NEPHROTIC

SYNDROME
 DEFINITION

PROTEINURIA
Nephrotic range

HYPOALBUMINEMIA

HYPERLIPIDEMIA

OEDEMA
 Nephrotic Range
Proteinuria

24 hour urine..40mg/m2/h…difficult

First morning urine sample…protein and

creatinine ratio….more than 2-3:1
 Classification of nephrotic
syndrome

ETOLOGICAL HISTOLOGICAL
CLASSIFICATION CLASISIFICATION

Primary MCD
NEPHROTIC FSGN
syndrome. Disease MN
limited to kidney MPGN

Secondary
NEPHROTIC
syndrome. Other
systems involved
 Causes of secondary
nephrotic syndrome Primary nephrotic syndrome
Membranous nephropathy (MN)[3]
•Hepatitis B Diagnosis of exclusion
•Sjogren's syndrome
•Systemic lupus erythematosus (SLE)
•Diabetes mellitus
•Sarcoidosis
•Syphilis
•Drugs
•Malignancy (cancer)

Focal segmental glomerulosclerosis (FSGS)[3]

•Hypertensive Nephrosclerosis
•Human immunodeficiency virus (HIV)
•Diabetes mellitus
•Obesity
•Kidney loss

Minimal change disease (MCD)[3]

•Drugs
Malignancy, especially Hodgkin's lymphoma
Primary nephrotic syndrome /idiopathic nephrotic syndrome

Steroid resistant INS

(SRNS)

Steroid sensitive IN
(SSNS)

response to steroids has a high correlation with histological

subtype and prognosis
 PATHOPHYSIOLOGY

PROTEINURIA /
HYPOALBUMINIA

Immune pathogenesis
Deregulation of T-cell
subsets.
Circulating factors
Cytokines/other molecules

Allergic response
Poison ivy, bee stings
 PODOCYTE BIOLOGY

Effacement of
podocytes is now
thought to be the
primary pathology.

-ve charge of the

basement
membrane is
also important.
 GENETICS.

Nephrin Podicin
Transmembrane protein Encoded by NPHS 2
encoded by NPHS 1 on on chromosome 1.
chromosome 19.(FINISH Autosomal recessive.
type congenital NS.

Mutations in α-actinin-4,
encoded by the gene
ACTN4 on chromosome
19 and TRPC6 on
chromosome 11, are
associated with
autosomal dominant
forms of FSGS
PATHOPHYSIOLOGY
continued….
Pathophysiology cont…
Decreased plasma oncotic
pressure may play a role in
increased hepatic lipoprotein
synthesis, as demonstrated
by the reduction of
hyperlipidemia in patients
with INS receiving either
albumin or dextran infusions
Decreased levels of Ig G and
increased losses of factor B.
Patients with nephrotic
syndrome are at increased
risk for thrombosis.
Abnormalities described in
INS include increased
platelet activation and
aggregation; elevation in
factors V, VII, VIII, and XIII
and fibrinogen; decreased
antithrombin III, proteins C
and S, and factors XI and
XII; and increased
activities of tissue
plasminogen activator and
plasminogen activator
inhibitor-1.
 INVESTIGATIONS

ESTABLISH nephrotic
syndrome
Primary or If Primary,
Nephrotic range secondary Whether
proteinuria nephrotic in renal
syndromes failure?....
Hypoalbuminemia
Renal
Hyperlipidemia functions.
 Investigations

Urea creatinine and Complement system

electrolytes

CBC ANA,Anti double

stranded DNA
antibodies.

Testing for hep B and C

Imaging;U/S abdomen
and chest.
Genetic testing. X ray chest.

Renal biopsy
INTERPRETATIONS
Anemia , raised urea
creatinine
,acidosis,hyperkalemia
,hyperphosphatemia,in
dicate
Chronic renal disease.
Hyponatremia may be due to
hyperlipidemia and due to
water
retention(pseudohyponatremia.
Raised Hb and
haemetocrat indicates
haemodilution.reduced
intravascular volume.
Platelet is raised.
Check liver
enzymes..for
Hepatitis B and C.and
do screening for
viruses.
 MANAGEMENT OF NEPHROTIC SYNDROME

patients aged 1-8

years with normal
kidney function
A trial
of corticosteroids is Normal kidney
the first step in functions
treatment of
idiopathic nephrotic No macroscopic
syndrome (INS) in gross haemeturia
which kidney
biopsy is not initially No symptoms of
indicated. systemic disease.

Normal complement
levels

Negative viral screen

No family hisory.
 IMPORTANT DEFINITIONS

RESPONSE; protein free urine on 3 consecutive days within 7

days.

RELAPSE; protein +ve urine on 3 consecutive days within

one week with edema.

FREQUENT RELAPSING NS; steroid sensitive nephrotic

syndrome with 2 or more relapses in 6 months or more than
3 in one year.

STEROID DEPENDANT; responder who relapses while

steroid is being tapered or within 14 days of stopping steroid
treatment.
INITIAL NON RESONDER; no response during initial 8
weeks of therapy.

LATE NON RESPONDER; an initial steroid

responder who fails to respond to 4 week treatment
in relapse.
 SSNS steroid sensitive nephrotic syndrome
Corticosteroids

INDUCTION THERAPY MAINTAINANCE THERAPY

Exclude active infections Oral prednisilone at

and other contraindications
to steroids
Oral prednisilone
60mg/m2/day…either single
or divided doses for 4
weeks.
40mg/m2/day single
morning dose at alternate
Days for 4-6 weeks.
Longer duration of
maintenance therapy
results in fewer relapses.

6 weeks therapy proves

better .
Relapse therapy Other therapy

For infrequent relapses Pneumococcal vaccines to

steroid therapy may be all the patients.
resumed at
60mg/m2/day until Diuretic therapy for
proteinuria resolves.. symptomatic edema. with
furosamide 2mg/kg/day.
Then switch to
40mg/m2/day for Anasarca with low
alternate days for 4 intravascular volume
weeks. ,albumin infusion, slow
1mg/kg/day can be
considered.
 HOME MONITORING

Home monitoring of urine

protein and fluid status is
important.

Parents should be trained to

monitor first morning urine by
dipstick.

Record of daily weight,urine

protein and steroid dose
should be kept in log book.

Any increase in urine protein or

daily weight should be reported
as early as possible.
 TREATING FREQUENT RELAPSERS AND SDNS

ALKYLATING AGENTS CALCINEURINE

INHIBITORS
Cyclophospamide
Chlorambucil Cyclosporin
Nitrogen mustard Tacrolimus

LEVAMISOLE MYCOPHENOLATE
MOFETIL
 DOSING AND REGIMENS

Cyclophosphamide (2–2.5 mg/kg daily) is given orally for 8-

12 weeks.

Steroids are usually overlapped with initiation of CYP

then tapered

Patients must have weekly CBC counts to monitor for

leukopenia.

Patients must also maintain adequate hydration and take

CYP in the morning (not at bedtime) to limit the risk of
hemorrhagic cystitis
 CYCLOSPORIN

CSA can be used in those children who fail to respond to, or

subsequently relapse after, treatment with CYP, or for children whose
families object to use of CYP

Initial doses of CSA are started at 5–6 mg/kg daily divided every
12 hours, adjusted for trough concentrations of 50–125 ng/mL

Low-dose steroids are continued for a variable length of time

Kidney function and drug levels must be carefully

monitored due to the risk of CSA induced
nephrotoxicity.
 Deterrence/Prevention

Yearly influenza vaccination is recommended to prevent serious

illness in the immunocompromised patient, as well as to prevent this
possible trigger of relapse.

Pneumococcal vaccination should be administered to all patients

with INS to reduce the risk of pneumococcal infection. Vaccination
should be repeated every 5 years while the patient continues to
have relapses.

Routine childhood vaccines with live virus strains are

contraindicated in patients taking steroids and until off steroid
treatment for a minimum of 1 month.

Because of the high risk of varicella infection in the immunocompromised

patient, in the nonimmune patient, post exposure prophylaxis with
varicella-zoster immune globulin is recommended. Patient with varicella-
zoster infection should be treated with acyclovir and carefully monitored

Routine, nonlive viral vaccines should be administered

according to their recommended schedules