The Many Faces of Minimal Change
Nephrotic Syndrome: An Overview
And Case Study
Martha A. Richardson
ephrotic syndrome is a disorder
N
that is characterized by high-
level protein excretion in the
urine (greater than 40 mg/m2/
hour), gravity-dependent edema, hypo-
albuminemia, hyperlipidemia, and in
some cases, hypertension. It is seen pri-
marily in the pediatric population, with
an incidence of approximately 2 to 3
occurrences per 100,000 children (Bogt
& Avner, 2007). Causes can be idio-
pathic, congenital, or secondary.
The most common cause in the
pediatric population is idiopathic and
is often referred to as primary
nephrotic syndrome in the literature.
In contrast, it only accounts for ap-
proximately one-quarter of the adult
cases (Niaudet, 2004). Between 1967
and 1974, the International Study of
Kidney Disease in Children (ISKDC)
(1978, 1981) conducted a multicenter,
prospective study of 521 children
with primary nephrotic syndrome.
The population consisted of children
with primary nephrotic syndrome
who were biopsied prior to initiation
of treatment. Ninety percent of the
patients fell into one of three
histopathological categories. Seventy-
six percent had minimal change
nephrotic syndrome (MCNS) (also
called minimal change disease
[MCD]), 6.9% had focal and segmen-
tal glomerulosclerosis (FSGS), and
Martha A. Richardson, RN, CPNP, is a
Certified Pediatric Nurse Practitioner, Nephrology
Clinic, Children’s Medical Center Dallas, Dallas,
TX, and a member of ANNA’s Dallas Chapter.
She may be contacted directly via email at
Martha.richardson@childrens.com
Author Note: The use of Rituximab to achieve
reduction or elimination of proteinuria in nephrotic
syndrome is off-label use and still considered experi-
mental.
Statement of Disclosure: The author reported no
actual or potential conflict of interest in relation to
this continuing nursing education activity.
Nephrology Nursing Journal September-October 2012
Continuing Nursing
Education
Copyright 2012 American Nephrology Nurses’ Association
Richardson, M.A. (2012). The many faces of minimal change nephrotic syndrome: An
overview and case study. Nephrology Nursing Journal, 39(5), 365-374.
Idiopathic nephrotic syndrome is the most common form of nephrotic syndrome in the
pediatric population. Three major histopathological findings have been identified. The
most common is that of minimal change nephrotic syndrome. Most of these cases respond
well to oral steroids and achieve long-term remission. For those that become steroid
dependent, the clinical course can be quite difficult. The case study included demon-
strates some of the difficulties that can be encountered and questions that still exist with
management of this diagnosis.
Key Words: Nephrotic syndrome, high-level protein excretion, prednisone,
steroid treatment, proteinuria, renal biopsy, focal and segmental
glomerulosclerosis, histopathology, edema, hypertension, hyperlipi-
demia, infection, thromboembolism, immunoglobulin M, rituximab,
pediatrics.
Goal
To provide an overview of nephrotic syndrome, its signs and symptoms, and treatment
options in the pediatric population.
Objectives
1. Define nephrotic syndrome.
2. Explain the diagnosis process for determining nephrotic syndrome in a pediatric
patient.
3. Discuss treatment options for nephrotic syndrome in the pediatric population.
4. Describe steroid-dependent and steroid-resistant complications to treatment in
patients being treated for nephrotic syndrome.
5. Identify possible alternatives to steroid treatment in the patient with nephrotic syn-
drome who is steroid-dependent or steroid-resistant.
This offering for 1.5 contact hours is provided by the American Nephrology Nurses’
Association (ANNA).
American Nephrology Nurses’ Association is accredited as a provider of continuing nursing
education by the American Nurses Credentialing Center Comission on Accreditation.
ANNA is a provider approved by the California Board of Registered Nursing, provider number
CEP 00910.
Accreditation status does not imply endorsement by ANNA or ANCC of any commercial product.
This CNE article meets the Nephrology Nursing Certification Commission’s (NNCC’s) continu-
ing nursing education requirements for certification and recertification.
Vol. 39, No. 5 365
The Many Faces of Minimal Change Nephrotic Syndrome: An Overview and Case Study
7.5% had membranoproliferative
glomeruloanephritis (MPGN).
One purpose of the ISKDC
(1978, 1981) study was to further eval-
uate the accuracy of identifying the
underlying glomerular disease based
on clinical presentation to avoid the
need of performing a renal biopsy
prior to starting treatment. Resear-
chers found that the child’s response
to corticosteroids was a more reliable
prediction of MCNS versus FSGS.
Patients could be classified as steroid-
sensitive or steroid-resistant. Those
classified as steroid-sensitive achieved
complete remission within eight
weeks of starting steroid therapy. The
study also showed that when the child
was steroid-sensitive, the diagnosis
was most likely MCNS, and a renal
biopsy, an invasive and expensive
diagnostic tool, could be avoided
(ISKDC, 1981). This study estab-
lished the first guidelines for treating
idiopathic nephrotic syndrome and
provided a platform for further inves-
tigations that, in turn, have increased
our knowledge base and improved
our approach to the care of children
with this disorder.
Over the years, since the findings
of the ISKDC study were published,
there have been changes in the popu-
lation that present with nephrotic syn-
drome. For example, Srivastava,
Simon, and Alon (1999) found an
increase in the incidence of FSGS in
comparison to data provided by the
ISKDC study. They reviewed data on
pediatric patients with nephrotic syn-
drome from 1984 to 1995 cared for at
their facility. Data from their facility
revealed the proportion of MCD and
FSGS was 52.7% and 23%, respec-
tively, in contrast to 76.4% and 6.9%
for MCD and FSGS, respectively
(ISKDC, 1978, 1981). Ethnic differ-
ences, with the incidence of FSGS
being higher in African Americans
than in Caucasians, were noted in
both this study as well as in the study
by Kim et al. (2005). There was a
higher incidence of FSGS versus
MCNS, with prevalence of FSGS
being higher in African Americans
compared to the Caucasians. They
also noted a higher incidence of the
366
development of steroid resistance
after initial steroid responsiveness
than was noted in the ISKDC study.
The authors pointed out that the
increase in FSGS in their findings in
comparison to the ISKDC study may
have been due to a higher rate of
older children and African-American
children in their study group popula-
tion.
Another change is in the termi-
nology used to describe response to
steroids. It has broadened beyond
steroid-responsive and steroid-resist-
ant to include frequent relapsing ne-
phrotic syndrome and steroid-de-
pendent nephrotic syndrome
To address these changes and de-
velop more current guidelines based
on published literature for use in
practice and research, the Children’s
Nephrotic Syndrome Consensus
Conference was formed (Gipson et
al., 2009). The selected members of
this group were all North American
pediatric nephrologists. They were
provided with a total of 344 articles
for review. The guidelines that result-
ed from this review provide recom-
mendations for evaluation and treat-
ment based on presentation and re-
sponse to initial steroid therapy.
Therapy guidelines are provided for
initial therapy, infrequent-relapse,
frequently relapsing, steroid-depend-
ent, and steroid-resistant nephrotic
syndrome. Frequently relapsing is
defined as two or more relapses with-
in six months of the initial therapy, or
four lapses or more in any 12-month
period. Steroid-dependent is defined
as relapsing during taper of steroids
or within two weeks of completion
of steroid therapy. Steroid-resistant
refers to those who are not in remis-
sion after four weeks of steroid
therapy.
Minimal Change Nephrotic
Syndrome
Steroid-sensitive nephrotic syn-
drome is more common in boys than
girls, with a peak incidence between 1
and 4 years of age (Hodson, Alexander,
& Graf, 2008). Incidence based on
geographical and ethnic background
Nephrology Nursing Journal
varies. It appears to be less common
in African and African-American
children.
The onset of high-level protein-
uria (greater than 40 mg/m2/hour) is
usually preceded by an upper respira-
tory infection. In some children, the
onset can also follow insect bites, bee
stings, or poison ivy (Bogt & Avner,
2007). The pathology behind the
increased permeability at the level of
the podocyte that in turn allows the
excretion of large amounts of protein
is still not clearly understood. It is sus-
pected that there is an abnormality in
T-cell function due to the positive
response to T-cell-suppressing agents.
Evidence supports a T-cell-activated
permeability factor, but the specific
players and changes involved remain
unknown (Hodson et al., 2008).
Treatment of Proteinuria
The primary goal of treatment is
to control the abundant proteinuria
and keep the patient in remission.
Initial treatment since the 1950s has
been the use of intensive corticos-
teroid therapy (Hodson et al., 2008).
Because of the clear benefits of this
approach, no placebo-controlled
studies were done. The ISKDC study
(1981) set dosing guidelines, and these
then became the control group for
randomized control studies that fol-
lowed. This has led to a more effec-
tive and standardized treatment regi-
men for the corticosteroids. At initial
presentation, the recommended dos-
ing of prednisone by the ISKDC
(1981) was 60 mg/m2/day (maximum
of 80 mg/day), given as a single dose
or divided into two doses per day for
four weeks, followed by 40 mg/m2 in
divided doses for three consecutive
days out of seven for four weeks.
Remission is defined as protein
excretion of 4 mg/m2/hour or less or
negative-trace of protein on urine dip-
stick (Hodson et al., 2008). Studies
that followed have provided improv-
ed dosing regimens that increase time
to relapse. A review of two meta-
analyses (one of 5 trials and one of 7
trials) that compared duration of
steroid therapy for initial onset
September-October 2012 Vol. 39, No. 5
revealed supporting data that extend-
ed therapy of three to seven months
compared to two months resulted in
fewer relapses within a 12 to 24-
month period (Filler, 2003; Hodson,
Knight, Willis, & Craig, 2000). There
was no significant increase in steroid-
related complications with the pro-
longed dosing regimen. The guide-
lines set by the Children’s Nephrotic
Syndrome Consensus Conference
recommend an initial dosing regimen
of steroids as 60 mg/m2 per day for
six weeks followed by a six-week
course of 40 mg/m2 on alternate days
(Gipson et al., 2009). No further
steroid weaning is required. With
relapses, the length of dosing with
steroids is shortened. The initial high
daily dose is only given until the urine
protein excretion normalizes for three
consecutive days followed by the
lower alternate day dose for four
weeks. Further tapering after comple-
tion of four weeks is only recom-
mended for the child with frequently
relapsing nephrotic syndrome.
For the child who experiences
frequent relapses or is steroid-
dependent, the chances of unwanted
side effects from prolonged use of cor-
ticosteroids increases. Adverse effects
reported in clinical trials have includ-
ed growth retardation; hypertension;
significant weight gain; cushingoid
features; ophthalmic disorders, such
as cataracts and increased intraocular
pressure; behavioral disorders, such
as aggression, sleep disturbances, and
hyperactivity; and osteopenia (Hodson
et al., 2008). The use of other medica-
tions becomes necessary to decrease
proteinuria and avoid the complica-
tions of prolonged steroid use. These
may include alkylating agents, such as
chlorambucil and cyclophasphamide;
calcinurin inhibitors, such as cyclo-
sporine and tacrolimus; immunosup-
presants, such as mycophenolate
mefetil; and antiproteinuric therapy
with angiotensin-converting enzyme
inhibitors (ACE1) and angiotensin
receptor blockers (ARBs) (Gipson et
al., 2009; Ulinski & Aoun, 2010). The
use of levamisole is mentioned, but it
is no longer available universally to
include the United States. In cases
Nephrology Nursing Journal September-October 2012
where proteinuria persists despite
these treatments, some practitioners
have tried a more aggressive ap-
proach with use of rituximab (Betjes
& Roodnat, 2009; Gilbert, Hulse, &
Rigden, 2006; Hofstra, Deegan, &
Wetzels, 2007; Smith, 2007). A re-
view of case studies where rituximab
has been used is presented later in
this article. Its use is still considered
experimental, and formal research
studies regarding its efficacy are
needed.
Renal Biopsy
The question of when to perform
a renal biopsy has been an ongoing
discussion since the ISKDC (1978,
1981) published its recommendations.
Assessment of prognosis and deci-
sions regarding treatment should be
based on the prediction of the under-
lying disorder, and a strong correla-
tion was noted between steroid
responsiveness and findings of
MCNS on renal biopsy, especially in
children with primary nephrotic syn-
drome presenting at 6 years of age or
younger (ISKDC, 1978, 1981). In this
group, a renal biopsy is not consid-
ered necessary prior to starting treat-
ment with corticosteroids. Such a pre-
diction for non-responders was not as
clear, and biopsy was recommended
before the initiation of further treat-
ment. Gulati, Sharma, Sharma, Gupta,
and Gupta (2002) noted the persistent
diversity that still existed regarding
the need for renal biopsy in this pop-
ulation and did a prospective study in
their center. After review of data, they
concluded that all children presenting
with nephrotic syndrome younger
than 1 year of age should be biopsied
due to the high incidence of non-
MCD lesions in this group. Recom-
mendations for biopsy in children 1
through 16 years of age included
those that present with nephrotic syn-
drome and have unusual clinical fea-
tures (such as hypertension or hema-
turia) and/or laboratory abnormali-
ties (such as abnormal renal functions
or low complement C3), and/or
steroid non-responders. Gulati et al.
(2002) also found that no biopsy was
Vol. 39, No. 5
needed before initiating treatment
with cyclophosphamide in the steroid
responders, requiring more aggres-
sive therapy; data showed the predic-
tive value of cyclophosphamide re-
sponsiveness correlated better with
steroid responsiveness than with
histopathology subtype. The most
current guidelines set by the
Children’s Nephrotic Syndrome Con-
sensus Conference (Gipson et al.,
2009) address the need for renal biop-
sy in children 1 to 18 years of age.
Due to the higher incidence of FSGS
in children 12 years of age and older,
it is recommended that a renal biopsy
be done prior to initiating treatment
with corticosteroids. Children who
present between the ages of 1 to 11
years should be biopsied if found to
be steroid-resistant (Gipson et al.,
2009).
Limitations to renal biopsy
include the need for an adequate
specimen to capture an affected
glomeruli. To diagnose FSGS, only a
single abnormal glomerulus needs to
be recognized. Obtaining a revealing
specimen is dependent on the num-
ber of affected glomeruli within the
kidney at the time of biopsy as well as
if they are located at the site from
which the biopsy was taken (Howie,
2003; Melk, 2008). Potential compli-
cations to consider include macro-
scopic hematuria, perirenal hema-
toma, infection, excessive blood loss
requiring transfusion, post-procedure
pain, and arteriovenous fistula (Melk,
2008). Since renal biopsies in children
are commonly done under anesthesia
and sedation, the potential complica-
tions associated with these interven-
tions need to be considered.
Disease-Associated Complications
Edema
Edema is frequently the first rec-
ognized clinical sign of nephrotic syn-
drome at the time of diagnosis and
relapse. Without prompt response
with appropriate treatment measures,
it can get quite severe, and the child
can become symptomatic with as-
cites, pleural effusion, and/or weep-
367
The Many Faces of Minimal Change Nephrotic Syndrome: An Overview and Case Study
ing tissues. This also leaves the patient
at increased risk of infection. The
pathophysiology that results in the
edema may be related to the hypoal-
buminemia that develops as a result
of the high level proteinuria. Re-
duction of plasma oncotic pressure
occurs, leading to interstitial leakage
of fluid and hypovolemia and result-
ing in activation of the rennin-
angiotensin-aldosterone system with
sodium retention. This theory is cur-
rently under debate. After review of
the literature, Doucet, Guillaume, and
Deschenes (2007) noted that clinical
and experimental data suggest the
edema in nephrotic syndrome devel-
ops due to changes in intrinsic prop-
erties of the endothelial capillary bar-
riers rather than changes in plasma
oncotic pressure. Further, increased
sodium retention may be related to a
dysregulation that occurs in a regula-
tory pathway rather than hyperaldos-
teronemia (Doucet et al., 2007). The
specific pathway is still unknown, and
further research is needed.
Initiation of treatment at the first
signs of edema is preferred. Treat-
ment measures include the restriction
of oral salt intake and modest fluid
restriction (Gipson et al., 2009).
According to the guidelines set by the
Children’s Nephrotic Syndrome
Study Group, a sodium restriction of
1500 to 2000 mg daily is recommend-
ed. If the edema continues to increase
and the child becomes symptomatic,
the child may require hospitalization
for treatment with albumin infusions
and diuretics. Complications of this
more aggressive approach can be
quite severe. The albumin infusions
have been noted to cause hyperten-
sion, pulmonary edema, and conges-
tive heart failure. Excessive use of
diuretics can lead to hypovolemia
and hyponatremai, as well as renal
failure (Bogt & Avner, 2007; Gipson
et al., 2009).
Hypertension
Gipson et al. (2009) found that
13% to 51% of children with nephrot-
ic syndrome have hypertension.
Hypertension can be related to the
disease process as well as the use of
368
corticosteroids. The most recent
guidelines set by the Children’s
Nephrotic Syndrome Study Group
recommend that the blood pressure
be controlled so that it remains below
the 90th percentile for the child’s age,
gender, and height. Blood pressure
usually improves with resolution of
proteinuria. Many treatment modali-
ties used to address hypertension are
also used for the reduction of urinary
protein excretion and edema. These
include lowering salt intake and the
use of ACE inhibitors and/or ARBs.
The ability of the ACE inhibitors and
the ARBs to lower proteinuria and
slow progression of renal disease has
been clearly demonstrated in the liter-
ature (Kunz, Friedrich, Wolbers, &
Mann, 2008). The increased effective-
ness of the combined use of these
drugs is still in debate. A small num-
ber of studies have shown them to be
beneficial (Kunz et al., 2008; Wolf &
Ritz, 2005). At present, the recom-
mendation to use these in combina-
tion is reserved for patients who are
not benefitted by monotherapy. Of
note, the population involved in these
studies reviewed was primarily mid-
dle-aged and not pediatric. Docu-
mentation of side effects was also lim-
ited. With the use of these drugs,
there is the potential for hyper-
kalemia. Females need to be educated
regarding teratogenic effects.
Hyperlipidemia
The presence of hyperlipidemia is
a common finding in the child with
nephrotic syndrome. It may be related
to the hypoalbuminemia and the dis-
ruption of lipid metabolism (Querfeld,
1999). With the resolution of protein-
uria, there is a rapid normalization in
the serum lipid levels. Therefore, long-
term complications are of more con-
cern in children with refractory pro-
teinuria. Recommended treatment is
the limitation of dietary fat intake to
less than 30% of calories, saturated fat
to less than 10% of calories, and less
than 300 mg/day of dietary choles-
terol. The use of drug therapy is limit-
ed to those with persistent elevations in
serum cholesterol (Gipson et al., 2009).
Nephrology Nursing Journal
Infection
Infection is the most common
serious complication in children with
nephrotic syndrome as a result of the
disease process as well as the drug
therapies commonly used. Children
with nephrotic syndrome have low
serum immunoglobulin G (IgG) lev-
els due to urinary loss of IgG, abnor-
mal T lymphocyte function, and dis-
ruptions in the complement pathway,
which decreases the ability to opso-
nize encapsulated bacteria, such as Strep-
tococcus pneumonia (Gbadegesin &
Smoyer, 2008). The use of corticos-
teroids and immunosuppressants
increases their risk of infection and
can minimize the presenting signs
and symptoms related to infection.
Because of the increased susceptibili-
ty and masked presentations, the
healthcare provider must maintain a
high index of suspicion while caring
for this population.
The most serious and most com-
mon infection encountered is bacteri-
al peritonitis (Gbadegesin & Smoyer,
2008; Gipson et al., 2009). Early stud-
ies identified Streptococcus pneumonia as
the most common pathogen responsi-
ble, and a study by Gorensek, Lebel,
and Nelson (1988) also found this to
be true. However, Gorensek et al.
(1988) also noted a rise in the inci-
dence of gram-negative organisms.
Predisposing factors, in addition to
the impaired immune response,
include the presence of ascites and
hypoalbuminemia. Signs and symp-
toms include fever, abdominal ten-
derness and pain, peritoneal signs,
nausea and vomiting, and signs of
sepsis. The work-up should include
the analysis of peritoneal fluid for
gram stain, cell count, and culture.
Because of the increased morbidity
and mortality associated with this
complication, initiation of antibiotic
therapy should be considered before
the results of the culture are received.
Gorenesk et al. (1988) noted a high
incidence of negative cultures despite
strong clinical presentations and
stressed the importance of an ade-
quate amount of peritoneal fluid to
increase the yield of reliable results.
September-October 2012 Vol. 39, No. 5
In an attempt to prevent this type of
infection, the use of pneumococcal
vaccine is recommended. The initial
series of pneumococcal vaccine dur-
ing infancy is now a part of the rec-
ommended immunization schedule
for all children.
Children with underlying med-
ical conditions, such as nephrotic syn-
drome, require increased coverage.
The initial course consists of a pneu-
mococcal polysaccharide-protein con-
jugate vaccine (PCV). This was PCV
7, which only covered seven sero-
types (Centers for Disease Control
and Prevention, 2010). On February
10, 2010, the U.S. Food and Drug
Administration (FDA) approved
PCV 13 that covers 13 serotypes and
has taken the place of PCV 7. With
this came changes to the immuniza-
tion schedule for both children with
and without underlying medical con-
ditions to include the recommenda-
tion that all children receive PVC 13
despite completion of the PCV 7
series. In addition to the PCV series,
it is also recommended that immuno-
compromised patients receive the 23-
valent pneumococcal polysaccharide
vaccine (PPSV23). One dose after 2
years of age is recommended, with
revaccination 5 years after the first
dose. Immunization schedules are
updated as new research findings
become available, and it is recom-
mended that the caregiver responsi-
ble for patients with nephrotic syn-
drome review the most current pub-
lished immunization schedules for
children with underlying medical
conditions to provide appropriate
coverage. It is also important to have
an accurate accounting of the child’s
immunization history to provide the
appropriate schedule of vaccine
The need to defer administration
of live vaccines to children on corti-
costeroid therapy and/or immuno-
suppressant drug therapy leaves them
at increased risk for certain viral
infections. Varicella infection can be
life-threatening to this population.
Verification of immunization history
and/or immune status is important. If
exposure occurs in the immunosup-
pressed, non-immune child, then
Nephrology Nursing Journal September-October 2012
varicella immune globulin (VZIG)
should be administered within 96
hours to help prevent systemic infec-
tion (Gbadegesin & Smoyer, 2008).
Thromboembolism
Thromboembolism is an uncom-
mon but potentially life-threatening
complication that can be seen in the
patient with nephrotic syndrome. It is
more commonly seen in the adult
nephrotic patient, with an incidence
of approximately 25%. The incidence
in the pediatric nephrotic population
is approximately 3% (Kerlin, Ayoob,
& Smoyer, 2012). Its occurrence also
varies based on type of nephrotic syn-
drome. In the pediatric population,
the higher incidence is seen in con-
genital nephrotic syndrome, second-
ary nephrotic syndrome, and mem-
branous nephropathy or similar histo-
logical process. In children with onset
of nephrotic syndrome past the first
year of life, there appears to be an
increased risk of thromboembolism
with increasing age. This puts adoles-
cents at greatest risk. Thrombo-
embolism is most often a complica-
tion encountered early in the course
of the disease with the presence of
nephrotic range proteinuria.
The pathophysiology involved in
thrombus formation in nephrotic syn-
drome is not fully understood. It is
most likely a multifactorial process
that could include non-renal influ-
ences, such as genetic predisposition.
There are changes that occur within
the coagulation system due to the dis-
ease process, as well as side effects of
medication management regimens
that put these individuals at increased
risk. Changes in the kidney that create
a state of increased permeability and
the leakage of high molecular weight
proteins result in the loss of proteins
that play a major role in the anticoag-
ulation pathway, such as antithrombin
and protein S. In addition, there are
proteins in the coagulation pathway
that are of higher molecular weights
that are not excreted and appear to
become markedly elevated, such as
fibrinogen, factor V, and factor VIII
(Kerlin et al., 2012). There is also
increased synthesis by the liver of clot-
Vol. 39, No. 5
ting factors I, II, V, VII, X, and XIII
(Gbadegeson & Smoyer, 2008).
Thrombocytosis is a common finding
in nephrotic syndrome, but the signif-
icance that this state plays in abnormal
thrombus formation remains debat-
able. Some evidence suggests there is
a state of hyperaggregability, which
could be quite significant (Kerlin et al.,
2012). There is also the state of
intravascular volume depletion as the
result of hypoalbuminemia, hyperlipi-
demia, and in some cases, the use of
diuretics.
The thromboembolism can oc-
cur in a vein or artery. Venous presen-
tation is more common. There should
be a high suspicion for renal vein
thrombosis in those patients that pres-
ent with macrohematuria, flank pain,
and/or renal failure. Treatment of this
disorder is the same as in the patient
without nephrotic syndrome. Prophy-
lactic use of anticoagulation therapy
has been proposed for individuals at
highest risk, but more research is
needed to identify specific risk criteria
and evaluate efficacy as well as safety
before such an intervention becomes
a formal recommendation (Kerlin et
al., 2012). Gbadegesin and Smoyer
(2008) state that children with neph-
rotic syndrome with a history of
thromboembolism should be treated
with prophylactic anticoagulation
therapy during any future relapses to
help prevent recurrence of this com-
plication.
Prognosis
Patients who respond well to
prednisone and achieve prolonged
remission will most likely outgrow the
disorder with maintenance of good
renal function. The prognosis for pa-
tients that become steroid-dependent
or are steroid-resistant is less clear. Re-
search has shown that reducing protein-
uria is renoprotective (Ruggenenti,
Perna, & Remuzzi, 2003). The goal of
every treatment regimen is to achieve
long-lasting remission of proteinuria
and preserve kidney function. Main-
tenance of renal function is of primary
importance, but the need to preserve
quality of life cannot be underestimat-
369
The Many Faces of Minimal Change Nephrotic Syndrome: An Overview and Case Study
ed. Kyrieleis et al. (2009) studied
patients with a history of frequently
relapsing nephrotic syndrome who
had been followed in their program
and were still experiencing relapses
after 16 years of age into adulthood to
gain a better understanding of long-
term outcomes. The study group was
rather small, with only 15 participat-
ing, and all patients had good renal
function with normal creatinine clear-
ance. Complications noted were pri-
marily due to prolonged use of corti-
costeroids and other treatment strate-
gies. Complications included osteo-
porosis, hypertension, and decreased
visual acuity secondary to cataracts
and myopia, as well as decreased
sperm count and motility in males
treated with cyclophosphamide.
Kyrieleis and colleagues (2009) con-
cluded that less toxic and more effec-
tive therapies need to be developed
for this population. Toxic effects may
not be apparent for several years, and
longitudinal study of new and current
therapies is needed.
Brief Review of the Literature
On Immunoglobulin M (IgM)
Nephropathy and the Use
Of Rituximab
Significance of IgM
In the case study presented
below, the renal biopsy revealed min-
imal change disease with immuno-
globulin M (IgM) staining. The ques-
tion arises as to the significance of the
IgM and a return to the debate of
whether some histopathological find-
ings are individual disorders or just
spectrums of the same disorder, as
well as whether the presence of IgM-
positive immunofluorescence on
renal biopsy (IgM+IF) is a clinically
significant finding in predicting a
more difficult course of the disorder.
In a study that evaluated 64 children
ages 2 to 14 years with history of renal
biopsies that showed IgM+IF be-
tween 1985 to 1997, Zeis et al. (2001)
concluded that IgM nephropathy is a
distinct clinicopathological entity.
The children were followed over a 1-
to 12-year period; 20 children had
370
nephrotic level proteinuria (greater
than or equal to 40 mg/hour per m2),
and 44 children had non-nephrotic
range proteinuria and/or microscopic
hematuria (3 to 5 red blood cells per
high power field). Due to the high
prevalence of IgM+IF in the non-
nephrotic population, the researchers
saw it as distinct nephropathy.
Thirteen of the children with IgM+IF
had a second biopsy that showed
FSGS. Nine of these children showed
histology consistent with minimal
change nephrotic syndrome (MCNS)
on first biopsy, while 4 showed diffuse
mesangial hypercellularity (DMH).
The study also revealed an increased
incidence of transition from MCNS
to DMH to FSGS among the patients
with IgM+IF.
A retrospective chart analysis
study by Swartz, Eldin, Hicks, and
Feig (2009) was performed on 170
children who had had a renal biopsy
due to steroid-dependent or steroid-
resistant nephrotic syndrome. Fifty-
five of the biopsies showed minimal
change disease (MCD), the hisologi-
cal finding suggestive of minimal
change nephrotic syndrome; 43
showed mesangial hypercellulatriy
(MH); and 72 revealed focal and seg-
mental glomerulosclerosis (FSGS).
Findings of IgM+IF were noted in
44% of the MCD cases, 47% of the
MH cases, and 19% of the FSGS
cases. They found that children with
MCD and IgM+IF had a poor
response to steroids and a relatively
poor response to adjuvant therapy.
Prognosis was similar to that of chil-
dren with FSGS, with 17% progress-
ing to chronic kidney disease.
Myllymaki, Saha, Mustonen,
Helin, and Pasternack (2003) con-
ducted a longitudinal study of adult
and pediatric patients with renal biop-
sy findings consistent with IgM
nephropathy. Their focus was to iden-
tify factors that may predict the natu-
ral course of IGM nephropathy and
incidence of FSGS. They were also
looking at any characteristics that
may favor the progression to FSGS.
One hundred and ten biopsies
obtained between October 1977 and
July 1998 and evaluated at Tampere
Nephrology Nursing Journal
University Hospital, Tampere, Finland,
met their criteria for IgM nephropa-
thy. Indications for biopsy included
nephrotic syndrome (proteinuria with
3.5g/24 hours or greater with de-
creased serum albumin less than
3g/dL and edema), asymptomatic
proteinuria (protein excretion of
greater than 0.15 g/24 hours), hema-
turia, or proteinuria and hematuria.
Thirty-six patients were children
between 1 to 15 years of age. Of these
pediatric patients, 32 had nephrotic
syndrome and 4 had asymptomatic
proteinuria. The indication for biopsy
for the other 4 pediatric patients was
asymptomatic proteinuria. Seventy-
four adults ranged in age from 17 to
75 years. Indication for biopsy for 18
of these patients was nephrotic syn-
drome with a protein excretion level
of 3.5 g/24 hours or greater; for 33
patients, it was asymptomatic protein-
uria defined as a protein excretion of
0.15 g/24 hours; for 18 patients,
hematuria was defined as three or
more erythrocytes/high-power field
of urinary sediment; and 5 patients
had both proteinuria and hematuria.
Corticosteroids were used to treat 17
of the adults and 33 of the children
diagnosed with nephrotic syndrome.
Overall, more than one-half of the
population in the study was steroid-
dependent, and about one-third was
steroid-resistant. It was concluded
that response to steroids is consider-
ably worse in IgM nephropathy than
in MCD. As for progression to FSGS,
only 10% of the patients in the study
had a repeat renal biopsy performed,
and less than half showed a
histopathological picture of FSGS.
All patients fell into either the
nephrotic syndrome or asymptomatic
proteinuria group. The authors con-
cluded that based on their findings,
two different diseases within the diag-
nosis of IGM nephropathy may exist.
In an attempt to gain a better
understanding of incidence and histo-
ry of IGM nephropathy in the popu-
lation served at their center, Singhai
et al. (2011) conducted a retrospective
study of patients with renal biopsies
diagnosed as IgM nephropathy. Pa-
tients were selected from all adoles-
September-October 2012 Vol. 39, No. 5
cents (aged 13 years and older) and
adults with nephrotic syndrome from
Western India cared for at that facility
from January 2004 to September
2009. There were 117 patients who
met criteria of having IgM on renal
biopsy. Steroid dependency was the
most common presentation followed
by steroid resistance. The incidence
of IgM was found to be 4.3%, which
they noted was similar to previous
studies in other populations. They
attempted to evaluate the pathogenic
role as well as the role of IgM deposits
in therapeutic management, but no
consensus was reached. A very high
level of circulating IgM immune com-
plexes was noted. The authors
described IgM nephropathy as an ill-
understood glomerulonephritis.
The Southwest Pediatric Neph-
rology Study Group (1985) collected
data from multiple centers in the
United States on children under 18
years of age with a biopsy that
revealed FSGS in an attempt to gain
a better understanding of the charac-
teristics of this disorder. In contrast to
the studies above, these authors noted
no relationship between the presence
of IGM and/or DMH in predicting a
poorer prognosis or progression to
renal failure. They did note, however,
that the presence of DMH was less in
patients with long-term disease, sug-
gesting this is an early response in the
course of the disease.
More recent studies suggest that
controlling proteinuria can be a prob-
lem in the patient population with
nephrotic syndrome and IgM+IF on
renal biopsy. One finding fairly con-
sistent in the research is the increased
incidence of IgM in the steroid-
dependent and steroid-resistant neph-
rotic syndrome patient population, as
well as high incidence of progression
to FSGS. The question still exists as to
whether IgM nephropathy represents
a separate disease or is just an entity
in the progression from MCD to
FSGS. Existence of IgM+IF in pa-
tients with non-nephrotic-level pro-
teinuria supports the view that it rep-
resents a separate nephropathy, but
more studies that look at similar pop-
ulations are needed. After review of
Nephrology Nursing Journal September-October 2012
the literature, Swartz et al. (2009)
noted that the significance of the pres-
ence of IgM remains controversial.
Finding an answer to this question
will not be easy.
Some problems in researching
histopathological changes within the
kidney were demonstrated in a study
by Siegel et al. (1981). These authors
wanted to determine the histopatho-
logic types of lesions present in chil-
dren with frequently relapsing
steroid-dependent nephrotic syn-
drome at the time when more aggres-
sive treatment with cyclophos-
phamide was initiated. They found
that since the ISKDC guidelines had
been published, very few biopsies
were done in patients that responded
to initial prednisone therapy. Their
presenting histopathologic picture is
unknown and is only assumed to be
consistent with MCD. There may
have been other pathological changes
present that were not identified. In
this study, renal biopsies occurred
approximately six years after initial
diagnosis, and only 47% of the chil-
dren had minimal change histology,
24% had mesangial proliferative
changes, and 29% had FSGS. If
MCD was truly present at the time of
initial treatment, then the theory of a
progressive process warrants atten-
tion. Limitations with the biopsy itself
make the study of this theory even
more difficult. As pointed out earlier
in the discussion on biopsy, to diag-
nose FSGS, only one affected
glomeruli needs to be present. It is
not guaranteed that the biopsy site
chosen will provide a specimen that
contains a true representation of the
existing histophathology.
Role of Rituximab
The pathogenesis of steroid-de-
pendent and steroid-resistant minimal
change nephrotic syndrome is still not
clearly understood. Clinical observa-
tions have implicated B-cell involve-
ment and led to the fairly recent, ex-
perimental use of rituximab (Rituxan®)
for the treatment of persistent, high-
level proteinuria (Gilbert et al., 2006).
The success of this approach has been
Vol. 39, No. 5
noted in the literature, mostly through
the presentation of case studies. Clini-
cal research findings regarding the use
of rituximab are still quite limited.
Gilbert et al. (2006) presented the
case report of a female patient who
was diagnosed with nephrotic syn-
drome at 18 months of age. She ini-
tially responded well to steroid thera-
py but experienced multiple relapses.
At 3 years of age, a renal biopsy was
done, and findings were consistent
with MCNS. Between the ages of 2 to
15 years, she relapsed 37 times.
During this period of time, she had
been treated with various steroids and
various immunosuppressants without
success. Treatment with rituximab
was received at 15 years of age.
Response was favorable, and she
went into remission. Nine months
later, she relapsed, and steroid thera-
py was initiated. This approach was
once again unsuccessful, and a second
treatment of rituximab was given. She
responded well. Eight weeks after
treatment, she remained in remission.
Similar cases were reported by
Smith (2007) and Hofstra et al. (2007).
Smith (2007) presented the case study
of a male patient who was diagnosed
with nephrotic syndrome at 3 years of
age. Renal biopsy was done due to
frequent relapses during treatment
with steroids, and findings were con-
sistent with MCNS. Treatment with
various immunosuppressants was
unsuccessful, and he received ritux-
imab therapy after 11 years of multi-
ple relapses. He went into remission
shortly after completion of the thera-
py and was still in remission 9 months
after on tacrolimus and prednisolone.
Hofstra et al. (2007) reported the suc-
cessful use of rituximab in a 20-year-
old female who was originally diag-
nosed with idiopathic nephrotic syn-
drome at 2 years of age. A renal biop-
sy done at 4 years of age showed
MCNS. Various treatment regimens
were used over the years, and she
went into remission for short periods
of time. At 18 years of age, her high-
level proteinuria persisted while on
prednisone, mycophenolate mofetil,
and tacrolimus. She was treated with
rituximab, and within 2 weeks,
371
The Many Faces of Minimal Change Nephrotic Syndrome: An Overview and Case Study
Figure 1
Case Study
The following case study demonstrates how dynamic
minimal change nephrotic syndrome (MCNS) can be. It also
shows some of the challenges the practitioner faces when
trying to effectively manage a somewhat unpredictable disor-
der such as this.
TC, an 11-month-old male, presented to the emergency
department with a 6-day history of increasing edema in his
face, abdomen, legs, and scrotum. Urinalysis showed a high
level of proteinuria (greater than 40 mg/m2/hour). Serum lab
studies revealed good kidney function with normal BUN of 18
mg/dL and creatinine of 0.4 mg/dL. His serum albumin was
low at 1.8 g/dL, and cholesterol was elevated at 389 mg/dL.
Electrolytes remained normal. TC was diagnosed with
nephrotic syndrome, and he was admitted to the hospital for
medical management and family education. Medical manage-
ment included daily oral steroid therapy with prednisolone to
treat proteinuria, as well as enalapril to control mild hyperten-
sion and proteinuria. He also received albumin and
furosemide IV for treatment of severe edema.
Initial response to the oral steroids was encouraging, and
his level of proteinuria improved. Treatment with the daily dose
of oral prednisolone and enalapril was continued after dis-
charge. He was in remission within 4 weeks from presentation.
After completing 6 weeks of daily steroid dosing, the steroids
were weaned to every other day. Three weeks later, he was
diagnosed with acute otitis media. Urinalysis showed 1+ pro-
tein. Steroids were held at the same weaning dose. TC’s pro-
teinuria continued to increase, and he developed facial,
extremity, scrotal, and abdominal edema. He was placed back
on corticosteroid therapy at 60 mg/m2/day. Response was poor,
and he was eventually admitted to the hospital with increased
abdominal distension and pain with a diagnosis of peritonitis
and pleural effusion. Urinalysis showed 4+ proteinuria and
large blood upon admission. Serum creatinine was slightly ele-
vated at 0.8 mg/dL with a low serum albumin of 1.5 g/dL. Since
he was no longer responding to the steroid therapy, oral
tacrolimus was added to his medication regimen, and a kidney
biopsy was done to clarify the diagnosis. The kidney biopsy
findings were consistent with MCNS and included mesangial
hypercellularity with mesangial IgM deposition. No change in
treatment plan was indicated.
After 5 to 6 months, TC was finally weaned off the pred-
nisolone. The tacrolimus and enalapril were continued. He
remained in remission for 6 months. When he did relapse, it
took 6 to 7 months to get him off the corticosteroid therapy.
He remained in remission and off the steroids for approxi-
mately 9 months. During this time, the tacrolimus dose was
decreased. He did quite well and showed no signs of relapse
even during febrile illnesses. When he eventually did relapse,
he was started back on the high-dose steroids. Response
was not prompt, and adjustments in his tacrolimus dose were
required to reduce his level of protein excretion. Over time, he
372 Nephrology Nursing Journal
showed signs of becoming steroid dependent, with relapses
occurring before he was completely weaned off the pred-
nisolone. Eventually, he became steroid-resistant. Other med-
ications were added to his medication regiment, including
losartan and mycophenolate mofetil. The level of edema he
was experiencing became more difficult to manage.
Recurrent admissions to the hospital were required. His
serum albumin remained quite low, and he developed a sig-
nificant pleural effusion. Despite aggressive medical treat-
ment, his high-level proteinuria persisted, and his serum
albumin remained at or below 0.8 g/dL. He had intermittent
mild increases in his serum creatinine, but overall, it
remained within normal limits for his age. The family was
introduced to the possible benefits as well as side effects of
a course of IV rituximab. They agreed to the treatment.
TC received a dose of rituximab once per week for 4
weeks. He was seen in the clinic two months after his last
dose, and urinalysis showed a significant decrease in his pro-
tein excretion. The small dose of steroid that he was on was
discontinued, and he continued on his medication regimen of
tacrolimus, mycophenolate mofetil, enalapril, and losartan.
Four months after the rituximab, he was in remission, and his
serum albumin was up to 1.5 g/dL.
The next challenge was decreasing the oral immunosup-
pressive therapy he was on. Discussion of the need to
decrease his medication was met with some resistance by
the parents. TC’s clinical course had been quite stressful for
the family, emotionally and financially. They understood that
the rituximab treatments had increased his state of immuno-
suppression and agreed to a conservative weaning
approach. Before changes to his medication regimen could
be implemented, TC developed persistent watery stools
along with periodic episodes of non-bilious, non-bloody eme-
sis. The stool was described as greasy-looking and foul-
smelling.
Serum laboratory studies were done and ruled out
Epstein Barr Virus (EBV) and Parvovirus. His signs and
symptoms were suspicious for Giardia infection, so he was
started on a treatment of metronidazole (Flagyl®). Clinical sta-
tus improved with cessation of emesis and decrease in
watery stools. His appetite returned, and he gained some of
his weight back. Unfortunately, the improved state of health
did not last, and his symptoms returned with even greater
weight loss. TC was admitted to the hospital for a GI work up.
Test results and cultures were unremarkable. His urinalysis
remained negative for protein, and the decision was made to
discontinue the mycophenolate mofetil. Within 2 weeks, the
vomiting had stopped, the watery stools had decreased sig-
nificantly in amount and frequency, and he started to gain
weight. One month later, he remained in remission and had
gained 4 kg in body weight. He continues on a medication
regimen of tacrolimus, enalapril, and losartan.
September-October 2012 Vol. 39, No. 5
showed a significant decrease in pro-
teinuria. She was in partial remission
4 months after treatment.
Betjes and Roodnat (2009) pre-
sented a case report of a 26-year-old
male with IgM nephropathy who was
treated with rituximab and went into
complete remission. This patient was
diagnosed with nephrotic syndrome
at 3 years of age. Due to multiple
relapses, he was biopsied at 14 years
of age, and a diagnosis of IgM
nephropathy was made. Treatment of
high-level proteinuria with cyclophos-
phamide and cyclosporine was
unsuccessful, and he was in Stage V
chronic kidney disease by 22 years of
age. After two years of peritoneal dial-
ysis, he received a living related
donor kidney transplant. Within one
month of transplant, he was showing
hematuria and progressive protein-
uria. A repeat renal biopsy revealed
the recurrence of IgM nephropathy.
Steroid pulse therapy was unsuccess-
ful, and he was eventually treated
with rituximab. Response was good,
and he was still in remission a year
after treatment.
In a multicenter study, Gulati et al.
(2010) evaluated the response of
patients with steroid-resistant and
steroid-dependent nephrotic syn-
drome to treatment with rituximab.
Charts were reviewed on 57 patients
from three different tertiary care cen-
ters. Two centers were located in the
Unites States and one in India. All
patients had a history of receiving
some form of immunosuppressant
therapy that was ineffective at achiev-
ing/maintaining remission. They were
followed for at least 12 months after
receiving rituximab. The steroid-resist-
ant group contained 3 adults and 30
children; 15 of these patients remained
in remission for 12 to 48 months after
infusion, and 18 had no response to
treatment. In the group that achieved
remission, 64.7% had minimal change
disease on renal biopsy, and 31.2% had
FSGS. There were 24 patients in the
steroid-dependent group. All were
children. At 12 months after treatment,
20 patients achieved sustained remis-
sion. After 12 to 38 months, 17
remained in remission, and a signifi-
Nephrology Nursing Journal September-October 2012
cant decline in the number of relapses There have been advances in the
per year in those without sustained treatment of steroid-dependent and
remission was noted. steroid-resistant nephrotic syndrome,
The use of rituximab for improv- yet many questions remain. Ap-
ing proteinuria in steroid-dependent proaches to treating persistent high-
and steroid-resistant MCNS looks level proteinuria beyond steroids still
promising. Some patients in these vary. Long-term consequences of
case studies suffered complications of drugs used to treat this population are
long-term steroid use. Initiating ritux- not well understood. The case study
imab is still one of the many unan- (see Figure 1) questions the implica-
swered questions. It does have some tions of a diagnosis of MCNS when
documented life-threatening compli- histopathological findings include
cations, including progressive miltifo- IgM. Does this mean that the family
cal leukoencephalopathy and acute should expect a more complicated
lung injury (Gulati et al., 2010), which course with the remission of protein-
need to be taken into consideration uria becoming more difficult to
before proceeding with treatment. achieve over time? What is the right
Unfortunately, the long-term conse- time to introduce a more aggressive
quences of rituximab therapy in this treatment, such as rituximab? Further
population are not known. Controlled research is needed to bring light to
studies regarding its dosing, efficacy, these difficult issues.
and safety are needed.
References
Summary Betjes, M.G., & Roodnat, J.I. (2009).
The nephrology nurse is an Resolution of IgM nephropathy after
essential member of the team in the rituximab treatment. American Journal
of Kidney Diseases, 53(6), 1059-1062.
management of the patient with Bogt, B.A., & Avner, E.D. (2007). Idio-
nephrotic syndrome. It is important pathic nephrotic syndrome. In R.M.
to have an understanding of the com- Kliegman, R.E. Behrman, H.B. Jenson,
plexity of this diagnosis to provide the & B.F. Stanton (Eds.), Nelson textbook
patient and family with the appropri- of pediatrics (18th ed., pp. 2192-2194).
ate support. Ongoing education of the Philadelphia, PA: Saunders Elsevier.
family is essential for the successful Centers for Disease Control and
management of these children due to Prevention (CDC). (2010). Preven-
the key role they play in identification tion of pneumococcal disease among
of symptoms and adherence to treat- infants and children – Use of 13-
valent pneumococcal conjugate vac-
ment plans. The family needs to cine and 23-valent pneumococcal
understand that the treatment plan is polysaccharide vaccine: Recommen-
not always well defined, and multiple dations of the Advisory Committee
changes to the plan may be made on Immunization Practices (ACIP).
over time. The nephrology nurse is in Morbidity and Mortality Weekly Report,
an excellent position to detect 59(RR-11), 1-20.
improvements or complications early Doucet, A., Guillaume, F., & Deschenes,
with the disease process and/or treat- G. (2007). Molecular mechanism of
ment regimen. Prompt changes in the edema formation in nephrotic syn-
plan of care can lead to enhanced drome: Therapeutic implications.
Pediatric Nephrology, 22, 1983-1990.
patient outcomes.
Nephrology Nursing Journal Editorial Board Statements of Disclosure
In accordance with ANCC governing rules Nephrology Nursing Journal Editorial Board statements of disclosure
are published with each CNE offering. The statements of disclosure for this offering are published below.
Paula Dutka, MSN, RN, CNN, disclosed that she is a consultant and research coordinator, is on the speaker’s
bureau, and has sat on the advisory board for Genentech.
Patricia B. McCarley, MSN, RN, ACNPc, CNN, disclosed that she is on the Consultant Presenter Bureau for
Amgen, Genzyme, and OrthoBiotech. She is also on the Advisory Board for Amgen, Genzyme, and Roche and
is the recipient of unrestricted educational grants from OrthoBiotech and Roche.
Vol. 39, No. 5 373
The Many Faces of Minimal Change Nephrotic Syndrome: An Overview and Case Study
Filler, G. (2003). Treatment of nephrotic
syndrome in children and controlled
trials. Nephrology Dialysis Transplanta-
tion, 18(Suppl. 6), vi71-vi78.
Gbadegesin, R., & Smoyer, W.E. (2008).
Nephrotic syndrome. In D.F. Geary
& F. Schaefer (Eds.), Comprehensive
pediatric nephrology (pp. 205-218).
Philadelphia, PA: Mosby
Gilbert, R.D., Hulse, E., & Rigden, S.
(2006). Rituximab therapy for
steroid-dependent minimal change
nephrotic syndrome. Pediatric Neph-
rology, 21, 1698-1700.
Gipson, D.S., Massengill, S.F., Yao, L.,
Nagaraj, S., Smoyer, W.E., Mahan,
J.D., … Greenbaum, L.A. (2009).
Management of childhood onset
nephrotic syndrome. Pediatrics, 124(2),
747-757.
Gorensek, M., Lebel, M.H., & Nelson,
J.D. (1988). Peritonitis in children
with nephrotic syndrome. Pediatrics,
81(6), 849-856.
Gulati, A., Sinha, A., Jordan, S.C., Hari,
P., Dinda, A.K., Sharma, S., …
Bagga, A. (2010). Efficacy and safety
of treatment with rituximab for diffi-
cult steroid-resistant and -dependent
nephrotic syndrome: Multicenter
report. Clinical Journal of American
Society of Nephrology, 5(12), 2207-2212.
Gulati, S., Sharma, A.P., Sharma, R.K.,
Gupta, A., & Gupta, R.K. (2002). Do
current recommendations for kidney
biopsy in nephrotic syndrome need
modifications? Pediatric Nephrology,
17, 404-408.
Hodson, E.M., Alexander, S.I., & Graf, N.
(2008). Steroid-sensitive nephrotic
syndrome. In D.F. Geary & F.
Schaefer (Eds.), Comprehensive pedi-
atric nephrology (pp. 239-253).
Philadelphia, PA: Mosby.
Hodson, E.M., Knight, J.F., Willis, N.S., &
Craig, J.C. (2000). Corticosteroid
therapy in nephrotic syndrome: A
meta-analysis of randomized con-
trolled trials. Archives of Disease in
Childhood, 83, 45-51.
Hofstra, J.M., Deegens, J.K., & Wetzels,
J.F. (2007). Rituximab: Effective
treatment for severe steroid-depend-
ent minimal change nephrotic syn-
drome? Nephrology Dialysis Transplant,
22, 2100-2101.
Howie, A.J. (2003). Pathology of minimal
change nephropathy and segmental
sclerosing glomerular disorders.
Nephrology Dialysis Transplantation,
8(Suppl. 6), vi33-vi38.
International Study of Kidney Disease in
Children (ISKDC). (1978). Nephrotic
374
syndrome in children: Prediction of
histopathology from clinical and lab-
oratory characteristics at the time of
diagnosis. Kidney International, 13,
159-165.
International Study of Kidney Disease in
Children (ISKDC). (1981). The pri-
mary nephrotic syndrome in chil-
dren. Identification of patients with
minimal change nephrotic syndrome
from initial response to prednisone.
The Journal of Pediatrics, 98(4), 561-
564.
Kerlin, B.A., Ayoob, R., & Smoyer, W.E.
(2012). Epidemiology and patho-
physiology of nephrotic syndrome –
Associated thromboembolic disease.
Clinical Journal of the American Society
of Nephrology, 7, 513-520.
Kim, J.S., Bellew, C.A., Silverstein, D.M.,
Aviles, D.H., Boineau, F.G., &
Vehaskari, V.M. (2005). High inci-
dence of initial and late steroid resist-
ance in childhood nephrotic syn-
drome. Kidney International, 68, 1275-
1281.
Kunz, R., Friedrich, C., Wolbers, M., &
Mann, J.F. (2008). Meta-analysis:
Effect of monotherapy and combina-
tion therapy with inhibitors of the
rennin-angiotensin system on pro-
teinuria in renal disease. Annals of
Internal Medicine, 148(1), 30-48.
Kyrieleis, H.A., Lowik, M.M., Pronk, I.,
Cruysberg, H.R., Kremer, J.A., Oyen,
W.J., … Levtchenko, E.N. (2009).
Long-term outcome of biopsy-
proven, frequently relapsing mini-
mal-change nephrotic syndrome in
children. Clinical Journal of American
Society of Nephrology, 4(10), 1593-1600.
Melk, A. (2008). Tools for renal tissue
analysis. In D.F. Geary & F. Schaefer
(Eds.), Comprehensive pediatric nephrol-
ogy (pp. 55-61). Philadelphia, PA:
Mosby.
Myllymaki, J., Saha, H., Mustonen, J.,
Helin, H., & Pasternack, A. (2003).
IgM nephropathy: Clinical picture
and long-term prognosis. American
Journal of Kidney Disease, 41(2), 343-
350.
Niaudet, P. (2004). Steroid sensitive idio-
pathic nephrotic syndrome in chil-
dren. In E.D. Avner, W.E. Harmon,
& P. Niaudet, (Eds.), Pediatric nephrol-
ogy (5th ed., pp. 543-556).
Philadelphia, PA: Lippincott Williams
& Wilkins.
Querfeld, U. (1999). Should hyperlipi-
demia in children with the nephrotic
syndrome be treated? Pediatric
Nephrology, 13, 77-84.
Nephrology Nursing Journal
Ruggenenti, P., Perna, A., & Remuzzi, G.
(2003). Regarding progression of
chronic renal disease: The neglected
issue of residual proteinuria. Kidney
International, 63, 2254-2261.
Siegel, N.J., Gaudio, K.M., Krassner, L.S.,
McDonald, B.M., Anderson, F.P., &
Kashgarian, M. (1981). Steroid-
dependent nephrotic syndrome in
children: Histopathology and relaps-
es after cyclophosphamide treat-
ment. Kidney International, 19, 454-
459.
Singhai, A.M., Vanikar, A.V., Goplani,
K.R., Kanodia, K.V., Patel, R.D.,
Suthar, K.S., … Trivedi, H.L. (2011).
Immunoglobulin M nephropathy
nephropathy in adults and adoles-
cents in India: A single-center study
of natural history. Indian Journal of
Pathology and Microbiology, 54(1), 3-6.
Smith, G.C. (2007). Is there a role for rit-
uximab in the treatment of idiopath-
ic childhood nephrotic syndrome?
Pediatric Nephrology, 22, 893-898.
Southwest Pediatric Nephrology Study
Group. (1985). Focal segmental
glomerulosclerosis in children with
nephrotic syndrome: A report of the
Southwest Pediatric Nephrology
Study Group. Kidney International, 27,
442-449.
Srivastava, T., Simon, S.D., & Alon, U.S.
(1999). High incidence of focal seg-
mental glomerulosclerosis in neph-
rotic syndrome of childhood. Pedia-
tric Nephrology, 13, 13-18.
Swartz, S.J., Eldin, K.W., Hicks, M.J., &
Feig, D.I. (2009). Minimal change
disease with IgM+ immunofluores-
cence: A subtype of nephrotic syn-
drome. Pediatric Nephrology, 24, 1187-
1192.
Ulinski, T. & Aoun, B. (2010). Pediatric
idiopathic nephrotic syndrome: Treat-
ment strategies in steroid dependent
and steroid resistant forms. Current
Medicinal Chemistry, 17(9), 847-853.
Wolf, G., & Ritz, E. (2005). Combination
therapy with ACE inhibitors and
angiotensin II receptor blockers to
halt progression of chronic renal dis-
ease: Pathophysiology and indica-
tions. Kidney International, 67, 799-
812.
Zeis, P.M., Kavazarakis, E., Nakopoulou,
L., Moustaki, M., Messaritaki, A.,
Zeis, M.P., & Nicolaidou, P. (2001).
Glomerulopathy with neangial IgM
deposits: Long-term follow up of 64
children. Pediatrics International, 43,
287-292.
September-October 2012 Vol. 39, No. 5
ANNJ1217

ANSWER/EVALUATION FORM
The Many Faces of Minimal Change Nephrotic Syndrome: An Overview and Case Study
Martha A. Richardson, RN, CPNP
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1.5 Contact Hours
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Note: If you wish to keep the journal intact, you may photocopy the answer sheet or access this activity at
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1. What would be different in your practice if you applied what you have learned
To provide an overview of nephrotic syn-
from this activity? (Response Required)
drome, its signs and symptoms, and treat-
____________________________________________________________ ment options in the pediatric population.
____________________________________________________________
Please note that this continuing nursing education activity does not
____________________________________________________________ contain multiple-choice questions. This activity substitutes the multi-
ple-choice questions with an open-ended question. Simply answer
____________________________________________________________ the open-ended question(s) directly above the evaluation portion of
the Answer/Evaluation Form and return the form, with payment, to
____________________________________________________________ the National Office as usual.

Strongly Strongly
Evaluation disagree agree
2. By completing this offering, I was able to meet the stated objectives:
a. Define nephrotic syndrome. 1 2 3 4 5
b. Explain the diagnosis process for determining nephrotic syndrome in a pediatric patient. 1 2 3 4 5
c. Discuss treatment options for nephrotic syndrome in the pediatric population. 1 2 3 4 5
d. Describe steroid-dependent and steroid-resistant complications to treatment in patients
being treated for nephrotic syndrome. 1 2 3 4 5
e. Identify possible alternatives to steroid treatment in the patient with nephrotic syndrome who is
steroid-dependent or steroid-resistant. 1 2 3 4 5
3. The content was current and relevant. 1 2 3 4 5
4. This was an effective method to learn this content. 1 2 3 4 5
5. Time required to complete reading assignment: _________ minutes.
6. I am more confident in my abilities since completing this material. 1 2 3 4 5

I verify that I have completed this activity ________________________________________________________________________________

(Signature)

Nephrology Nursing Journal September-October 2012 Vol. 39, No. 5 375

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