Glomerulonephritis is an inflammatory process primarily involving the glomerulus, though at times the renal vasculature, interstitium, and tubular epithelium may also be affected. Glomerular inflammation can result in damage to any of the three major components of the glomerulus: the basement membrane, the mesangium, or the capillary endothelium. Identification of the specific histopathologic pattern of glomerular injury by renal biopsy is often the most helpful technique available for defining the cause of glomerulonephritis.
Diseases causing glomerulonephritis can be classified according to whether they present as either a nephritic or a nephrotic syndrome, though some glomerular disease processes can present with components of both.
Glomerular diseases presenting as nephritic syndromes are associated with a clinical presentation of hypertension, edema, a urine sample showing red blood cells, red blood cell casts, and a moderate degree of proteinuria. Glomerular diseases presenting as nephrotic syndromes are characterized by heavy proteinuria (> 3.5 g/24 h) and frequently hypoalbuminemia, hyperlipidemia, and edema.
Diseases causing glomerulonephritis can also be classified according to whether they cause only renal abnormalities (primary renal diseases) or whether the renal abnormalities result from a systemic disease (secondary renal diseases).
In an individual suspected of having glomerulonephritis, the initial evaluation should include the following procedures and determinations:
A. Urinalysis: Dipstick and microscopic evaluation will reveal evidence for hematuria, proteinuria, and cellular elements including red cells, white cells, and casts.
B. Twenty-Four Hour Urine for Protein Excretion and Creatinine Clearance: This quantifies the amount of proteinuria and establishes the presence of nephrotic syndrome and documents the degree of renal dysfunction.
C. Creatinine Clearance: Documents the degree of renal dysfunction.
D. Urine and Serum Protein Electrophoresis: These studies identify monoclonal or Bence Jones proteins suggestive of multiple myeloma or amyloidosis.
E. Further Tests: Depending on the history and the results of the preliminary evaluation, further tests may be warranted, including complement levels (CH50, C3, C4), ASO titer, anti-GBM antibody levels, cryoglobulins, C3 nephritic factor, renal ultrasound, and renal biopsy.
Poststreptococcal glomerulonephritis is characterized by the abrupt onset of tea-colored urine, oliguria, edema, and variable degrees of hypertension. Urinary abnormalities include hematuria and red cell casts and proteinuria, which is usually mild to moderate and not in the nephrotic range (< 3.5 g/24 h). Renal tubular cells, leukocytes, and hyaline and granular casts may be seen. The creatinine clearance is mildly reduced. Urinary sodium is low, with fractional excretion often less than 0.5%. Antistreptolysin O (ASO), antistreptokinase, and antihyaluronidase titers may rise, but this rise may be blunted by previous treatment with antibiotics. There is usually a decrease in serum complement levels, both total hemolytic complement (CH50) and the level of C3.
Poststreptococcal glomerulonephritis is an immune complex-mediated disease presenting on light microscopy as a diffuse proliferative glomerulonephritis. Immunofluorescence shows IgG and C3 in a granular pattern along the capillary basement membrane and in mesangial regions. Electron microscopy shows large, dense subepithelial deposits or "humps".
The disorder is usually self-limiting, with 95% of individuals recovering normal renal function within 2 months after onset. About 5% develop rapidly progressive glomerulonephritis, with a small number of these individuals progressing to end-stage renal disease.
In some adults, hypertension and proteinuria may persist, and chronic renal failure may develop after 10-20 years. There is no specific treatment except for antihypertensives, salt restriction, and diuretics. Corticosteroids have not been shown to be of any value.
Infections with pathogens other than streptococci can cause a similar postinfectious glomerulonephritis. Glomerulonephritis can occur in association with subacute infective endocarditis, peritoneoventricular shunt infections, and bacterial abscesses of the lung and abdominal cavity. Treatment of the underlying infection may resolve the glomerulonephritis as well.
IgA nephropathy (Berger's disease) is usually a primary renal disease, but the same renal lesion can be seen in Henoch-Schonlein Henoch-Schönlein syndrome. IgA nephropathy is the most common form of acute glomerulonephritis in the USA and is even more common in Asian countries. The cause is unknown.
This disorder tends to present as an episode of macroscopic hematuria, frequently in association with an upper respiratory infection (50%), gastrointestinal symptoms (10%), or a flu-like illness (15%). In contrast to poststreptococcal glomerulonephritis, there is no significant latent period, and hypertension and edema are uncommon. Gross hematuria usually lasts 2-6 days. Proteinuria rarely exceeds 1-2 g/d, though 10% of patients can present with nephrotic syndrome. About half of individuals with gross hematuria will have only a single episode; the remainder will have recurrent episodes over many years. Fifty percent of patients with IgA nephropathy eventually develop progressive loss of renal function, with this course being more common in adults than in children. The presence of hypertension early in the course, male sex, and proteinuria greater than 3 g/d are indicators for progressive disease.
The serum IgA level is increased in 30-50% of patients; in such cases the IgA level is helpful diagnostically, though a normal value does not rule out the diagnosis. Serum complement levels are usually normal. Most individuals will also have granular deposits of IgA in the dermal capillaries of otherwise normal skin.
This disease classically presents with palpable purpura caused by a leukocytoclastic vasculitis, arthralgias, and abdominal symptoms, including colic, nausea, and melena. Purpuric skin lesions are often located on the lower extremities, though the platelet count is normal. Males are affected in the greatest numbers, and the disease is commoner in children. Renal insufficiency is common with a nephritic presentation. The renal lesion is identical to that of IgA nephropathy with mesangial deposition of IgA, but the clinical presentations of these disorders are clearly different. Most individuals will recover renal function completely and seldom go on to end-stage renal disease.