Richard J. Hamburger

Influence of Hemodialysis on Gentamicin Pharmacokinetics, Removal During Hemodialysis, and Recommended Dosing

BACKGROUND AND OBJECTIVES Aminoglycoside antibiotics are commonly used in chronic kidney disease stage 5 patients. The purpose of this study was to characterize gentamicin pharmacokinetics, dialytic clearance, and removal by hemodialysis and to develop appropriate dosing strategies. Design Setting, Participants, and Measurements: Eight subjects receiving chronic, thrice-weekly hemodialysis with no measurable residual renal function received gentamicin after a hemodialysis session. Blood samples were collected serially, and serum concentrations of gentamicin were determined. RESULTS Median (range) systemic clearance, volume of distribution at steady state, and terminal elimination half-life were 3.89 ml/min (2.69-4.81 ml/min), 13.5 L (8.7-17.9 L), and 39.4 h (32.0-53.6 h), respectively. Median (range) dialytic clearance, estimated amount removed, and percent maximum rebound were 103.5 ml/min (87.2-132.7 ml/min), 39.6 mg (19.7-43.9 mg), and 38.7% (0%-71.8%), respectively. Gentamicin dialytic clearance was statistically significantly related to creatinine dialytic clearance (r(2) = 0.52, P = 0.04), although this relationship is not likely to be strong enough to serve as a surrogate for gentamicin monitoring. The pharmacokinetic model was used to simulate gentamicin serum concentrations over a one-wk period. CONCLUSIONS In clinical situations where gentamicin is used as the primary therapy in a patient receiving hemodialysis with a CAHP hemodialyzer, conventional doses after each dialysis session are not as efficient at achieving treatment targets as predialysis dosing with larger doses.

Primary glomerulonephritis complicating diabetic nephropathy: report of seven cases and review of the literature

Glomerulonephritis has been recognized as a rare complication of diabetes mellitus. The clinical, pathologic, and laboratory findings for 18 diabetic patients were reviewed. Eight of these patients (44 per cent) were found to have primary glomerulonephritis in addition to diabetic nephropathy. Although this series may not represent the true incidence of complicating glomerulonephritis in diabetes, it is probable that the incidence of this condition has been underestimated. An additional 26 previously reported cases are reviewed.

Levofloxacin pharmacokinetics in ESRD and removal by the cellulose acetate high performance-210 hemodialyzer

BACKGROUND No published data are available describing the pharmacokinetics of intravenous levofloxacin in patients with end-stage renal disease (ESRD). Objectives of this study are to determine the pharmacokinetics and dialytic clearance of levofloxacin and develop dosing strategies in these patients. METHODS Eight noninfected subjects receiving long-term thrice-weekly hemodialysis, with no measurable residual renal function, were administered intravenous levofloxacin, 250 mg, over 1 hour after a scheduled hemodialysis session. Blood samples were collected serially during the interdialytic period, during the next intradialytic period, and immediately after the next hemodialysis session. Serum concentrations of levofloxacin were determined by high-performance liquid chromatography. Differential equations describing a 2-compartment open-infusion pharmacokinetic model were fit to each individual subjects serum concentration-time data by iterative nonlinear weighted least-squares regression analysis using Adapt II (Biomedical Simulations Resource, University of Southern California, Los Angeles, CA). Ratios of maximum serum concentration (C(max)) to minimum inhibitory concentration (MIC) were calculated for common respiratory pathogens by using MIC for 90% of isolates (MIC90) data from published studies. RESULTS All subjects completed the study, and no adverse events were reported. Median systemic clearance, volume of distribution at steady state, elimination half-life, and C(max) were 37.0 mL/min (range, 12.8 to 42.7 mL/min), 103.3 L (range, 39.8 to 139.3 L), 34.4 hours (range, 28.4 to 39.3 hours), and 5.2 microg/mL (range, 4.1 to 11.3 microg/mL), respectively. Median dialytic clearance and levofloxacin reduction ratios were 84.4 mL/min (range, 61.8 to 107.6 mL/min) and 0.244 (range, 0.181 to 0.412), respectively. Median C(max)-MIC90 ratios were 10 or greater for Haemophilus influenzae, Moraxella catarrhalis, Enterobacter cloacae, and Klebsiella pneumoniae, approximately 5 for Streptococcus pneumoniae, and less than 1 for Pseudomonas aeruginosa. CONCLUSION The administration of levofloxacin to patients with ESRD as 500 mg initially, followed by 250 mg every 48 hours, will provide adequate C(max)-MIC ratios after the first and subsequent doses for most patients with respiratory tract infections caused by organisms with levofloxacin MICs of 1 microg/mL or less.

Calcitriol in dialysis patients.

We conducted a 7‐month randomized, single, double, single‐blind comparison of calcitriol (1,25(OH)2D3) with vitamin D3 in 22 hemodialysis patients to study the effects on the biochemical abnormalities associated with osteodystrophy. Calcitriol was given for 3 mo. All patients had initial pre study calcium values ≤9.5 mg/100 ml, and phosphate values ≤4.5 mg/100 ml. Data were analyzed using the Normalized Trend Index (NTI). Calcitriol induced a rise in calcium (8.7 to 10.25 mg/100 ml) (p < 0.001) and a fall in alkaline phosphatase (p < 0.005), while D3 had no appreciable effect. The mean dose of calcitriol during treatment was 0.579 µg/day while that for D3 was 706 IU/day. The effect on serum phosphate concentration was variable. Hypercalcemia as high as 13.2 mg/100 ml occurred in 2 of 13 patients on 1,25(OH)2D3, but in every instance promptly returned to normal with dose reduction. No other adverse effects were noted with therapy. We conclude that calcitriol reverses the biochemical abnormalities of osteodystrophy. Since its effects are rapidly reversed with discontinuation, the drug is probably safe as well as effective.

Selection of patients for renal rehabilitation

John Patrick Donohue, MD, i s professor of urology and chairman o f the Transplantation Committee a t Indiana University Medical Center (IUMC) and Veterans Administration Hospital in Indianapolis. He earned his MD degree at Corne!l University Medical College. Richard Hamburger, MD, i s assistant professor of medicine a t IUMC in the Renal-Medicine Division. H e earned his MD degree a t Jefferson Medical College. Stuart Kleit, MD, i s associate professor o f medicine and chief o f the Renal Division at IUMC. H e received his MD degree from the University o f Florida Medical School. Dana L. Shires, Jr., MD, i s associate professor of medicine a t IUMC. Dr. Shires earned an MD degree at the University of Florida. K. P. Bradley, MD, is the former director o f Renal Medicine at the Veterans Hospital in Indianapolis. H e earned his MD degree a t the University of Florida. Aleiandro M. de Quesada, MD, i s assistant professor of medicine at IUMC and staff physician, Renal Medicine at the VA Hospital in Indianapolis. H e earned his MD degree at the University of Havana, Cuba. Angenieta A. Biegel, MD, i s associate professor of Medicine at Indiana University, with an emphasis on clinical immunology and allergy. She received her M D degree from the University of Leiden, Netherlands. A. A. Glover, MD, i s director of surgery a t Marion County General Hospital. H e earned his MD from Vanderbilt University, Nashville, Tan. Austin L. Gardner, MD, i s chief o f the Vascular Clinic, Marion County General Hospital, and on the Transplantation Committee a t IUMC and Methodist Hospital. H e earned his MD degree at Indiana University School o f Medicine and attended the University o f London on a Fulbright Scholarship in Surgery.