Endocrine Abstracts

There are just over 600 children in the UK on renal replacement therapy, with an annual take-on rate of around 100. There are many more in chronic renal failure (CRF). The main complications are poor growth, renal osteodystrophy and an increased risk of cardiovascular disease in early adulthood, all of which are inter-related.

The main player in renal osteodystrophy is hyperparathyroidism, which develops early in the course of CRF. PTH levels can be manipulated using phosphate binders and activated vitamin D. However, there is controversy surrounding the optimum PTH levels to aim for. This is for 2 reasons: firstly, bone biopsies have demonstrated PTH resistance in dialysis patients, leading to the suggestion that PTH levels should be maintained at 3 to 5 times the upper limit of normal in order to prevent low turnover bone disease; secondly, current 'intact' PTH assays pick up circulating C terminal PTH fragments (principally 7-84PTH) that circulate in uraemia, so that they may overestimate PTH. Newer assays that measure 1-84 PTH only give lower results. Also, the ratio of 1-84 to 7-84PTH may be important, as 7-84 PTH may be antagonistic to 1-84PTH. We have shown that if the PTH is maintained within the normal range from early in the course of CRF, this ratio remains normal and can be correlated with growth. The proportion of circulating PTH fragments increases as CRF progresses and with PTH levels above or below the normal range.

Both low and high turnover bone diseases have been linked to calcification of the vascular media, a phenomenon that occurs in CRF and in particular in dialysis patients. One cause is metastatic calcification, due to abnormal levels of calcium, phosphate and PTH; another is transformation of vascular smooth muscle cells into osteoblasts; bone related and bone specific proteins can be found in calcified plaques.