Robert M. Kalicki

Sodium Thiosulfate Pharmacokinetics in Hemodialysis Patients and Healthy Volunteers

BACKGROUND AND OBJECTIVES Vascular calcification is a major cause of morbidity and mortality in dialysis patients. Human and animal studies indicate that sodium thiosulfate (STS) may prevent the progression of vascular calcifications. The pharmacokinetics of STS in hemodialysis patients has not been investigated yet. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS STS was given intravenously to 10 hemodialysis patients on- and off-hemodialysis. Additionally, STS was applied to 9 healthy volunteers once intravenously and once orally. Thiosulfate concentrations were measured by using a specific and sensitive HPLC method. RESULTS In volunteers and patients, mean endogenous thiosulfate baseline concentrations were 5.5 ± 1.82 versus 7.1 ± 2.7 μmol/L. Renal clearance was high in volunteers (1.86 ± 0.45 ml/min per kg) and reflected GFR. Nonrenal clearance was slightly, but not significantly, higher in volunteers (2.25 ± 0.32 ml/min per kg) than in anuric patients (2.04 ± 0.72 ml/min per kg). Hemodialysis clearance of STS was 2.62 ± 1.01 ml/min per kg. On the basis of the nonrenal clearance and the thiosulfate steady-state serum concentrations, a mean endogenous thiosulfate generation rate of 14.6 nmol/min per kg was calculated in patients. After oral application, only 4% of STS was recovered in urine of volunteers, reflecting a low bioavailability of 7.6% (0.8% to 26%). CONCLUSIONS Given the low and variable bioavailability of oral STS, only intravenous STS should be prescribed today. The biologic relevance of the high hemodialysis clearance for the optimal time point of STS dosing awaits clarification of the mechanisms of action of STS.

Use of the pentasaccharide fondaparinux as an anticoagulant during haemodialysis

No data about the use of the pentasaccharide fondaparinux, a highly selective indirect inhibitor of factor Xa, in patients treated with haemodialysis are available. Therefore, we investigated the pharmacokinetics and -dynamics of fondaparinux in 12 patients during haemodialysis. The anti-Xa activity (expressed as fondaparinux equivalent) was monitored, a semiquantitative clotting scale (SQCS) ranging from 0 (no visible traces of coagula) to 3 (complete clotting of the dialysis circuit) was applied, and the digital compression time necessary to achieve haemostasis at the puncture site was determined. After an initial period, when the regular heparin dose was replaced once weekly by fondaparinux, 0.05 mg/kg, the pentasaccharide was administered for nine consecutive haemodialysis sessions. Peak anti-Xa activity increased from 0.61 +/- 0.14 microg/l after the first dose to 0.89 +/- 0.24 microg/l after dose 9 (P < 0.001), whereas predialysis anti-Xa activity steadily rose to 0.32 +/- 0.09 microg/l (P < 0.001). A sufficient but slightly less effective anticoagulation with a mean SQCS of 1.19 +/- 0.71 (n = 121) was obtained by fondaparinux as compared with 0.65 +/- 0.58 (n = 60, P < 0.005) by 4,825 +/- 1,703 U of unfractionated heparin. Mean digital compression time rose slightly during fondaparinux from 23.7 +/- 7.4 minutes to 24.8 +/- 7.5 minutes (P < 0.05) and, more important, six of the 12 patients reported minor bleeding problems during the interdialytic interval. Thus, fondaparinux can be used to prevent circuit clotting during haemodialysis; however, accumulation results in an interdialytic increase of anti-Xa activity. Therefore, fondaparinux should be reserved for patients requiring systemic anticoagulation on the days off dialysis.

Red Cell Survival in Relation to Changes in the Hematocrit: More Important than You Think

The management of anemia in patients with chronic renal failure has greatly improved with the availability of recombinant human erythropoietin in the late 1980s, leading to a considerable reduction in mortality and morbidity and to an improvement in quality of life. The findings from recent controlled clinical outcome trials have resulted in a rather narrow, generally accepted therapeutic hematocrit target range. However, currently available dosing algorithms do not permit achievement and maintenance of target values within the therapeutic range in many patients. One possible explanation for this failure may be the ignorance of a finite erythrocyte lifespan not integrated into most algorithms. The purpose of this article is to underline the essential role played by the erythrocyte lifespan in the erythropoietic response to recombinant human erythropoietin and to encourage the integration of this concept in the future development of computer-assisted decision support systems.

Clinical Validation of a Peritoneal Dialysis Prescription Model in the PatientOnLine Software

Peritoneal transport characteristics and residual renal function require regular control and subsequent adjustment of the peritoneal dialysis (PD) prescription. Prescription models shall facilitate the prediction of the outcome of such adaptations for a given patient. In the present study, the prescription model implemented in the PatientOnLine software was validated in patients requiring a prescription change. This multicenter, international prospective cohort study with the aim to validate a PD prescription model included patients treated with continuous ambulatory peritoneal dialysis. Patients were examined with the peritoneal function test (PFT) to determine the outcome of their current prescription and the necessity for a prescription change. For these patients, a new prescription was modeled using the PatientOnLine software (Fresenius Medical Care, Bad Homburg, Germany). Two to four weeks after implementation of the new PD regimen, a second PFT was performed. The validation of the prescription model included 54 patients. Predicted and measured peritoneal Kt/V were 1.52 ± 0.31 and 1.66 ± 0.35, and total (peritoneal + renal) Kt/V values were 1.96 ± 0.48 and 2.06 ± 0.44, respectively. Predicted and measured peritoneal creatinine clearances were 42.9 ± 8.6 and 43.0 ± 8.8 L/1.73 m(2)/week and total creatinine clearances were 65.3 ± 26.0 and 63.3 ± 21.8 L/1.73 m(2) /week, respectively. The analysis revealed a Pearsons correlation coefficient for peritoneal Kt/V of 0.911 and Lins concordance coefficient of 0.829. The value of both coefficients was 0.853 for peritoneal creatinine clearance. Predicted and measured daily net ultrafiltration was 0.77 ± 0.49 and 1.16 ± 0.63 L/24 h, respectively. Pearsons correlation and Lins concordance coefficient were 0.518 and 0.402, respectively. Predicted and measured peritoneal glucose absorption was 125.8 ± 38.8 and 79.9 ± 30.7 g/24 h, respectively, and Pearsons correlation and Lins concordance coefficient were 0.914 and 0.477, respectively. With good predictability of peritoneal Kt/V and creatinine clearance, the present model provides support for individual dialysis prescription in clinical practice. Peritoneal glucose absorption and ultrafiltration are less predictable and are likely to be influenced by additional clinical factors to be taken into consideration.

The Validation of a New Visual Anaemia Evaluation Tool HemoHue HH1 in Patients with End-Stage Renal Disease.

In chronic haemodialysis patients, anaemia is a frequent finding associated with high therapeutic costs and further expenses resulting from serial laboratory measurements. HemoHue HH1, HemoHue Ltd, is a novel tool consisting of a visual scale for the noninvasive assessment of anaemia by matching the coloration of the conjunctiva with a calibrated hue scale. The aim of the study was to investigate the usefulness of HemoHue in estimating individual haemoglobin concentrations and binary treatment outcomes in haemodialysis patients. A prospective blinded study with 80 hemodialysis patients comparing the visual haemoglobin assessment with the standard laboratory measurement was performed. Each patients haemoglobin concentration was estimated by seven different medical and nonmedical observers with variable degrees of clinical experience on two different occasions. The estimated population mean was close to the measured one (11.06 ± 1.67 versus 11.32 ± 1.23 g/dL, P < 0.0005). A learning effect could be detected. Relative errors in individual estimates reached, however, up to 50%. Insufficient performance in predicting binary outcomes (ROC AUC: 0.72 to 0.78) and poor interrater reliability (Kappa < 0.6) further characterised this method.

Sweet and sour—a patient with life-threatening metabolic acidosis and acute renal failure

A 49-year-old man consulted the emergency department with a brief history of moderate headache, anomia and ataxia. There was no fever, and no evidence of infection, trauma or alcohol intake. His medications included mirtazepin and escitalopram for a history of depression. On first examination, the patient was confused and incoherent without focal neurologic signs. Electrocardiogram, head CT-scan, chest X-ray and lumbar puncture showed no abnormalities. Initial laboratory findings (haematology, serum electrolytes, creatinine, urea, glucose, C-reactive protein, ethanol) were within normal limits. A moderate leucocytosis of 13.3 g/l was noted. Could this be basilartype migraine or something else? In the course of the following hours, the patient developed hyperventilation. Why is he hyperventilating? Could it be a psychogenic cause? Blood gas analysis showed a pronounced metabolic acidosis (pH 7.2, base excess −18.4 mmol/l, serum bicarbonate 6.2 mmol/l). What would be your next step? Giving a bicarbonate infusion? Measure the anion and the osmolar gap.

Disseminated cryptococcal infection in a patient who had kidney transplant: discrepancy between clinical symptoms and microbiological findings

A 29-year-old man complained of a 2-day history of frontal headache and new-onset fever but no other symptoms. Two months prior to admission, he underwent his third kidney transplantation. Clinical and laboratory examinations were unremarkable. Brain MRI showed a meningeal irritation consistent with viral meningitis. A diagnosis of cryptococcal meningitis and fungaemia was made after detection of a remarkably high and visible load of Cryptococcus neoformans in the cerebrospinal fluid.