Christopher E. Keel, DO
Raju Thomas, MD, MHA, FACS
BASICS
DESCRIPTION
• Inflammation of the glomerulus mediated through humoral and cell-mediated immune mechanisms including immunoglobins, complement, and circulating T cells usually in response to an infection (typically streptococcal).
• The inflammation and immunologic response results in immune deposits in the glomerulus.
• Onset of symptoms is usually acute and includes oliguria, hypertension, hematuria, proteinuria, and renal impairment.
• Poststreptococcal acute GN is the onset of GN after a preceding group A β-hemolytic streptococcal infection, most commonly of the pharynx or skin.
– Most common glomerulonephritis affecting children.
• Synonym(s): Acute nephritic syndrome; Postinfectious glomerulonephritis.
EPIDEMIOLOGY
Incidence
• Poststreptococcal GN, the most common form, occurs most frequently in children between 2 and 10 yr of age but can occur at any age with a slight predominance of males over females
– 10% cases are in adults >40 yr of age
– 20/100,000/yr
Prevalence
• Most patients have a complete recovery, with resolution of clinical signs within a few weeks.
• The reported incidence of chronic renal insufficiency is 0–20%.
RISK FACTORS
• Occurs with infection of specific types of group A β-hemolytic streptococci, and these vary by site of infection. It occurs more commonly after pharyngitis than pyoderma:
– Pharyngitis is associated with types 1, 3, 4, 12, 25, 49 with the more common sporadic variety following infection with type 12.
– Pyoderma is associated with types 2, 49, 55, 57, 60.
Genetics
N/A
PATHOPHYSIOLOGY
• Tends to occur with impetigo in the late summer and with streptococcal pharyngitis in the winter.
• Note that cases of postinfective GN have also been reported from other bacteria (Pneumococcus, Staphylococcus, Meningococcus) and after viral infections (chickenpox, hepatitis).
• The exact mechanism of renal injury from poststreptococcal GN is not clear. IgG and C3 deposits are found at the capillary wall and in the mesangium. It is unclear if the inflammatory response is due to circulating immune complexes, complexes in situ, or both.
– The antigen or antigens activate the alternative complement pathway and result in renal damage.
ASSOCIATED CONDITIONS
• Pharyngitis
• Hematuria
• Hypertension
• UTI
• Acute renal failure
• Rapid decrease in renal function heralds the syndrome of rapidly progressive glomerulonephritis
GENERAL PREVENTION
No specific prevention measures; prompt treatment of strep infections may reduce risk
DIAGNOSIS
HISTORY
• Recent episode of pharyngitis or skin infection.
• Pharyngitis usually precedes renal disease by 8–14 days.
• Time between purulent skin disease and acute nephritis is widely variable.
• Severity varies from asymptomatic microhematuria to anuric renal failure.
• Gross hematuria occurs in 30–50%.
• Volume overload occurs in up to 2/3 of patients and may be severe enough to cause congestive heart failure and pulmonary edema.
• Hypertension occurs in up to 80%. Severity may not correlate with the degree of volume overload.
• Hypertensive encephalopathy (seizures, confusion, coma) is the presenting feature in 5%.
• Often patient has contact with individuals complaining of similar symptoms.
PHYSICAL EXAM
• Patients may have periorbital edema, peripheral edema, HTN
• Transient oliguria will be present in half of patients
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Throat swabs are rarely positive.
• Urinalysis (1):
– Hematuria may be microscopic or gross and is present in all cases.
– Microscopic analysis shows dysmorphic red blood cells and red cell casts.
– >30% of red blood cells having dysmorphic features is a highly sensitive test for glomerular disease.
– Red blood cell cast present after acute pharyngitis episode is pathognomic for poststreptococcal GN.
• Proteinuria may also be present and is usually mild (no more than 2+ on dipstick), but some may have proteinuria to the nephrotic range.
• Evaluate proteinuria with a spot urine protein-to-creatinine ratio:
– Normal <0.2.
– Nephrotic range proteinuria being >2.0.
• Basic chemistry profile may reveal elevated BUN and creatinine consistent with ARF.
– Urea can be raised disproportionately to creatinine.
• Mild normochromic, normocytic anemia due to hemodilution.
• Hyponatremia may be present due to volume overload.
• Acidemia and hyperkalemia may occur in those with severely depressed renal function.
• ESR will be elevated.
• Serum complement levels, in particular, C3 will be depressed early in the disease in 90%:
– Normalizes 2–6 wk after onset.
– Prior penicillin therapy may attenuate the fall in C3.
– If C3 remains depressed beyond this interval, look for other causes.
• Antistreptolysin-O and antihyaluronidase titers may be obtained and may be elevated in poststreptococcal GN (2).
• Not all strains of streptococci will cause these elevations and site of infection may affect which is present.
Imaging
• No imaging is indicated to identify poststreptococcal GN.
• CXR may identify fluid overload.
Diagnostic Procedures/Surgery
• Renal biopsy not indicated in poststreptococcal GN unless symptoms persist or renal function deteriorates due to progressive disease
• Renal biopsy, thus, indicated if:
– Persistently low C3 beyond 8 wk
– Persistent heavy proteinuria after 6 mo
– Atypical presentation—nephrotic syndrome, severe acute renal failure with estimated GFR <30 mL/min/1.73 m2
– Atypical course—failure of renal function to improve after initial improvement during the acute phase which usually lasts no more than 2 wk
Pathologic Findings
• IgG and C3 deposits are found at the capillary wall and in the mesangium on renal biopsy.
• Rapidly progressive GN is characterized pathologically by crescents forming from the cells of Bowman capsule.
• Typically >50% of glomeruli should have crescents to be called rapidly progressive GN. This may result from any of the immunologically mediated types of GN, but most frequently occurs with antiglomerular basement membrane disease, antineutrophil cytoplasmic antibody GN, and Henoch–Schönlein purpura nephritis.
DIFFERENTIAL DIAGNOSIS
• Anaphylactoid purpura
• IgA nephropathy
• Alport’s disease
• Membranoproliferative glomerulonephritis
• Other postinfective glomerulonephritis
• Infective endocarditis
• Rapidly progressive glomerulonephritis
• Systemic lupus erythematosus
TREATMENT
GENERAL MEASURES
• Supportive care and reassurance.
• Monitor weight and serum sodium daily during acute phase.
• Bed rest does not influence rate of recovery.
• Antibiotics do not change the course of illness once established but should be given to reduce infection-related morbidity.
• Restrict protein until azotemia clears.
MEDICATION
First Line
• Treatment is supportive for this condition and directed at the effects of renal insufficiency and HTN.
• Sodium and water restriction is indicated in patients who show signs of fluid overload (400 mL/m2/d).
• Loop diuretics, calcium channel blockers, and vasodilators are mainstays in the treatment of resultant HTN.
– Furosemide 2–4 mg/kg/dose IV
Titrate dose based on clinical response.
Second Line
• Patients should be treated with a 10-day course of penicillin antibiotics to prevent the spread of the nephritogenic organisms. This will not alter the course of the disease.
• Erythromycin is substituted if penicillin allergic.
• Family members of patients with acute GN should be cultured for group A β-hemolytic streptococci and treated if positive.
SURGERY/OTHER PROCEDURES
Renal biopsy if indicated (see evaluation)
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
N/A
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
• Most patients have a complete recovery, with resolution of clinical signs within a few weeks.
• The reported incidence of chronic renal insufficiency is 0–20%.
• Microscopic hematuria may persist for months up to 2 yr, and mild proteinuria may persist for years following an episode of poststreptococcal GN.
COMPLICATIONS
• Rarely does poststreptococcal GN progress to crescentic or rapidly progressive GN resulting in ESRD. Most cases resolve with no sequelae. Chronic renal failure or marked decline in glomerular filtration rate is very rare
• It is rare to result in severe HTN, seizures, anuria, hyperkalemia, or death.
• Hypertensive retinopathy or encephalopathy
• Rapidly progressive glomerulonephritis
• Microhematuria may persist for years
• Nephrotic syndrome (10%)
• Obesity may increase risk for residual renal injury
FOLLOW-UP
Patient Monitoring
• Subsequent urinalysis to ensure hematuria has resolved
• Periodic BP monitoring
Patient Resources
• National Kidney Foundation website
http://www.kidney.org/atoz/content/glomerul.cfm
• MedlinePlus http://www.nlm.nih.gov/medlineplus/ency/article/000484.htm
REFERENCES
1. Tu WH, Shortliffe LD. Evaluation of asymptomatic, atraumatic hematuria in children and adults. Nat Rev Urol. 2010;7(4):189–194.
2. Lee MN, Shaih U, Butani L. Effect of overweight/obesity on recovery after post-infectious glomerulonephritis. Clin Nephrol. 2009;71(6):632–636.
ADDITIONAL READING
• http://kidney.niddk.nih.gov/kudiseases/pubs/glomerular/index.htm
• Kliegman RM. Nelson Textbook of Pediatrics. 18th ed. New York, NY: Saunders, 2007.
• Lau KK, Wyatt RJ. Glomerulonephritis. Adolesc Med Clin. 2005;16(1):67–85.
• Wong W. Starship Children’s Health Clinical Guidelines on Glomerulonephritis – Acute, 2009 – http://www.adhb.govt.nz/starshipclinicalguidelines/_Documents/Glomerulonephritis.pdf
See Also (Topic, Algorithm, Media)
• Acute Kidney Injury, Adult (Renal Failure, Acute)
• Acute Kidney Injury, Pediatric (Renal Failure, Acute)
• Glomerulonephritis, Chronic
CODES
ICD9
• 446.21 Goodpasture’s syndrome
• 580.4 Acute glomerulonephritis with lesion of rapidly progressive glomerulonephritis
• 580.9 Acute glomerulonephritis with unspecified pathological lesion in kidney
ICD10
• M31.0 Hypersensitivity angiitis
• N00.9 Acute nephritic syndrome with unsp morphologic changes
• N01.9 Rapidly progr nephritic syndrome w unsp morphologic changes
CLINICAL/SURGICAL PEARLS
• Dysmorphic RBC on microscopic urinalysis suggest the diagnosis.
• Prior pharyngitis or skin infection suggests diagnosis of acute glomerulonephritis.
• With supportive care, recovery is usually rapid and complete with an excellent prognosis.