Laboratory Studies
Laboratory studies in patients with suspected membranous nephropathy are intended to evaluate the status of the kidneys and to search for an underlying cause. Tests include the following:
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Urine microscopy: Urine sediment is typically nephrotic, with oval fat bodies and fatty casts; however, in mild cases, the urinalysis may reveal proteinuria without formed elements in the sediment.
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Serum creatinine
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Blood urea nitrogen
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Serum albumin
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Proteinuria (quantitative) with a 24-hour urine collection: A ratio of spot urine protein to creatinine is easier to obtain, and the findings may be sufficient for screening purposes.
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Creatinine clearance
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Antinuclear antibodies
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Anti–double-strand DNA, if results from antinuclear antibody testing are positive
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Hepatitis B serology (if positive, DNA quantitation)
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Hepatitis C (if positive, RNA quantitation)
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Syphilis serology
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Complement levels
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Cryoglobulin, particularly if hepatitis C and/or low levels of complement are found
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Lipid profile
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Urinary C5b-9
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Urinary beta-2 microglobulin (worse prognosis with an increased level)
Measurement of antibodies against the M-type phospholipase A2 receptor (anti-PLA2R antibodies) is used for diagnosis, determining prognosis, and monitoring response to therapy in membranous nephropathy. [1, 19, 21] Anti-PLA2R antibodies have high specificity (close to 100%) and sensitivity (70-80%) for diagnosis. [22] Patients with absent or low anti-PLA2R levels are more likely to undergo spontaneous remission, whereas patients with high baseline anti-PLA2R antibody levels tend to achieve remission of proteinuria significantly later than those with low baseline levels, and are at greater risk of failing to achieve remission. [23]
An exhaustive workup for malignancy is not recommended because most cases of membranous nephropathy are not associated with cancer. However, because some increase in the rate of occult malignancy is recognized in patients with newly diagnosed membranous nephropathy, (1) ensure that age-appropriate health screening (eg, mammography, sigmoidoscopy) has been performed, and (2) investigate any clues from the initial patient history and physical examination.
Procedures
Although Kidney Disease: Improving Global Outcomes (KDIGO) guidelines emphasize that kidney biopsy remains the “gold standard” for the diagnosis of glomerular diseases, the 2021 KDIGO guidelines dropped the requirement of kidney biopsy for confirmation of the diagnosis of membranous nephropathy in patients who have nephrotic syndrome and a positive PLA2R antibody test. However, the guidelines stress that a kidney biopsy can provide important additional information in these cases. [19]
Histologic Findings
Pathologic features can be observed using light microscopy, immunofluorescence microscopy, and electron microscopy.
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Light microscopy: The mesangium is normal, with no hypercellularity. All glomeruli are involved. The capillary walls are thickened with patent capillary lumina. Subepithelial deposits are seen; with trichrome stain, they are shown to have spikes.
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Immunofluorescence microscopy: Use strong granular capillary wall staining for immunoglobulin G (IgG), with C3 and both kappa and lambda light chains.
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Electron microscopy
A considerable diversity of prognosis is seen with idiopathic membranous nephropathy. In a study of 105 patients with idiopathic membranous nephropathy, 2 different groups were identified on the electron microscopic findings. In the homogeneous type, only 1 patient developed end-stage renal failure, and earlier remission occurred in this group. With regard to secondary outcome, increased age, focal segmental glomerular sclerosis, arteriolosclerosis, and heterogeneous type of electron microscopic findings were independent risk factors.
Stage 1: Features appear normal using light microscopy, but, with electron microscopy, a few electron-dense deposits are seen along the capillary walls.
Stage 2: Numerous and larger deposits with spikes are seen.
Stage 3: New extracellular material surrounds the deposits.
Stage 4: Initial electron-dense deposits become electron-lucent, and capillary walls become thickened.
