Faculty Bibliography

BACKGROUND: Urinary oxalate excretion is an important contributor to calcium oxalate stone formation. Methods of reducing oxalate excretion are not wholly satisfactory, and no controlled trials using them have been performed to prevent stone recurrence. Some lactic acid bacteria can degrade oxalate in vitro. This study sought to reduce urinary oxalate excretion in calcium stone formers with idiopathic hyperoxaluria. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: A randomized, double-blind, placebo-controlled trial was performed of Oxadrop, a mix of four lactic acid bacterium species. This preparation previously reduced oxalate excretion in stone formers with idiopathic and enteric hyperoxaluria. Patients were selected from two stone prevention clinics. Twenty people with calcium stones and idiopathic hyperoxaluria (>40 mg/d) were enrolled and randomly assigned 1:1 in placebo and active preparation arms. Both groups took 3.6 g of granulate each day: Either placebo or the experimental preparation. Participants performed two consecutive 24-h urine collections at baseline, at 28 d of therapy, and at 56 d, after being off the preparation for 4 wk. Diet was replicated at each point. RESULTS: There was no effect of the study preparation: Mean 24-h urinary oxalate excretion in placebo-treated patients was 73.9 mg at baseline and 72.7 mg after treatment, whereas the Oxadrop-treated patients had 59.1 mg at baseline and 55.4 mg after treatment. The preparation was well tolerated; three participants on active treatment experienced mild constipation. CONCLUSIONS: In this randomized, placebo-controlled trial, Oxadrop did not reduce urinary oxalate excretion in participants with idiopathic hyperoxaluria

CONTEXT: High plasma homocysteine levels are a risk factor for mortality and vascular disease in observational studies of patients with chronic kidney disease. Folic acid and B vitamins decrease homocysteine levels in this population but whether they lower mortality is unknown. OBJECTIVE: To determine whether high doses of folic acid and B vitamins administered daily reduce mortality in patients with chronic kidney disease. DESIGN, SETTING, AND PARTICIPANTS: Double-blind randomized controlled trial (2001-2006) in 36 US Department of Veterans Affairs medical centers. Median follow-up was 3.2 years for 2056 participants aged 21 years or older with advanced chronic kidney disease (estimated creatinine clearance < or =30 mL/min) (n = 1305) or end-stage renal disease (n = 751) and high homocysteine levels (> or = 15 micromol/L). INTERVENTION: Participants received a daily capsule containing 40 mg of folic acid, 100 mg of pyridoxine hydrochloride (vitamin B6), and 2 mg of cyanocobalamin (vitamin B12) or a placebo. MAIN OUTCOME MEASURES: The primary outcome was all-cause mortality. Secondary outcomes included myocardial infarction (MI), stroke, amputation of all or part of a lower extremity, a composite of these 3 plus all-cause mortality, time to initiation of dialysis, and time to thrombosis of arteriovenous access in hemodialysis patients. RESULTS: Mean baseline homocysteine level was 24.0 micromol/L in the vitamin group and 24.2 micromol/L in the placebo group. It was lowered 6.3 micromol/L (25.8%; P < .001) in the vitamin group and 0.4 micromol/L (1.7%; P = .14) in the placebo group at 3 months, but there was no significant effect on mortality (448 vitamin group deaths vs 436 placebo group deaths) (hazard ratio [HR], 1.04; 95% CI, 0.91-1.18). No significant effects were demonstrated for secondary outcomes or adverse events: there were 129 MIs in the vitamin group vs 150 for placebo (HR, 0.86; 95% CI, 0.67-1.08), 37 strokes in the vitamin group vs 41 for placebo (HR, 0.90; 95% CI, 0.58-1.40), and 60 amputations in the vitamin group vs 53 for placebo (HR, 1.14; 95% CI, 0.79-1.64). In addition, the composite of MI, stroke, and amputations plus mortality (P = .85), time to dialysis (P = .38), and time to thrombosis in hemodialysis patients (P = .97) did not differ between the vitamin and placebo groups. CONCLUSION: Treatment with high doses of folic acid and B vitamins did not improve survival or reduce the incidence of vascular disease in patients with advanced chronic kidney disease or end-stage renal disease. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00032435

The treatment of cystinuria is hampered by methods used to measure urinary lithogenicity. Most cystine assays cannot reliably distinguish cystine from soluble thiol drug-cysteine complexes. We used a solid-phase assay of urinary cystine capacity in a large sample of patients with cystinuria. A known amount of solid-phase cystine is added to urine. In supersaturated urine, cystine precipitates onto added crystals, so the solid phase recovered after incubation will be greater than that added. We studied the effect of cystine-binding thiol drugs (CBTD) to solubilize cystine and determined correlates of cystine capacity in patients who were and were not taking CBTD. Increasing concentrations of D-penicillamine, tiopronin and captopril dissolved cystine in urine with similar efficacy. A general linear model in which 24 h cystine excretion was the dependent variable showed that creatinine, urea nitrogen, and sodium excretions were associated with cystine excretion (P<0.02, all three). Urine volume, pH, and cystine excretion strongly correlated with cystine capacity (P<0.001). Tiopronin had no effect on supersaturation in a cross-sectional analysis. A subset of supersaturated samples, with negative cystine capacity, occurred mainly among women not taking CBTD. For this subset, capacity differed significantly between CBTD users and non-users; use of CBTD avoided extremes of supersaturation. Female enrichment in the supersaturated group was accounted for in part by underprescription of CBTD to women. This assay of cystine capacity was reliable in the presence of CBTD. It should be useful in monitoring patients' response to dietary interventions and administration of fluid, citrate, and CBTD.

Extracorporeal elimination of drugs and toxins is a critical component in the management of poisonings, though specific techniques and indications remain a matter of debate. Conventional hemodialysis is frequently the treatment of choice because of its widespread availability and proven effectiveness for certain drugs and toxins. With the increased availability of continuous renal replacement therapy (CRRT) modalities, there is yet another therapeutic option, but one that has yet to find a definitive role in this field. The continuous nature of these therapies is attractive for the management of acute renal failure, but the relatively slower clearance rates as compared to conventional hemodialysis is a distinct drawback in patients with acute xenobiotic-induced toxicity. There are abundant case reports as well as a few small case series in the medical literature documenting the use of CRRT, but specific techniques and the clinical outcomes vary considerably. Therefore one cannot draw definitive conclusions regarding benefit. Some patients, particularly those who are hemodynamically unstable and are not candidates for conventional hemodialysis, may warrant a trial of CRRT. However, at the present time, routine use for the treatment of poisoning is not supported. Controlled trials to better clarify its role would be beneficial, though such studies would be extremely difficult to conduct in this field. We believe that the intelligent application of extracorporeal modalities requires a thorough knowledge of drug pharmacokinetics, of the techniques utilized, and a skeptical analysis of the available literature

Chitosan is a positively charged non-absorbable cellulose-like fibrillar biopolymer derived from shellfish which forms films with negatively charged surfaces. We hypothesized that negatively charged oxalate in the intestinal lumen could attach to the positively charged tertiary amino group of chitosan. We studied the effects of chitosan on intestinal oxalate absorption by measuring urinary oxalate excretion following an oral oxalate load with and without accompanying oral chitosan. The subjects consumed a fixed diet and collected urine for 24 h, in divided periods, during control and experimental protocols. Urine was collected with HCl and thymol as a preservative. For the control period, the subjects consumed an oxalate load, 50 g of cooked spinach, with water for lunch; the post-prandial urine collection was divided into three periods of 2 h. For the experimental period, 1 week later, the subjects consumed the same diet as that during the control period, but added 2 g of chitosan to the oxalate load. Post-prandial urinary oxalate excretion was expressed as mg oxalate/g creatinine. The spinach load was associated with a significant post-prandial increase in urinary oxalate during the control period of 25.7+/-12.8 mg/g creatinine. Accompanying the oxalate load with chitosan was well tolerated. There was no decrease in post-prandial urinary oxalate excretion during the experimental period: oxalate excretion rose by 31.3+/-16.9 mg/g creatinine (P=0.57, NS). We conclude that chitosan does not reduce acute intestinal oxalate absorption and therefore does not affect post-prandial urinary oxalate excretion

BACKGROUND: Charcoal hemoperfusion (CHP) has been one of the preferred methods to enhance the elimination of certain toxins in selected poisoned patients. However, the availability of CHP may be limited because of the expense of cartridges, their narrow indications, and their limited shelf life. Improvements in hemodialysis (HD) technology may contribute to making CHP obsolete. We investigated the availability of CHP in in-hospital HD units at hospitals receiving ambulances dispatched through New York City's emergency response system, hereafter referred to as 911-receiving hospitals, and their recent history of CHP use in poisoned patients. METHODS: The medical directors or managers of all in-hospital HD units in the 911-receiving hospitals of New York City were contacted by E-mail and/or telephone. Participants were administered a standard survey that included questions regarding the availability of CHP cartridges and the date and indication for last CHP use. Participants at institutions that did not stock CHP cartridges were questioned about their opinions on the utility of CHP. RESULTS: Forty-two in-hospital HD units were surveyed, of which 34 (81%) completed the survey. Ten units (29%) had CHP cartridges available for immediate use. Each of these 10 units stocked between 1 and 4 adult-size CHP cartridges, and 1 unit stocked 2 pediatric-size CHP cartridges. Nine units had in-date CHP cartridges, and 1 unit had only expired CHP cartridges. Only 3 units performed CHP in the past 5 years (2 units, theophylline poisonings; 1 unit, aluminum overload). In the 24 units without CHP cartridges, 21 directors believed that most common toxins could be removed effectively through HD and thus CHP rarely was indicated. Only 1 director cited expense as a factor in not stocking CHP cartridges. Two directors reported no specific reason for not stocking the cartridges. CONCLUSION: CHP cartridges are available in only approximately one third of 911-receiving hospitals in New York City. CHP is infrequently performed to enhance toxin elimination in poisoned patients

BACKGROUND: Because chronic kidney disease (CKD) may be associated with gastrointestinal bleeding from trivial mucosal lesions, we hypothesized that the predictive value of a positive fecal occult blood test (FOBT) result for clinically important colonic lesions would decrease as the stage of CKD worsened. METHODS: We prospectively identified 1,225 consecutive asymptomatic average-risk patients who were referred for colonoscopy to evaluate a positive FOBT result. Using the Modification of Diet in Renal Disease equation, we estimated glomerular filtration rate (GFR) and staged the severity of CKD by using standard criteria as follows: normal/stage 1 (GFR > or = 90 mL/min/1.73 m2 [> or = 1.50 mL/s]), stage 2/3 (GFR 30 to 89 mL/min/1.73 m2 [0.50 to 1.48 mL/s]), and stage 4/5 (GFR < 30 mL/min/1.73 m2 [< 0.50 mL/s] or dialysis). RESULTS: Clinically important lesions were identified in 23.9% of 531 individuals with none/stage 1 CKD, 32.8% of 497 subjects with stage 2/3 CKD, and 42.6% of 197 patients with stage 4/5 CKD (P < 0.001). Compared with patients with none/stage 1 CKD, adjusted odds of identifying a clinically important lesion were 1.61 (95% confidence interval, 1.21 to 2.15) in subjects with stage 2/3 CKD and 2.33 (95% confidence interval, 1.62 to 3.36) in patients with stage 4/5 CKD. Prevalences of adenomas of 1 cm or greater (15.1% versus 20.1% versus 22.8%; P = 0.007), carcinomas (5.1% versus 10.1% versus 13.2%; P < 0.001), and vascular ectasias (1.7% versus 2.4% versus 6.1%; P = 0.003) increased with the severity of CKD. CONCLUSION: Contrary to our initial hypothesis, we found that the predictive value of a positive FOBT result for clinically important colonic lesions increased as the severity of CKD worsened