Nephrotic Syndrome in Children
Author: Angela Ciuntu, Associate professor
Pediatry No.1 Department
SMPhU “NicolaeTestemiţanu”
Nephrotic syndrome is a common type of kidney disease seen in children. Historically,
Roelans is credited with the first clinical description of nefrothic syndrome in the late
fifteenth century, whereas Zuinger later provided a detailed description of the clinical
course of the disease and its importance as a cause of chronic renal failure in the
presteroid era.
Nephrotic syndrome is characterized by massive proteinuria, hipoalbuminemia, and
edema, although additional clinical features such as hyperlipidemia are also usually
present. In the first few years of life, children with or this condition often show
periorbital swelling with or without generalized edema.
Nephrotic syndrome develops when the loss of protein in urine exceeds the rate of
albumin synthesis in the liver, resulting in hypoalbuminemia and edema. Nephrotic
syndrome may be caused by variety of glomerular and systemic diseases, but by far the
most common type in childhood is idiopathic nephrotic syndrome. Before the
introduction of antibiotics, corticosteroids, and other immunosuppressive therapies,
nephrotic syndrome was associated with mortality as 67 %, usually following
Between 1967 and 1974m the International Study of Kidney Disease in Chidhood
(ISKDC) enrolled 521 children age 12 weeks to 16 years with idiopathic nephritic
syndrome in order to evaluate the histopathologic, clinical, and laboratory
characteristics of nephritic syndrome in children. The renal biopsy studies
demonstrated that about 80 % of children had either minimal change disease (MCD
mesangioproliferative glomerulonephritis (Mes PGN 2,3 %). Subsequently the ISKDC
demonstrated that the response to corticosteroids was higly predictive of renal
histology, with 93 % of children with MCD achieving complete remission following
an 8-week course of prednisone. However, between 25 % and 50 % of children with
Mes PGN or FSGS on biopsy also responded of prednisone.
At the moment there is no diagnostic marker for children displaying with nephrotic
syndrome that can be used as a predictor of steroid responsiveness or resistance. The
most important prognostic marker for children with nephrotic syndrome is their
response to steroid treatement. Initial steroid treatement can be avoided only in
patients with a family history of SRNS or in those who have a know gene mutation.
TABLE 1. Definitions Used in Idiopathic Nephrotic Syndrome
Nephrotic syndrome
Initial responder
Initial nonresponder/
steroid resistance
Infrequent relapce
Frequent relapce
Steroid dependence
Late nonresponder
Edema, proteinuria > 40 mg/m2/hr or protein/creatinine ratio
> 0,2 g/mmol (> 2 g/g) or 50 mg/kg/day or 3-4 + on urine
dipstick, hypoalbuminemia < 25 g/L (< 2,5 mg/100ml)
Urinary protein excretion ≤ 4 mg/m2/hr or 0-trace of protein
on urine dipstick or protein/creatinine ratio < 0,02 g/mmol (<
2 g/g) for 3 consecutive days
Attainment of complete remission within initial 8 weeks of
corticosteroid therapy
Failure to achieve remission during initial 8 weeks of
corticosteroid therapy
Urinary protein > 40 mg/m2/hr or protein/creatinine ratio>
0,2 g/mmol (> 2 g/g) or 2 + protein or more on urine dipstick
for 3 consecutive days
One relapce within 6 months of initial response or one to
three relapses in any 12- months period
Two or more relapses within 6 months of initial response or
four or more relapses in any 12- months period
Two consecutive relapses during corticosteroid therapy or
within 14 days of ceasing therapy
Proteinuria for > 8 weeks following one or more remissions
Nephrotic Syndrome: Diagnosis of nephritic syndrome requires the presence of
edema, massive proteinuria (> 40 mg/m2/hr or a urine protein/creatinine ratio > 2,0
mg/mg), hypoalbuminemia (< 2,5 g/dl).
Remission: Remission is characterized by a marked reduction in proteinuria (< 4
mg/m2/hr or urine albumin dipstick of to trace for 3 consecutive days) in association
with resolution of edema and normalization of serum albumin to at least 3,5 g/dl.
Relapce: Relapce is defined as reccurence of massive proteinuria (> 40 mg/m2/hr,
urine protein/creatinine ratio > 2,0 mg/mg, or urine albumin dipstick ≥ 2 + on 3
consecutive days), most often in association with recurrence of edema.
Steroid-Sensitive Nephrotic Syndrome: Patients who enter remission in response
to corticosteroid treatment alone are referred to as having steroid-sensitive nephrotic
syndrome (SSNS).
Steroid-Resistant Nephrotic Syndrome: Among pediatric nephrologists there are
two definitions of Steroid-Resistant Nephrotic Syndrome (SRNS). The definitions
introduced by the International Study of Kidney Disease in Children (ISKDC) and
used by the Arbeitsgemeinschaft fȕr Pȁdiatrische Nephrologie (APN) is widely
accepted as follows: No urinary remission within 4 weeks of prednisone therapy
60mg/m2/day. The other definition, employed by the Society of French Speaking
Pediatric Nephrologists, states: No urinary remission following 4 weeks of prednisone
60mg/m2/day followed by three intravenous pulses of methylprednisolone.
Steroid-Dependent Nephrotic Syndrome: some patients respond to initial
corticosteroid treatment by entering complete remission but develop a relapse either
while still receiving steroids or within 2 weeks discontinuation of treatment following
a steroid taper. Such patients typically require continued low-dose treatment with
steroids to prevent development of relapse, and are therefore reffered to as having
steroid-dependent nephrotic syndrome (SDNS).
Frequent Relapsing Nephrotic Syndrome: patients in this goup enter complete
remission in response to steroids. Thery remain in remission for several weeks
following discontinuation of treatment but develop frequent relapses. If relapses occur
4 or more times in any 12-months period, these patients are referred to as having
frequent relapsing nephrotic syndrome (FRNS).
Both SDNS and FRNS patients are at increased risk of developing complications of
nephrotic syndrome and complications from frequent use of steroids and other
immunosuppressive agents.
The incidence of SRNs varies throughout the world.
In Europe, the United States, and Australia, the overall incidence of idiopathic
nephrotic syndrome is 1 to 3 per 100.000 children below age 16, with a cumulative
prevalence of 16 per 100.000 children. The incidence is higher in Asian, African
American, and Arab children. In Asian children residing in northern England, the
overall rates are 7,4 (95 % confidence intervals [CI] 5,3-9,5) for South Asian children
compared with 1,6 (95 % CI 1,3-1,8) per 100.000 children per year for non- South
Asian children with 88 % responsive to corticosteroids. In Libya an incidence of 11,6
per 100.000 children was reported, with 98 % responsive to corticosteroids. In African
American children, rates of 2,8 to 3,6 per 100.000 per year have been reported
compared with 1,8 to 2,3 in Caucasian children.
SSNS is more common in boys than in girls, with a male/femaleratio of around 2:1
and a peak incidence between 1 and 4 years. There is a decreasing trend with
increasing age in the proportion with SSNS (Table 2). SSNS is lesscommon in African
and African American children. In South Africa only 7,2 % of 236 African children
had SSNS compared with 62 % of 286 African children. In the past 2 decades the
proportion of children with idiopathic nephrotic syndrome who respond to
corticosteroids appears to be falling when compared with 1978 ISKDC data. Among
159 Canadian children age 6 months to 19 years, the proportion with SSNS fell from
81 % between 1985 and 1993 to 65 % between 1993 and 2002; this was accompanied
by an increase in biopsy-documented FSGS have been reported from South Africa and
the United States.
Age also correlates with both the frequeny of presention and the biopsy findings
associated eith nephrotic syndrome. The most common age for presentation is 2 years
and 70 % to 80 % of cases occur in children younger than. To somme extent age also
predicts the histologic lesion associated with nephrotic syndrome. Children diagnosed
bef age 6 represented 79,6 % of those with FSGS and only 2,6 % of those
membranoproliferative glomerulonephritis (MPGN). With these data were analyzed on
the basis of renal histology, median ages at presentation were found to be 3 years
excluding the first year of life, these data combined su that the likelihood of having
MCNS decreases with increases age, whereas the likelihood of having the less
favorable diagnosis of FSGS or MPGN increases.
The histologic lesion associated with nephrotic syndrome has important
ramifications for the likelihood of response steroid treatement. Although almost 80 %
of children diagnosed with nephrotic syndrome in a multicenter International Study of
Kidney Diseases in Children (ISKDC) entered remission following an initial 8-week
course prednisone, when these children were analyzed based histology, steroid
responsiveness was found in 93 % of with MCNS compared with only 30 % of those
with FSGS and 7 % of those with MPGN. In addition to histology response to steroids
also vries with geographic location ethnicity. Whereas 80 % of children in western
countries be steroid responsive, studies from South Africa, Nigeria more recently
Ghana show that only 9 % to 50 % of children with nephrotic syndrome are steroid
The etiology of nephrotic syndrome is also age depend. Most cases appearing in the
first 3 months of life are re as congenital nephrotic syndrome (CNS) and are genetic
diseases. Although there has been no systematic of the etiology of nephrotic syndrome
presenting in the the first year of life (3 to 12 months), there are data sugg that up to
40% of cases during this time may also be during genetic causes. Beyond the first year
of life and in the decade, most cases are due to primary or idiopathic nephrotic
syndrome cases increases beyond the first 10 years of life.
A T-Cell Disease
In 1974 a series of clinical observations led Dr. Shaloub to propose that SRNS was
due to an abnormality in T-cell function. Nephrotic syndrome had been observed in
patients with Hodgkins lymphoma and cases of thymoma. The desease was noted to
remit in children who had measles, which led some to propose using measles as a
therapeutic strategy. A major effect of the measles virus is that it inhibits cell-mediated
immunity, thereby shutting down T-cell function. Furthermore, the response of
nephrotic syndrome to T-cell suppressive agents such as steroids or calcineurin
inhibitors also supported their role in nephrotic syndrome. These features all suggest
that lymphocytes are key cells in SSNS.
A Circulating Factor
MCD appears to exist in a spectrum with FSGS. A proportion of children with MCD
on clinical and histologic grounds develop FSGS. In both there appears to be a
circulating factor, with FSGS children being less responsive to therapeutic agents for
various reasons. Within this group is a subset of children in which the disease resides
in structural changes in the glomeruli with genetic mutations in key glomerular slit
process proteins, including nephrin, podocin, Actinin 4, and WT-1. These are
described elsewhere but in brief are associated with no response to steroids and
progression to endstage renal failure, and do not show evidence of a circulating factor
as demostrated by rapid recurrence of disease in a transplanted kidney. The timing of
response with the return to normal function taking days to weeks is also supportive of
slow podocyte recovery from an injurious cytokine. The higher rates of recurrence in
children with FSGS receiving living-related kidneys suggests that there may be a
degree of HLA restriction of response, which is also supported by HLA-linkage
studies showing that increased incidence of desease is tied to certain alleles such as
HLA B8, B13, DWQ2, DQB10301, and DR7.
Over the years vartous growth factors and cytokines have been proposed as
pathogenic in SSNS. The initial identification of the vascular permiability factor
(VPF), now called vascular endothelial growth factor (VEGF), was thought to have
identified the key protein leading to nephrotic syndrome. However, identification of
this protein in norm urine delayed further investigation of its role. More recen it has
been noted to be increased in urine during relapses nephrotic syndrome though
circulating levels are unchange suggesting that VEGF levels reflect the concomitant
proteinuria. Recent tissue-restricted knockouts of VEGF in mice restricted to
podocytes have demonstrated a key role for loc VEGF in maintaining glomerular
endothelial integrity and again have reinforced its importance, though perhaps more
locally, in maintaining permeability. Soluble immun response suppressor (SIRS) was
also identified as a cytokine in patients with SRNS, but again the inability to consistent
characterize this protein despite many mechanistic observations led to its exclusion as
the likely factor.
Other circulating factors have been proposed, and development of a functional assay
of glomerular permeability by Dr. Savin in the late 1990s identified a proteinuric
factor that was small, highly glycosylated, and hydrophobic. The appeared likely to
allow fractionation of nephrotic sera, wh would allow identification of the factor.
Other, observation that protein A coluns could remove the nephrotic factor
posttransplant also seemed to point to identifying features.
The central abnormality in all cases of nephrotic syndrome is the development of
massive proteinuria. Although the molecular basis for this is still speculative, there is
evidence in the literature that nephrotic syndrome may be a consequence of a primary
glomerular defect, circulating factors, or an immunological abnormality.
Primary Glomerular Defect
One of the most important functions of the kidney is the filtration of blood by
glomeruli, which allows excretion of fluid and waste products while retaining the
majority of blood proteins and all blood cells within the vasculature. This process of
filtration is made possible by the glomerular filtration barrier, which is made up of
specialized fenestrated endothelial cells, the glomerular basement membrane (GBM).
Neighboring podocyte foot processes are connected to each other by networks of
specialized cell-cell junctions known as slit diaphragms. In addition, the GBM has an
abundant supply of negatively charged heparin sulfate proteoglycan, resulting in
negatively charged molecules being relatively more restricted from passage than
positively charged molecules of the same size. In health, molecules greater than 42 A
in diameter, or more than 200 kDa, are unable to cross the filtration barrier. This
restriction depends largely on the structural integrity of the podocyte foot processes
and slit diaphragms, as well as the GBM charge. In nephrotic drome there of negative
charge of the
GBM. O morphologic changes in podocytes that occur during
development of nephrotic syndrome include sweiling, retraction, effacement
(spreading) of the podocyte distal foot proces vacuole formation, occurrence of
occluding junctions, placement of slit diaphragms, and detachment of podocyte from
the GBM.
The importance of podocyte and slit diaphragm struc to the pathogenesis of
nephrotic syndrome is further forced by recent observations in humans and axperiment
animals that mutations in genes encoding some of the diaphragm proteins or their
transcription factors can SRNS and/or FSGS.
Table 2. Etiologies of Nephrotic Syndrome (Beyond 3 Months of Age)
 Autosomal recessive FSGS due to mutation in gene encoding
podocin (NPHS2)
 Autosomal dominant diffuse mesangial sclerosis (DMS) due to
mutation in gene encoding WTI
 Autosomal dominant FSGS due to mutation in gene encoding αactinin 4
 Autosomal dominant FSGS due to mutation in gene encoding
CD2-associated protein (CD2AP)
Minimal change nephrotic syndrome (MCNS)
Focal segmental glomerulosclerosis (FSGS)
Mesangial proliferative glomerulonephritis
Membranoproliferative glomerulonephritis (MPGN)
Membranous nephropathy (MN)
Ig M nephropathy
Ciq nephropathy
 Autosomal dominant FSGS due to mutation in gene encoding
transient receptor potential cation chan 6 (TRPC6)
 Hepatitis B and C
Henoch-Schonlein purpura
Systemic lupus erythematosus
Diabetes mellitus
Fabry's disease
Glutaric acidemia
Glycogen storage disease
Mitochondrial cytopathies
 Leukemia
and oncologic  Lymphoma (Hodgkin's most likely can lead minimal change)
 Sickle cell disease
Nonsteroidal antiinflammatory drugs (NSAIDs)
Angiotensin converting enzyme inhibitors (ACEIs)
Bee stings (MCNS)
Food allergies
Obesity (usually with FSGS)
Circulating factors
There are experimental data to support the existence of soluble mediators that may
alter capillary wall permeability in nephrotic syndrome. Evidence for this includes
development of
nephrotic syndrome in newborn babies born to mothers with
nephrotic syndrome who apparently transferred a soluble factor to their fetuses in
utero, marked reduction of proteinuria following treatement with protein A
immunoadsorption in various types of primary nephrotic syndrome, recurrence of
FSGS in transplanted kidneys in patients with induced by treatement with protein A
immunoadsorption due to presumed removal of circulating factors, and induction of
enhanced glomerular permeability in experimental animals injected with serum from
patient with FSGS recurrence in transplanted kidneys. Furthertmore, inhibitors of
glmerular permeability have also been isolated from the serum of children with FSGS
and identified as components of apolipoproteins, suggesting that an imbalance between
serum permeability factors and permeability inhibitors may have a pathogenic role in
Immunological Abnormality
The theory that nephrotic syndrome may be due to dysregulation of the immune
system has existed for more than 30 years. There are numerous reports of
abnormalities of both the humoral and cellular immune responses during relapse of
nephrotic syndrome. However, the idea that nephrotic syndrome may be due to
dysregualtion of T lymphocyte function was first proposed by Shalhoub and his
colleagues. Evidence for this includes responsiveness of most forms of primary
nephrotic syndrome to corticosteroids, alkylating agents, calcineurin inhibitors, and
mycophenolate mofetil, all of which are known inhibitors of T lymphocyte function,
induction of remission of nephrotic syndrome following infections with measles and
malaria, diseases known to depress cell-mediated immunity, and identification of
MCNS as a paraneoplastic manifestation of Hodgkin's diseases and other
lymphoreticular malignancies. Other reports have also suggested an important role of
the cell-mediated immunyti during relapses of MCNS alterations in t cell subsets
during relapses, and increased cell surface expression of IL-2 receptors on T cells,
reflective of T cell activation. In addition, numerous cytokines, released in part by T
lymphocytes, have been reportedto be variably altered during nephrotic syndrome. It
should be noted, however, that despite numerous reports, none of these cytokines has
proven to be both present in the majotity of cases of MCNS and able to induce
significant proteinuria in experimental animals.
Massive proteinuria
Reduced intravascular
oncotic pressure
Fluid shift to extravascular
volume depletion
of ANP
of SNS
Release of ADH
volume depletion
Continued salt
and water intake
Fig. 1. Underfill hypothesis of edema formation in nephrotic syndrome.
History and Physical Examination
In a child with periorbital or generalized edema, the primary care physician can
quickly make this diagnosis by documenting significant proteinuria with more than 2+
albumin on urine dipstick or a spot urine protein/creatinine ratio greater than 2 mg/mg
and serum albumin of less than 2,5 g/dl. In addition, a careful history should exclude
possible complications and identify children with atypical presentations that might
reflect other serious systemic illnesses. It should include an evaluation of any
abdominal distension, which is usually due to ascites and sometimes tension may be
accompanied by abdominal discomfort, persistent abdominal pain may be abdominal
discomfort, persistent abdominal pain may be due to primary bacterial peritonitis (a
potentially life-threatening complication), gut edema, or relative gut ischemiadue to
hypoperfusion secondary to intravascular volume depletion. Other causes of an acute
abdomen should also be considered.
Regarding physical examination, blood pressure should be carefully determined
in nephrotic children, it can be either low (due to intravascular volume depletion) or
elevated (due to neurohumoral responses to hypovolemia, intrinsic renal causes, or
occasionally renal vein thrombosis). Hypertension has been reported in up to 21 % of
children 6 years and under with biopsy-confirmed MCNS, and may be present in up to
50 % of children with other histologic types.
Laboratory Evaluation
Diagnosis of nephrotic syndrome is confirmed by the triad of generalized edema,
proteinuria, albuminuria (> 2+ on dipstick or urine protein/creatinine ratio (>2mg/mg),
and hypoalbuminemia (serum albumin < 2,5 g/dl), although hypercholesterolemia is
also commonly present.
In patients with a typical presentation, serum studies should include an evaluation
of complete blood count, electrolytes, blood urea nitrogen (BUN), creatinine, and
albumin levels. For patients at an older age at presentation or with atypical
presentation, additional serum studies to exclude secondary causes of nephrotic
syndrome should include C3 and C4 complement levels; antinuclear antibody (ANA)
and possibly anti-double-stranded DNA; HIV antibody; hepatitis A, B, and C
serologies, and consideration of other viral serologies such as HIV antibodies.
Because immunosuppressive therapy is the mainstay of treatment for most cases
of childhood nephrotic syndrome, many pediatric nephrologists recommend placing a
PPD (purified protein derivative) test to screen for occult tuberculosis before
instituting immunosuppression.
Renal ultrasound does not usually have a role in the evaluation of childhood
nephrotic syndrome. However, in thesetting of a nephrotic child who develops gross
hematuria, thrombocytopenia, or unexplained persistent hypertension, renal ultrasound
should be considered to exclude possible development of renal vein thrombosis.
Renal Biopsy
More than 80 % of children with idiopathic nephrotic syndrome will respond to
steroid therapy by entering complet remission. Based on this statistic, an initial trial of
4 weeks of high-dose daily steroid therapyis usually prescribe in children under 10
before considering renal biopsy. Is general, renal biopsy is indicated only in the setting
of atypical features such as age at onset (less than 1 year or m than 10), SDNS or
SRNS, gross or persistent microscopic hematuria or presence of red cell casts,
abnormal serologies, or significant persistent renal failure.
Specific Therapy
The initial treatement for new-onset nephrotic syndrome erally includes
60mg/m2/day (maximum 80 mg/d) of prednisone for 4 to 8 weeks, followed by
40mg/m2 every e day for 4 to 8 weeks, and then a gradual taper until discontinued.
In patients, FRNS and SDNS, alternative agentswith potential steroid sparing
effects are often used, including cyclophosphamide, levamisole, cyclosporine,
tacrolimus, and mycophen mofetil. In patients with SRNS, however, the most monly
used agents include cyclosporine, tacrolimus, hi dose intravenous methylprednisolone,
and mycopheno mofetil (MMF), although the efficacy of almost all tha agents is lower
in these patients compared with FRNS SDNS patients.
General Management
Patients with nephrotic syndrome have increased total b fluid and sodium during
active disease. General measure control edema include salt restriction, moderate fluid
restriction, and judicious use of diuretics. Dietary recommendation include
maintenance of protein intake at approximately to 140 % of the RDA for age, as well
as avoidance of satural fats that can worsen hyperlipidemia.
Because the intravascular volume status in children nephrotic syndrome is
typically low, diuretics should ally be used only when significant intravascular depi
has been either excluded or corrected. Typically corre of intravascular depletion can be
achieved by ini intravenous 25 % albumin at 1-2 g/kg/d either as a contin infusion or
divided q 6-8 hours. Albumin treatement should continue for 4 to 6 hours before initial
administration of diuretics to minimize the risk of worsening any intravascular volum
depletion that may be present.
The most commonly used diuretic in this setting is the loop diuretic furosemide. It
acts by inhibiting the sodium-potassium-2 chloride transporter in the thick ascending
limb of the loop of Henle. During nephrotic syndrome, however, several factors may
impair its efficacy. Because furosemide is higly protein bound, hypoalbuminemia may
result in reduced delivery of albumin- bound furosemide to the proximal tubular cells
for secretion into the tubular lumen. Hypoalbuminemia also causes an increased
volume of distribution of furosemide due to diffusion of the free drug into the
expanded interstitial compartment.
Measures to overcome resistance to furosemide include increased dose,
coadministration with albumin, and coadministration with distal tubular diuretics.
Doses ranging from 200 % to 300 % of normal can often achieve the desired clinical
effects, although high doses in the presence of significant renal impairment may
increase the risk for ototoxicity, which has been shown to be related to the peak levels.
Clinically effective dosing strategies for intravenous furosemide in nephrotic children
with normal renal function typically range from 0,5-1 mg/kg q 6-12 hours, although
reports in children with cardiac disease have shown that continuous infusion of
furosemide results in a more efficient diuresis compared with intermittent
When diuretics are used, physicians should watch closely for common and
serious side effects of 3 agents, which include increased risk of thrombosis, electrolyte
disturbances such as hypokalemia and metabolic alkalosis, pypercalciuria and
nephrocalcinosis, and ototoxicity.
Hyperlipidemia is commonly found in children with nephrotic syndrome. The
characteistic lipid profile includes elevations in total plasma cholesterol, very-lowdensity lipoprotein (VLDL), and low-density lipoprotein (LDL) cholesterol,
triglyceride, and lipoprotein A, as well as variable alterations (more typically
decreased) in high-density lipoprotein (HDL) cholesterol. Although hyperlipidemia in
children with SSNS is often transiet and usually returns to normal after remission,
children with SRNS refractory to therapy often have sustained hyperlipidemia.
The potential usefulness of hydroxymethylglutaryl CoA (HMG CoA) reductase
inhibitors (statins) in children with SRNS has been reported in a few uncontrolled
Antiproteinuric Agents
Angiotensin converting enzyme inhibitors (ACEIs) are increasingly being used in
the management of persistent proteinuria and control of hypertension in children with
SRNS or SDNS. The antiproteinuric effects of ACEIs are due to thein ability to reduce
glomerular capillary plasma flow rate, decrease transcapillary hydraulic pressure, and
alter the permselectivity of the glomerular filtration barrier.
 Infection
 Thromboembolism
 Cardiovascular Disease
 Respiratory Distress
 Bone Disease
 Acute renal Failure
 Other Complications
TABLE 3. Complications of Nephrotic Syndrome
Disseminated Varicella Infection
Coronary artery disease
Pleural effusion
Pulmonary embolism
Venous (more common) or arterial (less common) thrombosis
Acute renal failure
Renal vein thrombosis
Reduced bone mineral density
Hypothyroidism, clinical and subclinical (more common in CNS)
Cerebral venous thrombosis
Infection, hypertension
Growth impairment, reduced bone density, posterior capsular
cataracts, avascular necrosis of femoral head
Alkylating agents
Hemorrhagic cystitis, dose-related oligospermia and premature
ovarian failure, increased risk of malignancy
Gingival hyperplasia, hirsutism, hyperkalemia, encephalopathy
mofetil (MMF)
Nausea, vomiting, diarrhea, constipation, dose-related leukopenia,
The single most important prognostic factor for maintenance of long-term normal
renal function in nephrotic syndrome is the patient's initial response to corticosteroids.
Although children who enter complete remission during an 8-week initial course of
oral corticosteroids have an excellent prognosis, the prognosis for those who fail to
enter remission is more guarded. Overall, close to 80 % of newly diagnosed children
treated with corticosteroids will achieve complete remission.