Nephrotic Syndrome

• Etiology1. Idiopathic nephrotic syndrome (90%)– Minimal change disease (85%)– Focal segmental glomerulosclerosis (10%)– Mesangial proliferation (5%)

2. Glomerulonephritis; Membranous nephropathy; and membranoproliferative glomerulonephritis (10%)

Idiopathic Nephrotic Syndrome

• Approximately 90% of children with nephrotic syndrome have idiopathic nephrotic syndrome

• Male:female ratio (2:1) • Peak incidence: 2 – 6 yr• The initial episode and subsequent relapses

may follow minor infections and, occasionally, reactions to insect bites, bee stings, or poison ivy.

Idiopathic Nephrotic SyndromeMinimal Change Disease

Mesangial Proliferation

Focal segmental

glomerulosclerosis

Light Microscopy

Normal or minimal increase in mesangial cells and matrix

Diffuse increase in mesangial cells and matrix

Mesangial proliferation and segmental scarring

Idiopathic Nephrotic SyndromeMinimal Change Disease

Mesangial Proliferation

Focal segmental

glomerulosclerosis

Immunofluorescence

Negative Trace to 1+ mesangial IgM and/or IgA staining

IgM and C3 staining in the areas of segmental sclerosis

Idiopathic Nephrotic SyndromeMinimal Change Disease

Mesangial Proliferation

Focal segmental

glomerulosclerosis

Electron Microscopy

Effacement of epithelial foot processes

Increased numbers of mesangial cells and matrix; effacement of the epithelial cell foot processes

Segmental scarring of the glomerular tuft with obliteration of the glomerular capillary lumen

Idiopathic Nephrotic SyndromeMinimal Change Disease

Mesangial Proliferation

Focal segmental

glomerulosclerosis

Steroid response

>95% 50% 20%

Characteristics

• Proteinuria– >3.5 g/24 hr in adults– >40 mg/m2/hr in children– Spot urine protein to creatinine ratio >2.0

• Hypoalbuminemia– <2.5 g/dl

• Edema• Hyperlipidemia

Proteinuria

• Results from increased permeability of glomerular basement membrane (GBM) to plasma protein

Degrees of proteinuria• Mild less than

0.5g/m2/day• Moderate 0.5 –

2g/m2/day• Severe more than

2g/m2/day

Types of proteinuria• Selective proteinuria:

where proteins of low molecular weight .such as albumin, are excreted more readily than protein of HMW

• Non selective :• LMW+HMW are lost

in urine

Hypoalbuminemia

• Due to hyperproteinuria– Mainly albumin

Edema

• plasma oncotic pressure transudation of fluid from the intravascular compartment to the interstitial space

• intravascular volume renal perfusion (activates RAAS) tubular reabsorption of sodium water retention

Hyperlipidemia

• Hypoalbuminemia stimulates generalized hepatic protein synthesis

• Diminished catabolism of lipids

Complications

• Infection (major)– Bacterial peritonitis – most frequent– Sepsis– Pneumonia– Cellulitis– UTI

• Commonly caused by S. pneumoniae and E.coli

Complications

• All children with nephrotic syndrome should receive polyvalent pneumococcal vaccine (if not previously immunized), ideally administered when the child is in remission and off of daily prednisone therapy.

• Nonimmune nephrotic children in relapse exposed to varicella should receive varicella zoster immune globulin (VZIG) within 72 hr of exposure.

Complications

• Thromboembolic events– increased prothrombotic factors (fibrinogen,

thrombocytosis, hemoconcentration, relative immobilization)

– decreased fibrinolytic factors (urinary losses of antithrombin ill, proteins C and S)

• Prophylaxis is not indicated

Prognosis

• Steroid-responsive nephrotic syndrome– Repeated relapses– Decrease in frequency as the child grows older

Prognosis

• Children who respond to steroids rapidly and those who have no relapses during the first 6 mo after diagnosis tend to follow an infrequently relapsing course

Prognosis

• Steroid-resistant nephrotic syndrome– most often caused by focal segmental

glomerulosclerosis– Generally have a much poorer prognosis

Prognosis

• Recurrent nephrotic syndrome develops in 30-50% of transplant recipients with focal segmental glomerulosclerosis.

Prevention

• Cannot be totally prevented– Usually follows minor infections, reactions to

insect bites, bee stings, or poison ivy

BioPsychoSocial

• It is important to indicate to the family that:1. The child with steroid-responsive nephrotic

syndrome will not develop chronic renal failure2. The disease is generally not hereditary, and 3. The child (in the absence of prolonged

cyclophosphamide therapy) will remain fertile.

BioPsychoSocial

• To minimize the psychological effects of the condition, the physician should emphasize that the child should be considered normal when in remission and may have unrestricted diet and activity, without the need for urine testing for protein.

BioPsychoSocial

• Affected children may attend school and participate in physical activities as tolerated.