To preserve patient privacy and for didactic purposes, case descriptions and pathology reports have been anonymized and partially fictionalized. The pathology images are representative images from a mixture of similar cases.

Invited Speakers

Jonathan Slater
Jonathan SlaterCase Presenter | Baystate Medical Center, Springfield, MA, USA | No conflict of interest reported
Ali Poyan Mehr
Ali Poyan MehrNephrology Discussant | Beth Israel Deaconess Medical Center, Boston, MA, USA | Conflict of interest reported: Mallinckrodt - Glomerular Disease Consultant and Research Grant
Helmut Rennke
Helmut RennkeNephropathology Discussant | Brigham Women's Hospital, Boston, MA, USA | No conflict of interest reported
Dr. Adib Khouzami
Dr. Adib KhouzamiHigh Risk Maternal Fetal Medicine Discussant | Johnstown, PA, USA | No conflict of interest reported

Case

The patient is a young female in her late 20s, with a history of nephrotic range proteinuria over the past 7 years (4-7 grams) who is trying to become pregnant.

She was initially seen a few years ago, with labs pertinent for 24hr urinary protein 3500 mg; ANA 1:160 C3/C4 and all serologies normal/negative.

She underwent a biopsy at that time (below as biopsy #1): Consistent with immune complex, proliferative glomerulonephritis.

Given lack of a specific diagnosis, and persistent heavy proteinuria, a second biopsy was performed several months later (below as biopsy #2):

Nephrotic range proteinuria throughout the next several years: urinary protein: 3500-4600 mg/24hr. Mycophenolate was prescribed without much effect.

A few years later she underwent a 3rd biopsy (below as biopsy #3).  

Medications:
A history of mycophenolate, cyclophosphamide, prednisone, and leuprolide use.
Furosemide
Valsartan
Vitamin D

Physical Exam:
BP 138/88, 1 to 2+ lower extremity edema.
No rash, joint effusion, or other focal findings.

Laboratory and other data:
Currently, urinary albumin/creatinine of 5000
ANA 1:160; dsDNA titer 8 (normal reference <1)

Short term follow up:
Cyclophosphamide/steroids/leuprolide: European Protocol completed:
Repeat serologies all neg w ANA 1:80 and no sDNA; Salb always > 3.4, SCr always < 0.9; UAC remains approximately 3000-4000 now on valsartan, and azathioprine maintenance.

Kidney Pathology

Pathology images pending

Biopsy #1: Mesangial and focal endocapillary proliferative glomerulonephritis (lobular accentuation), with a small cellular crescent, peripheral and perihilar FSGS, tubule-interstitial without significant changes. IF and EM findings suggestive of resolving or evolving immune complex mediated process.

IF: Diffuse and focal granular staining of GBM with IgG (3+), kappa and lambda (1-2+), IgA (mild), segmental peripheral and para-mesangial granular and focal confluent IgM (1-2+), C3 and C1q with rare segmental granular staining (trace-1+).

EM: Segmental double contours, and pale subepithelial, intramembranous sub-endothelial, and para-mesangial areas, suggesting immune deposits. Fine granular and fibrillary deposits in lamina densa, sub-endothelial, and mesangial locations. Scant sub-epithelial and intramembranous electron dense deposits are seen. No hump-like deposits, and no TBM deposits.  No tubule-reticular inclusions. There is sub-endothelial cell interposition, and focal sub-endothelial lucency.

Biopsy #2:  Approximately 50% of glomeruli are globally sclerosed. Thickened GBM with spike-like projections, as well as double contours. No acute endocapillary inflammation, fibrinoid necrosis, or cellular crescents. IF: Sparse granular staining for IgG (2+), IgA (trace), IgM(trace) and C3(2+) along the capillary loops and GBM. some at mesangial area. There is also diffuse linear staining for IgG (3+), IgA (2+), IgM (1+) along the GBM. Polyclonal and all IgG classes stained. Arteriolar walls with some C3 staining.  EM: Capillary loops markedly distorted by the presence of numerous sub-epithelial, several subendothelial, and intramembranous electron-dense deposits. Double contours due to sub-endothelial deposits with prominent cellular interposition. Deposits are finely granular.  No tubuloreticular inclusions.

Biopsy #3: A pattern of membranoproliferative glomerulonephritis with focal endocapillary proliferation. Immune complexes are present in both linear, and granular pattern and localize to capillary loops. Segmental sclerosis in ~50% of glomeruli. IFTA of ~20%. Finding similar to those in the previous biopsies. Current biopsy with a slight different pattern of electron dense deposits, with subepithelial and intramembranous deposits that are IgG dominant. DD: autoimmune, post-infectious, membranous LN (potentially class V with mesangial alterations), lupus-like process, drug induced, or viral hepatitis.

Questions posed & summary of key discussion points

1. Patient’s presentation was never consistent with SLE given it lacks other findings to meet criteria. Nevertheless, SLE remains high on differential based on her biopsy. Can this be a non lupus immune complex GN, or renal limited lupus, perhaps a class V variant?
2. Further therapeutic management: Continue current Tx with azathioprine and tapering STD?
3. Would you consider rituximab vs tacrolimus vs other?
4. How to monitor her response?
5. Would you consider repeat kidney Bx?
6. What does the linear staining mean and how do we interpret the Bx?