Download MBBS Pediatric PPT 8 Nephrotic Syndrome Lecture Notes

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