This document provides guidelines for the management of nephrotic syndrome in children. It defines nephrotic syndrome and outlines its typical and atypical presentations. For typical presentations, initial treatment involves prednisolone for 12 weeks to induce remission. Relapses are treated with additional courses of prednisolone. Frequent relapses may be treated with low-dose alternate day prednisolone or immunosuppressants like levamisole, cyclophosphamide, cyclosporin or mycophenolate mofetil to reduce steroid usage and dependency. The guidelines cover monitoring, complications prevention and vaccination recommendations.
This presentation was done by Dr. Julius P. Kessy,MD. An intern Doctor at Dodoma Regional Referral Hospital (DRRH) during pediatrics unit clinical meeting and supervised by Dr. Christina K. Galabawa,MD,Mmed2, Pediatrics and Child Health, University of Dodoma (UDOM) in November, 2017.
This presentation was done by Dr. Julius P. Kessy,MD. An intern Doctor at Dodoma Regional Referral Hospital (DRRH) during pediatrics unit clinical meeting and supervised by Dr. Christina K. Galabawa,MD,Mmed2, Pediatrics and Child Health, University of Dodoma (UDOM) in November, 2017.
Febrile seizure / Pediatrics
Simple vs. Complex seizure
Possible explanation of febrile seizure
Risk Factors for Febrile Seizures
Risk Factors for Recurrence of Febrile Seizure
Risk Factors for Occurrence of Subsequent Epilepsy After a Febrile Seizure
Genetic Factors
Evaluation
Lumbar Puncture
Optional LP
Electroencephalogram
Blood Studies
Neuroimaging
TREATMENT
Febrile seizure / Pediatrics
Simple vs. Complex seizure
Possible explanation of febrile seizure
Risk Factors for Febrile Seizures
Risk Factors for Recurrence of Febrile Seizure
Risk Factors for Occurrence of Subsequent Epilepsy After a Febrile Seizure
Genetic Factors
Evaluation
Lumbar Puncture
Optional LP
Electroencephalogram
Blood Studies
Neuroimaging
TREATMENT
acute glomerulonephritis in pediatrics by ritu gahlawatRitu Gahlawat
Case Scenario
A child 14 yrs. old, was apparently normal one week back, when he developed puffiness around the eye and face from last 7 days, insidious in onset, gradually progressive, from the peri-orbital region to the whole of face, more during morning hours and then decreases as the day progresses.
Then mother noticed swelling of bilateral lower limbs from 5 days, insidious in onset, gradually progressed from feet to half of the lower limb, more during morning hours and decreases as the day progresses.
Then he started to develop headache, insidious in onset, gradually progressive, more in the occipital region, not associated with vomiting, blurring vision, confusion, altered sensorium, seizures.
This was followed by cola coloured urine from four days, sudden onset, present throughout the urinary stream, not precipitated by any food item, no history of pain during micturition, fever, urgency, increased frequency of micturition, regular drug intake, associated with decreased urine output present from past one week initially used to pass 7-8 times/day and now only 3-4 times/day.
History of fever with sore throat present 3 weeks back, which resolved on its own in 3-4 days.
Introduction
Acute glomerulonephritis is a common disease in children and it is one of the diseases that are presented commonly with hematuria which means red urine (blood in urine).
Acute Glomerulo Nephritis in all probabilities results secondary to a proceeding streptococcal (beta-haemolytic type 2) infection of throat or skin.
A history of upper respiratory infection.
Acute glomerulonephritis is an immune-mediated inflammatory disease of the capillary loops in the renal glomeruli. The antigen-antibody complex deposition within the glomeruli results in glomerular injury which is manifested as hematuria, oliguria, Edema and hypertension.
More common in male than females.
Most common in preschool and early school age children with a peak age of onset of 6-7 years.
On average responsible for 2 to 4% of pediatric admission in India.
Accounts for about 90% of renal diseases in childhood.
Varies with the prevalence of nephritogenic strains of streptococci and the likelihood of cross-infection.
Presumed cause: antigen-antibody reaction secondary to an infection in the body.
Initial infection:
Usually either an upper respiratory infection or a skin infection, usually one to 3 weeks before the onset of symptoms.
Most frequent causative agent- nephritogenic strains of group- A beta- hemolytic streptococcus (type 2), acute post- streptococcal glomerulonephritis is the most common.
Most cases are post infectious and have been associated with pneumococcal, viral infection, acute post streptococcal glomerulonephritis is the most common of the post infectious renal disease in childhood, streptococcal pharyngitis is more common in the winter.
Urinary symptoms:
Decreased urine output
Bloody or brown- colored urine
Malaise
Mild headache
GIdisturbance
Albumin versus fresh frozen plasma in managing diuretic resistant edema in ch...iosrphr_editor
This study was carried out to compare the efficacy, cost effectiveness and outcome of albumin with fresh frozen plasma (FFP) in the treatment of diuretic resistant edema in childhood idiopathic nephrotic syndrome.Methods: Fifty four patients with idiopathic NS were enrolled in this prospective analytic study. Patients with moderate to severe edema with serum albumin <15 gm/L were given albumin and FFP dividing into two groups. Group-A, received intravenous albumin- 1 gm/kg/day and Group-B intravenous FFP 15ml/kg/day. Total number of albumin and FFP infusion were determined by edema reduction. Cost effectiveness was also calculated. Results: Diagnosis of NS and biochemical parameters were same in both groups. Dry weight was achieved in Group-A in 6.66± 3.710 days and in Group-B 6.66± 3.038 days. In Group-A the number of albumin infusion required was 1.44±0.697 and Group-B FFP infusion required was 3.11± 1.5 (p=0.0001). Group A needed 4608.00 ($57.6) taka for albumin whereas Group B needed only 2177.00($ 27.2) taka for FFP (p=0.0001). No significant complications were observed in both the groups.Conclusion: FFP costs half than albumin and same duration required reducing edema but the cost-effectiveness may place FFP as a better choice especially in developing countries of the world.
Nephrotic syndrome, Characterized by heavy proteinuria>3.5g/m/day in adults,>...FarsanaM
Nephrotic syndrome, in paediatric patients(children), mainly Minimal change nephrotic syndrome (MCNS),Characterized by heavy proteinuria>3.5g/m/day in adults,>1g/m/day in children, hypoalbuminemia <2.5g/dL, oedema, hyperlipidemia 200mg/dL, Pathogenesis of MMCNS injury to the glomerular visceral epithelial cell( Podocyte) foot processes
Nephrotic syndrome, Characterized by heavy proteinuria>3.5g/m/day in adults,>...
Nephrotic syndrome
1. Guideline for the Management of Nephrotic
Syndrome
Renal Unit
Royal Hospital for Sick Children
Yorkhill Division
Nephrotic Syndrome Version: 1.1 Page 1 of 8
Author: Renal Clinicians Group Authorised by: Dr J Beattie Issue Date: November 2005
Date of Review: October 2007 Q Pulse Ref: YOR-REN-019
Please note: the following guideline has not been assessed according to
the AGREE (Appraisal of Guidelines for Research and Evaluation) criteria.
This will take place at the next guideline review.
2. Nephrotic Syndrome Version: 1.1 Page 2 of 8
Author: Renal Clinicians Group Authorised by: Dr J Beattie Issue Date: November 2005
Date of Review: October 2007 Q Pulse Ref: YOR-REN-019
Contents Page(s)
1. Introduction 2
2. Definition of Nephrotic Syndrome 2-3
3. Initial Investigation 3
4. Referral to Paediatric Nephrology 3
5. Complications 4
5.1 Hypovolaemia 4
5.2 Infection 4
5.3 Thrombosis 4
6. Treatment of Initial Presentation of Nephrotic
Syndrome
4
6.1 Prednisolone 4-5
6.2 Albumin 5
6.3 Penicillin Prophylaxis 5
6.4 Salt/Fluid Restriction 5
6.5 Vaccination 5
7. Relapse of Nephrotic Syndrome 6
8. Treatment of Relapse of Nephrotic Syndrome 6
8.1 Prednisolone 6
8.2 Albumin 6
8.3 Salt Restriction 6
8.4 Penicillin 6
8.5 Vaccination 6
9. Treatment of Frequent Relapses 6-7
9.1 Low Dose Alternate Day Prednisolone 7
9.2 Levamisole 7
9.3 Cyclophosphamide 7
9.4 Cyclosporin 7
9.5 Mycophenylate Mofitil (MMF) 7
10. Follow Up 8
11. Future Guideline Review 8
1. Introduction
This guideline represents our current practice within the Renal Unit and are intended
for use by clinicians. These guidelines are based on previous recommendations
reviewed in the light of recent literature and will be update regularly. They cover
many aspects of the management of “typical” nephrotic syndrome, but they are
not exhaustive, and many not be relevant for children with “atypical” nephrotic
syndrome. There is always a paediatric nephrology consultant on call for the unit
who will be happy to discuss difficult or unusual cases.
2. Definition of Nephrotic Syndrome
• Nephrotic range proteinuria (> 1g/m2
/day)
• Hypoalbuminaemia (<25 g/l)
• Oedema
3. Nephrotic Syndrome Version: 1.1 Page 3 of 8
Author: Renal Clinicians Group Authorised by: Dr J Beattie Issue Date: November 2005
Date of Review: October 2007 Q Pulse Ref: YOR-REN-019
Classification
• Idiopathic (primary) nephrotic syndrome
o Minimal change (80-90%)
o Focal segmental glomerulosclerosis (FSGS) (10-20%)
• Secondary nephrotic syndrome (HSP, SLE, MPGN)
• Congenital nephrotic syndrome
This document relates only to the management of idiopathic nephrotic
syndrome. Children who present with the typical features of nephrotic syndrome
(see below) are generally responsive to steroid treatment and a renal biopsy,
were it performed, would be likely to show minimal change nephrotic syndrome.
Those with atypical features are more likely to be unresponsive to steroid
treatment, and a biopsy more likely to show FSGS or one of the other forms of
nephrotic syndrome.
Therefore children with typical features are started on steroids without recourse
to renal biopsy. Those with atypical features should therefore undergo renal
biopsy before receiving steroid treatment.
Nephrotic Syndrome
Typical Features Atypical Features
Age 1-10 years <1yr, >10years
Normotensive Hypertensive
Normal Adrenal Function Elevated Creatinine
+/- microscopic haematuria Macroscopic Haematuria
3. Initial Investigation
The following investigations should be performed in all children:
• Blood:FBC, U+E’s; Creatinine; LFT’s; ASOT; C3/C4; Varicella titres
• Urine: Urine culture andUrinary protein/creatinine ratio
• BP
• Urinalysis including glucose
• A urinary sodium concentration can be helpful in those at risk of
hypovolaemia.
• Varicella status should be known in all children commencing steroids.
• Hepatitis B status may be appropriate in children at high risk.
4. Referral to Paediatric Nephrology
• Age < 1 yr
• Age > 10-12 yrs
• Persistent hypertension
• Macroscopic haematuria
• Low C3/C4
• Failure to respond to steroids within 4 weeks
4. Nephrotic Syndrome Version: 1.1 Page 4 of 8
Author: Renal Clinicians Group Authorised by: Dr J Beattie Issue Date: November 2005
Date of Review: October 2007 Q Pulse Ref: YOR-REN-019
5. Complications
The main complications of nephrotic syndrome are hypovolaemia, infection and
thrombosis.
5.1 Hypovolaemia
The initial examination of children with nephrotic syndrome needs to include
an assessment of their intravascular volume. Whilst these children may be
very oedematous, they may also be intravascularly depleted. Signs of
intravascular depletion are cool peripheries (capillary refill time > 2 secs), a
core-peripheral temperature gap of > 2o
C, and tachycardia. Hypotension is a
late sign of hypovolaemia, but paradoxical hypertension may be present. A
urinary sodium of < 10 mmol/l is a useful investigation to confirm
hypovolaemia.
5.2 Infection
Loss of complement components and possibly immunoglobulins results in an
increased risk of infection. Consider antibiotic prophylaxis whilst patients have
significant proteinuria.
5.3 Thrombosis
Loss of proteins such as anti-thrombin III contributes to a pro-coagulant
state. This might be exacerbaterd by hypovolaemia.
6. Treatment of Initial Presentation of Nephrotic Syndrome
6.1 Prednisolone
When the diagnosis of nephrotic syndrome has been made, prednisolone
treatment can be started in children with typical features. Children with atypical
features should be referred to paediatric nephrology for consideration of renal
biopsy.
There is increasing evidence that longer initial courses of prednisolone are
associated with a lower incidence of relapse, and therefore a 12-week initial
course is recommended. The dose of prednisolone is based on surface area.
• 60 mg/m2
/day for 4 weeks (maximim 80 mg)
• 40 mg/m2
/on alternate days for 4 weeks (maximum 60mg)
• Reduce dose by 5-10mg/m2
each week for another 4 weeks then stop
Prednisolone can be given as a single dose in the morning with food, or as
divided doses during the day. Patients should be issued with a steroid warning
card, and they should be aware of the side effects and risks of steroid treatment.
Varicella status should be documented clearly in the casenotes and on HISS. If
5. prednisolone causes gastric irritation, start ranitidine 2mg/kg bid for the duration
of steroid treatment.
6.2 Albumin
As discussed above the clinical indications for albumin are
• Clinical hypovolaemia
• Symptomatic oedema
A low serum albumin alone is not an indication for intravenous albumin.
If there is evidence of hypovolaemia, give 1 g/kg 20% albumin (5ml/kg) over 4 -
6 hours. Give 2mg/kg of iv frusemide mid-infusion. If clinically shocked give
10ml/kg 4.5% albumin. Children should be closely monitored during albumin
infusions, and where possible they should be administered during working hours.
6.3 Penicillin Prophylaxis
Whilst nephrotic, children are at increased risk of infection, particularly with
encapsulated organisms such as pneumococcus. There is no evidence that
antibiotic prophylaxis is of benefit, and some centres do not use prophylaxis.
Penicillin V can be given while there is proteinuria and discontinued when the
child goes into remission. Grossly oedematous children are at risk of cellulitis and
may benefit from antibiotic prophylaxis.
Dose: Under 5 yrs 125 mg bid
5yrs or above 250 mg bid
6.4 Salt/Fluid Restriction
A low salt diet is used to try to prevent further fluid retention and oedema. Fluid
restriction may also be helpful. These restrictions are lifted once the child goes
into remission.
6.5 Vaccination
Pneumococcal vaccination is recommended for children with NS. Consider giving
at the time of diagnosis. Varicella vaccination is only available on a named
patient basis.
Response To Treatment
Most children with nephrotic syndrome will respond to steroid treatment
within 2-4 weeks. A remission is defined as 3 or more days of trace or
negative on dipstick testing. Treatment is continued for a total of 12
weeks as outlined above. If proteinuria persists beyond the first 4 weeks
of steroid treatment, then children should be referred for renal biopsy.
Nephrotic Syndrome Version: 1.1 Page 5 of 8
Author: Renal Clinicians Group Authorised by: Dr J Beattie Issue Date: November 2005
Date of Review: October 2007 Q Pulse Ref: YOR-REN-019
6. Nephrotic Syndrome Version: 1.1 Page 6 of 8
Author: Renal Clinicians Group Authorised by: Dr J Beattie Issue Date: November 2005
Date of Review: October 2007 Q Pulse Ref: YOR-REN-019
7. Relapsing Nephrotic Syndrome
Up to 60 - 70 % of children with nephrotic syndrome may have one or more
relapse. These are diagnosed if there is +++ or ++++ proteinuria for 3 or more
days. Urine should be checked initially twice weekly, then weekly after the first
episode, and the families instructed to get in contact should a relapse of
proteinuria occur, or if there is ++ for more than 1 week.
8. Treatment of Relapse Nephrotic Syndrome
8.1 Prednisolone
Prednisolone treatment should be restarted once a relapse has been diagnosed.
• 2mg/kg daily (maximum 80 mg) until the urine is negative or trace for 3 days
• 40 mg/m2
(maximum 60 mg) on alternate days for 4 weeks then stop or taper
the dose over 4-8 weeks
8.2 Albumin
The indications for albumin infusion are as for the initial presentation. It is less
likely to be needed during a relapse.
8.3 Salt Restriction
Whilst there is proteinuria (>++) a no added salt diet is advised.
8.4 Penicillin
Whilst there is proteinuria (>++) penicillin can be given.
8.5 Vaccination
Consider giving varicella vaccine between relapses in children who are varicella
seronegative.
Referral to/Discussion with Paediatric Nephrology
• Frequent relapsers
• Steroid dependency
• Steroid toxicity
9. Diagnosis and Treatment of Frequent Relapses
Frequent relapsers are diagnosed if there is:
• 2 or more relapses within the first 6 months of presentation
• 4 or more relapses within any 12 month period
This becomes steroid dependency if the relapses are occurring during steroid
tapering.
Varicella status should be repeated 6 monthly in those who are non-
immune.
7. Nephrotic Syndrome Version: 1.1 Page 7 of 8
Author: Renal Clinicians Group Authorised by: Dr J Beattie Issue Date: November 2005
Date of Review: October 2007 Q Pulse Ref: YOR-REN-019
If children have frequent relapses, strategies should be adopted to try to reduce the amount
of steroid required.
9.1 Low Dose Alternate Day Prednisolone
Low dose alternate day steroid treatment (< 10-15 mg/alt days) may prevent relapses, and
result in less steroid being given overall.
9.2 Levamisole
Levamisole may be beneficial for children who have occasional relapses. It is less useful for
children who are steroid dependent. The dose is 2.5 mg/kg/ on alt days for 6 months to a
year in the first instance. Reversible neutropenia is a rare but recognised side-effect. A FBC
should be checked monthly for the first 3 months. This drug is not licensed in the UK, and
has to be imported.
9.3 Cyclophosphamide
For children with frequent relapses or those who are steroid dependent consider a course of
Cyclophosphamide 3 mg/kg/day for 8 weeks or equivalent. It is best to avoid cutting the
tablets. FBC should be monitored for the first few weeks of treatment.
9.4 Cyclosporin
Cyclosporin at a dose of 2.5 mg/kg bid usually for 1 year may be useful as a steroid sparing
agent. Levels should be checked after 1-2 weeks; aim for a 12 hour trough of 70 – 120
nmol/l (85-145 ug/l). For children under 5 yrs of age, tid dosing may be necessary.
Monitor BP and renal function.
9.5 Mycophenylate Mofitil (MMF)
There is some experience of using MMF in children with difficult to treat NS. It
may be useful for those children showing signs of cyclosporin toxicity. Doses of
600mg /m2
/bid have been used. FBC should be monitored for leucopenia. The
use of MMF is associated with gastro-intestinal intolerance, mainly diarrhoea. This
is an unlicensed indication for MMF.
8. 10. Follow Up
GENERAL CONSIDERATIONS DURING FOLLOW UP
For children on long-term steroids:-
1) Monitor BP
2) Monitor growth (including bone age and pubertal stage where
appropriate)
3) Monitor weight – dietetic review where appropriate
4) Glycosuria / HbA1c
5) Bone mineral density / calcium supplements
6) Ophthmology review
7) VACCINATION
Pneumococcal: recommended for all children with NS.
Varicella: consider in varicella negative children with frequent relapses.
Aim to administer vaccine when prednisolone dose is low.
11. Future Guideline Development
• Should any aspect of this guideline change before the planned review (i.e.
new technology or procedural change) then this guideline should be
updated accordingly.
• Future review of this guideline should make use of the AGREE document to
ensure that up-to-date evidence and best clinical practice has been used to
inform this guideline. For further information regarding guideline
development, please contact the Chairperson of the Multi-Professional
Clinical Practice Committee.
Nephrotic Syndrome Version: 1.1 Page 8 of 8
Author: Renal Clinicians Group Authorised by: Dr J Beattie Issue Date: November 2005
Date of Review: October 2007 Q Pulse Ref: YOR-REN-019