AN OBSERVATIONAL STUDY ON THE CLINICOPATHOLOGIC FEATURES OF RENAL MONOCLONAL IMMUNOGLOBULIN DEPOSITION DISEASE

Introduction:

Monoclonal immunoglobulin deposition disease (MIDD) in kidney is characterised by the deposition of monoclonal immunoglobulins on glomerular basement membrane and tubular basement membrane. Monoclonal immunoglobulins are secreted as a result of clonal proliferation of abnormal plasma cell or B cell lineage. MIDD comprises Light chain deposition disease (LCDD) with deposits of either kappa or lambda, Heavy chain deposition disease (HCDD) with deposits of single heavy chain, Light and heavy chain deposition disease (LHCDD) with deposits of monoclonal light chain and heavy chain. LCCD could reportedly have concomitant light chain cast nephropathy (LCCN) in the biopsy. This study aims to analyse the clinicopathologic characteristics of monoclonal immunoglobulin deposition disease reported at single pathology centre.

Methods:

We conducted observational study of all the native kidney biopsies reported as monoclonal immunoglobulin deposition disease from 2018 to 2024. The panel for immunofluorescence study included IgG, IgA, IgM, C3, C1q, kappa and lambda light chains. All the pathology slides were reviewed. The clinicopathologic parameters were analysed based on the glomerular morphologies as well as between MIDD and MIDD+LCCN groups. The statistical analysis was performed using SPSS software version 21. p value of <0.05 is statistically significant.

Results:

23,182 biopsies were reviewed. 60 cases of MIDD and 73 cases of MIDD+LCCN were identified, the biopsy incidence being 0.25% and 0.31% respectively. The pathologic spectrum included LCDD (41), HCDD (7), LHCDD (12), LCDD+LCCN (69) and LHCDD+LCCN (4). Of the total 133 cases, 94 were males. 65.4% presented with acute kidney injury and 53.3% required haemodialysis. All the cases had proteinuria while 45.1% were in nephrotic range. The mean serum creatinine at presentation was 5.2±3.5 mg/dl. 35.3% were known cases of multiple myeloma at the time of biopsy. One patient had Hodgkin lymphoma. There was no clinical suspicion of hematologic disorder in the rest. The glomeruli exhibited three morphologies - normocellular (54.1%), mild mesangial matrix increase (12.7%), nodular glomerulosclerosis (33%). None had endocapillary hypercellularity, crescents. The tubular basement membrane appeared prominent. PAS-negative casts were observed in the tubular lumen of LCCN cases, accompanied by giant cell reaction. All cases showed negative staining by Congo red. Patients with nodular glomerulosclerosis presented with nephrotic syndrome (Table 1).

The cases with normocellular glomeruli had sub-nephrotic proteinuria and IFTA of <25% in the biopsy. MIDD+LCCN group had significant presentation of acute kidney injury, sub-nephrotic proteinuria and higher serum creatinine than MIDD group (Table 2). The biopsy of MIDD+LCCN group had predominantly lambda deposits and normocellular glomeruli.

Conclusions:

Renal biopsy with a systematic analysis of the immunofluorescence findings is essential for the diagnosis of MIDD. Only 35% of patients with MIDD had clinical or laboratory features of multiple myeloma. There is a wide spectrum of renal histopathological lesions in MIDD. MIDD with concomitant light chain cast nephropathy is associated with normal glomeruli in the biopsy and presents with acute kidney injury, higher serum creatinine and increased dialysis requirement than isolated MIDD.

I have no potential conflict of interest to disclose.

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