Download MBBS Pediatric PPT 8 Nephrotic Syndrome Lecture Notes

Nephrotic and Nephritic

syndrome

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Learning objectives

Definition of Nephrotic syndrome
Etiopathogenesis of nephrotic syndrome
Clinical manifestation

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Evaluation
Management
outcome
Post streptococcal GMN
Introduction

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

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Definition

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

children

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

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

test)

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

timed-sample).

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Etiology

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

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membranoproliferative, congenital (Finnish type)

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

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Hodgkin lymphoma, diabetes mellitus,

amyloidosis, malaria (P. malariae), intrauterine

infections (syphilis,

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toxoplasmosis,cytomegalovirus) and other

infections like HIV, parvovirus B19,hepatitis B and

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C virus, drugs like d-penicillamine, gold and

toxins or allergies (bee sting, poison ivy, food

allergy).

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Pathophysiology

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

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Urine protein loss leads to hypoalbuminemia


decreased oncotic pressure

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transudation of fluid

Reduction in intravascular volume and decrease renal

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perfusion pressure

Pathophysiology

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Mechanism of lipid elevation:
Hypoalbuminemia stimulates generalized hepatic

protein synthesis including lipoprotein

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Lipid catabolism is diminished due to decrease in

lipoprotein lipase
Clinical Features

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clinical

Minimal change Mesangial

Focal segmental

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disease

proliferation

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glomerulosclero

sis

Incidence

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85%

10%

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5%

Age at

2-6years

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2-10years

2-10years

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presentation
Hypertension

10%

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10-45%

35-45%

Microscopic

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10-20%

45-90%

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60-80%

Hematuria
Response to

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95%

50-60%

20-30%

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prednisolone
Likelihood of

95%

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50-60%

20-30%

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maintaining renal

function

Cont...

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clinical

Minimal change Mesangial

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Focal segmental

disease

proliferation

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glomerulosclero

sis

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Light Microscopy

Normal

Increase in

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Focal or segmental

mesangial cells

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glomerular

hyalinization

Immunofluoresce- Normal

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Negative or

Focal or segmental

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nt microscopy

variable IgM and

deposition of Igm

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C3 deposition

and C3

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Electron

Fusion of foot

Increase in

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Fine granular

microscopy

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processes of

mesangial cells

deposits in

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podocytes

and matrix,small

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subendothelial

scattered electron regions

dense deposits in

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mesangium
Initial evaluation

Detailed evaluation

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The height, weight and blood pressure should be

recorded

Regular weight record

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Physical examination is done to detect infections and

underlying systemic disorder

Infections should be treated before starting therapy

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with corticosteroids.

Investigations

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

and electrolytes

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

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Indications for kidney biopsy

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

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Gross hematuria, persistent microscopic hematuria or low

serum C3.

Sustained hypertension.

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

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corticosteroid therapy.

Before treatment with cyclosporin A or tacrolimus.

Management of Nephrotic

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syndrome

Relief of edema
Hypertension

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

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syndrome

Remission: Urine albumin nil or trace (or proteinuria

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

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specimens.

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

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

having been in remission previously.

Infrequent relapses: <2 relapses in 6 months of initial

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response or <4 relapses within any 12 months period.

Frequent relapses: Two or more relapses in initial six

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months or more than three relapses in any twelve

months.
Definition related to nephrotic

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syndrome

Steroid dependence Two consecutive relapses when

on alternate day steroids or within 14 days of its

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discontinuation.

Steroid resistance Absence of remission despite

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

per day for 4 weeks

Treatment of initial episode

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

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relapse

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

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Treatment of frequent repalse or

steroid dependent

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Low dose steroids with-

Levamisole
Cyclophosphamide
Calcineurin inhibitor : Cyclosporin,Tacrolimus

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Mycophenolate mofetil (MMF)
Toxicity of drugs

Side effects of prednisolone

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Hirsutism
Obesity
Hypertension
Behavioral problems
Cataracts

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Striae
Growth failure
Side effects of Levamisole

The chief side effect of levamisole is leukopenia

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

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weeks.

Side effects of Cyclophosphamide

Leucopenia

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Hemorrhagic cystitis
Alopecia
Skin rash
Nausea
Side effects of Cyclosporin

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Hypertension
Cosmetic symptoms
Gum hypertrophy
Hirsutism

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Nephrotoxicity
hypercholesterolemia and elevated transaminases may

occur

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Estimation of blood levels of creatinine is required

every 2-3 months and a lipid profile annually.

Side effects of MMF

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

months

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

Few studies comparing one study with another

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Levamisole has a modest steroid sparing effect and is

a satisfactory initial choice

Treatment with cyclophosphamide is preferred in

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patients showing:

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

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thrombosis, and

III. poor compliance or difficult follow up

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Complications

Infection
Thrombosis
Hypertension

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Hypovolumic shock
Corticosteroid side effects
Malnutrition
Outcome

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

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

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Acute glomerulophritis

Glomerulonephritis refers to a group of glomerular

diseases characterise by inflammatory changes in the

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glomeruli and manifesting as acute nephritic

syndrome which is characterized by-

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Abrupt onset of hematuria
Oligouria
Edema
Hypertension
Subnephrotic range proteinuria

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Azotemia
Causes of Acute GMN

Post infectious: Bacterial-Streptococcal,

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staphylococcal, pnemococcal, meningococcal.

Bacterial endocarditis, infected ventriculoatrial shunt

and prosthesis can cause acute GMN. Viral- Hepatitis

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B and C, mumps, HIV, varicella, infectious

mononucleosis. Parasitic- malaria and toxoplasmosis

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

granulomatosis

Pathogenesis

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

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progressive, mesangioproliferative glomerulonephritis, SLE,

bacterial endocarditis, cryoglobulinemia

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

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

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

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Anti-glomerular basement membrane antibody positive Good

pasture syndrome.
Post streptococcal

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Glomerulonephritis

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

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Etiology

Follows a pharyngeal or cutaneous infection by the

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nephritogenic strains of hemolytic Group A

streptococcus1 to 4 week preceding streptococcal

throat/skin infection

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Strain M type 1,4 and 12 causing pharyngitis and

49,55,57 and 60 causing pyoderma

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Typical example of immune complex disease
Pathogenesis

Immune complex deposition
Glomeruli enlarged

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Ischemia
Capillary wall narrowing
Deposits of IgG and C3

Clinical feature

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

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following cutaneous infection- 2 to 4 weeks

Puffiness around eye and pedal edema
Cola colored urine
Oliguria

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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

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weeks
Laboratory investigations

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

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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.

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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

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

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

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Management

Presence of ARF and Hypertension requires hospitalisation
Bed rest
Diet

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Weight
Fluid restriction
Antibiotics
Diuretics
Alkalinization of urine

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Hypertension
LVF
ARF
Outcome and prognosis

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Overall excellent prognosis( >95% complete recovery,

<1% develop RPGN))

Symptoms resolves within 1 month

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Gross hematuria and proteinuria disappear within 2

weeks

Microscopic hematuria may last for years

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Recurrence rare

Difference between acute nephritis

and nephrotic syndrome

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Acute nephritis

Nephrotic syndrome

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Characterized by hematuria,

Characterized by heavy

edema, hypertension, oligouria

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proteinuria, hpo albuminemia,

edema,hyperlipidemia

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90% post infective, immune

90% idiopathic

complex

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Relapses common

Usually only 1 attack

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Retraction of epithelial foot

Immune complex deposition

process

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Urine: Alb 1+/2+, hematuria,

Urine: Selective proteinuria, No

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RBC cast

RBC

Blood urea/creat raised

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Blood urea/ creat normal
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