Proteinuria in membranous lupus nephritis: the pathology is in the podocyte

Patients with membranous lupus glomerulonephritis (MLN) can present with a broad range of urine protein excretion. The glomerular lesion underlying this functional abnormality has been presumed to be immune complexes which aggregate in the subepithelial area. However, the amount of proteinuria often fails to correlate with the quantity of immune deposits demonstrable on fluorescent and electron microscopy. The purpose of this study is to determine the correlation of alterations of the morphologic components of the glomerular capillary wall with the amount of proteinuria in MLN.

We conducted a retrospective clinicopathologic study of patients with lupus nephritis (n=236). In those with pure MLN and proteinuria (n=20), the degree of immune aggregates in the capillary walls and mesangium was detailed using fluorescent and electron microscopy. The degree of foot process effacement (FPE) was detailed using electron microscopy.

Eleven patients had nephrotic range proteinuria (≥ 3 g proteinuria/g creatinine (g/g)) and nine demonstrated subnephrotic range proteinuria (<3 g/g) (nephrotic, 8.3 ± 5.1 g/g vs. subnephrotic, 1.63 ± 0.83 g/g, p=0.001). All patients demonstrated peripheral capillary wall granular deposits by immunofluorescence microscopy, and the degree of moderate (2+) to severe (3+) deposition was not different (nephrotic, 8/11, 73% vs. subnephrotic, 5/9, 55%, p=0.64). By electron microscopy, FPE (88.6 ± 11% vs. 48.3 ± 36.1%, p=0.002) and foot process width (1798 ± 736 nm vs. 1000 ± 333 nm, p=0.008) was greater in the nephrotic group compared with subnephrotic. There were no other histopathologic differences between the groups.

In patients with MLN, a distinguishing morphologic feature of those with nephrotic range proteinuria is diffuse visceral epithelial cell FPE. We conclude that nephrotic range proteinuria in patients with MLN may be a manifestation of concomitant glomerular visceral epithelial cell dysfunction.