#1737 The role of oxalate in end-stage kidney disease

Abstract Background and Aims Oxalate is an end-product of metabolism and in human biology, it derives from endogenous and exogenous sources, and it is almost completely excreted by the kidney. We owe our knowledge of oxalate metabolism to a condition called primary hyperoxaluria (PH). PH is a rare, autosomal recessive, progressive disease caused by excessive hepatic production and elevated oxaluria. This condition leads to recurrent nephrolithiasis, nephrocalcinosis and eventually, kidney failure. As GFR declines oxalate accumulates leading to systemic oxalosis, characterized by extra renal deposit of calcium oxalate that is not only extremely debilitating, but also resistant to treatment. High plasma oxalate, however, is not only present in patients with PH, but can also affect patients with end-stage kidney disease (ESKD), especially those requiring hemodialysis (HD) or peritoneal dialysis (PD). Moreover, recent evidence suggests the role of oxalate as a uremic toxin involved in inflammation and atherogenesis, two well-known cardiovascular risk factors, even in the absence of PH. Our aim was to investigate the presence of calcium oxalate crystals in peripheral arteries of patients with ESKD. Method We included 14 adult patients affected by ESKD and scheduled to receive a living donor kidney transplant at Royal Free Hospital in London. We investigated iliac artery patch biopsies, discarded tissue that is normally the site for the transplant anastomosis. The presence of microcalcifications in the samples was investigated with microCT, whereas biochemical composition (specifically the presence of calcium oxalate monohydrate (COM) and brushite crystals) was examined using FTIR spectroscopy. Specifically, FTIR qualitative analysis was performed by recording spectra of every ESKD and control sample and comparing them to the spectral signatures of COM and brushite powders. Quantitative analysis was performed by manually calculating the contribution of COM and brushite in the samples, from the amplitude of characteristic absorption peaks at 1317 cm−1 and 879 cm−1, respectively. Lastly, the presence of calcium oxalate crystals was investigated with light microscopy (polarized light) on sectioned tissues with Von Kossa and H&E stainings. The study had ethics committee approval. Results Patients’ baseline characteristics are shown in Table 1 . 7 patients received a pre-emptive kidney transplant, 3 patients were undergoing HD and 4 patients were undergoing PD at transplantation. Four samples presented calcifications at microCT. One sample was heavily calcified (Fig. 1a), the other three presented spot calcifications (Fig. 1b–d). From the FTIR spectra's qualitative analysis, no major differences could be seen between the pre-emptive, PD and HD group, even after grouping the samples according to the presence of microcalcifications at microCT (Fig. 1e). Interestingly, the amplitude of the signal at 879 cm−1, that we attributed to brushite, was higher in the controls, followed by the non-calcified and the calcified group. The amplitude of the signal at 1317 cm−1, that we identified as the COM signature, did not differ significantly among the three groups (Fig. 1e). From the FTIR spectra's quantitative analysis, no differences could be seen between the manually calculated amplitude for the COM and brushite peaks between the pre-emptive, HD, PD and control groups (Fig. 1f–g). At the Von Kossa staining, calcifications either in the media or adventitia could be seen in 6 samples out of 14. No intimal calcification was observed. No calcium oxalate crystals were detected under polarized light (Fig. 1h–o). Conclusion Starting from the hypothesis that even transient hyperoxalemia in ESKD patients may favor the ectopic deposition of calcium oxalate crystals and therefore increase the cardiovascular morbidity and mortality of ESKD patients, we investigated arterial tissue for the presence of COM crystals. Although we couldn't find any calcium oxalate crystals, we cannot exclude that a high level of oxalate within tissue causes a direct or an indirect detrimental effect on endothelial cells and worsens these patients’ cardiovascular outcomes.