Faculty Bibliography

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

A twin study of genetic and dietary influences on nephrolithiasis: A report from the Vietnam Era Twin (VET) Registry. Background. Nephrolithiasis is a complex phenotype that is influenced by both genetic and environmental factors. We conducted a large twin study to examine genetic and nongenetic factors associated with stones. Methods. The VET Registry includes approximately 7500 male-male twin pairs born between 1939 to 1955 with both twins having served in the military from 1965 to 1975. In 1990, a mail and telephone health survey was sent to 11,959 VET Registry members; 8870 (74.2%) provided responses. The survey included a question asking if the individual had ever been told of having a kidney stone by a physician. Detailed dietary habits were elicited. In a classic twin study analysis, we compared concordance rates in monozygotic (MZ) and dizygotic (DZ) twins. We also conducted a cotwin control study of dietary risk factors in twins discordant for stones. Results. Among dizygotic twins, there were 17 concordant pairs and 162 discordant pairs for kidney stones. Among monozygotic twins, there were 39 concordant pairs and 163 discordant pairs. The proband concordance rate in MZ twins (32.4%) was significantly greater than the rate in DZ twins (17.3%) (chi(2)= 12.8; P < 0.001), consistent with a genetic influence. The heritability of the risk for stones was 56%. In the multivariate analysis of twin pairs discordant for kidney stones, we found a protective dose-response pattern of coffee drinking (P= 0.03); those who drank 5 or more cups of coffee were half as likely to develop kidney stones as those who did not drink coffee (OR = 0.4, 95% CI 0.2, 0.9). Those who drank at least 1 cup of milk per day were half as likely to report kidney stones (OR = 0.5, 95% CI 0.3, 0.8). There were also marginally significant protective effects of increasing numbers of cups of tea per day and frequent consumption of fruits and vegetables. Other factors such as the use of calcium supplements, alcohol drinking, consumption of solid dairy products, and the amount of animal protein consumed were not significantly related to kidney stones in the multivariate model. Conclusion. These results confirm that nephrolithiasis is at least in part a heritable disease. Coffee, and perhaps tea, fruits, and vegetables were found to be protective for stone disease. This is the first twin study of kidney stones, and represents a new approach to elucidating the relative roles of genetic and environmental factors associated with stone formation