Nephrotic Syndrome

Ron Christian Neil T. Rodriguez, MD

1st Year Pedia Resident
Nephrotic Syndrome

 Heavy proteinuria (>3.5g/24 hrs)

 Urine protein:creatinine ratio >2
 Triad: Hypoalbuminemia (</= 2.5g/dL), Edema, Hyperlipidemia (cholesterol >
200 mg/dL)
 Two types:
 Idiopathic/Primary – Majority of cases
 Secondary – caused by other diseases such as HSP, SLE, malignancy, and infections

Reference: Nelson’s Book of Pediatrics, 21st Ed

Pathology

Podocyte
effacement, Increased
Immune and non- Massive
decreased number permeability of
immune insults to proteinuria,
of functional the glomerular
podocytes hypoalbuminemia
podocytes, altered capillary wall
slit diaphtagm

Reference: Nelson’s Book of Pediatrics, 21st Ed

Clinical Complications of Nephrotic
Syndrome
 Edema – most common; two hypothesis: Underfill and Overfill
 Goal of therapy is to gradually reduce edema with judicious use of diuretics,
sodium restriction, and cautious use of intravenous albumin infusion
 Hyperlipidemia
 Increased susceptibility to infections
 Hypercoagulability

Reference: Nelson’s Book of Pediatrics, 21st Ed

Idiopathic Nephrotic Syndrome

 Most common type of nephrotic syndrome; also called primary nephrotic

syndrome
 No known direct cause
 Male>Female
 Types:
 Minimal change disease
 Mesangial proliferation
 Focal segmental glomerulonephritis (FSGN)
 Membranous nephropathy
 Membranoproliferative glomerulonephritis (MPGN)

Reference: Nelson’s Book of Pediatrics, 21st Ed

Minimal Change Disease

 Most common (85% of idiopathic); most common in boys than girls (2:1)
 Appears between ages 2-6 years old
 Light microscopy: Normal or minimal increase in mesangial cells and matrix
 Electron microscopy: Effacement of epithelial cell foot processes
 Clinical manifestations: Mild edema (periorbital and pedal)  generalized
edema (ascites, pleural effusion, genital edema); anorexia, irritability,
abdominal pain, diarrhea
 NO HYPERTENSION AND GROSS HEMATURIA
 Responds well to corticosteroid therapy

Reference: Nelson’s Book of Pediatrics, 21st Ed

Mesangial Proliferation

 Least common idiopathic nephrotic syndrome (5% of cases)

 Light microscopy: Diffuse increase in mesangial cells and matrix
 Immunofluorescence: Mesangial IgM and/or IgA staining
 Electron microscopy: Increased numbers of mesangial cells and matrix as well
as effacement of the epithelial foot processes
 50% responds to corticosteroid therapy

Reference: Nelson’s Book of Pediatrics, 21st Ed

Focal Segmental Glomerulosclerosis
(FSGS)
 Focal (present only in a proportion of the glomeruli) and segmental (localized
to >/= 1 interglomerular tufts)
 Accounts for 10% of nephrotic syndrome cases
 Light microscopy: Mesangial cell proliferation and segmental scarring
 Immunofluorescence: IgM and C3 staining in areas of segmental sclerosis
 Electron microscopy: segmental scarring of the glomerular tufts with
obliteration of the glomerular capillary lumen
 Only 20% respond to prednisone, with others progressing to end-stage renal
disease

Reference: Nelson’s Book of Pediatrics, 21st Ed

Secondary Nephrotic Syndrome

 May be secondary to membranous nephropathy, membranoproliferative

glomerulonephritis, postinfectious glomerulonephritis, lupus nephritis, and
Henoch Schonlein purpura
 Age > 8 years, with hypertension, hematuria, renal dysfunction, extrarenal
symptoms (rash, arthalgias, fever), or dec serum complement levels

Reference: Nelson’s Book of Pediatrics, 21st Ed

Congenital Nephrotic Syndrome

 Nephrotic syndrome appearing upon birth to first 3 months of life

 Primary – inherited from autosomal recessive disorders
 At birth: Edema, Massive proteinuria, Delivered with an enlarged placenta (>25% of
infant’s weight)
 Prenatal: Elevated maternal and amniotic alpha-fetoprotein levels
 Tx: Albumin and diuretics, nephrectomy, ACE inhibitors, and/or indomethacin
 Secondary – caused by other factors (ex. Infections)
 Tx: Treat underlying cause

Reference: Nelson’s Book of Pediatrics, 21st Ed

Diagnosing Nephrotic Syndrome

 Urinalysis – confirmatory test; 3+ to 4+ proteinuria, microscopic hematuria,

 First morning urine protein:creatinine ratio - urine:protein ratio >2.0
 Serum electrolytes
 BUN and Creatinine - normal creatinine, elevated if with decreased renal
perfusion
 Albumin - <2.5 g/dL
 Cholesterol and triglyceride levels – both elevated

Reference: Nelson’s Book of Pediatrics, 21st Ed

Diagnosing Nephrotic Syndrome

 To rule out secondary causes of nephrotic syndrome (children >/= 10 yrs)

 Complement C3 – usually normal
 ANA
 Serum dsDNA
 Hepatic profile
 HIV (in high risk populations)
 Renal biopsy – NOT routinely done if clinical picture is likely MCD

Reference: Nelson’s Book of Pediatrics, 21st Ed

Treatment

 First episode and with mild to moderate edema – often managed as outpatients
 If with MCD, do renal biopsy first, before initiating treatment
 Corticosteroids: Prednisone/Prednisolone x single daily dose (2 mkday) for 4-6
weeks, followed by alternate-day prednisone for 8 weeks to 5 months
 Edema: Hospitalization required. Do fluid restriction, sodium restriction
(<1,500 mg daily), diuretics (usually furosemide), albumin infusion (with
severe generalized edema)
 Exercise extreme caution in furosemide  aggressive diuresis = intravascular
volume depletion  increased risk of ARF and intravascular thrombosis
 Rapid albumin infusion can lead to volume overload, hypertension, heart failure,
and pulmonary edema

Reference: Nelson’s Book of Pediatrics, 21st Ed

Treatment

 Dyslipidemia: Low-fat diet (limited to <30% or <300 mg/dL dietary fat intake,
10% saturated fat intake)
 Infections: Blood culture drawn prior to start of antibiotics. Antibiotics should
be broad enough to cover Pneumococcus and Gram-negative bacteria, which
is usually 3rd-Generation cephalosporin
 Thromboembolism: evaluated first by appropriate imaging studies; heparin,
LMW heparin, warfarin are choices of therapy
 Obesity and Growth: dietary counseling

Reference: Nelson’s Book of Pediatrics, 21st Ed

Relapse of Nephrotic Syndrome

 Urine protein:creatinine ratio of >2 or >/= 3+ protein on urine dipstick for 3

consecutive days
 Common in younger children, often triggered by upper respiratory and GI
infections
 Treated similarly as initial episodes, but with shortened prednisone courses
 Initially treated with daily high dose prednisone until remission, then tapered to
alternate day therapy (varies on frequency of relapses)

Reference: Nelson’s Book of Pediatrics, 21st Ed

Steroid Resistance

 Failure to achieve remission over 8 weeks after corticosteroid therapy

 Requires further work-ups: kidney biopsy, evaluation of kidney function, urine
protein quantation, dipstick testing
 Usually caused by FSGS (80% of cases), MCD, or membranoproliferative
glomerulonephritis
 Associated with 50% risk for end-stage renal disease within 5 years if
remission is not achieved

Reference: Nelson’s Book of Pediatrics, 21st Ed

Alternatives to Corticosteroids

 Cyclophosphamide – prolongs duration of remission, reduces relapses

 Side effects: neutropenia, disseminated varicella, hemorrhagic cystitis, alopecia,
sterility, increase in risk of malignancy
 Given 2 mg/kg OD for 8-12 weeks with alternate day prednisone therapy
 WBC must be monitored; if <5,000/mm3, discontinue drug
 Calcineurin inhibitors (cyclosporine, tacrolimus) – for steroid resistant
nephrotic syndrome
 Side effects: hypertension, nephrotoxicity, hirsutism, gingival hyperplasia

Reference: Nelson’s Book of Pediatrics, 21st Ed

Immunizations

 Pneumococcal and Influenza vaccinations annually to both patient and their

contacts
 Defer vaccination with live vaccines if prednisone dose is below either 1
mg/kg daily or 2 mg/kg on alternate day therapy, or treated with
cyclophosphamide or cyclosporine
 Varicella immunoglobulin may be given if with close contact to varicella
infected individuals

Reference: Nelson’s Book of Pediatrics, 21st Ed

Prognosis

 Steroid responsive nephrotic syndrome may have repeated relapses but

decreases in frequency as children increase in age
 Steroid resistant nephrotic syndrome have a poorer prognosis
 30-50% of FSGS patients who receive kidney transplants have recurrent
nephrotic syndrome

Reference: Nelson’s Book of Pediatrics, 21st Ed

Thank you!