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.

Enhanced gastrointestinal passive paracellular permeability contributes to the obesity-associated hyperoxaluria

Most kidney stones (KS) are composed of calcium oxalate and small increases in urine oxalate enhance the stone risk. Obesity is a risk factor for KS, and urinary oxalate excretion increases with increased body size. We previously established the obese ob/ob ( ob) mice as a model (3.3-fold higher urine oxalate) to define the pathogenesis of obesity-associated hyperoxaluria (OAH). The purpose of this study was to test the hypothesis that the obesity-associated enhanced small intestinal paracellular permeability contributes to OAH by increasing passive paracellular intestinal oxalate absorption. ob Mice have significantly higher jejunal (1.6-fold) and ileal (1.4-fold) paracellular oxalate absorption ex vivo and significantly higher (5-fold) urine [13C]oxalate following oral gavage with [13C]oxalate, indicating increased intestinal oxalate absorption in vivo. The observation of higher oxalate absorption in vivo compared with ex vivo suggests the possibility of increased paracellular permeability along the entire gut. Indeed, ob mice have significantly higher fractions of the administered sucrose (1.7-fold), lactulose (4.4-fold), and sucralose (3.1-fold) excreted in the urine, reflecting increased gastric, small intestinal, and colonic paracellular permeability, respectively. The ob mice have significantly reduced gastrointestinal occludin, zonula occludens-1, and claudins-1 and -3 mRNA and total protein expression. Proinflammatory cytokines and oxidative stress, which are elevated in obesity, significantly enhanced paracellular intestinal oxalate absorption in vitro and ex vivo. We conclude that obese mice have significantly higher intestinal oxalate absorption and enhanced gastrointestinal paracellular permeability in vivo, which would likely contribute to the pathogenesis of OAH, since there is a transepithelial oxalate concentration gradient to drive paracellular intestinal oxalate absorption. NEW & NOTEWORTHY This study shows that the obese ob/ob mice have significantly increased gastrointestinal paracellular oxalate absorption and remarkably enhanced paracellular permeability along the entire gut in vivo, which are likely mediated by the obesity-associated increased systemic and intestinal inflammation and oxidative stress. A transepithelial oxalate concentration gradient driving gastrointestinal paracellular oxalate absorption exists, and therefore, our novel findings likely contribute to the hyperoxaluria observed in the ob/ob mice and hence to the pathogenesis of obesity-associated hyperoxaluria.

High expression of SLC26A6 in the kidney may contribute to renal calcification via an SLC26A6-dependent mechanism

Background Solute-linked carrier 26 gene family 6 (SLC26A6), which is mainly expressed in intestines and kidneys, is a multifunctional anion transporter crucial in the transport of oxalate anions. This study aimed to investigate the role of kidney SLC26A6 in urolithiasis. Methods Patients were divided into two groups: stone formers and nonstone formers. Samples were collected from patients following nephrectomy. Lentivirus with Slc26a6 (lentivirus-Slc26a6) sequence and lentivirus with siRNA-Slc26a6 (lentivirus-siRNA-Slc26a6) sequence were transfected into rats’ kidneys respectively and Slc26a6 expression was detected using Western blot and immunohistochemical analyses. After administering ethylene glycol, oxalate concentration and prevalence of stone formation between the transgenic and control groups were measured using 24-h urine analysis and Von Kossa staining, respectively. Results Immunohistochemical and Western blot analyses indicated that stone formers had a significantly higher level of expression of SLC26A6 in the kidney compared with the control group. After lentivirus infection, the urinary oxalate concentration and rate of stone formation in lentivirus-Slc26a6-tranfected rats increased remarkably, while lentivirus-siRNA-Slc26a6-transfected rats showed few crystals. Conclusion The results showed that high expression levels of renal SLC26A6 may account for kidney stone formation. Downregulating the expression of SLC26A6 in the kidney may be a potential therapeutic target to prevent or treat urolithiasis.

Oxalates are Found in Many Different European and Asian Foods - Effects of Cooking and Processing

Plant foods contain a surprising number of different toxins. A few well-known plants, including some grown in Thailand are known to contain high levels of oxalates however, some plants have not yet been fully investigated. A few plants have become fashionable to promote health because they contain antioxidants but some of these plants will contain oxalates as well. In many cases there is little published data to confirm the oxalates levels of these plants. If plant leaves are boiled before they are consumed this allows soluble oxalate to be leached out and discarded in the cooking water. This means that the cooked food contains considerably lower levels of soluble oxalates than the original raw plants. Cooking in a wok generally concentrates the oxalate contents as much of the cooking water is removed as steam. However, during cooking some of the soluble oxalates can combine with free calcium in the food and be converted to insoluble oxalates; these are not absorbed in the digestive tract. The preparation of juices using fruit or vegetables are being promoted as healthy alternatives, this poses further problems, as they may be prepared from raw vegetable leaves, such as spinach, which contain high levels of oxalates. These juices are not cooked so the oxalate concentration is not reduced during their preparation. Recent research has shown that the addition of calcium salts to these juices can considerably reduce the soluble oxalate content of the drink prepared without changing the taste.