Laura W. Fleming

Plasma Retinol and Retinol Binding Protein Concentrations in Patients on Maintenance Haemodialysis with and without Vitamin A Supplements

Plasma retinol and retinol-binding protein (RBP) concentrations have been estimated in patients on maintenance haemodialysis over a 4-year period. For the first 2 years multivitamin supplements containing vitamin A were taken, and for the second 2 years no vitamin A supplements were given. Mean plasma retinol concentrations decreased significantly but only from 3.8 times normal to 3.1 times normal after vitamin A supplements stopped. There was no significant change in th high plasma RBP levels. Ultracentrifugation of plasma at a salt density of 1.21 showed that nearly all the retinol was associated with RBP in the high density protein fraction, as it is with normal subjects. Column chromatography confirmed that there was no increase in plasma retinyl esters in the renal failure patients, as is found in hypervitaminosis A due to drug overdosage. The high plasma retinol and RBP levels remained remarkably stable in individual patients throughout the 4-year study. The increase in plasma RBP was possibly related to residual urine output. The results are compatible with a feedback mechanism whereby the extent of the increase in plasma RBP as renal failure develops controls the consequent high plasma level of retinol.

Haemoglobin and Serum Iron Responses to Periodic Intravenous Iron-Dextran Infusions during Maintenance Haemodialysis

Patients with chronic renal failure who were on maintenance haemodialysis, were given monthly 600 mg iron intravenously as iron-dextran complex to a body replacement total of 5-6 g iron. Those patients who had been on maintenance haemodialysis for a long period and had received numerous blood transfusions failed to show a rise in haemoglobin levels. Those patients who received iron from the commencement of maintenance dialysis, and who had not received blood transfusions, showed a significant increase in haemoglobin concentrations which has been maintained for more than 18 months after iron therapy ceased, despite a concurrent decrease in serum iron concentrations. Pre-treatment and post-treatment levels of serum iron are not of predictive value for the success of iron treatment, neither for the haemoglobin nor the serum iron response. A body replacement dose of iron given intravenously over a year benefits the majority of patients on maintenance haemodialysis and is recommended for the treatment of their anaemia.

Massive obesity treated by intermittent fasting: A metabolic and clinical study

Abstract The effect of ten day periods of starvation, alternating with ten day periods of low caloric intake, has been studied in a male patient who originally weighed over 200 kg. Metabolic balance and clinical studies extended over a period of nineteen months, during which time 290 days were spent fasting. Weight loss has been assessed in the light of the concurrent losses of nitrogen, calcium, phosphorus and potassium. The rates of loss of calcium and potassium increased later in the study and reasons for this have been discussed. We suggest that the calcium losses may have been due to the resorption of bone unnecessary once the demands of excessive weight were removed. Potassium losses may have indicated an intracellular potassium deficit.

Chemical Reactivity of Aluminium‐based Pharmaceutical Compounds used as Phosphate‐binders

Abstract— Several aluminium‐containing substances, including antacids used as phosphate‐binders in treating renal failure, have been analysed in‐vitro under different pH conditions for the release of Al3+ ions and for binding of phosphate. Control experiments on different forms of pure aluminium hydroxide validated the methods. At pH 2 it was the most amorphous forms which released Al3+ most rapidly. These aluminium ions, available for absorption by the patient, were released from all antacids tested, but no firm phosphate‐binding was detected while the pH remained at 2. Phosphate was bound at pH 8, by adsorption onto the surface of aluminium hydroxide. No significant amounts of free Al3+ exist in solution at pH 8, since at that pH aluminium hydroxide is precipitated. The most amorphous forms of this solid were the most efficient phosphate‐binders. Alumino‐silicate salts require prior exposure to acid to produce free Al3+ before they can act as phosphate‐binders, whereas amorphous aluminium hydroxide acts as an efficient phosphate‐binder without prior exposure to acid. Chemical principles are employed to show why aluminium release and phosphate‐binding are separate and independent processes. Methods are proposed for maximizing the activity of phosphate‐ binders in‐vivo, while minimising aluminium release.

The effect of dialysate magnesium on plasma and erythrocyte magnesium and potassium concentrations during maintenance haemodialysis.

The effects on plasma and erythrocyte potassium and magnesium concentrations of low ( < 0.2 mEq/l) as compared with orthodox (1.50 mEq/l) dialysate magnesium concentrations have been studied in six patients on maintenance haemodialysis. On low magnesium dialysis, plasma magnesium concentrations were significantly decreased from hypermagnesaemic to normal levels but the high erythrocyte magnesium concentrations were unchanged. The plasma potassium decrease, usual during each dialysis, was unaffected. In contrast, erythrocyte potassium concentrations, which did not change during individual dialyses, were high when orthodox magnesium was present in the dialysate, and normal during low magnesium dialysis. Low magnesium dialysis has biochemical advantages in that it corrects hypermagnesaemia and maintains normal erythrocyte potassium concentrations which otherwise would be increased.

Blood pressure control during maintenance haemodialysis with isonatric (high sodium) dialysate

Isonatric (high sodium) dialysis has several advantages, including relative freedom from cramps. The diastolic blood pressures and body weights of nine originally hypertensive patients on maintenance haemodialysis have been recorded for 15 months throughout alternating periods on isonatric (145 mEq/l) and low (132·5 mEq/l) dialysate sodium concentration. Isonatric dialysis resulted in a temporary 1-2 kg increase in mean pre-dialysis weight, requiring increased ultrafiltration. This coincided with a slight increase in mean pre-dialysis diastolic blood pressure which was corrected when post-dialysis body weights were lowered to compensate for the increased weight gain between dialyses. Once the ‘ideal’ individual post-dialysis body weight for each patient was established, pre-dialysis diastolic pressures less than 90 mmHg were achieved routinely. Ten subsequent patients who have never received low sodium dialysis also have well controlled pressures. These findings are contrary to the orthodox view that low sodium dialysis is mandatory to avoid hypertension.

Effect of Carbohydrate Intake on the Urinary Excretion of Magnesium, Calcium and Sodium in Fasting Obese Patients

The urinary excretion of magnesium, calcium and sodium has been measured in 19 obese patients undergoing 12 days on complete fast (days 1-12) followed by 6 days of carbohydrate supplementation (days 13-18), while receiving no mineral supplements or either calcium, magnesium or sodium supplements. Magnesium and calcium followed different excretion patterns during the 12 days fast. The oral administration of 107 g carbohydrate daily during days 13-19 resulted in a marked decrease in the urinary excretion of magnesium, calcium and sodium by the non-, calcium- and sodium-supplemented patients, but there was no carbohydrate-induced reduction in magnesium excretion in the magnesium-supplemented patients. The kidney appears capable of selectively influencing calcium and sodium reabsorption, without magnesium excretion being affected. It is suggested that involvement in increased renal gluconeongenesis during fasting renders the renal tubule incapable of maximally conserving both divalent and monovalent ions. The increased tubular reabsorption of urinary constituents induced by carbohydrate administration probably stems from the concomitant reduction in gluconeogenesis.

Relationship between plasma and erythrocyte magnesium and potassium concentrations in fasting obese subjects

Abstract During 18-day fasts undertaken by 19 obese patients, plasma magnesium concentrations decreased in those given no mineral supplements or given calcium or sodium supplements, but did not decrease in those given magnesium supplements. The extent of the decreases ranged from 9% in the nonsupplemented group to 25% in the sodium-supplemented group. Plasma potassium concentrations decreased more gradually in all patients, irrespective of magnesium supplementation. Erythrocyte magnesium concentrations remained unchanged in all patients. Erythrocyte potassium concentrations decreased by between 5% and 9% in those patients who had a decreased plasma magnesium concentration, but did not change in the patients who were given magnesium supplements. These findings indicate a possible effect of extracellular magnesium concentration, or of some other correlate of magnesium supplementation, on potassium distribution and transport between extra- and intracellular compartments.

Bone Mineral Content Measured by Direct Photon Absorptiometry in a Normal Population and in Patients on Maintenance Haemodialysis

Bone mineral assessment, by monoenergetic photon absorption in vivo, has been carried out at a standard site in the radial shaft of 39 male and 54 female control subjects from a normal population, and in 13 patients who have been on maintenance haemodialysis for periods varying between 3 months and 5 years. Mean bone mineral content (±S.D.) was 1.22 ± 0.13 g. per cm. of shaft segment length for the normal male and 0.87 ± 0.08 g. per cm. for the normal female control subjects. Only 2 of the haemodialysed patients had values outwith the 95 per cent confidence limits of the normal range. In the patients a correlation was noted between the current plasma alkaline phosphatase level and the bone mineral content. Bone scanning by photon absorption is recommended as a convenient and sensitive method for routine clinical assessment of bone status.

Treatment of Ultrafiltration Loss in Continuous Ambulatory Peritoneal Dialysis

Laura W. Fleming, Department of Medicine, University of Dundee, Ninewalls Hospital and Medical School, Dundee DD1 9SY (UK) Dear Sir, Like Wolfish [1] we noticed that in patients on CAPD with poor ultrafiltration (defined as output volume < input volume using 1.36% w/v dextrose Dianeal 137 bags) the overnight dwell-time resulted in unacceptably high gains of both fluid and osmoles from the peritoneal dialysis fluid. In these patients the net fluid loss over 24 h was very low, or even negative, since with poor ultrafiltration during the daytime dwells, they could never eliminate what they had gained overnight, let alone their dietary fluid intake. We found that our good ultrafilterers were neither better nor worse on long dwells compared with short dwells (fig. 1). Our poor ultrafilterers on the other hand gained considerably more fluid after long dwells compared with short dwells, and this applied to both high strength and low strength glucose bags. This disadvantage associated with the overnight dwell led us to assess discontinuing it in patients with poor ultrafiltration. We have been using CAPD with an empty peritoneum overnight in adult patients with poor ultrafiltration with very encouraging results. Wolfish [1] described the benefits seen in 1 infant, and we can confirm that comparable benefits are seen in adult patients who have developed loss of ultrafiltration unassociated with peritonitis as described by Faller and Marichal [2↑. In 3 adults ultrafiltration capacity improved by 740 to 950 ml per 24 h when their normal four exchanges per 24 h (3 daytime and 1 overnight) were changed to four exchanges between 8 a.m. and 10 p.m. and the peritoneum left empty overnight. One further patient was able in this way to reduce from four to two 3.86%-glucose bags per 24-hour period litre + 2.0 I I I J. + 1.0 -I-IT J_ Removed