Acute Glomerulonephritis Workup

Updated: Dec 16, 2018
  • Author: Malvinder S Parmar, MBBS, MS, FRCPC, FACP, FASN; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Workup

Approach Considerations

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 (GN). 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.

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Initial Blood Tests

A CBC is performed. A decrease in the hematocrit may demonstrate a dilutional anemia. In the setting of an infectious etiology, pleocytosis may be evident.

Electrolyte levels are measured (particularly the serum potassium), along with BUN and creatinine (to allow estimation of the glomerular filtration rate [GFR]). The BUN and creatinine levels will exhibit a degree of renal compromise. GFR may be decreased. 

The ESR is usually increased.

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Complement Levels

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, renal diseases characteristic of membranoproliferative GN (MPGN) or poststreptococcal GN (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 renal diseases such as immune complex disease, idiopathic rapidly progressive GN, 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.

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

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Urinalysis and 24-Hour Urine Study

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 renal dysfunction and proteinuria. With this test, it is important to remember that creatinine clearance is a “steady-state” measurement. Because of rapidly changing renal function, the creatinine clearance may not reveal the true picture; therefore, it is better to wait until renal function has stabilized before performing creatinine clearance.

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Streptozyme Test

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 renal 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.

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Blood and Tissue Culture

Blood culture is indicated in patients with fever, immunosuppression, intravenous (IV) drug use history, indwelling shunts, or catheters.

Cultures of throat and skin lesions to rule out Streptococcus species may be obtained.

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Other Laboratory Tests

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

The antinuclear antibody test is useful for patients with acute GN 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).
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Radiography and Computed Tomography

Chest radiography is needed in patients with a cough, with or without hemoptysis (eg, granulomatosis with polyangiitis [Wegener granulomatosis], Goodpasture syndrome, 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.

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Ultrasonography and Echocardiography

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.

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Renal Biopsy

Although acute glomerulonephritis can be diagnosed clinically without a biopsy, in many cases renal biopsy may have an important role in the workup of glomerulonephritis because histology guides both prognosis and therapy. Renal biopsy may be required for definitive diagnosis, particularly in primary renal diseases. Renal 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 renal disease and patients with an atypical presentation, including massive proteinuria, nephrotic syndrome, or a rapid rise in creatinine level without resolution.

Renal biopsy guides the classification of glomerulonephritis into one of the five following etiologic groups [20]

  • 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. [20]

In a study of the types and characteristics of GN found in patients with HIV infection, Nebuloni et al reviewed 73 renal biopsies and found that immune complex GNs predominated in the biopsied patients (40 cases), with mesangial proliferative and MPGN being the most common of these (10 and 8 cases, respectively). [21] The authors also reported unusual characteristics in the immune complex GNs, including multiple-site deposits and frequent sclerotic tendencies.

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Histologic Findings

Diffuse endocapillary proliferative changes are found. The most common histologic patterns are diffuse (72.1%), focal (12.8%), and mesangial (8.1%) proliferative GN in adults. [6] 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 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.
Light microscopy (periodic acid-Schiff stain X 40) 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.

Immunofluorescence may show fine, granular deposits of IgG in a “starry sky” appearance (see the first image below). In poststaphylococcal GN, however, dominant or codominant deposition of IgA or C3 along the glomeruli is a common feature. [1] Large subepithelial deposits may be observed on electron microscopy (see the second image below). Crescents may be observed.

Immunofluorescence (X25): Fine granular deposits o 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.
Ultrastructure (electron microscopy): Photograph s 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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