The trigger-maintenance model of persistent mild to moderate hyperoxaluria induces oxalate accumulation in non-renal tissues

Persistent mild to moderate hyperoxaluria (PMMH) is a common side effect of bariatric surgery. However, PMMH's role in the progression to calcium oxalate (CaOx) urolithiasis and its potential effects on non-renal tissues are unknown. To address these points, a trigger + maintenance (T + Mt) model of PMMH was developed in rats (Experiment 1). The trigger was an i.p. injection of PBS (T PBS ) or 288 μmol sodium oxalate (T 288 ). Maintenance (Mt) was given via minipumps dispensing PBS or 7.5–30 μmol potassium oxalate/day for 28 days. Urinary oxalate ranged from 7.7 ± 0.8 μmol/day for T PBS + Mt PBS to 18.2 ± 1.5 μmol/day for T 288 + Mt 30 ( p ≤ 0.0005). All rats receiving T 288 developed CaOx nephrocalcinosis, and many developed ‘stones’. This was also true for Mt doses that did not elevate urinary oxalate above that of T PBS + Mt PBS ( p > 0.1) and for rats that did not have a detectable surge in urinary oxalate post T 288 . When T PBS was administered, CaOx nephrocalcinosis did not develop regardless of the Mt dose even if urinary oxalate was elevated compared to T PBS + Mt PBS ( p ≤ 0.0005). One of the risks associated with PMMH is oxalate accumulation within tissues. Hence, in a second set of experiments (Experiment 2) different doses of oxalate (Mt 0.05 , Mt 15 , Mt 30 ) labeled with 14 C-oxalate ( 14 C-Ox) were administered by minipump for 13 days. Tissues were harvested and 14 C-Ox accumulation assessed by scintillation counting. 14 C-Ox accumulated in a dose dependent manner ( p ≤ 0.004) in bone, kidney, muscle, liver, heart, kidney, lungs, spleen, and testis. All these tissues exhibited 14 C-Ox concentrations higher ( p ≤ 0.05) than the plasma. Extrapolation of our results to patients suggests that PMMH patients should take extra care to avoid dietary-induced spikes in oxalate excretion to help prevent CaOx nephrocalcinosis or stone development. Monitoring for oxalate accumulation within tissues susceptible to damage by oxalate or CaOx crystals may also be required.