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.

Association between glomerular filtration rate and extracellular fluid volume in normal subjects and patients with renal impairment.

The aim of the study was to determine the extent to which glomerular filtration rate (GFR) measured with one filtration marker is associated with extracellular fluid volume (ECV) measured independently with another. Cr-51-EDTA and iohexol were injected simultaneously into opposite arms in 20 normal volunteers and 60 patients. Cubital samples taken bilaterally at 20, 40, 60, 120, 180 and 240 min were assayed for marker injected contralaterally. GFR was scaled to body surface area of 1.73 m(2) (GFR/BSA). GFR was also expressed as marker transit time (GFR/ECV) and ECV as the product of marker transit time and GFR/BSA. In normal subjects, changes between fasting and non-fasting ECV/BSA correlated positively with changes in GFR/BSA, but not GFR/ECV. GFR/BSA and GFR/ECV correlated positively (regression slope approximately 4 ml.min(-1).litre(-1)) and negatively (-2.7 ml x min(-1) x litre(-1)), respectively, with ECV/BSA. The difference, 6.7 ml x min(-1) x litre(-1), expressed as a fraction of average scaled GFR ( approximately 90 ml x min(-1)) is close to the reciprocal of average ECV/BSA (13.5 litres.1.73 m(-2)), consistent with the expected slope of the regression on ECV/BSA of the difference-to-average ratio of GFR/BSA and GFR/ECV. In contrast, in 29 patients with impaired GFR (estimated from plasma creatinine), ECV/BSA correlated inversely with GFR/ECV (slope approximately -5 ml x min(-1) x litre(-1)) but showed no relation with GFR/BSA. We conclude that in normal subjects GFR/BSA increases in response to increasing ECV/BSA, but the increase is not proportionate, leading to a weak inverse association between GFR/ECV and ECV/BSA. When ECV is expanded in patients with renal impairment, however, there is no GFR response, leading to a reduction in GFR/ECV.

Regulation of renal function by the gastrointestinal tract: potential role of gut-derived peptides and hormones.

The concept of a regulatory link between the gastrointestinal tract and kidneys is not new. The idea that dietary intake and composition can affect renal function is perhaps self-evident, but defining this relationship, especially in terms of sensors and effectors, is proving more difficult. That the gastrointestinal tract can exert some control over renal function was strengthened by the early observation that oral ingestion of a sodium chloride load has a greater natriuretic effect than when the same amount is given intravenously. This effect was subsequently shown to be independent of changes in aldosterone and atrial natriuretic peptide, although not necessarily angiotensin-II. However, the nature of any intestinal natriuretic peptide remains uncertain, despite suggestions that various gut-derived hormones, including guanylin and uroguanylin, may be involved. There is also an emerging concept of gastrointestinal taste and taste-like receptor mechanisms present throughout the gastrointestinal tract, which may govern the excretion of other key electrolytes, including potassium and phosphate. The evidence for gut sensors of nutrients such as proteins, amino acids, glucose, and acid is now becoming more established. Thus, we can anticipate the existence and eventual characterization of several gut ion sensors.

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.

In the still of the night.

With medical general practitioners soon being able to buy themselves out of the requirement to provide overnight cover for their patients, for how much longer will the veterinary profession be able to sustain its 24-hour commitment? Here, Professor Bob Michell argues that it is time for the profession to rethink how it provides out-of-hours services--and, with the RCVS about to review the situation, concludes that something will have to change.

Iatrogenic hypocalcaemia during parenteral fluid therapy of diarrhoeic calves.

Acid-base balance and electrolyte concentrations, including ionised calcium, were monitored during intravenous fluid therapy of 11 collapsed diarrhoeic suckler calves aged five to 10 days. Six healthy calves of similar age and type were used to provide control data. All the diarrhoeic calves were severely acidotic (TCO2<12 mmol/litre). Isotonic sodium bicarbonate (1-3 per cent) was administered until the metabolic acidosis was half corrected, as indicated by the TCO2 increasing to 17 to 24 mmol/litre when the infusion was changed to an extracellular volume replacement fluid containing 144 mmol/litre Na+, 35 mmol/litre HCO3-, 4 mmol/litre K+ and 113 mmol/litre Cl- which was administered until the calf was discharged. Milk feeding was started as soon as the calf had a suck reflex. The treatment was successful in 10 calves. At admission the diarrhoeic calves were hypocalcaemic compared with the control calves, but their ionised calcium was significantly higher, with significantly less calcium being protein bound. Treatment with isotonic sodium bicarbonate resulted in a significant improvement in acid-base balance, but both total and ionised calcium decreased significantly, the decrease in ionised calcium being proportionately greater owing partly to a significant increase in the protein binding of calcium. The mean total, bound and ionised calcium concentrations were all significantly lower in the treated calves after they had received isotonic sodium bicarbonate than in the control calves. Further treatment with replacement fluid had no significant effect on any of the parameters apart from pCO2 which increased significantly. Milk feeding had no significant effect on plasma calcium concentrations. The calves' mean ionised calcium concentration was significantly lower at the end of the treatment than before it, but there was no difference in the mean total and bound calcium concentrations. The calves' mean plasma potassium and magnesium concentrations decreased significantly during the course of the treatment.