Download MBBS (Bachelor of Medicine, Bachelor of Surgery) Pediatric PPT 8 Nephrotic Syndrome Lecture Notes
Nephrotic and Nephritic
syndrome
Learning objectives
Definition of Nephrotic syndrome
Etiopathogenesis of nephrotic syndrome
Clinical manifestation
Evaluation
Management
outcome
Post streptococcal GMN
Introduction
Important chronic disease in children
80% children show remission with steroid
Most patients have multiple relapses
Definition
Heavy proteinurea>3.5 gm/24 hr or >40 mg/m2/hr in
children
Hypoalbunemia <2.5 gm%
Oedema
Hyperlipidemia (serum cholestrol>200mg/dl)
Nephrotic range proteinurea
Early morning protein is 3+/4+ (dipstick or boiling
test)
Spot protein/creatinine ratio >2 mg/mg or
Urine albumin excretion >40 mg/m2 per hr (on a
timed-sample).
Etiology
Idiopathic: 90%
minimal change 85%, mesangial proliferation , FSG ,
membranoproliferative, congenital (Finnish type)
Secondary: 10%
SLE, anaphylactoid purpura, sickle cell disease,
Hodgkin lymphoma, diabetes mellitus,
amyloidosis, malaria (P. malariae), intrauterine
infections (syphilis,
toxoplasmosis,cytomegalovirus) and other
infections like HIV, parvovirus B19,hepatitis B and
C virus, drugs like d-penicillamine, gold and
toxins or allergies (bee sting, poison ivy, food
allergy).
Pathophysiology
Increase in permeability of glomerular BM
T- cell dysfunction
Mechanism of edema:
Urine protein loss leads to hypoalbuminemia
decreased oncotic pressure
transudation of fluid
Reduction in intravascular volume and decrease renal
perfusion pressure
Pathophysiology
Mechanism of lipid elevation:
Hypoalbuminemia stimulates generalized hepatic
protein synthesis including lipoprotein
Lipid catabolism is diminished due to decrease in
lipoprotein lipase
Clinical Features
clinical
Minimal change Mesangial
Focal segmental
disease
proliferation
glomerulosclero
sis
Incidence
85%
10%
5%
Age at
2-6years
2-10years
2-10years
presentation
Hypertension
10%
10-45%
35-45%
Microscopic
10-20%
45-90%
60-80%
Hematuria
Response to
95%
50-60%
20-30%
prednisolone
Likelihood of
95%
50-60%
20-30%
maintaining renal
function
Cont...
clinical
Minimal change Mesangial
Focal segmental
disease
proliferation
glomerulosclero
sis
Light Microscopy
Normal
Increase in
Focal or segmental
mesangial cells
glomerular
hyalinization
Immunofluoresce- Normal
Negative or
Focal or segmental
nt microscopy
variable IgM and
deposition of Igm
C3 deposition
and C3
Electron
Fusion of foot
Increase in
Fine granular
microscopy
processes of
mesangial cells
deposits in
podocytes
and matrix,small
subendothelial
scattered electron regions
dense deposits in
mesangium
Initial evaluation
Detailed evaluation
The height, weight and blood pressure should be
recorded
Regular weight record
Physical examination is done to detect infections and
underlying systemic disorder
Infections should be treated before starting therapy
with corticosteroids.
Investigations
Urinalysis
Complete blood count
Blood levels of Proteins, lipids, urea and creatinine
and electrolytes
ASLO and C3: gross hematuria
Appropriate test ?HbSAg, HIV and tuberculosis
Renal biopsy
Indications for kidney biopsy
At Onset
Age of onset <1 year or >10 years
Gross hematuria, persistent microscopic hematuria or low
serum C3.
Sustained hypertension.
Renal failure not attributable to hypovolemia.
Suspected secondary causes of nephrotic syndrome.
After Initial Treatment
Proteinuria persisting despite 4-weeks of daily
corticosteroid therapy.
Before treatment with cyclosporin A or tacrolimus.
Management of Nephrotic
syndrome
Relief of edema
Hypertension
Identify and treat infection
Specific treatment regimen
Complication
Definition related to nephrotic
syndrome
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.
Infrequent relapses: <2 relapses in 6 months of initial
response or <4 relapses within any 12 months period.
Frequent relapses: Two or more relapses in initial six
months or more than three relapses in any twelve
months.
Definition related to nephrotic
syndrome
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 4 weeks
Treatment of initial episode
Oral prednisolone
2 mg/kg/day 6weeks
1.5 mg/kg/EOD 6 weeks
Treatment of infrequent
relapse
Prednisolone 2 mg/kg/day till remission and then
Prednisolone 1.5 mg/kg/day for 4 weeks
Treatment of frequent repalse or
steroid dependent
Low dose steroids with-
Levamisole
Cyclophosphamide
Calcineurin inhibitor : Cyclosporin,Tacrolimus
Mycophenolate mofetil (MMF)
Toxicity of drugs
Side effects of prednisolone
Hirsutism
Obesity
Hypertension
Behavioral problems
Cataracts
Striae
Growth failure
Side effects of Levamisole
The chief side effect of levamisole is leukopenia
Flu-like symptoms,
Liver toxicity
Convulsions and skin rash are rare
The leukocyte count should be monitored every 12-16
weeks.
Side effects of Cyclophosphamide
Leucopenia
Hemorrhagic cystitis
Alopecia
Skin rash
Nausea
Side effects of Cyclosporin
Hypertension
Cosmetic symptoms
Gum hypertrophy
Hirsutism
Nephrotoxicity
hypercholesterolemia and elevated transaminases may
occur
Estimation of blood levels of creatinine is required
every 2-3 months and a lipid profile annually.
Side effects of MMF
Gastrointestinal discomfort, diarrhea and leukopenia.
Leukocyte counts should be monitored every1-2
months
Treatment is withheld if count falls below 4000/mm3.
Choice of agent
Few studies comparing one study with another
Levamisole has a modest steroid sparing effect and is
a satisfactory initial choice
Treatment with cyclophosphamide is preferred in
patients showing:
I. significant steroid toxicity
II. severe relapses with episodes of hypovolemia or
thrombosis, and
III. poor compliance or difficult follow up
Complications
Infection
Thrombosis
Hypertension
Hypovolumic shock
Corticosteroid side effects
Malnutrition
Outcome
Steroid responsive - >90%
Relapses- >70%
Mortality ? 2-5%
Patient and parents education
Urine examination at home
Maintain diary showing result of urine protein
Ensure normal activity and school attendance
Appropriate immunization
Acute glomerulophritis
Glomerulonephritis refers to a group of glomerular
diseases characterise by inflammatory changes in the
glomeruli and manifesting as acute nephritic
syndrome which is characterized by-
Abrupt onset of hematuria
Oligouria
Edema
Hypertension
Subnephrotic range proteinuria
Azotemia
Causes of Acute GMN
Post infectious: Bacterial-Streptococcal,
staphylococcal, pnemococcal, meningococcal.
Bacterial endocarditis, infected ventriculoatrial shunt
and prosthesis can cause acute GMN. Viral- Hepatitis
B and C, mumps, HIV, varicella, infectious
mononucleosis. Parasitic- malaria and toxoplasmosis
Systemic vasculitis: HSP, SLE, PAN, Wegner's
granulomatosis
Pathogenesis
Immune complex mediated disease
i. Immune complex Glomerulonephritis (70%)
? Low serum complement C3- poststreptococcal, rapidly
progressive, mesangioproliferative glomerulonephritis, SLE,
bacterial endocarditis, cryoglobulinemia
? Normal serum complement C3- IgA nephropathy, H-S purpura
ii. Pauci-immune glomerulonephritis (30%)
Anti-neutrophil cytoplasmic antibody positive wegener's
granulomatosis, polyarteritis nodosa
iii. Anti GBM disease(<1%)
Anti-glomerular basement membrane antibody positive Good
pasture syndrome.
Post streptococcal
Glomerulonephritis
Following group A beta-hemolytic streptococci
School age children
Boys are more frequently affected
Etiology
Follows a pharyngeal or cutaneous infection by the
nephritogenic strains of hemolytic Group A
streptococcus1 to 4 week preceding streptococcal
throat/skin infection
Strain M type 1,4 and 12 causing pharyngitis and
49,55,57 and 60 causing pyoderma
Typical example of immune complex disease
Pathogenesis
Immune complex deposition
Glomeruli enlarged
Ischemia
Capillary wall narrowing
Deposits of IgG and C3
Clinical feature
Rare below 3 years of age
Acute onset
Latent period: Following pharyngitis- 1 to2 weeks and
following cutaneous infection- 2 to 4 weeks
Puffiness around eye and pedal edema
Cola colored urine
Oliguria
Hypertension
Atypical presentation : Convulsion, Pul edema, ARF, CHF
Course of the disease- acute phase: 4-10 days, azotemia
and hypertension:persist for 2 weeks, gross hematuria: 1-2
weeks
Laboratory investigations
Urine : 1+/2+ protein, dysmorphic RBC's, and red cell, leukocyte or granular
cast, nephrotic range poteinuria in < 5% cases
Hemogram: Anemia, mild leucocytosis, ESR
Biochemistry: C3 (normal- 77-195 mg/ dL) becomes normal in 6 to 8 weeks.
Evidence of streptococcal infection: Throat swab culture, elevated ASO ( for
pharyngeal infection+ve in 80%), elevated antideoxyribonucleases-B anti-
hyaluronidase antibodies ( for cutaneous infection), streptozyme test
Others- X- ray chest, ECG
renal biopsy- to exclude other diseases in patients with-
? ARF
? normal C3 level
? without evidence of preceding streptococcal infection
? persistant gross hematuria and hypertension (>3 weeks)
? prolonged diminished renal functions (> 2 weeks)
? persistent low serum C3 (>8weeks)
Management
Presence of ARF and Hypertension requires hospitalisation
Bed rest
Diet
Weight
Fluid restriction
Antibiotics
Diuretics
Alkalinization of urine
Hypertension
LVF
ARF
Outcome and prognosis
Overall excellent prognosis( >95% complete recovery,
<1% develop RPGN))
Symptoms resolves within 1 month
Gross hematuria and proteinuria disappear within 2
weeks
Microscopic hematuria may last for years
Recurrence rare
Difference between acute nephritis
and nephrotic syndrome
Acute nephritis
Nephrotic syndrome
Characterized by hematuria,
Characterized by heavy
edema, hypertension, oligouria
proteinuria, hpo albuminemia,
edema,hyperlipidemia
90% post infective, immune
90% idiopathic
complex
Relapses common
Usually only 1 attack
Retraction of epithelial foot
Immune complex deposition
process
Urine: Alb 1+/2+, hematuria,
Urine: Selective proteinuria, No
RBC cast
RBC
Blood urea/creat raised
Blood urea/ creat normal
Thank you
This post was last modified on 07 April 2022