Randall-type heavy chain deposition disease (HCDD) is a rare disorder characterized by tissue deposition of a truncated monoclonal immunoglobulin heavy chain lacking the first constant domain. Pathophysiological mechanisms are unclear and management remains to be defined. Here we retrospectively studied 15 patients with biopsy-proven HCDD of whom 14 presented with stage 3 or higher chronic kidney disease, with nephrotic syndrome in 9. Renal lesions were characterized by nodular glomerulosclerosis, with linear peritubular and glomerular deposits of γ-heavy chain in 12 patients or α-heavy chain in 3 patients, without concurrent light chain staining. Only 2 patients had symptomatic myeloma. By serum protein electrophoresis/immunofixation, 13 patients had detectable monoclonal gammopathy. However, none of these techniques allowed detection of the nephrotoxic truncated heavy chain, which was achieved by immunoblot and/or bone marrow heavy chain sequencing in 14 of 15 patients. Serum-free kappa to lambda light chain ratio was abnormal in 11 of 11 patients so examined. Immunofluorescence studies of bone marrow plasma cells showed coexpression of the pathogenic heavy chain with light chain matching the abnormal serum-free light chain in all 3 tested patients. Heavy chain sequencing showed first constant domain deletion in 11 of 11 patients, with high isoelectric point values of the variable domain in 10 of 11 patients. All patients received chemotherapy, including bortezomib in 10 cases. Renal parameters improved in 11 patients who achieved a hematological response, as assessed by normalization of the free light chain ratio in 8 cases. Tissue deposition in HCDD relates to physicochemical peculiarities of both variable and constant heavy chain domains. Early diagnosis and treatment with bortezomib-based combinations appear important to preserve renal prognosis. Thus, monitoring of serum-free light chain is an indirect but useful method to evaluate the hematological response.

In MCN, the presence of numerous casts and diffuse tubular atrophy is associated with poor renal prognosis. These data suggest that additional strategies to reduce FLC burden should be considered in patients with extensive cast formation.

l'amylose AL et des autres maladies à dépôt d'immunoglobulines monoclonale

No abstract

Introduction:Predominantly monotypic plasma cell infiltrates are an uncommon renal finding in patients with malignant lymphoplasmacytic proliferation.Case presentation:We report the case of a 52-year-old man with chronic kidney disease and significant proteinuria associated with a monoclonal immunoglobulin spike (IgGκ). Kidney biopsy revealed the presence of atypical multinucleated CD138+ plasma cells with voluminous nuclei stained exclusively with a κ antibody. Electron microscopy showed mesangial and segmental parietal electron-dense, nonorganized hyaline deposits without immunogold labeling for the κ light chain. The bone marrow aspirate revealed 6% of apparently mature plasmocytes without dystrophy. We therefore concluded that the patient had an indolent multiple myeloma with specific renal involvement in the form of malignant monotypic interstitial plasmacytic infiltration. We initiated a specific chemotherapy regimen including bortezomib–cyclophosphamide–dexamethasone. After 4 months of follow-up, creatinine levels had improved slightly and free κ light-chain levels had decreased significantly within the normal range.Conclusion:This case highlights the need to consider neoplastic interstitial plasma cell infiltration systematically in patients diagnosed with an apparently benign monoclonal gammopathy and to consider adaptation of the chemotherapy regimen, to improve renal function.