In vitro Removal of Therapeutic Drugs with a Novel Adsorbent System

Background/Aim: Substances in the middle molecular weight range have been shown to play a significant pathogenetic role in as diverse disorders as end-stage renal disease and multiple organ failure. To overcome the limitations in the amount removed by hemofilters, new sorbents with a high biocompatibility are actively being developed. Furthermore, biocompatible sorbents by their nonspecific adsorptive behavior could have great impact on detoxification treatment in exogenous intoxications. We performed an in vitro evaluation of a newly developed highly biocompatible sorbent cartridge (Betasorb(R)), examining its adsorptive capacity concerning therapeutic drugs. Methods: Uremic blood spiked with a range of therapeutic drugs was recirculated for 2 h in an in vitro hemoperfusion circuit containing a Betasorb device for hemoperfusion. The drug concentrations before and after the passage of the cartridge were measured, and the total amount removed was calculated. Results: The sorbent showed effective removal of glycopeptide antibiotics, digoxin, theophylline, phenobarbital, phenytoin, carbamazepine, and valproic acid. Moderate removal could be demonstrated for tacrolimus and cyclosporine A; aminoglycosides were removed to a small extent only. Conclusions: Betasorb hemoperfusion shows a potent adsorptive capacity concerning therapeutic drugs (except aminoglycosides) and could be of major value in the treatment of intoxications. On the other hand, drug monitoring and possible adjustments are necessary during Betasorb hemoperfusion to maintain the therapeutic ranges of the drugs in blood. Copyright (C) 2002 S. Karger AG, Basel

Assessment of arterial stiffness, oxidative stress and inflammation in acute kidney injury

Background: It is well know that arterial stiffness, oxidative stress and inflammation are features of chronic kidney disease. The arterial changes have a multitude of potential interconnected causes including endothelial dysfunction, oxidative stress, inflammation, atherosclerosis and vascular calcification. There is evidence that arterial stiffness becomes progressively worse as CKD progresses. The contribution of the biochemical changes of uremic toxicity to arterial stiffness is less clear. The aim of this study is to elucidate the vascular changes in acute kidney injury. We hypothesise that arterial stiffness will be increased during acute kidney injury and this will return to normal after kidney function recovers

Optimising intraperitoneal gentamicin dosing in peritoneal dialysis patients with peritonitis (GIPD) study

Background: Antibiotics are preferentially delivered via the peritoneal route to treat peritonitis, a major complication of peritoneal dialysis (PD), so that maximal concentrations are delivered at the site of infection. However, drugs administered intraperitoneally can be absorbed into the systemic circulation. Drugs excreted by the kidneys accumulate in PD patients, increasing the risk of toxicity. The aim of this study is to examine a model of gentamicin pharmacokinetics and to develop an intraperitoneal drug dosing regime that maximises bacterial killing and minimises toxicity

Do circulating cytokines really matter in sepsis?

Do circulating cytokines really matter in sepsis? Sepsis remains the major cause of mortality worldwide, claiming millions of lives each year. The past decade has seen major advances in the understanding of the biological mechanisms involved in this complex process. Unfortunately, no definitive therapy yet exists that can successfully treat sepsis and its complications. In this review, we will address the significance of circulating cytokines in the pathophysiology of sepsis and its relevance to new approaches in extracorporeal therapies

Evaluation and Initial Management of Acute Kidney Injury

The evaluation and initial management of patients with acute kidney injury (AKI) should include: (1) an assessment of the contributing causes of the kidney injury, (2) an assessment of the clinical course including comorbidities, (3) a careful assessment of volume status, and (4) the institution of appropriate therapeutic measures designed to reverse or prevent worsening of functional or structural kidney abnormalities. The initial assessment of patients with AKI classically includes the differentiation between prerenal, renal, and postrenal causes. The differentiation between so-called “prerenal” and “renal” causes is more difficult, especially because renal hypoperfusion may coexist with any stage of AKI. Using a modified Delphi approach, the multidisciplinary international working group, generated a set of testable research questions. Key questions included the following: Is there a difference in prognosis between volume-responsive and volume-unresponsive AKI? Are there biomarkers whose patterns (dynamic changes) predict the severity and recovery of AKI (maximal stage of AKI, need for RRT, renal recovery, mortality) and guide therapy? What is the best biomarker to assess prospectively whether AKI is volume responsive? What is the best biomarker to assess the optimal volume status in AKI patients? In evaluating the current literature and ongoing studies, it was thought that the answers to the questions posed herein would improve the understanding of AKI, and ultimately patient outcomes