Basics
Description
- Glomerulonephritis presents with the nephritic syndrome: hematuria with RBC casts, hypertension, azotemia, and edema. Proteinuria and oliguria may also be present.
- Acute glomerulonephritis is associated with inflammation and cell proliferation in the glomerular tuft. It may be rapidly progressive.
- Chronic glomerulonephritis indicates permanent damage has occurred.
Epidemiology
- Acute poststreptococcal glomerulonephritis (APSGN) can occur in anyone >2 years but is most frequently found in boys 5-15 years old. It can be sporadic or epidemic.
- Incidence of APSGN has declined over the last 2 decades.
- Chronic glomerulonephritis occurs more often at the end of the 1st decade of life and in adults.
Genetics
Genetic predisposition: hereditary nephritis (e.g., X-linked Alport syndrome)
Etiology
Can be categorized based on serum complement levels and presence of renal versus systemic disease
- Low serum complement level: systemic diseases
- Vasculitis and autoimmune disease (e.g., systemic lupus erythematosus [SLE])
- Subacute bacterial endocarditis (SBE)
- Shunt nephritis
- Cryoglobulinemia
- Low serum complement level: renal diseases
- APSGN
- Membranoproliferative glomerulonephritis, C3 glomerulopathy
- Normal serum complement level: systemic diseases
- Microscopic polyangiitis
- Granulomatosis with polyangiitis (Wegener)
- Henoch-Sch ¶nlein purpura (HSP)
- Hypersensitivity vasculitis
- Anti-GBM disease (Goodpasture syndrome)
- Normal serum complement level: renal diseases
- IgA nephropathy
- Idiopathic rapidly progressive glomerulonephritis
- Pauci-immune glomerulonephritis (renal-limited ANCA vasculitis)
- Immune-complex disease
Diagnosis
History
- Macroscopic hematuria (tea-colored urine) in many
- Reduced urine output, edema
- Dyspnea, fatigue, lethargy
- Headache
- Seizures (hypertensive encephalopathy)
- Symptoms of a systemic disease such as fever, rash (especially on the buttocks and legs, posteriorly), arthralgia, and weight loss
- Preceding sore throat, upper respiratory infection (7-14 days), or preceding impetigo (14-28 days) suggests APSGN.
- An upper respiratory infection in the few days prior to macroscopic hematuria may suggest IgA nephropathy.
Physical Exam
- Hypertension
- Signs of volume overload (e.g., edema, jugular venous distention, hepatomegaly, basal pulmonary crepitation, a gallop rhythm)
- Impetigo or pyoderma
- Signs of vasculitis such as rash, Raynaud phenomenon, and vascular thrombosis
- Signs of other systemic disorder (SLE)
- Signs of chronic kidney disease, such as short stature, pallor, sallow skin, edema, pericardial friction rub, pulmonary rales, breath that smells of urine, clonus
Diagnostic Tests & Interpretation
Lab
Initial Lab Tests
- Urine
- Microscopy of the urine for dysmorphic erythrocytes and erythrocyte casts: hallmark of nephritis
- Proteinuria
- Evidence of prior strep infection
- Throat culture for β-hemolytic Streptococcus (result is positive in only 15-20% with sporadic APSGN)
- Antistreptolysin O and anti-DNAse B titers: positive result in patients with preceding acute poststreptococcal infection
- Streptozyme test: A mixed antigen test for β-hemolytic Streptococcus (ASO, anti-DNAse, anti-streptokinase, anti-hyaluronidase, etc.) has 85-90% sensitivity and specificity; sensitivity is increased by serial testing.
- Complement C3 serum level will be low in APSGN and in several other causes of acute glomerulonephritis.
- Blood chemistry
- Can be normal in acute glomerulonephritis
- Serum creatinine generally <1.5 — normal in uncomplicated APSGN
- In chronic glomerulonephritis, serum chemistries will reflect the degree of chronic kidney disease (i.e., raised serum urea and creatinine). The serum potassium and phosphate levels may be elevated and the calcium level decreased.
- In chronic kidney disease: normocytic, normochromic, or hypochromic microcytic anemia
Imaging
- Chest radiograph to look for pulmonary edema and determine cardiac size if severe edema or respiratory symptoms are present
- Renal ultrasound if presentation or course not typical of APSGN. The ultrasound is to assess the size and parenchymal texture.
Diagnostic Procedures/Other
Electrocardiogram to assess ventricular size and for T-wave changes in cases of hyperkalemia
Pathologic Findings
In APSGN, light microscopy reveals enlarged, swollen glomerular tufts and mesangial and endothelial cell proliferation, with polymorphonuclear leukocyte infiltration. There is granular deposition of C3 and IgG on immunofluorescence, and electron-dense subepithelial deposits or humps are seen on electron microscopy. The histology varies in chronic glomerulonephritis and depends on the cause. Rapidly progressive glomerulonephritis is associated with crescent formation.
Differential Diagnosis
- Acute postinfectious glomerulonephritis (nephritogenic strains of group A β-hemolytic streptococci, Pneumococcus, Staphylococcus, Mycoplasma, Epstein-Barr virus)
- Infection-related (hepatitis B and C, syphilis)
- IgA nephropathy
- Membranoproliferative glomerulonephritis
- Autoimmune glomerulonephritis (e.g., SLE)
- Immune-complex glomerulonephritis
- Hereditary glomerulonephritis
- Tubulointerstitial nephritis
- Hemolytic uremic syndrome
- Pyelonephritis
Treatment
Aimed toward treating hypertension, renal failure, and the underlying cause of glomerulonephritis
Medication
- The following may be required:
- Loop diuretics (furosemide) for volume, BP, and potassium control
- Antihypertensive agents; vasodilators such as calcium channel blockers (e.g., nifedipine, isradipine, amlodipine) as 1st-line agents; IV hydralazine, labetalol, nicardipine, or nitroprusside may be required to treat severe refractory hypertension or posterior reversible encephalopathy syndrome (PRES). Avoid ACE inhibitors or angiotensin receptor blockers (ARBs) in case of hyperkalemia or acute kidney injury (AKI).
- Serum potassium-lowering agents (sodium polystyrene sulfonate [Kayexalate], furosemide, bicarbonate, insulin/glucose, β-agonists). IV calcium is used to stabilize the myocardium in severe hyperkalemia (with T-wave changes); dialysis in severe renal failure with significant hyperkalemia
- Phosphate binders (calcium carbonate)
- Immunosuppressive agents such as prednisone, cyclophosphamide, mycophenolate mofetil, and rarely rituximab or eculizumab are used in the treatment of vasculitis-associated glomerulonephritis, membranoproliferative glomerulonephritis, rapidly progressing glomerulonephritis, or disorders of complement regulation. Plasmapheresis may be used to treat rapidly progressing glomerulonephritis, especially with multisystem (pulmonary, CNS) involvement or severe acute renal failure requiring dialysis.
- Penicillin is used in active poststreptococcal glomerulonephritis to prevent rheumatic fever and the spread of nephritogenic strains but generally does not affect the course of the renal disease. It may be indicated in exposed individuals in epidemic APSGN and household contacts of sporadic cases.
Additional Therapies
General Measures
- APSGN is typically a self-limited disease. Acute supportive therapy is usually sufficient.
- Dietary salt restriction
- The therapy of chronic glomerulonephritis depends on the underlying disease process; it may include immunosuppressive medications and, ultimately, the management of chronic kidney disease.
Inpatient Considerations
Initial Stabilization
Treat hypertensive encephalopathy and life-threatening electrolyte disturbances immediately.
Admission Criteria
- Hypertension
- Severe edema, pulmonary edema
- Acute kidney injury
Ongoing Care
Follow-up Recommendations
In APSGN, improvement usually occurs within 3-7 days, hypertension is not sustained, and macroscopic hematuria is transient. Watch for ongoing oliguria, unresolved hypertension, increasing proteinuria, or progressive azotemia. Complement levels return to normal within 6-8 weeks of the initial presentation.
Alert
- Microscopic hematuria may be present up to 2 years after an episode of poststreptococcal glomerulonephritis.
- Recurrent gross hematuria calls the diagnosis of APSGN into question.
- If complement levels do not return to normal after presumed APSGN, consider SLE and MPGN.
Patient Monitoring
- To control seizures, treat the hypertension; anticonvulsants play a secondary role.
- Look for and treat hyperkalemia.
- Monitor the degree of acute kidney injury.
- Home testing: BP monitoring may be required.
- Be certain to recognize fluid overload.
- Be certain to recognize the type of renal failure: acute versus chronic.
- Long-term monitoring for hypertension and/or progressive proteinuria may be indicated in some populations (5-10% may develop progressive proteinuria within 20 years).
Diet
Restrictions of intake of fluid, sodium, potassium, and phosphate are initially required.
Prognosis
- Prognosis is excellent in APSGN and variable for other causes of glomerulonephritis in childhood.
- APSGN rarely recurs.
Complications
- Hypertension
- Acute renal failure
- Hyperkalemia
- Volume overload (e.g., congestive cardiac failure, pulmonary edema, hypertension)
- Chronic kidney disease
Additional Reading
- Ahn SY, Ingulli E. Acute poststreptococcal glomerulonephritis: an update. Curr Opin Pediatr. 2008;20(2):157-162. [View Abstract]
- Lau KK, Wyatt RJ. Glomerulonephritis. Adolesc Med. 2005;16(1):67-85. [View Abstract]
- Ornstein BW, Atkinson JP, Densen P. The complement system in pediatric systemic lupus erythematosus, atypical hemolytic uremic syndrome, and complocentric membranoglomerulopathies. Curr Opin Rheumatol. 2012;24(5):522-529. [View Abstract]
- Pan CG. Evaluation of gross hematuria. Pediatr Clin North Am. 2006;53(3):401-412. [View Abstract]
- Wong W, Morris MC, Zwi J. Outcome of severe acute post-streptococcal glomerulonephritis in New Zealand children. Pediatr Nephrol. 2009;24(5):1021-1026. [View Abstract]
Codes
ICD09
- 583.9 Nephritis and nephropathy, not specified as acute or chronic, with unspecified pathological lesion in kidney
- 580.9 Acute glomerulonephritis with unspecified pathological lesion in kidney
- 582.9 Chronic glomerulonephritis with unspecified pathological lesion in kidney
- 580.0 Acute glomerulonephritis with lesion of proliferative glomerulonephritis
- 583.2 Nephritis and nephropathy, not specified as acute or chronic, with lesion of membranoproliferative glomerulonephritis
ICD10
- N05.9 Unsp nephritic syndrome with unspecified morphologic changes
- N00.9 Acute nephritic syndrome with unsp morphologic changes
- N03.9 Chronic nephritic syndrome with unsp morphologic changes
- N05.5 Unspecified nephritic syndrome with diffuse mesangiocapillary glomerulonephritis
SNOMED
- 36171008 Glomerulonephritis (disorder)
- 19351000 Acute glomerulonephritis (disorder)
- 20917003 Chronic glomerulonephritis (disorder)
- 68544003 Acute post-streptococcal glomerulonephritis (disorder)
FAQ
- Q: When do serum complement levels return to normal?
- A: Serum complement levels (C3) return to normal within a 6-8-week period in APSGN. Persistently low C3 levels suggest a cause other than APSGN and renal biopsy should be considered with persistent urinary abnormalities (hematuria and/or proteinuria).
- Q: What are the indications for renal biopsy in acute glomerulonephritis?
- A: Patients in whom there is sustained hypertension, ongoing or progressive azotemia, or persistent proteinuria of >1.5 mg/mg should be biopsied.