Glomerulonephritis, Poststreptococcal Workup
- Author: Duvuru Geetha, MD, MRCP; Chief Editor: Vecihi Batuman, MD, FACP, FASN more...
Laboratory Studies
- Evidence of preceding streptococcal infection
- 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 2 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 acute poststreptococcal glomerulonephritis (APSGN).
- In general, the antibody titers are elevated at 1 week, peak at 1 month, and fall toward preinfection levels after several months.
- Elevated BUN and creatinine values
- This reflects 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.
- Serologic findings
- 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 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
- 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.
Imaging Studies
- Chest radiographs may show findings of congestive heart failure.
- Renal ultrasound images usually reveal normal-sized kidneys bilaterally.
Procedures
- APSGN is often a clinical diagnosis and requires the detection of glomerulonephritis and evidence of preceding streptococcal infection.
- Atypical features in the early phase 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
Histologic Findings
- Pathologic findings of changes in gross appearance
- 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
- 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.[4]
- 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
- 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.[10]
- 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.
- Electron microscopy
- 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. The deposits are discrete and are commonly found on the part of the glomerular basement membrane overlying the mesangium.
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