y Nephrotic syndrome is primarily a pediatric disorder
and is 15 times more common in children than adults.
y The incidence is 2 3/100,000 children per year, and the
vast majority of affected children will have steroidsensitive minimal change disease. O2
Slide 2 O2
y The characteristic features of nephrotic syndrome are: y heavy proteinuria (>3.5?g/24?hr in adults or 40?mg/m2 /hr in children) y hypoalbuminemia (<2.5?g/dL) y Edema y hyperlipidemia
y Most children (90%) with nephrotic syndrome have a
form of the idiopathic nephrotic syndrome.
y Causes of idiopathic nephrotic syndrome include:
y minimal change disease (85%) y mesangial proliferation (5%) y focal segmental glomerulosclerosis (10%).
y The remaining 10% of children with nephrotic syndrome
have secondary nephrotic syndrome related to glomerular diseases such as:
membranous nephropathy or membranoproliferative glomerulonephritis
y The underlying abnormality in nephrotic syndrome is
an increase in permeability of the glomerular capillary wall
which leads to massive proteinuria and O3 hypoalbuminemia.
Slide 7 O3
The cause of the increased permeability is not well understood. In minimal change disease, it is possible that T-cell dysfunction leads to alteration of cytokines, which causes a loss of negatively charged glycoproteins within the glomerular capillary wall.
y The mechanism of edema formation in nephrotic syndrome is
In most instances: urinary protein loss leads tohypoalbuminemia which causes a decrease in the plasma oncotic pressure and transudation of fluid from the intravascular compartment to the interstitial space. The reduction in intravascular volume decreases renal perfusion pressure, activating the renin-angiotensin-aldosterone system, which stimulates tubular reabsorption of sodium.
Because of the decreased plasma oncotic pressure. exacerbating the edema.The reduced intravascular volume also stimulates the release of antidiuretic hormone.
. fluid shifts into the interstitial space. which enhances the reabsorption of water in the collecting duct.
y focal segmental glomerulosclerosis.
y Idiopathic nephrotic syndrome includes three
y minimal change disease y mesangial proliferation.y Approximately 90% of children with nephrotic
syndrome have idiopathic nephrotic syndrome.
y More than 95% ofchildren with minimal change
disease respond to corticosteroid therapy.
y Findings on immunofluorescence microscopy are y typically negative.
y Minimal change disease (85% of total cases)the
glomeruli appear normal or show a minimal increase in mesangial cells and matrix. and electron microscopy simply reveals effacement of the epithelial cell foot processes.
y Immunofluorescence microscopymay reveal trace to 1+
mesangial IgM and/or IgA staining.
y Mesangial proliferation (5% of total cases) is
characterized by a diffuse increase in mesangial cells and matrix on light microscopy.
y Electron microscopy reveals increased numbers of
mesangial cells and matrix as well as effacement of the epithelial cell foot processes.
y Approximately 50% of patients with this histologic
lesion respond to corticosteroid therapy.
y Electron microscopy shows segmental scarring of the
glomerular tuft with obliteration of the glomerular capillary lumen.
y Immunofluorescence microscopy shows IgM and C3
staining in the areas of segmental sclerosis.y Focal segmental glomerulosclerosis (10% of total
cases). glomeruli show mesangial proliferation and segmental scarring on light microscopy.
and leads to end-stage renal failure in most patients.
y The disease is frequently progressive.
vesicoureteral reflux. and intravenous heroin abuse.
y Approximately 20% of patients with focal segmental
glomerulosclerosis respond to prednisone.y A similar lesion may be seen with HIV infection.
involving all glomeruli.
y The idiopathic nephrotic syndrome is more common
in males than in females (2:1) and most commonly appears between the ages of 2 and 6 yr.
y It has been reported as early as 6 mo of age and
. or poison ivy.y The initial episode and subsequent relapses may follow
minor infections and. reactions to insect bites.
y Children usually present with mild edema. which is
initially noted around the eyes and in the lower extremities. occasionally. bee stings.
y Anorexia. with the development
of ascites. abdominal pain. irritability.y Nephrotic syndrome may initially be misdiagnosed as
an allergic disorder because of the periorbital swelling that decreases throughout the day. and genital edema. and diarrhea are
y Hypertension and gross hematuria are uncommon. pleural effusions.
y The edema becomes generalized.
and y protein malnutrition. y congestive heart failure.
y Includes :
y Protein-losing enteropathy. y acute or chronic glomerulonephritis. y hepatic failure.
y The urinalysis reveals 3+ or 4+ proteinuria y Microscopic hematuria may be present in 20% of
y Urinary protein excretion exceeds 3.5?g/24?hr in adults
and 40?mg/m2 /hr in children
may be increased because of diminished renal perfusion resulting from contraction of the intravascular volume.0 y The serum creatinine value is usually normal.y Spot urine protein to creatinine ratio exceeds 2.
y Renal biopsy is not required for diagnosis in most
.y The serum albumin level is generally less than
y Serum cholesterol and triglyceride levels are elevated y C3 and C4 levels are normal.
and HenochSchönlein purpura nephritis may all have a nephrotic component.
y Membranous nephropathy.Secondary Nephrotic Syndrome
y Nephrotic syndrome also occurs as a secondary feature
of many forms of glomerular disease. membranoproliferative
glomerulonephritis. lupus nephritis. postinfectious glomerulonephritis.
Henoch-Schönlein purpura nephritis
etc.y In general. secondary nephrotic syndrome should be
suspected in patients with: y age > 8 yr y Hypertension y Hematuria y Renal dysfunction y Extrarenal symptomatology (rash. arthralgias. or y depressed serum complement levels.).
y Acute Poststreptococcal Glomerulonephritis y This disease is a classic example of the acute nephritic
syndrome characterized by :
y Sudden onset of gross hematuria y Edema y Hypertension y Renal insufficiency.
. Etiology and Epidemiology
y Acute poststreptococcal glomerulonephritis follows
infection of the throat or skin by certain nephritogenic strains of group A ß-hemolytic streptococci..
y The factors that allow only certain strains of
streptococci to be nephritogenic remain unclear.
y Poststreptococcal glomerulonephritis commonly
follows streptococcal pharyngitis during cold weather months and streptococcal skin infections or pyoderma during warm weather months.
y Epidemics of nephritis have been described in
association with both throat (serotype 12) and skin (serotype 49) infections. this disease is most commonly sporadic.
. all glomeruli appear enlarged
and relatively bloodless and show diffuse mesangial cell proliferation with an increase in mesangial matrix.
y On light microscopy. the
kidneys appear symmetrically enlarged.Pathology
y As in most forms of acute glomerulonephritis.
y Although morphologic studies and a depression in the
serum complement (C3) level strongly suggest that post-streptococcal glomerulonephritis is mediated by immune complexes
y The precise mechanisms by which nephritogenic
streptococci induce complex formation remain to be determined..
y Poststreptococcal glomerulonephritis is most common
in children aged 5 12 yr and uncommon before the age of 3 yr. y The typical patient develops an acute nephritic y syndrome 1 2 wk after an antecedent streptococcal pharyngitis or 3 6 wk after a streptococcal pyoderma.
y Depending on the severity of renal involvement.
patients may develop various degrees of :
y edema y hypertension y oliguria
.y The severity of renal involvement varies from
asymptomatic microscopic hematuria with normal renal function to acute renal failure.
y Encephalopathy may also result directly from the toxic
effects of the streptococcal bacteria on the central nervous system.
.y Patients may develop encephalopathy and/or heart
failure owing to hypertension or hypervolemia.
y Edema typically results from salt and water retention
and nephrotic syndrome may develop in 10 20% of cases.
y Specific symptoms such as: y Malaise y Lethargy y Abdominal or flank pain y Fever
y Acute subglottic edema and airway compromise y The acute phase generally resolves within 6 8 wk. y Urinary protein excretion and hypertension usually
normalize by 4 6 wk after onset.
y Persistent microscopic hematuria may persist for 1 2 yr
after the initial presentation
proteinuria. and polymorphonuclear leukocytes.Diagnosis
y Urinalysis demonstrates red blood cells (RBCs).
y A mild normochromic anemia may be present from
hemodilution and low-grade hemolysis.
y The serum C3 level is usually reduced in the acute
phase and returns to normal 6 8 wk after onset
frequently in association with RBC casts.
y A positive throat culture report may support the
diagnosis or may simply represent the carrier state.
.y Confirmation of the diagnosis requires clear evidence
of invasive streptococcal infection.
y A rising antibody titer to streptococcal antigen(s)
confirms a recent streptococcal infection. I
y The antistreptolysin O titer is commonly elevated after
a pharyngeal infection but rarely increases after streptococcal skin infections
y The clinical diagnosis of poststreptococcal
glomerulonephritis is quite likely in a child presenting with acute nephritic syndrome. evidence of recent streptococcal infection. and a low C3 level.
y It is important to consider other diagnoses such as
systemic lupus erythematosus and an acute exacerbation of chronic glomerulonephritis
y Renal biopsy should be considered only in the presence
y acute renal failure y nephrotic syndrome y absence of evidence for streptococcal infection y or normal complement levels
90%) Subacute bacterial endocarditis (90%) Visceral abscess "Shunt" nephritis (90%) Cryoglobulinemia (58%)
y Low serum complement level y Systemic diseases
y y y y y
SLE (focal. 75%. diffuse.
Type I (50-80%).y Renal diseases
Acute postinfectious glomerulonephritis (>90%) MPGN . type 2 (80-90%)
y Normal serum complement level y Systemic diseases
y y y y y
Polyarteritis nodosa group Hypersensitivity vasculitis Wegener granulomatosis HSP Goodpasture syndrome
y Renal diseases
y y y y y
IgA (or IgG-IgA) nephropathy Idiopathic rapidly progressive glomerulonephritis (RPGN) Anti-glomerular basement membrane (GBM) disease Negative immunofluorescence findings Immune complex disease
y Other potential complications include heart failure. and uremia.
. seizures. hypocalcemia. hyperphosphatemia.
y Hypertension is seen in 60% of patients and may be
associated with hypertensive encephalopathy in 10% of cases.Complications
y Acute complications of this disease result primarily
from hypertension and acute renal dysfunction. acidosis.
y Family members of patients with acute
glomerulonephritis should be cultured for group A ßhemolytic streptococci and treated if culture positive.
y Early systemic antibiotic therapy for streptococcal
throat and skin infections does not eliminate the risk of glomerulonephritis.
y Management is directed at treating the acute effects of
renal insufficiency and hypertension..
y Although a 10-day course of systemic antibiotic
therapy with penicillin is recommended to limit the spread of the nephritogenic organisms. antibiotic therapy does not affect the natural history of glomerulonephritis.
diuresis. vasodilators.y Sodium restriction.
. or angiotensin-converting enzyme inhibitors are standard therapies used to treat hypertension. and pharmacotherapy
with calcium channel antagonists.
.2-0.2-1.5-2.0 mcg/kg/min y Labetolol 0.0 mkdose y Hydralazine 0.5-1.treatment:
y antibiotics y Penicillin V 50-100KU/kg/day x10 days y Erythromycin y sodium and fluid restriction (20cc/kg/day) y diuresis (Furosemide 1 mkdose) y correct hypertension y Nifedipine 0.5 mkday TID y Captopril 0.0 mkday TID y Sodium nitroprusside 0.25-0.
. and hypertension.
y Mortality in the acute stage can be avoided by
appropriate management of acute renal failure. Prognosis
y Complete recovery occurs in more than 95% of
children with acute poststreptococcal glomerulonephritis.
. cardiac failure.
y The acute phase may be severe and lead to glomerular
hyalinization and chronic renal insufficiency. the diagnosis of acute poststreptococcal
glomerulonephritis must be questioned in patients with chronic renal dysfunction because other diagnoses such as membranoproliferative glomerulonephritis may be present.
y Recurrences are extremely rare.
y aka Berger Nephropathy y most common chronic glomerular disease y predominance of IgA within mesangial deposits of the
glomerulus in the absence of systemic diseases y abN in the IgA immune system y linked to genetic abN (6q22-23)
y manifestations: y mild to moderate hypertension y edema y gross or microscopic hematuria y proteinuria y normal complement levels y elevated serum IgA level
y prognosis: y progressive kidney disease develops in 20-30%. 15-20 years after onset y poor prognostic indicators:
y y y
persistent hypertension diminished renal function heavy or prolonged proteinuria
y treatment: y blood pressure control y immunosuppressants y renal transplantation
y aka Alport Syndrome y caused by mutations in the genes coding for type IV
collagen y 85% are X-linked
y pathology: y mesangial proliferation and capillary wall thickening y tubular atrophy. interstitial inflammation and fibrosis y presence of foam cells
recurrent corneal erosions) leiomyomatosis
y manifestations: y asymptomatic microscopic hematuria y progressive proteinuria y extrarenal:
sensorineural hearing loss visual abnormalities (anterior lenticonus. macular flecks.
y prognosis: y progressive renal dysfunction occurs in 75% y treatment: y no specific treatment y careful management of hypertension. and electrolyte imbalance y dialysis y renal transplantation
involvement of the heart. and kidneys y common among adolescent females y occurs in 30-70% of all cases y WHO classification is based on:
y light microscopy y immunofluorescence y electron microscopy
. CNS. rash. weight loss.
hematologic abN.Lupus Nephritis
y SLE is characterized by fever. lungs. arthritis.
crescent formation y sclerosing lesions
y Class I y no histologic abN y Class II (mesangiopathy) y mesangial widening and hypercellularity y Class III (focal segmental LN) y mesangial deposits in all glomeruli y capillary wall necrosis.
sclerosis y necrosis y Class V (membranous LN) y pure membranous GN
y Class IV (diffuse proliferative LN) y most common. most severe form y massive mesangial and subendothelial deposits y crescent formation.
y acute nephritic syndrome.Lupus Nephritis
y manifestations: y asymptomatic hematuria or proteinuria. or y nephrotic syndrome
y diagnosis: y SLE criteria y high ANA titer y high anti-dsDNA titer y low serum C3 level y renal biopsy
should be performed in all patients with SLE
y treatment: y initial: Oral corticosteroids
Prednisone or Prednisolone 1-2 mkday BID or TID with gradual tapering for 4 to 6 months
y cytotoxic agents: y Cyclophosphamide y Azathioprine y IV corticosteroids (methylprednisolone) y plasmapheresis
hypertension. diabetes mellitus) y cytotoxic effects (malignancy.Lupus Nephritis
y prognosis: y renal failure is the most common cause of death among patients with SLE
y prolonged steroid use (growth retardation.
obesity. osteoporosis. infertility) y intercurrent infections y thromboses
y Henoch-Schönlein Purpura Nephritis
y aka anaphylactoid purpura y small vessel vasculitis with skin. abdominal y y y y
manifestations renal involvement in 40-60% immune complex formation similar clinical findings except ureteritis no controlled data on treatment protocols
y Polyarteritis nodosa y large vessel vasculitis with rash. arthralgia. anticoagulants. and nephritis y malignant hypertension and weight loss y renal involvement in 40-70%
y y y
capillary thrombosis fibrinoid necrosis capsular infiltration with crescent formation
y treatment: y supportive (steroids. cytotoxic agents) y antihypertensives