Cochran, Malcolm (1975)
M.D. thesis, University of Birmingham.
The observations that form the basis of this thesis were made mainly between 1969 and 1971, following a study of urine acidifying mechanisms in a group of patients, most of whom had renal stones. The patients generally had a substantial reduction in glomerular filtration rate, a urine acidifying defect, and a number had clinically apparent osteomalacia. However, the association of the osteomalacia with the chronic metabolic acidosis seemed at least as strong as with the degree of uraemia, raising again the old question of whether a causal connection existed between acidosis and renal bone disease.
We know that most creatures exposed to direct sunlight have evolved a metabolism that far from accumulating Vitamin D, tends rather to inactivate and excrete it, presumably to reduce the risk of toxic effects. Perhaps for similar reasons, the hydroxylating enzyme in the kidney seems to have a relatively limited capacity for increasing production of 1,25-dihydroxycholecalciferol. A greater capacity for 1,25-dihydroxycholecalciferol production would require the existence of a stronger counter-regulatory mechanism than appears to be provided by calcitonin, for example. Thus if evolution has given any consideration to the patient with chronic renal failure, it is to ensure protection against toxic hypercalcaemia, and it is clear that the effects of 1-hydroxylation failure of Vitamin D may appear in non-fatal uraemia. This does not mean that acidosis is irrelevant, however, because any adverse effect that it might have would be of critical importance in a situation where synthesis of the active metabolite of Vitamin D were already impaired.
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