|Year : 2021 | Volume
| Issue : 1 | Page : 98-102
Outcome of furosemide stress test in patients with oliguric acute kidney injury
Hassan A Attia1, Mahmoud M Emara1, Mohammed G Elnazer2
1 Internal Medicine Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Egypt
2 Internal Medicine Department, Shebin El-Kom Teaching Hospital, Shebin El-Kom, Egypt
|Date of Submission||13-Mar-2019|
|Date of Decision||01-Apr-2019|
|Date of Acceptance||08-Apr-2019|
|Date of Web Publication||27-Mar-2021|
Mohammed G Elnazer
Internal Medicine Department, Shebin El-Kom Teaching Hospital, Shebin El-Kom 32717, Menoufia
Source of Support: None, Conflict of Interest: None
The aim of this study is to evaluate the outcome of furosemide stress test (FST) in patients with oliguric acute kidney injury (AKI) and its effect on increasing urine output compared with the effect of dialysis.
AKI is a common complication of critical illness; 7–10% of ICU patients present with AKI during their ICU stay and about 45–60% of them are associated with high mortality while the early detection of adult patients with AKI may provide the opportunity to treat and prevent the extension to chronic kidney injury.
Patients and methods
A cohort study was conducted on two groups: one group included 40 cases who received FST following 80 mg furosemide intravenous shots upon inclusion in this study. The second group included 40 cases who did not respond to 80 mg furosemide intravenous shots and then received standard management by dialysis. Data were collected and tabulated.
There is no significant difference between both groups of the study regarding: outcome (progression to grade III according to the Acute Kidney Injury Network III, length of stay in ICU, and mortality) and urine output.
FST does not have an additional privilege over standard management (by dialysis) in the treatment of AKI.
Keywords: acute kidney injury, chronic kidney disease, dialysis, furosemide
|How to cite this article:|
Attia HA, Emara MM, Elnazer MG. Outcome of furosemide stress test in patients with oliguric acute kidney injury. Menoufia Med J 2021;34:98-102
|How to cite this URL:|
Attia HA, Emara MM, Elnazer MG. Outcome of furosemide stress test in patients with oliguric acute kidney injury. Menoufia Med J [serial online] 2021 [cited 2021 Dec 4];34:98-102. Available from: http://www.mmj.eg.net/text.asp?2021/34/1/98/311987
| Introduction|| |
Acute kidney injury (AKI) patients are cared for by a multitude of specialists including but not limited to: emergency medicine physicians, internal medicine physicians, and intensivists ,. Patients who develop AKI often require renal replacement therapy (RRT); however, clinicians often disagree about the timing of the initiation of RRT ,. During the Acute Kidney Injury Network (AKIN) multidisciplinary consensus meeting, the question that was ranked highest was 'When RRT should be initiated? RRT is an invasive procedure with inherent risks, and one would not want to initiate this therapy if renal function is expected to improve without intervention . Since serum creatinine and oliguria are often late signs of significant AKI, more sensitive diagnostic tests are required. This clinical need has led to the development of multiple candidate AKI biomarkers . As AKI biomarker levels change over time depending on the timing and severity of injury, a functional assessment of renal function might enhance the biomarker performance. Since most common form(s) of intrinsic AKI involve acute tubular injury, furosemide stress test (FST) was proposed for the treatment of renal tubular dysfunction .
The aim of this study is to evaluate the outcome of FST in patients with oliguric AKI and its effect on increasing urine output (UOP) compared with the effect of dialysis.
| Patients and methods|| |
This study was conducted on 80 patients with AKI admitted to the ICU of Shebin El-Kom Teaching Hospital, Egypt from February 2017 to February 2018. Informed consents were taken from the enrolled patients and/or their relatives and the study protocol was approved by Medical Ethics Committee of the Hospital. The study population was divided randomly into two groups: the first group included 40 consecutive patients who received FST following 80 mg furosemide intravenous shots upon inclusion in the study and the second group included 40 consecutive patients who did not respond to 80 mg furosemide intravenous shots and then received standard management by dialysis.
Patients more than 18 years old with oliguric AKI stages I and II according to AKIN classification.
Patients with stage III–IV AKI according to AKIN classification; patients with renal allograft, patients who had allergy to loop diuretics, and patients with obstructive uropathy.
The enrolled oliguric patients with AKI grades I and II according to AKIN classification were subjected to: full history with medical examination and hemodynamic monitoring (blood pressure and central venous pressure) measurement before and after 1 h, and after 2 h from FST considering the use of mean arterial blood pressure according to the equation: mean arterial blood pressure = diastolic pressure + 1/3 pulse pressure.
Then all patients were subjected to the following investigations: complete urine examination including (volume, specific gravity, cells, and casts), complete blood count, serum urea and creatinine before and after FST, serum sodium and potassium levels, echocardiographic examination 2 h after FST with the presence of basal echocardiography before this condition 'with focus on ejection fraction as a determinant parameter and estimated the glomerular filtration rate (GFR).
The patients were injected initially with 80 mg intravenous furosemide in divided doses that started with 40 mg intravenous followed by assessment of UOP for 30 min. If the UOP less than 400 ml, reinject the patient with another 40 mg intravenous furosemide, and evaluate the UOP for 30 min. If the UOP less than 400 ml, start furosemide continuous intravenous infusion with a rate 10–40 mg/h for 24 h for group I and start dialysis for group II. The infusion will start with 10 mg/h for 6 h and then increase the rate to 20 mg/h, if the desired UOP is not reached (50 ml/h) after 6 h, increase the rate of infusion to 30 mg/h for another 6 h and then to 40 mg/h at last 6 of 24 h of the study. The outcome of the studied patients was made considering the progression to AKIN-III with need for regular dialysis and length of stay in ICU.
Data were fed to the computer and analyzed using IBM SPSS software package version 20.0. (IBM Corp., Armonk, New York, USA) . Qualitative data were described using number and percent. The Kolmogorov–Smirnov test was used to verify the normality of distribution. Quantitative data were described using range (minimum and maximum), mean, SD, and median. Significance of the obtained results was judged at the 5% level. The used tests were: χ2-test (for categorical variables, to compare between different groups), Fisher's exact (correction for χ2 when >20% of the cells have an expected count of <5), Student's t-test (for normally distributed quantitative variables to compare between the two studied groups) and Mann–Whitney test (for abnormally distributed quantitative variables to compare between two studied groups) considering that the P value up to 0.05 is significant and the P value up to 0.01 is highly significant.
| Results|| |
The demographic data of the patients included in the study did not significantly differ [Table 1].
In the first 6 h, there was a statistically significant increase in UOP in group I after the first and second hours (P = 0.026 and 0.008, respectively), as well as cumulative UOP over 6 h (P = 0.003), compared with group II [Table 2].
|Table 2: Comparing urine output within the first 6 h of infusion (group I) and dialysis (group II)|
Click here to view
As regards the GFR there is statistically highly significant difference between the two groups on the day of admission and day 1 only as P value of 0.002 and 0.019, respectively, and it is noticed that GFR is increasing progressively by time [Table 3].
|Table 3: Comparing glomerular filtration rate during the follow-up days between the two groups|
Click here to view
The serum potassium was significantly higher in group I than in group II only on day 1 and 2 with a P value of 0.023 and 0.005, respectively [Table 4].
|Table 4: Comparing the serum potassium level ‘serum potassium’ during the follow-up days between the two groups|
Click here to view
As regards hypotension as a side effect in group I, 11 patients suffered from hypotension representing 27.5% whereas no patients in group II suffered from this side effect which is statistically significant (P < 0.001; [Table 5]).
|Table 5: Comparing frequency of hypotension within the first 6 h between the two groups|
Click here to view
As regards the length of stay in the ICU, in group I the mean length of stay was 4.81 ± 1.85 days with a range from 3 to 10 days while in group II the mean was 4.8 ± 2.38 days with a range from 3 to 14 days; there was no statistically significant difference between the two groups.
As regards mortality in group I there were five (12.5%) patients who died (by multiorgan failure), while in group II there was only one (2.5%) patient who died; there is no statistically significant difference between both groups.
| Discussion|| |
AKI is well recognized for its impact on the outcome of patients admitted to the ICU; early diagnosis and management may prevent progression to more severe renal injury and need of more invasive and costly treatment. The pursuit of biomarkers for the early diagnosis of AKI and its outcome is an area of intense contemporary research. Recent studies have suggested a functional test, namely the FST (administrating a high bolus dose of furosemide) for a possible therapeutic role for patients with AKIN stages I and II .
In this study, we included 80 patients admitted to Shebin El-Kom Teaching Hospital ICU from February 2017 till February 2018. The patients were divided into two groups. Group I included 40 consecutive patients who received FST dose and group II included 40 consecutive patients who received standard management by dialysis.
As regards the UOP, our study demonstrated that diuresis was maximum within first 2 h after inclusion in both groups This is in concordance with Lakhmir , who found that maximum diuresis occurred in the second and the third hour after receiving a high dose of furosemide and Koyner et al. , who found that maximum diuresis was in the first 2 h. Also Shilliday et al.  found that maximum urine flow rate was within first 6 h after administration of furosemide. In this study, the most significant difference in UOP between groups I and II was found to be on the first and the second hour after inclusion as well as cumulative UOP after 6 h, where it was higher in group I than in group II.
Upon addressing serum creatinine level, this study showed that there was a gradual decline in both groups over 3 days of follow-up but with statistical significance was only demonstrated in group I versus group II on the first day; however, Shilliday et al.  and Grams et al.  stated that the significant improvement in creatinine was on the second day after receiving furosemide.
Similarly, GFR showed progressive improvement in this study in the follow-up period but no significant difference between the two groups which agreed with Heyman et al.  and Koyner et al. , who stated that GFR showed progressive improvement after receiving either high bolus dose of furosemide or standard management with no significant difference as well.
As regards the side-effects noticed in both groups, hypotension occurred only in the group receiving FST dose, whereas no cases suffered from hypotension in group II with the frequency of this side effect being significantly higher in group I. This is in contrast to Lakhmir , where they reported no frequency of hypotension with a bolus dose of furosemide.
Concerning hypokalemia it was noticed in six (15%) patients in group I versus five (12.5%) patients in group II. Greenberg  stated that hypokalemia tends to occur more in patients receiving higher doses of furosemide; nonetheless, no statistically significance difference concerning hypokalemia was noticed between our two study groups.
The outcome parameters in this study included progression to AKIN-III and the need for dialysis, length of ICU stay, and hospital mortality. As for progression of AKI and the need for regular dialysis, our study found that group II showed a higher tendency of AKI progression and need for regular dialysis (after failure of the first three successive sessions of dialysis to give us the desired UOP) than group I; however, there was no statistically significant difference. Various studies stated that UOP within 2 h of receiving bolus dose of furosemide predicted the progression to AKIN-III and regular dialysis as suggested by Koyner et al.  who found that UOP within 2 h was a good predictor of progression to AKIN-III and the need for regular dialysis. Ho and Sheridan  and Chawla and Davison  stated that sustained urinary output response to furosemide at the early stage of AKI may be considered as a 'proxy' for having a mild AKI and having a lower of risk of requiring dialysis, in addition to Lakhmir , who found that the total UOP in the first 2 h after giving the FST dose with a cutoff value of 200 ml had the best sensitivity (87%) and specificity (87%) to predict the progression to AKIN-III and dialysis.
Concerning the length of ICU stay, our study found that there was no statistically significant difference between the two groups as regards the length of ICU stay, which was in concordance with Ho and Sheridan  and Ahmed et al. , who stated that there was no significant difference of administrating higher dose of furosemide in shortening the length of ICU stay versus conventional doses. However, this was disconcordant with Ahlstrom , who found that the length of stay was significantly shorter in the group who received a high bolus of furosemide.
In this study, we found that in group I there were five patients who died representing 12.5%, while in group II there was only one patient who died representing 2.5%, there was no statistically significant difference between both groups. That was in concordance with Shilliday et al. , Ho and Sheridan , and Ahmed et al. , who found that there was no significant difference in mortality of patients who received higher doses of furosemide in contrast to those receiving lower doses. But Uchino et al.  and Mehta et al.  disagreed as they found that furosemide increases the risk of intrahospital mortality.
| Conclusion|| |
FST does not have an additional privilege over standard management (by dialysis) in the treatment of AKI.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Bellomo R, Kellum JA, Ronco C. Acute kidney injury. Lancet 2012; 380
Coca SG, Singanamala S, Parikh CR. Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney Int 2012; 81
Koyner JL, Garg AX, Coca SG, Sint K, Thiessen-Philbrook H, Patel UD, et al
. Biomarkers predict progression of acute kidney injury after cardiac surgery. J Am Soc Nephrol 2012; 23
Clarkson MR, Friedewald JJ, Eustace JA, Rabb H. Acute Kidney Injury. In Brenner B (Ed.), The Kidney. Brenner and Rector's: 2007; pp: 943-987.
Amy WW. Acute renal failure. in: Habermann TM, Ghoshby AK, editors. Mayo Clinic Internal Medicine Concise Textbook. Florida, United States. CRC Press; 2008. pp. 584–590.
Bagga A, Bakkaloglu A, Devarajan P. Improving outcomes from acute kidney injury: report of an initiative. Pediatr Nephrol 2007; 22
Bagshaw SM, George C, Bellomo R. A comparison of the RIFLE and AKIN criteria for acute kidney injury in critically ill patients. Nephrol Dial Transplant 2008; 23
Kirkpatrick LA, Feeney BC. A simple guide to IBM SPSS statistics for version 20.0. Student ed. Belmont, Calif.: Wadsworth, Cengage Learning; 2013; 11
Lakhmir S. Diagnostic criteria for acute kidney injury. Crit Care 2013; 17
Koyner JL, Davison DL, Brasha-Mitchell E, Chalikonda DM, Arthur JM, Shaw AD, et al
. Furosemide stress test and biomarkers for the prediction of AKI severity. J Am Soc Nephrol 2015; 26
Shilliday IR, Quinn KJ, Allison ME. Loop diuretics in the management of acute renal failure: a prospective, double-blind, placebo-controlled, randomized study. Nephrol Dial Transplant 1997; 12
Grams ME, Estrella MM, Coresh J, Brower RG, Liu KD, National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network. Fluid balance, diuretic use, and mortality in acute kidney injury. Clin J Am Soc Nephrol 2011; 6
Heyman SN, Rosen S, Epstein FH, Spokes K, Brezis ML. Loop diuretics reduce hypoxic damage to proximal tubules of the isolated perfused rat kidney. Kidney Int 1994; 45
Greenberg A. Diuretic complications. Am J Med Sci 2000; 319
Ho KM, Sheridan DJ. Meta-analysis of furosemide to prevent or treat acute renal failure. Br Med J 2006; 333
Kellum JA. Diagnostic Criteria for Acute Kidney Injury: Present and Future. Crit Care Clin 2015; 31
Ahmed US, Iqbal HI, Akbar SR. Furosemide in acute kidney injury – a vexed issue. Austin J Nephrol Hypertens 2014; 1
Toft P, Gilsaa T. Akut nyresvigt hos den kritisk syge patient [Acute renal failure in critically ill patients]. Ugeskr Laeger 2007; 169
Uchino S, Doig GS, Bellomo R, Beginning and Ending Supportive Therapy for the Kidney (B.E.S.T. Kidney) Investigators. Diuretics and mortality in acute renal failure. Crit Care Med 2004; 32
Mehta RL, Godin M, Bouchard J. Fluid balance in patients with acute kidney injury: emerging concepts. Nephron Clin Pract 2013; 123
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]