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 9164140)] as compared to
furosemide administered alone [880 mL/day
(95% CI 5102105)], 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;16:4814.
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;55:62933.
5. Akcicek F. Diuretic effects of frusemide in pa-
tients with nephrotic is it potentiated by intra-
venous albumin? Br Med J 1995;310:1023.
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;16:44854.
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.


Authors 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 furosemides 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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