The document provides information about nephrotic syndrome in children, including: - A case presentation of a 2-year-old male toddler with nephrotic syndrome presenting with fever, cough, facial swelling, decreased urine output, and hypoalbuminemia. - Definitions of nephrotic syndrome as characterized by massive proteinuria, hypoalbuminemia, edema, and hyperlipidemia. The most common cause is idiopathic nephrotic syndrome. - Histologic classifications of nephrotic syndrome including minimal change disease, focal segmental glomerulosclerosis, mesangial proliferative glomerulonephritis, and membranoproliferative

1. Nephrotic syndrome in children
Dr. Sabona Lemessa (Assistant professor in pediatrics
and child health, JUMC)
8/12/2022 1

2. Outline
 Case
 Introduction
 Definition
 Etiology
 Pathogenesis
 Classification
 Clinical features
 Diagnosis
 Treatment
 Prognosis
 Reference
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3. Case-1
 A 2-year-old male toddler weighing 15 kg presented with a history of fever
which is high grade continuous type associated with chills and rigors.
 The patient had cough (wet cough more in amount) whitish colour sputum
not foul smelling.
 Swelling over face was present which initially started around peri-orbital
(which is more during morning) and gradually progressed to face which
decreases by evening.
 The toddler had decreased urine output (oligouria). The baby was delivered
by C-section and weighed 2.75 kg after birth.
 On examination pitting type of oedema was present over lower limbs and
swelling over face was present.
 The urine dipstick indicated for proteinuria, no signs of haematuria and
blood test shows hypoalbuminaemia of 2.0 g/dL indicating nephrotic
syndrome (NS).
 Serologic testing for active infections: anti-streptolysin-O titer was positive
 The lipid levels were markedly increased
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4. 1. How do you proceed with management?
2. What complication should be anticipated?
3. What is most likely cause of Nephrotic syndrome in this age group?
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5. case-2
 A seven year old boy who presented with a history of generalized body
swelling of a month duration; fever, breathlessness, prostration and reduced
urinary output of two weeks duration.
 He has been on management for steroid sensitive nephrotic syndrome,
MCD, diagnosed at the age of four years. His parents were not compliant
with his medical reviews, and would rather practice self-medication
whenever he fell ill.
 He had four relapses in the past three years and in each occasion he
achieved remission following recommencement of prednisolone.
 He was lost to follow-up for more than a year before re-presenting to
hospital in a critical state.
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6. cont...
 At presentation, he was acutely ill-looking, in severe respiratory distress,
febrile with axillary temperature of 37.8˚C, and could not walk.
 He was moderately pale, had peri-orbital fullness and generalized pitting
oedema involving the entire lower limbs, abdominal and thoracic walls,
sacral region, scrotum and penis.
 His weight was 58 kg (expected weight for his age is 22 kg). He was
tachypneic and tachycardic with respiratory and pulse rates of 60 breaths
per minute and 120 beats per minute respectively. His blood pressure was
100/60 mmHg, oxygen saturation was 92% on room air.
 The heart was not enlarged clinically. Heart sounds were normal but distant
due to the oedematous chest wall. No murmur or gallop rhythm was heard.
He could not lie down flat in bed but felt better when propped up.
 Both lung fields were dull to percussion with reduced air entry and
crepitation posteriorly. His abdomen was markedly distended, shiny, tense
and mildly tender.
 Ascites was demonstrable by fluid thrill and abdominal organs were
difficult to palpate. Neurological examination was normal.
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7.  Laboratory values on admission were as follows:
 urinalysis revealed proteinuria 4+, pH of 6 and specific gravity of 1.020. Urine
microscopy showed few granular casts.
 Serum electrolytes were… Na+ 145 mmol/L, K+ 5.5 mmol/L, Cl− 116 mmol/L,
HCO3− 20 mmol/L, creatinine 1.9 mg/dl, and urea 35 mg/dl.
 albumin was 15 g/L, and serum cholesterol was 360 mg/dl. An early morning
protein creatinine ratio was 6mg/mg.
 Hb-8 g/dl, WBC-14,000 × 109/mm3 (N-70% L-30%) and platelet-
200,000/mm3
 Bladder catheterization yielded about 5 mls of concentrated urine which was
sent for microscopy culture and sensitivity.
 The result showed significant growth of Escherichia coli bacteria.
1.What is current diagnosis of this patient?
2. How do you proceed with management?
3. What are complications he had related to current diagnosis?
4. Is it possible to predict the condition of the patient?
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8. Introduction
 Glomerular injury may be a result of genetic, immunologic, perfusion, or
coagulation disorders
 Genetic disorders of the glomerulus may result from
mutations in DNA exons encoding proteins located within the
glomerulus, interstitium, or tubular epithelium;
mutations in regulatory genes controlling DNA transcription;
abnormal posttranscriptional modification of RNA transcripts; or
abnormal posttranslational modification of proteins
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9. cont...
 In immune complex–mediated diseases, antibody is produced against,
and combines with, a circulating antigen that is usually unrelated to the
kidney
 The coagulation system may be activated directly, after endothelial cell
injury that exposes the thrombogenic subendothelial layer (thereby
initiating the coagulation cascade), or
 It may be activated indirectly, after complement activation.
Consequently, fibrin is deposited within glomerular capillaries or
within Bowman's space as crescents.
Activation of the coagulation cascade can also activate the kinin
system, which produces additional chemotactic and anaphylatoxin-
like factors.
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10. cont...
 Abnormal amounts of protein may appear in the urine from three possible
mechanisms:
glomerular proteinuria, which occurs as a result of disruption of
the glomerular capillary wall;
Tubular proteinuria, a tubular injury or dysfunction that leads to
ineffective reabsorption of mostly low-molecular- weight proteins;
and
Increased production of plasma proteins-
in multiple myeloma, rhabdomyolysis, or hemolysis:-which
may cause the production or release of very large amounts of
protein that are filtered at the glomerulus and
overwhelm the absorptive capacity of the proximal tubule.
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11. Glomerular Proteinuria
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12. Cont…
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13. Nephrotic syndrome
 Nephrotic syndrome is among the most common types of kidney diseases
seen in children.
 It is characterized by massive proteinuria, hypoalbuminemia, and edema,
 hyperlipidemia are usually also present.
 The most common cause of nephrotic syndrome in children is idiopathic
nephrotic syndrome (INS), also called nephrosis
 Nephrotic-range proteinuria is defined as:-
proteinuria > 3.5 g/24 hr or a urine protein:creatinine ratio > 2.
hypoalbuminemia (≤2.5 g/dL), pitting edema and
hyperlipidemia (cholesterol > 200 mg/dL).
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14. Definitions cont....
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15. cont...
 affects 1-3 per 100,000 children < 16 yr of age.
 Without treatment, nephrotic syndrome in children is associated with a high
risk of death, most commonly from infections.
 Fortunately, 80% of children with nephrotic syndrome respond to
corticosteroid therapy
 The peak age of presentation of nephrotic syndrome is 2 years, and
 70–80% of cases of nephrotic syndrome occur in children less than 6 years
of age.
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16. cont...
 Age of onset may also be predictive of the underlying histologic lesion
causing nephrotic syndrome.
 A male preponderance in children, with a male to female ratio of up to
3.8:1.
 In comparison, only 50% of those with FSGS, and 2.6% of those with
MPGN present before 6 years.
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17. Etiology
 Most children with nephrotic syndrome have a form of primary or
idiopathic nephrotic syndrome.
 Glomerular lesions associated with idiopathic nephrotic syndrome include
minimal change disease (the most common), focal segmental
glomerulosclerosis,
membranoproliferative glomerulonephritis,
C3 glomerulopathy, and membranous nephropathy
 Secondary to systemic diseases such as
systemic lupus erythematosus, Henoch-Schönlein purpura,
malignancy (lymphoma andleukemia), and
infections (hepatitis, HIV, and malaria).
hereditary proteinuria syndromes are caused by mutations in genes
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18. Pathogenesis
 Role of the Podocyte:-
 increased permeability of the glomerular capillary wall, which
leads to massive proteinuria and hypoalbuminemia.
plays a crucial role in the development of proteinuria and the
progression of glomerulosclerosis and functions as structural
support of the capillary loop,
is a major component of the glomerular filtration barrier to proteins,
and
is involved in synthesis and repair of the glomerular basement
membrane.
Podocyte injury or genetic mutations of genes producing podocyte
proteins may cause nephrotic-range proteinuria
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19. cont...
 In idiopathic, hereditary, and secondary forms of nephrotic syndrome, there
are immune and nonimmune insults to the podocyte that lead to:-
foot process effacement of the podocyte,
a decrease in number of functional podocytes, and
altered slit diaphragm integrity.
The end result is increased protein leakiness across the glomerular
capillary wall into the urinary space.
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20. Role of the Immune System
 T-cell dysfunction that leads to cytokine release that affects glomeruli and
causes increased permeability and
 Immune system dysfunction that leads to the production of circulating
factors
(soluble urokinase plasminogen activator receptor is one example)
that alter podocytestructure and/or function, resulting in proteinuria.
 B-cell involvement is also suggested by reports of remission after
administration of rituximab, an anti-CD20 antibody.
 Minimal change nephrotic syndrome (MCNS) may occur after viral
infections and allergen challenges.
 Abnormalities in the cell-mediated immune system have long been
implicated in the pathogenesis of MCNS
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21. Minimal change nephrotic syndrome
 Depressed levels of immunoglobulin G (IgG) and increased levels of IgM
have been well documented in MCNS.
 In addition, decreased levels of factor B and factor D have also been noted
during relapses.
 depressed cell-mediated immunity during relapses of MCNS, alterations in
T-cell subsets during relapses and
 increased cell surface expression of interleukin-2 (IL-2) receptor on
T cells, reflecting T-cell activation
 corticosteroids may act directly on the podocytes, rather than through
modulation of the immune system
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22. Focal segmental glomerulosclerosis
 FSGS may occur either as a primary or a secondary disease such as in
association with
reflux nephropathy, hereditary nephropathies,
sickle cell disease, HIV nephropathy, obesity, and
nephropathy associated with heroin use.
 The pathogenesis of primary FSGS can be separated into four categories:
podocyte injury- immunologic, toxic, or inflammatory pathways,
and typically results in effacement or spreading of the podocyte
foot processes along the GBM.
genetic mutations- SRNS and/or FSGS
 NPHS1, NPHS2, Wilms’ tumor suppressor gene WT1,
αACTN4
hemodynamic factors- Glomerular hypertension
proposed to be the capillary stretch and
mechanical stress on the podocytes induced by increased
transglomerular pressure.
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23. Histologic classification
1. Minimal change nephrotic syndrome:- also known as nil disease,
is a renal biopsy specimen featuring no obvious glomerular or
tubular abnormalities on light microscopy
slight increase in mesangial matrix or cellularity, an occasional
sclerosed glomerulus, or slight tubular atrophy,
although the presence of a segmental scar or evidence of
glomerular collapse on light microscopy
in a younger-age child, predominantly male, with low likelihood of
hypertension and hematuria.
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24. cont....
2. Focal segmental glomerulosclerosis
scarring within the glomerulus (glomerulosclerosis) that is seen in
some
but not all glomeruli (focal distribution)
Furthermore, the glomerular scars when present are only seen in a
portion of the involved glomeruli (segmental distribution)
The lesions consist of mesangial cell proliferation and segmental
scarring on light microscopy
Immunofluorescence microscopy is positive for IgM and C3
staining in the areas of segmental sclerosis.
Electron microscopy demonstrates segmental scarring of the
glomerular tuft with obliteration of the glomerular capillary lumen
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25. cont...
3. Mesangial proliferative glomerulonephritis
characterized by increased mesangial matrix and cellularity, but
glomerular crescents and adhesions may sometimes be seen.
Immunofluorescence is usually negative, but may show mesangial
IgM deposition.
The incidence of biopsy-proven MesPGN in untreated children
with nephrotic syndrome is approximately 2–5%.
microscopic hematuria (100%) and hypertension (25%)
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26. cont...
4. Membranoproliferative glomerulonephritis
uncommon histologic lesion associated with the childhood
nephrotic syndrome
On light microscopy, all forms of MPGN are characterized by
an increased mesangial matrix and cellularity,
capillary wall thickening, and
a characteristic lobular appearance of the glomeruli.
an older age at presentation, a slight female predominance,
systolic hypertension in approximately 50% and diastolic
hypertension in 25%.
Nearly 60% had microscopic hematuria at onset,
75% had hypocomplementemia (low C3), and 50% had azotemia.
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27. cont...
5. Membranous nephropathy:-
the least common histologic lesion
The pathogenesis of MGN in humans is unknown,
but it is believed to be an autoimmune disorder mediated by
immune complexes formed in situ.
The antibody responsible for this lesion is probably directed against
an antigen within the kidney,
resulting in the formation of subepithelial deposits.
The renal biopsy features of MGN on light microscopy
normal glomeruli with diffuse thickening of the
glomerular capillary walls.
Mesangial proliferation is characteristically absent
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28. Clinical and Biological Features
 The disease may occur during the first year of life, but it usually starts
between the ages of 2 and 7 years.
 The onset is often preceded by an upper respiratory tract infection.
 The disease is characterized by a sudden onset, edema being the major
presenting symptom.
 It becomes clinically detectable when fluid retention exceeds 3–5 % of
body weight.
 Microscopic hematuria is found in up to 30 %, but gross hematuria is
unusual in INS and suggests an alternative primary diagnosis.
 Patients occasionally present with hypertension due to-
intravascular volume depletion and
activation of the renin–angiotensin system.
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29. Atypical Features of Nephrotic Syndrome Suggesting Alternative Diagnoses
 Age <3–12 months and >12 years
 Sustained serum creatinine elevation
 Hypertension
 Gross hematuria
 Low serum C3 or C4
 Evidence of specific infection (HBV, HCV, HIV)
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30. cont...
 Urinalysis
Proteinuria is detected by dipstick testing 3 or 4+.
Quantitative evaluation gives figures ranging from less than 1 g to
more than 10 g/day.
The nephrotic range proteinuria is defined as >50 mg/kg/day or 40
mg/m2/hr
In most cases, proteinuria is highly selective, consisting of albumin
and lower molecular weight proteins.
Macroscopic hematuria is rare, occurring in 3 % of patients.
Microscopic hematuria is present in 30 % of cases and has no
histopathologic or prognostic significance.
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31. cont...
 Blood Chemistry
Serum proteins are markedly reduced below 50 g/l in 80 % of
patients and below 40 g/l in 40 %.
Albumin concentration usually falls below 20 g/l and may be less
than 10 g/l.
Electrophoresis shows not only low albumin levels but also increased
α-2 globulins and,
to a lesser extent, β-globulins, while γ-globulins are decreased.
IgG is markedly decreased, IgA slightly reduced,
IgM is increased, while IgE is normal or increased
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32. cont...
 Hyperlipidemia is a consequence of -
an increased hepatic synthesis of cholesterol, triglycerides, and
lipoproteins;
a decreased catabolism of lipoproteins due to a decreased activity
of lipoprotein lipase which normally transforms VLDL to LDL via
IDL; and
a decreased LDL receptor activity and
an increased urinary loss of HDL
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33. cont...
 Hematology
Hemoglobin levels and hematocrit are increased in patients with
plasma volume contraction.
Anemia with microcytosis may be observed, probably related to
urinary loss of siderophilin
The urinary loss of erythropoietin may also contribute to anemia
Thrombocytosis is common and may reach 5.108 or 109/l.
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34. Complications
 Hypovolemia- observed typically at onset or early during a relapse
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35. cont...
 Infections- The most common
infection is peritonitis,
 often with Streptococcus
pneumoniae
 E. coli, streptococcus B,
Haemophilus influenzae, and
 other gram-negative organisms.
 prophylactic antibiotics in high-
risk patients like-
age < 2 years, steroid
resistant and
frequent relapsing patients,
children with a previous
Pneumococcal infection
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36. cont...
 Thrombosis:-
 occur within the first 3 months
after the onset of nephrotic
syndrome.
 Children aged >12 years are at
higher risk of this complication
than younger children
 may indicated in case of:-
 Development of pain or asymmetric
swelling of an extremity, respiratory
distress,
 acute oliguria or gross hematuria, or
neurologic symptoms
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37. cont...
 Growth
Growth may be severely affected in children with persistent
nephrotic syndrome.
Depletion of hormones due to urinary losses is a possible cause of
stunting.
Hypothyroidism related to urinary loss of iodinated proteins has
been observed and may be corrected .
A low plasma IgF1 and IgF2 level associated with a urinary loss of
the carrier proteins has also been reported
8/12/2022 37

38. cont...
 Acute Renal Failure-
A reduction of the GFR, secondary to hypovolemia, infection, or
thrombosis, is frequent
Marked oliguria may occur in children
Oliguric renal failure may be the presenting symptom
 May be due to intravascular volume depletion (prerenal failure) or
renal hypoperfusion, use of nephrotoxic drugs,
renal venous thrombosis, or sepsis.
 usually reversible, especially with intravenous infusion of albumin
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39. cont...
 Chronic Renal Failure
occurs in 50 % or more of the steroid resistant patients after a
follow-up of 10 years.
Poor prognostic factors of chronic renal failure were
asymptomatic proteinuria at presentation, initial renal failure,
higher proportion of glomeruli with segmental sclerosis.
8/12/2022 39

40. Management
 Steroid therapy is applied in all cases of INS whatever the histopathology, even
in patients with FSGS.
 Before initiation of steroid therapy, blood pressure, weight, height has to be
measured and
 A response occurs in most cases within 10–15 days (median 11 days)
 About 80% of the responders will do so within the first two weeks of treatment
and 90% within four weeks.
 whereas less than 10 % go into remission after 2–4 more weeks of a daily
regimen
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41. cont...
 First Episode-
prednisolone 60 mg/m2 or 2 mg/kg (maximum dose 80 mg) once daily
for 6 weeks
Single daily dose is said to reduce steroid toxicity
followed by 40 mg/m2 (1.5mg/kg) given as a single dose on alternate
days for a further 6 weeks after a meal
to prevent gastrointestinal upsets and then stopped.
Some authors recommend prolonged glucocorticoid therapy for 6 months
after the initial, intense therapy
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44.  A retrospective follow-up study conducted at comprehensive specialized hospitals
of the Tigray region, Ethiopia, by reviewing eight years of follow-up data on charts
of children with an initial diagnosis of the nephrotic syndrome from 2011 to 2018
 there were 174 children newly diagnosed with an idiopathic nephrotic syndrome
that fulfilled the inclusion criteria and were included in the study for analysis
 minimum follow-up of 1 month and a maximum of 67 months.
 62 (35.6%) children included in the study developed relapse during the follow-up
period, and the rest 112 (64.4%) were censored
 64 (36.8%) did not develop relapse, 20 (11.5%) lost, 16 (9.2%) died, and 12(6.9%)
were transferred to other institutions.
 The median relapse time was found to be 16 months (95% CI 13-19)
 having undernutrition, high triglyceride level at initiation, baseline low serum
albumin level ≤1.5 g/dl, and residing in rural areas are independent predictors of
relapse in children with nephrotic syndrome at 95% confidence level.
8/12/2022 44

45. Management of relapsing disease
 The majority of children with nephrotic syndrome (50–70%) develop one
or more relapses of the disease.
 These relapses may be transient, with spontaneous remission occurring
within 4–14 days in some.
 Despite prolonged initial steroid use, about 40–50% of those with complete
remission of nephrotic syndrome subsequently develop either frequent
relapses or steroid-dependence
 Several factors appear to be associated with an increased risk for relapses
of nephrotic sundrome.
 less than 5 years of age, and among boys
 high during intercurrent infections like upper respiratory tract infection.
8/12/2022 45

46. cont...
 Relapse is defined as proteinuria of 2+ or more on urine dipstick for 3
consecutive days with or without edema
 Children can have transient proteinuria with viral respiratory infections
 Treatment is directed to suppress proteinuria and restore normal serum
protein concentrations and
to reduce the frequency of future relapses, both with minimal short-
and long-term adverse effects.
 ISKDC relapse regimen:
prednisolone 60 mg/m2 (maximum 80 mg) daily until urinary
protein turns negative or trace for three consecutive days
followed by alternate day therapy with 40 mg/m2 (maximum 60
mg) for 28 days or 14 doses.
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47. cont..
 Infrequently relapsing disease less than 2 relapses in 6 months or less then
3 relapses in one year, can be managed with the above ISKDC regimen.
 If the child is frequently relapsing: treat the child as an infrequent relapser
followed by alternate day prednisolone 0.1-0.5 mg/kg for 6 months and
then taper.
 If the child relapses while on alternate day prednisolone: add levamisole
2.5 mg/kg on alternate days for 6-12 months then prednisolone tapered and
levamisole continued for 2-3 years or increase the alternate day
prednisolone if tolerated.
 If the child develops steroid toxicity while on relapse regimen oral
cyclophosphamide 2- 3 mg/kg/day for 8 weeks with prednisolone 40
mg/m2 alternate day for the first 4 weeks then 20 mg/m2 for the second 4
weeks so that steroids are discontinued shortly after the discontinuation of
cyclophosphamide.
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52. Steroid resistant nephrotic syndrome
 Unresponsive proteinuria to 60 mg/m2 daily prednisolone given for at least
28 days.
 Renal biopsy indicated
 The majority of patients with SRNS will have FSGS, diffuse mesangial
proliferation, or MCNS by biopsy.
 DDX- membranoproliferative (mesangiocapillary) glomerulonephritis
(MPGN) and membranous nephropathy (MN).
 Children (or adolescents) with pathogenic mutations of genes encoding
structural podocyte proteins do not benefit from immunosuppressive
therapies but require supportive treatment and frequent monitoring.
 Rituximab does not appear to be effective in the majority of patients
resistant to glucocorticoids and other second-line agents.
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53. cont...
 Examples are podocin ( NPHS2 ) (in children), a-actinin 4 ( ACTN4 ), and
transient receptor potential cation channel type 6 ( TRPC6 ) mutation (in
adolescents and young adults).
 ACE inhibitors could be used to reduce the proteinuria either alone or in
combination with immunosuppressive therapy
 Salt restriction
 The 2012 KDIGO guideline advises against the use of cytotoxic agents
for SRNS.
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56. cont...
 Anti-infective therapy
Infection must be treated before starting steroids, not only to prevent the
risk of overwhelming sepsis during treatment
but also because occult infection may be responsible for steroid resistance
Edematous children shall receive prophylactic treatment with amoxicillin 50
mg/kg in two divided doses until the edema disappears.
 Any systemic infection like peritonitis, sepsis, cellulites warrants systemic
administration of combination of antibiotics penicillin and aminoglycosides for 7-
10 days.
 Immunizations
 Vaccines shall be given according to the standard schedule to a nephrotic child
 but if the child is on high dose daily steroids, live vaccines could be given safely
only after 3 months of discontinuation of prednisolone and 6 months after
discontinuation of cyclophosphamide.
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57. cont...
 Fluid and electrolyte balance
While the patient is edematous, salt restriction and maintenance fluid needs
should be reduced to about 70% of the normal.
If the child is hypovolemic rapid intravascular expansion with 20
ml/kg of normal saline shall be done.
Hypertension can occur as a side effect of steroid administration and
calcineurin inhibitors-
angiotensin converting enzyme inhibitor (ACEI) like enalapril or
calcium channel blocker like amlodipine or
beta blockers can be used to keep the blood pressure below the
90th percentile for age.
Elevation of the extremities to the level of the heart or higher
increases the tissue hydrostatic pressure-
returns fluid to the intravascular space and thus reduces the
edema.
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58. cont...
 Relief of severe anasarca or disabling edema can be achieved by-
 Intravenous 25% albumin infusion at a dose of 1 g/kg/dose, given over 3–4
hours,
 followed immediately by furosemide challenge (1–2 mg/kg/dose).
 This therapy may be cautiously repeated in severely edematous patients.
 The risk of aggressive albumin infusion therapy is sudden mobilization of subcutaneous
tissue fluid into the intravascular compartment,
 pulmonary edema, and congestive cardiac failure, Hypertension
 In general, gradually increasing the serum albumin level to approximately 2.8 g/dl is-
 adequate to restore intravascular oncotic pressure and volume, and
 little additional clinical benefit results from increasing the albumin level to
normal values.
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59. cont...
 Thromboemboli:- Prevention of this complication includes-
regular ambulation, avoidance of hemoconcentration due to hypovolemia,
avoidance of central venous catheter if possible, and
early treatment of sepsis or volume depletion.
Anticoagulation therapy in children with thrombotic events appears to be
effective
heparin, low-molecular-weight heparin, and warfarin are
therapeutic options.
Prophylactic warfarin may be given to patients with-
a plasma albumin concentration below 20 g/L,
a fibrinogen level greater than 6 g/L, or
an antithrombin III level less than 70% of normal
8/12/2022 59

60. cont..
 Immunizations
Vaccines shall be given according to the standard schedule to a nephrotic
child
but if the child is on high dose daily steroids, live vaccines could be
givensafely only after-
3 months of discontinuation of prednisolone and
6 months after discontinuation of cyclophosphamide.
 In Ethiopia, pneumococcal and varicella zoster vaccines are not available.
If a child acquires chickenpox, aggressive therapy with intra venous
acyclovir 1500 mg/m2/day divided in to three doses or
oral acyclovir 80 mg/kg/day divided into 4 doses for 10 days should be
given and
the dose of prednisolone shall be reduced to 0.5 mg/kg/day during this
time of infection.
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61. cont...
 Other measures
No need of mobility restriction.
No need of protein restriction.
Dyslipidemia should be managed with a low-fat diet.
Dietary fat intake should be limited to < 30% of calories with a
saturated fat intake of < 10% calories.
Dietary cholesterol intake should be < 300 mg/day
In addition to sodium restriction (<1,500 mg daily), water/fluid restriction
may be necessary if the child is hyponatremic.
A swollen scrotum may be elevated with pillows to enhance fluid removal
by gravity.
 Family and child education about the disease is very important for
subsequent management.
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62. Congenital nephrotic syndrome (CNS)
 Nephrotic syndrome that appears in the first 3 months of life and might
present before or at birth
 It has genetic bases for the disorder with unfavorable outcome unless the
cause is an infectious etiology.
 Primary congenital nephrotic syndrome has autosomal inheritance pattern
andmfamily history is important.
 In subsequent pregnancies congenital nephrotic syndrome may be detected
in utero by elevated alpha fetoprotein level in the amniotic fluid.
 Since congenital infections are common in resource limited countries,
secondary congenital nephrotic syndrome could be commoner than the
inherited variety.
 Secondary congenital nephrotic syndrome is a reversible disorder with
treatment of the underlying cause.
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63. cont...
 Most of congenital nephrotic syndrome cases are born prematurely, fetal
asphyxia could occur
 the placental weight is often more than 25% of the baby's birth weight and
might present as hydrops fetalis.
 Urinalysis shows proteinuria > 4 mg/kg/hr, hematuria and leukocyturia
might present
 but often appears late in the first year and end stage renal failure develops
by the age of 2-3 years.
 The outcome of congenital nephrotic syndrome incontrast to nephrotic
syndrome in older children is poor.
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64. Causes of congenital nephrotic syndrome
 Primary causes:
 Finish type (caused by mutations in the nephrin gene)
 Non-Finish type (caused by mutations in genes, like podocin)
Idiopathic nephrotic syndrome:
Minimal change nephrotic syndrome,
FSGS, Diffuse mesangial sclerosis
 Secondary causes: congenital infections like
Congenital syphilis
HIV
Congenital toxoplasmosis, Congenital cytomegalovirus
Congenital rubella
Hepatitis B and C, Malaria
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65. Treatment of CNS
 depends on definitive diagnosis
 Specific therapy for secondary causes of nephrotic syndrome:
antibiotics for syphilis,
antimicrobial and steroid for toxoplasmosis,
immunosuppressive for SLE
 If the secondary causes are excluded, trial of steroid therapy.
 congenital nephrotic syndrome of the autosomal recessive or the syndromic
variant does not respond to conventional therapy
so the goals of medical therapy are to provide adequate nutrition,
control of edema and hypertension and
prevent infection and thrombosis for possible successful renal
transplantation
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66. Prognosis of Nephrotic syndrome in children
 Most children with steroid-responsive nephrotic syndrome have repeated
relapses, which generally decrease in frequency as the child grows older.
 Idiopathic nephrotic syndrome should not be considered chronically ill and
should participate in all age-appropriate childhood activities and maintain
an unrestricted diet when in remission.
 Children with steroid-resistant nephrotic syndrome, most often caused by
FSGS, generally have a much poorer prognosis.
 These children develop progressive renal insufficiency, ultimately leading
to end-stage renal disease requiring dialysis or kidney transplantation.
 Recurrent nephrotic syndrome develops in 30–50% of transplant
recipients with FSGS.
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67. Reference
 Damte Shimelis, M.D, Hand book on the management of pediatric renal
problems in Ethiopia, March 2009.
 Kishore Phadke • Paul Goodyer, Martin Bitzan, Manual of Pediatric
Nephrology on glomerular diseases, Verlag Berlin Heidelberg 2014.
 Hannu Jalanko and Christer Holmberg, on Glomerular Disease, Pediatric
Nephrology 7th Edition.
 Rudolph P Valentini and William E Smoyer, on Nephrotic syndrome ,
Clinical Pediatric Nephrology 2nd Edition.
 Elif Erkan, on Nephrotic syndrome in children, Nelson 21st Edition.
 Patrick Niaudet, MD, on nephrotic syndrome in children, Uptodate 21.6.
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68. Thank you
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