This document presents the case of a 37-year-old female patient who was referred for nephrotic syndrome. Her workup found membranous glomerulonephritis on biopsy and elevated tumor markers. While no cancer was found on imaging, her presentation was consistent with cancer-associated membranous nephropathy. She responded well to immunosuppression with steroids and cyclophosphamide, improving her proteinuria over several months. The discussion centered around determining if her membranous nephropathy was primary or secondary to an occult malignancy, and the optimal treatment and surveillance for her condition.

1. Case Presentation
DR. NAMRA ANAM RESIDENT NEPHROLOGY NMU
DR. MALIHA JAUHAR SR NEPHROLOGY NHM

2. Brief Clinical Description
•A young married female 37 years of age was referred by a gynecologist to the
Nephrology OPD for management of Nephrotic syndrome. Patient had
developed gradually progressive massive abdominal distension over the period
of 3 months, which was associated with periorbital swelling, swelling of feet,
and shortness of breath which worsened with lying flat.
•No H/O skin rash, joint involvement, fever, oral ulcers or loss of hair, use of
drugs.
•No significant obstetrical or gynecological, treatment or family history.

3. Examination
BP 160/ 80
Pulse 82/min
Pedal Edema ++++
Periorbital Puffiness ++
Respiratory System Pleural Effusion
CVS Normal
GIT Ascites
CNS Normal

4. Lab Data
Hb 10G/dL V/M NEGATIVE
TLC 8.3 × 10³ /uL USG ABDOMEN GROSS ASCITES AND
MASSIVE PLEURAL EFF.
PLATELETS 344 × 10³ /uL SPOT PCR 10 MG/MG
CREATININE 0.83 MG/DL S/ ALBUMIN 1.2 G/dl
UREA 47 MG/DL FLPs DERANGED
U/PROTEIN 3+ Na + 132 MMOL/L
U/RBCs NIL K+ 3.4 MMOL/L
U/WBCc NIL Cl 113 MMOL/L

5. RENAL BIOPSY
GLOMERULI :
MINIMAL MEMBRANE THICKENING WITH OCCASIONAL POSSIBLE SPIKES ON SILVER STAIN.
IFTA :
MILD
IMMUNOFLUORESCENCE :
IgG MILD GRANULAR MEMBRANE STAINING
IgA, IgM, C1Q, C3 NEGATIVE
COCLUSION :
EARLY MEMBRANOUS GLOMERULONEPHRITIS

6. Membranous
Nephropathy

8. Introduction
• 20 to 30 percent cases of
NS in White adults with
rising incidence reported in
China
• Male predominance
• Average age is above 40
years

9. Causes of
MN

10. Target Antigens

14. BACK TO OUR CASE
Beta HCG levels 20.8
CA 125 levels 2355.7
PLA2R ABx NEGATIVE
Complement levels NORMAL
ANA NEGATIVE
Anti ds DNA NEGATIVE
Viral Markers NEGATIVE
MRI abdomen and Pelvis NO DISCRETABLE OVARIAN/CERVICAL/ UTERINE
LESION

15. Baseline characteristics of Cancer
Associated MN
•Older age groups ( 6th or 7th decade of life)
•Male predominance
•Cancer associated with MN was found in 20% of the cases before the diagnosis of MN, and for
the remaining 80% cancer was diagnosed at the time of or following the diagnosis of MN.
•In previous studies there was a low risk of incidence of cancer after 1 year of follow up and this
risk was reduced to negligible numbers after 5 years, however the new studies have shown the
risk of cancer even after 15 years of follow up in cohort studies.

16. Types of Cancer associated with MN
LUNG CANCER 26%
PROSTTAE CANCER 15%
COLORECTAL CANCER 11%
BREAST CANCER 7%
STOMACH AND ESOPHAGEAL CANCER 6%
BLADDER CANCER 5%
CERVIAL AND UTERINE CANCER 4%
RENAL CELL CANCER 2%
HEMATOLOGIC MALIGNANCIES 14%

17. HISTOPATHOLOGICAL DIFFERENCES
BETWEEN PRIMARY ANY SECONDARY MN
PRIMARY MEMBRANOUS SECONDARY MEMBRANOUS
ABSENCE OFPROLIFERATIVE FEATURES ON L/M MESANGIAL / ENDOCAPILLAY PROLIFERATION ON L/M
IgG 4 PREDOMINENCE ON IF Ig G1, Ig G2, Ig G3 PREDOMINENCE ON IF
MINIMAL Ig A, Ig M, C1Q STAINING ON IF POSITIVE Ig A, Ig M, C1Q STAINING ON IF
SUEPITHELIAL IMMUNE DEPOSITS ON E/M SUBENDOTHELIAL AND MESANGIAL IMMUNE
DEPOSITS ALONG SUBEPITHELIAL DEPOSITS ON E/M

18. PATHOGENESIS
•ABX AGAINST TUMOR ANTIGEN SIMILAR TO THE PODOCYTE ANTIGEN
•TUMOR ANTIGEN-ABX COMPLEX TRAPPED IN GLOMERULAR CAPILLARY WALL
•ABX AGAINST SUPEPITHELIAL IMPLANTED TUMOR ANTIGENS
•ANY EXTRINSIC PROCESS RESPONSIBLE FOR BOTH MN AND CANCER

20. BACK TO OUR CASE
•CONSERVATIVE MANAGEMNT WITH SUPPORTIVE AND SYMPTOMATIC TREATMENT CONTINUED
FOR 6 MONTHS.
•NO RESPONSE TO THE SUPPORTIVE TREATMENT, HER SYMPTOMS AND GFR WORSENED, WE
HAD TO CONSIDER IMMUNOSUPPRESSION.
•PATIENT RESPONDED WELL TO THE STEROIDS + CYCLO, CURRENTLY ON 4TH MONTH OF MPR.

21. BACK TO OUR CASE
MONTH SPOT PROTEIN CREATININE RATIO
(mg/mg)
CREATININE (mg/dl)
SEPTEMBER 10.2 1.8
OCTOBER 5.2 1.37
NOVEMBER - 0.8
DECEMBER 1.1 0.66

23. Ongoing studies in Membranous
Nephropathy
Belimumab + Rituximab ( Anti BAFF antibody)
Obinutuzumab ( Anti BAFF antibody)
Felzartamab ( Anti CD38 antibody)
Zanubrutinib (Bruton Tyrosine kinase inhibitors)
Iptacopan ( Complement Factor B inhibitor)

24. Points of discussion
Was that Primary / Secondary Membranous Nephropathy?
Should we go for a PET scan for the diagnosis of any occult malignancy?
For how long we need to do surveillance of this patient?
Is Rituximab first line therapy for Primary Membranous Nephropathy? Your opinion.

25. TAKE HOME MESSAGE!!!