Bony content of oxalate in patients with primary hyperoxaluria or oxalosis-unrelated renal failure

Abstract

Oxalate retention occurs in end-stage renal failure. Regular dialysis treatment does not prevent progressive accumulation of oxalate in cases of ESRF due to primary hyperoxaluria (PH), whereas such accumulation seldom seems to occur in oxalosis-unrelated ESRF. To elucidate this issue we have measured the bony content of oxalate on biopsies of the iliac crest taken from 32 uremic patients, 7 of them with ESRF associated with PH1 (6 cases) or PH2 (1 case). Ten subjects with normal renal function and no evidence of metabolic bone disease were taken as controls. Only trace amounts levels of oxalate were detected in normal subjects and oxalate to phosphate ratio was below 3:10,000. Non-PH dialyzed patients exhibited fivefold increases in oxalate levels, which rose to 5.1 ± 3.6 μmol/g bony tissue. Calcium oxalate was estimated to represent 0.18% of the hydroxyapatite content of bone. Oxalate amounts were neither related to pre-dialysis plasma levels of oxalate, nor with duration of dialysis treatment, suggesting that accumulation was not progressive disorder. Oxalate levels were slightly higher in patients with a low turnover osteodystrophy compared to those with a high turnover pattern. Dialyzed patients with PH had remarkable increases in oxalate levels, which ranged between 14.8 and 907 μmol/g bony tissue. Oxalate deposition appeared to be progressive in that oxalate levels were significantly related to time on dialysis. In three patients calcium oxalate was a significant fraction of the mineralized bone. The occurrence of calcium oxalate crystals affected the histomorphometric patterns, that were featured by an increase in resorptive areas and a decrease in bone formation rate. We suggest that oxalate measurement in bony tissue gives reliable information of the status of oxalate burden in dialyzed patients. In this study oxalate deposition in bone has emerged as a non-progressive and meaningless event in patients with oxalosis-unrelated ESRF. Conversely, in patients with primary hyperoxaluria on maintenance hemodialysis, it evolves following a pattern so relentless that such patients should clearly be considered for organ transplantation as soon as possible.