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

Czech version

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‘ workplace: 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: Vnitř Lék 2009; 55(11): 1089-1096
Category: Case Reports

Overview

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

Sources

1. Randall RE, Williamson WC jr, Mulinax F et al. Manifestation of systemic light chain deposition. Am J Med 1976; 60: 293– 299.

2. Heilman RL, Velosa JA, Holley KE et al. Long term follow up and response to chemotherapy in patients with light chain deposition disease. Am J Kidney Dis 1992; 20: 34– 41.

3. Pozzi C, Fogazzi GB, Banfi G et al. Renal disease and patient survival in light chain deposition disease. Clin Nephrol 1995; 43: 281– 287.

4. Cogné M, Preud’homme JL, Bauwens M. Structure of monoclonal kappa chain of the V kappa IV subgroup in the kidney and plasma cells in light chain deposition disease. J Clin Invest 1991; 87: 2186– 2190.

5. Wahner-Roedler DL, Kyle RA. Heavy chain diseases. Best Pract Res Clin Hematol 2005; 18: 729– 746.

6. van Ingen G, van Bronswijk H, Meijer CJ et al. Light chain deposition disease without detectable light chains in serum or urine. Report of a case and review of the literature. Neth J Med 1991; 39: 142– 147.

7. Sakakima M, Fujigaki Y, Tsuji T et al. High dose chemotherapy and stem cell support in a patient of light- and heavy‑chain deposition disease with abnormal marrow cell surface antigens and no monoclonal protein. Intern Med 2005; 44: 970– 974.

8. Steuhl KP, Knorr C, Rohrbach JM et al. Paraproteinemic corneal deposits in plasma cell myeloma. Am J Ophthalmol 1991; 111: 312– 318.

9. Pelletier G, Fabre M, Attali P et al. Light chain deposition disease presenting with hepatomegaly: an association with amyloid‑like fibrils. Postgrad Med J 1988; 64: 804– 808.

10. Kijner CH, Yousem SA. Systemic light chain deposition disease presenting as multiple pulmonary nodules. A case report and review of the literature. Am J Surg Pathol 1988; 12: 405– 413.

11. Girelli CM, Lodi G, Rocca F. Kappa light chain deposition of the liver. Eur J Gastroenterol Hepatol 1998; 10: 429– 430.

12. Wohl P, Chadimová M, Englis M et al. Light chain deposition disease as a cause of renal failure. Čas Lék Česk 1998; 137: 721– 724.

13. Merta M, Rysavá R, Zabka J et al. Kidney involvement in light‑chain deposition disease. Sb Lek 2002; 103: 397– 403.

14. Zhu L, Herrera GA, Murphy- Ullrich JE et al. Pathogenesis of glomerulosclerosis in light chain deposition disease. Role for transforming growth factor‑beta. Am J Pathol 1995; 147: 375– 385.

15. Preud’homme JL, Aucouturier P, Touchard G et al. Monoclonal immunoglobulin deposition disease (Randall type). Relationship with structural abnormalities of immunoglobulin chains. Kidney Int 1994; 46: 965– 972.

16. Venkataseshan VS, Faraggiana T, Hughson MD et al. Morphologic variants of light‑chain deposition disease in the kidney. Am J Nephrol 1988; 8: 272– 279.

17. Salant DJ, Sanchorawala V, D’Agati VD. A case of atypical light chain deposition disease – diagnosis and treatment. Clin J Am Soc Nephrol 2007; 2: 858– 867.

18. Baur A, Stäbler A, Lamerz R et al. Light chain deposition disease in multiple myeloma: MR imaging features correlated with histopathological findings. Skeletal Radiol 1998; 27: 173– 176.

19. Ferrario F, Rastaldi MP. Histopathological atlas of renal diseases: light chain deposition disease. J Nephrol 2005; 18: 499– 502.

20. Gokden N, Barlogie B, Liapis H. Morphologic heterogeneity of renal light‑chain deposition disease. Ultrastruct Pathol 2008; 32: 17– 24.

21. Joh K. Pathology of glomerular deposition diseases. Pathol Int 2007; 57: 551– 565.

22. Gu X, Herrera AG. Light chain mediated acute tubular interstitial nephritis: a poorly recognized pattern of renal disease in patients with plasma cell dyscrasia. Arch Pathol Lab Med 2006; 130: 165– 169.

23. Ganeval D, Noël LH, Preud’homme JL et al. Light chain deposition disease: Its relation with AL type amyloidosis. Kidney Int 1984; 26: 1– 9.

24. Hofmann‑Guilaine C, Nochy D, Jacquot C et al. Association light chain deposition disease (LCDD) and amyloidosis. One case. Pathol Res Pract 1985; 180: 214– 219.

25. Jacquot C, Saint- Andre JP, Touchard Get al. Association of systemic light‑chain deposition disease and amyloidosis: a report of three patients with renal involvement. Clin Nephrol 1985; 24: 93– 98.

26. Lin J, Markowitz GS, Valeri AM et al. Renal monoclonal immunoglobulin deposition disease. The disease spectrum. J Am Soc Nephrol 2001; 12: 1482– 1492.

27. Pozzi C, D’Amico M, Fogazzi GB et al. Light chain deposition disease with renal involvement: clinical characteristics and prognostic factor. Am J Kidney Dis 2003; 42: 1154– 1163.

28. Leung N, Lager DJ, Gertz MA et al. Long‑term outcome of renal transplantation in light‑chain deposition disease. Am J Kidney Dis 2004; 43: 147– 153.

29. Royer B, Arnulf B, Martinez F et al. High dose chemotherapy in light chain or light and heavy chain deposition disease. Kidney Int 2004; 65: 642– 648.

30. Barraclough KA, Dowling JP, Schwarer AP et al. Sequential autologous peripheral blood stem cell transplantation and kidney transplantation of light chain deposition disease. Nephrol Dial Transplant 2007; 22: 1268– 1269.

31. Brockhurst I, Harris KP, Chapman CS.Diagnosis and monitoring a case of light‑chain deposition disease in the kidney using a new, sensitive immunoassay. Nephrol Dial Transplant 2005; 20: 1251– 1253.

32. Firkin F, Hill PA, Dwyer K et al. Reversal of dialysis dependent renal failure in light chain deposition disease by autologous peripheral blood stem cell transplantation. Am J Kidney Dis 2004; 44: 551– 555.

33. Gertz MA, Lacy MQ, Lust JA et al. Phase II trial of high‑dose dexamethasone for untreated patients with primary systemic amyloidosis. Med Oncol 1999; 16: 104– 109.

34. Hassoun H, Flombaum C, D’Agati VD et al. High‑dose melphalan and auto- SCT in patients with monoclonal Ig deposition disease. Bone Marrow Transplant 2008; 42: 405– 412.

35. Kastritis E, Migkou M, Gavriatopoulou M et al. Treatment of light chain deposition disease with bortezomib and dexamethasone. Haematologica 2009; 94: 300– 302.

36. Kirkpatrick CJ, Curry A, Galle J et al. Systemic kappa light chain deposition and amyloidosis in multiple myeloma: novel morphological observations. Histopathology 1986; 10: 1065– 1076.

37. Lambotte O, Dürrbach A, Ammor M et al. Association of a POEMS syndrome and light chain deposit disease: first case report. Clin Nephrol 2001; 55: 482– 486.

38. Lorenz EC, Gertz MA, Fervenza FC et al. Long‑term outcome of autologous stem cell transplantation in light chain deposition disease. Nephrol Dial Transplant 2008; 23: 2052– 2057.

39. Pineda- Roman M, Tricot G. High‑dose therapy in patients with plasma cell dyscrasias and renal dysfunction. Contrib Nephrol 2007; 153: 182– 194.

40. Samanez C, Domingo A, Cibeira MT. Development of rapidly progressive liver light chain deposition under VAD chemotherapy in multiple myeloma. Eur J Haematol 2006; 76: 83– 85.

41. Sanchorawala V, Wright DG, Seldin DC et al. An overview of the use of high‑dose melphalan with autologous stem cell transplantation for the treatment of AL amyloidosis. Bone Marrow Transplant 2001; 28: 637– 642.

42. Weichman K, Dember LM, Prokaeva T et al. Clinical and molecular characteristics of patients with non‑amyloid light chain deposition disorders, and outcome following treatment with high dose melphalan and autologous stem cell transplantation. Bone Marrow Transplantatin 2006; 38: 339– 343.

43. Leung N, Slezak JM, Bertstralh EJ. Acute renal insufficiency after high dose melphalan in patients with primary systemic amyloidosis during stem cell transplantation. Am J Kidney Dis 2005; 45: 102– 111.

44. Comezo RL. Managing systemic light chain amyloidosis. J Natl Compr Canc Netw 2007; 5: 179– 187.

45. Bedossa P, Fabre M, Paraf F et al. Light chain deposition disease with liver dysfunction. Hum Pathol 1988; 19: 1008– 1014.

46. Bhargava P, Rushin JM, Rusnock EJ et al. Pulmonary light chain deposition disease. Report of five cases and review of literature. Am J Surg Pathol 2007; 31: 267– 276.

47. Popovic M, Tavcar R, Glavac D et al. Light chain deposition disease restricted to the brain: the first case report. Hum Pathol 2007; 38: 179– 184.

48. Doubek M, Brychtova Y, Tomiska M et al. Idiopathic systemic capillary leak syndrome misdiagnosed and treated as polycythemia vera. Acta Haematol 2005; 113: 150– 151.