Treatment of Severe Edema in Children with Nephrotic

Syndrome with Diuretics Alone — A Prospective Study

Gaurav Kapur,* Rudolph P. Valentini,* Abubakr A. Imam,† and Tej K. Mattoo*
*Carman and Ann Adams Department of Pediatrics, Division of Pediatric Nephrology and Hypertension, Children’s
Hospital of Michigan, Wayne State University, Detroit, Michigan; and †Division of Pediatric Nephrology and
Hypertension, Children’s Hospital Medical Center of Akron, Akron, Ohio

Background and objective: Severe edema in children with nephrotic syndrome (NS) may be associated with volume
contraction (VC) or volume expansion (VE). Usually, severe edema in children is treated with intravenous (IV) albumin and
diuretics, which is appropriate for VC patients. However, in VE patients, this can precipitate fluid overload. The objective of
this study was to evaluate treatment of severe edema in NS with diuretics alone.
Design, setting, participants, & measurements: Thirty NS patients with severe edema were enrolled in this prospective study
in two phases. VC was diagnosed based on fractional excretion of sodium (FeNa) <1%. VC patients received IV albumin and
furosemide. VE patients received IV furosemide and oral spironolactone. On the basis of phase 1 observations, FeNa <0.2%
identified VC in 20 phase 2 patients.
Results: All phase 1 patients had FeNa <1%. Phase 1 patients when reanalyzed based on a FeNa cutoff of 0.2%; it was noted
that VC patients had higher BUN, BUN/creatinine ratio, urine osmolality, and lower FeNa and urine sodium compared with
VE patients. Similar results were observed in phase 2. VC patients had significantly higher renin, aldosterone, and antidiuretic
hormone levels. In phase 2, 11 VE patients received diuretics alone and 9 VC patients received albumin and furosemide. There
was no difference in hospital stay and weight loss in VC and VE groups after treatment.
Conclusions: FeNa is useful in distinguishing VC versus VE in NS children with severe edema. The use of diuretics alone
in VE patients is safe and effective.
Clin J Am Soc Nephrol 4: 907–913, 2009. doi: 10.2215/CJN.04390808

I
diopathic nephrotic syndrome (NS) is a common renal
disease in children. Children with severe edema are usu-
ally hospitalized and treated with intravenous (IV) albu-
min and diuretics. In contrast to adults, children are often more
severely hypoalbuminemic and edematous, necessitating hos-
pitalization and IV albumin administration. Albumin is rou-
tinely used in children because of (1) low serum oncotic pres-
sure due to hypoalbuminemia, (2) reports of diuretic resistance
and decreased efficacy in NS (1– 4), (3) increased diuresis when
diuretics are given after IV albumin (1,5,6), and (4) a reluctance
to treat patients with diuretics only because of concerns about
dehydration and increased risk of thromboembolic complica-
tions.
The routine use of albumin for severe edema (7) in children
with NS is based on two mutually exclusive hypotheses pro-
posed for the pathogenesis of edema (8 –11). According to the
underfill hypothesis, severe hypoalbuminemia decreases intra-
vascular oncotic pressure, leading to circulatory volume deple-
tion and subsequent sodium/water retention (8 –11). The over-
fill mechanism proposes a primary renal defect in sodium
Received August 28, 2008. Accepted February 23, 2009.
Published online ahead of print. Publication date available at www.cjasn.org.
Correspondence: Gaurav Kapur, Children’s Hospital of Michigan, Carman and
Ann Adams Department of Pediatrics, 3901 Beaubien Boulevard, Detroit, MI
48201. Phone: 313-745-5604; Fax: 313-966-0039; E-mail: gkapur@med.wayne.edu
excretion leading to sodium/water retention and thereby hy-
pervolemia and edema (8 –11). The underfill hypothesis is be-
lieved to be more common (7,12). Also, clinically it is not
possible to differentiate severely edematous NS patients with
intravascular volume expansion (VE) from those with intravas-
cular contraction (VC) (7,12). Hence, the pediatric practitioners
are reluctant to only treat the former group of patients with
diuretics. The objective of this study was to evaluate the use of
diuretics alone for the treatment of severe edema in a subset of
children with NS, identified as VE.
Materials and Methods
This is a prospective cohort study of children admitted to the pedi-
atric nephrology service at the Children’s Hospital of Michigan with NS
and severe edema (October 2003 to August 2006). The study, which was
approved by the Human Investigation Committee at Wayne State
University, was conducted in two phases. The difference between the
two phases was the criteria used for differentiating VE and VC patients.
Definitions
NS. NS was defined as the presence of profound proteinuria (ran-
dom urine protein creatinine ratio ⬎3.0) (13), hypoalbuminemia (serum
albumin ⱕ2.5 g/dl), and edema.
Severe Edema. Severe edema was defined as evidence of 3⫹ or more
pitting edema and ascites. (Pitting edema graded by study personnel on
a scale of 0 to 4, with 0 being no edema and 4⫹ being grossly swollen
leg with prolonged pitting upon pressure).

Copyright © 2009 by the American Society of Nephrology ISSN: 1555-9041/405–0907

908 Clinical Journal of the American Society of Nephrology
Fractional Excretion of Sodium. Fractional excretion of sodium
(FeNa) was calculated on spot urine by the formula FeNa ⫽ (urine
sodium ⫻ serum creatinine)/(plasma sodium ⫻ urine creatinine)
Phase 1
Inclusion Criteria. Inclusion criteria included the following: (1)
Signed consent for the study [parental consent for all and patient assent
(age ⬎12 yr)], (2) children aged 1 to 18 yr, and (3) admitted with NS and
severe edema.
Exclusion Criteria. Exclusion criteria were (1) altered sensorium, (2)
seizures, (3) fever ⱖ38.3°C, (4) gross hematuria, (5) reduced GFR
[⬍90ml/min/1.73 m2 (estimated by Schwartz formula (14))], (6) 25%
increase in serum creatinine from baseline value (if available), (7)
clinical peritonitis, (8) patients on diuretic(s) and angiotensin convert-
ing enzyme inhibitors, and (9) patients with history of clot (arterial or
venous) or family history of thrombotic disorders.
Laboratory Evaluation. As per our institutional protocol, the labora-
tory evaluation of such patients on admission includes serum chemis-
try (sodium, potassium, bicarbonate, BUN, creatinine, calcium, magne-
sium, and phosphorus), complete blood count with differential,
urinalysis and a spot urine protein, and urine creatinine. The patients’
electrolytes, hemoglobin (Hb) and hematocrit (Hct) were then moni-
tored daily during their hospital stay. The study was designed so that
the patients did not have any additional blood draws. The additional
tests done upon admission included (1) serum osmolality, (2) urine
osmolality, (3) urine sodium (UNa), and urine creatinine
Criteria Used for Diagnosing Intravascular Volume Status. Patients
with FeNa ⬍1% were considered as VC and those with FeNa of ⬎1%
were considered as VE.
Phase 2
On the basis of phase 1 observations, the FeNa criterion for the VC
and VE groups was modified. Patients with FeNa ⬍0.2% were identi-
fied as VC and those with FeNa ⱖ0.2% were identified as VE. The
inclusion/exclusion criteria were similar to phase 1, except that the
patients on immune suppression at hospitalization were excluded from
phase 2. This change was prompted to exclude the potential effects of
immunosuppressants on NS and tubular transport, thereby excluding
them as a variable in FeNa interpretation. The laboratory workup was
similar to phase 1, except that plasma renin activity (PRA), serum
aldosterone, and serum antidiuretic hormone (ADH) levels were also
checked.
Treatment Plan
The treatment for NS and severe edema was the same for both
phases. All patients were treated with (1) fluid restriction to two-thirds
of maintenance (15); (2) sodium restriction to ⬍2 mEq/kg per d; (3)
prednisone, per International Study of Kidney Disease in Children
regimen (16) (started after routine workup for new NS patients and
immediately upon admission in relapsed NS patients). The VC group
received IV albumin (25%) at 0.5 g/kg twice daily over 2 to 3 h followed
by IV furosemide at 1 mg/kg per dose (maximum 40 mg) at the end of
albumin infusion for severe edema. The VE group received diuretics, IV
furosemide at 1 mg/kg per dose (maximum 40 mg) twice daily, and
oral spironolactone at 2.5 mg/kg per d divided twice daily (maximum
100 mg twice daily, dose rounded to 25-mg tablets or its multiples) for
severe edema. The criteria for patient withdrawal were (1) a 50%
increase in serum creatinine and (2) clinical deterioration as evidenced
by (a) development of study exclusion criteria and (b) worsening
edema despite treatment.
Clin J Am Soc Nephrol 4: 907–913, 2009
Analytical Techniques
Serum chemistries were measured by an automated analyzer (Vitrios
250 Chemistry System, Ortho-Clinical Diagnostics, NY). Serum aldo-
sterone was measured by an RIA kit (Coat-a-count aldosterone, DPC,
Los Angeles, CA). PRA and serum ADH were assayed at Esoterix
Laboratories (Austin, TX).
Statistics
SPSS14.0 was used for statistical analysis. Continuous variables were
evaluated as mean ⫾ SD in both groups. The difference between the
mean of two groups was compared by independent t test. Treatment
trends in each group were evaluated by paired t test. Correlations
between laboratory parameters were expressed as a Pearson correlation
coefficient (negative r value indicated an inverse correlation; a positive
value indicated direct correlation). A P value ⬍0.05 was considered
statistically significant for all of the statistics. Because of the wide range
for normal hormonal concentrations, hormonal levels were also com-
pared by nonparametric (Kruskal-Wallis test). These data are not
shown because results were similar to parametric test (independent t
test).
Results
During phase 1 of the study, 16 patients were admitted
with severe edema and NS. Of these, six were excluded
because of fever (2), medications (2) [enalapril (1) and furo-
semide (1)], and decrease in GFR to ⬍90ml/min/1.73 m2 (1).
One more patient was excluded because the treatment was
started before laboratory testing. The mean age of the 10
phase 1 patients was 6.9 ⫾ 4.6 yr (range 1.4 to 15). Of these
ten patients, 9 (90%) patients were caucasian and 1 (10%)
patient was black/African American. Two patients were on
immunosuppression (corticosteroids) for their NS. Present-
ing symptoms were generalized swelling (100%), decrease in
urine output (100%), and increased thirst (20%). None of the
patients had dizziness, postural hypotension, muscle
cramps, delayed capillary refill, or orthostatic hypotension.
The laboratory results (Table 1) revealed that of the ten
patients with FeNa ⬍1%, five patients (patients # 2, 5, 7, 8, 9;
Table 1) had higher UNa (⬎20 mEq/L), and lower BUN,
Hb/Hct, and urine osmolality, which did not support VC in
these patients. Reanalysis of the data in these patients using
FeNa ⬍0.2% as a cutoff for VC was then done, because these
patients were on a normal sodium diet (125 to 250 mEq/d)
and had a normal GFR (17). These patients could then be
divided in two groups: VC group with FeNa ⬍0.2% and VE
group with FeNa ⱖ0.2% (Table 2). VC patients had signifi-
cantly higher BUN, BUN/creatinine ratio, FeNa, and signif-
icantly lower serum and UNa concentration compared with
VE patients. Although not statistically significant, mean Hb/
Hct, urine osmolality, and urine-to-serum osmolality ratio
(UOsm/SOsm), were higher in the VC group compared with
the VE group. These observations prompted us to redefine
the FeNa criterion for intravascular volume status, leading to
phase 2 of the study.
During phase 2, 42 patients were admitted with severe
edema and NS. Of these, 22 patients were excluded [immuno-
suppression (14), fever (4), and decrease in GFR to ⬍90ml/
min/1.73 m2 (4)]. The mean age of 20 patients (30% girls, 70%
Clin J Am Soc Nephrol 4: 907–913, 2009 Diuretics for Severe Edema in Nephrotic Syndrome 909

boys) included in phase 2 was 7.6 ⫾ 4.7 yr. The racial distribu-

(ml/min/1.73
tion of phase 2 patients included 9 (45%) black/African Amer-
GFR ican and 11 (55%) caucasian. The main presenting symptoms

124
124
104
109
160
142
165
140
160
149
m2)
were generalized swelling (100%) and decrease in urine output
(100%). None of the patients upon presentation had diarrhea,
vomiting, increased thirst, dizziness, postural hypotension,
FeNa

0.03
0.31
0.02
0.01
0.51
0.05
0.18
0.58
0.58
0.01
muscle cramps, orthostatic hypotension, or delayed capillary
refill. On the basis of FeNa, these patients were grouped as VC
(mg/dl) (mMol/L) (mOsm/kg) Creatinine (mOsm/kg) Creatinine (mMol/L)

(FeNa ⬍0.2%, n ⫽ 9) and VE (FeNa ⬎0.2%, n ⫽ 11). A com-

UNa

5
116
5
5
83
18
87
95
59
5
parison between the two groups before treatment is presented
in Table 2. Noteworthy were statistically significant higher
serum BUN, BUN/creatinine ratio, urine osmolality, and
UOsm/SOsm in the VC group as compared with the VE group.
Protein/
Urine

5.99
5.88
28.0
15.5
54.9
12.1
2.4
13.0
36.7

12.2
Also VC patients had statistically significant lower FeNa and
spot UNa. During both phases, there was no significant differ-
ence in the mean serum albumin and urine protein/creatinine
Osmolality

ratio in the two groups (Table 2).

Urine

512
834
900
1270
454
1163
926
581
387
1020

Serum aldosterone, PRA, and ADH concentration were eval-

uated as other indicators of volume status in the study cohort
(n ⫽ 17). VC patients had significantly higher renin, aldoste-
rone, and ADH concentration in comparison to the VE group
(Table 2, VC ⫽ 8, VE ⫽ 9). As a further measure of aldosterone
BUN/

47.5
13.3
45.0
36.6
32.5
31.6
33.3
30.0
30.0
37.5

effect, urinary potassium index (18,19) [(UK ⫻ 100)/(UK ⫹

UNa)] was also evaluated (n ⫽ 12). Similar to serum aldoste-
rone, urinary potassium index was significantly higher in the
Osmolality

VC group (n ⫽ 6, mean ⫽ 91.4 ⫾ 5.1) compared with the VE

Serum

280
293
281
295
287
305
292
288
294
285

group (n ⫽ 6, mean 32.8 ⫾ 14.9). The correlation between these

known hormonal indicators of VC with FeNa was also evalu-
ated. A statistically significant negative correlation between
FeNa and the evaluated hormones was noticed [renin (r ⫽
Sodium

⫺0.692, P ⫽ 0.003), aldosterone (r ⫽ ⫺0.529, P ⫽ 0.035), ADH

123
141
127
129
132
133
133
134
135
134

(r ⫽ ⫺0.642, P ⫽ 0.01)]. Hence, lower FeNa and thereby VC

correlated with higher renin, aldosterone, and ADH concentra-
tion, supporting our identification of volume status on the basis
Creatinine
Serum
Table 1. Details of patients included in phase 1 of the study

0.40
0.90
0.40
0.60
0.40
0.60
0.30
0.50
0.40
0.40

of FeNa.
SBP/DBP, systolic blood pressure/diastolic blood pressure.

Table 3 shows treatment effect on patient’s BUN, serum

creatinine, Hb/Hct, heart rate (HR) and systolic blood pressure
(SBP) in the study groups (paired t test). In the VC group there
SBP/DBPb Albumin
(mmHg) (gm/dl)
Serum

1.5
2.2
1.3
1.3
1.4
1.6
2.0
1.5
1.7
1.9

was a decrease in mean Hb/Hct, BUN, and creatinine after

treatment. In comparison, VE patients showed an increase in
the mean Hb/Hct, BUN, and creatinine, suggestive of mild VC
with diuretic therapy. Also, the VC group had an increase in
84/49
112/64
108/74
129/96
104/66
127/85
82/63
113/59
128/56
108/78

mean HR and SBP with albumin, consistent with mobilization

of the extracellular fluid into the intravascular compartment.
The VE group showed a decrease in mean HR and SBP, indi-
(yr)/ HR (beats/

cating that these patients were not volume contracted at initi-

min)

ation of diuretic therapy.

87
72
135
112
68
85
100
85
80
97

Percentage weight loss (net weight loss from admission

weight) and duration of hospitalization were evaluated as in-
M, male; F, female

dicators of treatment efficacy. There was no significant differ-

Gendera

3/M
14/M

8/M
8/M
15/M

4/M
8/M
5/M

ence in duration of hospitalization (VC group 4.04 ⫾ 2.3 d

1.4/F

3/F

versus VE group 3.30 ⫾ 0.82 d; P ⫽ 0.29), percentage weight loss

Patient Age

after 1 d of hospitalization (VC group 2.6 ⫾ 1.9% versus VE

group 4.06 ⫾ 2.6%; P ⫽ 0.13), and at the end of treatment (VC
group 8.92 ⫾ 4.8% versus VE group 7.37 ⫾ 3.47%; P ⫽ 0.37)
b
a
10

between the two groups (Table 4).

1
2
3
4
5
6
7
8
9
910 Clinical Journal of the American Society of Nephrology Clin J Am Soc Nephrol 4: 907–913, 2009

Table 2. Comparison of laboratory results at admission of VC group (FeNa ⬍0.2%) and VE group (FeNa ⱖ0.2%)
Phase 1a Phase 2b
Laboratory Result
VC VE P VC VE P

New-onset NS 3 3 8 9
Infrequent relapsing NS 0 1 1 2
Frequently relapsing NS 2 1 0 0
Age (years) 6.5 7.4 0.77 5.8 9.1 0.13
HR before treatment (beats/min) 103.2 81.0 0.07 96.8 93.9 0.68
SBP before treatment (mmHg) 111.2 109.8 0.9 108.9 114.3 0.29
BUN (mg/dl) 18.6 12.4 0.00 16.4 11.7 0.05
BUN/creatinine 39.7 27.8 0.03 36.9 21.3 0.01
Hb at admission (gm/dL) 15.2 13.8 0.16 13.5 12.1 0.05
Hct at admission (%) 43.0 40.2 0.31 39.5 36.0 0.06
Sodium (mMol/L) 129.2 135.0 0.05 134.2 136.3 0.19
Albumin (gm/dl) 1.5 1.8 0.23 1.71 1.69 0.97
Serum osmolality (mOsm/kg) 289.2 290.8 0.75 290.7 290.5 0.97
Urine osmolality (mOsm/kg) 973.0 636.4 0.08 1026.0 621.1 0.00
UNa (mMol/L) 7.6 88.0 0.00 7.1 96.1 0.00
Urine protein/creatinine ratio 24.1 13.3 0.33 15.3 15.2 0.33
UOsm/SOsm 3.3 2.2 0.07 3.5 2.1 0.00
FeNa 0.02 0.43 0.00 0.02 0.61 0.01
Admission GFR (ml/min/1.73 m2) 125.6 149.6 0.07 136.8 128.4 0.47
PRA (ng/dl per h) 553 179 0.00
Serum aldosterone (ng/ml) 29.4 3.4 0.01
Serum ADH (pg/ml) 5.9 1.6 0.00
a
Results for phase 1 (VC group, n ⫽ 5; VE group, n ⫽ 5).
b
Results for phase 2 (VC group, n ⫽ 9; VE group, n ⫽ 11).

Therapeutic Complication are hypervolemic (20). Hence, potentially 67% (normo/euv-

One patient in phase 2 who was classified as VE and only
received diuretics for severe edema (FeNa ⬍0.2% on admis-
sion) was switched to albumin therapy after 48 h of treatment
because of electrolyte abnormalities [included in statistical
analysis in VE group for admission evaluation only (Table 2)
and not in outcome data (Table 3 and 4)]. This patient’s admis-
sion evaluation was: sodium 141 mEq/L, BUN 16 mg/dl, cre-
atinine 0.4 mg/dl, BUN/creatinine ratio 47.5, urine osmolality
1119 mosm/kg, UOsm/SOsm 3.77, FeNa 0.28, PRA 146 ng/dl per
h, aldosterone 4 ng/ml, and ADH 5.9 pg/ml. This patient
demonstrated initial weight loss (2% in initial 48 h of diuretic
treatment) and rise in Hb/Hct. He was switched to albumin
plus diuretics per treatment protocol after 48 h of treatment
because of rise in serum creatinine (0.7 mg/dl, ⬎50% increase
from admission value; Na 133 mEq/L, serum BUN 30 mg/dl,
BUN/creatinine ratio 42.9). Another patient developed a rise in
creatinine (admission 0.7 mg/dl; post-treatment 0.9 mg/dl)
that normalized upon stopping diuretics.
Discussion
This is the first study reporting the use of diuretics only in the
treatment of a subset of children with NS identified prospec-
tively on the basis of FeNa ⱖ0.2% without any complications.
Analysis of 217 previously reported patients with NS from 10
studies showed that 42% of patients are normovolemic and 25%
olemic) of NS patients can be treated with diuretics alone.
However, the published literature on diuretics alone in severe
edema is mostly limited to reports of its use in patients (usually
adults) with chronic edema and obvious signs of volume over-
load as in GN and chronic renal failure (21–25).
In addition to various studies reporting modest to trivial
change in diuretic resistance with albumin (7,26), albumin ther-
apy has been associated with complications related to fluid
overload (5). In a study of patients with NS, albumin treatment
was associated with delayed response to corticosteroid treat-
ment and more frequent relapses after remission compared
with patients not receiving albumin (27). Although the contri-
bution of albumin to progressive tubulointerstitial injury is
under investigation (28), clinically it is known that patients
with frequently relapsing or treatment-resistant NS have a poor
prognosis.
Vande Walle et al. evaluated the pathophysiology of edema
in NS under controlled salt and water intake and proposed the
presence of a subset of patients with overfilling who can be
safely treated with diuretics alone (18,19,29,30). Laboratory in-
dices used in the past to differentiate VE from VC include
PRA/aldosterone, atrial natriuretic peptide, FeNa, and urine
osmolality (19,30,31). They proposed that patients with NS and
VE have normal FeNa and can be managed by diuretics alone
Clin J Am Soc Nephrol 4: 907–913, 2009 Diuretics for Severe Edema in Nephrotic Syndrome 911

Table 3. Treatment response of VC patients treated with IV albumin (VC; n ⫽ 9, left panel) and VE patients with
treated with diuretics only (VE; n ⫽ 10a, right panel) during phase 2. The P value represents paired t test
comparison within each group before and after treatment
Patients with FeNa ⬍0.2% Patients withFeNa ⱖ0.2%
and Treated with IV and Treated with Diuretics
Result albumin (n ⫽ 9) Only (n ⫽ 10a)

Mean P Mean P

HRb 96.8 0.32 93.5 0.22

HR1c 102.4 87.9
SBPb 108.9 0.52 114.1 0.26
SBP1c 110.9 109.6
HRb 96.8 0.94 93.5 0.23
HRFd 96.4 90.0
SBPb 108.9 0.80 114.1 0.55
SBPFd 110.3 112.8
Hbb 13.5 0.01 12.17 0.04
HbFe 12.2 12.65
Hctb 39.5 0.01 36.23 0.01
HctFe 35.7 37.9
BUNb 16.4 0.16 11.0 0.27
BUNdsf 13.1 13.1
Serum creatinineb 0.47 0.18 0.63 0.34
Creatdsf 0.41 0.66
a
One patient switched from diuretics alone to IV albumin/diuretics was excluded.
b
Values before treatment.
c
HR1/SBP1, HR/SBP after 1 h of IV albumin or IV furosemide.
d
HRF/SBPF, HR/SBP at the end of IV albumin or IV furosemide.
e
HbF/HctF, Hb/Hct at discharge.
f
BUNds/Creatds, BUN/serum creatinine at discharge.

Table 4. Outcome results of the study patients with FeNa ⱖ0.2% and treated with diuretics alone and of the
patients with FeNa ⬍0.2% treated with IV albumin followed by diuretics
Diuretics
Result IV Albumin followed by Diuretics P
Onlya

Percentage weight loss after day 1 of 4.06 ⫾ 2.60 2.63 ⫾ 1.93 0.13
hospitalization
Percentage weight loss at the end of 7.37 ⫾ 3.47 8.92 ⫾ 4.80 0.37
treatment
Duration of hospitalization 3.30 ⫾ 0.82 4.04 ⫾ 2.34 0.29
a
One patient that was switched from diuretics alone to IV albumin/diuretics was excluded.

(18,19,30). In their studies, mean FeNa in NS patients with early
relapse with hypovolemic symptoms was 0.3%, notably lower
than that seen in those without hypovolemic (1.1%) symptoms
(18,30). The difference in the FeNa between their study and
ours is most likely related to sodium intake of the patients.
FeNa for patients on a normal home diet (sodium intake 125 to
150 mEq/d) and normal GFR is 0.2 to 0.3% (17). Therefore,
phase 1 results were reanalyzed and criteria for VC and VE
changed for study phase 2 using a cutoff of 0.2% for FeNa.
Hormonal evaluation in the study groups coupled with a sig-
nificant inverse correlation between FeNa and levels of the
vasoactive hormones supported our hypothesis that avid so-
dium retention is indicative of hypovolemia and patients not
having avid sodium retention are non-hypovolemic. Treatment
trends in the VC and VE group on Hb/Hct, HR, creatinine, and
no side effects in the VE group receiving diuretics alone also
supported study categorization based on FeNa.
Another study (mean age 5.97 ⫾ 2.9 yr) evaluated volume
load in minimal-change NS by measuring inferior vena cava
diameter on echocardiography and treating all patients with
diuretics alone (furosemide and/or amiloride) (32). These
patients underwent a starvation period before evaluation
912 Clinical Journal of the American Society of Nephrology
(32), unlike our study cohort who was on a non-restricted
home diet.
The suboptimal response to diuretic-only treatment in one
patient could be due to high ADH levels (patient; 5.9 pg/ml,
group 1; 5.9 pg/ml, group 2; 1.6 pg/ml). Persistent ADH se-
cretion leading to salt and water retention could be secondary
to osmotic (33) or volume-mediated (34) stimulus, as hypothe-
sized by other researchers. The patient was switched to albu-
min and furosemide per protocol despite no clinical signs and
symptoms of dehydration. It is possible that the patient would
have continued to respond to diuretics alone because the pa-
tient did respond to diuretics alone by losing 2% of the admis-
sion weight in the first 48 h of treatment. All other patients
treated with diuretics alone showed no complications or
change in study outcome criteria.
In conclusion, diuretic therapy alone is safe in pediatric pa-
tients with NS presenting with severe edema and FeNa ⬎0.2%.
Future studies with larger patient numbers are needed to con-
firm these preliminary findings, in which severely edematous
patients could potentially be treated as outpatients by oral
diuretics.
Disclosures
None.
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