Download MBBS Pediatric PPT 8 Nephrotic Syndrome Lecture Notes

--- Content provided by‍ FirstRanker.com ---

Learning objectives

Definition of Nephrotic syndrome
Etiopathogenesis of nephrotic syndrome
Clinical manifestation

--- Content provided by‍ FirstRanker.com ---

Evaluation
Management
outcome
Post streptococcal GMN
Introduction

--- Content provided by⁠ FirstRanker.com ---

Important chronic disease in children
80% children show remission with steroid
Most patients have multiple relapses

--- Content provided by‌ FirstRanker.com ---

Definition

Heavy proteinurea>3.5 gm/24 hr or >40 mg/m2/hr in

children

--- Content provided by⁠ FirstRanker.com ---

Hypoalbunemia <2.5 gm%
Oedema
Hyperlipidemia (serum cholestrol>200mg/dl)
Nephrotic range proteinurea

--- Content provided by‍ FirstRanker.com ---

Early morning protein is 3+/4+ (dipstick or boiling

test)

--- Content provided by​ FirstRanker.com ---

Spot protein/creatinine ratio >2 mg/mg or
Urine albumin excretion >40 mg/m2 per hr (on a

timed-sample).

--- Content provided by‌ FirstRanker.com ---

Etiology

Idiopathic: 90%
minimal change 85%, mesangial proliferation , FSG ,

--- Content provided by‌ FirstRanker.com ---

membranoproliferative, congenital (Finnish type)

Secondary: 10%
SLE, anaphylactoid purpura, sickle cell disease,

--- Content provided by​ FirstRanker.com ---

Hodgkin lymphoma, diabetes mellitus,

amyloidosis, malaria (P. malariae), intrauterine

infections (syphilis,

--- Content provided by⁠ FirstRanker.com ---

toxoplasmosis,cytomegalovirus) and other

infections like HIV, parvovirus B19,hepatitis B and

--- Content provided by​ FirstRanker.com ---

C virus, drugs like d-penicillamine, gold and

toxins or allergies (bee sting, poison ivy, food

allergy).

--- Content provided by​ FirstRanker.com ---

Pathophysiology

Increase in permeability of glomerular BM
T- cell dysfunction
Mechanism of edema:

--- Content provided by FirstRanker.com ---

Urine protein loss leads to hypoalbuminemia


decreased oncotic pressure

--- Content provided by⁠ FirstRanker.com ---

transudation of fluid

Reduction in intravascular volume and decrease renal

--- Content provided by‍ FirstRanker.com ---

perfusion pressure

Pathophysiology

--- Content provided by FirstRanker.com ---

Mechanism of lipid elevation:
Hypoalbuminemia stimulates generalized hepatic

protein synthesis including lipoprotein

--- Content provided by‌ FirstRanker.com ---

Lipid catabolism is diminished due to decrease in

lipoprotein lipase
Clinical Features

--- Content provided by⁠ FirstRanker.com ---

clinical

Minimal change Mesangial

Focal segmental

--- Content provided by‌ FirstRanker.com ---

disease

proliferation

--- Content provided by FirstRanker.com ---

glomerulosclero

sis

Incidence

--- Content provided by‍ FirstRanker.com ---

85%

10%

--- Content provided by‍ FirstRanker.com ---

5%

Age at

2-6years

--- Content provided by‍ FirstRanker.com ---

2-10years

2-10years

--- Content provided by FirstRanker.com ---

presentation
Hypertension

10%

--- Content provided by FirstRanker.com ---

10-45%

35-45%

Microscopic

--- Content provided by‍ FirstRanker.com ---

10-20%

45-90%

--- Content provided by‍ FirstRanker.com ---

60-80%

Hematuria
Response to

--- Content provided by‍ FirstRanker.com ---

95%

50-60%

20-30%

--- Content provided by‌ FirstRanker.com ---

prednisolone
Likelihood of

95%

--- Content provided by⁠ FirstRanker.com ---

50-60%

20-30%

--- Content provided by⁠ FirstRanker.com ---

maintaining renal

function

Cont...

--- Content provided by‍ FirstRanker.com ---

clinical

Minimal change Mesangial

--- Content provided by FirstRanker.com ---

Focal segmental

disease

proliferation

--- Content provided by FirstRanker.com ---

glomerulosclero

sis

--- Content provided by‍ FirstRanker.com ---

Light Microscopy

Normal

Increase in

--- Content provided by FirstRanker.com ---

Focal or segmental

mesangial cells

--- Content provided by FirstRanker.com ---

glomerular

hyalinization

Immunofluoresce- Normal

--- Content provided by‌ FirstRanker.com ---

Negative or

Focal or segmental

--- Content provided by FirstRanker.com ---

nt microscopy

variable IgM and

deposition of Igm

--- Content provided by​ FirstRanker.com ---

C3 deposition

and C3

--- Content provided by FirstRanker.com ---

Electron

Fusion of foot

Increase in

--- Content provided by‍ FirstRanker.com ---

Fine granular

microscopy

--- Content provided by⁠ FirstRanker.com ---

processes of

mesangial cells

deposits in

--- Content provided by‌ FirstRanker.com ---

podocytes

and matrix,small

--- Content provided by‌ FirstRanker.com ---

subendothelial

scattered electron regions

dense deposits in

--- Content provided by⁠ FirstRanker.com ---

mesangium
Initial evaluation

Detailed evaluation

--- Content provided by‍ FirstRanker.com ---

The height, weight and blood pressure should be

recorded

Regular weight record

--- Content provided by FirstRanker.com ---

Physical examination is done to detect infections and

underlying systemic disorder

Infections should be treated before starting therapy

--- Content provided by​ FirstRanker.com ---

with corticosteroids.

Investigations

--- Content provided by‌ FirstRanker.com ---

Urinalysis
Complete blood count
Blood levels of Proteins, lipids, urea and creatinine

and electrolytes

--- Content provided by‍ FirstRanker.com ---

ASLO and C3: gross hematuria
Appropriate test ?HbSAg, HIV and tuberculosis
Renal biopsy

--- Content provided by⁠ FirstRanker.com ---

Indications for kidney biopsy

At Onset
Age of onset <1 year or >10 years

--- Content provided by‍ FirstRanker.com ---

Gross hematuria, persistent microscopic hematuria or low

serum C3.

Sustained hypertension.

--- Content provided by​ FirstRanker.com ---

Renal failure not attributable to hypovolemia.
Suspected secondary causes of nephrotic syndrome.
After Initial Treatment
Proteinuria persisting despite 4-weeks of daily

--- Content provided by​ FirstRanker.com ---

corticosteroid therapy.

Before treatment with cyclosporin A or tacrolimus.

Management of Nephrotic

--- Content provided by‍ FirstRanker.com ---

syndrome

Relief of edema
Hypertension

--- Content provided by‌ FirstRanker.com ---

Identify and treat infection
Specific treatment regimen
Complication
Definition related to nephrotic

--- Content provided by⁠ FirstRanker.com ---

syndrome

Remission: Urine albumin nil or trace (or proteinuria

<4 mg/m2/h) for 3 consecutive early morning

--- Content provided by FirstRanker.com ---

specimens.

Relapse: Urine albumin 3+ or 4+ (or proteinuria >40

--- Content provided by‌ FirstRanker.com ---

mg/m2/h) for 3 consecutive early morning specimens,

having been in remission previously.

Infrequent relapses: <2 relapses in 6 months of initial

--- Content provided by‌ FirstRanker.com ---

response or <4 relapses within any 12 months period.

Frequent relapses: Two or more relapses in initial six

--- Content provided by​ FirstRanker.com ---

months or more than three relapses in any twelve

months.
Definition related to nephrotic

--- Content provided by‌ FirstRanker.com ---

syndrome

Steroid dependence Two consecutive relapses when

on alternate day steroids or within 14 days of its

--- Content provided by⁠ FirstRanker.com ---

discontinuation.

Steroid resistance Absence of remission despite

--- Content provided by FirstRanker.com ---

therapy with daily prednisolone at a dose of 2 mg/kg

per day for 4 weeks

Treatment of initial episode

--- Content provided by​ FirstRanker.com ---

Oral prednisolone
2 mg/kg/day 6weeks
1.5 mg/kg/EOD 6 weeks
Treatment of infrequent

--- Content provided by‍ FirstRanker.com ---

relapse

Prednisolone 2 mg/kg/day till remission and then
Prednisolone 1.5 mg/kg/day for 4 weeks

--- Content provided by FirstRanker.com ---

Treatment of frequent repalse or

steroid dependent

--- Content provided by​ FirstRanker.com ---

Low dose steroids with-

Levamisole
Cyclophosphamide
Calcineurin inhibitor : Cyclosporin,Tacrolimus

--- Content provided by​ FirstRanker.com ---

Mycophenolate mofetil (MMF)
Toxicity of drugs

Side effects of prednisolone

--- Content provided by FirstRanker.com ---

Hirsutism
Obesity
Hypertension
Behavioral problems
Cataracts

--- Content provided by⁠ FirstRanker.com ---

Striae
Growth failure
Side effects of Levamisole

The chief side effect of levamisole is leukopenia

--- Content provided by‍ FirstRanker.com ---

Flu-like symptoms,
Liver toxicity
Convulsions and skin rash are rare
The leukocyte count should be monitored every 12-16

--- Content provided by‌ FirstRanker.com ---

weeks.

Side effects of Cyclophosphamide

Leucopenia

--- Content provided by​ FirstRanker.com ---

Hemorrhagic cystitis
Alopecia
Skin rash
Nausea
Side effects of Cyclosporin

--- Content provided by‌ FirstRanker.com ---

Hypertension
Cosmetic symptoms
Gum hypertrophy
Hirsutism

--- Content provided by FirstRanker.com ---

Nephrotoxicity
hypercholesterolemia and elevated transaminases may

occur

--- Content provided by‌ FirstRanker.com ---

Estimation of blood levels of creatinine is required

every 2-3 months and a lipid profile annually.

Side effects of MMF

--- Content provided by⁠ FirstRanker.com ---

Gastrointestinal discomfort, diarrhea and leukopenia.
Leukocyte counts should be monitored every1-2

months

--- Content provided by FirstRanker.com ---

Treatment is withheld if count falls below 4000/mm3.
Choice of agent

Few studies comparing one study with another

--- Content provided by⁠ FirstRanker.com ---

Levamisole has a modest steroid sparing effect and is

a satisfactory initial choice

Treatment with cyclophosphamide is preferred in

--- Content provided by FirstRanker.com ---

patients showing:

I. significant steroid toxicity
II. severe relapses with episodes of hypovolemia or

--- Content provided by⁠ FirstRanker.com ---

thrombosis, and

III. poor compliance or difficult follow up

--- Content provided by FirstRanker.com ---

Complications

Infection
Thrombosis
Hypertension

--- Content provided by FirstRanker.com ---

Hypovolumic shock
Corticosteroid side effects
Malnutrition
Outcome

--- Content provided by⁠ FirstRanker.com ---

Steroid responsive - >90%
Relapses- >70%
Mortality ? 2-5%
Patient and parents education

--- Content provided by‌ FirstRanker.com ---

Urine examination at home
Maintain diary showing result of urine protein
Ensure normal activity and school attendance
Appropriate immunization

--- Content provided by⁠ FirstRanker.com ---

Acute glomerulophritis

Glomerulonephritis refers to a group of glomerular

diseases characterise by inflammatory changes in the

--- Content provided by⁠ FirstRanker.com ---

glomeruli and manifesting as acute nephritic

syndrome which is characterized by-

--- Content provided by FirstRanker.com ---

Abrupt onset of hematuria
Oligouria
Edema
Hypertension
Subnephrotic range proteinuria

--- Content provided by FirstRanker.com ---

Azotemia
Causes of Acute GMN

Post infectious: Bacterial-Streptococcal,

--- Content provided by⁠ FirstRanker.com ---

staphylococcal, pnemococcal, meningococcal.

Bacterial endocarditis, infected ventriculoatrial shunt

and prosthesis can cause acute GMN. Viral- Hepatitis

--- Content provided by FirstRanker.com ---

B and C, mumps, HIV, varicella, infectious

mononucleosis. Parasitic- malaria and toxoplasmosis

--- Content provided by⁠ FirstRanker.com ---

Systemic vasculitis: HSP, SLE, PAN, Wegner's

granulomatosis

Pathogenesis

--- Content provided by​ FirstRanker.com ---

Immune complex mediated disease
i. Immune complex Glomerulonephritis (70%)
? Low serum complement C3- poststreptococcal, rapidly

--- Content provided by‌ FirstRanker.com ---

progressive, mesangioproliferative glomerulonephritis, SLE,

bacterial endocarditis, cryoglobulinemia

? Normal serum complement C3- IgA nephropathy, H-S purpura

--- Content provided by⁠ FirstRanker.com ---

ii. Pauci-immune glomerulonephritis (30%)
Anti-neutrophil cytoplasmic antibody positive wegener's

granulomatosis, polyarteritis nodosa
iii. Anti GBM disease(<1%)

--- Content provided by‌ FirstRanker.com ---

Anti-glomerular basement membrane antibody positive Good

pasture syndrome.
Post streptococcal

--- Content provided by⁠ FirstRanker.com ---

Glomerulonephritis

Following group A beta-hemolytic streptococci
School age children
Boys are more frequently affected

--- Content provided by⁠ FirstRanker.com ---

Etiology

Follows a pharyngeal or cutaneous infection by the

--- Content provided by⁠ FirstRanker.com ---

nephritogenic strains of hemolytic Group A

streptococcus1 to 4 week preceding streptococcal

throat/skin infection

--- Content provided by‍ FirstRanker.com ---

Strain M type 1,4 and 12 causing pharyngitis and

49,55,57 and 60 causing pyoderma

--- Content provided by FirstRanker.com ---

Typical example of immune complex disease
Pathogenesis

Immune complex deposition
Glomeruli enlarged

--- Content provided by FirstRanker.com ---

Ischemia
Capillary wall narrowing
Deposits of IgG and C3

Clinical feature

--- Content provided by‌ FirstRanker.com ---

Rare below 3 years of age
Acute onset
Latent period: Following pharyngitis- 1 to2 weeks and

--- Content provided by⁠ FirstRanker.com ---

following cutaneous infection- 2 to 4 weeks

Puffiness around eye and pedal edema
Cola colored urine
Oliguria

--- Content provided by‍ FirstRanker.com ---

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

--- Content provided by​ FirstRanker.com ---

weeks
Laboratory investigations

Urine : 1+/2+ protein, dysmorphic RBC's, and red cell, leukocyte or granular

--- Content provided by‍ FirstRanker.com ---

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.

--- Content provided by‌ FirstRanker.com ---

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

--- Content provided by‍ FirstRanker.com ---

Others- X- ray chest, ECG
renal biopsy- to exclude other diseases in patients with-
? ARF
? normal C3 level

--- Content provided by​ FirstRanker.com ---

? without evidence of preceding streptococcal infection
? persistant gross hematuria and hypertension (>3 weeks)
? prolonged diminished renal functions (> 2 weeks)
? persistent low serum C3 (>8weeks)

--- Content provided by​ FirstRanker.com ---

Management

Presence of ARF and Hypertension requires hospitalisation
Bed rest
Diet

--- Content provided by⁠ FirstRanker.com ---

Weight
Fluid restriction
Antibiotics
Diuretics
Alkalinization of urine

--- Content provided by‌ FirstRanker.com ---

Hypertension
LVF
ARF
Outcome and prognosis

--- Content provided by‍ FirstRanker.com ---

Overall excellent prognosis( >95% complete recovery,

<1% develop RPGN))

Symptoms resolves within 1 month

--- Content provided by FirstRanker.com ---

Gross hematuria and proteinuria disappear within 2

weeks

Microscopic hematuria may last for years

--- Content provided by‍ FirstRanker.com ---

Recurrence rare

Difference between acute nephritis

and nephrotic syndrome

--- Content provided by‌ FirstRanker.com ---

Acute nephritis

Nephrotic syndrome

--- Content provided by‌ FirstRanker.com ---

Characterized by hematuria,

Characterized by heavy

edema, hypertension, oligouria

--- Content provided by‍ FirstRanker.com ---

proteinuria, hpo albuminemia,

edema,hyperlipidemia

--- Content provided by‌ FirstRanker.com ---

90% post infective, immune

90% idiopathic

complex

--- Content provided by‌ FirstRanker.com ---

Relapses common

Usually only 1 attack

--- Content provided by⁠ FirstRanker.com ---

Retraction of epithelial foot

Immune complex deposition

process

--- Content provided by FirstRanker.com ---

Urine: Alb 1+/2+, hematuria,

Urine: Selective proteinuria, No

--- Content provided by‌ FirstRanker.com ---

RBC cast

RBC

Blood urea/creat raised

--- Content provided by⁠ FirstRanker.com ---

Blood urea/ creat normal
Thank you