Poststreptococcal Glomerulonephritis Workup

Updated: Aug 07, 2016
  • Author: Duvuru Geetha, MD, MRCP; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Workup

Laboratory Studies

Laboratory studies in acute poststreptococcal glomerulonephritis (APSGN) include tests to provide evidence of preceding streptococcal infection, renal function studies, and serologic studies.

Evidence of preceding streptococcal infection can be determined as follows:

  • Antibody titers to extracellular products of streptococci are positive in more than 95% of patients with pharyngitis and 80% of patients with skin infections.
  • The antistreptolysin (ASO), antinicotinamide adenine dinucleotidase (anti-NAD), antihyaluronidase (AHase), and anti–DNAse B are commonly positive after pharyngitis, and anti–DNAse B and AHase titers are more often positive following skin infections
  • ASO titers are frequently used to document streptococcal infection, but a more sensitive test is the streptozyme test, which tests antibodies to ASO, anti–DNAse B, AHase, and anti-NAD
  • Studies suggest that the relatively unavailable antizymogen titer test is superior to both anti–DNAse B and ASO titers
  • Antizymogen titers that are two dilutions higher than the mean in healthy controls are reported to have a sensitivity of 88% and a specificity of 85% in the diagnosis of streptococcal infection in patients with glomerulonephritis
  • High antibody titers to glyceraldehyde phosphate dehydrogenase are also found in persons with APSGN
  • In general, the antibody titers are elevated at 1 week, peak at 1 month, and fall toward preinfection levels after several months

Renal function studies

Elevated blood urea nitrogen (BUN) and serum creatinine values reflect the decrease in the glomerular filtration rate that occurs in the acute phase. The elevations are usually transient.Their failure to normalize within several weeks or months indicates that the patient may not have a true APSGN and suggests seeking an alternative diagnosis. Patients who have the crescentic form of glomerulonephritis have rapid deterioration and, often, incomplete recovery of renal function.

Serology

Serologic findings are as follows:

  • Low serum complement levels indicative of an antigen-antibody interaction are a universal finding in the acute phase of APSGN
  • Most patients have marked depression of serum hemolytic component CH50 and serum concentrations of C3
  • The decrease in C3 concentration typically occurs before the increase in ASO titers [11]
  • The activation of the alternative pathway of the complement system is thought to be responsible for the hypocomplementemia
  • In some patients, the levels of C2 and C4 may also be decreased, but to a lesser extent, suggesting that both classic and alternate pathways of the complement system are activated
  • In most uncomplicated cases, the complement levels return to normal in 6-8 weeks. Prolonged hypocomplementemia suggests an alternative diagnosis
  • Occasionally, low complement levels persist for 3 months
  • The level of reduction of serum complement levels does not have any prognostic significance
  • Circulating immune complexes and cryoglobulins are found in 60% of cases, and rheumatoid factor is found in 43% of cases

Urinalysis

Findings are as follows:

  • Results are always abnormal
  • Hematuria and proteinuria are present in all cases
  • Urine sediment has red blood cells, red blood cell casts, white blood cells, granular casts, and, rarely, white blood cell casts
  • Dysmorphic red blood cells indicative of glomerular hematuria can usually be detected by performing phase-contrast microscopy
  • Red blood cell casts are best detected in first, early-morning urine specimens examined by the physician immediately after the patient voids
  • Hematuria usually resolves within 3-6 months but may persist as long as 18 months
  • Microscopic hematuria may be present in patients in whom the disease has otherwise clinically resolved
  • Proteinuria may be mild or so severe that it causes nephrotic syndrome
  • Approximately 5-10% of patients with APSGN have nephrotic-range proteinuria
  • Proteinuria usually disappears in 6 months. A mild increase in urinary protein excretion is present in 15% at 3 years and 2% at 10 years
  • Patients with nephrotic-range proteinuria in the acute phase or persistent heavy proteinuria have a worse prognosis. This is often associated with an evolution to a garlandlike pattern of immune deposits as the disease progresses

Other studies

In a study of 28 pediatric patients with APSGN, Taskesen et al found that on clinic admission, the plasma levels of NT-proBNP (an N-terminal peptide left over when the prohormone for brain natriuretic peptide [proBNP] is cleaved to produce active BNP) were higher in these patients than in the 26 healthy children making up the control group. [19] Moreover, the NT-proBNP levels were significantly higher in six patients with APSGN who were found to have left ventricular dysfunction than they were in the patients with APSGN in whom no ventricular dysfunction was diagnosed. The authors suggested that in some patients with APSGN, determination of NT-proBNP levels may prove helpful in the assessment of left ventricular volume overload and cardiac function.

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Imaging Studies

Imaging study results may include the following:

  • Chest radiographs may show findings of congestive heart failure.
  • Renal ultrasound images usually reveal normal-sized kidneys bilaterally.
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Histologic Findings

Pathologic findings of changes in gross appearance findings are as follows:

  • The kidneys are symmetrically enlarged to approximately 25-50% of normal.
  • They are pale in appearance, and the cut surfaces bulge because of interstitial edema.
  • The glomeruli may stand out as reddish or gray translucent dots.
  • The cut surfaces may have tiny red speckles caused by red blood cells in the lumen of the Bowman space and tubules.

Light microscopy findings are as follows:

  • The most striking finding is hypercellularity of the glomeruli. All glomeruli are affected (diffuse) and usually to an approximately equal degree. The glomerular tufts are larger than normal, and the cells are more numerous.
  • The cell types typically present include endothelial and mesangial cells and migrant inflammatory cells, which include polymorphonuclear leukocytes and monocytes. [20]
  • Polymorphonuclear leukocytes are present in large numbers, hence the term exudative glomerulonephritis.
  • Necrosis in the glomerular tuft is not typically found.
  • The individual lobules are wider than usual and may have a clubbed appearance.
  • Generally, the glomerular capillary walls are not thick.
  • In some patients, crescent formation may be found, but usually, only a small percentage of glomeruli are affected by crescents.
  • The tubules are normal in the majority of cases.
  • When proteinuria is present, hyaline droplets (protein reabsorption droplets) may be present in the proximal convoluted tubules.
  • In patients with severe exudative glomerulonephritis, polymorphonuclear leukocytes may be present in the lumen.
  • The degree of interstitial involvement is variable. The interstitial areas show edema and infiltration with polymorphonuclear leukocytes and mononuclear cells. The arteries and arterioles are normal.

Immunofluorescence findings (see the image below) are as follows:

  • In biopsy samples taken in the first 2-3 weeks of illness, deposits of immunoglobulin G and C3 in a diffuse granular pattern are present along the glomerular capillary wall and mesangium.
  • Immunoglobulin M may be present in small amounts. Significant amounts of IgA suggest an alternative diagnosis.
  • Sorger et al have described 3 different patterns of immunofluorescence called the garland pattern, the starry sky pattern, and the mesangial pattern. [21]
  • The starry sky pattern is an irregular, finely granular pattern with small deposits often situated on the glomerular basement membrane overlying the mesangium. This pattern is often seen in the early phase of the disease.
  • The starry sky pattern may turn into the mesangial pattern, which is characterized by granular deposition of C3 with or without immunoglobulin G. It seems to be most closely related to a resolving pattern.
  • In approximately 25% of patients, the deposits are large and densely packed and aggregate into a ropelike or garlandlike pattern. These correspond to the humps on the subepithelial side of the glomerular capillary wall seen with electron microscopy. These types of deposits may persist for months and may be associated with the persistence of proteinuria and the development of glomerulosclerosis.
Kidney biopsy from a 7-year-old child with acute p Kidney biopsy from a 7-year-old child with acute poststreptococcal glomerulonephritis. Immunofluorescence (C3) shows a granular capillary and mesangial staining pattern with segmental areas of “lumpy-bumpy” staining (white arrows). Courtesy of Laura Kidd, MD, Pathology and Laboratory Medicine, Tulane University Medical School.

Electron microscopy findings are as follows:

  • Many of the ultrastructural changes confirm the findings from light microscopy evaluations.
  • The number of endothelial, mesangial, and infiltrating inflammatory cells is increased.
  • The glomerular basement membrane is usually normal in thickness and contour, although occasionally patchy thickening may be noted.
  • The most consistent and classic diagnostic finding is the presence of glomerular subepithelial electron-dense immune-type deposits, often referred to as humps (see the image below). The deposits are discrete and are commonly found on the part of the glomerular basement membrane overlying the mesangium.
Kidney biopsy from a 7-year-old child with acute p Kidney biopsy from a 7-year-old child with acute poststreptococcal glomerulonephritis. Electron microscopy image shows rare large subepithelial deposits, or “humps” (arrows). Courtesy of Laura Kidd, MD, Pathology and Laboratory Medicine, Tulane University Medical School.
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Renal Biopsy

Atypical features in the early phase of APSGN that suggest the need for renal biopsy include the following:

  • Absence of the latent period between streptococcal infection and acute glomerulonephritis
  • Anuria
  • Rapidly deteriorating renal function
  • Normal serum complement levels
  • No rise in antistreptococcal antibodies
  • Extrarenal manifestations of systemic disease
  • No improvement or continued decrease in the glomerular filtration rate at 2 weeks
  • Persistence of hypertension beyond 2 weeks

Atypical features in the recovery phase that mandate a renal biopsy include the following:

  • Failure of glomerular filtration rate to normalize by 4 weeks
  • Persistent hypocomplementemia beyond 6 weeks
  • Persistent microscopic hematuria beyond 18 months
  • Persistent proteinuria beyond 6 months
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