Glomerulonephritis
The 5 Minute Pediatric Consult
Kevin E.C. Meyers
DEFINITION
Glomerulonephritis (GN) presents with hematuria, oliguria, hypertension, and volume overload. Acute GN (AGN) is associated with inflammation and proliferation of the glomerular tuft. AGN may be rapidly progressive (RPGN). Chronic GN (CGN) implies that permanent damage has occurred.
PATHOPHYSIOLOGY
Causes
- 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
- Acute poststreptococcal GN (APSGN)
- Membranoproliferative glomerulonephritis (types 1, 2, and 3)
- Normal serum complement level: systemic diseases
- Polyarteritis nodosa group
- Wegener vasculitis
- Henoch-Schönlein purpura
- Hypersensitivity vasculitis
- Visceral abscess
- Normal serum complement level: renal diseases
- IgA nephropathy
- Idiopathic rapidly progressive glomerulonephritis
- Immune-complex disease
- Pauci-immune glomerulonephritis
PATHOLOGY
In APSGN, light microscopy reveals enlarged, swollen glomerular tufts, mesangial and epithelial cell proliferation, with polymorphonuclear cell infiltration. There is granular deposition of C3 and IgG on immunofluorescence, and electron-dense subepithelial deposits or humps on electron microscopy. The histology varies in CGN and depends on the cause. RPGN is associated with crescent formation.
EPIDEMIOLOGY
- APSGN can occur in all ages but is most frequent in males between 5 and 15 years.
- Incidence of APSGN in the United States has declined in the past two decades.
- GN occurs more often at the end of the first decade of life and in adults.
- Genetic predisposition
- Familial GN (e.g., Alports, X-linked)
- Autoimmune diseases (e.g., SLE, familial)
COMPLICATIONS
- Acute renal failure
- Hyperkalemia
- Hypertension
- Volume overload (congestive cardiac failure, pulmonary edema, hypertension)
- Chronic renal failure
PROGNOSIS
Prognosis is excellent in APSGN and variable for other causes of GN in childhood.
- Acute postinfectious GN (Lancefield group A (b-hemolytic streptococci, pneumococcus, Mycoplasma, mumps, Epstein-Barr virus)
- Infection-related (hepatitis B and C, syphilis)
- IgA nephropathy
- Membranoproliferative GN
- Autoimmune GN (e.g., SLE)
- Familial GN
- Acute interstitial nephritis
- Hemolytic-uremic syndrome
- Pyelonephritis
HISTORY
- Macroscopic hematuria (coke-colored urine)
- Sore throat
- Impetigo
- A prior upper respiratory infection (URI) of at least 1 week or skin lesions in the proceeding 3 to 4 weeks suggests APSGN.
- A URI in the proceeding few days suggests IgA nephropathy.
- Reduced urine output
- 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
Special Questions
Establish the time relationship between a sore throat and the AGN. The onset of APSGN is usually associated with a time delay of more than 1 week.
Look for:
- Hypertension
- Pallor
- Signs of volume overload (edema, jugular venous distention, hepatomegaly, basal pulmonary crepitation, and a triple cardiac rhythm)
- Signs of vasculitis, such as rash, loss of fingertip pulp space tissue, Raynaud, and vascular thrombosis
- Signs of a systemic disorder (see vasculitis above)
- Signs of chronic renal insufficiency, such as short stature, pallor, sallowness, edema, excoriations, pericardial friction rub, pulmonary rales and effusion, uriniferous breath, asterixis, myoclonus, and neuropathy
TESTS
- Throat culture for b-hemolytic streptococcus (positive in 15%–20% with APSGN)
- Microscopy of the urine for crenated RBCs and RBC casts. CBC is normal in AGN; with chronic renal insufficiency, a normocytic normochromic or hypochromic microcytic anemia is found.
- Serum chemistries will reflect the degree of renal failure (raised serum urea and creatinine). The serum potassium and phosphate will be elevated and the calcium decreased.
- ASOT (antistreptolysin-O) titer: positive in 60% of patients with APSGN
- Streptozyme test: a mixed antigen test for b-hemolytic streptococcus. Together, the ASOT plus Streptozyme tests have a greater than 85% sensitivity.
- Complement C3 serum level will be low in APSGN and in other causes of GN, as detailed above.
- ECG to assess ventricular size and for hyperkalemia
Imaging
- CXR to look for pulmonary edema and cardiac size
- Renal ultrasound if presentation or course is not typical of APSGN. The ultrasound is to assess the size and parenchymal texture.
PITFALLS
- Look for and treat hyperkalemia.
- To control seizures, treat the hypertension; anticonvulsants have a secondary role.
- Monitor the degree of renal failure.
- Home testing: Blood pressure monitoring may be required.
DIET
Restricted fluid, sodium, potassium, and phosphate are initially required.
DRUGS
The following may be required:
- Loop diuretics (furosemide) for volume, blood pressure, and potassium control
- Antihypertensive agents: Vasodilators such as calcium channel blockers (nifedipine, isradipine, amlodipine) and loop diuretics are useful as first-line agents. Intravenous hydralazine, labetalol, nicardipine, or nitroprusside may be required to treat severe refractory hypertension.
- Serum potassium-lowering agents (kayexalate, furosemide, bicarbonate, insulin/glucose, salbutamol). Intravenous calcium is used to stabilize the myocardium in severe hyperkalemia.
- Phosphate binders
- Immunosuppressive agents such as prednisone, cyclophosphamide, and sometimes azathioprine are used in the treatment of vasculitis-associated GN, membranoproliferative GN, and RPGN. Plasmapheresis may be used to treat RPGN. Penicillin is used in APSGN but does not affect the course of the disease.
DURATION
APSGN is a self-limiting disease. Acute therapy is usually sufficient. The therapy of CGN depends on the underlying disease process, may include immunosupressives, and, ultimately, depends on the management of CRF.
Drug doses may need modification if conflicts with other treatments arise. In APSGN, improvement usually occurs within 3 to 7 days, hypertension is not sustained, and macroscopic hematuria is transient. Watch for ongoing oliguria, unresolved hypertension, increasing proteinuria, or progressive azotemia.
PITFALLS
- Not checking a serum potassium level stat
- Not recognizing fluid overload
- Not recognizing the severity and type of renal failure
| COMMON QUESTIONS AND ANSWERS |
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Q: When does the complement return to normal?
A: Hemolytic complement levels (C3) return to normal within a 6- to 8-week period in APSGN. Persistently low C3 levels suggest a cause other than APSGN.
Q: What are the indications for renal biopsy in AGN?
A: Patients in whom there is sustained hypertension, ongoing or progressive azotemia, or persistent proteinuria of more than 1.5 g/d should be biopsied.
ICD-9-CM 580.9
Clark G, White RH, Glasgow EF, et al. Poststreptococcal glomerulonephritis in children: clinicopathological correlations and long-term prognosis. Pediatr Nephrol 1988;2:381–388.
Cole B, Salinas-Madrigal L. Acute proliferative glomerulonephritis and crescentic glomerulonephritis. In: Holliday M, Barratt TM, Avner ED, eds. Pediatric nephrology, 3rd ed. Baltimore: Williams & Wilkins, 1994:697–718.
Jordan S, Lemire JM. Acute glomerulonephritis. diagnosis and treatment. Pediatr Clin North Am 1982;29:857–873.
Madaio MP, Harrington JT. The diagnosis of acute glomerulonephritis. N Engl J Med 1984;309:1299–1302.
Copyright © 2000 Lippincott Williams & Wilkins
M. William Schwartz, Louis M. Bell, Jr., Peter M. Bingham, Esther K. Chung, David F. Friedman and Andrew E. Mulberg, The 5 Minute Pediatric Consult