Saudi J Kidney Dis Transpl 2012;23(2):371-373 © 2012 Saudi Center for Organ Transplantation Letter to the Editor

Co-administration of Albumin and Furosemide in Patients with the Nephrotic Syndrome

To the Editor, We read with interest the article by Gafari et al on co-administration of albumin and furo-semide in adults with the nephrotic syndrome (NS).1 Impaired response to loop diuretics in the NS could be due to decreased delivery of furosemide into the tubular lumen, hypovo-lemia, and reduced glomerular filtration rate (GFR). Gafari et al have demonstrated higher urine volumes and urinary sodium excretion when furosemide was co-administered with albumin as compared to when albumin or furo-semide was administered alone. They also showed increased GFR with albumin infusion. While several studies have demonstrated that albumin infusion can enhance diuresis in the NS,2-4 others have failed to do so.5,6 We, in a randomized controlled cross-over trial, have shown that co-administration of human albu-min with furosemide infusion caused a further increase in urine volume, and sodium and chloride excretion as compared to furosemide infusion alone in children with the NS.7 We also found that high doses of furosemide alone, given as infusion, improved diuresis and natriuresis from the baseline which suggests that poor furosemide delivery to the tubules can be partly overcome by administering high doses of furosemide as infusion. We measured urine osmolality and calculated osmolal clearance and free water clearance in our patients. Co-administration of albumin with

furosemide increased osmolal clearance [1600 mL/day (95% CI 916–4140)] as compared to furosemide administered alone [880 mL/day (95% CI 510–2105)], but there was a reduction in free water clearance. The free water clea-rance was negative in patients who received albumin and furosemide infusion (−190 mL/day) and those who were given furosemide infusion alone (−162 mL/day). Negative free water clearance and increased solute fluid clearance suggests that the levels of anti-diuretic hor-mone were elevated and that our patients were in a state of hypovolemia. An elevated blood urea/creatinine ratio, which is an indicator of low intravascular volume, further substantiated this finding. Our results suggested that admi-nistration of human albumin did not signifi-cantly correct hypovolemia. It is possible that intravascular expansion did occur in these pa-tients but these patients reverted back to hypo-volemia due to profound natriuresis and diu-resis. We speculated that natriuresis and diu-resis occurred chiefly due to potentiation of effects of furosemide following improved drug delivery to the tubules rather than intravascular volume expansion.

Dr. Pankaj Hari, Dr. Arvind Bagga Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India E-mail: pankajhari@hotmail.com

Saudi Journal of Kidney Diseases

and Transplantation

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References

1. Ghafari A, Mehdizadeh A, Alavi-Darazam I, Rahimi E, Kargar C, Sepehrvand N. Co-admi-nistration of albumin-furosemide in patients with the nephrotic syndrome. Saudi J Kidney Dis Transpl 2011;22:471-5.

2. Davison AM, Lambie AT, Verth AH, Cash JD. Salt poor human albumin in management of nephrotic syndrome. Br Med J 1974;16:481–4.

3. Eadington DW, Plant WD, Winney RJ. Albumin in the nephrotic syndrome. Br Med J 1995;310: 1333.

4. Fliser D, Zurbruggen D. Coadministration of albumin and frusemide in patients with neph-rotic syndrome. Kidney Int 1999;55:629–33.

5. Akcicek F. Diuretic effects of frusemide in pa-tients with nephrotic is it potentiated by intra-venous albumin? Br Med J 1995;310:102–3.

6. Han JS, Na KY. Does albumin preinfusion po-tentiates diuretic action of frusemide in pa-tients with nephrotic syndrome. J Korean Med Sci 2001;16:448–54.

7. Dharmaraj R, Hari P, Bagga A. Randomized cross-over trial comparing albumin and fruse-mide infusions in nephrotic syndrome. Pediatr Nephrol 2009;24:775-82.

Author’s Reply To the Editor, On behalf of all the co-authors, I would like to thank Dr. Hari and Dr. Bagga for their inte-rest in our study. In the letter, they have pre-sented the results of their study, which confirm most of our findings too. Similarly, they have found that the co-administration of albumin and furosemide in patients with the NS can lead to an increase in sodium excretion and urine volume when compared with administra-tion of furosemide alone.1,2 It is accepted that the GFR has a strong rela-tionship with serum albumin level, as the se-rum albumin level (g/dL) is one of the six va-riables in the MDRD formula for estimating the GFR.3 We have also mentioned that the difference between groups receiving furosemide alone and furosemide with albumin could not

be explained solely by the increase in GFR in the group receiving albumin, and could suggest an improvement in furosemide’s diuretic effects in addition.2 Since Hari et al found negative free water clearance and increased solute fluid clearance among their findings; they suggested that the increased natriuresis and diuresis occurred chiefly due to improved delivery of furose-mide to the tubules rather than intravascular volume expansion.1 Of course, we believe that these two factors (improved drug delivery and increased intravascular volume) are not funda-mentally distinct and separate phenomena, since intravascular volume expansion leads to higher renal blood flow and probably higher GFR, which consequently can increase the de-livery of furosemide to the tubules and maxi-mize its influence. Although some studies are against the syner-gistic effect of albumin and furosemide in increasing the diuresis,4-7 most of the recent studies are advocating their co-administration.1,2,8 The studies which failed to find any poten-tiation effect of albumin infusion on the diu-retic efficacy of furosemide in patients with the NS may have some methodological errors (e.g. patient selection). For example, the study of Akcicek et al enrolled patients who were not resistant to diuretics,4 which can justify the reason they failed to find a synergy between albumin and furosemide. Elwell et al conduc-ted a systematic review in 2003 in this regard, which concluded that the administration of albumin to enhance diuretic efficacy should be reserved for patients with severe hypoalbu-minemia.8 We suggest that all the available studies should be critically appraised and included in a new meta-analysis to draw a final conclusion. Dr. Nariman Sepehrvand, National Institute of Health Research, Tehran University of Medical Sciences, No. 78, Italia Street, Keshavarz Boulevard, Tehran, Iran E-mail: nariman256@gmail.com

Letter to the Editor 372

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