Monoclonal IgG kappa (IgGk) associated crescentic glomerulonephritis: A case of PGNMID in disguise

Sowmiya D

Physician Assistant, Kauvery hospital, Hosur, Tamil Nadu

Abstract

Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a rare and distinct entity characterized by glomerular deposition of monoclonal immunoglobulins, often mimicking immune complex – mediated glomerulonephritis.

We present a unique case of crescentic glomerulonephritis initially suggestive of rapidly progressive glomerulonephritis, which upon further immunofluorescence and subclass staining revealed monoclonal IgGk deposits, consistent with PGNMID. PGNMID is always a diagnostic challenge as the clone detection rate is very low and our case is associated with unusual aggressive crescentic morphology.

This case underscores the importance of detailed immunopathology evaluation in atypical glomerulonephritis presentations and highlights the diagnostic overlap between PGNMID and other forms of crescentic glomerulonephritis. Early recognition is critical for appropriate therapeutic intervention and prognostic stratification.

Introduction

Proliferative glomerulonephritis with monoclonal immunoglobulin (PGNMID) is a rare and under recognized form of glomerulonephritis characterized by deposition of a single IgG subclass and light chain in the glomeruli, most commonly IgG3k. First described by Nasr et al.in 2004, PGNMID occupies a unique position within the spectrum of monoclonal gammopathy of renal significance (MGRS), where a seemingly indolent or undetectable clone causes significant renal injury.

Despite its distinct immunofluorescence profile, PGNMID often mimics other glomerular diseases on light microscopy; including membranoproliferative glomerulonephritis, post infectious glomerulonephritis, or even lupus nephritis. Crescentic glomerulonephritis is a rare but increasingly recognized manifestation of PGNMID, often leading to diagnostic confusion and delayed treatment. Because circulating monoclonal proteins may be absent in up to 70% of patients, PGNMID remains a histopathologic diagnosis that depends on kidney biopsy with immunofluorescence and electron microscopy.

We present a diagnostically challenging case of crescentic glomerulonephritis with monotypic IgGk deposits. This case underscores the need for heightened clinical suspicion and specialized staining to correctly identify PGNMID, especially when standard serologic and hematologic evaluations are inconclusive.

Case Presentation

Chief complaints

51-year-aged male presented with complaints of bilateral leg swelling since 3months and history of uncontrolled hypertension since six months.

History of Present Illness

Presented with complaints of bilateral lower limb swelling since three months, associated with facial puffiness

No h/o haematuria, pyuria, graveluria

H/o uncontrolled hypertension for three months. Blood pressure readings have remained elevated at home despite adherence to prescribed three classes of antihypertensive medications. No associated fever, joint pain or urinary symptoms reported.

No h/o use of NSAIDS

Past History

Known to have Hypertension since three years

H/o taking Ayurveda medicine for weight loss and HTN for two months

(Lost 13kg in two months)

No known history of diabetes mellitus, tuberculosis or any chronic illness.

No history of renal disease, autoimmune disorders or haematological malignancy.

No prior history of similar symptoms.

Family History

No known familial kidney disease or autoimmune disorders

Non – consanguineous parents

Social History

Nonsmoker, No alcohol or drug use

Physical Examination

Vitals:

BP – 170/100, HR – 70/min, Afebrile

SpO2 – 98% on RA

No pallor, icterus or lymphadenopathy

Bilateral non-tender pitting pedal edema extending up to thighs

Normal S1 and S2, no murmurs, gallops or rubs

Peripheral pulses intact and symmetrical

Chest clear to auscultation bilaterally

No crackles, rhonchi or signs of pulmonary edema

Soft, non-tender, no organomegaly, No ascites or renal angle tenderness

Alert and oriented, cranial nerves intact; no focal neurological deficits

Investigations

Test	Values
Serum Creatinine	1.6mg/dL
Total Protein	3.7 g/dl
Albumin	1.8 g/dl
Globulin	1.9g/dl
Lipid Profile	Total Cholesterol - 237mg/dL
	Triglycerides - 183mg/dL
	HDL - 28mg/dL
	LDL - 173mg/dL
	VLDL - 37mg/dL
	LDL/HDL Ratio - 6.18 Ratio
	CHO/HDL - 9%
Urine Routine	Albumin - 3+
	RBC-6-8/hpf
	Pus-2-4/hpf
	No RBC casts
Urine Protein/Creatinine Ratio spot	Micro protein - 492 mg/dL
	Creatinine - 61.0 mg/dL
	Ratio - 8.06
Urine 24hrs Protein	8862 mg/dL

Renal Biopsy

Investigations: Identification of clone

Test	Values
Serum Protein Electrophoresis	No M band
Serum Free Light Chain Ratio	Kappa - 69.1
	Lambda - 38
	Ratio – 1:818
Bone Marrow Cytology for FISH (Fluorescence In Situ Hybridization)	Negative
ANCA, ANA ,Anti GBM	Negative

Serum protein electrophoresis

Test	Values
Total Protein	4.83 g/dl
Albumin	2.65 g/dl
Globulin	2.18 g/dl
Alpha 1	0.34 g/dl
Alpha 1	0.69 g/dl
Beta 1	0.35 g/dl
Beta 2	0.35 g/dl
Gama	0.45 g/dl

Bone Marrow Biopsy: Norm cellular marrow with trilineage hematopoiesis and no significant abnormality

Flow cytometry: Negative for lymphoma

Clone Detection Rate: Clone detection rate in PGNMID is less than 30%

Diagnostic challenges: Challenges are at multiple levels while approaching MGRS

Diagnosis

Clinical clues:

Rapidly progressive renal dysfunction (acute rise in serum creatinine)
Nephrotic range proteinuria with microscopic haematuria
Absence of systemic symptoms or extra renal involvement

Renal Biopsy Findings

Light microscopy:
Diffuse endocapillary proliferation with segmental cellular and fibro cellular crescents
Mild mesangial expansion and hyper cellularity

Immunofluorescence (IF)

Monoclonal IgGk deposition in a granular pattern along capillary walls and mesangium
Negative for IgA,IgM,C1q and lambda light chains
Strong positivity for IgG subclass and kappa light chain only

Final Diagnosis

Proliferative Glomerulonephritis with Monoclonal IgGk Deposits (PGNMID) associated with Monoclonal Gammopathy of Renal Significance (MGRS) presenting as Crescentic Glomerulonephritis.

Management

Given the diagnosis of proliferative glomerulonephritis with monoclonal IgGk deposits (PGNMID) presenting as crescentic GN, and in the absence of detectable serum or urine monoclonal protein, the patient was managed as a case of Monoclonal Gammopathy of Renal Significance (MGRS). The aggressive histology warranted prompt, clone-directed therapy to halt ongoing glomerular injury.

1. Clone Directed Therapy: Bortezomib Based Regimen

Patient received 3 cycles of bortezomib, cyclophosphamide and dexamethasone (BCD Regimen). Each cycle included 4 weekly doses totalling 12 doses over 3 months.

BCD Protocol (Per Dose):
Bortezomib 1.3mg/m2 subcutaneously
Cyclophosphamide 500mg intravenously
Dexamethasone 40mg intravenous injection
This regimen was administered on a weekly schedule with each cycle spanning 28days

2. Rationale

Bortezomib, a proteasome inhibitor, targets plasma cells producing the nephrogenic monoclonal IgG.
Cyclophosphamide provides cytotoxic immunosuppression and complements anticlonal effects.
High-dose dexamethasone enhances plasma cell apoptosis and reduces glomerular inflammation.

3. Clinical Response

Following completion of the 3-cycle BCD regimen (12 doses total), the patient showed:
Improved renal function (decline in serum creatinine)
Reduced proteinuria
Resolution of edema and stabilization of eGFR
No need for dialysis
No significant adverse effects such as neuropathy or cytopenia
Supportive management:
Blood pressure control with ACE inhibitors/ARBS once renal function allowed
Loop diuretics for volume overload
Monitoring for hematologic toxicity and peripheral neuropathy during therapy
PJP prophylaxis considered during treatment due to high-dose corticosteroid use
Herpes prophylaxis and antifungal prophylaxis
Nutritional support and anaemia management as part of CKD care

4. Follow-up plan

Continued close follow up with nephrology and medical oncology
Repeat clonal workup (e.g., serum free light chains, bone marrow biopsy) if relapse occurs
Monitoring for potential transformation into overt plasma cell dyspraxia or lymphoma

Outcome

Creatinine at present is 1.1 mg/dl and 24 hr urine protein at present is 150 mg/day

Conclusion

This case highlights the diagnostic complexity of PGNMID, particularly when presenting with a crescentic pattern that mimics other forms of rapidly progressive glomerulonephritis. The identification of monoclonal IgG3k deposits, despite an initially unremarkable hematologic evaluation, underscores the importance of detailed immunopathology workup in atypical or resistant glomerulonephritis cases.

Recognition of PGNMID as part of the MGRS spectrum is critical, as it shifts the treatment approach from conventional immunosuppression to clone-directed therapy aimed at the underlying pathogenic B-cell or plasma cell clone. In our patient, early initiation of clone-directed therapy resulted in clinical stabilization and prevention of further renal decline.

As evidence continues to emerge, this case reinforces the need for heightened clinical suspicion, advanced diagnostic techniques, and a precision medicine approach in managing rare monoclonal glomerulopathies. Early diagnosis and targeted treatment can significantly alter the disease trajectory and improve patient outcome in PGNMID.

Monoclonal IgG kappa (IgGk) associated crescentic glomerulonephritis: A case of PGNMID in disguise

Monoclonal IgG kappa (IgGk) associated crescentic glomerulonephritis: A case of PGNMID in disguise

Sowmiya D

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