes are extreme. There was further evidence that canine blood pressure rises with age.

Intravenous solutions for fluid therapy in calf diarrhoea.

Five commercially available parenteral solutions were compared for their effectiveness in correcting the disturbances associated with diarrhoea induced by Escherichia coli. Each solution (saline, Hartmann's, Darrow's, Plasmalyte +/- glucose) was tested on eight Jersey calves less than a week old and weighing approximately 25 kg. Each calf received 8.5 litres over three days, at about 20 ml kg-1 h-1. Solutions such as saline or Plasmalyte which had higher concentrations of sodium were more effective at correcting dehydration and electrolyte disturbances than those with less sodium (Darrow's, Hartmann's) but only those with bicarbonate precursors (lactate, acetate, gluconate) were effective in correcting metabolic acidosis. The additional potassium in Darrow's was predictably unhelpful in correcting hyperkalaemia and the additional glucose in Plasmalyte-glucose, despite some beneficial effects, undermined its effectiveness in correcting acidosis. These results suggest that solutions for intravenous treatment should probably contain about 150 mmol litre-1 Na+, 5 mmol litre-1 K+ and about 50 mmol litre-1 of a mixture of bicarbonate and precursors. Neither of the commonly used solutions (saline or Hartmann's) is thus ideal.

A simple method for measuring glomerular filtration rate in dogs.

A technique for measuring glomerular filtration rate (by six-sample plasma clearance) and extracellular fluid volume is described. The results obtained for glomerular filtration rat per extracellular fluid volume with a three blood sample technique are also presented. Concurrently with the blood sample techniques measuring plasma clearance, glomerular filtration rate per extracellular fluid volume was also measured using an external radiation detector and no blood samples. The validity of expressing glomerular filtration rate per extracellular fluid volume (rather than per body weight or surface area) and the clinical utility of the results obtained with the external radiation detector are discussed.

Non-invasive measurement of arterial blood pressure in dogs: a potential indicator for the identification of stress.

The reproducibility of indirect measurements of arterial pressure in dogs was assessed using the Dinamap 1846 SX oscillometric monitor and tail cuffs. Measurements on different days correlated excellently in 20 working dogs, with indistinguishable group means for systolic, diastolic and mean arterial pressure, whereas heart rates differed, though not significantly. The similarity of the means did not simply result from 'cancelling out' of individual variations; the rank correlation was also highly significant (P < 0.01 diastolic, P < 0.002 systolic). Remeasurement in the veterinary clinic, rather than 'neutral territory' showed significant increases in pressure but not heart rate. Anticipation of work raised systolic pressure whereas heart rate and diastolic pressure were unchanged. Exposure of a dog to a known stressor for that individual (sound) raised systolic and diastolic pressure as well as heart rate; diastolic pressure was the fastest to recover, heart rate the slowest. The data are compared with other observations on non-invasive blood pressure measurement in both dogs and humans.

Plasma and extracellular volume in calves: comparison between isotopic and 'cold' techniques.

While isotopic techniques have largely superseded traditional markers for the determination of the volume of fluid compartments in vivo, they are not always convenient, especially with diarrhoeic animals. A direct comparison was therefore made in week-old calves between Evans blue and radio-iodinated serum albumin as measures of plasma volume and thiocyanate or 24sodium as measures of extracellular fluid space. The correlation coefficients were excellent (1.00, 0.96; P < 0.001) and the calves had plasma and extracellular fluid volumes of 72 +/- 2 and 438 +/- 2 ml kg-1, respectively. The latter value is, though high, typical of young animals and comparable with other data in calves.

A comparison of direct and indirect (oscillometric) measurements of arterial blood pressure in anaesthetised dogs, using tail and limb cuffs.

Oscillometric measurements of arterial blood pressure were compared with direct measurements in anaesthetised dogs being monitored during routine surgery. Readings were obtained with tail cuffs and limb cuffs and the reproducibility (precision) of the readings from various cuff sites was also compared in conscious dogs. Tail cuffs gave the best precision in conscious dogs and the closest correlation with direct measurements in anaesthetised dogs, especially for systolic pressure. The proximal hindlimb site gave results with a slightly lower precision.

Effect of induced hypomagnesaemia on the toxicity of imidocarb in calves.

The hypothesis that the toxic effects of imidocarb mediated by reduced cholinesterase activity might be intensified by hypomagnesaemia was tested in calves. Hypomagnesaemia was induced in 12 males (50 kg) using an artificial milk based on a commercial nondairy coffee creamer. Although plasma magnesium levels reached 0.33 mmol litre-1 in two weeks no clinical signs were detected. In 12 control calves a daily magnesium supplement of 0.6 g was inadequate although the published requirement is 0.45 g; it was raised to 1.2 g to keep plasma magnesium normal. Lighter calves developed hypomagnesaemia more readily and fast-growing calves had lower plasma urea concentrations. Plasma calcium, but not plasma magnesium, showed significant positive correlation with plasma albumin. The only statistically significant effects of hypomagnesaemia were slight elevations of white cell count and plasma sodium. The hypomagnesaemic and normomagnesaemic calves were divided into two equal groups and treated with 3.3 mg kg-1 of imidocarb dipropionate or a placebo. The drug produced the expected clinical signs of mild toxicity and depression of cholinesterase but no other adverse effects. Transient slight depressions of plasma calcium and potassium concentration, a transient rise of plasma sodium and elevation of creatine kinase occurred. None of the effects of imidocarb treatment was intensified by hypomagnesaemia except, perhaps, constriction of the pupils; generally, hypomagnesaemic animals were affected less.