1. 6
MANSOURA UNIVERSITY CHILDREN’S HOSPITAL
2014
Protocols of management of
Nephrotic syndrome in children
Pediatric Nephrology Unit
2. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
2
Table of content:
1. Definitions and inclusion criteria.
2. Symptomatic management of nephrotic syndrome (NS).
3. Renal biopsy indications and precautions.
4. Protocols for steroid responsive NS.
5. Protocols for steroid resistant NS.
6. Protocols for membranous nephropathy.
7. Protocols for IgA nephropathy.
3. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
3
Definitions and inclusion criteria
Criteriafor diagnosis of Nephrotic syndrome:
First AM urine protein/creatinine(Up/cr) ratio>2 Essential for diagnosis
Hypoalbuminemia–Serum albumin<2.5gdl.
±
Edema.
Hyperlipedemia.
SDNS: Relapse during maintenance or within 2 weeks after the stoppage of
treatment.
FRNS: Two or more relapses within 6 months.
Infrequent relapse: One relapse within 6 months of initial response, or one to
three relapses in any 12-month period.
Steroid resistant Nephrotic syndrome: (SRNS)
Lack of complete remission despite treatment with prednisoloneat a dose of
2 mg/kg/day (60 mg/m2
/day) for 4 weeks.
Lack of remission after 4 weeks ….at the firstepisode of nephrotic syndrome.
Late resistance
Patients who are steroid sensitiveinitially, but show steroid resistanceduring
a subsequentrelapse.
Complete remission:
Negative/trace Albustix result on first AM urine specimens for 3 consecutive
days with quantitative (Up/cr <0.2) confirmation in one of the samples.
Partial remission:
No Edema
>50% reduction in first AM Up/cr from presenting ratio and absolute Up/cr
(0.2-2)(non nephrotic proteinuria)
Relapse:
Edema
Recurrence of ≥ 2+ proteinuria by urine dipstick on first AM urine specimens
for 3 consecutive days within 1 week in absence of URTI, with quantitative
confirmation of nephrotic-range proteinuria (Up/cr >2.0) in one of the
samples.
4. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
4
Indications of renal biopsy at initial presentation (atypical NS):
Gross hematuria.
Elevated serumcreatinine with absence of prerenaletiology.
Low complement level (C3).
Extra-renal symptoms such as malar rash or purpura.
Age less than 1 year and der than 10 years of age.
Sustained hypertension (persistentelevation of blood pressureabove95th
percentile for age).
Patient relapsed during first 2 weeks of maintenance therapy
(45mg/m2/EOD).
All patients with atypical NS will start full dose steroid therapy till result of
biopsy
All drug doses should be calculated using patient’s dry weight
Dry weight: --- last known body weight before developing edema if
unknown ………….use weigth for height
Available oral prednisone/prednisilone preparations:
Hostacortin 5mg/tablet
Solupred 5mg/tablet
Solupred 20mg/tablet
Prednisolone 5mg/tablet
Predsolsyrup 1 mg/ml
Predsolforte syrup 3mg/ml
Xilone syrup 1mg/ml
Xilone forte syrup 3mg/ml
Initial therapy:
Initial prednisone therapy is 60 mg/m2
per day for6 weeks.
45 mg/m 2/
EODfor 6 weeks(if patient relapsed during first 2 weeks of this
step consider renal biopsy).
30mg/m2/EOD for 2 weeks.
15mg/m2/EOD for 2 weeks.
5. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
5
Induction Therapy for Initial Idiopathic Nephrotic Syndrome
Induction order: Date / /20 SA:
First Week
/ /
Second Week
/ /
Third Week
/ /
Fourth Week
/ /
60 mg/m2/d 60 mg/m2/d 60 mg/m2/d 60 mg/m2/d
Dose: ………………. Dose: ……………….. Dose: ……………….. Dose: ……………
Assessment at end of 4 weeks:
Clinical:
BW: oedema: blood pressure:
Laboratory:
U/A : Pr/cr: serum albumin:
Decision: :
SSNS& continue week 5, 6 SRNS for biopsy
Fifth Week
/ /
Sixth Week
/ /
60 mg/m2/d 60 mg/m2/d
Dose: ……………….. Dose: ……………
Available oral prednisone/prednisilone preparations:
Hostacortin 5mg/tablet
Solupred 5mg/tablet
Solupred 20mg/tablet
Prednisolone 5mg/tablet
Predsol syrup 1 mg/ml
Predsolforte syrup 3mg/ml
Xilone syrup 1mg/ml
Xilone forte syrup 3mg/ml
Disprelone 20mg/tablet
Name:…………………… Age: sex: dry weight :
7. جامعــةالمنصــورةMansoura University
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وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
7
First relapse and infrequent relapse
Steroid therapy of 60 mg/m2
per day until proteinuria disappeared for 4-5
days(confirmed by 3 urine analysis). A maximum period of 4 weeks on
60mg/m2 /day if no remission …….late steroid resistant.
Alternate day prednisone of 45 mg/m2
for an additional six weeks and
tapering of 15mg/m2
every 2 weeks.
Induction: 60mg/m2
/d till proteinuria disaapear: max 4 weeks
Date / /20 SA:
First Week
/ /
Second Week
/ /
Third Week
/ /
Fourth Week
/ /
60 mg/m2/d 60 mg/m2/d 60 mg/m2/d 60 mg/m2/d
Dose: ………………. Dose: ……………….. Dose: ……………….. Dose: ……………
Maintenance therapy: Date / /20 SA:
Week 1
/ /
Week 2
/ /
Week 3
/ /
Week 4
/ /
45 mg/m2/EOD 45 mg/m2/EOD 45 mg/m2/EOD 45 mg/m2/EOD
Dose: ………………. Dose: ……………….. Dose: ……………….. Dose: ……………
Week 7
/ /
Week 8
/ /
30 mg/m2/EOD 30 mg/m2/EOD
Dose: ………………. Dose: ………………..
Name:…………………… Age: sex: dry weight :
Week 5
/ /
Week 6
/ /
45 mg/m2/EOD 45 mg/m2/EOD
Dose: ………………. Dose: ………………..
Week 9
/ /
Week 10
/ /
15mg/m2/EOD 15 mg/m2/EOD
Dose: ………………. Dose: ………………..
8. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
8
Management of SDNS and FRNS
A
1- Steroid induction (60mg/m2
/day) until proteinuria has disappeared for four to
five days (confirmed by 3 urine analysis)………..startmaintenance
2- Low dose steroid (15 mg/m2
EOD) for 6 months.
If relapse occurs
B
1- Steroid induction (60mg/m2
/day) until proteinuria has disappeared for four to
five days (confirmed by 3 urine analysis)………..start maintenance
2- Low dose steroid (30 mg/m2
EOD) for 6 months.
If relapse occurs
C
1- Steroid induction (60mg/m2
/day) until proteinuria has disappeared for
four to five days (confirmed by 3 urine analysis)………..startmaintenance
2-Levamizolprotocol(2.5 mg/kg/EOD max dose 150mg/d for 12months) Start
at beginning of steroid maintainence .
(Follow up CBC every 2 weeks for risk of neutropenia).
3. Steroid therapy maintenance:Tapering over 1 year
D
MMF protocol
If relapse occurs
Renal Biopsy
Others Idiopathic
Regardless the pathological type of idiopathic NS
E
Calcineurin inhibitors
F
Cyclophosphamide
9. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
9
Induction Therapy for SSSDNS & SSFRNS
(60mg/m2/day) until proteinuria disappeared(max 4 weeks) for 4-5 days
(confirmed by 3 urine analysis)………..start maintenance
Patient Name:………………………………………Age : Sex : Dry weigth:
Induction order: Date / /20 SA:
First Week
/ /
Second Week
/ /
Third Week
/ /
Fourth Week
/ /
60 mg/m2/d 60 mg/m2/d 60 mg/m2/d 60 mg/m2/d
Dose: ………………. Dose: ……………….. Dose: ……………….. Dose: ……………
Induction order: Date / /20 SA:
First Week
/ /
Second Week
/ /
Third Week
/ /
Fourth Week
/ /
60 mg/m2/d 60 mg/m2/d 60 mg/m2/d 60 mg/m2/d
Dose: ………………. Dose: ……………….. Dose: ……………….. Dose: ……………
Induction order: Date / / 20 SA:
First Week
/ /
Second Week
/ /
Third Week
/ /
Fourth Week
/ /
60 mg/m2/d 60 mg/m2/d 60 mg/m2/d 60 mg/m2/d
Dose: ………………. Dose: ……………….. Dose: ……………….. Dose: ……………
18. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
1
8
Rituximab protocol for SDNS, FRNS
Indications:
1. Multiple drug resistance(cyclosporine, mycofenolate mofetil, tacrolimus,
cyclophosphamide).
2. Severe adverse effects of other immune suppressives.
Contra-indications torituximabtherapy:
1. Anaphylaxis to rituximab.
2. Relative contra-indications:
*Allergy to rituximab- infusion reactions are common and can usually be
managed with pre-medication and slow infusion
*Pneumonitis- due to risk RALI (Rituximab associated lung injury).
Side effects of rituximab:
Infusion reaction Late adverse effects
Sore throat
Wheezing, cough, Dyspnea
Fever
Skin rash
Nausea , vomiting
Bradycardia tachycardia
HypertensionHypotension.
Nasal stiffnes
Leg pain.
Sepsis
Granulocytopenia
Liver failure
fever
Baseline, pre-treatment prior to first dose:
Test Date Result
DEXA
Ophthalmology assessment for cataracts
Viral serology: HIV, HBsAg, HBsAb, HBcAb,
HCV
Polyomavirus PCR (Blood)
Renal biopsy
Serum creatinine
Serum calcium/phosphorus
Urine protein/creatinine ratio
Liver function test
CD19 (peripheral blood)
CD20 (peripheral blood)
Complete blood picture
Premedications: (30-60 minute before each infusion):
19. جامعــةالمنصــورةMansoura University
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وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
1
9
1. Prednisolone 0.5mg/kg
2. Avil: intravenous/8 hours.
3. Paracetamole:
10-15mg/kg/dose/6 hours intravenous.
4. Withhold or decrease dose of antihypertensive medications 12
hours before dose for risk of hypotension.
Sulfamethoxazole/trimethoprime prophylaxis:
(5mg/kg to max 160/800mg 3 days per week) for 6 months.
Available preparations:
MabThera ampoule 500mg/50ml
Rituxan ampoule 100mg/10ml
Rituximab 100mg/10ml, 500mg/50ml.
Preparation of rituximab(just before infusion):
Just before administration, rituximabshouldbe diluted with 0.9% sodium
chloride injection to a final concentration of 1-4 mg/mL.
A 1-mg/mL dilution(each 1ml of Rituximab diluted in 10 ml saline) is
preferable to facilitate adjustments in the infusion and to avoid adverse
effects.
Rituximab should not be mixed with other medications or i.v. fluids
because there is a lack of compatibility data.
Preparedinfusions are stable inpolyvinyl chloride or polyethylenebags at
2-8 C (36-46 °F) for 24 hours and at room temperature for an additional 12
hours.
Unused portions of undiluted drug must be discarded because of the
absence of a preservative.
Infusion of rituximab:
20. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
2
0
1. Central or peripheral i.v. catheter.
2. Should never be given by i.v. push or bolus injection.
3. Blood pressure and temperature monitoring /hour during and 24
hours after infusion.
4. Infusion over 6-8 hours(Gradual increase rate of infusion every hour
if no infusion reaction)(10ml/min 1st
hour, 20ml/min 2nd
hour, 30
ml/min 3rd
, 40ml/min 4th
hour then 50 ml/min from 5th
hour to end
of infusion).
Dose of rituximab in SDNS: 375mg/m2/dose weekly for 4 doses
(max 500mg/dose):
1. If B cell depletion us confirmed on day 5-7 of first infusion (CD 19<1%),
No more doses.
2. If B cell depletion not achieved after first infusion repeat infusion till B cell
depletion is achieved for maximum 4 doses
Week 1 Week 2 Week 3 Week 4
Date: Date: Date: Date:
Dose: mg Dose: mg Dose: mg Dose: mg
Day 5 CD19:
(Target <1%)
Day 5 CD19:
(Target <1%)
Day 5 CD19:
(Target <1%)
Day 5 CD19:
(Target <1%)
Day 7
protein/creatinine:
Day 7
protein/creatinine:
Day 7
protein/creatinine:
Day 7
protein/creatinine:
Weeks 5-52:
Monthly check liver function test, creatinine, Ca, Phos, (CD19),
Immunoglobulins, urine microscopy and Pr:Cr.
Other immunsuppresive therapy can be tapered gradually and may be
completely stopped after 6 months of Rituximab.
Relapse after RituximabassociatedwithB cell reconstitutionduring initial
12 months Rituximab therapy:
Bring patient into remission first by steroids then Single dose Rituximab
375mg/m2 to max 500mg and confirm B cell depletion (CD 19 < 1%) at 1
week if depletion not achieved repeat weekly infusion up to max 4 doses.
Written consent must be obtained from legal guardians of
patient before starting protocol after explanation of drug
benefits and potential side effects.
21. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
2
1
Protocols of management of SRNS
Renal Biopsy
1- All children with SRNS, whether initial or late, should undergo a renal biopsy
before starting specific treatment.
2- You should obtain informed consent fromthe parents before performing renal
biopsy (look at renal biopsychick list)
3-The histological specimen mustbe examined by:
1. Light microscopy
2. Immunofluorescencemicroscopy
3. Electron microscopic in indicated cases by the consultant.
Renal Biopsy
Others Idiopathic
Regardless the pathological type of idiopathic NS
Calcineurin inhibitors
MMF protocol
Cyclophosphamide
Rituximab protocol
All SRNS shouldreceive Antiproteinuric drugs as long as proteinuriapersist:
Captopril 0.5 mg/kg/singledaily dose Doses can be upgraded guided
Lisinopril 0.05-mg/kg/singledaily dose by blood pressureand kidney
Losartan, valsartan 0.5-1 mg/kg/singledaily dose function
Available preparations
Captopril:
Capoten, captopril, farcopril 25, 50mg/tab Hpopress 12.5,25 mg/tab
Lisinopril:
Zestril, sinopril5,10,20 mg/tab Lisopril, lisinopril 10mg/tab
Maxipril 5, 20 mg/tab.
Losartan:
cozAAr, losartan 50,100mg/tab
Valsartan:
Tareg 40,80,160,320 mg/tab
24. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
2
4
Side effects of cyclophospahmide:
Alopecia, marrow suppression,
Vomiting, hemorrhagic cystitis,
risk of systemic infection
Precautions for Pulse Cyclophosphamide Therapy
* Available preparation:
- Endoxan (200 mg) dissolved in 10 cc saline or 1 gm dissolved in 50cc.
* Administration:
- Calculated dose is put in 150cc saline and given over 1hour infusion.
- Total cumulative dose of Cyclophosphamide: 168 mg/kg/protocol.
Investigations before every Endoxan pulse:
1. CBC.
2. Serum creatinine.
3. Urine analysis.
4. SGOT,SGPT, Bilirubin.
* Precautions before Endoxan administration:
CBC Should be done twoweeks after endoxandose and if: -
a- Total WBCS < 4000 /cmm.
b- Absolute neutrophil count <1000 /cmm.
c- Platelets <150,000.
Do the following:
1- Postpone dose of Endoxan till recover of leucocytic count.
2- Give IV methyl prednisolone (solu - medrol) 30 mg / kg / day
(Maximum1 gm) for 3 days( persistentleucopenia)(excludeinfection)
3. Granulocyte colony stimulating factor for persistentneutropenia
4- Bone marrowaspirationif still leucopenic .
5- Reductionof next dose of endoxanby 25%.
* Precautions during and after endoxan administration:
1- Ensure adequate hydration:
Fluid intake should be 1-1.5 times normal daily maintenance.
2- Mesna: (Uromitexan 100 mg / ml):
* Dose: 60% of total endoxan dosage OR (360 mg / m2).
* Administration: Total dose is fractionated and given direct IV as follow:
- Just before endoxan.
- Just after endoxan.
- 3 hours after endoxan.
- 6 hours after endoxan.
- 9 hours after endoxan.
3- Furosemide (lasix ampoule 10 mg/ml):
1-2 mg / kg / divided every 8-12 hours are given IV.
25. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
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Chapter:ProtocolofNS
2
5
4- Antiemetics: (If vomiting occurs), you can give:
* Zofran (2 mg / ml).
- Dose: 0.15 mg / kg / dose IV.
* Primperan (5 mg / ml).
- Dose: 0.2 mg / kg / every 12 hours IV.
* Dexamethazone (4 mg / ml).
- Dose: 0.5 mg / kg / every 12 hours IV.
Patients withimpairedkidney function, oliguriaor anuria:
Give 75% of calculatedendoxandose.
Endoxan is added to total dose mesna and only 25-50 cc saline infusions over
2 hours.
Bladder irrigation:
2ml mesna + 100 ml cold saline one hour before endoxan
2ml mesna + 100 ml cold saline just after endoxan
1ml mesna + 50 ml cold saline /2 hours for 24 hours
1ml mesna+ 50 ml cold saline /4 hours for 24 hours.
Patients withimpaired hepatic function:
If SGOT, SGPT 3 folds or more above normal and/or serum bilirubin above 3 mg/dl
………. Give 75% of calculated endoxan dose.
28. جامعــةالمنصــورةMansoura University
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وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
2
8
Needed investigations before starting the protocol:
1. Recent serum creatinine.
2. Lipid profile.
3. Result of renal biopsy.
* Induction3-6 months:
-Cyclosporine 5-6mg/kg/dailyBID(start 5mg/kgand adjustaccording to serum
level)
-Cyclosporine 2.5mg/kg/daily BID if basal serum creatinine is high.
-morning and evening doses should be equal.
** Maintenance for 3-5 years:
--Cyclosporine 3-5mg/kg/day BID. Titrate dose according to the therapeutic
level.
-Maintain the lowest effective dose based on efficacy (protienuria) and safety
(S.cr.).
“Trough level” :
(150-200 ng/ml) during induction.
(80-120 ng/ml)during maintenance
Available preparations of cyclosporine:
Solution = Sandimmune Neo-oral, or Apramione[50 ml bottle (100mg/ml)].
Capsules = Sandimmune or Apramione 25,50,and100 mg.
The capsule should not be crushed or evacuated.
The syrup is photosensitive.
Most common side effects:
2. Nephrotoxicity, hypertension.
3. Hypertrichosis, gingival hyperplasia
4. Dyslipidemia
Serum level: should be done
1. 2 weeks after starting induction.
2. 2 weeks after starting maintenance
3. Every 3 months during maintenance
4. Within 2 weeks after any dose modification.
Serum creatinine should be done :
1. Before starting therapy
2. 2 weeks after induction.
3. Every 3 months during maintenance.
30. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
3
0
Protocol of Mycophenolate Mofetil (MMF) in SRNS
Patient Name:………………………Age: sex:
Date Dry
wt
SA Oral Pred.maintenance MMF
Week 1-2
Week 3-4
Week 5-6
Week 7-8
Week 9-10
Week 11-12
Week 13-14
Week 15-16
5th month
6th month
7th month
8th month
9th month
10th month
11th month
12th month
1- Concurrent Oral Prednisone:
1st week- 4th week : 30 mg/m2/day EOD
5th -10th week: 45 mg/m2/day EOD
11th -12th week : 30 mg/m2/day EOD
13th - 14th week : 15 mg/m2/day EOD
15th week-12th month 7.5mg/m2 /EOD
2- MMF:
*Initial starting dose: 300- 400 mg/m2/ dose BID (max.2 gm/day)
*Maintenance dose: 600 mg/m2/dose BID. It should be started after
initial starting dose by 2 weeks if WBC counts not showing leucopenia.
A-Reassess proteinuria after two months of (MMF)
* partial or complete remission continues the protocol for 12 months.
* No remission Stop the protocol.
B-Available preparations: Cellcept Capsules, 500 mg, and 250 mg,
Mofetil tablets 500mg, 250 mg
Myfortic tablets 180, 360 mg
31. جامعــةالمنصــورةMansoura University
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Chapter:ProtocolofNS
3
1
Protocol of Tacrolimus (TAC) In SRNS
Patient Name:……………………………….…………………………….…… Serial No.:………………………………...……………………………..
Dry Weight:…………………………………..……………….…………… Surface area:………....……….……………….………….………..…..
Date Dry
wt
SA TAC dose Oral Pred. dose
week 1-2
/ /
Serum level of TAC and adjust dose
week 3-4 / /
Week 5-6
Week 7-8 / /
3rd month / /
Serum level of TAC and adjust dose
Week13-14
Week 15-16 / /
5th month / /
6th month / /
Serum level of TAC and adjust dose
7th month / /
8th month / /
9th month / /
Serum level of TAC and adjust dose
10th month / /
11th month / /
12th month / /
1. TAC:
-starting dose 0.1mg/kg/d divided in 2 doses for one year.
-can dose up to 0.3mg/kg/d till reaching serum level of TAC:
(9.8-19.4ng/ml) by the whole blood ELIZA assay or
(0.5-1.5ng/ml) by serum high pressure liquid chromatography.
-available preparation prograph 0.5mg, 1mg, 5mg Cap .
2. Oral Prednisone (Concomitant with TAC):
-30mg/m2/day for 4weeks
-45mg/m2/EOD for 6weeks
-30mg/m2/EOD for 2weeks
-15mg/m2/EOD for 2weeks
32. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
3
2
3. Precautions:
Before starting TAC, the followings should be done ALB/crratio, Serum Cr,
Albumin , CBC, OGTT.
Serum level of TAC done 2 week after starting treatment then / 3 m.
F.U the patient each 2 weeks in 1st month then once monthly.
4. Relapse on TAC:
add oral prednisone 60mg/m2/d till complete remission , tapering over two
months.
Pearls on TAC:
It's a macrolid antibiotic isolated from fungus (streptomyces tsukubaensis).
Mechanism of action: calcineurin inhibitor (potent cytokine suppressor more than cyclosporin with
less nephrotoxicity).
Common side effects:
-Diarrhea (commonest) dose of TAC
-Hyperglycaemia Regular monitoning of RBG
-Hypertension Add anti-hypertensive
33. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
3
3
Rituximab protocol for SRNS
Indications:
1. Multiple drug resistance( steroid , cyclosporine, mycofenolate mofetil,
tacrolimus, cyclophosphamide).
2. Severe adverse effects of other immune suppressives.
Contra-indications torituximabtherapy:
1. Patient with SRNS known to have gene mutation for nephrotic syndrome
2. Anaphylaxis to rituximab.
3. Relative contra-indications:
*Allergy to rituximab- infusion reactions are common and can usually be
managed with pre-medication and slow infusion
*Pneumonitis- due to risk RALI (Rituximab associated lung injury).
Side effects of rituximab:
Infusion reaction Late adverse effects
Sore throat
Wheezing, cough, Dyspnea
Fever
Skin rash
Nausea , vomiting
Bradycardia tachycardia
HypertensionHypotension.
Nasal stiffnes
Leg pain.
Sepsis
Granulocytopenia
Liver failure
fever
Baseline, pre-treatment prior to first dose:
Test Date Result
DEXA
Ophthalmology assessment for cataracts
Viral serology: HIV, HBsAg, HBsAb, HBcAb,
HCV
Polyomavirus PCR (Blood)
Renal biopsy
Serum creatinine
Serum calcium/phosphorus
Urine protein/creatinine ratio
Liver function test
CD19 (peripheral blood)
CD20 (peripheral blood)
Complete blood picture
34. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
3
4
Premedications: (30-60 minute before each infusion):
5. Prednisolone 0.5mg/kg
6. Avil: intravenous/8 hours.
7. Paracetamole:
10-15mg/kg/dose/6 hours intravenous.
8. Withhold or decrease dose of antihypertensive medications 12
hours before dose for risk of hypotension.
Sulfamethoxazole/trimethoprime prophylaxis:
(5mg/kg to max 160/800mg 3 days per week) for 6 months.
Available preparations:
MabThera ampoule 500mg/50ml
Rituxan ampoule 100mg/10ml
Rituximab 100mg/10ml, 500mg/50ml.
Preparation of rituximab(just before infusion):
Just before administration, rituximabshouldbe diluted with 0.9% sodium
chloride injection to a final concentration of 1-4 mg/mL.
A 1-mg/mL dilution(each 1ml of Rituximab diluted in 10 ml saline) is
preferable to facilitate adjustments in the infusion and to avoid adverse
effects.
Rituximab should not be mixed with other medications or i.v. fluids
because there is a lack of compatibility data.
Preparedinfusions are stable inpolyvinyl chloride or polyethylenebags at
2-8 C (36-46 °F) for 24 hours and at room temperature for an additional 12
hours.
Unused portions of undiluted drug must be discarded because of the
absence of a preservative.
35. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
3
5
Infusion of rituximab:
5. Central or peripheral i.v. catheter.
6. Should never be given by i.v. push or bolus injection.
7. Blood pressure and temperature monitoring /hour during and 24
hours after infusion.
8. Infusion over 6-8 hours(Gradual increase rate of infusion every hour
if no infusion reaction)(10ml/min 1st
hour, 20ml/min 2nd
hour, 30
ml/min 3rd
, 40ml/min 4th
hour then 50 ml/min from 5th
hour to end
of infusion).
Dose of rituximab in SRNS: 375mg/m2/dose weekly for 4 doses
(max 500mg/dose)
Week 1 Week 2 Week 3 Week 4
Date: Date: Date: Date:
Dose: mg Dose: mg Dose: mg Dose: mg
Day 5 CD19:
(Target <1%)
Day 5 CD19:
(Target <1%)
Day 5 CD19:
(Target <1%)
Day 5 CD19:
(Target <1%)
Day 7
protein/creatinine:
Day 7
protein/creatinine:
Day 7
protein/creatinine:
Day 7
protein/creatinine:
Weeks 5-52:
Monthly check liver function test, creatinine, Ca, Phos, (CD19),
Immunoglobulins, urine microscopy and Pr:Cr.
Other immunsuppresive therapy should be continued during and 6 months
after rituximab course then gradually tapered to lowest effective dose
maintaining patient in remission.
Relapse after RituximabassociatedwithB cell reconstitutionduring initial
12 months Rituximab therapy:
Single dose Rituximab 375mg/m2 to max 500mg and confirm B cell
depletion (CD 19 < 1%) at 1 week if depletion not achieved repeat weekly
infusion up to max 4 doses.
Written consent must be obtained from legal guardians of
patient before starting protocol after explanation of drug
benefits and potential side effects.
36. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
3
6
Protocol for Management of Membranoproliferative GN (MPGN)
Patient Name:………………………………………
Body Weight:…………………………………………
Serial No.:……………………………………………….
Surface Area:…………………………………………
A- If the child is detected by incidental finding of urinary abnormalities without
hypertension, renal impairment, or nephritis:
* No treatment.
* Observe closely.
B- If the child has hypertension, heavy Proteinuria, or Nephrotic syndrome:
1- Methyl Predinsolone 10-20mg/kg/day, max. 1gm, I.V daily for 5-6 dose
Date Dose
1st
2nd
3rd
4th
5th
6th
/ /
/ /
/ /
/ /
/ /
/ /
………………………
………………………
………………………
………………………
………………………
………………………
2- Then, oral prednisolone 40-60mg/m2/max 60mg oral EOD reducing it
gradually over 12-24 months
Date Dose Date Dose
7th day
2nd month
3rd month
4th month
5th month
6th month
/ /
/ /
/ /
/ /
/ /
/ /
.…tab/EOD
.…tab/EOD
.…tab/EOD.
…tab/EOD
.…tab/EOD
.…tab/EOD
7th month
8th month
9th month
10th month
11th month
12th month
/ /
/ /
/ /
/ /
/ /
/ /
.…tab/EOD
.…tab/EOD
.…tab/EOD
.…tab/EOD
.…tab/EOD
.…tab/EOD
3- Daily dipryidamole: 4-10mg/kg/day.
C- If the child has significant renal impairment and crscentic glomerulonphritis:
See RPGN protocols.
37. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
3
7
Protocol of Membranous Nephropathy
1. Performappropriate investigations toexclude secondary causes inall
cases of biopsy-provenMN:
Infection: Hepatitis B, C, TB, Syphilis, leprosy, CMV.
Drugs: Captopril, NSAIDs, Gold, Pencillamine.
Autoimmune disorders: SLE, RA, autoimmune thyroididtis
Neoplasm: carcinoma of bladder breast, pancreas, lymphoma, leukemia.
Others: DM, Sarcoidosis, Sicklecell disease, postrenal transplantation.
2. Idiopathic membranous nephropathy:
Non nephrotic proteinuria
Refractory cases
Asmptomatic/non
nephrotic proteinuria
Nephrotic syndrome/
nephrotic range proteinuria
ACE inhibitors/ARBs
Lipid lowering agents
(statins)
Prednisone (4-8 weeks)
Steroid sensitive Steroid resistant
Cyclical corticosteroids
cyclophosphamide
regmine
Cyclosporine or
tacrolimus protocols
for SRNS
Rituximab
Alternate day steroids
Taper over 3-6 months
38. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
3
8
Corticosteroid/Cyclophosphamide protocol for Idiopathic MN
Patient Name:………………………SA: Age: Dry weight :
1.Cyclical corticosteroid Cyclophosphamide regmine
2.Renoprotective therapy 3. Lipid lowering agent
Continued for additional 6 months after Statins 10-20 mg/day
cyclical steroid /cyclophosphamide regmine
Date Drug Dose
Available preparations of oral
methylprednisilone:
Urbasone retard 4, 8 mg/tab
1st Month / / 2nd Month / / 3rd Month / /
Methylprednisone 1gm/day
for 3 days:
Day1: / /
Day2: / /
Day3: / /
Oral
methylprednislone
0.5mg/kg/day for 27 days
Dose: BW:
Date: / --- /
Cyclophosphamide
500mg/m2
SA: ……………..
DOSE: ……………..
Methylprednisone 1gm/day for 3
days:
Day1: / /
Day2: / /
Day3: / /
Oral methylprednislone
0.5mg/kg/day for 27 days
Dose: BW:
Date: / --- /
Serum creatinine: Serum creatinine: Serum creatinine:
4th Month / / 5th Month / / 6th Month / /
Cyclophosphamide
500mg/m2
SA: ……………..
DOSE: ……………..
Methylprednisone 1gm/day
for 3 days:
Day1: / /
Day2: / /
Day3: / /
Oral methylprednislone
0.5mg/kg/day for 27 days
Dose: BW:
Date: / --- /
Cyclophosphamide
500mg/m2
SA: ……………..
DOSE: ……………..
Serum creatinine: Serum creatinine: Serum creatinine:
Date Drug Dose
39. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
3
9
Conditions associated with NS
Edema:
• Patients with underfilling edema:
– Glomerular filtration rate greaterthan 75 percent of normal
– Minimal change disease ofacute onset
– Severe hypoalbuminemia (often below 1 g/dL)
– Nephrotic patients with low FENa(< 1%)
• Patients with elevatedintravascularvolume:
– Glomerular filtration rate less than 50 percent of normal
– Plasma albumin concentrationof greaterthan 2 g/Dl
– Hypertension.
• MANAGEMENT
• Diet
– Dietary sodium restriction(to approximately 2 g of sodium per
day)
– protein intake of around 130–140%ofthe recommended daily
allowance according to statural age
– Hypovolemia:
Rapid infusion of plasma (20 ml/kg) OR
Albumin 20%(1 g/kg)administrated
• Diuretics:
INDICATIONS:
o Severe edema, after hypovolemia has been corrected.
40. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
4
0
TYPES:
o Furosemide: ( 1–2 mg/kg).
o Spironolactone (5–10 mg/kg)
o Amiloride (0.2–0.5mg/kg)
• Albumin:
o IV 25% albumin at 1-2 g/kg/d
o Either as a continuous infusion or divided q 6-8 hours.
o Albumin treatment should continue for 4 to 6 hours before
initial administration of diuretics to minimize the risk of
worsening any intravascular volume depletion that may be
present.
Severedema:
• Furosemide plus albumin:
– to increase the rate of diuretic delivery to the kidney.
– Immediately effective but not long-lasting.
– NOTE : respiratory distress with congestive heartfailure
Refractoryedema with serious effusions:
– Immersion of the body up to the neck in a bath
– Drainage of ascitesand/or pleural effusions
41. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
4
1
Thromboemboli :
– Mobilization.
– Avoidance of hemoconcentration
– early treatment of sepsis orvolume depletion.
– Prophylactic warfarin
– High risk patients with:
1. Plasma albumin concentrationbelow 20 g/l
2. fibrinogen level 6 g/l
3. Antithrombin III level below 70% of normal.
– Patients at risk may also be treated with low-dose aspirin and
dipyridamole.
– Heparin:
– Given initially if thrombi do occur
– Alone or with thrombolytic agents.
42. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
4
2
Resume of Nephrotic Syndrome
Date Serial No.
Name Age Sex:
* Diagnosis:
1ry NS: Non Relapser Infrequent Relapser Frequent Relapser
Steroid Dependent Steroid Resistant: Initial
Late
2ry NS:
* Initial presentation:
Date 24h Proteinuria S. Albumin
Age
Haematuria
- ve
+ ve Micro
Macro
S. Cholesterol
BL.Pr. S. Creatinine
Other C3
Others Others
* Response to steroid protocol:
Responder: Clinical Ws Lab: Ws
Non responder:
* Biopsy
Initial biopsy Repeated biopsy
Date
Indication
Findings MCNS
FSGS
DMP
MPGN
Other
MCNS
FSGS
DMP
MPGN
Other
Complication
Complications of the disease Thrombosis
Infection
Other
Current Condition
43. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
4
3
اقـــــــــرار
أقرأناوليأمرل الطف/..................................................................................................................
ذذالذانذيعذذم..............................................................................................................................وذوذالمحجذذبقس
الكلبمستشفاألطفالالجامعبالموافقةعلىعملعينةمالكلذألهميذةلذلتشذيي
الحالةمععلمباحتمالحدوثمضاعفاتنتيجةالعينةقديؤدإلاستئصالكاملللكل.
وليأمرالطفل،،،،،،،
أوافقعلىاءرإجالعينةالأوافقعلىإجراءالعينة
االسم/.............................................................االسم/...................................................................
التوقيع/..........................................................التوقيع/..................................................................
رقمالبطاقة/........................................................رقمالبطاقة/..................................................................
التاريخ/.......................................................التاريخ/..................................................................
44. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
4
4
Requirements for Renal Biopsy
Indications for renal biopsy & attendant name:
…………………………………………………………………….…………………………………..
Admission to nephrology floor at leastone day before the biopsy.
Meeting with biopsy clarificationteam.
Please do:
PT
APTT
Bleedingtime
Clotting time
Virologyscreen
HbsAg
HCV Antibody
HIV
Agreement of radiologist.
Consentof parents or responsible person.
Please sendthe patient to 1st
floor ultrasound room with suitable needle &
biopsy gun to start the renal biopsy process
People who will attend the renal biopsy:
Radiologyattendant
Nephrologists
Pathologytechnician
45. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
4
5
Steps of Renal Biopsy:
Sedation (dosage)
Pethidine . Diazepam .
Ketamine . Other .
Please specify
The patient lie on ………………………………………………………………..…
Take three cores from……………………………………………………………
One for ordinarymicroscope examination.
One for immunefluorescent assessment.
One for frozen section preservation for electron
microscopy examination.
After Biopsy:
Patient will lie on same side of biopsy for at least12 hours, no working.
Stop oral feeding till the patient is fully conscious.
Give I.V fluids maintenance dose.
We cangive pain killers (acetaminophen, paracetamole)15mgkgdose
What the Nurses will do After:
Measure pulse & blood pressure every 10 min. in the 1st hour,
every 30 min. in the next 2 hours, then every 2 hours till morning.
Observe abdominal girth every 4 hours.
Discharge the patient in the next day if there is no contraindication or complications.
Give patient appointment after one week to discuss the result of the
renal biopsy.
46. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
4
6
Renal Biopsy Audit
The whole of this survey will be scanned. In order that forms are read
correctly please use a black pen and mark the boxes with an X
Record Number
Operator(s)
Hospital Number
Referral Centre
Date of Biopsy
Native
Transplant
Inpatient
/ /
Day Case
Weight (Kg) Sedation (dosage)
. Pethidine . Diazepam .
Ketamine . Other .
Please specify
Play Preparation Yes No
Parent in Attendance Throughout Yes No
Information Sheet and Story Book Received Yes No
Number of Passes Needle
Tru-cut 14g Springloaded 16g
Indication Complications
Transplant Hypoxia (oxygen required
on return to ward bed)
Yes No
Haematuria
Protenuria
Acute glomerulonnephritis Gross haematuria Yes No
Hypertension
Transplant Yes No
Nephrotic syndrome steroid sensitive
Nephrotic syndrome steroid resistant
Pain requiring regular analgesic Yes No
Nephrotic syndrome atypical
Acute renal failure
Chronic renal failure Delay in discharge Yes No
47. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
4
7
Pre Cyclosporin
Return to ward Yes No
Other
Pathology review
Number of Glomeruli Adequate
LM Yes No N / R
LM Yes No N / R
EM Yes No N / R
Acute interstitial nephritis (AIN) Macroscopic polyarteritis nodes
Acute post infectious (proliferative) glomer Membranous nephropathy
Acute tubular necrosis Mesangiocapillary glomerulonephritis Type 1
Alport's syndrome Mesangiocapillary glomerulonephritis Type 2
Alport – like syndrome Mesangiocapillary glomerulonephritis Type 3
Amyloid Macroscopic polyarteritis nodes
Analgesic nephropathy Minimal change nephrotic syndrome
Anti-GBM disease Nephrocalcinosis
Autosomal dominant PKD Nephrocalcinosis
Autosomal recessive PKD Normal
Balkan nephropathy Polycystic Kidney Disease (other)
Chronic renal failure – uncertain aetiology Focal segmental glomerulosclerosis (primary)
Cis-plantinum toxicity Proliferative glomerulonephritis
Congential nephrotic syndrome (DMS) Pyelonephritis secondary to urolithiasis
Congential nephrotic syndrome (Finnish) Reflux nephropathy
Congential nephrotic syndrome (FSGS) Renal artery stenosis
Congential nephrotic syndrome (minimal change) Renal artery thrombosis
Congential nephrotic syndrome (unspecified) Renal trauma
Cortical necrosis Renal vein thrombosis
Crescentic glomerulonephritis Systemic lupus erythematosis
Cyclosporin nephrotoxicity Thin basement membrane
D+ haemolytic uraemic syndrome Tuberous sclerosis PKD
D- haemolytic uraemic syndrome Vasculitis (unspecified)
Drug nephrotoxicity unspecified Wegner's granulomatosis
2008
48. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
4
8
Glomerulonephiritis (unspecified) Wilm's nephropathy
Henoch Schonlein nephritis Wilm's tumour
IgA nephropathy Other
If 'Other', please state
Transplant
Acute parenchymal Acute vascular Mixed acute
Chronic rejection Acute interstitial nephritis Infarction
Cyclosporin toxicity Acute tubular necrosis Other
Normal End stage kidney
49. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
4
9
اقـــــــــرار
أقرأناوليأمرل الطف/..................................................................................................................
اليعانم...............................................................................................................................................
والمحجذذوذذذبقسالكلذذذذفذبمستشذذالذاألطفالجذذامعذذةذبالموافقذذىذعلتلقذذذذذطفلذذارذعق
االندوكسا(Cyclophosphamide)ألهميةلمععلمذباحتمذالحذدوثمضذاعفاتمذ
ا هالدواء.وأاألطباءالمعالجوقدأطلعونعلىه هالمضاعفاتونسبةحدوثها.
وليأمرالطفل،،،،،،،
أوافقعلىإعطاءارالعقالأوافقعلىإعطاءارالعق
االسم/.............................................................االسم/...................................................................
التوقيع/..........................................................التوقيع/..................................................................
رقمالبطاقة/........................................................رقمالبطاقة/..................................................................
التاريخ/.......................................................التاريخ/..................................................................
50. جامعــةالمنصــورةMansoura University
مستشفـياألطفـالChildren's Hospital
وحدةأمراضالكليNephrology Unit
Last updated August 2014
Chapter:ProtocolofNS
5
0
اقـــــــــرار
أقرأناوليأمرل الطف/..................................................................................................................
اليعانم...............................................................................................................................................
والمحجذذوذذذبقسالكلذذذذفذبمستشذذالذاألطفالجذذامعذذةذبالموافقذذىذعلتلقذذذذذطفلذذارذعق
الذيماذريتوكس(Rituximab)ذةذألهميذذلذعذمذذعلمذالذباحتمذدوثذحذاعفاتذمضذذما ذذه
الدواء.وأاألطباءالمعالجوقدأطلعونعلىه هالمضاعفاتونسبةحدوثها.
وليأمرالطفل،،،،،،،
أوافقعلىإعطاءارالعقالأوافقعلىإعطاءارالعق
االسم/.............................................................االسم/...................................................................
التوقيع/..........................................................التوقيع/..................................................................
رقمالبطاقة/........................................................رقمالبطاقة/..........................................................
التاريخ/....................................................... ` التاريخ/..................................................................