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

Česká verzia

Authors: Z. Adam ¹; M. Krejčí ¹; L. Pour ¹; S. Štěpánková ²; Z. Čermáková ³; L. Voska ⁴; V. Teplan ⁵; A. Křivanová ¹; R. Hájek ¹; J. Mayer ¹
Authors place of work: Interní hematoonkologická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MU Dr. Jiří Vorlíček, CSc. ¹; Interní hepatogastroenterologická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MU Dr. Jan Lata, CSc. ²; Oddělení klinické biochemie FN Brno, pracoviště Bohunice, přednosta doc. MU Dr. Milan Dastych, CSc. ³; Pracoviště klinické a transplantační patologie IKEM Praha, přednostka prim. MU Dr. Eva Honsová, Ph. D. ⁴; Klinika nefrologie, Transplantcentrum IKEM Praha, přednosta prof. MU Dr. Vladimír Teplan, DrSc. ⁵
Published in the journal: Vnitř Lék 2009; 55(11): 1089-1096
Category: Case Reports

Summary

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 fi ndings confi rmed 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 μmol/l) before application of conditioning regimen. High dose therapy was complicated by with deterioration of renal function, creatinine increased to 600 μmol/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 μmol/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.

Key words:
light chain deposition disease – monoclonal gammapathy – multiple myeloma – renal insuficiency – nephrotic syndrome – high dose chemotherapy with autologous peripheral stem cell transplantation

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