A RARE CASE OF MGRS – PGNMID WITH LIGHT CHAIN RESTRICTION ONLY

Introduction:

The diagnosis of Monoclonal gammopathy of renal significance(MGRS) is always challenging. In 2004, Nasr et al first defined proliferative glomerulonephritis with monoclonal immunoglobulin G deposition which is characterized by a single IgG subclass with a single light chain subtype deposited in the glomerulus. It is a rare disease with an autologous kidney biopsy rate of 0.17% to 0.21% which is roughly 8 times lower than AL amyloidosis and 2 times lower than MIDD. It is commonly seen in middle aged individuals with a mean age of around 55 years. 20% patients are above the age of 70 years. PGNMID as such has only 30% clone detection rate. The subtype of PGNMID with light chain restriction only was found to have higher clone detection rates

Methods:

A 60-year-old male patient came to our hospital with complaints of progressive swelling of lower limbs with shortness of breath and decreased urine output since 1 week. He also developed uremic symptoms like nausea and vomiting since 4 days. On physical examination he had bilateral pitting pedal edema and pallor was present. On investigation patient was found to have anemia with Hemoglobin 8.9 gm/dl and renal failure with serum urea and creatinine of 151mg/dl and 7.7 mg/dl respectively. His serum albumin was low 2.9 gm/dl. His urine routine examination showed active sediments and nephrotic range proteinuria. Kidney sizes and echoes were normal on ultrasound scan. The patient was initiated on dialysis in view of uremic symptoms and a renal biopsy was performed to identify the cause of rapidly progressive glomerulonephritis.

Results:

The renal biopsy revealed significant peripheral and mesangial coarse granular deposits of C3c and kappa light chains with insignificant deposits of IgA, IgM, C1q. MPGN pattern glomerulonephritis with deposits of kappa light chain and C3c was found to be present. Hence a diagnosis of Proliferative glomerulonephritis with monoclonal immune deposits – light chain type (PGNMID-LC) - to rule out underlying monoclonal paraproteinemia with evidence of chronicity with global glomerulosclerosis (10/14) and mild IFTA (20%), vessel changes of accelerated HTN/TMA was made. In an attempt to identify the underlying clone and other organ involvement further investigations like skeletal survey was done. Chest X ray revealed B/L blunting of CP angle suggestive of B/L Pleural effusion while X ray Neck revealed Wedge compression of C5 vertebra. X ray B/L shoulder joint, X ray skull and X ray pelvis were Normal. Serum free light chain assay report is shown in figure 3. Serum Protein electrophoresis,Serum immunofixation, Bone marrow aspirate and biopsy were normal. The underlying pathogenic plasma cell clone could not be identified hence the patient was started on empirical chemotherapy for a hypothetic plasma/B cell clone. Patient continued to have renal dysfunction was managed with maintenance hemodialysis. Due to high recurrence rate post transplant, transplantation was not considered in this patient

Conclusions:

LC only variant of PGNMID is associated with a high detection rate of pathogenic plasma cell clone. Monoclonal Immunoglobulin is identified by serum and urine IF in 65% and 73 % respectively, with abnormal serum free light chain in 83% and detectable BM plasma cell clone in 88%. Activation of alternate complement pathway by monoclonal Ig LC likely plays a role in its pathogenesis. In a study by Nasr et al, 17% patients had complete renal remission, 13% had partial remission,
13% had persistent renal dysfunction and 53% reached ESRD. The median time to ESRD was 28 months in their study while our patient continued to be on dialysis in spite of the chemotherapy.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.