5 mL/kg/h for 6 h [38]. The current Lapatinib supplier KDIGO Clinical Practice Guideline for Acute Kidney Injury [38] even suggests using isotonic crystalloids rather than colloids (albumin or starches) as initial management for expansion of intravascular volume in patients at risk for AKI or with AKI (recommendation level 2, grade B).On the other hand, acute oliguria (urine output <0.5 mL/kg/h for a couple of hours) may be a strong indicator for acute hypovolaemia, a condition where acute volume resuscitation with colloids might be indicated.Taking into account the current guidelines [38] and the increasing risk of kidney injury after prolonged administration of HES, we suggest an expansion of the exclusion criteria not only to renal failure (as this has been considered in previous trials in the past) but rather to AKI in the future.

6. We suggest the following three-step approach:1. If there is any evidence of pre-existing renal failure or even AKI, HES should not be given.2. If there is no evidence of pre-existing renal failure or AKI but acute oliguria is present, HES might be indicated in combination with crystalloids, as oliguria could simply be the consequence of acute hypovolaemia.3. If oliguria is unresponsive to acute volume resuscitation using HES within a time period of maximum 6 h, HES should be stopped.The next fundamental problem in the interpretation of the endpoints of previous studies, in particular need for RRT, is that standardised definitions for starting RRT have not yet been used in any of these studies, as no consensus exists so far.

Further, RRT is not a single homogeneous therapy but rather there are diverse modes of therapy and various ways of providing RRT that might affect its efficacy and patient outcome [29-31]. These aspects refers to the mode (intermittent vs. continuous), timing of RRT initiation and discontinuation, dose, and practice variations (type of dilution, type of anticoagulation, and so on).In this respect, we believe, as far as ‘need for RRT’ is used as a relevant study endpoint, a standardised study protocol clarifying mode, dose, type of anticoagulation and rules for starting and stopping of RRT are mandatory. This may be particularly of interest in multicenter trials were indication for RRT may differ between centres.7. We suggest that indication of RRT should be defined within a study protocol in advance in future studies, when RTT is used as a relevant study endpoint.

The final aspect that we would like Dacomitinib to address is quality of data documentation and providing raw data for meta-analyses. This issue primarily refers to large clinical trials whose results and conclusions have a major impact on medical practice, but also on the registration authority in the EMA or the Food and Drug Administration (FDA). In smaller studies, standardisation of any study protocol and adequate data collection is often simple, but sample size is also insufficient to power for relevant clinical endpoints.