Podocytopathy in patients with monoclonal gammopathy: three patients and literature review

Abstract

Background: Renal manifestations of monoclonal gammopathies are of increasing interest among nephrologists. Typical manifestations include light chain cast nephropathy, amyloidosis or renal damage mediated by monoclonal immunoglobulin deposition. Podocytopathies in the setting of an underlying monoclonal gammopathy constitute a rare manifestation of these diseases and, although being described in the literature, remain a challenge since most data derive from case reports.

Methods: A retrospective review of the clinical data of Hospital del Mar and Hospital Vall d'Hebron was performed to identify patients with minimal change disease (MCD) or focal and segmental glomerulosclerosis (FSGS) in the setting of neoplasms that produce monoclonal (M) protein. Additionally, a literature review on this topic was performed. This study aims to describe the clinical characteristics and outcomes of these patients.

Results: Three patients were identified to have podocytopathy and monoclonal gammopathy between the years 2013 and 2020. All three were males and >65 years of age. Two patients were diagnosed with MCD and one patient was diagnosed with FSGS. All patients underwent a kidney biopsy and light and electron microscopic studies were performed. The underlying causes of monoclonal gammopathy were multiple myeloma in two cases and Waldeström macroglobulinemia in one case. Two patients developed nephrotic syndrome during the follow-up. All patients were under active hematological treatment. One patient presented a complete remission of proteinuria whereas the other two presented a partial remission.

Conclusions: Podocytopathies may infrequently be found in patients with monoclonal gammopathies. Patients with overt glomerular proteinuria and hematological disorders with M protein should undergo a kidney biopsy for prompt diagnosis and to specify a prognosis. In addition, further study on this matter must be done to understand the pathophysiology and treat these patients appropriately.

Keywords: MGRS; Wäldestrom disease; focal segmental glomerulosclerosis; minimal change disease; multiple myeloma; podocytopathy.

Figure 1:

Patient 1. Optical morphology of the glomeruli. H&E: hematoxylin and eosin stain; PAS: periodic acid-Schiff stain; JMS: Jones methenamine stain; TRIM: Masson's trichrome. Magnification ×600.

Figure 2:

Patient 1. Cortical tubules showing a diffuse increase in protein reabsorption. Absence of abnormal casts. Jones methenamine stain; magnification ×400.

Figure 3:

Patient 1. Electron microscopy findings showing podocyte foot process effacement (black arrows) and microvillus transformation (white arrows).

Figure 4:

Patient 2. Electron microscopy showing podocyte foot process effacement (black arrows), microvillus transformation (white arrows) and occasional cytoplasmic pseudocysts (red arrow).