First case of proliferative glomerulonephritis with monoclonal immunoglobulin deposits in French Guiana "case report"

¹Nephrology-Dialysis Department, CHU de Guyane/Site de Saint-Laurent-du-Maroni, French Guiana

^&Corresponding author
Arriel Makembi Bunkete, Nephrology-Dialysis Department, CHU de Guyane/Site de Saint-Laurent-du-Maroni, French Guiana

Introduction    

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a rare kidney disease classified as a monoclonal gammopathy of renal significance. It is characterized by monotypic glomerular immunoglobulin deposits, primarily IgG3, with complement activation. First described in 2004 [1], PGNMID typically presents in individuals around the sixth decade of life, although younger patients can also be affected [2]. The disease is confined to the kidneys and presents as a chronic glomerulopathy with a poor renal prognosis [3]. The underlying pathophysiology of PGNMID remains incompletely understood. It is thought to arise from a dysregulated clonal proliferation of B cells or plasma cells producing monoclonal immunoglobulins, which then deposit within glomeruli, leading to complement activation and subsequent renal damage [4]. Unlike other monoclonal gammopathies, PGNMID does not always present with detectable circulating monoclonal proteins, making diagnosis challenging. Advanced imaging techniques and genetic studies are currently being explored to better understand the mechanisms leading to its development. Epidemiologically, PGNMID remains underreported, in part due to the necessity of renal biopsy with immunofluorescence to confirm the diagnosis. Many cases are misdiagnosed as immune-complex-mediated glomerulonephritis or post-infectious glomerulonephritis. Furthermore, the clinical presentation is highly variable, ranging from asymptomatic proteinuria to rapidly progressive glomerulonephritis leading to dialysis [5]. We report the first documented case of PGNMID in French Guiana, diagnosed in a 59-year-old patient at the stage of end-stage renal disease requiring dialysis.

Patient and observation     

Patient information: a 59-year-old Amerindian man with a history of chronic arterial hypertension and post-infectious glomerulonephritis in 2016 presented with symptoms of progressive renal failure.

Timeline of current episode: over six months, the patient developed fatigue, weight loss, and oliguria. He had no known hematologic or malignant disease, and had experienced multiple episodes of uncontrolled hypertension.

Clinical findings: upon admission, the patient exhibited generalized edema, uncontrolled hypertension (180/110 mmHg), and significant proteinuria. Laboratory tests revealed worsening renal function, with a creatinine level of 520 µmol/L and proteinuria of 2.14 g/24h. The urine sediment showed microscopic hematuria without dysmorphic red blood cells. His immunological workup, including antinuclear antibodies and anti-neutrophil cytoplasmic antibodies, was negative. Serum protein electrophoresis did not detect any monoclonal gammopathy. Viral serologies for hepatitis B, hepatitis C, and HIV were negative.

Diagnostic assessment: a renal biopsy was performed, which showed extensive interstitial fibrosis (90%) and a monotypic IgG3 lambda deposit on immunofluorescence (Figure 1), confirming the diagnosis of PGNMID [5]. Electron microscopy demonstrated granular immune deposits within the glomeruli, reinforcing the immunofluorescence findings. The extent of fibrosis suggested a late-stage disease with a limited potential for functional recovery.

Diagnosis: the final diagnosis was proliferative glomerulonephritis with monoclonal IgG3 lambda deposits (PGNMID) at an advanced fibrotic stage. Other causes of glomerulonephritis were ruled out based on negative serology and histopathology.

Therapeutic interventions: given the advanced fibrosis and renal failure, the patient was initiated on dialysis. Supportive therapy included antihypertensive treatment with angiotensin-converting enzyme inhibitors, dietary adjustments to manage protein intake, and close monitoring of electrolyte balance. Due to the advanced state of the disease, targeted therapy with immunosuppressive agents was not initiated.

Follow-up and outcome of interventions: the patient remained on dialysis, with no significant improvement in renal function. A multidisciplinary approach was adopted to optimize his quality of life, focusing on blood pressure control, nutritional support, and psychological counseling to help him adjust to long-term dialysis.

Patient perspective: the patient and his family were informed about the diagnosis and prognosis. Despite the need for dialysis, the patient expressed appreciation for the medical care received and agreed to participate in long-term follow-up.

Informed consent: the patient provided written consent for publication of this case.

Discussion     

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a rare and recently described form of monoclonal gammopathy of renal significance (MGRS), first identified as a distinct entity in 2004 by Nasr et al. [2]. Proliferative glomerulonephritis with monoclonal immunoglobulin deposits affects both sexes and typically presents around the sixth decade of life [2,3]. However, the true prevalence remains underestimated due to the need for renal biopsy and specialized immunofluorescence staining to confirm the diagnosis [4]. In some cases, it may be misclassified as post-infectious glomerulonephritis or membranoproliferative GN. The literature suggests a growing recognition of PGNMID, particularly with increasing access to advanced pathology services, but the condition remains underreported, especially in developing regions [1].

Diagnosis hinges on identifying monotypic immunoglobulin deposits in the glomeruli, most frequently IgG3 with a single light chain (often lambda), as seen in our patient [1,5]. Unlike other monoclonal gammopathies, PGNMID may not be associated with detectable serum or urine monoclonal proteins [2,4], making histological assessment paramount. Electron microscopy typically shows granular electron-dense deposits, helping differentiate PGNMID from other glomerulopathies like fibrillary or immunotactoid glomerulonephritis [6,7]. In our case, the presence of IgG3 lambda deposits and 90% interstitial fibrosis indicated a late and irreversible stage of the disease, highlighting the importance of early biopsy and comprehensive immunopathologic evaluation.

Management of PGNMID remains controversial. In patients with preserved renal function, therapies targeting the clonal B or plasma cells (e.g., corticosteroids, rituximab, bortezomib) have been proposed to reduce monoclonal protein production [4,8]. However, evidence remains limited, and no randomized clinical trials have yet established a standardized approach. In advanced stages with extensive fibrosis, as in our patient, therapeutic options are limited, and supportive care with dialysis becomes the only viable strategy [2,4]. Some reports suggest a risk of recurrence post-transplantation in allografts, indicating persistent underlying clonal activity [9,10].

This case is unique as it is the first reported in French Guiana, underscoring the importance of recognizing PGNMID even in regions with limited diagnostic infrastructure. The patient had a history of post-infectious glomerulonephritis (PIGN), raising the question of whether PGNMID may sometimes follow or mimic PIGN. Some studies suggest that immune activation following infection may unmask or trigger clonal immunoglobulin production [5]. This case reinforces the need to reevaluate presumed PIGN cases with atypical evolution, especially in older patients or those with persistent proteinuria. The absence of circulating monoclonal proteins does not rule out PGNMID, and renal biopsy remains essential.

Conclusion     

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a rare but serious condition with a poor renal prognosis. Our case highlights the importance of renal biopsy and immunofluorescence in diagnosing PGNMID, particularly in patients with unexplained progressive renal failure. Early recognition is critical to improve outcomes, but in advanced cases, as seen here, dialysis may be the only therapeutic option. Further research is needed to develop more effective treatment strategies and to elucidate the underlying pathophysiology of this enigmatic disease.

Competing interests     

The authors declare no competing interests.

Authors' contributions     

Patient management: Arriel Makembi Bunkete, Florence Fermigier, Malika Belgrine, Modi Sidibe. Data collection: Arriel Makembi Bunkete, Modi Sidibe, Gloria Ningaro Timem. Manuscript drafting: Arriel Makembi Bunkete. Manuscript revision: Malika Belgrine, Florence Fermigier, Timoté Davodoun, Irénée Djiconkpode. All the authors have read and agreed to the final manuscript.

Acknowledgements     

We warmly thank Professor Sophie Ferlicot, Head of the Department of Anatomical and Cytological Pathology at AP-HP Kremlin-Bicêtre, for reviewing the biopsy and kindly providing us with the relevant information.

Figure     

Figure 1: indirect immunofluorescence showing granular staining for immunoglobulin G subclass 3. Immunofluorescence of the kidney biopsy demonstrates granular glomerular deposits positive for immunoglobulin G subclass 3 (IgG3), supporting the diagnosis of PGNMID; no staining for other IgG subclasses or light chains was observed

References