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Purpose: The safety of high-dose iron sucrose infusion in hospitalized patients with chronic kidney disease was studied., Methods: A retrospective analysis was conducted at a 478-bed community hospital. A medical informatics search was performed to identify all hospitalized patients who were prescribed i.v. iron sucrose to deliver elemental iron 300 mg every other day for three doses between January and December 2002. Patients were eligible for inclusion in the analysis if they had chronic kidney disease, had an estimated creatinine clearance of <60 mL/min, and were prescribed the above regimen. Information on iron administration, vital signs, hematologic values, and iron indexes was gathered from patients' medical records. Medical record review was also used to identify possible adverse events., Results: A total of 73 patients met eligibility criteria and received a total of 167 doses of iron sucrose. Twenty adverse events were judged as possibly related to iron sucrose administration and included nausea (n = 8 events), reduced blood pressure (n = 4), vomiting (n = 2), dysgeusia (n = 2), constipation (n = 2), fatigue (n = 1), and anxiety (n = 1). The majority of these adverse events were low in severity, as determined by an objective scale. No severe adverse events occurred. There was no association between infusion rate and the occurrence of potential adverse events (p = 0.44)., Conclusion: Every-other-day i.v. infusion of iron sucrose, to deliver elemental iron 300 mg/dose, was associated with adverse events that were relatively uncommon, minor in severity, and unlikely to require medical intervention.

Unlabelled: Measuring total body water in peritoneal dialysis patients using an ethanol dilution technique., Background: The accuracy with which total body water (TBW) is estimated is a direct determinant of the reliability of Kt/V urea measurements in peritoneal dialysis (PD) patients. Ethanol dilution has been previously shown to be a reliable measure of TBW. Advances in breath alcohol technology make this a feasible clinical tool., Methods: We gave 19 fasting chronic PD patients 0.3 g/kg of ethanol (EtOH) orally on two separate occasions. Breath alcohol concentrations (BrACs), determined by dual-beam infrared analysis, were recorded at baseline and periodically thereafter until BrACs were less than 0.01%. The TBW was then determined by standard pharmacokinetic techniques., Results: TBW measurements were reproducible, with a mean between-run difference of -0.004 liter/kg (95% limits of agreement -0.040 to 0. 032 by Bland-Altman). The Watson equations tended to underestimate TBW, with a mean difference (EtOH - Watson) of +3.0 liters (SD 4.0 liters, P = 0.004) and a mean absolute difference of 4.1 liters (SD 2.7 liters, range -4.4 to 9.5 liters). Kt/V was calculated from dialysate and urine collection, using V as determined from TBW estimates from EtOH and Watson. The mean Kt/V(EtOH) was 2.31 (SD 0. 50) compared with 2.46 (SD 0.52) using Watson. The mean absolute difference between the two Kt/V estimates was 0.26 (SD 0.20, range -0.87 to 0.57), with Kt/V overestimated by Watson in 14 patients. EtOH was well tolerated, and the procedure was completed in about four hours., Conclusions: Measuring V by the BrAC technique does not require blood sampling, is reliable, and is reproducible. It is a potentially useful method for a periodic determination of volume that may allow for more accurate Kt/V measurement in PD patients.

Objective: To investigate the pharmacokinetic characteristics of intraperitoneal fluconazole in patients undergoing continuous cycling peritoneal dialysis (CCPD)., Design: Prospective, nonrandomized, single-dose, open-label study., Participants: Five noninfected volunteer CCPD patients., Interventions: Patients received a single dose of intraperitoneal fluconazole 200 mg during their long daytime dwell. Blood samples were collected before and 1, 3, 6, 12 (end of first dwell), 24 (after overnight cycling), 48, 72, 96, and 120 hours after dosing. Used dialysate was collected throughout the study. Unless the patient was anuric, urine was collected for the first 48 hours., Main Outcome Measure: Fluconazole concentrations were assayed by gas-liquid chromatography. Pharmacokinetic parameters were calculated using standard noncompartmental techniques., Results: The bioavailability of intraperitoneal fluconazole was 96% +/- 2% over a 12-hour dwell, absorption half-life was 2.5 +/- 1.2 hours, serum elimination half-life was 71.65 +/- 12.76 hours, and volume of distribution was 0.66 +/- 0.13 L/kg. Peritoneal clearance was 5.96 +/- 0.93 mL/min and proportional to total dialysate volume. Renal clearance was proportional to renal creatinine clearance., Conclusions: Current treatment guidelines for fungal peritonitis suggest fluconazole 200 mg intraperitoneally every 24 hours. Our data suggest that this dose, administered every 48 hours, is more than sufficient to maintain serum and peritoneal concentrations above the minimum inhibitory concentration for most Candida spp. Other factors, such as residual renal function and dialysis prescription, may also need to be considered.

Aminoguanidine is an investigational agent that may slow or prevent many diabetes-related complications. Since the elimination of aminoguanidine is dependent on renal function, its pharmacokinetics was investigated in eight chronic renal failure patients maintained on hemodialysis. Each patient received 300 mg of aminoguanidine hydrochloride during both an interdialytic and an intradialytic period. During the interdialytic period, the maximum aminoguanidine concentration (Cmax) and time to reach Cmax was 4.5 micrograms/mL and 1.5 hours, respectively. The terminal elimination half-life in these patients was prolonged (37.9 hours). The renal clearance was 2.1 mL/min. Only 8.7% of the administered dose was recovered unchanged in the urine, which is markedly reduced from what is recovered in urine in subjects with normal renal function. There was a positive correlation between the renal clearance of aminoguanidine and the patients' residual renal function (P < 0.05). During hemodialysis, the half-life of aminoguanidine was shortened to 3.9 hours. The hemodialysis clearance of aminoguanidine was 203.6 mL/min. After cessation of hemodialysis, a significant rebound in plasma aminoguanidine concentrations (mean, 39%) was observed. Thus, the dose of aminoguanidine hydrochloride will need to be significantly reduced in patients with end-stage renal disease. Given the interdialytic and intradialytic pharmacokinetics of aminoguanidine, three times weekly dosing after each hemodialysis session is suggested.