SP1
Lupus podocytopathy: lupus related or mere coincidence?
Marilina Antonelou1, Terence Cook1,2, Tom Cairns1 and Liz Lightstone1,2
1
Imperial College Healthcare NHS Trust Lupus Centre
2
Department of Medicine, Imperial College London
BACKGROUND: Lupus podocytopathy describes the presentation of significant proteinuria in
patients with SLE with renal biopsy features consistent with minimal change disease and absence of
immune aggregate deposition in glomerular capillary walls, rather than classic lupus nephritis (LN). It
was not part of the classification of LN revised by the ISN/RPS in 2003. The finding of minimal
change glomerulopathy in patients with SLE raises the question of whether these patients could have
two uncommon but distinct pathologies or whether podocytopathy is a manifestation of SLE.
METHODS: Retrospective review of 545 biopsies from 348 patients presenting between 1996 and
2012. Since 2008, renal biopsies with glomerular epithelial foot process effacement (FPE), and no, or
sparse, immune deposits have been classified as lupus podocytopathy by our renal pathologist. Pre
2008, we looked for biopsies with ISN/RPS Class I, II, III(c) or IV(c) and extensive FPE.
RESULTS: 15 patients were identified. At biopsy, 8 were nephrotic (PCR≥300) and 7 subnephrotic
(PCR≥100). Mean duration of SLE was 13.9±10.4years. 87% had high titre ANA, 60% positive ENA
and 80% normal complement levels. Biopsy showed minimal mesangial deposits in 60% and
extensive FPE in 93%. No statistically significant difference was found in the presence of mesangial
(p=0.62), sparse/rare subepithelial (0.61) and intramembranous deposits (0.18) between the two
groups. Renal impairment was more frequent in nephrotic patients at biopsy (Table 1). Treatment
included steroids (2), Rituximab+mycophenolate mofetil+steroids (5), Rituximab+steroids+
cyclophosphamide (2), tacrolimus+steroids (4), tacrolimus (2). One patient required haemodialysis in
the context of severe nephrotic syndrome and pericardial tamponade and had two further nephrotic
relapses requiring haemodialysis over 28months follow-up. At latest follow-up (48.6±29.4months),
mean uPCR 54.6±37.7 in nephrotic and 69.3±84.2 in subnephrotic (p-value 0.68), sCR
157.6±113.0umol/L in nephrotic, 95.7±53.3umol/L in subnephrotic(p-value 0.22). Three patients with
chronically impaired function at baseline had worse function at follow-up.
Table 1. Laboratory findings at time of biopsy
Nephrotic
n
PCR
Microscopic haematuria (n)
8
Subnephrotic
p value
7
778.75±752.16
7
150.14 ±65.99
5
0.50
0.57
Albumin (g/dL)
25.50±11.09
29.71±3.54
0.34
Haemoglobin(g/dL)
11.63±2.28
12.50±0.91
0.35
Creatinine (mg/dl)
209.25±208.41
95.14±31.75
0.18
CONCLUSION: Lupus podocytopathy is rare and appears to be associated with high frequency of
ENA and high titre ANA. Proteinuria resolves as does presentation with AKI. However, patients who
present nephrotic with chronically impaired function fare badly. It remains unclear whether lupus
podocytopathy is a manifestation of SLE or coexisting minimal change in patients with lupus.
However, the extensive glomerular epithelial cell changes and limited mesangial, intramebranous and
subendothelial changes can support that podocytopathy is the driving mechanism for proteinuria
instead of immune aggregate deposition. In view of novel podocyte targeted therapies classification
is important for diagnosis and prognosis.