Investigating oxythiamine levels in children undergoing kidney transplantation and the risk of immediate post-operative
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ORIGINAL ARTICLE
Investigating oxythiamine levels in children undergoing kidney transplantation and the risk of immediate post-operative metabolic and hemodynamic decompensation Or Golan 1 & Roger Dyer 2 & Graham Sinclair 3 & Tom Blydt-Hansen 1 Received: 7 May 2020 / Revised: 31 August 2020 / Accepted: 22 September 2020 # IPNA 2020
Abstract Background Oxythiamine is a uremic toxin that acts as an antimetabolite to thiamine and has been associated with cases of Shoshin beriberi syndrome in adults. We sought to identify whether surgical stress and ischemia/reperfusion injury may precipitate functional thiamine deficiency in children peritransplant. Methods We retrospectively analyzed a cohort of pediatric kidney transplant recipients. Oxythiamine levels were measured in pre-transplant serum samples by mass spectrometry and tested for association with severity of lactic acidosis in the first 24 h posttransplant. Secondary outcomes included association with hyperglycemia and indicators of dialysis adequacy (DA). Results Forty-seven patients were included in the analysis. Median oxythiamine levels differed by modality, measuring 0.67 nM (IQR 0.31, 0.74), 0.34 nM (IQR 0.28, 0.56), and 0.25 nM (IQR 0.17, 0.38) for peritoneal dialysis (PD), hemodialysis (HD), and no dialysis, respectively (p = 0.05). Oxythiamine was associated with 24-h lactate levels (r = 0.38, p = 0.02) and negatively associated with DA (r = − 0.44, p = 0.02). Median oxythiamine levels were higher in patients with poor DA (0.92 nM (IQR 0.51, 1.01) vs. 0.40 nM (IQR 0.24, 0.51), p < 0.01). Sensitivity analysis showed absence of residual association of oxythiamine with 24-h lactate or dialysis modality, but remained significant for DA (p = 0.03). One patient manifested Shoshin beriberi syndrome (oxythiamine 2.03 nM). Conclusions Oxythiamine levels are associated with DA at transplant. Patients on PD with no residual kidney function and low DA manifest the highest oxythiamine levels and may be at an increased risk for developing acute Shoshin beriberi syndrome in the early post-transplant period. Keywords Chronic kidney disease . Uremic toxins . Oxythiamine . Functional thiamine deficiency . Transplantation . Lactic acidosis . Children
Introduction In chronic kidney disease (CKD), waste products of metabolism accumulate as renal clearance declines. When waste products reach harmful concentrations with progression to
* Tom Blydt-Hansen [email protected] 1
University of British Columbia (Pediatrics), Vancouver, British Columbia, Canada
2
British Columbia Children’s Hospital Research Institute (Analytical Core for Metabolomics and Nutrition), Vancouver, British Columbia, Canada
3
University of British Columbia (Pathology & Laboratory Medicine), Vancouver, British Columbia, Canada
kidney failure, they are considered as uremic toxins. Uremic toxins are defined by their ability to negatively interfere with biological functions, a common example being antimetabolites. Antimetabolites are molecules that interfere with normal cellular metabolic proce
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