This document provides guidelines for the management of steroid sensitive nephrotic syndrome according to recent recommendations from the Indian Academy of Pediatrics (IAP). It defines key terms like nephrotic syndrome, remission, relapse, frequent relapse, and steroid resistance. It outlines the treatment approach for initial episodes, relapses, and frequent relapses. This includes use of prednisone and steroid-sparing agents like levamisole. It also discusses difficult to treat cases and use of calcineurin inhibitors for patients who do not respond to standard therapies.

1. MANAGEMENT OF
STEROID SENSITIVE
NEPHROTIC SYNDROME
( RECENT IAP GUIDELINES)
DR. MEHBUB UL HAQUE

2. NEPHROTIC SYNDROME
• Nephrotic Syndrome is the clinical manifestation of Primary
Glomerular disease that is characterized by
• 1) Heavy Protenuria / Nephrotic range proteinuria
2) Hypoalbuminemia
3) Hyperlipidemia
4) Edema
2

3. COMPARISON BETWEEN DEFINATIONS OF 2018
INDIAN
SOCIETY OF PAEDIATRIC NEPHROLOGY ( ISPN)
GUIDELINE ,
2021 ISPN GUIDELINES AND 2021 KIDNEY DISEASE
IMPROVING GLOBAL OUTCOMES (KDIGO) GUIDELINES

4. HEAVY PROTEINURIA IS DEFINED AS :
(1) UNINE DIPSTIC 3+
(2) 24 HOUR URINE PROTEIN > 3.5 GM
(3) URINE PROTEIN CREATININE RATIO > 2
HYPOALBUMINEMIA IS DEFINED AS:
(1) < 3.0 GM/DL [ IAP]
(2) < 2.5 GM/DL [ NELSON]
HYPERLIPIDEMIA IS DEFINED AS :
(1) SERUM CHOLESTEROL > 200 MG/DL
4

5. ■ NEPHROTIC SYNDROME AFFECTS 1-3 PER
1,00,000
CHILDREN < 16 YEAR AGE
■ WITHOUT TREATMENT THE MORTALITY IS VERY
HIGH
MOSTLY FROM INFECTIONS
■ FORTUNATELY 80 % OF CHILDREN WITH
NEPHROTIC
SYNDROME RESPONDS TO CORTICOSTEROID

6. DEFINITIONS REGARDING NEPHROTIC
SYNDROME
• REMISSION
Urine protein nil or trace, Up/Uc < 0.2
For three consecutive days in early morning urine
specimen

7. RELAPSE
Urine protein > 3 + in dipstic, Up/ Uc >2
For three consecutive days in early morning urine
specimen
in a patient that have been in remission
previously
7

8. PARTIAL REMISSION
Urine protein 1 + or 2 + in dipstic, Up/Uc > 0.2 <
2
Or
24 hour urine protein 4-40 mg/m²/day, Serum
albumin >3g/dl
And
Absence of Edema

9. FREQUENT RELAPSE
ISPN 2021 ISPN 2018 KDIGO
2021
1 ) MORE THAN EQUAL TO 2 1 ) MORE THAN EQUAL TO 2 1) MORE THAN
EQUAL TO 2
RELAPSE IN FIRST 6 MONTH RELAPSE IN FIRST 6 MONTH RELAPSE IN
6 MONTH
AFTER INITIAL THERAPY AFTER INITIAL THERAPY 2) MORE
THAN EQUAL TO 4
2 ) MORE THAN EQUAL TO 3 2) MORE THAN EQUAL TO 4 RELAPSE IN
1 YEARS

10. DIFFICULT TO TREAT STEROID SENSITIVE
DISEASE
• TWO COMPONENTS ARE INCLUDED IN THIS CATEGORY
1) FREQUENT RELAPSE OR SIGNIFICANT STEROID TOXICITY
WITH IN FREQUENT RELAPSE
2) FALIURE OF > 2 STEROID SPARING AGENTS ( INCLUDING
LEVAMISOLE , CYCLOPHOSPHAMIDE , MYCOPHENOLATE
MOFETIL
10

11. STEROID DEPENDENCY
Two consecutive relapse when on alternate day steroid
therapy
Or
Within 14 days of discontinuation of the
therapy
11

12. STEROID RESISTANCE
ISPN 2021 ISPN 2018 KDIGO 2021
LACK OF COMPLETE LAKE OF COMPLETE LACK OF
COMPLETE
REMISSION DESPITE REMISSION DESPITE REMISSION
DESPITE
OF DAILY THERAPY OF DAILY THERAPY OF DAILY
THERAPY
WITH PREDNISONE WITH PREDNISONE WITH
PREDNISONE
FOR 6 WEEKS FOR 4 WEEKS FOR 4 WEEKS

13. TREATMENT OF INITIAL
EPISODE
OF NEPHROTIC
SYNDROME

14. GOAL : 1) To confirm diagnosis
2) To rule out any secondary cause
3) To screen for complications
14
INVESTIGATION AT THE FIRST EPISODE OF NEPHROTIC
SYNDROME

15. INVESTIGATION: 1) CBC [ Complete Blood Count ]
2) Blood for Urea , Creatinine ,
Electrolytes
3) Blood for total Protine , Albumin
, and
Cholesterol
4) Uninalysis and qualitative
estimation of

16. ADDITIONAL INVESTIGATION :
INDICATION : 1) GROSS HAEMATURIA OR PERSISTENT
MICROSCOPIC
HAEMATURIA
2) SUSTAINED HYPERTENSION
3) AKI WITHOUT HYPOVOLEMIA
4) SUSPECTED OTHER SECONDARY CAUSE
TEST : 1) COMPLEMENT C3 & C4
2) ANA ( Antinuclear Antibody )
3) ASO ( Anti Sreptolysin O )
16

17. INDICATION : 1) HISTORY OF JAUNDICE
2) HISTORY OF ANY OTHER LIVER
DISEASE
TEST : 1) HBSAg
2) Anti HCV
3) Serum Transaminase
17

18. INDICATION: 1) TUBERCULIN TEST
POSITIVE
2) HISTORY OF CAONTACT
3) SUSPECTED LOWER
RESPIRATORY
TRACT INFECTION
TEST : CHEST RADIOGRAPHY

19. ROLE OF KIDNEY BIOPSY IN TREATMENT OF SSSS
○ The large majority of patients with SSSS show minimal
change disease
and less commonly FSGN or Mayeloproliferative GN .
○ So the kidney biopsy is not routinely required in children
with idiopathic
nephrotic syndrome.
○ Patient with frequent relapse also do not require kidney
biopsy before
initiating therapy with steroid sparing agents like
Levamisole , Cyclo-

20. 2o INDICATIONS FOR KIDNEY BIOPSY
1) Age of onset is more than 12 years
2) Gross Haematuria
3) Persistent Microscopic Haematuria ( > 5 RBC / HPF in 3 or
more times )
4) AKI not attributed to Hypovolemia
5) Systemic Features e.g fever , rash , arthralgia , low
compliment C3
6) Initial or late corticosteroid resistance
7) Prolonged therapy with CNI / Calcineurin Inhibitors ( >
30-36 months )

21. COMPARISON BETWEEN ISPN 2021 , ISPN 2018 AND KDIGO
2021 . GUIDELINES FOR PREDNISONE THERAPY OF
INITIAL EPISODE
ISPN 2021 ISPN 2028 KDIGO 2021

22. IAP GUIDELINES FOR APPROACH TO
TREATMENT
OF FIRST EPISODE OF NEPHROTIC
SYNDROME

23. ☆ However estimation of body surface area involves
complex
formulae with variable results and calculation
using weight
is convenient experts prefer to administer
prednisolone
based on body surface area because calculation
using body
weight causes relative underdoosing in young

24. ☆☆ There is no evidence to support therapy with
preparation
other than prednisolone or its active
metabolite
Use of Defzacort , Betamethasone ,
Dexamethasone
or Methylprednisolone is nor recommended
☆☆☆ Prednisolone always given with food
☆☆☆☆ Use of Antacid , Ranitidine or PPI is not

25. TREATMENT OF RELAPSE OF
NEPHROTIC SYNDROME

26. IAP GUIDELINES FOR APPROACH TO THE
TREATMENT . OF RELAPSE OF
NEPHROTIC SYNDROME

27. ●A RELAPSE CONVENTIONALLY EMPERICALLY
BEEN
TREATED AS OUTLINED IN PREVIOUS SLIDE
, BUT
THE GUIDELINES VARY IN DURATION OF
THERAPY.
● REMISSION IS USUALLY ACHIEVED BY 7-
10 DAYS

28. ● IN CASE OF PERSISTENT PROTEINURIA,
DAILY
THERAPY MAY BE EXTENDED TO MAXIMUM
6
WEEKS
● LACK OF REMISSION DESPITE OF
TREATMENT
OF 6 WEEKS DAILY PREDNISOLONE

29. TREATMENT OF FREQUENT
RELAPSE OF NEPHROTIC
SYNDROME

30. MANAGEMENT OF FREQUENT RELAPSE AND STEROID
DEPENDENCE
● The guideline Suggests mainly two therapies for the
management of
frequent Relapse : 1) Long-term corticosteroid therapy
2) Non-corticosteroid therapy

31. LONG TERM CORTICOSTEROID THERAPY
IN PATIENTS WITH FREQUENT RELAPSE THE GUIDELINE
SUGGESTS . LONG TERM CORTICOSTEROID THERAPY
WITH PREDNISOLONE
AT TAPERING DOSE OF O.5–0.7 mg/kg ON ALTERNATE
DAY FOR
6 MONTH . THE MEDICATION CAN BE TAPPERED TO
0.2~0.3mg/kg

32. ☆ Alternate-day Prednisolone therapy
during
Fever or Respiratory tract infection :
Evidence suggests that more than half of
relapses
in STEROID SENSITIVE NEPHROTIC SYNDROME
occurs following upper respiratory tract
infection .
So the recommendation is start same dose
daily
therapy for 5-7 days during fever or

33. NON-CORTICOSTEROID THERAPY
● IN PATIENTS WITH FAILLING ALTERNATE DAY
THERAPY
WITH PREDNISOLONE RECOMMENDATION IS THERAPY
WITH LEVAMISOLE OR MYCOPHENOLATE MOFETIL
(MMF)
● IN PATIENTS WITH SIGNIFICANT STEROID TOXICITY
HIGH
STEROID THRESHOLD OR FALIURE OF LEVAMISOLE
THERAPY

34. FEATURES OF STEROID TOXICITY
1) HYPOGLYCEMIA ( fasting glucose > 100mg/dl , post-parandial
glucose
> 140 mg/dl or HbA1c > 5.7
2) OBESITY ( body mass index > equivalent of 27 kg/m² in adults)
3) SHORT STATURE ( hight < 2 SD for age with hight velocity < - 3
SD for age
4) RAISED INTRAOCULAR PRESSURE
5) MYOPAYHY

35. DETAILS OF IMMUNOSUPPRESSIVE MEDICATIONS FOR FREQUENT
RELAPSE

36. DIFFICULT TO TREAT STEROID SENSITIVE NEPHROTIC
SYNDROME
• ■ A PROPORTION OF PATIENT WITH STEROID SENSITIVE NEPHROTIC
SYNDROME SHOW
DISEASE CHARACTERISED BY MULTIPLE RELAPSES DESPITE OF THERAPY WITH
STEROID-
SPARING AGENTS AND/ OR MEDICATION-ASSOCIATED TOXICITY.
DIFFICULT TO TREAT NEPHROTIC SYNDROME IS DEFINED AS PATIENTS WITH
i) FREQUENT RELAPSE OR INFREQUENT RELAPSE WITH SIGNIFICANT
STEROID
TOXICITY

37. TREATMENT OF DIFFICULT TO STEROID SENSITIVE NEPHROTIC
SYNDROME
• ■
• ■■ PATIENTS WITH STEROID SENSITIVE NEPHROTIC
SYNDROME
USUALLY TREATED WITH CALCINEURIN INHIBITORS (
CNI ) ,
EITHER CYCLOSPORINE OR TACROLIMUS
■ PATIENTS WHO HAVE FAILED CNI OR HAVE
RECEIVED
THESE AGENTS FOR PROLONGED DURATION