PARATHYROID FUNCTION IN CHRONIC RENAL FAILURE

Abstract

A collection has been made of 134 personal and published cases of azotaemic osteodystrophy in which adequate information was available concerning the pathological state of the bones. Measurements were available of the plasma calcium, plasma phosphate, and blood-urea-nitrogen in all cases, and of plasma bicarbonate and plasma proteins in a representative sample. The plasma levels of calcium and phosphate in the whole series of 134 cases were not related reciprocally but were correlated directly. These data were further analysed by allocating each case to either of two sub-groups, according to the type of pathological lesions present in the bones. In one group there was evidence of defective mineralization of skeletal tissues, in the form of either rickets or osteomalacia, and the plasma-calcium was found to be statistically sub-normal. In the other group there was no primary defect of mineralization but the lesions of generalized osteitis fibrosa were present and the plasma calcium was statistically normal. There was no significant correlation between the plasma levels of calcium and phosphate in either sub-group; and the plasma phosphate was significantly higher in the group with the higher plasma calcium levels. The data indicate that in patients with renal osteodystrophy, contrary to general belief, the plasma calcium varies independently of the plasma phosphate. Since these results imply differences in parathyroid function among patients with azotaemic osteodystrophy, a survey has also been made of the recorded parathyroid weights in chronic renal failure. Generalized osteitis fibrosa and the accompanying normal levels of plasma calcium are associated with greater parathyroid hypertrophy than is found in most cases of chronic renal failure or cases with defective mineralization. The various data are interpreted in relation to the known metabolic disturbances and natural history of azotaemic osteodystrophy. By analogy with states of simple vitamin D deficiency, it is suggested that hypocalcaemia and relative unresponsiveness to the calcaemic action of parathyroid hormone are related to an acquired resistance to vitamin D. The group of cases with a statistically normal plasma-calcium prove that the parathyroid glands can function effectively in some patients with chronic renal failure, irrespective of the level of the plasma phosphate. The size of the glands and the effects of sub-total parathyroidectomy in patients of this group suggest that the normal plasma calcium results from an increased production of parathyroid hormone. The more advanced renal failure in the normocalcaemic, as compared with the hypocalcaemic, cases could mean that the development of an effective degree of secondary hyperparathyroidism is a function of the duration of the renal disease. It seems likely that when the parathyroid response is sufficient to overcome the effects of the vitamin D resistance it also entails the development of generalized osteitis fibrosa, healing of the defect of mineralization and an increased liability to metastatic calcification.