Wednesday, March 15, 2017

Lupus Podocytopathy

I recently finished my 2nd month on the consult service which was a very exciting time for me because I saw patients with every class of Lupus with different kinds of presentations. It was especially rewarding because I biopsied majority of these patients myself and then followed their course through diagnosis, initiation of immunosuppression and witnessed improvement in subsequent clinic visits. I find Lupus Nephritis most fascinating among all the GNs.
One of the most interesting cases I saw since the beginning of fellowship was of a 36 yrs. old woman who presented with joint pain, malar rash, photosensitivity, worsening generalized edema and nephrotic range proteinuria of 8 grams. She had 2 prior renal biopsies- one with a diagnosis of Minimal Change Disease and the second one 2 years ago with FSGS tip lesion and Class 2 lupus Nephritis.
On her current presentation, she met the ACR criteria of diagnosis of SLE. We biopsied her again and essentially found the exact same lesion- FSGS tip lesion with Class 2 lupus nephritis.  There were only scant mesangial deposits, no endocapillary proliferation or necrosis and weak but full house staining on IM. EM showed diffuse foot process effacement. We diagnosed her with Lupus Podocytopathy and she was started on high dose steroids and immunosuppression with MMF with subsequent rapid resolution of symptoms and proteinuria to 0.8 grams within 2 weeks. It remains to be seen how she continues to respond to the treatment and if she remains in remission. She still is likely to relapse in future and switch to a different class of lupus nephritis along her course.
Podocytopathy is a glomerular disease which occurs due to extrinsic or intrinsic primary podocyte injury. Lupus Podocytopathy occurs in association with new or relapse of SLE signs and symptoms.
It is a rare presentation of Lupus Nephritis - the reported incidence is 1.33% of patients with Lupus Nephritis. So far there have been 22 reported cases in literature. Up until the early 2000s, nephrotic syndrome in a patient with class 2 lupus was deemed as a coincidence.  The work of Dube et al, Hertig et al and Kraft et al lead to an understanding that the appearance of nephrotic syndrome in a patient with Class 2 lupus (without any endocapillary proliferation or GBM deposits) coincided with Lupus flare or appearance of Lupus symptoms. Among these patients, the nephrotic syndrome appears best correlated with podocytopathy rather than subepithelial electron dense deposits, mesangial deposits, or mesangial hypercellularity. The currently used ISN/RPS classification of Lupus Nephritis does not include Lupus Podocytopathy.
A more recent article in CJASN in April 2016 studied a cohort of 50 Chinese SLE patients (the largest so far) with diffuse Foot Process Effacement and class 1 and 2 lupus nephritis.  They included minimal change  disease (MCD) in 13 cases, mesangial proliferation in 28 cases, and FSGS in nine cases.They have proposed a list of criteria to diagnose Lupus Podocytopathy and suggest revision of ISN/RPS classification of Lupus nephritis to include Lupus podocytopathy as a distinct entity. The immunologic and molecular mechanism of Lupus podocytopathy has not yet been fully studied but the T-cell abnormalities in both the disorders could be the unifying pathogenic mechanism in the occurrence of MCD or FSGS in SLE.

There is very limited data currently on the treatment of this group of patients as almost all of it comes from observational studies. But so far, we know that patients with Lupus Podocytopathy are highly steroid responsive. Those who have an FSGS lesion are prone to more relapses and incomplete remission as compared to the ones with MCD, and also need immunosuppressive agents with steroids. Both nephrologists and renal pathologists need to be aware of this entity as a cause of nephrotic syndrome in patients with SLE
Posted by Manasi Bapat, Nephrology Fellow, Mount Sinai Hospital, NY

1 comment:

menaan palamuthusingam said...

This commentry nicely depicts the importance of incorporating Lupus podocytopathy as a distinct group of the lupus classification. However, some people also include collapsing glomerulopathy in lupus patients, but i think it is important to keep these separate as the minimal change-like podocytopathy responds really well to steroids and collapsing glomerulopathy probably has a very different background (possibly related to APOL1 variants, as both SLE and collapsing GP are more common in blacks).