A classical twin study was performed to assess the relative contributions of genetic and environmental factors to serum levels of calcium, phosphate and magnesium, urinary levels of calcium, sodium and potassium, and creatinine clearance. The subjects were 1747 adult female twin pairs: 539 monozygotic and 1208 dizygotic. The intraclass correlations were calculated, and maximum-likelihood model fitting was used to estimate genetic and environmental variance components. The intraclass correlations for all of the variables assessed were higher in monozygotic twin pairs. The heritabilities (with 95% confidence intervals) obtained from model fitting were: serum calcium, 33% (21–45%); serum phosphate, 58% (53–62%), serum magnesium, 27% (15–39%); 24h urinary potassium, 40% (27–51%); 24h urinary calcium, 52% (41–61%); 24h urinary sodium, 43% (30–54%); fractional excretion of sodium, 52% (44–59%); serum creatinine, 37% (25–49); calculated creatinine clearance, 63% (54–72%). This study provides evidence for the importance of genetic factors in determining urinary and blood levels of the major electrolytes involved in blood pressure regulation. Identifying heritability is the first step on the way to finding specific genes, which may improve our insight into the pathophysiology of the metabolism of these electrolytes, and thereby improve our understanding of the aetiology of complex diseases such as renal failure and hypertension.

1. Serum sialic acid is a reputed cardiovascular risk factor, but the reason why this is so is not clear. We therefore studied its relationship with other known cardiovascular risk factors (particularly those associated with insulin resistance) in 100 healthy young subjects (54 females and 46 males, age 20.7±0.89 years). 2. There was a significant univariate correlation between serum total sialic acid and fasting plasma insulin. Serum total sialic acid also correlated with fasting plasma glucose concentration and serum cholesterol and triacylglycerol. 3. In females there was a strong univariate correlation between serum total sialic acid and plasma fasting insulin and glucose concentrations, although in males there was a weaker univariate correlation between serum total sialic acid and fasting plasma glucose and the insulin resistance index. In addition, serum total sialic acid significantly correlated with systolic blood pressure, fasting serum cholesterol and triacylglycerol concentrations and body mass index in the females. In males serum total sialic acid significantly positively correlated with fasting serum cholesterol and triacylglycerol concentrations, and correlated inversely with the hip/waist ratio. 4. In multiple regression analysis of the 100 subjects serum total sialic acid correlated independently with fasting serum cholesterol, glucose and also plasma insulin concentrations. In females serum total sialic acid independently correlated with systolic and diastolic blood pressure, and serum cholesterol and fasting plasma glucose concentrations, although there was no significant independent correlation between serum total sialic acid and any of the other variables in the males.

1. Disturbances of sodium and water homoeostasis may contribute to the close association between diabetes, hypertension and proteinuria. We therefore studied the patterns of two natriuretic hormones, plasma atrial natriuretic peptide and urinary dopamine, in 165 Chinese patients with non-insulin-dependent diabetes mellitus controlled by diet or oral hypoglycaemic agents on two occasions over a 6-week period. Patients were divided into three groups based on the mean value of two 24 h urinary albumin excretion measurements. In group 1, 88 patients had normoalbuminuria (urinary albumin excretion ≤ 30 mg/day), in group 2, 48 patients had microalbuminuria (urinary albumin excretion between 30 and 300 mg/day), and in group 3, 29 patients had macroalbuminuria (urinary albumin excretion ≥ 300 mg/day). 2. The supine systolic blood pressure (mean ± sd ) was higher in patients with abnormal albuminuria (group 1: 140.9 ± 27.4 mmHg; group 2: 158.1 ± 26.4 mmHg; group 3: 166.7 ± 23.9 mmHg; F = 13.1, P <0.001, analysis of variance). Urinary sodium output was similar in these three groups of patients. The geometric means (anti-logarithm of 95% confidence interval logarithm) of plasma atrial natriuretic peptide concentrations increased with increasing proteinuria [group 1: 33.3 (29.9–37.1) pg/ml; group 2: 39.1 (34.2–44.6) pg/ml; group 3: 50 (38.6–54.7) pg/ml; F = 4.24, P <0.01; analysis of variance], whereas those of urinary dopamine output were related inversely to proteinuria [group 1: 1291.7 (1167.2–1437.0) nmol/day; group 2: 1142.3 (975.9–1337.2) nmol/day; group 3: 982.7 (775.7–1245) nmol/day; F = 3.10, P <0.05, analysis of variance]. Using stepwise multiple regression analysis, plasma atrial natriuretic peptide concentration ( r 2 = 0.31, F = 56.2, P <0.001) was associated with supine systolic blood pressure (β = 0.56, P <0.001), which was ( r 2 = 0.38, P <0.001) related to urinary albumin excretion (β = 0.23, P <0.001). In patients with urinary albumin excretion > 30 mg/day, plasma atrial natriuretic peptide concentration was negatively correlated with urinary dopamine output ( r = −0.25, P <0.02). 3. Based on these observations, we hypothesize that, in patients with non-insulin-dependent diabetes mellitus, defective dopamine mobilization in the renal tubules may cause impaired natriuresis with increased blood pressure. A compensatory rise in the plasma atrial natriuretic peptide concentration may then contribute to the development of abnormal albuminuria.

1. The increase in glomerular filtration rate after a protein meal is believed to be mediated by hormonal factors. Since natriuresis is often observed after a protein meal, it was postulated that the increase in glomerular filtration rate after a protein meal might be mediated by atrial natriuretic peptide. 2. Subjects were given a low, medium or high protein meal. Fluid intake was controlled so as to avoid significant extracellular fluid volume expansion. It was found that the creatinine clearance, the urea excretion, the fractional sodium excretion and the potassium excretion were elevated in all subjects after protein meals ( P <0.05). These effects were not observed in subjects given a carbohydrate control meal. 3. The plasma atrial natriuretic peptide concentrations remained unchanged in all subjects except those given a high protein meal ( P <0.05). There was no significant relationship between plasma atrial natriuretic peptide concentrations and creatinine clearance before or after a protein meal. 4. The data suggest that a high protein meal induces a minor increase in plasma atrial natriuretic peptide concentration, whereas a low or medium protein meal does not. It is unlikely that the change in creatinine clearance after a protein meal can be explained by a change in plasma atrial natriuretic peptide levels.

1. Erythrocyte sodium, sodium transport (ouabain-sensitive efflux rate of sodium, o M os Na , and ouabain-sensitive efflux rate constant of sodium, o M os Na ), sodium-potassium activated ouabain-sensitive adenosine triphosphatase (Na + , K + -ATPase) activity and [ 3 H]ouabain-binding capacity were measured in 15 patients with chronic renal failure and in 10 healthy subjects. 2. As a group, patients with chronic renal failure had a lower erythrocyte sodium and o M os Na compared with healthy subjects. 3. When patients were divided according to their erythrocyte sodium (greater or less than 4 mmol/kg of cells), in the group of patients whose erythrocyte sodium was less than 4 mmol/kg of cells (group A) the o M os Na was higher than that in healthy subjects and the o M os Na , Na + , K + -ATPase activity and [ 3 H]ouabain-binding capacity were the same as those in healthy subjects. In the subgroup of patients with renal failure whose erythrocyte sodium content was greater than 4 mmol/kg of cells (group B) the o M os Na was less and plasma urea concentration higher than in group A and Na + , K + -ATPase activity, [ 3 H]ouabain-binding capacity and o M os Na were lower than in healthy subjects. 4. These results suggest that in early chronic renal failure there is stimulation of ‘sodium pumps’ (without alteration in their number), which causes a lowering of erythrocyte sodium content, and that as the disease progresses there is inhibition of the ‘sodium pumps’ as well as a reduction in membrane permeability so that erythrocyte sodium is near normal.

1. The blood concentrations of 3-hydroxybutyrate and alanine were measured before and after they were separately injected into obese patients who were taking a 1.68 MJ (400 kcal) diet and again when they had starved for 4 days and 28 days. 2. The disappearance of the injected metabolite was exponential and its half-life and volume of distribution were calculated. 3. The concentration of ketones (both 3-hydroxybutyrate and acetoacetate) was raised in the patients when they were taking the low-calorie diet and increased a further sevenfold during starvation. This further increase was associated with an increase in the half-life of injected 3-hydroxybutyrate. 4. The pre-injection concentration of alanine almost halved during starvation and the half-life of injected alanine increased. 5. If the changes in half-life of exogenous 3-hydroxybutyrate and alanine apply to endogenous metabolites, then these results suggest that the increase in blood ketone concentration during starvation is at least partly due to a decreased clearance of ketones and the decrease in blood alanine concentration is associated with a marked decrease in production rate of alanine.

1. Studies were carried out on six normal male subjects to determine the short-term effect of increasing the dietary consumption of animal protein on the urinary risk factors for stone-formation, namely, volume, pH, calcium, oxalate, uric acid and glycosaminoglycans. 2. An increase of 34 g/day of animal protein in the diet significantly increased urinary calcium (23%) and oxalate (24%). Total urinary nitrogen increased by an average of 368 mmol/day. The accompanying increase in dietary purine (11 mmol of purine nitrogen/day) caused a 48% increase in the excretion of uric acid. 3. The overall relative probability of forming stones, calculated from a combination of the risk factors, was markedly increased (250%) throughout the period of high animal protein ingestion.

1. Three groups of 10-days-old chicks were fed on one of three diets having phosphorus contents of 0·08 mol/kg, 0·14 mol/kg or 0·21 mol/kg. Ten days later duodenal calcium absorption by the ligated loop technique in vivo , and plasma calcium and phosphorus concentrations, were measured. In addition the metabolism in vitro of 25-hydroxycholecalciferol [25-(OH)D 3 ] by kidney homogenates was studied. 2. In the low phosphorus group (0·08 mol/kg) calcium absorption and the activity of 25-(OH)D 3 -1-hydroxylase were significantly higher than those of the high phosphorus group (0·21 mol/kg). However, in the medium phosphorus group (0·14 mol/kg), calcium absorption was significantly higher although the activity of 25-(OH)D 3 -1-hydroxylase was not significantly higher when compared with the high phosphorus group (0·21 mol/kg). 3. It is concluded that in phosphorus deprivation, unlike in calcium deprivation, a diet very low in phosphorus is required to stimulate the renal 25-(OH)D 3 -1-hydroxylase activity.