Reviewer's report 
 The Changes in Renal Function after a Single Dose of intravenous Furosemide in Patients with Title: 
Compensated Liver cirrhosis 
 1  17 August 2006 Version: Date: 
 Laurent Spahr Reviewer: 
Reviewer's report: 
General 
General 
This paper by Assi et al. reports on renal changes following standard and very high dose of a loop diuretic in 
a small group of patients with compensated non ascetic cirrhosis. 
Major concern: I have some problems in understanding the rationale of the study. Accordingly, it is 
commonly accepted that the renal response to diuretics in compensated nonascitic cirrhosis without associated renal disease is not a clinical problem. A satisfactory natriuretic response is observed using standard doses of loop diuretics (i.e: furosemide 40 mg). It is only when creatinine clearance is less than 
about 40 ml/min that the diuretic and natriuretic effect may be altered. This situation is always observed in 
decompensated cirrhosis with ascites. 
Aim: in the aim  section, the authors wanted to determine whether the renal response may identify 
patients with a more aggressive course . However, this information is not available in this paper. 
Design of the study: it is not clear to me how the patients have been attributed to study groups. Were thy 
randomly selected? 
The renal effect after IV furosemide starts within minutes and lasts 3 to 4 hours. Why having chosen a 90 
repeat DMSA? 
Furosemide 120 mg represents a supramaximal dose for a patient with compensated cirrhosis. A 80 mg 
dose would have been sufficient, probably. Patients: they are described as having no ascites. Was this based on clinical examination or using ultrasonography? 
Statistics: Due to the non normal distribution of values, data should be expressed as median and range. 
The changes following pharmacological intervention should be expressed as % changes. Please use international units (not mg/dl&). In the statistical section, comparisons between three groups  is written. 
What is the third group? 
Results: the authors should provide % changes in both groups. I am concerned about the safety of receiving 
IV furosemide 120 mg. It is said that none of the patients deteriorate the renal perfusion , but I would like 
to see serum creatinine or creatinine clearance at day 5 and 10, for example. In the forth paragraph, 
Discussion section, the authors say: &diuretic use in cirrhotic patients without ascites is associated with 
renal dysfunction . This statement underlines the risk of administer furosemide 120 mg in the patients!!! 
80% of the patients had a decreased value of DMSA. Was this compared in an age and sex-matched control group? If yes, data should be provided. Patients in both groups increased their DMSA values to the same extent, but the natriuretic response was higher in the 120 mg group. Baseline urinary Na excretion 
should be given to appreciate the effect of the loop diuretic. In compensated cirrhosis, values in the range of 
40 to 80 mEq per day can be observed. Due to the small size of the groups, individual values should be 
illustrated. In the view of the small size of the groups studied and the absence of information on the outcome, 
interpretation of this loop-diuretic test  and diuretic-DMSA test  is limited and not clinically relevant at 
this stage. Discussion: the authors state that it is safe to administer a single IV bolus of furosemide  but do not 
provide data to support it. Furthermore, they claim that they identified a subgroup of patients not 
responsive  to furosemide. This is suprising in the view of a > 80 mEq Na in all patients&. The 
response  and non response  is not defined in the Methods. 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can be 
reached) Provide baseline data on urinary sodium excretion Provide values in %, as well as illustration of individual changes 
Give information on groups randomization 
Provide serum creatinine data in the follow-up (days) 
Give values of the control group for DMSA 
Give information on patients follow-up to correlate with DMSA and/or 8 hours Na excretion 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author can be trusted to correct) 
Correct the numerous grammatical and spelling errors 
------------------------------------------------------------------------------- Discretionary Revisions (which the author can choose to ignore) 
 Unable to decide on acceptance or rejection until the authors have responded to the major What next?: 
compulsory revisions 
 An article of limited interest Level of interest: 
 Needs some language corrections before being published Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests 
Reviewer's report 
 The Changes in Renal Function after a Single Dose of intravenous Furosemide in Patients with Title: 
Compensated Liver cirrhosis 
 1  17 August 2006 Version: Date: 
 Laurent Spahr Reviewer: 
Reviewer's report: 
General 
General 
This paper by Assi et al. reports on renal changes following standard and very high dose of a loop diuretic in 
a small group of patients with compensated non ascetic cirrhosis. 
Major concern: I have some problems in understanding the rationale of the study. Accordingly, it is 
commonly accepted that the renal response to diuretics in compensated nonascitic cirrhosis without associated renal disease is not a clinical problem. A satisfactory natriuretic response is observed using standard doses of loop diuretics (i.e: furosemide 40 mg). It is only when creatinine clearance is less than 
about 40 ml/min that the diuretic and natriuretic effect may be altered. This situation is always observed in 
decompensated cirrhosis with ascites. 
Aim: in the aim  section, the authors wanted to determine whether the renal response may identify 
patients with a more aggressive course . However, this information is not available in this paper. 
Design of the study: it is not clear to me how the patients have been attributed to study groups. Were thy 
randomly selected? 
The renal effect after IV furosemide starts within minutes and lasts 3 to 4 hours. Why having chosen a 90 
repeat DMSA? 
Furosemide 120 mg represents a supramaximal dose for a patient with compensated cirrhosis. A 80 mg 
dose would have been sufficient, probably. Patients: they are described as having no ascites. Was this based on clinical examination or using ultrasonography? 
Statistics: Due to the non normal distribution of values, data should be expressed as median and range. 
The changes following pharmacological intervention should be expressed as % changes. Please use international units (not mg/dl&). In the statistical section, comparisons between three groups  is written. 
What is the third group? 
Results: the authors should provide % changes in both groups. I am concerned about the safety of receiving 
IV furosemide 120 mg. It is said that none of the patients deteriorate the renal perfusion , but I would like 
to see serum creatinine or creatinine clearance at day 5 and 10, for example. In the forth paragraph, 
Discussion section, the authors say: &diuretic use in cirrhotic patients without ascites is associated with 
renal dysfunction . This statement underlines the risk of administer furosemide 120 mg in the patients!!! 
80% of the patients had a decreased value of DMSA. Was this compared in an age and sex-matched control group? If yes, data should be provided. Patients in both groups increased their DMSA values to the same extent, but the natriuretic response was higher in the 120 mg group. Baseline urinary Na excretion 
should be given to appreciate the effect of the loop diuretic. In compensated cirrhosis, values in the range of 
40 to 80 mEq per day can be observed. Due to the small size of the groups, individual values should be 
illustrated. In the view of the small size of the groups studied and the absence of information on the outcome, 
interpretation of this loop-diuretic test  and diuretic-DMSA test  is limited and not clinically relevant at 
this stage. Discussion: the authors state that it is safe to administer a single IV bolus of furosemide  but do not 
provide data to support it. Furthermore, they claim that they identified a subgroup of patients not 
responsive  to furosemide. This is suprising in the view of a > 80 mEq Na in all patients&. The 
response  and non response  is not defined in the Methods. 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can be 
reached) Provide baseline data on urinary sodium excretion Provide values in %, as well as illustration of individual changes 
Give information on groups randomization 
Provide serum creatinine data in the follow-up (days) 
Give values of the control group for DMSA 
Give information on patients follow-up to correlate with DMSA and/or 8 hours Na excretion 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author can be trusted to correct) 
Correct the numerous grammatical and spelling errors 
------------------------------------------------------------------------------- Discretionary Revisions (which the author can choose to ignore) 
 Unable to decide on acceptance or rejection until the authors have responded to the major What next?: 
compulsory revisions 
 An article of limited interest Level of interest: 
 Needs some language corrections before being published Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests 
Please review this paper.
user
Reviewer's report 
 The Changes in Renal Function after a Single Dose of intravenous Furosemide in Patients with Title: 
Compensated Liver cirrhosis 
 1  17 August 2006 Version: Date: 
 Laurent Spahr Reviewer: 
Reviewer's report: 
General 
General 
This paper by Assi et al. reports on renal changes following standard and very high dose of a loop diuretic in 
a small group of patients with compensated non ascetic cirrhosis. 
Major concern: I have some problems in understanding the rationale of the study. Accordingly, it is 
commonly accepted that the renal response to diuretics in compensated nonascitic cirrhosis without associated renal disease is not a clinical problem. A satisfactory natriuretic response is observed using standard doses of loop diuretics (i.e: furosemide 40 mg). It is only when creatinine clearance is less than 
about 40 ml/min that the diuretic and natriuretic effect may be altered. This situation is always observed in 
decompensated cirrhosis with ascites. 
Aim: in the aim  section, the authors wanted to determine whether the renal response may identify 
patients with a more aggressive course . However, this information is not available in this paper. 
Design of the study: it is not clear to me how the patients have been attributed to study groups. Were thy 
randomly selected? 
The renal effect after IV furosemide starts within minutes and lasts 3 to 4 hours. Why having chosen a 90 
repeat DMSA? 
Furosemide 120 mg represents a supramaximal dose for a patient with compensated cirrhosis. A 80 mg 
dose would have been sufficient, probably. Patients: they are described as having no ascites. Was this based on clinical examination or using ultrasonography? 
Statistics: Due to the non normal distribution of values, data should be expressed as median and range. 
The changes following pharmacological intervention should be expressed as % changes. Please use international units (not mg/dl&). In the statistical section, comparisons between three groups  is written. 
What is the third group? 
Results: the authors should provide % changes in both groups. I am concerned about the safety of receiving 
IV furosemide 120 mg. It is said that none of the patients deteriorate the renal perfusion , but I would like 
to see serum creatinine or creatinine clearance at day 5 and 10, for example. In the forth paragraph, 
Discussion section, the authors say: &diuretic use in cirrhotic patients without ascites is associated with 
renal dysfunction . This statement underlines the risk of administer furosemide 120 mg in the patients!!! 
80% of the patients had a decreased value of DMSA. Was this compared in an age and sex-matched control group? If yes, data should be provided. Patients in both groups increased their DMSA values to the same extent, but the natriuretic response was higher in the 120 mg group. Baseline urinary Na excretion 
should be given to appreciate the effect of the loop diuretic. In compensated cirrhosis, values in the range of 
40 to 80 mEq per day can be observed. Due to the small size of the groups, individual values should be 
illustrated. In the view of the small size of the groups studied and the absence of information on the outcome, 
interpretation of this loop-diuretic test  and diuretic-DMSA test  is limited and not clinically relevant at 
this stage. Discussion: the authors state that it is safe to administer a single IV bolus of furosemide  but do not 
provide data to support it. Furthermore, they claim that they identified a subgroup of patients not 
responsive  to furosemide. This is suprising in the view of a > 80 mEq Na in all patients&. The 
response  and non response  is not defined in the Methods. 
------------------------------------------------------------------------------- 
Major Compulsory Revisions (that the author must respond to before a decision on publication can be 
reached) Provide baseline data on urinary sodium excretion Provide values in %, as well as illustration of individual changes 
Give information on groups randomization 
Provide serum creatinine data in the follow-up (days) 
Give values of the control group for DMSA 
Give information on patients follow-up to correlate with DMSA and/or 8 hours Na excretion 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author can be trusted to correct) 
Correct the numerous grammatical and spelling errors 
------------------------------------------------------------------------------- Discretionary Revisions (which the author can choose to ignore) 
 Unable to decide on acceptance or rejection until the authors have responded to the major What next?: 
compulsory revisions 
 An article of limited interest Level of interest: 
 Needs some language corrections before being published Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests 
assistant