Insidious rifampin-associated renal failure with light-chain proteinuria

Abstract Abstract 1875 Poster Board I-900 Study purpose: To explore how free light chain (FLC) removal by high cut-off haemodialysis (HCO-HD) has been adopted into clinical practice for the management of renal failure secondary to multiple myeloma. Describing treatment patterns and the laboratory and clinical outcomes associated with its use. Methods: A chart audit of patients treated with FLC removal by HCO-HD, using the Gambro HCO 1100 dialyser, was performed in 16 dialysis centers across 9 countries. Patient demographics, treatment patterns and dialysis side-effects were recorded. In addition, the following outcomes were measured: dialysis independence and reductions in serum FLCs concentrations at 12 and 21 days. Results: Data for 66 patients was entered. Patients had an average age of 65.1 (SD×10.1); 42 of them (63.64%) were male and 24 (36.36%) were female. Sixteen (24%) presented with relapsing myeloma and 50 (76%) had de novo disease. On average, each patient received 13 HCO-HD sessions (SD×8). Forty-one patients became dialysis independent (62.12%), after an average of 12 sessions. Dialysis related side-effects were reported in 6% of all patients. Forty patients (60.61%) were reported to have a sustained reduction in serum FLC concentrations by day 12. By day 21 this had increased to forty-one (62.12%). Among the patients who achieved a sustained reduction in serum FLC concentrations, 28 (70%) had a decline in FLC levels of more than 50% by day 12 and 34 (82.93%) by day 21. Among patients who achieved sustained reduction of more than 50% in serum FLC concentrations by day 12, 75% became dialysis independent. In comparison only 53% of those with a reduction of less than 50% became dialysis independent (p×0.007). Furthermore, among patients who achieved sustained FLC reduction of greater than 75%, 81% became dialysis independent. The rate of dialysis independence was also significantly higher in patients with de novo disease compared with those with relapsing myeloma (64% versus 56%, p×0.04). Conclusion: Free light chain removal by HCO-HD was well tolerated and associated with a very high rate of dialysis independence in patients with renal failure secondary to multiple myeloma. Rates of renal recovery were greater in patients with de novo myeloma and those who achieved an early reduction in serum FLC concentrations. Disclosures: No relevant conflicts of interest to declare.

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Rapid Reduction of Light-Chains and Proteinuria in Multiple Myeloma (MM) Patients with Light Chain Induced Acute Renal Failure Treated with Lenalidomide and Dexamethasone

Blood ◽

10.1182/blood.v118.21.5114.5114 ◽

2011 ◽

Vol 118 (21) ◽

pp. 5114-5114

Author(s):

Heinz Ludwig ◽

Josef Thaler ◽

Jan Koren ◽

Ludek Pour ◽

Ercan Müldür ◽

...

Keyword(s):

Renal Failure ◽

Renal Function ◽

Median Time ◽

Light Chain ◽

De Novo ◽

Light Chains ◽

High Risk Population ◽

Renal Response ◽

Increased Risk ◽

Grade 3

Abstract Abstract 5114 Introduction: Light chain-induced renal failure (LC-ARF) is a severe complication of MM associated with increased risk of infections, dependency on chronic hemodialysis and shortened survival. Reversibility of renal impairment depends on the degree of renal damage, the duration of renal failure and the quality of response to anti-myeloma therapy. In this phase II trial we assess the efficacy of lenalidomide-dexamethasone in reducing pathogenic light chains and restoring renal function. In addition, we analyze the kinetics of treatment response in patients with LC-ARF. Patients and Methods: 24 patients with LC-ARF as formerly defined (JCO 2010) have been enrolled so far. Age (median): 65.5 years (range: 46–78 years), Gender: male/female: 12/12. All patients presented with ISS stage III. 20 (83.3%) had de novo MM and 4 (16.7%) previously treated, but relapsing disease. Median GFR was 19.9 ml/min (range 6.1 – 37.2 ml/min). ECOG performance was 0 in 6, I-II in 14 and III-IV in 4 patients, respectively. One patient died before first study medication, 3 patients died within the first cycle and 2 patients dropped out early (< 2 cycles). Lenalidomide was given from d 1–21 with dose adaptation according to GFR. Dexamethasone 40 mg was administered on d 1–4, 9–12, 17–20 during cycle 1; thereafter 1x/week. Cycles were repeated q 4 weeks. Results: Presently, 17 patients are evaluable for response (completed ≥2 cycles and fully documented). The median number of cycles is 9 (range 2–9). CR was achieved in 5 (31.3%), nCR in 4 (25%), VGPR in 2 (12.5%) and PR in 5 (25%) patients, respectively, yielding an ORR (CR+nCR+VGPR+PR) of 94% for the evaluable and 69.6% for the ITT population. Median time to best tumor response was 132 days. The greatest proportional reduction in 24 hour urinary excretion (86%) in responding patients occurred within the first 4 weeks of therapy, with only little further improvement beyond that time (figure 1). Renal response was assessed as formerly defined (JCO 2010). 3 patients achieved CRrenal, 3 PRrenal and 5 MRrenal, yielding an ORRrenal in 11 patients (64.7% of the evaluable and 47.8% of the ITT population). Median time to best renal response was 83 days. 3 of 10 dialysis dependent patients became dialysis independent. Median GFR of evaluable patients increased from 15.2 (range 6.1 – 35.1 ml/min) at baseline to a median best GFR of 28.3 ml/min (range 11.3 – 101.1 ml/min) (p<0.0075). The greatest increase in median GFR was noted in the 5 patients with CR (26.7 to 60.9 ml/min, p<0.024) while in those with nCR/VGPR/PR a less pronounced improvement in GFR (10.6 to 22.4 ml/min, p<0.025) was observed Tolerance: Full documentation of adverse events is presently available in 23 patients. Four patients died, 1 (4.3%) each due to infection and cardiac arrest and 2 (8.7%) with unknown causes of death (sudden death). Grade 3/4 anemia, thrombopenia and leucopenia, were seen in 11 (47.8%), 7 (30.4%), and 3 (13%) patients, respectively. Other common grade 3/4 toxicities were infection/sepsis in 9 (39.1%), and cardiac dysfunction in 5 (21.7%) patients, respectively. Exanthema and fatigue were seen in 2 patients (8.7%), and pulmonary embolism and macula edema in 1 patient each (4.3%). Conclusions: LD showed significant anti-myeloma activity with an overall response rate of 94% in the evaluable and of 69.9% in the ITT population. The greatest proportional decrease in 24 hour proteinuria (86%) was obtained already within the first 4 weeks of therapy while renal recovery occurred with delay only. Improvement in renal function was obtained in 65% of the evaluable and in 48% of the ITT population. Toxicity of the LD regimen with the lenalidomide dose adjusted to GFR was as expected in this high risk population. Updated results will be presented. Disclosures: Ludwig: Celgene: Research Funding, Speakers Bureau.

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Combined Bendamustine, Prednisone and Bortezomib (BPV) In Patients With Relapsed Or Refractory Multiple Myeloma and Light Chain Induced Renal Failure

Blood ◽

10.1182/blood.v122.21.3203.3203 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3203-3203 ◽

Cited By ~ 1

Author(s):

Wolfram Pönisch ◽

Barbara Moll ◽

Dietger Niederwieser

Keyword(s):

Multiple Myeloma ◽

Renal Failure ◽

Renal Dysfunction ◽

Light Chain ◽

Severe Side Effect ◽

Renal Response ◽

Group A ◽

Severe Renal Dysfunction ◽

Grade 3 ◽

Group B

Abstract Introduction Serious renal failure represents a main complication of Multiple Myeloma (MM). An estimated 25% to 50% of patients are affected during the course of their disease. These patients are at increased risk for infections and have a significantly worse prognosis. Small phase I/II studies suggest that treatment with chemotherapy and/or new substances results in recovery of renal function in more than 25%. The window of opportunity for reversal of renal impairment is rather small making an immediate and highly active treatment strategy mandatory. Bortezomib and bendamustine have turned out to be quickly acting and effective drugs in the treatment of MM. Methods Between March 2005 and March 2013, 36 patients (median age 64; range 32-81 years) with relapsed/refractory MM and light chain induced renal failure (creatinine clearance <60ml/min) were treated with bendamustine 60mg/qm on day 1 and 2, bortezomib 1.3mg/qm on day 1, 4, 8 and 11, and prednisone 100mg on day 1, 2, 4, 8 and 11. Cycles were repeated every 21 days. Patients were divided into two groups: group A (n=20) consisted of patients with moderate or severe renal dysfunction (eGFR 15-59ml/min) and group B (n=16) of patients with renal failure/dialysis (eGFR <15ml/min). Results The median number of the BPV-treatment was 2 (1-7) cycles. 24 patients (67%) responded after at least one cycle of chemotherapy with 3 CR, 3 nCR, 6 VGPR, and 12 PR. Six patients had MR, 2 patients stable disease and 4 patients had a progress. With a median follow up of 22 months of the surviving patients, median PFS and OS for patients with moderate or severe renal dysfunction (group A) were 10 months and 25 months, respectively. Outcome for these patients was significantly better compared to patients with renal failure/dialysis (group B) with a median PFS and OS of 3 months and 7 months, respectively (p<0.02). Eleven patients showed a CRrenal, 5 patients a PRrenal and 15 patients a MRrenal. Median time to first renal response and best renal response were 21 days and 42 days, respectively. The most common severe side effect was grade 3-4 thrombocytopenia in 81% of the patients. Grade 3-4 neutropenia was observed in 50% of the patients. Moderate to severe infections were seen in 13 patients. Summary These results indicate that the combination of bortezomib, bendamustine and prednisone is effective and well tolerated in patients with relapsed/refractory MM and light chain induced renal failure. Disclosures: No relevant conflicts of interest to declare.

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Efficacy Of Lenalidomide Treatment In Multiple Myeloma (MM) Patients – a Report of Polish Myeloma Group

Blood ◽

10.1182/blood.v122.21.3236.3236 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3236-3236

Author(s):

Lidia Usnarska-Zubkiewicz ◽

Jakub Debski ◽

Aleksandra K. Butrym ◽

Wojciech Legiec ◽

Marek Hus ◽

...

Keyword(s):

Renal Failure ◽

Disease Progression ◽

Light Chain ◽

Response Rate ◽

Conflicts Of Interest ◽

Staging System ◽

Total N ◽

Light Chain Disease ◽

Disease Stabilization ◽

Beta 2

Abstract The aim of the multi-centre observational study was to evaluate the efficacy of lenalidomide (len) therapy in patients (pts) with resistant or relapsed MM as well in pts who continued treatment with len due to complications from the earlier lines of the therapy. The study involved 306 pts, 153 women and 153 men, aged 26-89 years (mean 60,5); on the onset of lenalidomide therapy 115 pts (38,8 %, Cohort 1, C1) were diagnosed with resistant MM, 135 pts (44,1%, Cohort 2, C2) had relapse of the disease, and 56 (18,3 %, Cohort 3, C3 ) len was instituted as continuation therapy due to polyneuropathy. In Stage I, II and III according to Durie - Salmon staging system there were 36, 88 and 182 pts respectively; 23 pts developed renal failure. 179 pts had IgG myeloma, 78 – IgA, 31pts were diagnosed with light chain disease, 13 – with non-secretory myeloma, 3- IgM, 2 -IgD and 196 with kappa light chain disease. Prior to len therapy the pts received 1-9 treatment lines (mean:3); 83 pts underwent megachemiotherapy. Average time from diagnosis to start of len treatment was 47 months (1-230). In 284 (92,8%) pts, len was administered at the dose of 25mg p.o , on days 1-21, in the remaining 22 (7,2%) pts (14, 3, 5 pts respectively) at the dose of 15mg, 10mg or 5 mg for 21 days, and dexamethasone (dx) at the dose of 20 mg on days 1-4, 8-11. 28 pts received only len at the dose of 25 mg for 21 days; individual pts were administered len with bortezomib or bendamustin and dexamethasone. The cycles were repeated every 28 days. All the pts were administered aspirin 75mg as the prophylaxis of deep vein thrombosis. Therapeutic response was evaluated on the basis of modified criteria of the European Group for Blood and Marrow Transplantation in all pts. At the time of the assessment 32 (10,45% ) pts have completed 1-2 cycles, 48 (15,7%) 3-4 cycles, the others 6 and more. The response rate was highest in pts continuing treatment, significantly higher than in resistant and relapsed myeloma. The response rate in group 1 and 2 was comparable 68,7% i 85,7%.(tabl ) respectively.ResponseResistant MM n=115 (C1);Relapsed MM n=135 (C2);Treatment continuation n=56 (C3);Total (n=306)CR/sCR10 (8,7 %)13 (9,6 %)15 (26,8 %)38VGPR11 (9,6 %)19 (14,1%)19 (33,9 %)49PR58 (50,4%)70 (51,9 %)16 (28,6 %)144SD29 (25,2 %)21 (15,6 %)3 (5,3 %)53PD7 (6,1 %)12 (8,9 %)3 (5,3 %)22Response:79 (68,7%)102 (85,7%)50 (89,2%)No response:36 (31,3%)33 (27,7%)6 (10,%)PC1:C2 =0,2266PC1:C3=0,0033PC2:C3=0,0321 The percentage of all responses was significantly higher in pts without renal insufficiency compared to those with renal failure (224/283 vs. 11/23) p= 0,0006, and in the group of pts whose serum beta-2-microglobulin was <3.5 mg/L compared to those with beta-2-m > 3.5 mg/L 89/112 vs 45/68 p=0,0316. There were no significant differences in response to len, depending on the number of previous lines of treatment 1 vs.> 1, stage ISS, and underwent or no megachemotherapy. The median TTP was 14.0 months in pts who responded to treatment with len and dx (CR, nCR, VGPR, PR). The TTP in pts with disease stabilization, or disease progression was significantly shorter (p = 0.0000), median 5.0 months. The median TTP was 9.0 months in pts with resistant MM, 8.0 months in pts with relapsed MM, and was significantly shorter (p = 0.00007) compared with median TTP in pts continuing treatment (16.50 months). The median OS was 15.0 months in pts who responded to treatment with len and dx (CR, nCR, VGPR, PR), and it was significantly longer (p = 0.00000) than the median OS in pts with disease stabilization, or disease progression (median 8.0 months). In pts with resistant MM median OS was 10.50 months, in pts with relapsed MM -11.0 months, and were significantly shorter (p = 0.00077) comparing to pts continuing treatment (18.0 months). Summary Lenalidomide with dexamethasone is an orally administrated and effective both in resistant and relapsed patients as well as maintenance therapy. Disclosures: No relevant conflicts of interest to declare.

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

Blood ◽

10.1182/blood.v124.21.3484.3484 ◽

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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Association between immunoglobulin isotypes and cytogenetic risk groups in multiple myeloma.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e19510 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e19510-e19510

Author(s):

Ramya Muddasani ◽

Angela Ramdhanny ◽

Gabriel Lutz ◽

Meredith Akerman ◽

Albert Ho ◽

...

Keyword(s):

Renal Failure ◽

Light Chain ◽

Risk Group ◽

Risk Groups ◽

Organ Damage ◽

Categorical Variables ◽

End Organ Damage ◽

Immunoglobulin Isotypes ◽

Lytic Lesions ◽

Standard Risk

e19510 Background: Cytogenetic abnormalities (CA) carry prognostic significance in MM. Immunoglobulin isotypes also predict disease behavior, with non-IgG subtypes historically being associated with poorer outcomes. We hypothesized that MM non-IgG isotype and higher risk CA are associated with greater degree of marrow infiltration (BM%) and presence of end organ damage at presentation. Methods: 552 MM patients were retrospectively analyzed using a multi-institution repository of BM%, isotype, and CA risk groups stratified by mSMART criteria. A subset of 110 patients were used to assess clinical comparisons and associations between CA, isotype, and end organ damage using the chi-square or Fisher’s exact test for categorical variables and the Mann-Whitney test to compare between groups for continuous variables. Results: There was a higher BM% seen in the intermediate risk group compared to standard risk group (50% vs 20%, p < 0.04). A lower BM% was seen in the IgG subtype compared to other isotypes (27% vs 45%, p < 0.02). CA including del(13q), del(16q), dup(1p), dup(1q), t(4;14), t(11;14), and trisomy 11 were associated with a higher BM%. When comparing isotypes to CA risk groups, IgA isotype was associated with greater risk, including del(13q) and del(16q). IgG isotype was associated with trisomy 11, while light chain MM correlated with higher risk CA including del(17p), and dup(1q). Lytic lesions on presentation were more frequent in patients with trisomy 11 and less frequently in IgA MM. Anemia presented more in IgA MM, and renal failure in patients with t(14;16). Conclusions: Lower BM% was found in IgG isotype MM, which correlated with standard risk CA, whereas light chain MM was associated with higher risk CA; this risk group being more likely to present with renal failure. Unexpectedly, lytic lesions on presentation correlated with non-IgA isotype and better risk CA. Further studies are needed to confirm these findings prospectively to determine if they can predict end organ damage in patients with specific isotypes or CA groups.

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Evaluation of the Impact of Renal Failure on Correlation and Concordance Between 2 Free Light Chain Assays

Clinical Lymphoma Myeloma & Leukemia ◽

10.1016/j.clml.2016.08.012 ◽

2016 ◽

Vol 16 (12) ◽

pp. 693-704 ◽

Cited By ~ 4

Author(s):

Caroline Moreau ◽

Brice Autier ◽

Thibault Cavey ◽

Emmanuel Rouger ◽

James Norwood ◽

...

Keyword(s):

Renal Failure ◽

Light Chain ◽

Free Light Chain ◽

The Impact

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Epidemiological and Clinical Characteristics of Monoclonal Gammopathy of Renal Significance (MGRS) in South America

Blood ◽

10.1182/blood-2018-99-113198 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5856-5856

Author(s):

Camila Peña ◽

Gonzalo P Mendez ◽

Natalia Paola Schutz ◽

Eloisa Riva ◽

Ricardo Valjalo ◽

...

Keyword(s):

Renal Failure ◽

Renal Biopsy ◽

Plasma Cell ◽

Light Chain ◽

Monoclonal Gammopathy ◽

Clinical Characteristics ◽

Protein Electrophoresis ◽

Renal Response ◽

Series Study

Abstract Background Monoclonal gammopathy of renal significance (MGRS) is a recently defined entity. It is a group of renal diseases due to paraprotein deposition from a small B lymphocyte or plasma cell clon, not meeting the criteria for an overt gammopathy-associated neoplasm. Despite this feature, the secondary kidney damage may be severe and irreversible; therefore, its early recognition and treatment are crucial. There are few studies on MGRS in the international literature, and no reported data from Latin America (LA). Aims To describe epidemiological and clinical characteristics of patients diagnosed with MGRS in LA. To evaluate patients outcomes. Material and methods This is an international multicentric retrospective case series study. All members of GELAMM (Grupo de estudio latinoamericano de Mieloma Múltiple) were invited to participate. Patients with diagnosis of MGRS according to the IMWG definition were included. All cases had pathological diagnosis provided by a renal biopsy. Epidemiological and clinical data were collected from clinical records in a standardized report form. Renal response was arbitrarily defined as the partial or total recovery of renal failure or renal symtoms at the end of treatment. Statistical analysis was performed by descriptive statistics using STATA 12. Results We received data from 18 patients, from centers in Chile, Argentina and Uruguay. Median follow up was 22,5 months. The patients characteristics are shown in table 1. The median age was 58 years (36 to 78 years). Male to female ratio was 1:1,25. Twelve had history of hypertension and one patient of renal transplantation. Anemia was present in 78% of cases (mean 10,7g/dL +/-2,3), hypoalbuminemia in 72% (mean 2,8g/dL +/-0,7), renal failure in 83% (mean creatinine of 4,6mg/dL +/- 4,8) with 47% of these (7 patients) requiring renal replacement therapy (RRT). Proteinuria was measured in 16 patients. Its average was 4,4gr (range 0,12 - 11,5gr/24hrs). LDH and calcemia were normal in all cases. Half of the patients presented as a nephrotic syndrome. Regarding histological subtypes, the most frequently diagnosed was the proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID). The paraprotein most frequently found was Kappa, and in the renal biopsy was IgG Kappa deposition (table 1). Serum protein electrophoresis (sPEP) was performed in all cases. Only 8 out 18 patients underwent urine protein electrophoresis (uPEP) and 14 had urine and serum immunofixation (IFX) done. Serum free light chain (sFLC) were performed in 94% of the patients. The paraprotein identification according to each of this exams is shown in figure 1. Seventeen patients received treatment; 13 received an anti-plasma cell drug, 7 a thalidomide based regimen and 6 a bortezomib based regimen. The patient with IgM MGRS was treated with a rituximab based regimen. Regarding renal responses, there were no data in 5 patients. Nine out 13 of the patients achieved renal response: 3 achieved partial recovery and 9 complete recovery. Three patients become RRT independent. There was no mortality in our cohort. No patient relapsed, but 3 progressed: 1 to multiple myeloma (MM), 1 to systemic amyloidosis and another to systemic light chain deposition disease (LCDD). Discussion Only 18 cases from 3 South American countries were collected. The lack of hematologists in some countries, difficulties in achieving a renal biopsy, non-availability of immunofluorescence in the histological studies and few experienced pathologists could be some of the problems in our region. Our cohort is of rather young patients, which is probably related to the fact that these patients are mostly undergoing renal biopsy. We believe, however, that the incidence of MGRS (similar to what happens with MGUS), increases with age, which could mean a problem of underdiagnoses. As expected, nephropathies frequently associated with MM were found: AL amyloidosis and LCDD. However, the most common renal pathology was PGNMID, a rare entity. This data must be corroborated with a larger study. The high sensitivity of sFLC to identify the paraprotein was corroborated and highlighted the importance of this test in the follow up. Half of patients achieved a renal response, which reinforces the fact that they must be promptly treated. Conclusion According to our knowledge, this is the larger cases series study in LA, and we hope it will be a contribution to the knowledge of this pathology. Disclosures No relevant conflicts of interest to declare.

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