Nephrotic syndrome is characterized by heavy proteinuria, hypoalbuminemia, edema, and hyperlipidemia. The most common cause is minimal change disease. Treatment involves corticosteroids as initial therapy, with cyclophosphamide or other immunosuppressants used for frequent relapses or steroid resistance. Supportive care focuses on managing edema, diet, and preventing infections, which are a major complication. Kidney biopsy may be needed to identify underlying renal pathology or guide treatment decisions.

1. DR. GORDHAN DAS
MBBS,MCPS,FCPS
Associate Professor
MedicineDepartment

2. DEFINITION
 Nephrotic syndrome is the clinical manifestation of
glomerular diseases associated with heavy (nephrotic-
range) proteinuria.
 The triad of clinical findings associated with
nephrotic syndrome arising from the large urinary
losses of protein are hypoalbuminemia (≤3 g/dl) ,
edema, and hyperlipidemia.

3. CLASSIFICATION
ETOLOGICAL CLASSIFICATION Primary nephrotic
syndrome: (90%)
Disease limited to kidney
Not associated with a systemic disease
Secondary nephrotic syndrome(10%) – associated with
systemic disease such as HSP,SLE, amyloidosis.
 primary NS is also classified according to
their response to steroid therapy as
steroid sensitive or steroid-resistant.

4. HISTOLOGICAL CLASSIFICATION:
 Primary NS or idiopathic nephrotic syndrome includes
four
1. Minimal change glomerular disease(MCD) (85%)
2. Diffuse mesangial proliferation (DMP)
3. Focal and segmental glomerulosclerosis(FSGS)
4.MCD or DMP associated with IgM deposits in the
mesangium

5. PATHOPHYSIOLOGY
Complex disturbances in
immune system
Genetic mutation / mutation in
proteins
Extensive effacement of podocyte
foot processes
Increased permeability of
glomerular basament membrane
Massive proteinuria
Decreased osmotic pressure and
increased hydrostatic pressure
in capillaries
Hypoalbuminemia

6. Edema
Decreased circulatory blood volume
- hypovolemia
Increased RAS activity
Increased sodium and water reabsorption
Hemo concentration
Increased ADH due to osmoreceptor
stimulation
Increased water retention
Worsening of
edema

7. Hypoalbuminemia
Increased protien synthesis by
liver along with excessive
production of lipids and
fibrinogen
Hyper lipidemia
Lipiduria- lipid casts in
urine
hypercoagulability
Urinary loss of
coagulation
factors

9. INVESTIGATIONS
TO CONFIRM DIAGNOSIS:
Urine analysis:
Nephroticrange proteinuria-
Urinary dipstick showing 3 + / 4+ protein Urine
protein : creatinine ratio >2 Proteinuria- 40mg/m2/hr,
24 hour urine 50mg/kg/24 hr
Selective proteinuria seen in Minimal change
NS
RBC may be present in NS with significant
lesions(MPGN,FSGS)

10. Serum proteins -Total proteins decreased
Hypoproteinemia(<2.5 gm/dl) AG ratio-
reversed
Lipid profile - sr.cholesterol - increased

11. TO SCREEN COMPLICATIONS:
 CBC:
Anemia(microcytic hypochromic anemia)
Raised platelet count
TC,DC(raised in infections)
 RFT: Serum urea and creatinine-raised in CRF
BEFORE STARTING THERAPY:
 ANA levels
 Mantoux

12. MANAGEMENT

13. SPECIFIC TREATMENT
Treatment of the Initial Episode:
Adequate treatment of the initial episode, both in terms of
dose and duration of corticosteroids is important.
Medication: The standard medication for treatment is
prednisolone or prednisone

14.  Treatment regimen:
Initial episode of nephrotic syndrome treated with
prednisolone 1 to 2 mg/kg/day in single or divided
doses for 6 weeks.

15.  Remission: Urine albumin nil or trace (or proteinuria <4
mg/m2/h) for 3 consecutive early morning specimens.
 Relapse: Urine albumin 3+ or 4+ (or proteinuria >40
mg/m2/h) for 3 consecutive early morning specimens,having
been in remission previously.
 Frequent relapses: Two or more relapses in initial six months
or more than three relapses in any twelve months.
 Steroid dependence: Two consecutive relapses when on
alternate day steroids or within 14 days of its discontinuation.
 Steroid resistance: Absence of remission despite therapy with
daily prednisolone at a dose of 2 mg/kg per day for 8 weeks.

16. b)cyclophosphamide (2 mg/kg/day) may be
administered along with alternate day prednisolone (1-
1.5 mg/kg) for 12 weeks.
In view of safer toxicity profile, cyclophosphamide is
usually preferred
The total leukocyte count should be monitored every
2-3 weeks and treatment is discontinued if leukocyte
count falls below 4000/mm3.
Treatment with cyclophosphamide may rarely cause
alopecia, nausea and vomiting.
Treatment with cyclophosphamide may be considered
in patients showing: (i) significant steroid toxicity, (ii)
severe relapses with hypovolemia or thrombosis, and
(iii) poor compliance or follow up.

17.  Steroid resistant nephrotic syndrome:
 Defined as the failure to achieve remission after 8 wk of
corticosteroid therapy.
 steroid-resistant nephrotic syndrome require further
evaluation, including a diagnostic kidney biopsy,
evaluation of kidney function, and quantitation of urine
protein excretion (in addition to urine dipstick testing).
 Steroid-resistant nephrotic syndrome is usually caused by
FSGS (80%), MCNS, or membranoproliferative
glomerulonephritis.
 SRNS and specifically FSGS, is associated with a 50% risk
for end-stage kidney disease.

18.  Calcineurin inhibitors (cyclosporine or tacrolimus)
are recommended as initial therapy for children with
steroid-resistant nephrotic syndrome.
Cyclosporine - administered in a dose of 4-5 mg/kg daily for
12-24 months.
Therapy is continued with prednisolone in a dose of 1.5
mg/kg on alternate days for 4 weeks, and then tapered
gradually
Side effects:- hypertension, gum hypertrophy and
hirsutism may occur, in which case the dose of cyclosporine
may be reduced to 3 mg/kg/day

19. Tacrolimus :
 Is an alternative agent, administered at a dose of 0.1-0.2
mg/kg daily for 12-24 months.
 Side effects include hyperglycemia, diarrhea and rarely
neurotoxicity (headache,seizures).
 Blood levels of creatinine and glucose should be
estimated
every 2-3 months.

20. Mycophenolate mofetil(mmf ):
Is given at a dose of 800-1200 mg/m2 along with tapering
doses of prednisolone for 12-24 months.
side effects include gastrointestinal discomfort, diarrhea
and leukopenia.
Leukocyte counts should be monitored every 1-2 months
treatment is withheld if count falls below 4000/mm3.
The lack of renal,hemodynamic and metabolic toxicity
with this agent makes it an attractive alternative to
calcineurin inhibitors.

22.  The advantages of using these drugs should be balanced
against their potential toxicity.
 Treatment with cyclophosphamide may be considered in
patients showing:
(i) significant steroid toxicity
(ii)severe relapses with hypovolemia or thrombosis
(iii)poor compliance or follow up.
 Cyclosporin is recommended for patients that continue to
show steroid dependance or frequent relapses despite a course
of levamisole and cyclo-phosphamide.

23. SUPPORTIVE
This forms an important aspect of managing
with nephrotic syndrome.

24. DIET
 A balanced diet adequate in protein and calories is
recommended.
 Patients with persistent proteinuria are prone to mal-
nutrition and should receive 2-2.5 g/kg of protein
daily.

25.  Salt restriction is not necessary in most patients with
steroid responsive nephrotic syndrome.
 Corticosteroids stimulate the appetite, and advice should
be given about ensuring physical activity and preventing
excessive weight gain.

26. EDEMA
 Control of edema is an integral part of supportive care.
 Since treatment with corticosteroids usually leads to diuresis
within 5-10 days, diuretics are avoided unless edema is
significant.
 Patients with persistent edema and weight gain of 7-10% are
treated with oral frusemide (1-3 mg/kg daily).
 Additional treatment with potassium sparing diuretics is not
required if frusemide is used at this dose for less than one
week.

27.  For patients with refractory edema, a combination of
diuretics and albumin infusion is used.
 Albumin (20%) is given as an infusion at a dose of 0.5-1
g/kg over 2-4hr, followed by administration of
frusemide (1-2 mg/kg IV)
 While infusion of albumin results in increased urine
output, the effect is not sustained and repeated
administration might be necessary.
 Patients receiving albumin should be observed for
respiratory distress, hypertension and congestive heart
failure.

28. PATIENT EDUCATION
 A proportion of patients, especially those
(i)with early onset of nephrotic syndrome
(ii)with a frequently relapsing course
(iii)requiring treatment with alkylating agents or
Cyclosporine may continue to show relapses beyond
adolescence
 Parental motivation and involvement is essential in
the
long-term management of these children.

29.  They should be provided information about the disease,
its expected course and risk of complications and the
following are emphasized:
(a)Urine examination for protein at home using dipstick,
sulfosalicylic acid or boiling test.
 The examination should be done every morning during a
relapse, during intercurrent infections or if there is even
mild periorbital puffiness.
 The frequency of urine examination is reduced, to once or
twice a week, before development of significant edema is
stressed.

30. (b)Maintain a dairy showing results of urine protein
examination, medications received and intercurrent
infections.
(c)Ensure normal activity and school attendance
(d)Since infections are an important cause of morbidity,
patients should receive appropriate immunization and
other measures for protection.

31. KIDNEY BIOPSY
 Performed before therapy with calcineurin inhibitors.
 A biopsy is required to identify the underlying renal
disease in certain cases.
INDICATIONS
• Gross hematuria, persistent microscopic hematuriaor low
serum C3.
• Sustained hypertension.
• Renal failure not attributable to hypovolemia.
• Suspected secondary causes of nephrotic syndrome.
• Proteinuria persisting despite 4-weeks of daily
corticosteroid therapy
.
• Before treatment with cyclosporin or tacrolimus

32. COMPLICATIONS
Patients with steroid sensitive nephrotic syndrome are at
risk for certain complications, early detection of which is
necessary.
Infections
Thrombosis
Hypovolemia
Hypertension
Corticosteroid side effects

33. INFECTIONS
 Common infections include peritonitis, cellulitis and
pneumonia.
 Viral and bacterial infections may occasionally precipitate
relapses in patients previously in remission.

34.  The dose of prednisolone should be tapered to 0.5
mg/kg/day or lower during the infection.
 Patients with nephrotic syndrome who are Mantoux
positive but show no evidence of tuberculosis should
receive prophylaxis with INH for six months.
 Those showing evidence of active tuberculosis should
receive standard therapy with anti-tubercular drugs

35. INFECTION CLINICAL
FEATURES
COMMON
ORGANISM
TREATMENT
PERITONITIS Abdominal
pain,tenderness,di
stension,vomitings
,ascitic
fluid>100leucocyte
s/mm3 with >50%
neutrophils
Str.pneumoniae,st
r.pyogens, e.coli
Ceftriaxone/cefotaxim
e for 7-10days
Ampicillin and
aminoglycosides for 7-
10 days
PNEUMONIA Fever,cough,tachy
pnea,intercostal
retractions,crepita
tions
Str.pneumoniae
H.Influenza
Staph.aureus
Oral:
amoxycillin,coamoxycl
av,erythromycin
Parenteral: ampicillin
and aminoglycoside or
Cefotaxime/ceftriaxon
e for 7-10 days.

37. THROMBOSIS
 Persons with nephrotic syndrome are at risk for venous
and, rarely, arterial thrombosis.
CAUSES:
 Increased fibrinogen levels
 Loss of antithrombin-iii,protein-c,protein-s

38.  USG, Doppler studies and cranial MRI are useful in
confirming the diagnosis.
 Patients with thrombotic complications require urgent
treatment.
 The treatment includes correction of dehydration and
other complications, and use of heparin or low
molecular weight heparin (SC) initially, followed by oral
anticoagulants on the long term.
 There is no role for prophylactic treatment with
anticoagulants in patients with hypoalbuminemia and
edema.

39. HYPERTENSION
This may be detected at the onset of nephrotic
syndrome
or later due to steroid toxicity.
Therapy is initiated with ACE inhibitors, calcium channel
blockers or β adrenergic antagonists,keeping the blood
pressure at less than the 90th percentile

40. CORTICOSTEROID SIDE
EFFECTS
 Parents should be explained about the side effects of the
medications, including increased appetite, impaired
growth, behavioral changes, risk of infections, salt and
water retention, hypertension and bone demineralization.
 All patients should be monitored for cushingoid features
and blood pressure; six-monthly record of height and
weight, and yearly evaluation for cataract should be done.
 Patients on prolonged (>3 months) treatment with
steroids should receive daily supplements of oral calcium
(500 t0 1000 mg daily) and vitamin D (125-250 IU).

41. THE END