Glycolate determination detects type I primary hyperoxaluria in dialysis patients

Abstract

The detection of type I primary hyperoxaluria is based on the finding of exceedingly high oxalate excretion which is associated with increased glycolate excretion. The differential diagnosis of this disease may become a difficult task once end-stage renal disease (ESRD) and anuria have supervened. The various procedures thus far proposed to obviate this circumstance are complex, inaccurate or not reproducible. In this paper we propose the accurate liquid chromatographic determination of glycolate in blood and dialysate as a means to detect type I primary hyperoxaluria in patients on maintenance hemodialysis (RDT). The method is based on the enzymatic conversion of glycolate to glyoxylate coupled with alpha-keto acid derivatization with phenylhydrazine. The resulting phenylhydrazone is then resolved by high-performance liquid chromatograph (HPLC). With this method, plasma glycolate in 12 healthy controls was 7.8 +/- 1.7 mumol/liter, almost twentyfold less than previously reported. Five dialysis patients with high serum oxalate, of whom four with primary hyperoxaluria and one with Crohn's disease and presumed enteric oxalate hyperabsorption, were checked by this method and compared to nine patients with oxalosis-unrelated ESRD. The patients with hyperoxalemia were also evaluated for their response to pyridoxine therapy. The measurement of glycolate in blood drawn prior to and at the end of the dialysis session as well as in the dialysate soundly discriminated the patients with type I hyperoxaluria from all the other dialysis patients. Glycolate measurement was shown to be much more powerful than oxalate in that patients with oxalosis-induced ESRD exhibited an almost two hundred and fiftyfold increase compared to the oxalosis-unrelated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma Profiles and Dialysis Kinetics of Oxalate in Patients Receiving Hemodialysis

“…that is 310± 126 umol/24 h [37], Increased oxalate appearance has been reported in a previous study on dialy sis patients [12], and pyridoxine deficiency, which is referred to as being common in this setting [38], has been implicated in its pathogenesis. Our patients exhibited no abnormality in oxalate metabolism, and pyridoxine deficiency was un likely to occur, as also supported by normal levels of plasma glycolate [39]. Instead, the close correlation of OxAR with both PGR and Gurea, suggested that nitrogen balance-relat ed or nutritional factors might be common determinants of oxalate metabolism.…”

“…Second, plasma levels above the saturation threshold of calcium oxalate were measured in the very minority of the tested samples, and in no instance was this threshold ex ceeded more than 1.5 times. Third, as drawn in figure 2, preand postdialysis plasma levels of oxalate were far below those measured by us by the same IC technique (i.e., 162±24 and 60.4±14.0 pmol/l, pre-and postdialysis, re spectively) in patients on RDT and with primary hyperoxal uria, in which systemic oxalosis had been clearly document ed [39].…”

Gas chromatographic–mass spectrometric urinary metabolome analysis to study mutations of inborn errors of metabolism

“…Even after the end-stage of renal failure and anuria, the molecular diagnosis of PH1 can be achieved by targeting glycolate (Marangella et al, 1991) and oxalate in the blood. The quantification of oxalate should be done carefully to avoid the generation of any oxalate after blood sampling (France, Windleborn, & Wallace, 1985;Costello & Landwehr, 1988).…”

Primäre Hyperoxalurie und Nierentransplantation: Neue Aspekte zur Diagnostik, Prävention und Therapie

“…Neben der wiederholten Oxalat-Bestimmung im 24-Stunden-Urin empfiehlt sich bei nachgewiesener Hyperoxalurie zunächst die Bestimmung des Urin-Glykolates, um den Typ zu bestimmen (36). Als Normwert für die Urin-Glykolat-Ausscheidung werden bis 70 mg/ 1,73 m 2 Körperoberfläche/Tag angegeben.…”