title: [Complete remission of nephrotic syndrome and improvement of renal function in a patient with light chain deposition disease following high dose chemotherapy with transplantation of autologous haematopoietic stem cells. A case study and review of literature].
abstract: Light chain deposition disease (LCDD) damages most frequently kidneys, and less frequently other organs. The incidence of LCDD is lower than the incidence of AL-amyloidosis. Symmetric swelling of both legs was the first sign of nephrotic syndrome with renal insufficiency in our female patient. Renal biopsy specimen revealed the diagnosis of LCDD. Bone marrow biopsy contained 40% of plasma cells. Bone survey showed no osteolytic changes. These findings confirmed the diagnosis of multiple myeloma (MM) Durie Salmon stage IB with LCDD. The patient was initially treated with 4 cycles of VAD (vinkristine, adriamycine, dexamethasone) chemotherapy with no response. Followed collection of peripheral haematopoietic stem cells and later high dose chemotherapy with reduced dose of melphalan 140 mg/sqm and autologous peripheral haematopoietic stem cells transplantation. Melphalan dose was reduced because of renal insufficiency (serum creatinine 290 micromol/l) before application of conditioning regimen. High dose therapy was complicated by with deterioration of renal function, creatinine increased to 600 micromol/l. Worsening of renal function was most likely caused by nephrotoxicity of melphalan in nephrotic syndrome. This has been previously described in patients with AL-amyloidosis, and nephrotic syndrome who were treated with high dose melphalan. This phenomenon was entitled "post conditioning renal insufficiency". Hypoalbuminemia hypoproteinemia and reduced intravascular volume and renal damage caused by amyloid deposits as well as probably, amorphous non-amyloid deposits of monoclonal immunoglobulin are likely to have contributed to nephrotoxicity of the high dose of melphalan. However, worsening of renal insufficiency was facilitated by the mucositis-associated sepsis. Follow-up examination one month after high dose chemotherapy showed complete remission, that was confirmed by further examinations. In the course of the first year after high dose chemotherapy renal function gradually improved and nephrotic syndrome completely disappeared (complete kidney remission). Proteinuria declined to 2-3 g/24 hours and glomerular filtration slowly improved. Three years after high dose chemotherapy the patient is still in complete remission of multiple myeloma and free of nephrotic syndrome, with slightly increased creatinine (160 micromol/l) that, nevertheless, has had an improving tendency over last 3 years. The present case study illustrates accomplishment of complete haematological remission with high dose chemotherapy followed by autologous haematopoietic stem cells transplantation despite complete resistance of the disease to the standard chemotherapy VAD in a patient with MM and LCDD. We draw the reader's attention to the possibility of nephrotoxic effects of high dose melphalan (post conditioning renal insufficiency) in patients with nephrotic syndrome caused by light chain deposits as AL-amyloid or amorphous light chains deposits (LCDD)and we document the importance of plasma free light chain detection.
authors.affiliation: Interní hematoonkologická klinika Lékarské fakulty MU a FN Brno. z.adam@fnbrno.cz
authors.forename: Z
authors.initials: Z
authors.lastname: Adam
authors.forename: M
authors.initials: M
authors.lastname: Krejcí
authors.forename: L
authors.initials: L
authors.lastname: Pour
authors.forename: S
authors.initials: S
authors.lastname: Stepánková
authors.forename: Z
authors.initials: Z
authors.lastname: Cermáková
authors.forename: L
authors.initials: L
authors.lastname: Voska
authors.forename: V
authors.initials: V
authors.lastname: Teplan
authors.forename: A
authors.initials: A
authors.lastname: Krivanová
authors.forename: R
authors.initials: R
authors.lastname: Hájek
authors.forename: J
authors.initials: J
authors.lastname: Mayer
mesh_terms: D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000276:immunology*; D007668:Kidney / Q000473:pathology; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D009101:Multiple Myeloma / Q000150:complications / Q000276:immunology / Q000628:therapy*; D009404:Nephrotic Syndrome / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D012074:Remission Induction; D014182:Transplantation, Autologous
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007147:Immunoglobulin Light Chains; D008558:Melphalan