Faculty Bibliography

Thrombosis of hemodialysis vascular access grafts represents a major medical and economic burden. Experimental and clinical models suggest a role for antiplatelet agents in the prevention of thrombosis. The study was designed to determine the efficacy of the combination of aspirin and clopidogrel in the prevention of graft thrombosis. The study was a randomized, double-blind trial conducted at 30 hemodialysis units at Veterans Affairs medical centers. Participants undergoing hemodialysis with a polytetrafluoroethylene graft in the arm were randomized to receive either double placebos or aspirin (325 mg) and clopidogrel (75 mg) daily. Participants were to be monitored while receiving study medications for a minimum of 2 yr. The study was stopped after randomization of 200 participants, as recommended by the Data Safety and Monitoring Board because of a significantly increased risk of bleeding among the participants receiving aspirin and clopidogrel therapy. The cumulative incidence of bleeding events was significantly greater for those participants, compared with participants receiving placebos [hazard ratio, 1.98; 95% confidence interval (CI), 1.19 to 3.28; P = 0.007]. Twenty-three participants in the placebo group and 44 participants in the active treatment group experienced a bleeding event (P = 0.006). There was no significant benefit of active treatment in the prevention of thrombosis (hazard ratio, 0.81; 95% CI, 0.47 to 1.40; P = 0.45), although there was a trend toward a benefit among participants who had not experienced previous graft thrombosis (hazard ratio, 0.52; 95% CI, 0.22 to 1.26; P = 0.14). In the hemodialysis population, therapy with aspirin and clopidogrel was associated with a significantly increased risk of bleeding and probably would not result in a reduced frequency of graft thrombosis

BACKGROUND: There is a growing body of evidence regarding the association between cystic fibrosis (CF) and nephrolithiasis and the role that Oxalobacter formigenes may have in that association. METHODS: We performed a MEDLINE search of 'cystic fibrosis and nephrolithiasis' and 'Oxalobacter formigenes.' Epidemiological and experimental evidence and possible mechanisms explaining the association were critically reviewed. RESULTS: Of patients with CF, 3.0% to 6.3% are affected with nephrolithiasis, a percentage greater than that of age-matched controls without CF, in whom the rate is 1% to 2%. Studies have suggested possible mechanisms for the association, including hyperuricosuria, hyperoxaluria, primary defects in calcium handling caused by mutation of the CF transmembrane regulator (CFTR), hypocitraturia, and lack of colonization with O formigenes, an enteric oxalate-degrading bacterium. The absence of colonization could be related to frequent courses of antibiotics. CONCLUSION: Although the incidence of stones in patients with CF may be increased compared with controls without CF, many possible mechanisms are implicated. The relative contributions of these mechanisms remain uncertain. Future directions may include specific identification of lithogenic risks and therapy aimed at stone prevention in this population

Fish gallbladders are consumed in rural areas of Asia as a traditional medicine to improve symptoms of arthritis, decreased visual acuity, and impotence. Consumption of large amounts of this traditional medicine can result in systemic toxicities; in particular, acute renal failure. We reviewed records of all admissions to Cho Ray Hospital (Ho Chi Minh City, Vietnam) between January 1995 and December 2000 after this ingestion. Clinical courses and outcomes were similar in 16 of 17 patients. Within hours, patients experienced profuse vomiting (n = 16) and diarrhea (n = 15). All developed acute renal failure, with a mean serum creatinine concentration of 14.7 +/- 3.9 mg/dL (1,299.5 +/- 344.8 micromol/L). Four patients administered intravenous fluid (IVF) developed extracellular fluid volume overload, as did 1 patient not administered IVF. Time to peak creatinine concentration was 8.6 +/- 3.0 days, which was accompanied by decreased urine volume (174.7 +/- 161.6 mL/24 h). Blood pressure remained normal, with a mean arterial pressure of 91 +/- 12 mm Hg. Twelve patients required renal replacement therapy. A mean of 1.9 +/- 1.1 hemodialysis sessions was performed per patient. Sixteen patients recovered renal function; 1 patient died of fulminant hepatic failure. Kidney biopsies showed features of acute tubular injury. Acute renal failure after fish gallbladder ingestion is characterized by a failure to respond to IVF, an 8.6-day interval to peak creatinine level, frequent need for dialysis therapy, and findings on renal biopsy consistent with acute tubular necrosis. Acute renal failure after fish gallbladder ingestion has an excellent prognosis. However, death from fulminant hepatic failure can occur

In 1988, a consensus conference was held at the National Institutes of Health to develop guidelines for prevention and treatment of kidney stones. The recommendations regarding the medical evaluation of stone formers and treatment directed at stone prevention are reviewed. The relevance of those 1988 guidelines is evaluated for continued pertinence. Most of the recommendations promulgated in the consensus statement remain useful today. One significant change is the current consensus that dietary calcium restriction is no longer considered appropriate therapy, as there is no evidence that it actually prevents stones and has as a consequence the potential to worsen bone demineralization

PURPOSE: An increased risk of nephrolithiasis has been associated with the ingestion of grapefruit juice in epidemiological studies. To our knowledge the basis of this effect of grapefruit juice has not been studied previously. We studied the effect of grapefruit juice consumption on urinary chemistry and measures of lithogenicity. MATERIALS AND METHODS: Ten healthy men and women between ages of 25 and 40 years participated. Each subject drank 240 ml. of tap water at least 3 times daily for 7 days during the control period. This period was followed by a second 7 days experimental period during which they drank 240 ml. of grapefruit juice 3 times daily. In each 7-day period urine was collected for 24 hours during the last 3 days. Urine chemical analysis was performed, supersaturations of calcium oxalate, calcium phosphate and uric acid were calculated and urinary lithogenicity was measured. RESULTS: Urine volume and creatinine excretion were the same during the control and experimental periods. Grapefruit juice ingestion was associated with an increase in mean oxalate excretion plus or minus standard deviation of 41.1 +/- 9.2 to 51.9 +/- 12.0 mg. per 24 hours (p = 0.001) and in mean citrate excretion of 504.8 +/- 226.5 to 591.4 +/- 220.0 mg. per 24 hours (p = 0.01). There was no net change in the supersaturation or upper limit of metastability of calcium oxalate, calcium phosphate or uric acid. Crystal aggregation and growth inhibition by urinary macromolecules was not affected by grapefruit juice ingestion. CONCLUSIONS: Offsetting changes in urine chemistry caused by the ingestion of grapefruit juice led to no net change in calculated supersaturation. No changes in lithogenicity were demonstrated. The results do not demonstrate an effect of grapefruit juice for increasing lithogenicity. The basis of the observations of epidemiological studies remain unexplained

BACKGROUND: Iron deficiency remains a common cause of hyporesponsiveness to epoetin in hemodialysis patients. However, considerable controversy exists regarding the best strategies for diagnosis and treatment. METHODS: As part of a multicenter randomized clinical trial of intravenous versus subcutaneous administration of epoetin, we made monthly determinations of serum iron, total iron binding capacity, percentage transferrin saturation, and serum ferritin. If a patient had serum ferritin <100 ng/mL or the combination of serum ferritin <400 ng/mL and a transferrin saturation <20%, he/she received parenteral iron, given as iron dextran 100 mg at ten consecutive dialysis sessions. We analyzed parenteral iron use during the trial, the effect of its administration on iron indices and epoetin dose, and the ability of the iron indices to predict a reduction in epoetin dose in response to parenteral iron administration. RESULTS: Eighty-seven percent of the 208 patients required parenteral iron to maintain adequate iron stores at an average dose of 1516 mg over 41.7 weeks, or 36 mg/week. Only two of 180 patients experienced serious reactions to intravenous iron administration. Two thirds of the patients receiving parenteral iron had a decrease in their epoetin requirement of at least 30 U/kg/week compared with 29% of patients who did not receive iron (P = 0.004). The average dose decrease 12 weeks after initiating iron therapy was 1763 U/week. A serum ferritin <200 ng/mL had the best positive predictive value (76%) for predicting a response to parenteral iron administration, but it still had limited clinical utility. CONCLUSIONS: Iron deficiency commonly develops during epoetin therapy, and parenteral iron administration may result in a clinically significant reduction in epoetin dose. The use of transferrin saturation or serum ferritin as an indicator for parenteral iron administration has limited utility

PURPOSE: We measured the concentration and solubility of cystine in urine from patients with cystinuria or calcium stones and from normal subjects to determine whether urine cystine supersaturation can be calculated from a standard nomogram of solubility versus pH or needs to be measured directly. We also evaluated whether increasing pH of the 24-hour collection recovered enough crystallized cystine to increase cystine supersaturation. MATERIALS AND METHODS: Cystine concentration, pH and usual stone risk factors were measured on 50 ml. aliquots of 24-hour collections from 24 patients with cystinuria, 22 calcium stone formers and 15 normal subjects. After 48 hours of incubation with sodium bicarbonate, a second aliquot was taken from the 24-hour collection for cystine concentration. The original urine at its ambient pH was incubated with an excess of cystine crystals for 24, 48, 72 or 96 hours at 37C to determine solubility and kinetics of equilibration. RESULTS: Cystine solubility varied so widely at any pH range that no predictive nomogram could be relied on for calculating supersaturation. Addition of sodium bicarbonate to the 24-hour urine significantly increased cystine concentration. Urine from stone formers had higher cystine solubility than urine from normal subjects. CONCLUSIONS: Clinical management of cystinuria can be improved by direct measurement of cystine solubility because it varies widely at any given pH. Increasing 24-hour collection pH with sodium bicarbonate additionally improves accuracy of supersaturation measurement by recovering crystallized cystine