Kyle Wood

Glyoxal Formation and Its Role in Endogenous Oxalate Synthesis

Calcium oxalate kidney stones are a common condition affecting many people in the United States. The concentration of oxalate in urine is a major risk factor for stone formation. There is evidence that glyoxal metabolism may be an important contributor to urinary oxalate excretion. Endogenous sources of glyoxal include the catabolism of carbohydrates, proteins, and fats. Here, we review all the known sources of glyoxal as well as its relationship to oxalate synthesis and crystal formation.

Sensitivity of Human Strains of Oxalobacter formigenes to Commonly Prescribed Antibiotics

OBJECTIVE To determine the sensitivity of 4 strains of Oxalobacter formigenes (Oxf) found in humans--HC1, Va3, CC13, and OxK--to varying concentrations of commonly prescribed antibiotics. Oxf gut colonization has been associated with a decreased risk of forming recurrent calcium oxalate kidney stones. METHODS For each strain and each antibiotic concentration, 100 μL of an overnight culture and 100 μL of the appropriate antibiotic were added to a 7-mL vial of oxalate culture medium containing 20 mM oxalate. On the fourth day, vials were visually examined for growth, and a calcium oxalate precipitation test was performed to determine whether Oxf grew in the presence of the antibiotic. RESULTS All 4 Oxf strains were resistant to amoxicillin, amoxicillin/clavulanate, ceftriaxone, cephalexin, and vancomycin, and they were all sensitive to azithromycin, ciprofloxacin, clarithromycin, clindamycin, doxycycline, gentamicin, levofloxacin, metronidazole, and tetracycline. One strain, CC13, was resistant to nitrofurantoin, and the others were sensitive. Differences in minimum inhibitory concentration between strains were demonstrated. CONCLUSION Four human strains of Oxf are sensitive to a number of antibiotics commonly used in clinical practice; however, minimum inhibitory concentrations differ between strains.

The association of cardiovascular disease and metabolic syndrome with nephrolithiasis.

Purpose of review This review describes the relationship between nephrolithiasis, vascular disease and metabolic syndrome. Recent findings There is increasing evidence that kidney stone formation is associated with a number of systemic problems including cardiovascular disease, metabolic syndrome and its components. Some of these associations are bidirectional. The reasons for these associations are not totally clear, but potential factors include metabolic responses associated with these disorders that promote a stone forming milieu in urine, environmental factors such as diet, oxidative stress and inflammation and molecular changes impacting the transport of certain analytes in urine. Summary Urologists need to be cognizant of these associations as they may be able to contribute to an early diagnosis of a significant medical problem, or provide counseling to patients to prevent their occurrence.

The Impact of Dietary Calcium and Oxalate Ratios on Stone Risk

OBJECTIVE To determine whether the ratio of dietary calcium and oxalate consumption at mealtime affects gastrointestinal oxalate absorption and urinary oxalate excretion. METHODS A study was conducted with 10 non-stone-forming adults placed on controlled diets with daily calcium and oxalate contents of 1000 and 750 mg, respectively. Subjects consumed a balanced calcium/oxalate ratio diet for 1 week, observed a minimum 1-week washout period, and subsequently consumed an imbalanced calcium/oxalate ratio diet for one week. Urine specimens were collected on the last 4 days of each diet. Outcome measures included urinary creatinine, calcium, and oxalate as well as the Tiselius index for assessing urinary calcium oxalate supersaturation. RESULTS Total daily calcium excretion, oxalate excretion, and Tiselius index were similar between balanced and imbalanced dietary phases. There were significant differences in calcium excretion (mg/g creatinine) between balanced and imbalanced diets in the 1-6 PM (83.1 vs 110.2, P <.04), 6-11 PM (71.3 vs 107.2, P <.02), and 11 PM-8 AM collections (55.0 vs 41.8, P <.02). There was significantly higher oxalate excretion on the balanced diet in the 1-6 pm time period (28.1 vs 16.7, P <.01). There were no differences in the Tiselius index in these collections. CONCLUSION These results demonstrate that the sequence of ingesting relatively large amounts of oxalate does not significantly affect calcium oxalate stone risk if the recommended daily quantity of dietary calcium is consumed.

Oxalate and sucralose absorption in idiopathic calcium oxalate stone formers.

OBJECTIVES To better understand intestinal oxalate transport by correlating oxalate and sucralose absorption in idiopathic calcium oxalate stone formers. Oxalate has been hypothesized to undergo absorption in the large and small intestine by both paracellular and transepithelial transport. Sucralose is a chlorinated sugar that is absorbed by paracellular mechanisms. METHODS Idiopathic calcium oxalate stone formers were recruited to provide urine specimens on both a self-selected diet and after a meal containing 90 mg of (13)C(2-)oxalate and 5 g of sucralose, and a stool sample for determination of Oxalobacter formigenes colonization. The 24-hour urine collections were fractionated into the first 6 hours and the subsequent 18 hours. Sucralose and oxalate excretion were measured during these periods and used to estimate absorption. RESULTS Thirty-eight subjects were evaluated. The majority of both the (13)C(2-)oxalate and sucralose absorption occurred within the 0-6-hour collection. The (13)C(2-)oxalate and sucralose absorptions were significantly correlated at the 0-6 hour, the 6-24 hour, and the total 24-hour time periods (P <.04). All 5 oxalate hyperabsorbers(>15% absorption) also absorbed significantly more sucralose during the 0-6 hour and whole 24-hour time points (P <.04). Oxalobacter formigenes colonization did not significantly alter oxalate absorption. CONCLUSIONS The results suggest that most oxalate is absorbed in the proximal portion of the gastrointestinal tract and that paracellular transport is involved. Augmented paracellular transport, as evidenced by increased sucralose absorption, may also influence oxalate absorption.

Oxalate Formation From Glyoxal in Erythrocytes

OBJECTIVE To determine whether glyoxal can be converted to oxalate in human erythrocytes. Glyoxal synthesis is elevated in diabetes, cardiovascular disease, and other diseases with significant oxidative stress. Erythrocytes are a good model system for such studies as they lack intracellular organelles and have a simplified metabolism. MATERIALS AND METHODS Erythrocytes were isolated from healthy volunteers and incubated with varying concentrations of glyoxal for different amounts of time. Metabolic inhibitors were used to help characterize metabolic steps. The conversion of glyoxal to glycolate and oxalate in the incubation medium was determined by chromatographic techniques. RESULTS The bulk of the glyoxal was converted to glycolate, but ~1% was converted to oxalate. Inclusion of the pro-oxidant, menadione, in the medium increased oxalate synthesis, and the inclusion of disulfiram, an inhibitor of aldehyde dehydrogenase activity, decreased oxalate synthesis. CONCLUSION The glyoxalase system, which utilizes glutathione as a cofactor, converts the majority of the glyoxal taken up by erythrocytes to glycolate, but a small portion is converted to oxalate. A reduction in intracellular glutathione increases oxalate synthesis and a decrease in aldehyde dehydrogenase activity lowers oxalate synthesis and suggests that glyoxylate is an intermediate. Thus, oxidative stress in tissues could potentially increase oxalate synthesis.

PD03-07 RNA INTERFERENCE OF HEPATIC LACTATE DEHYDROGENASE REDUCES URINARY OXALATE IN A MOUSE MODEL OF PRIMARY HYPEROXALURIA TYPE 1

performed 2x2 table analysis of relationships between the scores for each papillary feature at the level of the papillum and the level of the kidney. Finally, we calculated mean scores for each feature by kidney and used Pearson correlation coefficients to measure relationships between features at the kidney level. RESULTS: 85 patients were included with a total of 361 papillae graded. In table analysis of pitting scores by plaque scores, values deviated powerfully from chance (X1⁄463.997, p<0.00001). Increasing plaque scores were associated with decreasing percentage of pitting score zero. The presence of plaque without pitting is more often seen than pitting without plaque. A similar but less pronounced relationship was seen in the analysis of contour loss by pitting scores (X1⁄4 35.9461, p1⁄40.0029). Furthermore, contour loss and plaque scores showed a very strong relationship (X 1⁄4 57.2033, p<0.00001). Results of the papillum-level analysis are summarized in Figure 2. At the level of the kidney, the strongest relationship exists between mean RP and mean contour scores (rp1⁄40.4630, p1⁄40.0003). CONCLUSIONS: These data support our critical hypothesis that RP and attached calcium stone complex are shed from the papillum leaving behind a pitting defect on the papillary surface, which can then either heal over or, with repeated insult, progress to loss of papillary contour. We believe that understanding this sequence helps link renal physiology to a urologic endpoint.

MP24-04 URINARY OXALATE EXCRETION IN OBESE MOUSE MODEL

RESULTS: At 4 weeks post-transplant there was a 58% decrease in urinary calcium (p<0.001), an 18% decrease in urinary oxalate (p<0.01), a 0.7 unit pH increase (p<0.001), and 29% increase in GI alkali absorption (p<0.04) (Figure 1). There was also a 56% and 44% decrease in Slc26a3 protein expression in the cecum and ileum of the transplanted mice (p<0.01), respectively. Slc26a6 protein expression increased 162% in the cecum and decreased by 46% in the ileum of the transplanted compared to germ-free mice (p<0.01). Age matched control germ free mice showed none of these changes. CONCLUSIONS: Introduction of a GMB via fecal transplant to a germ free mouse leads to dramatic changes in urinary calcium and oxalate. Moreover, changes in urinary chemistry seen after fecal transplant were accompanied by significantly altered expression of intestinal transporters responsible for calcium and oxalate homeostasis. These results demonstrate for the first time that the GMB can modulate urinary parameters that are important determinants for USD.

MP13-17 ASSOCIATION OF OBESITY WITH INCREASED ENDOGENOUS OXALATE SYNTHESIS

INTRODUCTION AND OBJECTIVES:Urinary oxalate levels are affected by both dietary and endogenous components. Prior studies have demonstrated the positive correlation between weight/body mass index (B...

MP01-12 THE ASSOCIATION OF HEMOGLOBIN A1C AND URINARY OXALATE IN STONE FORMERS

RESULTS: As demonstrated in Figure 1 for the validation cohort, there was a strong relationship between expected 24-hour urine creatinine based on lean body mass and the measured urinary creatinine (r1⁄40.7, p<0.01), which was stronger than the relationship between measured urinary creatinine and weight (r1⁄40.5, p<0.01). Using the traditional metric of Cr/Kg, 38% of patients in our cohort were considered to have an inadequate 24-hour urine collection (Figure 1a), and there more dispersion among inadequate specimens. Using the regression model on the validation set (Figure 1b), 15% of specimens were considered inadequate, and the majority were due to under collection. CONCLUSIONS: Urinary creatinine is more strongly correlated to an individuals muscle mass rather than body weight. Our regression model demonstrated the utility of a lean body mass based 24-hour creatinine estimator that improves the ability to determine the adequacy of a 24-hour urine collection.