Myeloma light chain cast nephropathy, a review

2018 ◽  
Vol 32 (2) ◽  
pp. 189-198 ◽  
Author(s):  
Insara Jaffer Sathick ◽  
Maria Eleni Drosou ◽  
Nelson Leung
Keyword(s):  
Light Chain ◽  
Cast Nephropathy

Diagnosis of light chain cast nephropathy through immunostaining of the urine: Perfecting the “liquid biopsy”

2021 ◽  
Author(s):  
Juan Pablo Huidobro E ◽  
Fiorella Anghileri ◽  
Gonzalo P. Méndez ◽  
Gonzalo Barrera ◽  
Romina Reyes ◽  
...  
Keyword(s):  
Light Chain ◽  
Liquid Biopsy ◽  
Cast Nephropathy

Renal Impairment in Patients With Multiple Myeloma: A Consensus Statement on Behalf of the International Myeloma Working Group

2010 ◽  
Vol 28 (33) ◽  
pp. 4976-4984 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Evangelos Terpos ◽  
Asher Chanan-Khan ◽  
Nelson Leung ◽  
Heinz Ludwig ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Renal Impairment ◽  
Light Chain ◽  
Renal Injury ◽  
High Dose ◽  
Acute Renal Injury ◽  
High Dose Dexamethasone ◽  
Cast Nephropathy ◽  
High Dose Melphalan

Renal impairment is a common complication of multiple myeloma (MM). The estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula is the recommended method for the assessment of renal function in patients with MM with stabilized serum creatinine. In acute renal injury, the RIFLE (risk, injury, failure, loss and end-stage kidney disease) and Acute Renal Injury Network criteria seem to be appropriate to define the severity of renal impairment. Novel criteria based on eGFR measurements are recommended for the definition of the reversibility of renal impairment. Rapid intervention to reverse renal dysfunction is critical for the management of these patients, especially for those with light chain cast nephropathy. Bortezomib with high-dose dexamethasone is considered as the treatment of choice for such patients. There is limited experience with thalidomide in patients with myeloma with renal impairment. Thus, thalidomide can be carefully administered, mainly in the context of well-designed clinical trials, to evaluate if it can improve the rapidity and probability of response that is produced by the combination with bortezomib and high-dose dexamethasone. Lenalidomide is effective in this setting and can reverse renal insufficiency in a significant subset of patients, when it is given at reduced doses, according to renal function. The role of plasma exchange in patients with suspected light chain cast nephropathy and renal impairment is controversial. High-dose melphalan (140 mg/m2) and autologous stem-cell transplantation should be limited to younger patients with chemosensitive disease.

scholarly journals Renal biopsy in light chain cast nephropathy

Blood ◽  
2020 ◽  
Vol 135 (21) ◽  
pp. 1917-1917
Keyword(s):  
Renal Biopsy ◽  
Light Chain ◽  
Cast Nephropathy

scholarly journals Resolution of cast nephropathy following free light chain removal by haemodialysis in a patient with multiple myeloma: a case report

2008 ◽  
Vol 2 (1) ◽  
Author(s):  
Kolitha Basnayake ◽  
Colin Hutchison ◽  
Dia Kamel ◽  
Michael Sheaff ◽  
Neil Ashman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Case Report ◽  
Light Chain ◽  
Free Light Chain ◽  
Cast Nephropathy

Monoclonal immunoglobulin–mediated kidney disease: What is beyond amyloidosis in real practice?

2019 ◽  
Vol 3 (3) ◽  
pp. 105-112 ◽  
Author(s):  
Elena V Zakharova ◽  
Tatyana A Makarova ◽  
Ekaterina S Stolyarevich ◽  
Olga A Vorobyeva
Keyword(s):  
Kidney Disease ◽  
B Cell ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Monoclonal Immunoglobulin ◽  
B Cell Malignancies ◽  
Cast Nephropathy ◽  
Monoclonal Immunoglobulin Deposition Disease ◽  
Proximal Tubulopathy ◽  
Light Chain Proximal Tubulopathy

Background:Monoclonal immunoglobulin–mediated kidney disease with various patterns of damage may occur in patients with B-cell malignancies and non-malignant monoclonal gammopathies, and the latter are actually merged under the umbrella of monoclonal gammopathy of renal significance. Amyloidosis is the most well-known monoclonal immunoglobulin–related kidney damage. We focused on the rarer conditions and aimed to evaluate the non-amyloid spectrum of monoclonal immunoglobulin–mediated patterns of renal damage in real clinical practice.Methods:A single-center non-interventional retrospective study included 45 patients with pathology-proven non-amyloid monoclonal immunoglobulin–mediated kidney disease, followed during 2002–2018. Disease duration, proteinuria, serum creatinine, need for dialysis at the time of kidney biopsy, clinical diagnosis, and kidney pathology findings were analyzed.Results:No significant differences in the median age, disease duration at the time of biopsy, or main clinical presentation of kidney disease were found between patients with monoclonal gammopathy of renal significance and patients with B-cell malignancies. Pathology patterns like proliferative glomerulonephritis with monoclonal immunoglobulin deposits, membranous nephropathy, C3 glomerulopathy, cryoglobulinemic glomerulonephritis, and combinations of light chain proximal tubulopathy with monoclonal immunoglobulin deposition disease, and of C3 glomerulopathy with light chain proximal tubulopathy were found in monoclonal gammopathy of renal significance setting only. In contrast, light chain proximal tubulopathy alone, anti-glomerular basement glomerulonephritis, and combinations of cast nephropathy with light chain proximal tubulopathy, and cast nephropathy with monoclonal immunoglobulin deposition disease were associated with multiple myeloma only. Monoclonal immunoglobulin deposition disease, intracapillary monoclonal immunoglobulin M deposits, and cast nephropathy alone were seen in both settings.Conclusion:The presence of monoclonal gammopathy in patients with proteinuria and/or impaired kidney function demands kidney biopsy. Neither duration of kidney disease nor its clinical presentation allows differentiating malignant and non-malignant causes of monoclonal immunoglobulin–mediated renal damage. Several pathology patterns, even cast nephropathy, can be found both in cases of monoclonal gammopathy of renal significance and in cases of B-cell malignancies. Dual patterns of damage, including combinations of organized and non-organized deposits, or organized deposits with monoclonal immunoglobulin–induced damage without monoclonal immunoglobulin deposition, constitute up to 9%, mostly in multiple myeloma cases.

scholarly journals FP534EXTRACORPOREAL TREATMENTS FOR LIGHT CHAIN REMOVAL IN MYELOMA-INDUCED CAST NEPHROPATHY

2015 ◽  
Vol 30 (suppl_3) ◽  
pp. iii251-iii251
Author(s):  
Elena Mancini ◽  
Elena Zamagni ◽  
Marisa Santostefano ◽  
Beatrice Zannetti ◽  
Raffaella Rizzo ◽  
...  
Keyword(s):  
Light Chain ◽  
Cast Nephropathy

Lenalidomide and Dexamethasone for Acute Light Chain-Induced Renal Failure: Final Results of a Phase II Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3484-3484
Author(s):  
Heinz Ludwig ◽  
Elisabeth Rauch ◽  
Thomas Kuehr ◽  
Adam Zdenek ◽  
Adalbert Weissmann ◽  
...  
Keyword(s):  
Renal Failure ◽  
Serum Creatinine ◽  
Light Chain ◽  
Phase Ii Study ◽  
Renal Response ◽  
Cast Nephropathy ◽  
Protocol Population ◽  
Best Response ◽  
Grade 3 ◽  
Intent To Treat

Abstract Background: Acute renal failure (ARF) is a frequent complication of multiple myeloma (MM) and most frequently due to clonotypic light chains (LC) causing cast nephropathy, which is associated with fast deterioration of renal function, increased risk for infections and shortened survival. Here we present the final results of a phase II study employing lenalidomide-dexamethasone as treatment for patients with acute light-chain induced ARF. Patients and methods: 35 patients with LC-induced ARF have been enrolled. Cast nephropathy was confirmed in all 15 patients who had a renal biopsy. Patients with previously unknown MM must have presented with eGFR < 50ml/min and serum creatinine ³2.0mg/dL, and those with previously established diagnosis must have had documented eGFR ³ 60ml/min and serum creatinine ≤1.2mg/dL within 6 weeks before deterioration of eGFR to < 50ml/min and of serum creatinine to ≥ 2mg/dL due to LC-induced kidney injury. Nine cycles of Lenalidomide, day 1-21, q28 days, with dose adaptation according to eGFR (eGFR 30 – 50ml/min: 10 mg daily, eGFR < 30ml/min without requiring dialysis: 15mg q 48 hrs., eGFR < 30ml/min requiring dialysis: 5 mg daily following each dialysis) and dexamethasone (Dex), 40 mg, day 1-4, 9-12 and 17-21 during the first cycle and thereafter 40 mg once weekly were planned. Renal response was defined as previously described (Dimopoulos et al, Clin Lymphoma Myeloma. 2009, Ludwig et al. JCO 2010). Results: Patient's median age was: 66 (45-87), 28 patients had newly diagnosed and 7 previously established MM. 5.7% had ISS stage II, 94.3% stage III. 18 patients had light chain myeloma, 14 IgG, and 3 IgA isotype. Adverse cytogenetics t (4; 14) ± del17q ± 1q21 were detected in 14/29 patients. 4/35 patients died and 5 discontinued therapy (3 due to AEs, 1 due to PD, and 1 due to withdrawal of consent) within the first 2 cycles, leaving 26 patients for per protocol (PP) analysis. Median follow up was 17.7 months. Responses were seen in 25/35 (71.4%) patients; 7 (20%) had CR, 3 (8.6%) VGPR, 14 (40%) PR, and 1 (2.9%) MR. Median time to first and to best myeloma response was 28, and 92 days, respectively. Median baseline concentration of involved FLC was 5.465mg/L (range: 147–42.700mg/L) and 8350mg/L (range: 234– 35.500mg/L) in patients reaching ≥PR and ≤MR, respectively, and decreased significantly to a median of 95.75mg/L (range: 11.3–5.630mg/L, p <0.001) in the former, but not in the latter group. Renal response was observed in 16 (45.7%) of 35 patients (CRrenal, 5(14.2%), PRrenal, 7(20%), MRrenal, 5(14%)). Median time to renal and to best renal response was 28 and 157 days, respectively. Median eGFR increased significantly in patients with ≥ PR from 17.1ml/min at baseline to 39.1ml/min at best response (p<0.001), and from 23.7ml/min to 26.0ml/min in patients with ≤ MR (p=0.469) (figure 1A). Median PFS and OS were 5.5 and 21.8 months in the ITT and 12.1 and 31.4 months, respectively, in the PP group (figure 1B). Grade 3/4 anemia was seen in 43%, thrombocytopenia in 23% and neutropenia in 15% patients. Other non-haematologic AEs consisted mainly of grade 3-4/5 infection in 38%/9%, and of grade 3-4/5 cardiac toxicity in 11%/9% patients. Grade 3 diarrhea and vomiting/emesis were noted in 1 patient each. Conclusion: Lenalidomide (with dose adapted to eGFR) plus initial high dose Dex during the first cycle and low dose Dex during subsequent cycles resulted in rapid reduction of involved LC within 28 days in patients with ≥ PR. Overall, 71.4% of patients had a myeloma and 45.7% a renal response. Median eGFR increased significantly in patients with ≥ PR from 17.1ml/min at baseline to 39.1ml/min. Elderly patients experienced more toxicity and had more treatment discontinuations. Figure 1A. Median eGFR in patients with CR-PR and MR-NR at baseline and at best response. Figure 1A. Median eGFR in patients with CR-PR and MR-NR at baseline and at best response. Figure 1B. PFS and OS in the intent to treat and per protocol population. Figure 1B. PFS and OS in the intent to treat and per protocol population. Disclosures No relevant conflicts of interest to declare.

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