management of nephrotic syndrome

MANAGEMENT OF NEPHROTICSYNDROME

Dr C. Naveen Kumar,1st year Post Graduate

Dr Naveen Kumar CheriS.V. Medical College, Tirupati

Objectives

• To briefly review the definition & etiology of nephroticsyndrome.

• To understand the terminology pertaining to clinical course of nephrotic syndrome.

• To understand the management of nephroticsyndrome:

Specific management

Supportive care and management of complications

Management of congenital nephrotic syndrome


Definition

Nephrotic syndrome, is a manifestation of glomerular disease (due to various etiologies) characterized by,

Nephrotic range

proteinuria

• Early morning urine protein is 3+/4+

(on dipstick or boiling test) or

• Spot protein/creatinine ratio >2

mg/mg, or

• Urine albumin excretion >40 mg/m2

per hr (on a timed-sample) or

• Urine protein excretion > 50 mg/kg/24

hr

Hypoalbuminemia • Serum albumin < 2.5 g/dL

Hyperlipidemia • Serum cholesterol >200 mg/dL

Generalised EdemaDr Naveen Kumar Cheri

S.V. Medical College, Tirupati

Etiology of nephrotic syndrome

In 95% cases there is primary

glomerular abnormality. Remaining

are secondary to systemic disorder.


Specific Management


Evaluation at onset

• Essential investigations:

Urinalysis: Proteinuria, red cells, casts; Spot urine protein creatinine ratio

Blood levels of urea, creatinine, albumin, cholesterol

Complete blood count

Tuberculin test

• If required:

C3 and ASO titres (gross or persistent microscopic hematuria)

Chest X-ray (positive tuberculin test, history of TB contact)

HIV, HBV, HCV serology in highrisk groups

ANA (if features of SLE are present)

Urine culture (if clinical features of UTI are present)

USG abdomen (to ruleout anomalies in kidney)


Indications for renal biopsy• At Onset (If cause other than minimal change nephrotic

syndrome is suspected)

• Age of onset <1 year.

• 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 – steroid resistance.

• Before treatment with Cyclosporin A or Tacrolimus.


Management of the initial episode

• Appropriate therapy at the first episode is an important determinant of the long term course of the disease.

• Prednisolone is the drug of choice.

• It is given at a dose of 2 mg/kg per day (maximum 60 mg in single or divided doses) for 6 weeks, followed by 1.5 mg/kg (maximum 40 mg) as a single morning dose on alternate days for the next 6 weeks; therapy is then discontinued.


Following initial treatment with steroids for 12 weeks, the disease may take any of the following course:

Remission

Urine albumin nil or trace (or proteinuria <4

mg/m2/hr) for 3 consecutive early morning

specimens.

Relapse

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

mg/m2/hr) for 3 consecutive early morning

specimens, having been in remission previously.

Frequent

relapses

Two or more relapses in initial six months or more

than three relapses in any twelve months.

Infrequent

relapsesThree or less relapses a year.

Steroid

dependence

Two consecutive relapses when on alternate day

steroids or within 14 days of its discontinuation.

Steroid

resistance

Failure to achieve remission despite therapy with

daily prednisolone at a dose of 2 mg/kg per day for

4 weeks. Dr Naveen Kumar CheriS.V. Medical College, Tirupati

Treatment of relapse

• Relapse is defined as urine albumin 3+ or 4+ (or proteinuria >40 mg/m2/hr) for 3 consecutive early morning specimens, having been in remission previously.

• An URTI or some other infection usually precipitates a relapse.

• Appropriate therapy of an infection before starting therapy might result in spontaneous remission.

• Prednisolone is administered at a dose of 2 mg/kg/day (single or divided doses) until urine protein is trace or nil for three consecutive days.

• Subsequently, Prednisolone is given in a single morning dose of 1.5 mg/kg on alternate days for 4 weeks, and then discontinued.


Infrequent Relapsers

• An infrequent relapser is defined as initial responder with three or less relapses a year.

• They are managed using standard prednisolone regimen for each relapse.

• Such children are at a low risk for developing steroid toxicity.


Management of Frequent Relapsers and Steroid Dependence• Frequent relapse is defined as Two or more relapses in

initial six months or more than three relapses in any twelve months.

• Steroid dependence is defined as occurrence two consecutive relapses when on alternate day steroids or within 14 days of its discontinuation.

• Following treatment of a relapse, prednisolone is gradually tapered to maintain the patient in remission on alternate day dose of 0.5-0.7 mg/kg.

• A close monitoring of growth and blood pressure, and evaluation for features of steroid toxicity (cushingoidfeatures – obesity, hirsutism, striae, hypertension, impaired glucose tolerance, posterior subcapsular opacities, emotional problems & growth retardation) is essential.


Management of Frequent Relapsers and Steroid Dependence contd.• If prednisolone threshold to maintain remission less than

0.5-0.7mg/kg on alternate day and there is no steroid toxicity, it is continued for 9-18 months. And then breakthrough relapses are treated with standard therapy of relapse.

• If prednisolone threshold to maintain remission greater than 0.5-0.7mg/kg on alternate day and there is steroid toxicity, addition of following immunomodulators is suggested.

• Levamisole

• Cyclophosphamide

• Calcineurin inhibitors: Cyclosporin (CsA), Tacrolimus

• Mycophenolate mofetil (MMF)Dr Naveen Kumar Cheri


Levamisole

• Immunostimulant drug.

• Dose & duration: 2-2.5 mg/kg on alternate days for 12-24 months

• Concomitant steroid therapy: Prednisolone dose is gradually tapered to 0.25-0.5 mg/kg over a period of 8 months. Occasionally, it might be possible to discontinue Prednisolone.

• Side effects: Neutropenia, flu-like symptoms, liver toxicity, convulsions and skin rash.

• Monitoring:The leukocyte count should be monitored every 3-4 months.


Cyclophosphamide

• Immunosuppressive drug.

• Dose & duration: 2-2.5 mg/kg/day for 12 weeks. Should be started following remission of proteinuria.

• Concomitant steroid therapy: Prednisolone dose is gradually tapered to 1 mg/kg over a period of 6 months and then stopped.

• Side effects: Hemorrhagic cystitis, alopecia, nausea and vomiting, gonadal toxicity.

• Monitoring:Total leukocyte counts are monitored every 2 weeks;temporarily discontinued if the count falls below 4000/mm3.

• Use of more than one course (12 weeks) should preferably be avoided in view of gonadal toxicity.Dr Naveen Kumar Cheri


Calcineurin inhibitor : Cyclosporin (CsA)

• Immunosuppressive agent.

• Dose & duration: 4-5 mg/kg daily for 12-24 months.

• Concomitant steroid therapy: Prednisolone is gradually tapered to 0.25-0.5 mg/kg over 8 or more months. Occassionally it can be discontinued.

• Side effects: Hypertension, gum hypertrophy, hirsutism, nephrotoxicity, hypercholesterolemia and elevated transaminases.

• Monitoring: Plasma CsA levels should be kept between 80-120 ng/mL.

• Serum creatinine is monitored every 2-3 months.

• Lipid profile is checked annually.

• A repeat kidney biopsy, to examine for histological evidence of nephrotoxicity, should be done if duration of treatment is extended beyond 2 years.


Calcineurin inhibitor : Tacrolimus


• Dose & duration: 0.1-0.2 mg/kg daily for 12-24 months.

• Concomitant steroid therapy: Prednisolone is gradually tapered to 0.25-0.5 mg/kg over 8 or more months. Occassionally it can be discontinued.

• Side effects: Hyperglycemia, diarrhea and rarely neurotoxicity (headache, seizures).

• Preferred especially in adolescents, because of lack of cosmetic side effects (Gum hypertrophy & hirsutism).

• Monitoring: Serum creatinine and glucose every 2-3 months.

• A repeat kidney biopsy, to examine for histological evidence of nephrotoxicity, should be done if duration of treatment is extended beyond 2 years.


Mycophenolate mofetil (MMF)


• Dose & duration: 800-1200 mg/m2/day for 12-24 months.

• Concomitant steroid therapy: Prednisolone is gradually tapered over 12-24 months. Recent trials supported its use as a steroid sparing agent.

• Side effects: Gastrointestinal discomfort, diarrhea and leukopenia.

• Monitoring: Leukocyte counts every 1-2 months; Withheld if count falls below 4000/mm3


Choice of immunomodulator:

• First choice is Levamisole or Cyclophosphamide.

• Cycloposphamide is preferred in patients showing poor compliance or difficult follow-up, where 12 weeks therapy is beneficial.

• Relapses occurring during immunomodulatortherapy must be treated with regular Prednisolone relapse regimen.

• If there are two or more relapses over 6 months while on treatment with any of them, its replacement with an alternative medication should be considered.


Management of patients with steroid sensitive nephrotic syndromeDr Naveen Kumar Cheri


Steroid resistant nephrotic syndrome

• Failure to achieve remission despite therapy with daily prednisolone at a dose of 2 mg/kg per day for 4 weeks is called steroid resistance.

• Incidence approximately 10-20%.

• Initial resistance: Lack of remission at the first episode.

• Late resistance: Steroid sensitive initially, but show steroid resistance during subsequent relapse.

• All chidren with steroid resistant nephroticsyndrome should under go renal biopsy.


SRNS - renal biopsy rationale

• Most patients with steroid sensitive nephrotic syndrome (90%) show minimal change nephrotic syndrome on renal histology.

• 30-40% of SRNS patients show minimal change nephroticsyndrome,30-40% show FSGS.

• 20% patients with SRNS show membranoproliferativeglomerulonephritis, membranous nephropathy, IgA nephropathy and amyloidosis. These conditions differ in their evaluation and treatment.

• The response to therapy is determined by renal histology; patients with minimal change nephrotic syndrome show satisfactory response to therapy, while presence of FSGS or chronic tubulointerstitial changes is associated with unsatisfactory outcomes.


Treatment regimens for SRNS

There is lack of consensus regarding the most

appropriate regimen, the choice of initial treatment

depends on the preference of the physician. Duration of

therapy is for 2-3 years. Dr Naveen Kumar CheriS.V. Medical College, Tirupati

SRNS - Management

• All patients with SRNS should receive treatment with angiotensin converting enzyme inhibitors (e.g., Enalapril, Ramipril).

• These agents should be avoided if the estimated GFR is <30 ml/minute/1.73 m2.

• Angiotensin receptor blockers (e.g., Losartan,Valsartan) may be used in patients intolerant to ACE inhibitors, or as add-on therapy to achieve better antihypertensive and antiproteinuriceffect.

• Dyslipidemia should be managed by HMG CoA reductase inhibitors (e.g. Atrovastatin 10-20 mg daily). Target LDL level is <130 mg/dL.


Supportive care & Management of complications


Dietary management• A balanced diet, adequate in protein (1.5-2 g/kg) and

calories is recommended.

• Patients with persistent proteinuria should receive 2-2.5 g/kg of protein daily.

• Not more than 30% calories should be derived from fat.

• Treatment with corticosteroids stimulates appetite, so adequate physical activity is to be ensured to prevent excessive weight gain.

• Patients on prolonged (>3 months) treatment with steroids should receive daily supplements of oral calcium (250-500 mg/day) and vitamin D (125-250 IU/day).


Dietary management contd.• Salt restriction is not necessary in most patients with

steroid sensitive nephrotic syndrome

• Reduction of salt intake (1-2 g per day) is advised for those with persistent edema. Salt should not be added to salads and fruits, and snacks containing high salt avoided.

• Fluid restriction is needed in addition to Sodium restriction in children with persistent edema.

• Severe edema: Intake of fluid restricted to insensible water loss

• Moderate edema: Fluid intake = Insensible water loss (400 mL/m2/day) + Previous day's urine output

• Mild edema: Fluid is minimally restricted Dr Naveen Kumar Cheri


Edema – Underfill hypothesis

Heavy proteinuria

Hypoalbuminemia

Decreased plasma oncotic pressure

Transudation of fluid from intravascular to interstitial space

Decreased circulating blood volume (Underfill)

Activation of Renin-Angiotensin System

Elevated Aldosterone, Elevated Vasopressin

Sodium and water retention

EdemaDr Naveen Kumar Cheri


Edema – Overfill hypothesis

Heavy proteinuria

Proteolytic enzymes enter tubular lumen

Activation of Epithelial Sodium Channels (ENaC)

Increased blood volume (Overfill)

Edema

Hypoalbuminemia

Low plasma oncotic pressureIntrinsic

resistance of kidney to

ANP (Atrial Natriuretic

Peptide)


• Prednisolone therapy usually results

in diuresis with in 5-10 days.

• Diuretics shouldn’t be given to

patients with diarrhea, vomiting or

hypovolemia. .

• Gradual reduction of edema over one

week is preferred.

• Spironolactone added for patients

requiring Furosemide dose

>3mg/kg/day or used >1 week.

• Monitor weight, urine output, BP,

heart rate & serum electrolytes of

patients who are on IV diuretic

therapy.

• In case of refractory ascites

interfering with respiration,

paracentesis should be done.Patients receiving Albumin should be observed for

respiratory distress (pulmonary edema), hypertension and

congestive heart failure.

Edema – Management


Hypovolemia• May occur during severe disease relapse, following diuretic

administration particularly in children with poor oral intake, diarrhea and vomiting.

• Symptoms: Dizziness, lethargy, abdominal pain and leg cramps.

• Signs: Dry mucous membrane, orthostatic hypotension,raised hematocrit, elevated blood urea, uric acid, tachycardia, feeble pulses, cold extremities, slow capillary refill, low FENa & high urinary Potassium.

• Treatment: Rapid infusion of normal saline (10-20 mL/kg) over 20-30 minutes. Repeat another bolus if features of hypovolemia persist.

If no response with two blouses, Albumin infusion (5% Albumin at 10-15 mL/kg or 20% Albumin at 0.5-1 g/kg) is given.


InfectionsChildren with nephrotic syndrome are prone to develop infections because of:

• Low IgG levels

• Impaired T-lymphocyte function

• Edema fluid acting as potential culture medium

• Impaired tissue perfusion due to edema

• Low factor B (C3 pro-activator) & Factor D levels -decreased bacterial opsonization

• Immunosuppressive therapy

• Skin breaks due to stretching of edematous skin, are easy portal of entry for organisms.

ESR, leukocyte count are poor markers of infection in nephrotic syndrome. CRP, pro-calcitonin can be helpful instead. Dr Naveen Kumar Cheri


Infections contd.Spontaneous bacterial peritonitis:

• Streptococcus pneumoniae is the most common cause. Streptococcus pyogenes, gram negative organisms (E.coli, Hemophilus) are the other causative organisms.

• Presentation: Abdominal pain, nausea, vomiting, fever, diarrhea, tenderness & rigidity.

• Other causes of abdominal pain in nephrotic syndrome: splanchnic ischemia due to hypovolemia & gastritis due to steroid intake.

• Diagnosis: Examination of ascitic fluid (hazy/turbid), presence of leukocytes (>75-100/mm3) with >50% neutrophils & culture.

• Treatment: IV Ampicillin and Aminoglycoside or monotherapy with IV Ceftriaxone for 7-10 days.


Infections contd.


Infections contd.

Tuberculosis:

• Mantoux test is to be done before starting steroid therapy.

• Those with Mantoux positive but show no evidence of TB, should receive INH prophylaxis (10 mg/kg/day) for 6 months.

• Those showing evidence of active tuberculosis should receive standard anti-tubercular therapy.


Infections contd.Varicella:

• Varicella may be a severe illness in patients with nephroticsyndrome receiving corticosteroids or other immunosuppressive drugs.

• Susceptible patients (unimmunized / no history of Varicella), who are exposed to a case of chickenpox should therefore receive a single dose of Varicella Zoster Immunoglobulin (VZIG) or 400 mg/kg Intravenous Immunoglobulin (IVIG) within 96 hr of exposure.

• Patients who develop varicella should receive intravenous acyclovir (1500 mg/m2/day in 3 doses) or oral acyclovir (80 mg/kg/day in 4 doses) for 7-10 days.

• The dose of prednisolone should be tapered to 0.5 mg/kg/day or lower during the infection.


Stress doses of corticosteroids

• Children who have received high doses of corticosteroids (>1mg/kg daily) for more than 2 weeks in the past year are at risk of HPA (hypothalamo-pitutary-adrenal) axis suppression.

• Such children, during the periods of stress (infection, surgery & anesthesia) should be given,

IV hydrocortisone at 2-4 mg/kg/day, followed by

Oral Prednisolone 0.3-1 mg/kg/day

– for the duration of stress and then tapered rapidly.


Immunization

• Patients receiving prednisolone at a dose of 2 mg/kg/day or greater, or total 20 mg/day or greater for more than 14 days are considered immunocompromised.

• Such patients should not receive live attenuated vaccines; inactivated or killed vaccines are safe.

• Live vaccines can be administered once the child is off immunosuppressive medications for at least 4 weeks.

• Administration of some vaccines, e.g., Hepatitis B, Measles-Mumps-Rubella or Meningococcal vaccines may rarely precipitate a relapse.


Immunization contd.

Pneumococcal Vaccines:

• Children below 2 yr of

age

2-4 doses of the heptavalent conjugate

pneumococcal vaccine

• Previously

unimmunized children

between 2-5 yr

A priming dose of the conjugate vaccine

should be followed 8 weeks later, by the 23-

valent polysaccharide vaccine.

• Children older than 5 yrOnly a single dose of the polysaccharide

vaccine.

Revaccination after 5 yr is considered for children (<10-yr-old) with active

nephrotic syndrome.

Varicella vaccine: Patients in remission and not on immunosuppressive therapy should

receive the varicella vaccine.

12 months and 12 yr of age – Single dose

13 yr or older – 2 doses separated by an interval of at least 4 weeks


Thromboembolism• Incidence 2-5%. More common in steroid resistant nephrotic

syndrome than steroid sensitive nephrotic syndrome.

• Venous thrombosis more common than arterial thrombosis.

• Predisposing factors: Urinary loss of Anti-Thrombin III, protein C, protein S; elevated Fibrinogen levels; volume depletion caused by diuretic therapy or diarrhea; immobilization.

• Renal vein thrombosis: Oligoanuria, hematuria, flank pain

• Saggittal sinus & cortical vein thrombosis: Convulsions, vomiting, altered sensorium and neurologic deficits.

• Femoral vein thrombosis, mesenteric vein thrombosis & deep vein thrombosis leading to pulmonary embolism can occur.

• Diagnosis: USG, Doppler studies and MRI.


Thromboembolism contd.• Management: Correction of dehydration, IV Heparin or SC

LMWH initially followed by oral-anti coagulants on the long term.

• Prevention: Avoid prolonged bed rest, maintenance of hydration, avoid injudicious use of diuretics

• Prophylactic anti-coagulant therapy such as low dose aspirin is not routinely recommended in nephrotic syndrome.

• Prophylactic anti-coagulant therapy can be given in the setting of:

• Previous history of thromboembolism

• An underlying hypercoagulation disorder other than nephrotic syndrome

• Presence of a central venous catheterDr Naveen Kumar Cheri


Hyperlipidemia

• Hyperlipidemia in nephrotic syndrome is characterized by elevated LDL, IDL, VLDL and Lipoprotein (a). HDL levels are reduced or unchanged. LDL/HDL ratio is increased.

• Mechanism: Hypoalbuminemia upregulates HMG-CoA reductase and downregulates lipoprotein lipase, VLDLreceptor and hepatic triglyceride lipase.

• In steroid sensitive nephrotic syndrome, hyperlipidemia is associated with relapse and lipid levels fall once remission is achieved.


Hyperlipidemia contd.• Patients with steroid resistant nephrotic syndrome

with frequent relapses and persistent proteinuria tend to have continued dyslipidemia and require drug therapy.

• Management:

Dietary fat should be restricted to <30% of calories. Saturated fat should be <10% of total calorie intake. Dietary cholesterol intake should be <300 mg/day.

When dietary modification is not effective, HMG-CoA reductase inhibitors (Atrovastatin) can be used.


Hypertension• Hypertension may be present at the onset or may

appear late due to steroid toxicity.

• Goal is to maintain blood pressure to <90th percentile of normal.

• Management:

Low salt diet, exercise, weight reduction.

ACE inhibitors and Angiotensin Receptor Blockers are the first line agents as they also reduce proteinuria.

Calcium channel blockers and β2 agonists can also be used.


Education of parent• Parents should be provided information about the

course, complications & outcome of the disease.

• Urine examination with dipstick or by boiling method at home. Daily during relapse or during periods of infection. Once or twice a week during remission.

• Maintain a dairy containing information about proteinuria, medications & infections.

• Ensure that the child participates in all activities and sports during periods of remission. No restrictions are imposed.

• As infections constitute significant proportion of morbidity, need for appropriate immunization should be stressed.


CONGENITAL NEPHROTIC SYNDROME


Onset with in 3 months of lifeCongenital nephrotic

syndrome

Onset after 3 months of life

but before 1 year of life Infantile nephrotic syndrome

Onset after 1 year of lifeChildhood nephrotic

syndrome

Most common varieties of congenital nephroticsyndrome are:

• Finnish type due to Nephrin gene (NPHS1) mutation &

• Diffuse mesangial sclerosis due to Wilms tumor suppressor 1 (WT1) gene mutation.


PRIMARY CONGENITAL

NEPHROTIC SYNDROME

SECONDARY

CONGENITAL

NEPHROTIC SYNDROME

MALFORMATIONS &

SYNDROMES

• Nephrin (NPHS1) gene

mutation - Finnish type

• Podocin (NPHS2) gene

mutation

• Phospholipase C Epsilon-

1 (PLCE 1 - NPHS3)

gene mutation

• Infections (Congenital

Syphilis, Toxoplasmosis,

Rubella, CMV, Hepatitis

B, HIV & Malaria)

• SLE

• Neonatal antibodies

against neutral

endopeptidase

• WT1 gene mutation:

Denys-Drash syndrome,

Fraiser syndrome, WAGR

or isolated nephrotic

syndrome

• Laminin Beta 2 (LAM-β2)

mutation: Pierson

syndrome or isolated

nephrotic syndrome

• LMX1β gene mutation:

Nail-Patella Syndrome

• Galloway Mowat

syndrome

Etiology of congenital nephroticsyndrome


Clinical features• Proteinuria starts in-utero

• Born premature with large placenta (Weight of placenta >25% of birth weight of the baby)

• Edema soon after birth, abdominal distension, umbilical hernia, wide cranial sutures and fontanelle

• Failure to thrive, delayed development, hypothyroidism, repeated infections, spontaneous vascular thrombosis

• Prone for both hypotension and hypertension

• Galloway Mowat syndrome: Hiatal hernia, microcephaly, psychomotor retardation, hypotonia and seizures.

• Pierson syndrome: Microcoria

• Denys Drash syndrome: Ambiguous genitalia


Investigations• Nephrotic range proteinuria

• Low serum albumin

• Elevated TSH

• Dyslipidemia (Elevated triglycerides, elevated LDLcholesterol & low HDLcholesterol)

• Deranged renal function is seen beyond infancy

• Typical features are seen in renal biopsy done at 3-8 months of age

• USG findings depend on the age. (Kidney size is normal and corticomedullarydifferentiation is intact till 2 months of age)

• TORCH serology to detect congenital infections

Prenatal Diagnosis:

• Prenatal genetic testing by amniocentesis or chorionic villous biopsy to detect mutations

• Elevated AFP in amniotic fluid


Management• Goals: To provide good nutrition, control edema, prevent

thrombosis, prevent infection and allow the child to reach weight (9Kg) suitable for renal transplantation.

• Immunosupression has no role in the management of congenital nephrotic syndrome.There may be response to appropriate antimicrobial therapy for congenital syphilis and toxoplasmosis.

• Nutritional support:

• Calories 130 kc/kg/day

• Proteins 4 g/kg/day

• Vitamin D2 400 IU/day

• Vitamin E 2.5 - 3.0 mg/day

• Magesium40-60 mg/day in the absence of renal

failure

• Calcium

500 mg/day for <6 months

750 mg/day for 6-12 months

1000 mg/day for >12 months Dr Naveen Kumar CheriS.V. Medical College, Tirupati

Management contd.• Aggressive control of edema: By usage of loop and thiazide

diuretics. Albumin infusion (3 to 4 g/kg/day) with Furosemide 0.5 mg/kg/day may be needed for refractory edema.

• Thyroxine supplements: Thyroxine (6.25-12.5 μg/day) adjusted to TSH levels to control clinical or subclinical hypothyroidism

• Reduction of proteinuria:

o ACE inhibitors: Captopril 3-4 mg/kg/day or Enalapril 0.2-0.5 mg/kg/day

o Indomethacin: 1-2 mg/kg/day

o Unilateral nephrectomy

o Bilateral nephrectomy with continuous peritoneal dialysis


Management contd.• Anticoagulant therapy: Low dose Aspirin or Dipyridamole

and Warfarin to keep Partial Thromboplastin Time (PTT) at 20% to 30% of normal.

• Control of infections: Prophylactic use of antibiotics is not required but even minor infections need to be treated promptly.

• Renal transplantation: Done once the child reaches 9 Kg of weight.

Recurrence in transplanted kidney may respond to Steroids, Cyclophosphamide, Plasma Exchange or Rituximab (Anti-CD20).

Prognosis: Patient survival after 5 years is >90%. Graft survival after 5 years is >80%.

Due to the risk of chronic allograft nephropathy, second transplantation is inevitable when these patients become young adults.


References:• Nelson Textbook of Pediatrics – 19th edition

• IAPTextbook of Pediatrics – 5th Edition

• Indian Society of Pediatric Nephrology - Guidelines on the management of steroid sensitive nephroticsyndrome 2008

• Indian Society of Pediatric Nephrology - Guidelines on the management of steroid resistant nephroticsyndrome 2009

• Principles and Practice of Pediatric Nephrology by M. Vijaykumar, B.R. Nammalwar – 2nd Edition

• Pediatric Nephrology – R.N. Srivastava & Arvind Bagga– 5th Edition


Thank you


management of nephrotic syndrome

Health & Medicine