Bortezomib-based chemotherapy can improve renal and tubular functions in patients with light chain-associated Fanconi syndrome
Light chain-associated Fanconi syndrome (LCFS) is a disorder of renal proximal tubule due to immunoglobulin light chains. Cases of LCFS are rare and mostly sporadically reported, and treatment of this entity is still controversial. This single-center retrospective study included 22 patients diagnosed with LCFS in Peking Union Medical College Hospital. Monoclonal gammopathy of undetermined significance was diagnosed in 13 patients, and overt multiple myeloma in six patients, with two smoldering myeloma and one Waldenstrom macroglobulinemia. Light chain was mostly kappa type (90.9%). Baseline median estimated glomerular filtration rate was 66 (13–126) ml/min/1.73 m2, with one patient presented as end-stage renal disease. After a median follow-up of 37 months, three patients died. Twelve patients were treated with chemotherapy, including 7 with bortezomib-based regimens. Renal function was significantly improved in the group of patients who received chemotherapy (p = 0.026). Compared with other chemotherapy regimens, patients with bortezomib-based treatment had a better hematological response (p = 0.027) as well as a better proximal tubule outcome (p = 0.015). Chemotherapy likely outweighs supportive treatment in patients with LCFS. Bortezomib-based regimen seems to be a safe first-line therapy for management of those patients.
KeywordsLight chain-associated Fanconi syndrome Bortezomib Plasma cell Renal function Tubular function
XW designed and performed the study and took the lead in writing the manuscript. LZ, JF, YM, XC, and DZ performed the study and revised the manuscript. JL conceived the original idea, designed and performed the study, and revised the manuscript.
The authors thank the patients and their families. Institutional research funding was provided by the Peking Union Medical College New Star (2011, to LJ), the CAMS Innovation Fund for Medical Sciences (Grant No. 2016-12M-1-002), and The National Key Research and Development Program of China (Grant No. 2016YFC0901503).
Compliance with ethical standards
A written informed consent was obtained from each patient. This study was approved by the Ethics Committee of the hospital.
Conflict of interest
The authors declare that they have no conflict of interest.
- 3.Duquesne A, Werbrouck A, Fabiani B, Denoyer A, Cervera P, Verpont MC, Bender S, Piedagnel R, Brocheriou I, Ronco P, Boffa JJ, Aucouturier P, Garderet L (2013) Complete remission of monoclonal gammopathy with ocular and periorbital crystal storing histiocytosis and Fanconi syndrome. Hum Pathol 44(5):927–933CrossRefPubMedGoogle Scholar
- 4.Nishida Y, Iwama K, Yamakura M, Takeuchi M, Matsue K (2012) Renal Fanconi syndrome as a cause of chronic kidney disease in patients with monoclonal gammopathy of undetermined significance: partially reversed renal function by high-dose dexamethasone with bortezomib. Leuk Lymphoma 53(9):1804–1806CrossRefPubMedGoogle Scholar
- 6.Vignon M, Javaugue V, Alexander MP, el-Karoui K, Karras A, Roos-Weil D, Royer B, Asli B, Knebelmann B, Touchard G, Jaccard A, Arnulf B, Bridoux F, Leung N, Fermand JP (2017) Current anti-myeloma therapies in renal manifestations of monoclonal light chain-associated Fanconi syndrome: a retrospective series of 49 patients. Leukemia 31(1):123–129CrossRefGoogle Scholar
- 7.Matsushita K, Mahmoodi BK, Woodward M, Emberson JR, Jafar TH, Jee SH, Polkinghorne KR, Shankar A, Smith DH, Tonelli M, Warnock DG, Wen CP, Coresh J, Gansevoort RT, Hemmelgarn BR, Levey AS, Chronic Kidney Disease Prognosis Consortium (2012) Comparison of risk prediction using the CKD-EPI equation and the MDRD study equation for estimated glomerular filtration rate. Jama 307(18):1941–1951CrossRefPubMedGoogle Scholar
- 8.Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, Kumar S, Hillengass J, Kastritis E, Richardson P, Landgren O, Paiva B, Dispenzieri A, Weiss B, LeLeu X, Zweegman S, Lonial S, Rosinol L, Zamagni E, Jagannath S, Sezer O, Kristinsson SY, Caers J, Usmani SZ, Lahuerta JJ, Johnsen HE, Beksac M, Cavo M, Goldschmidt H, Terpos E, Kyle RA, Anderson KC, Durie BGM, Miguel JFS (2014) International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 15(12):e538–e548CrossRefPubMedGoogle Scholar
- 10.Palladini G, Dispenzieri A, Gertz MA, Kumar S, Wechalekar A, Hawkins PN, Schönland S, Hegenbart U, Comenzo R, Kastritis E, Dimopoulos MA, Jaccard A, Klersy C, Merlini G (2012) New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes. J Clin Oncol 30(36):4541–4549CrossRefPubMedGoogle Scholar
- 11.Health UDo, Services H. National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03, 2010. 2016Google Scholar
- 12.Messiaen T, Deret S, Mougenot B, Bridoux F, dequiedt P, Dion JJ, Makdassi R, Meeus F, Pourrat J, Touchard G, Vanhille P, Zaoui P, Aucouturies P, Ronco PM (2000) Adult Fanconi syndrome secondary to light chain gammopathy. Clinicopathologic heterogeneity and unusual features in 11 patients. Medicine (Baltimore) 79(3):135–154CrossRefGoogle Scholar