DS (Child) H J 2011; 27 (2) : 64-67

ORIGINAL ARTICLE

Low serum IgG level during remission: A

predictor of frequent relapse nephrotic
syndrome
Farid Ahmed1, Sanjeev Kumar Prasad2, Shireen Afroz3, Kanta Chowdhury4, Maruf-ul-
Quader5, Mohammed Hanif6

Abstract
Background: In general decreased serum IgG level in a patient with active nephrotic
syndrome reverts back towards normal during remission. But literature revealed
that patients who turned out to be frequent relapse nephrotic syndrome, in them
serum IgG remains in the lower range during remission. Persistently low serum IgG
level during remission may be a predictor of frequent relapse nephrotic syndrome.
Objective: To determine serum IgG level in children with nephrotic syndrome and also
to see whether this IgG level has any relationship with frequent relapse nephrotic syndrome.
Materials and Methods: This prospective study was conducted between May 2003 to
April 2004 in the Nephrology unit of Dhaka Shishu (Children) Hospital. Total 30 children
of first attack of nephrotic syndrome, age ranging from 1 to 10 year were included in
this study. Patients of initial attack of nephrotic syndrome were treated with standard
dose of oral prednisolone according to ISKDC protocol. They were followed up for 1
year and during this follow up period they were diagnosed as infrequent relapse
nephrotic syndrome, frequent relapse nephrotic syndrome and non relapser. Serum
IgG was estimated on 3 occasion; at the onset of the disease, after 6 weeks when the
patient achieved remission & again when the patient had first relapse.
Results: Among 30 patients 20 were male and 10 were female (Male: female= 2:1).
The serum IgG level at the onset showed no significant relation with the rate of
relapse (p=0.634).Serum IgG level during relapse showed near to significant relation
with the rate of relapse though not statistically significant (p=0.051). During remission
mean serum IgG level in frequent relapsers was 5.57± 0.72 (gm/L), in infrequent
relapsers was 9.35 ± 3.13 (gm/L) and those patients who had no relapse was 9.51±
3.62 (gm/L). During remission, serum IgG level in frequent relapse nephrotic syndrome
was significantly lower than infrequent relapse nephrotic syndrome (P<0.001).
Conclusion: During remission after initial attack of nephrotic syndrome, low level
of serum IgG has a relation with frequent relapse nephrotic syndrome and by
measuring serum IgG level in remission we can have an idea whether the patient will
suffer from frequent relapse nephrotic syndrome.
Key words: Predictor, Frequent relapse nephrotic syndrome, Serum IgG

1. Associate Professor of Paediatrics, Bangladesh Institute of Child Health (BICH), Dhaka Shishu Hospital
2. Former student, Bangladesh Institute of Child Health (BICH)
3. Associate Professor of Paediatric Nephrology, Dhaka Medical College & Hospital
4. Medical Officer, Dhaka Shishu (Children) Hospital
5. Research Assistant, National Institute of Kidney Diseases & Urology (NIKDU), Dhaka
6. Professor, Paediatric Nephrology, Bangladesh Institute of Child Health (BICH), Dhaka Shishu Hospital
Correspondence to: Dr. Farid Ahmed, Associate Professor, Bangladesh Institute of Child Health (BICH), Dhaka
Shishu Hospital, E-mail: farid_shamim@live.com

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Introduction
The natural history of primary idiopathic nephrotic
syndrome suggests off and on relapse and remission.
The International Study of Kidney Diseases in
Children (ISKDC) originally reported relapse rate of
76% to 97%, with frequently relapsing rate of up to
50%.1 Nephrotic syndrome is an important cause of
significant short-term morbidity and it can follow a
chronic relapsing course with long-term adverse
consequences. There is no serological, laboratory or
morphological criteria which could be predictive of the
future course of the disease following the initial episode.
However the number of relapses following the first 6
months of presentation is highly predictive of the
subsequent course.2 It has long been recognized that
an immunogenic stimulus can trigger idiopathic
nephrotic syndrome or cause recurrence of the disease.
Studies have shown that there are altered levels of
different immunoglobulin during relapse and remission
period of nephrotic syndrome.3-5 Different studies have
shown that there is low levels of IgG and IgA and raised
IgM in patients with idiopathic nephrotic syndrome
during relapse and the levels returns towards normal
during steroid induced remission. 6-10 It has also been
observed that urinary losses are not sufficient to reduce
IgG and IgA concentrations.11-13 This reciprocal
derangement of IgG and IgM in idiopathic nephrotic
syndrome led to the hypothesis that immunoglobulin
isotope switching by B cells was abnormal in nephrotic
syndrome.14-16 Few studies also reported no change
in the immunoglobulin levels between frequent
relapsers and infrequent relapsers.4 So this study was
aimed to see the levels of IgG in cases of frequent
relapse nephrotic syndrome when the patient was in
remission and also to see whether this IgG had any
role in predicting frequent relapse nephrotic
syndrome.
Materials and Methods
This prospective study was conducted in the
Nephrology unit of Dhaka Shishu Hospital from May
2003 to April 2004.Thirty children of first attack of
nephrotic syndrome between 1-10 year of age were
selected purposively as study population. First attack
of nephrotic syndrome patients having typical
features of minimal change nephrotic syndrome
without any other systemic disease were included
in this study. The criteria of diagnosis of minimal
change nephrotic syndrome was age between 1-10
year, more than 3 + proteinuria, blood pressure
within normal range for the age, sex and height of
the patient, normal C3 level, no hematuria, spot
urinary protein creatinine ratio more than 2.
Exclusion criteria was age less than 1 year and more
DS (Child) H J 2011; 27 (2)
than 10 years, nephrotic syndrome other than
minimal lesion, nephrotic syndrome having other
major illness.
All patients who fulfilled the inclusion criteria were
included in this study after taking informed consent
from the parent or legal guardian. Detailed history
was taken and clinical examination was done and
recorded on a data sheet. Laboratory investigations
including complete blood count, serum total protein,
serum albumin, serum cholesterol were done. Blood
urea, serum creatinine, serum IgG level were also
estimated on the first presentation before starting
therapy. Renal biopsy was done in certain cases who
failed to respond to the standard treatment with
prednisolone and those who presented with atypical
features. The serum IgG level was again estimated
after 6 weeks when the patient went into remission.
The third estimation of serum IgG was done when
the patient presented with first relapse.
These patients were treated with standard dose of
prednisolone (60 mg /m2/d) daily for 6 weeks and
then alternate day therapy was given for next 6
weeks. The study population were followed up
regularly at monthly interval with routine and
microscopic urine examination, spot urinary protein
creatinine ratio and serum cholesterol level with
blood pressure and anthropometric measurement.
Depending on their steroid response pattern, the
study subjects were divided into 3 groups according
to ISKDC definition as frequent relapse nephrotic
syndrome (FRNS) Group-I, infrequent relapse
nephrotic syndrome (IFRNS) Group-II, and non
relapsers Group-III, Data was entered in a computer
database and statistical analysis was done by SPSS
11. ANOVA (analysis of variance) test was done.
Level of significance was taken as p<0.05. Ethical
clearance was approved by institutional Ethical
Review Committee.
ISKDC definition of relapse
Relapse: urine albumin > 3+ or >40mg/m2/hour for
3 consecutive days, have been in remission
previously. FRNS: when there are two or more
relapses in six months of initial response or more
than three relapses in any twelve months period.
IFRNS: who relapses two or less in a period of six
months of initial response or <3 relapses in any 12
consecutive months.
Results
A total of 30 children with male to female ratio 2: 1,
mean age 34±21 months (range 1to10 year) were
included in this study.
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Table I
Association of serum level of IgG with different types of NS

Parameters Nephrotic Syndrome Mean ± SD 95% Cl for Mean P

Type N Lower Bound Upper Bound value
Serum IgG (gm/L) Infrequent relapse 11 2.36 ± 1.25 1.51 3.10 0.634
on admission Frequent relapse 13 1.97 ± 0.62 1.60 2.35
No relapse 06 2.15 ± 1.01 1.09 3.21
Serum IgG (gm/L) Infrequent relapse 11 9.35 ± 3.13 7.25 11.45 0.001
in remission Frequent relapse 13 5.57 ± 0.72 5.13 6.00
No relapse 06 9.51 ± 3.62 5.72 13.31
Serum IgG (gm/L) Infrequent relapse 11 2.69 ± 0.97 2.04 3.34 0.051
in relapse Frequent relapse 13 1.96 ± 0.77 1.50 2.43
No relapse 00 00 00

Table I shows association of mean serum IgG level
in different types of nephrotic syndrome on
admission, in remission and in relapse. Out of 30
patients, 11 (36.6%) patient were IFRNS,13(43.3%)
patient were FRNS and 6 (20%) patient had no
relapse over a period of 1 year .The serum IgG level
at the onset showed no significant relation with the
rate of relapse(p=0.634).Serum IgG level during
relapse showed near to significant relation with the
rate of relapse though not statistically significant
(p=0.051).On the other hand, serum IgG level in
remission showed significant relation with the rate
of relapse. The mean serum IgG level during
remission in patients who were frequent relapsers,
was found to be 5.57±0.7 (95% CL for mean=5.13-
6.00), which was statistically significant (p=0.001).
Table II
Relationship of serum level of IgG with serum
cholesterol and serum albumin
Serum IgG Serum P Serum P different type of nephrotic syndrome. In contrast to
Cholesterol value Albumin value
(mmol/L) (gm/L)
Mean±SD Mean±SD
<2 (gm/L) 12.68±4.4 0.945 13.05±3.1 0.020
> 2 (gm/L) 12.62±6.7 16.00±6.3
Relationship of serum IgG with serum cholesterol
and serum albumin in nephrotic syndrome was also
seen in this study (Table II).With serum IgG level
less than 2 gm/L the mean serum cholesterol level
was 12.68±4.4 (mmol/L) and when serum IgG level
was equal or more than 2 gm/L then the mean serum
cholesterol level was 12.62±6.7 (mmol/L). The level
of serum IgG had no significant relation with serum
cholesterol level (p=0.945).
On the other hand when the serum IgG level was
less than 2 gm/L then the mean serum albumin level
was 13.05±3.1 (gm/L) and when serum IgG level was
equal or more than 2 gm/L then the serum albumin
level was 16.0±6.3 (gm/L) which was statistically
significant (p=0.020). The serum IgG level varies
directly with the serum albumin level.
Discussion
In this study 43.4% children turned out to be FRNS
at the end of one year follow up which is almost
consistent with previous report.2 Serum IgG has
been documented to be low in nephrotic syndrome
patients and revert back towards normal when the
nephrotic syndrome patient goes into remission.6-10
We found the association of serum IgG with the
the previous study6-10 we found low serum IgG level
at the onset showed no significant relation with the
rate of relapse. Serum IgG level during relapse
showed a near to significant relation with the rate
of relapse though not statistically significant
(p=0.051).On the other hand, serum IgG level during
remission in patients who turned out to be frequent
relapse nephrotic syndrome showed a statistically
significant relation. The serum IgG level raised to
normal value during remission period but it
remained to low normal value in frequent relapse

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nephrotic syndrome in comparison to infrequent
relapse nephrotic syndrome and non-relapsers.
Increased frequency of relapse in these patients is
probably due to low immunity which persisted in
these patients as indicated by low serum IgG level
during the remission period. Therefore low serum
IgG level during the period of remission can be
considered to be a predictor of frequent relapse
nephrotic syndrome.
We have also seen the association of serum IgG level
with that of mean serum cholesterol and serum
albumin on initial presentation. It was evident that
mean serum cholesterol level remained unchanged.
As the systemic effect of high serum cholesterol level
are usually apparent after many years the precise
relation with relapse rate could not be determined
at early stages. Also serum cholesterol took a longer
time to come back to normal level as compared to
serum albumin in which a very rapid change was
there.
On the other hand, mean serum albumin level varied
significantly with the serum IgG level on initial
presentation. Thus we can say that the serum IgG
varies directly with serum albumin level.
Conclusion
In this study we have observed that in remission
the serum IgG level comes back to normal level in
infrequent relapse nephrotic syndrome and non-
relapsers but this serum IgG remains in the low
normal level in the frequent relapse nephrotic
syndrome. Thus we can conclude that persistently
low or low normal serum IgG level during the period
of remission is an important predictor of frequent
relapse in children with minimal change nephrotic
syndrome.
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