Patient Perspectives on Renal Replacement Therapy Modality Choice: A Multicenter Questionnaire Study on Bioethical Dimensions.

Background:Peritoneal dialysis (PD) incidence and prevalence in Germany are low compared with hemodialysis (HD), an underachievement with multifactorial causes. Patient perspectives on renal replacement therapy (RRT) choice play a growing role in research. To date, and to the best of our knowledge, the importance of bioethical dimensions in the context of RRT choice has not been analyzed. The aim of this multicenter questionnaire study was to delineate differences in patient perspectives of PD vs HD in terms of bioethical dimensions, thus helping nephrologists target potential PD candidates more efficiently.Methods:A total of 121 stable outpatients from 2 tertiary care hospitals and 4 dialysis clinics were surveyed for bioethical dimensions ("autonomy," "beneficence," "non-maleficence," "justice," and "trust") with ranking and Likert scale items. Inclusion criteria were RRT > 3 months, age ≥ 18 years, and sufficient cognitive and language skills.Results:A surprisingly high percentage of patients felt excluded from the RRT choice process. Peritoneal dialysis patients were more critical of RRT. They used more versatile information sources on RRT, whereas HD patients were mainly informed by their nephrologist. Peritoneal dialysis patients felt more often dissatisfied with RRT than HD patients and had less trust in their co-patients. However, PD patients felt less autonomy impairment regarding body integrity, fluid balance, and dialysis in general.Conclusions:Our study demonstrates that PD patients showed more scrutiny of their situation as patients, especially their co-patients. Their treatment empowered them toward feeling more autonomous than HD patients. These new insights into patient perspectives on RRT choice might facilitate modality choice for nephrologists.

Short- and long-term effects of the use of RAAS blockers immediately after renal transplantation.

BACKGROUND: The efficacy and safety of renin angiotensin aldosterone system blockers (RAASB's) if introduced immediately after renal transplantation have not been extensively investigated. METHODS: The medical charts of 142 kidney transplant recipients who received a RAASB in the early postoperative period and of 114 matched controls were analyzed. The RAASB was given primarily for blood pressure control. RESULTS: 117 patients continued to receive and 50 controls remained continuously free of the RAASB in the first year. The RAASB was added on average at postoperative day 8 and the mean duration of follow-up was 5.4 years. Systolic, blood pressure at treatment initiation was increased in the RAASB group (150 ± 17 vs. 141 ± 16, p < 0.001). At discharge from hospital and during follow-up blood pressure was similar in both groups, without differences in GFR, potassium and proteinuria. The endpoints "graft failure" and "graft failure or death from any cause" were significantly better in patients treated with RAASB's (p = 0.03 and p = 0.04, respectively). The treatment effects in the RAASB group persisted even after adjustment for demographic parameters, immunological risk factors, peritransplant risk factors, duration of dialysis prior to transplantation and medical comorbidities. CONCLUSIONS: Thus, RAASB's can be used effectively and safely to treat hypertension in the early postoperative period after kidney transplantation and are renoprotective in the long term.

Cotrimoxazole plasma levels, dialyzer clearance and total removal by extended dialysis in a patient with acute kidney injury: risk of under-dosing using current dosing recommendations.

BACKGROUND: Dosing of antibiotics in critically ill patients is challenging. It becomes even more difficult if renal or hepatic impairment ensue. Modern means of renal replacement therapy are capable of removing antibiotics to a higher rate than decades ago, leaving clinicians with a high degree of uncertainty concerning the dose of antibiotics in this patient population. Cotrimoxazole, a combination of trimethoprim (TMP) and sulfamethoxazole (SMX) is frequently used in the treatment of several infections including Pneumocystis jirovecii pneumonia (PCP). CASE PRESENTATION: Here we describe a patient with acute kidney injury in which we investigated the TMP and SMX levels during the course of an ICU stay. Cotrimoxazole was administered every six hours i.v. in a dose of TMP/SMX 15/75 mg/kg/day. Extended dialysis was performed with a high-flux dialyzer. Blood samples, as well as pre- and postdialyzer samples and aliquots of the collected spent dialysate were collected.Observed peak concentrations (Cmax) were 7.51 mg/l for TMP and 80.80 mg/l for SMX. Decline of blood levels during extended dialysis (TMP 64%; SMX 84%) was mainly due to removal by the dialysis procedure, illustrated by the high dialyzer clearances (median of 4 extended dialysis sessions: TMP 94.0 / SMX 51.0 ml/min), as well as by the absolute amount of both substances in the collected spent dialysate (median of 6 extended dialysis sessions: TMP 556 mg / SMX 130 mg). Within the limitation of a case report our data from 4 consecutive extended dialysis sessions suggest that this procedure substantially removes both TMP and SMX. CONCLUSIONS: Dose reduction, which is usually advocated in patients with acute kidney injury under renal replacement therapy, might lead to significant under-dosing. Pharmacokinetic studies for TMP/SMX dosing in this patient population are necessary to allow adequate dosing.

New high-cutoff dialyzer allows improved middle molecule clearance without an increase in albumin loss: a clinical crossover comparison in extended dialysis.

BACKGROUND: Accumulation of middle molecules is thought to have adverse effects in patients with acute kidney injury (AKI). Elimination of middle molecules by non-convective means, i.e. hemodialysis, remains difficult. The aim of the study was to investigate the removal characteristics of a new high permeability membrane in AKI patients undergoing extended dialysis (ED). PATIENTS AND METHODS: We performed a prospective, crossover study comparing the EMiC2 dialyzer (1.8 m(2), FMC, Germany) and AV 1000S (1.8 m(2), FMC) in 11 critically ill patients with AKI. ß2-Microglobulin, cystatin c, creatinine, and urea were measured before and after 0.5, 5.0 and 10 h of ED. Serum reduction ratios, dialyzer clearances, and mass in the total collected dialysate were determined. RESULTS: Dialyzer clearance of ß2-microglobulin (EMiC2: 52 ± 1.7 ml/min, AV 1000S: 41.7 ± 1.5 ml/min, p = 0.0002) and cystatin c (EMiC2: 47.2 ± 1.2 ml/min, AV 1000S: 34.2 ± 2.3 ml/min, p < 0.0001) was markedly different, as was the reduction of serum levels of ß2-microglobulin (EMiC2: 54.3 ± 3.6%, AV 1000S: 39.1 ± 4.5%, p = 0.025) and cystatin c (EMiC2: 38.9 ± 2.6%, AV 1000S: 28.0 ± 3.9%, p = 0.043). Additionally, we observed a higher total amount of these substances in the collected dialysate. There was no significant difference in the total amount of albumin eliminated per treatment. CONCLUSION: The new EMiC2 dialyzer enhances removal of middle molecules without an increase in albumin loss. The clinical relevance of this finding needs to be determined.

Angiopoietin-2 is a potential mediator of endothelial barrier dysfunction following cardiopulmonary bypass.

INTRODUCTION: Endothelial activation leading to vascular barrier dysfunction and organ failure is a well-recognized complication of cardiovascular surgery with cardiopulmonary bypass (CPB). The endothelial-specific angiopoietin-Tie2 ligand-receptor system has been identified as a non-redundant regulator of endothelial activation. Binding of angiopoietin-2 (Ang-2) to the Tie2 receptor antagonizes Tie2 signaling and renders the endothelial barrier responsive to pro-inflammatory cytokines. We aimed to study the time course and potential triggering factors of Ang-2 release after CPB, as well as the association of Ang-2 changes with surrogates of increased vascular permeability, organ dysfunction, and outcome. METHODS: Serum levels of Ang-2 from 25 adult patients (140 screened) were measured before and at 0, 12, and 24h following CPB procedure by in-house immuno-luminometric assay (ILMA), and compared with indices of organ dysfunction, duration of mechanical ventilation (MV), length of stay (LOS) in the intensive care unit (ICU), and hospital mortality. The effect of Ang-2 was studied in vitro by incubating high Ang-2 patient serum with endothelial cells (EC). RESULTS: Ang-2 levels steadily increased from 2.6 ± 2.4 ng/mL at 0 h up to 7.3 ± 4.6 ng/mL at 24h following CPB (P<0.001). The release of Ang-2 correlated with the duration of CPB, aortic cross-clamp time, and post-CPB lactate levels. Changes in Ang-2 during follow-up correlated with partial pressure of oxygen in arterial blood (PaO(2))/fraction of inspired oxygen (FiO(2)) ratio, alveolar-arterial oxygen tension difference (AaDO(2)), hemodynamics, fluid balance, and disease severity measures. Ang-2 levels at 12h predicted the duration of MV, ICU-LOS, and hospital mortality. High Ang-2 patient sera disrupted EC architecture in vitro, an effect reversed by treatment with the competitive Tie2 ligand angiopoietin-1 (Ang-1). CONCLUSIONS: Collectively, our results suggest that Ang-2 is a putative mediator of endothelial barrier dysfunction after CPB. These findings suggest that targeting the Ang/Tie2 pathway may mitigate organ dysfunction and improve outcome in patients undergoing CPB.

Pharmacokinetics of ampicillin/sulbactam in critically ill patients with acute kidney injury undergoing extended dialysis.

BACKGROUND AND OBJECTIVES: The fixed antibacterial combination of ampicillin and sulbactam is frequently used for various infections. Intact kidneys eliminate approximately 71% of ampicillin and 78% of sulbactam. Patients on thrice-weekly low-flux hemodialysis exhibit an ampicillin t(1/2) of 2.3 hours on and 17.4 hours off dialysis. Despite its frequent use in intensive care units, there are no available dosing recommendations for patients with AKI undergoing renal replacement therapy. The aims of this study were to evaluate the pharmacokinetics of ampicillin/sulbactam in critically ill patients with AKI undergoing extended dialysis (ED) and to establish a dosing recommendation for this treatment method. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Twelve critically ill patients with anuric AKI being treated with ED were enrolled in a prospective, open-label, observational pharmacokinetic study. Pharmacokinetics after a single dose of ampicillin/sulbactam (2 g/1 g) was obtained in 12 patients. Multiple-dose pharmacokinetics after 4 days of twice-daily ampicillin/sulbactam (2 g/1 g) was obtained in three patients. RESULTS: The mean dialyzer clearance for ampicillin/sulbactam was 80.1 ± 7.7/83.3 ± 12.1 ml/min. The t(1/2) of ampicillin and sulbactam in patients with AKI undergoing ED were 2.8 ± 0.8 hours and 3.5 ± 1.5 hours, respectively. There was no significant accumulation using a twice-daily dosage of 2 g/1 g ampicillin/sulbactam. CONCLUSIONS: Our data suggest that in patients treated with ED using a high-flux dialyzer (polysulphone, 1.3 m(2); blood and dialysate flow, 160 ml/min; treatment time, 480 minutes), a twice-daily dosing schedule of at least 2 g/1 g ampicillin/sulbactam, with one dose given after ED, should be used to avoid underdosing.

Daptomycin for a complicated urinary tract infection with vancomycin-resistant Enterococcus faecium in a renal transplant recipient.

There is an increasing prevalence of urinary tract infection (UTI) caused by multiresistant gram-negative enteric bacilli such as extended-spectrum beta-lactamase as well as Gram-positive enterococci whose vancomycin-resistance can be as high as 25%. We report on a 68-year-old Caucasian female with a UTI caused by a vancomycin-resistant Enterococcus faecium, only tested to be susceptible to gentamycin, linezolid and daptomycin. Within a day after administration of the bactericidal daptomycin clinical and laboratory signs of infection regressed and graft function recovered. Our case suggests that daptomycin might be an effective alternative for UTI caused by vancomycin-resistant enterococci.

Biopsy proven acute interstitial nephritis after treatment with moxifloxacin.

BACKGROUND: Acute interstitial nephritis (AIN) is an important cause of reversible acute kidney injury. At least 70% of AIN is caused by various drugs, mainly penicillins and non-steroidal anti-inflammatory drugs. Quinolones are only rarely known to cause AIN and so far cases have been mainly described with older fluoroquinolones. CASE PRESENTATION: Here we describe a case of biopsy proven interstitial nephritis after moxifloxacin treatment. The patient presented with fever, rigors and dialysis dependent acute kidney injury, just a few days after treatment of a respiratory tract infection with moxifloxacin. The renal biopsy revealed dense infiltrates mainly composed of eosinophils and severe interstitial edema. A course of oral prednisolone (1 mg/kg/day) was commenced and rapidly tapered to zero within three weeks. The renal function improved, and the patient was discharged with a creatinine of 107 micromol/l. CONCLUSION: This case illustrates that pharmacovigilance is important to early detect rare side effects, such as AIN, even in drugs with a favourable risk/benefit ratio such as moxifloxacin.

Minimal change nephrotic syndrome in an 82 year old patient following a tetanus-diphteria-poliomyelitis-vaccination.

BACKGROUND: The most common cause of idiopathic nephrotic syndrome in children and younger adults is the minimal change nephrotic syndrome (MCNS). In the elderly MCNS is relatively uncommon. Over the last decade some reports suggest a rare but possible association with the administration of various vaccines. CASE PRESENTATION: A 82-year old Caucasian female presented with pronounced nephrotic syndrome (proteinuria of 7.1 g/d, hypoproteinemia of 47 g/l). About six weeks prior to admission, she had received a combination vaccination for tetanus, diphtheria and poliomyelitis as a booster-vaccination from her general practitioner. The renal biopsy revealed typical minimal change lesions. She responded well to the initiated steroid treatment. As through physical examination as well as extensive laboratory and imaging studies did neither find any evidence for malignancies nor infections we suggest that the minimal change nephrotic syndrome in this patient might be related to the activation of the immune system triggered by the vaccination. CONCLUSION: Our case as well as previous anecdotal reports suggests that vaccination and the resulting stimulations of the immune system might cause MCNS and other severe immune-reactions. Increased awareness in that regard might help to expand the database of those cases.

Pharmacokinetics and dialysate levels of daptomycin given intravenously in a peritoneal dialysis patient.

In this report we present pharmacokinetic (Pk) data of daptomycin given intravenously in a peritoneal dialysis patient. Daptomycin plasma levels were within therapeutic range; however, half-life of the drug was prolonged compared to haemodialysis. Both plasma and dialysate levels were found to be consistently above the minimal inhibitory concentration for daptomycin sensitive strains.