Paediatric implications for some adult disorders : Scientific proceedings of the 4th Unigate Workshop, held at the Royal Academy of Physicians, St. Andrews Place, London, N.W. 1, May 1976 / edited by Donald Barltrop.
- Unigate Paediatric Workshop 1976 : Royal College of Physicians)
- Date:
- 1977
Licence: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Credit: Paediatric implications for some adult disorders : Scientific proceedings of the 4th Unigate Workshop, held at the Royal Academy of Physicians, St. Andrews Place, London, N.W. 1, May 1976 / edited by Donald Barltrop. Source: Wellcome Collection.
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![Metabolie causes of renal stone formation 13 to 5 fold in Type I primary hyperoxaluria [normal levels = 0-5-4'4 mg (6-7-59 ¡j.mol) glyoxylic acid per 24 hr per 1-73 m^]. Patients with Type II primary hyperoxaluria excrete 200-600 mg (0-943-1-886 mmol) of L-glyceric acid per 24 hr. Plasma oxalate determinations are of little clinical value at present, there being a ten fold discrepancy between the results of the best chemical methods and those obtained by isotope dilution analysis in vivo [9-18 (xg anhydrous oxalic acid per 100 ml (1-2 И-mol)]. It appears that the plasma oxalate concen¬ tration does not increase greatly until the terminal phase of the illness. Treatment There is no specific treatment for primary hyper¬ oxaluria. The patient should maintain a high rate of urine flow and surgical treatment should be the minimum necessary to relieve obstruction by stones, which will not pass spontaneously, and every attempt should be made to avoid removing any renal tissue. Complicating urinary infections should be treated vigorously, and cure should be proved bacterio- logically. Sufficient sodium orthophosphate or mag¬ nesium oxide should be given to materially increase the urinary phosphate or magnesium excretion. Orthophosphates act at least in part by increasing the excretion of pyrophosphate, which inhibits the aggregation of calcium oxalate crystals to form a stone. They are given in a dose equivalent to between about 1 and 2 g of elemental phosphorus per day, either as disodium hydrogen orthophosphate or as a mixture of disodium monohydrogen and mono- sodium dihydrogen salts, buffered at pH 7-4. Magnesium ions also inhibit crystallization and 200 mg of magnesium oxide is given 3 or 4 times daily. The urinary oxalate excretion is reduced by phar¬ macological doses of pyridoxine as high as 1 g per 24 hr in divided doses, in about one third of cases of primary hyperoxaluria. Attempts to reduce the urinary oxalate excretion by binding oxalate in the gut with cholestyramine and with aluminium hydroxide have proved un¬ successful (unpublished data). These observations are in accord with the results of early studies which suggested that the absorption of oxalate was not increased in primary hyperoxaluria (Archer et ai, 1958). A report that isocarboxazide reduced the urinary oxalate excretion in a case of primary hyper¬ oxaluria (Bourke et al., 1972) was not confirmed in another case (Watts, unpublished data), and the claim that succinimide reduced urinary oxalate ex¬ cretion (Thomas et al, 1971) was not confirmed in a small primate, the cynomolgus monkey, (Gibbs, unpublished data) although it has not so far been possible to repeat this study in man because the material is not available for pharmacological use in the United Kingdom. The observation that the a-hydroxyalkylsulphon- ates which are structural analogues of the hydrated glyoxylate ion and the glycolate ion, as shown below: Glyoxylate (anhydrous) OH I H-C—COO Glyoxylate (hydrated) OH I H-C—COO I H Glycolate R—C—SO, I ^ H Hydroxyalkyi sulphonate inhibited the oxidation of glyoxylate to oxalate in tissue systems in vitro, stimulated interest in the possible development of therapeutic inhibitors of oxalate synthesis. The higher members of the homo¬ logous series containing 4 or more carbon atoms, the branched chain compounds and the pyridyl- hydroxymethane sulphonates proved to be uniformly more effective than the alkyl derivatives of 1-3 carbon atoms, the potency of which increased with increasing chain length. They did not, however, re¬ duce the urinary oxalate excretion by cynomolgus monkeys when given orally (Gibbs, unpublished data); parenteral administration was not attempted. O'Keefe, Cies and Smith (1973) found that oxalate- hydrazide and oxamate hydrazide reduced the con¬ version of [CJglyoxylate to [Qoxalate when injected intravenously and simultaneously with the radioactive precursor, whereas sodium hydroxy- methane sulphonate, the simplest of the hydroxy- alkylsulphonates, did not do so. Oxalatehydrazide and oxamate hydrazide have the structures : Oxalatehydrazide Oxamate hydrazide These studies have not yet been extended to include feeding experiments in whole animals. Further work is needed to determine the best formulation, dosage, route of administration and the long term toxicity of the hydroxyalkyi sulphonates and the hydrazides before their possible value as inhibitors of oxalate synthesis is abandoned. The recognition of hereditary deficiency of subunit H of lactate dehydrogenase in a 64-year-old man, who presented with mild diabetes mellitus only and whose serum lactate dehydre- genase activity was about one-third of the lowor limit of the normal range suggests that it would not be impracticable to inhibit this enzyme partially for therapeutic purposes. Renal transplantation is not recommended in the treatment of primary hyperoxaluria because the transplanted kidney is progressively destroyed by](https://iiif.wellcomecollection.org/image/b18031298_0026.JP2/full/800%2C/0/default.jpg)
