Glomerulonephritis• Glomerulonephritis (GN) presents with hematuria with RBC casts, proteinuria, oliguria, hypertension, azotemia

and edema.

• Acute glomerulonephritis is associated with inflammation and proliferation of the glomerular tuft. It may be rapidlyprogressive.

• Chronic glomerulonephritis carries the indication that permanent damage has occurred.

EPIDEMIOLOGY

Acute poststreptococcal glomerulonephritis can occur in anyone >2 years, but is most frequently found in boys between 5–

15 years old.

Incidence

• Incidence of acute poststreptococcal glomerulonephritis in the US has declined over the last 2 decades.

• Chronic glomerulonephritis occurs more often at the end of the 1st decade of life and in adults.

RISK FACTORS

Genetics

Genetic predisposition:

• Familial glomerulonephritis (e.g., Alport syndrome, X linked)

ETIOLOGY

• Low serum complement level: Systemic diseases:

1. Vasculitis and autoimmune disease (e.g., systemic lupus erythematosus [SLE])

2. Subacute bacterial endocarditis (SBE)

3. Shunt nephritis

4. Cryoglobulinemia

• Low serum complement level: Renal diseases:

1. Acute poststreptococcal glomerulonephritis

2. Membranoproliferative glomerulonephritis (types 1, 2, and 3)

• Normal serum complement level: Systemic diseases:

1. Polyarteritis nodosa group

2. Wegener vasculitis

3. Henoch-Schönlein purpura

4. Hypersensitivity vasculitis

5. Visceral abscess

• Normal serum complement level: Renal diseases:

1. IgA nephropathy

2. Idiopathic rapidly progressive glomerulonephritis

3. Immune-complex disease

4. Pauci-immune glomerulonephritis

Diagnosis

SIGNS AND SYMPTOMS

• Macroscopic hematuria (dark brown urine)

• Sore throat

• Impetigo

• A prior upper respiratory infection that persists at least 1 week or skin lesions in the proceeding 3–4 weeks suggestsacute poststreptococcal glomerulonephritis.

• An upper respiratory infection in the previous few days suggests IgA nephropathy.

• Reduced output of urine

• 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

History

Special questions:

• Establish the time relationship between a sore throat and the acute glomerulonephritis. The onset of acute poststreptococcal glomerulonephritis is usually associated with a time delay of >1 week.

Physical Exam

Look for:

• Hypertension

• Pallor

• Signs of volume overload (e.g., edema, jugular venous distention, hepatomegaly, basal pulmonary crepitation, and

a triple cardiac rhythm)

• Impetigo or ecthyma (pyoderma)

• Signs of vasculitis such as rash, loss of fingertip pulp space tissue, Raynaud phenomenon, and vascular thrombosis

• Signs of a systemic disorder (see comment on vasculitis)

• Signs of chronic renal insufficiency such as short stature, pallor, sallow skin, edema, excoriations, pericardial friction rub, pulmonary rales and effusion, breath that smells of urine, asterixis, myoclonus, and neuropathy

TESTS

LABORATORY

• Urine:

1. Microscopy of the urine for crenated erythrocytes and erythrocyte casts—hallmark of nephritis

2. Proteinuria

• Evidence of previous strep infection:

1. Throat culture for β-hemolytic streptococcus (result is positive in 15–20% with acute poststreptococcal glomerulonephritis)

2. Antistreptolysin O titer: Positive result in 60% of patients with acute poststreptococcal glomerulonephritis.

3. Streptozyme test: A mixed antigen test for β-hemolytic streptococcus. Together, the antistreptolysin O

titerplus streptozyme tests have a >85% sensitivity.

4. Complement C3 serum level will be low in acute poststreptococcal glomerulonephritis and in other causes

of acute glomerulonephritis as detailed herein.

• Blood chemistry:

1. Can be normal in acute glomerulonephritis

2. In chronic glomerulonephritis, serum chemistries will reflect the degree of renal failure (i.e., raised

serum ureaand creatinine). The serum potassiumand phosphate levels will be elevated and the calcium level decreased.

3. With chronic renal insufficiency: Normocytic, normochromic, or hypochromic microcytic anemia

IMAGING

• Chest radiograph to look for pulmonary edema and determine cardiac size

• Renal ultrasound if presentation or course not typical of acute poststreptococcal glomerulonephritis. The ultrasoundis to assess the size and parenchymal texture.

DIAGNOSTIC PROCEDURES

Electrocardiogram:

• Electrocardiogram to assess ventricular size and for hyperkalemia

PATHOLOGICAL FINDINGS

In acute poststreptococcal glomerulonephritis, 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 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 (Lancefield group A β-hemolytic streptococci Pneumococcus,

Mycoplasma, mumps, Epstein-Barr virus)

• Infection related (hepatitis B and C, syphilis)

• IgA nephropathy

• Membranoproliferative glomerulonephritis

• Autoimmune glomerulonephritis (e.g., SLE)

• Familial glomerulonephritis

• Acute interstitial nephritis

• Hemolytic uremic syndrome

• Pyelonephritis

Treatment

INITIAL STABILIZATION

Treat hypertensive encephalopathy and life-threatening electrolyte disturbances immediately.

GENERAL MEASURES

• Acute poststreptococcal glomerulonephritis is a self-limiting disease. Acute therapy is usually sufficient.

• The therapy of chronic glomerulonephritis depends on the underlying disease process; it may include immunosuppressives and, ultimately, the management of chronic renal failure.

DIET

Restrictions of intake of fluid, sodium, potassium, and phosphate are initially required.

MEDICATIONS

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)

and loop diuretics are useful as first-line agents; IV hydralazine, labetalol, nicardipine, or nitroprusside may be required to treat severe refractory hypertension.

• Serum potassium-lowering agents (sodium polystyrene sulfonate [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 glomerulonephritis, membranoproliferative glomeru- lonephritis, and rapidly progressing glomerulone-phritis. Plasmapheresis may be used to treat rapidly progressing glomerulonephritis.

Penicillin is used in acute poststreptococcal glomerulonephritis, but does not affect the course of the disease.

Follow-up Recommendations

In acute poststreptococcal glomerulonephritis, 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 levelsreturn to normal within 6–8 weeks of the initial presentation.

CLINICAL:

• Microscopic hematuria may be present up to two years after an episode of poststreptococcal glomerulonephritis

• If complement levels do not return to normal after presumed poststreptococcal glomerulonephritis, one needs to

consider SLE and MPGN.

PATIENT MONITORING

• Look for and treat hyperkalemia.

• To control seizures, treat the hypertension; anticonvulsants play a secondary role.

• Monitor the degree of renal failure.

• Home testing: BP monitoring may be required.

• Do not fail to check serum potassium levels.

• Be certain to recognize fluid overload.

• Be certain to recognize the severity and type of renal failure.

DISPOSITION

Admission Criteria

• Hypertension , Edema, Renal failure

EXPECTED COURSE/PROGNOSIS

• Prognosis is excellent in acute poststreptococcal glomerulonephritis and variable for other causes of

glomerulonephritis in childhood.

• Acute poststreptococcal glomerulonephritis rarely recurs.

POSSIBLE COMPLICATIONS

• Acute renal failure

• Hyperkalemia

• Hypertension

• Volume overload (e.g., congestive cardiac failure, pulmonary edema, hypertension)

• Chronic renal failure

Frequently Asked Questions

• Q: When does the complement return to normal?

• A: Hemolytic complement levels (C3) return to normal within a 6–8-week period in acute poststreptococcal glomerulonephritis. Persistently low C3 levels suggest a cause other than acute poststreptococcal

glomerulonephritis.

• Q: What are the indications for renal biopsyin acute glomerulonephritis?

• A: Patients in whom there is sustained hypertension, ongoing or progressive azotemia, or persistent proteinuria of

>1.5 g/d should be biopsied.