Validation of phospholipase A2 receptor direct immunofluorescence staining in the diagnosis of primary membranous glomerulonephritis.

Distinguishing between primary and secondary subtypes of membranous glomerulonephritis (MGN) is critical for its clinical management. We prospectively compared direct immunofluorescence (DIF) staining for phospholipase A2 receptor (PLA2R) on frozen renal biopsy with the presence of detectable serum PLA2R antibody assessed by enzyme linked immunosorbent assay (ELISA) in the diagnosis of primary MGN. Forty-six patients with biopsy-proven MGN were enrolled from April 2017 to June 2019 with 31/46 (67.4%) being primary and 15/46 (32.6%) being secondary as determined by comprehensive clinical assessment. This is currently deemed to be the gold standard for distinguishing primary from secondary MGN. Amongst the 31 primary MGN patients, 24/31 were positive on PLA2R DIF staining compared to 18/31 being positive on the PLA2R ELISA (p=0.03). Amongst the 15 secondary MGN patients, 1/15 was positive on PLA2R DIF compared to 0/15 on PLA2R ELISA (p=1.0). In conclusion, the presence of PLA2R staining on DIF demonstrated superior sensitivity and similar specificity compared to the detection of circulating PLA2R antibodies by ELISA in the diagnosis of primary MGN in a cohort of 46 patients with biopsy-proven MGN. We suggest that DIF should be considered as part of routine work-up in all newly diagnosed cases of MGN.

Ultrastructural identification of a proximal tubulopathy without crystals in a relapsed multiple myeloma patient.

A multiple myeloma patient, who had been treated with a hematopoietic stem cell transplant, underwent a renal biopsy for investigation of a possible relapse of disease as indicated by increased serum creatinine and positive urinary Bence-Jones protein containing increased kappa light chain. Paraprotein-related renal disease was not evident by light microscopy or immunofluorescence microscopy however electron microscopy demonstrated a proximal tubulopathy with intracytoplasmic non-crystalline inclusions. The ultrastructural findings suggested possible end-organ involvement by the disease and follow-up studies subsequently revealed a relapsed multiple myeloma in the patient. The case exemplifies the usefulness of electron microscopy in detecting paraproteins that, in some instances, may be difficult to demonstrate by other techniques.