Assessment of Plasma Oxalate Concentration in Patients With CKD

Abstract

Introduction: Alterations in oxalate homeostasis are associated with kidney stone disease and progression of chronic kidney disease (CKD). However, accurate measurement of plasma oxalate (P Ox) concentrations in large patient cohorts is challenging as prompt acidification of samples has been deemed necessary. In the present study, we investigated the effects of variations in sample handling on P Ox results and examined an alternative strategy to the established preanalytical procedures. Methods: The effect of storage time at room temperature (RT) and maintenance of samples at À80 C was tested. P Ox was measured in 1826 patients enrolled in the German Chronic Kidney Disease (GCKD) study, an ongoing multicenter, prospective, observational cohort study. Results: We demonstrate that P Ox concentrations increased rapidly when samples were maintained at RT. This was most relevant for P Ox <10 mM, as concentrations more than doubled within a few hours. Immediate freezing on dry ice and storage at À80 C provided stable results and allowed postponement of acidification for >1 year. In the patients of the lowest estimated glomerular filtration rate (eGFR) quartile, median P Ox was 2.7 mM (interquartile range [IQR] <2.0-4.2) with a median eGFR of 25.1 ml/min per 1.73 m 2 (IQR 20.3-28.1). Conclusion: We conclude that immediate freezing and maintenance of plasma samples at-80 C facilitates the sample collection process and allows accurate P Ox assessment in large cohorts. The present study may serve as a reference for sample handling to assess P Ox in clinical trials and to determine its role in CKD progression.

Pathophysiology and Management of Hyperoxaluria and Oxalate Nephropathy: A Review

“…Studies have shown a good correlation between spot level and 24h excretion, with no significant diurnal pattern of oxalate excretion (18)(19). In individuals with stage 4 and 5 CKD, urinary oxalate excretion decreases and plasma oxalate starts to rise (20). Plasma oxalate levels are used to monitor primary hyperoxaluria patients with CKD and on dialysis, prior to transplantation (21)(22).…”

“…Accurate measurement of plasma oxalate concentration is however challenging. Prompt acidification or freezing of samples and storage at -80°C until acidification is required to prevent conversion of plasma ascorbate to oxalate (20). Moreover, plasma oxalate levels do not correlate well with eGFR and show significant intraindividual variation in patients with primary hyperoxaluria (21).…”

“…Approximately two-thirds of the patients have malabsorption-associated hyperoxaluria (20,32). We found that chronic pancreatitis and gastric bypass were the most common causes of oxalate nephropathy (48%) (32).…”

Plasma Oxalate Concentration and Patients With CKD

“…In the recent article by Pfau et al. , 1 “Assessment of Plasma Oxalate Concentration in Patients With CKD,” they reported a new simple procedure for evaluating plasma oxalate (POx) concentration that enabled the investigation of a large cohort of patients with chronic kidney disease (CKD). 1 They measured POx in 1826 patients with CKD and found stable results; furthermore, they reaffirmed a negative correlation between the estimated glomerular filtration rate and POx.…”

Author Reply to Comment on “Assessment of Plasma Oxalate Concentration in Patients With CKD” by Oka et al.

“…The Author Replies: We thank Oka et al. for the precise summary of our study “Assessment of plasma oxalate concentration in patients with CKD” 1 and their excellent suggestions for future investigations. As proposed, we added a regression line to the scatter plot that illustrates the correlation between estimated glomerular filtration rate and plasma oxalate concentration ( Figure 1 ) with the correlation coefficient r being −0.22 (Spearman correlation; P < 0.001).…”