Severe skin necrosis associated with heparin in hemodialysis.

Skin necrosis is a well-recognized although rare complication of continuous heparin therapy. We report the case of a 66-year-old diabetic woman with end-stage renal failure who received intermittent intravenous heparin during hemodialysis. She developed severe necrotic cutaneous ulcers over both legs, with typical histological findings. Thrombocytopenia never occurred but platelet studies demonstrated enhanced aggregation when heparin was added in vitro. Platelet-aggregating immunoglobulins produced in response to heparin can lead to thrombotic events. Thrombocytopenia usually develops prior to the onset of cutaneous lesions, but as in this case, may be absent. Heparin should be discontinued when the condition is recognized. Unfortunately, a poor outcome is frequently observed.

Acetazolamide in hemodialysis patients: a rational use after ocular surgery.

Acetazolamide is a weak diuretic used to decrease production of aqueous humor in the eye. Hemodialysis patients undergoing ocular surgery may benefit from acetazolamide; however, no pharmacokinetic data are available for this group of patients. We report a patient who received acetazolamide 250 mg every 6 hours after ophthalmic surgery and developed reversible neurological side effects associated with very high plasma concentrations. Using pharmacokinetic analysis, we suggest an alternate administration of acetazolamide for end-stage renal patients.

Irreversible renal failure associated with triamterene.

A 66-year-old man was admitted with acute oliguric renal failure. The patient was known to have chronic heart failure (ejection fraction 13%) and his medication included furosemide, digoxin and triamterene. Physical examination was unremarkable, and blood pressure was 170/80 mm Hg. Serum creatinine was 1,173 mumol/l. Renal ultrasound, CT scan and angiogram were normal. Despite correction of potential reversible factors and discontinuation of triamterene, renal function did not improve. Renal biopsy showed tubular obstruction with deposition of birefringent crystals and interstitial lymphocytic infiltration; the crystals emitted a blue autofluorescence at 425 nm, typical of triamterene. Renal tissue contained large amounts of triamterene (6.44 mg/g kidney at the initial biopsy and 400 micrograms/g kidney 5 months later). Triamterene has been previously reported to cause acute reversible renal failure, but to our knowledge, this is the first case of irreversible renal failure due to intratubular obstruction by triamterene crystal deposition.

Sensory nerve conduction in chronic uremic patients during the first six months of hemodialysis.

In an attempt to find the best electrophysiological indicator of improvement for the neuropathy present in patients with chronic renal failure undergoing hemodialysis, several types of nerve conduction were studied at the beginning of dialysis and six months later. Sural nerve conduction and late response latencies were recorded in addition to conventional motor and sensory nerve conductions. After six months of hemodialysis, sensory nerve conduction velocities in the median, ulnar and sural nerves were improved. These values appear to be the most sensitive indices of the beneficial effect of hemodialysis on the neuropathy.

Metronidazole kinetics in dialysis patients.

Five volunteers with normal renal function (NOR) and eight patients with renal insufficiency (REN) were given a single dose of 500 mg metronidazole (MET) intravenously over 26 minutes. Serial venous plasma samples were taken at certain intervals for 30 hours. Four of the eight REN patients were also given the drug at the start of hemodialysis and four simultaneous inflow-outflow samples were taken over 4 hours of dialysis. Plasma MET, the acetic acid metabolite (MTAC), and the hydroxymethyl metabolite (MTOH) were determined by high-pressure liquid chromatography assay. Plasma MET over time curves were analyzed with a nonlinear curve-fitting computer program (ASAAM-27) which employed a two-compartment open model. Plasma MET concentrations were similar in the NOR and REN groups. The volumes of distribution for MET--both V1 and Vdss--were similar in the two groups. Moreover, renal insufficiency did not affect the beta half-life (6.5 hours) or the plasma clearance (10.1 L/hr) of MET. Metabolite concentrations peaked at about 12 hours in both groups, but peak MTAC was five times higher in the REN group and peak MTOH twofold higher. Plasma clearance of MET by dialysis averaged 4.0 L/hr at 30 minutes, but thereafter ranged from 2.9 to 4.2 L/hr. Clearance of MTAC ranged from 5.8 to 7.8 L/hr and that of MTOH 2.7 to 5.6 L/hr. We concluded that renal failure does not alter MET disposition but is associated with significant accumulation of the metabolites of MET, possibly requiring a dose reduction. Moreover, an 8-hour hemodialysis eliminates approximately 50% of an administered dose of MET.

Biologic activity of metronidazole in plasma and urine of volunteers with normal or impaired renal function.

In this study, we have compared a bioassay procedure with high-pressure liquid chromatography (HPLC) for the determination of metronidazole levels in serum and urine. Plasma and urine of volunteers with normal or impaired renal function were obtained at various intervals after a single intravenous dose of 500 mg metronidazole. In plasma of normal volunteers 30 hours after dosing, the bioassay gave results comparable to the total values of the parent compound plus metabolites. In patients with renal failure, the course of the plasma regression curve of metronidazole as measured by the bioassay procedure was intermediate between the values of metronidazole alone and the total values of parent compound plus metabolites. Recovery of metronidazole activity in urine, as determined by this bioassay method, was somewhat less than one half (in normal volunteers) to one quarter (in patients with renal failure) of metronidazole plus metabolites as measured by HPLC. These discrepancies might be explained by the lower antibacterial activity of the hydroxy (congruent to 40%) and acetic acid (congruent to 2%) metabolites as compared with that of the parent compound in the test system used.

Intramural esophageal bleeding in a hemodialysis patient.

A case of intramural esophageal hemorrhage in a hemodialysis patient is described. The hemorrhage followed an episode of vomiting and violent retching. Spontaneous resolution occurred with conservative management. The clinical course resembled that of previous case reports of intramural esophageal hemorrhage, whether or not associated with chronic renal failure and intermittent hemodialysis.