Calcium oxalate saturation in dialysis patients with and without primary hyperoxaluria

Abstract

Calcium oxalate supersaturation of the blood is associated with deposition of crystals in various tissues. We measured the serum levels of oxalate, citrate, calcium, and magnesium to estimate their saturation in 112 hemodialysis patients without primary hyperoxaluria and two boys with primary hyperoxaluria. Serum levels of oxalate and citrate were determined by high-performance capillary electrophoresis, while calcium and magnesium were measured by ICP spectroscopy. The serum levels of oxalate, citrate, calcium, and magnesium were 44.9+/-16.5, 138.1+/-54.9 micromol/l, 2.30+/-0.28, and 1.07+/-0.18 mmol/l, respectively, while the levels in patients with primary hyperoxaluria were 83.9+/-34.3, 197.9+/-63.5 micromol/l, 2.53+/-0.15, and 1.14+/-0.34 mmol/l, respectively. Serum calcium oxalate saturation (SS), as calculated by the Equil program, was significantly correlated with the serum oxalate level. Most patients showed metastable supersaturation (1<SS<8.9), which was associated with a serum oxalate level of more than 30 micromol/l. Serum saturation exceeded the formation product (SS=8.9) in some specimens from patients with type 1 primary hyperoxaluria. The serum calcium oxalate saturation [SS(CaOx)] showed a significant positive correlation with the levels of oxalate [Ox], calcium [Ca], and citrate [Cit]: [SS(CaOx)]=-0.3562+34.634[Ox]+0.394[Ca]-0.483[Mg]+0.101[Cit], (all mmol/l, r=0.9848, P<0.01). This formula is useful for estimating the saturation. In conclusion, the serum oxalate level is a good indicator of calcium oxalate saturation and should be monitored accurately while keeping it lower in dialysis patients.

Plasma oxalate levels in prevalent hemodialysis patients and potential implications for ascorbic acid supplementation

“…Accordingly, we rely on surrogate markers to assess for risk of secondary oxalosis. As Ox precipitates at a blood level of 30 μM, this level is thought to be a 'threshold' for oxalosis to occur [13,14]. Our data in conjunction with past observations suggest that, if calcium oxalate precipitates are formed during the interdialytic period, such precipitates may dissolve post-HD and oxalosis does not ensue, as long as the post-HD P[Ox] is b30 μM.…”

“…Mean pre-HD P[Ox] was 22.3 μM; lower than the levels of 39-49.8 μM that were seen in older series when patients received less efficient HD [14,17,19,20]. The majority of prevalent HD patients now have a pre-HD P[Ox] b30 μM, a level above which oxalate may begin to deposit pathologically in organs, due in large part to calcium-oxalate supersaturation in the blood.…”

“…Oxalate (Ox), an AA-metabolite, may accumulate when the glomerular filtration rate decreases to b30 mL/min [12]. When plasma Ox concentration (P[Ox]) reaches 30 μM, Ox has the potential to precipitate with calcium [13,14]. These precipitates may then deposit pathologically in organs [15], leading to secondary oxalosis [16].…”

Oxalate, inflammasome, and progression of kidney disease

“…In primary hyperoxalurias the unbounded oxalate overproduction causes sheer CaOx supersaturation in plasma by exceeding the oxalosis cut-off > 30 μmol/L(β CaOx >1) [109, 110, 111] and extreme urinary excretion ranging between 1–2 mmol/1.73 m 2 in 24 hours [112]. In enteric hyperoxaluria the high oxalate absorption is often associated with diarrhea-induced volume depletion, metabolic acidosis and hypocitraturia, providing favorable conditions for oxalate accumulation and precipitation in renal tissue [5, 7, 65].…”

“…Moreover, in patients on dialysis maximal oxalate elimination of 6–10 mmol/1.73 m 2 per week in routine HD or peritoneal dialysis (PD) is insufficient to address supersaturation. Consequently, ESRD patients on dialysis tend to have even higher plasma oxalate levels ranging around 45 μmol/l [111, 119, 126, 127, 128]. These extreme plasma oxalate levels are only exceeded by those in PH patients with levels of 80–125 μmol/L commonly found [110, 111].…”