Diet-related urine collections: assistance in categorization of hyperoxaluria

Hyperoxaluria, one of the major risk factors for calcium oxalate urolithiasis and nephrocalcinosis, causes significant morbidity and mortality and should therefore be detected and treated as soon as possible. An early, consequent and adequate evaluation, but also a distinction between primary (PH) and secondary hyperoxaluria (SH) is therefore essential. We evaluated the usefulness of three consecutive 24-h urine collections under different diets [usual diet, (A), low oxalate diet, (B), high oxalate diet, (C)] to prove SH, or to find evidence of PH by changes in urinary oxalate excretion (Uox). We retrospectively analyzed results from 96 pediatric patients (47 females and 49 males, age 3–18 years) who presented with a history of nephrolithiasis, nephrocalcinosis and/or persistent hematuria in whom hyperoxaluria was found in an initial urine sample. The typical pattern of SH was found in 34 patients (mean Uox (A) 0.85 ± 0.29, (B) 0.54 ± 0.15 and (C) 0.95 ± 0.28 mmol/1.73m2/d). PH was suspected in 13 patients [(A) 1.21 ± 0.75; (B) 1.47 ± 0.51 and (C) 1.60 ± 0.82 mmol/1.73m2/d], but genetically proven only in 1/5 patients examined. No hyperoxaluria was found in 16 patients. Data were inconclusive in 33 patients. Urine collection under different diets is helpful to diagnose secondary hyperoxaluria and may provide evidence, that urinary oxalate excretion is normal. We have now established this procedure as our first diagnostic step before further, more extensive and more expensive evaluations are performed.

Contribution of Dietary Oxalate and Oxalate Precursors to Urinary Oxalate Excretion

Kidney stone disease is increasing in prevalence, and the most common stone composition is calcium oxalate. Dietary oxalate intake and endogenous production of oxalate are important in the pathophysiology of calcium oxalate stone disease. The impact of dietary oxalate intake on urinary oxalate excretion and kidney stone disease risk has been assessed through large cohort studies as well as smaller studies with dietary control. Net gastrointestinal oxalate absorption influences urinary oxalate excretion. Oxalate-degrading bacteria in the gut microbiome, especially Oxalobacter formigenes, may mitigate stone risk through reducing net oxalate absorption. Ascorbic acid (vitamin C) is the main dietary precursor for endogenous production of oxalate with several other compounds playing a lesser role. Renal handling of oxalate and, potentially, renal synthesis of oxalate may contribute to stone formation. In this review, we discuss dietary oxalate and precursors of oxalate, their pertinent physiology in humans, and what is known about their role in kidney stone disease.

Association of urinary sex steroid hormones with urinary calcium, oxalate and citrate excretion in kidney stone formers

Background Sex-specific differences in nephrolithiasis with respect to both distribution of prevalence and stone composition are widely described and may be influenced by sex hormones. Methods We conducted a cross-sectional analysis of the relationship between 24-hour urinary sex hormone metabolites measured by gas chromatography–mass spectrometry with urinary calcium, oxalate and citrate excretion in a cohort of 628 kidney stone formers from a tertiary care hospital in Switzerland, taking demographic characteristics, kidney function and dietary factors into account. Results We observed a positive association of urinary calcium with urinary testosterone and 17β-estradiol. Positive associations of urinary calcium with dehydroepiandrosterone, 5α-DH-testosterone, etiocholanolone, androsterone, and estriol were modified by net gastrointestinal alkali absorption or urinary sulfate excretion. As the only sex hormone, dehydroepiandrosterone was inversely associated with urinary oxalate excretion in adjusted analyses. Urinary citrate correlated positively with urinary testosterone. Associations of urinary citrate with urinary androsterone, 17β-estradiol and estriol were modified by urinary sulfate or sodium, or by sex. Conclusions Urinary androgens and estrogens are significantly associated with urinary calcium and citrate excretion, and associations are in part modified by diet. Our data furthermore reveal dehydroepiandrosterone as a novel factor associated with urinary oxalate excretion in humans.

P1215INVERSE ASSOCIATION BETWEEN DIALYSATE OXALATE REMOVAL AND INTRAPERITONEAL INFLAMMATION IN PERITONEAL DIALYSIS PATIENTS

Background and Aims Due to inadequate oxalate removal, hyperoxalemia is a well-established feature in end-stage renal disease (ESRD) patients. Considering the fact that oxalate is primarily removed by kidneys in healthy individuals, we hypothesized that oxalate elimination in peritoneal dialysis (PD) patients could be compensated by PD effluent (PDE). In addition, its dialysate concentration could be associated with intraperitoneal inflammation. In the present study, we investigated oxalate excretion in PDE and its association with intraperitoneal inflammation in PD patients. Method We performed a cross-sectional single-center observational study involving 30 PD patients (17 women and 13 men). The average age was 48.3 ± 9.2 years. Among them, there were 11 (37%) diabetics and 19 (63%) non-diabetic patients. The mean time on PD was 32 [18.5-47] months. Parameters of dialysis adequacy, cytokines concentration and oxalate removal levels with PDE were determined. The spectrophotometric method was performed for determining oxalate concentration in PDE using oxalate oxidase/peroxidase reagent (BioSystems, Spain). The ELISA method was used for the determination of interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) measurements in dialysate. For the statistical analysis, we used Kruskal-Wallis’s t-test and Spearman's rank correlation test. The median (Me) and interquartile ranges [Q25 - Q75] were calculated according to abnormal distribution. All statistical analyses were performed using MedCalc. Results No differences in peritoneal oxalate, IL-6, and MCP-1 excretion between diabetics and non-diabetic patients were observed (Table 1). However, the higher dialysate oxalate concentration was, the lower residual renal function was observed (r = - 0.69; p < 0.0001). Surprisingly, increased dialysate oxalate level was associated with low IL-6 (r = - 0.54; p = 0.002) (Fig. 1) and MCP-1 (r = - 0.7; p < 0.0001) (Fig. 2) concentrations in PDE. Conclusion To the best of our knowledge, the association between PDE oxalate excretion and proinflammatory mediators’ concentrations in PD patients has never been reported before. We suppose that peritoneal oxalate excretion might be involved in the intraperitoneal inflammation process. Further studies are needed to determine the possible pathogenetic role of dialysate oxalate removal in the conditions of intraperitoneal inflammation in PD patients.

Urinary Oxalate Excretion and Long-Term Outcomes in Kidney Transplant Recipients

Epidemiologic studies have linked urinary oxalate excretion to risk of chronic kidney disease (CKD) progression and end-stage renal disease. We aimed to investigate whether urinary oxalate, in stable kidney transplant recipients (KTR), is prospectively associated with risk of graft failure. In secondary analyses we evaluated the association with post-transplantation diabetes mellitus, all-cause mortality and specific causes of death. Oxalate excretion was measured in 24-h urine collection samples in a cohort of 683 KTR with a functioning allograft ≥1 year. Mean eGFR was 52 ± 20 mL/min/1.73 m2. Median (interquartile range) urinary oxalate excretion was 505 (347–732) µmol/24-h in women and 519 (396–736) µmol/24-h in men (p = 0.08), with 302 patients (44% of the study population) above normal limits (hyperoxaluria). A consistent and independent inverse association was found with all-cause mortality (HR 0.77, 95% CI 0.63–0.94, p = 0.01). Cause-specific survival analyses showed that this association was mainly driven by an inverse association with mortality due to infection (HR 0.56, 95% CI 0.38–0.83, p = 0.004), which remained materially unchanged after performing sensitivity analyses. Twenty-four-hour urinary oxalate excretion did not associate with risk of graft failure, post-transplant diabetes mellitus, cardiovascular mortality, mortality due to malignancies or mortality due to miscellaneous causes. In conclusion, in KTR, 24-h urinary oxalate excretion is elevated in 44% of KTR and inversely associated with mortality due to infectious causes.