Does renal damage occur after the administration of 32P for palliation of pain from skeletal metastases?
In normal adults, the maintenance of phosphate balance involves the reabsorption of 85-90% of filtered phosphate by the proximal tubule. At a glomerular filtration rate (GFR) of 125 ml min-1 and a plasma phosphate concentration of 1.3 mmol l-1, the filtered phosphate is approximately 235 mmol day-1. Following intravenous administration, 25-50% of 32P is excreted over 4-6 days in normal subjects. In spite of such extensive renal handling of phosphate and, therefore, of 32P, there are no data in the literature concerning possible 32P-related nephrotoxicity. Adult dosimetry values for the kidney after 32P are reported as 4.8 rad mCi-1 h-1 (0.048 mSev 37 MBq-1 h-1). The entry criteria for 32P therapy insist on a normal serum creatinine value, reflecting awareness of potential renal damage. To answer the fundamental question of whether there is demonstrable renal damage after 32P, we undertook serial measurements of GFR in patients given 32P for treatment of pain from skeletal metastases. Twenty-one patients who had normal pre-treatment renal function as shown by normal serum creatinine values were administered 32P orally in doses ranging from 277.5 to 466.2 MBq, with a mean of 425.5 MBq. Pre-treatment, GFR was estimated with 99Tcm-diethylenetriamine pentaacetate renography using the Gates protocol. Post-treatment, GFR was estimated serially as far as possible, at weeks, 1, 2, 3 and 4 and then every 4 weeks for another 3 months, at which point follow-up ceased. Serum creatinine was assessed pre-treatment and every 2 weeks until the end of follow-up, in addition to all other parameters and a clinical evaluation. Mean pre-treatment GFR was 87.5 ml min-1, with a range of 48.7-110 ml min-1. Not all patients could fulfil the entire follow-up schedule as designed, but we obtained a minimum of four follow-up tests, two before and two after 4 weeks post-treatment. GFR fell to 72% of the pre-therapy value during the first 4 weeks following therapy. By the sixteenth week, however, the mean value had returned to or exceeded the pre-treatment value. There was no change in serum creatinine values. At a time when multiple therapies are being considered, this early depression of GFR may be of importance. A closer assessment of altered renal function may be warranted and other sensitive tests of renal damage like microalbuminuria could be used.