Diffuse Proliferative Glomerulonephritis Workup

Updated: Mar 03, 2018
  • Author: Moro O Salifu, MD, MPH, FACP; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Workup

Laboratory Studies

On urinalysis, no specific finding can be used to accurately predict the presence of diffuse proliferative glomerulonephritis (DPGN). However, the finding of red blood cells and red blood cell casts strongly suggests glomerulonephritis. Proteinuria, white blood cells, and white blood cell casts may be present or absent. Renal biopsy should be obtained for histologic diagnosis and, in lupus, for classification.

In patients with systemic lupus erythematosus (SLE) who already have a histologic classification, an increase in urinary sediment abnormality should raise the suspicion of histologic transformation. A repeat biopsy may be indicated if reclassification will guide management.

A 24-hour urine collection is used for determination of protein and creatinine excretion. Creatinine in a 24-hour urine collection is used to determine completeness of the collection as well as to calculate creatinine clearance. On average, in adults younger than 50 years, creatinine excretion less than 15-20 mg/kg (lean body mass) for women or less than 20-25 mg/kg (lean body mass) for men suggests undercollection of the urine specimen. Values greater than these suggest overcollection. Overcollection and undercollection lead to inaccurate estimation of creatinine clearance and, therefore, of glomerular filtration rate (GFR).

A 24-hour urinary protein excretion in excess of 3.5 g is in the nephrotic range. A finding below 3.5 g indicates nonnephrotic proteinuria. A specific pattern for DPGN is not identified, but nephrotic-range proteinuria is more common.

Complete blood count (CBC) findings are as follows:

  • Anemia

  • Leukopenia, lymphopenia, and thrombocytopenia are often observed in SLE

On serum chemistry studies, serum creatinine and blood urea nitrogen levels often are elevated. Serum albumin may be low if the patient is nephrotic.

Serologic test results may include the following:

  • Positive antinuclear antibodies (ANAs) indicate lupus nephritis; 95% of patients with SLE have positive ANA, but this finding is not specific

  • Positive tests for anti–double-stranded DNA (anti-dsDNA) and anti-Smith (anti-Sm) antibodies are more specific for lupus (rising titers may indicate active or chronic disease)

  • Depressed complement levels of C3, C4, and CH50 may suggest SLE, infectious glomerulonephritis, poststreptococcal glomerulonephritis, or cryoglobulinemia.

  • Antineutrophil cytoplasmic antibody (ANCA) assays are positive (>1:40) in almost all cases of granulomatosis with polyangiitis (GPA; Wegener granulomatosis): 80-95% are cytoplasmic ANCA (C-ANCA), while 5-20% are perinuclear ANCA (P-ANCA). In one study, a positive result for C-ANCA was used to identify GPA, with a sensitivity and specificity of 65% and 88%, respectively, while a positive result for P-ANCA was used to identify GPA with a sensitivity and specificity of 75% and 98%, respectively.

  • Tests results that are positive for anti–glomerular basement membrane (GBM) antibodies indicate consideration of anti-GMB disease (ie, idiopathic) and Goodpasture syndrome. Circulating anti-GBM antibodies are present in over 90% of patients, although the antibody titer does not correlate well with the manifestations or course of either the pulmonary or renal disease.

  • A high titer of antistreptolysin O (ASO) shows recent streptococcal infection, indicating the possibility of poststreptococcal glomerulonephritis. Healthy children of school age (eg, 6-12 y) commonly have titers of 200-300 Todd units per mL. After streptococcal pharyngitis, the antibody response peaks at about 4-5 weeks. Antibody titers decline rapidly in the next several months and reach a slower decline after 6 months. Because 20% of patients with documented infection do not show a rise in the antistreptolysin titer, other antistreptococcal antibodies such as anti-deoxyribonuclease (DNAse) B, anti-DNAse, and antihyaluronidase should be tested if ASO findings are negative.

  • Throat culture findings for group A beta-hemolytic streptococci usually are negative at the time of glomerulonephritis, while ASO titers peak.

  • Serum IgA levels are elevated in as many as half of patients with IgA nephropathy.

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Imaging Studies

Renal ultrasonogram is used to determine renal size, confirm the presence of 2 kidneys, and rule out structural lesions that may be responsible for azotemia.

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Procedures

Kidney biopsy

Indications, contraindications, and complications of percutaneous renal biopsy are discussed in the article Azotemia. Renal biopsy is the criterion standard for diagnosis of anti-GBM nephritis. Obtain a renal biopsy for histologic diagnosis and, in lupus, for classification.

In patients with lupus who already have a histologic classification, an increase in urinary sediment abnormality should raise the suspicion of histologic transformation. A repeat biopsy may be indicated if reclassification will influence management.

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Histologic Findings

Light microscopy

Light microscopy (as seen in the image below) shows a marked hypercellularity of endothelial (ie, endocapillary) and mesangial cells, capillary loop thickening (ie, wire loops) or obliteration, and inflammatory cell infiltration. In severe forms, epithelial cell proliferation with crescent formation, necrosis, and sclerosis may be present. Inflammatory infiltration and fibrosis also may present in the interstitium. Endocapillary proliferation is typical of poststreptococcal glomerulonephritis.

Light microscopy (trichrome stain) shows globally Light microscopy (trichrome stain) shows globally increased cellularity, numerous polymorphonuclear cells, cellular crescent (at left of photomicrograph) and fibrinoid necrosis (brick red staining at right of photomicrograph). These findings are characteristic of diffuse proliferative glomerulonephritis.

Immunofluorescent microscopy

This technique shows (except in anti-GBM disease) a granular deposition of immunoglobulins, complement, and fibrin along the GBM, tubular basement membranes, and peritubular capillaries (as seen in the image below). Linear deposition occurs in the GBM in anti-GBM disease. Findings on immunofluorescence are negative in ANCA-associated glomerulonephritis. If radioimmunoassay is not available, indirect immunofluorescence can be used to detect circulating anti-GBM antibodies in 60-80% of patients by incubating the patient's serum with stored sections of healthy human kidneys.

Diffuse proliferative glomerulonephritis (DPGN). I Diffuse proliferative glomerulonephritis (DPGN). Immunofluorescent microscopy shows (except for anti–glomerular basement membrane [GBM] disease) a granular deposition of immunoglobulins, complement, and fibrin along the GBM, tubular basement membranes, and peritubular capillaries (image 2a). Linear deposition occurs in the GBM in anti-GBM disease (image 2b).

Electron microscopy

Using electron microscopy (as seen in the image below), electron-dense deposits are visible in the mesangial, subendothelial, intramembranous, and subepithelial locations. In SLE, the mesangial and subendothelial deposits produce the typical wire loop lesions observed using light microscopy. Tuboreticular inclusions may be observed within endothelial cells but are not pathognomonic. Tuboreticular inclusions also may be observed in HIV nephropathy. In anti-GBM disease, the deposits are linear and intramembranous. In poststreptococcal glomerulonephritis, the deposits are subepithelial and appear as humps. Few or no deposits are visible in ANCA-associated glomerulonephritis.

Diffuse proliferative glomerulonephritis (DPGN). U Diffuse proliferative glomerulonephritis (DPGN). Using electron microscopy, electron-dense deposits are visible in the mesangial, subendothelial, intramembranous, and subepithelial locations.
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