Acute Glomerulonephritis Workup

Urinalysis and sediment examination are crucial in the evaluation of patients with acute nephritic syndrome. Look for the following:

• Protein
• Blood
• Red blood cells (RBCs)
• White blood cells (WBCs)
• Dysmorphic RBCs
• Acanthocytes
• Cellular (ie, RBC, WBC) casts
• Granular casts
• Oval fat bodies

In some instances, marked sterile pyuria is present. The presence of RBC casts is almost pathognomonic of glomerulonephritis. Urine electrolyte, urine sodium, and fractional excretion of sodium (FENa) assays are needed to assess salt avidity.

Blood tests should include the following:

• Complete blood count (CBC)
• Blood urea nitrogen (BUN), serum creatinine, and serum electrolytes (especially serum potassium)
• Erythrocyte sedimentation rate (ESR)
• Complement levels (C3, C4, CH50)

Streptozyme testing may be useful. Imaging studies are helpful in some patients, for assessment of clinical signs suggesting extrarenal involvement or for structural evaluation of the kidneys.

Characteristic results on initial blood tests in acute glomerulonephritis include the following:

• CBC: A decrease in the hematocrit may indicate a dilutional anemia. In the setting of an infectious etiology, pleocytosis may be evident.
• Kidney function studies: BUN and and creatinine levels are elevated, indicating a degree of renal compromise. The  glomerular filtration rate (GFR) may be decreased
• Electrolytes: Potassium levels may be elevated in patients with significant renal functional impairment
• ESR: usually increased

Differentiation of low and normal serum complement levels may allow the physician to narrow the differential diagnosis. Results are not readily available to the emergency physician but may be useful to the consultant.

Low serum complement levels suggest the following systemic diseases: cryoglobulinemia, systemic lupus erythematosus (SLE), bacterial endocarditis, and shunt nephritis. Under the same conditions, kidney diseases characteristic of membranoproliferative glomerulonephritis (MPGN) or poststreptococcal glomerulonephritis (PSGN) also may be considered.

Normal serum complement levels suggest a visceral abscess, polyarteritis nodosa, Goodpasture syndrome, or Henoch-Schönlein purpura. In addition, normal complement levels suggest kidney diseases such as immune complex disease, idiopathic rapidly progressive glomerulonephritis, and immunoglobulin G (IgG) or immunoglobulin A (IgA) nephropathy.

Low C3 levels are found in almost all patients with acute poststreptococcal nephritis; C4 levels may be slightly low. Hypocomplementemia is noted in 73.9% of adult patients. Type III cryoglobulinemia may be present.

In patients with new-onset nephritis syndrome and a low C3 level, Chauvet et al report that the presence of anti–factor B autoantibodies may help distinguish new-onset PSGN from hypocomplementemic C3 glomerulopathy. ^[27]

If methicillin-resistant Staphylococcus aureus (MRSA) is the inciting agent, then hypocomplementemia is usually not present, but plasma immunoglobulins, especially IgA, are markedly elevated.

The urine is dark. Its specific gravity is greater than 1.020. RBCs and RBC casts are present.

Proteinuria is observed. With the qualitative estimation of proteinuria, determination of high-molecular-weight (HMW) protein (eg, fractional excretion of IgG [FEIgG]) and low-molecular-weight (LMW) protein (eg, alpha-1-microglobulin), may help predict the clinical outcome and may help in guiding steroid and immunosuppressive therapy, especially in patients with primary glomerular diseases with nephrotic syndrome.

The 24-hour urine protein excretion and creatinine clearance, though not indicated in the emergency department (ED) setting, may be helpful to document the degree of kidney dysfunction and proteinuria. With this test, it is important to remember that creatinine clearance is a “steady-state” measurement. Because of rapidly changing kidney function, the creatinine clearance may not reveal the true picture; therefore, it is better to wait until kidney function has stabilized before measuring creatinine clearance.

The streptozyme tests test includes many streptococcal antigens that are sensitive for screening but are not quantitative, such as DNAase, streptokinase, streptolysin O, and hyaluronidase.

The antistreptolysin O (ASO) titer is increased in 60-80% of patients. The increase begins in 1-3 weeks, peaks in 3-5 weeks, and returns to normal in 6 months. ASO titer is unrelated to severity, duration, or prognosis of kidney disease.

Increasing ASO titers or streptozyme titers confirm recent infection. In patients with skin infection, anti-DNAase B (ADB) titers are more sensitive than ASO titers for infection with Streptococcus.

Cultures of throat and skin lesions to rule out Streptococcus species may be obtained. Blood culture is indicated in patients with any of the following:

• Fever
• Immunosuppression
• Intravenous (IV) drug use history
• Indwelling shunts or catheters

Levels of antibody to nephritis-associated protease (NAPR) are elevated in streptococcal infections with glomerulonephritis but not in streptococcal infections without glomerulonephritis.

The antinuclear antibody test is useful for patients with acute glomerulonephritis and symptoms of underlying systemic illness, such as systemic lupus erythematosus and polyarteritis nodosa.

Other tests include the following:

• Anti-DNA antibodies
• Triglyceride levels
• Hepatitis B and C serologies
• Antineutrophil cytoplasmic antibody (ANCA)
• c-ANCA (ie, if granulomatosis with polyangiitis [Wegener granulomatosis] is suspected).

Chest radiography is needed in patients with a cough, with or without hemoptysis, to assess for granulomatosis with polyangiitis (Wegener granulomatosis), Goodpasture syndrome, and pulmonary congestion. Abdominal radiographic imaging (ie, computed tomography [CT]) is needed if visceral abscesses are suspected; also look for chest abscesses.

CT scan of the head without contrast may be necessary in any patient with malignant hypertension or altered mental status.

Bedside renal ultrasonography may be appropriate to evaluate kidney size, as well as to assess the echogenicity of the renal cortex, exclude obstruction, and determine the extent of fibrosis. A kidney size of less than 9 cm is suggestive of extensive scarring and a low likelihood of reversibility.

Echocardiography may be performed in patients with a new cardiac murmur or a positive blood culture to rule out endocarditis or a pericardial effusion.

Although acute glomerulonephritis (AGN) can be diagnosed clinically without a biopsy, in many cases kidney biopsy may have an important role in the workup of glomerulonephritis because histology guides both prognosis and therapy. Kidney biopsy may be required for definitive diagnosis, particularly in primary renal diseases. Kidney biopsy is not indicated as an emergency procedure, and it is generally not necessary for diagnosis of acute PSGN.

Candidates for biopsy are patients with an individual or family history of kidney disease and patients with an atypical presentation, including massive proteinuria, nephrotic syndrome, or a rapid rise in creatinine level without resolution.

Kidney biopsy guides the classification of glomerulonephritis into one of the five following etiologic groups ^[28] : 

• Immune complex–mediated glomerulonephritis (eg, lupus nephritis, IgA nephropathy, PSGN, fibrillary glomerulonephritis) 
• Antineutrophil cytoplasmic antibody (ANCA)–associated glomerulonephritis  
• Anti-glomerular basement membrane (GBM) glomerulonephritis
• Monoclonal immunoglobulin-mediated glomerulonephritis
• C3 glomerulopathy

In addition to identifying the etiology, biopsy will also determine the severity of the condition. It may also reveal the presence of other lesions that may or may not be related to the glomerulonephritis. ^[28]

In a study of the types and characteristics of glomerulonephritis found in patients with HIV infection, Nebuloni et al reviewed 73 kidney biopsies and found that immune complex glomerulonephritis predominated (40 cases), with mesangial proliferative and MPGN being the most common of these (10 and 8 cases, respectively). ^[29] The authors also reported unusual characteristics in the immune complex glomerulonephritis cases, including multiple-site deposits and frequent sclerotic tendencies.

Diffuse endocapillary proliferative changes are found. The most common histologic patterns are diffuse (72.1%), focal (12.8%), and mesangial (8.1%) proliferative glomerulonephritis in adults. ^[10] In postinfectious GN, the glomerulus is hypercellular with marked cellular infiltration (ie, polymorphonuclear neutrophils, monocytes) (see the images below).

Light microscopy (hematoxylin and eosin stain X 25): Photograph showing enlargement of glomerular tuft with marked decrease of urinary space and hypercellularity. The hypercellularity is due to proliferation of endogenous cells and polymorphonuclear leukocyte infiltrate. Photograph courtesy of Madeleine Moussa, MD, FRCPC, Department of Pathology, London Health Sciences Centre, London, Ontario, Canada.

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Light microscopy (periodic acid-Schiff stain X 40): Photograph showing enlargement of glomerular tuft with marked decrease of urinary space and hypercellularity. The hypercellularity is due to proliferation of endogenous cells and polymorphonuclear leukocyte infiltrate. Photograph courtesy of Madeleine Moussa, MD, FRCPC, Department of Pathology, London Health Sciences Centre, London, Ontario, Canada.

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Immunofluorescence may show fine, granular deposits of IgG in a “starry sky” appearance (see the first image below). In poststaphylococcal glomerulonephritis, however, dominant or codominant deposition of IgA or C3 along the glomeruli is a common feature. ^[2] Large subepithelial deposits may be observed on electron microscopy (see the second image below). Crescents may be observed.

Immunofluorescence (X25): Fine granular deposits of immunoglobulin G (IgG) along the basement membrane and mesangium, with "starry sky" appearance. Photograph courtesy of Madeleine Moussa, MD, FRCPC, Department of Pathology, London Health Sciences Centre, London, Ontario, Canada.

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Ultrastructure (electron microscopy): Photograph showing proliferation of endothelial cells and mesangial cells and leukocyte infiltrate associated with presence of large, subepithelial, electron-dense deposits (ie, "hump") (see arrow). Photograph courtesy of Madeleine Moussa, MD, FRCPC, Department of Pathology, London Health Sciences Centre, London, Ontario, Canada.

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