Acute Nephritic Syndrome

Acute Poststreptococcal Glomerulonephritis (APSGN)

• APSGN is the most frequent presentation of Acute Nephritic Syndrome (ANS)
• ANS presents with edema, hematuria, and hypertension with or without oliguria
• Approximately 95% of clinical cases have at least 2 manifestations, and 40% have the full-blown acute nephritic syndrome

Laboratory Studies

• Evidence of preceding streptococcal infection:
  • Antibody titers to extracellular products of streptococci are positive in more than 95% of patients with pharyngitis and 80% of patients with skin infections
  • Antistreptolysin (ASO), antinicotinamide adenine dinucleotidase (anti-NAD), antihyaluronidase (AHase), and anti-DNAse B are commonly positive after pharyngitis
  • Antibody titers are elevated at 1 week, peak at 1 month, and fall toward preinfection levels after several months
• Elevated BUN and creatinine values
• Serologic findings: low serum complement levels
• Urinalysis: results are always abnormal
• Imaging Studies: chest radiographs may show findings of congestive heart failure

Treatment of Relapses

• For infrequent relapses, steroids are resumed, although for a shorter duration than treatment during initial presentation
• Prednisone, 2 mg/kg/d (60 mg/m2/d), is given as a single morning dose until the patient has been free of proteinuria for at least 3 days
• Following remission of proteinuria, prednisone is reduced to 1.5 mg/kg (40 mg/m2) given as a single dose on alternate days for 4 weeks

Frequently Relapsing, Steroid-Dependent Disease, and Steroid-Resistant Disease

• Frequently-relapsing nephrotic syndrome (FRNS) is defined as steroid-sensitive nephrotic syndrome (SSNS) with 2 or more relapses within 6 months or three times or more within 1 year period
• Steroid-dependent nephrotic syndrome (SDNS) is defined as SSNS with 2 or more consecutive relapses during tapering or within 14 days of stopping steroids
• For FRNS and SDNS, prednisone treatment is prescribed at 2 mg/kg/d (60 mg/m2/d) as a single morning dose until the patient has been free of proteinuria for at least 3 days
• Steroid-resistant disease: children who continue to have proteinuria (2+ or greater) after 8 weeks of steroid therapy are considered steroid-resistant, and a diagnostic renal biopsy should be performed

Complications

• Acute phase:
  • Congestive heart failure
  • Azotemia
  • Early death secondary to congestive heart failure and azotemia
• Chronic phase:
  • Nephrotic-range proteinuria
  • Chronic renal insufficiency and end-stage renal disease

Management of APSGN

• Medical Care:
  • Symptomatic therapy is recommended for patients with acute poststreptococcal glomerulonephritis (APSGN)
  • The major goal is to control edema and blood pressure
  • During the acute phase of the disease, restrict salt and water
  • For hypertension not controlled by diuretics, usually calcium channel blockers or angiotensin-converting enzyme inhibitors are useful
• Prognosis:
  • The short-term prognosis of APSG in children is favorable
  • Fewer than 2% of children progress to end-stage renal disease
  • Hypertension and gross hematuria usually resolve over several weeks, although microscopic hematuria may persist for several years
  • Proteinuria resolves over several months

Nephrotic Syndrome

• Definition:
  • Pediatric nephrotic syndrome is defined by the presence of nephrotic-range proteinuria, hypoalbuminemia, hyperlipidemia, and edema
  • Nephrotic-range proteinuria in children is protein excretion of more than 40 mg/m2/h
  • A urine protein/creatinine value of more than 2 mg/mg indicates nephrotic range proteinuria
• Proteinuria:
  • The hallmark of NS is massive proteinuria
  • The cause of proteinuria is glomerular structural damage
• Hypoalbuminemia:
  • Excessive loss of plasma protein into urine
  • Decreased plasma oncotic pressure leads to transudation of fluid into interstitium
• Hypercholesterolemia:
  • Increased hepatic synthesis due to hypoalbuminemia and decreased oncotic pressure
  • Abnormalities in regulatory enzymes, such as lipoprotein lipase
• Edema:
  • Decreased plasma oncotic pressure leads to transudation of fluid into interstitium

Etiology

• Primary nephrotic syndrome (PNS) is associated with glomerular diseases intrinsic to the kidney and not related to systemic causes
• Secondary causes account for < 10% of childhood cases
• Examples of secondary causes:
  • Metabolic: as Diabetes mellitus
  • Immunologic: Henoch-Schönlein purpura, SLE
  • Drug-related: Interferon alfa, NSAIDs
  • Neoplastic: Leukemia, Lymphomas
  • Allergic: Antitoxins, Insect stings, Snake venoms
  • Bacterial: Infective endocarditis
  • Viral: Epstein-Barr virus infection, Hepatitis B and C

Clinical Manifestations

• Edema is the presenting symptom in about 95% of children with nephrotic syndrome
• Anorexia, irritability, fatigue, abdominal discomfort, and diarrhea are common
• Respiratory distress can occur, due to either massive ascites and thoracic compression, frank pulmonary edema, or effusions
• Children with nephrotic syndrome occasionally present with gross hematuria
• Hypertension can be present

Laboratory Investigations

• Laboratory tests should confirm:
  • Nephrotic-range proteinuria
  • Hypoalbuminemia
  • Hyperlipidemia