Renal Failure In Multiple Myeloma Research Articles

Autologous Hematopoietic Stem Cell Transplantation Improves Survival in Patients with Multiple Myeloma and End Stage Renal Disease

Background: The incidence of renal failure in multiple myeloma (MM) is nearly 50% and portends a poor prognosis. Patients with MM and end stage renal disease (ESRD) on dialysis have lower rates of hematopoietic stem cell transplantation (HSCT), presumably from lower referrals due to perceived high transplant-related morbidity and mortality. For those who undergo HSCT, survival outcomes have only been reported scantily. The objective of our study was to determine the HSCT utilization rate and long-term survival benefit among MM patients on dialysis using the US Renal Data System (USRDS), a national database for ESRD patients in the US. Methods: All ESRD patients in the USRDS database who initiated dialysis between 2004 and 2015 and had a diagnosis of MM were included. Diagnoses and HSCT were identified using international classification of disease (ICD) 9/10 codes in hospital, detailed or physician/supplier claims. Those who were less than 18 years of age, had missing data on age, race, sex, or ethnicity, or had no follow-up due to death at the time of entry into the USRDS were excluded. All statistical analysis was performed using SAS 9.4 and statistical significance was assessed using an alpha level of 0.05. Descriptive statistics were determined overall, by HSCT status, and by mortality. Simple logistic regression models were used to assess the potential for confounding of the demographic and clinical variables with HSCT status. Cox Proportional Hazards models were used to examine the association of HSCT and mortality. Results: In the study period, there were 19,121 ESRD patients with MM. The average age was 69.8 years (SD=10.8), 43% were female, 28% black and 2.8% other race; 8.5% were Hispanic. A total of 1538 (8%) patients had a HSCT. Kaplan-Meier survival curves showed significantly higher survival for those who received a HSCT versus those who did not receive a HSCT (p=0.0001). The mean time to death among those with HSCT was 2.15 years (SE=0.03) compared to those without a HSCT was 1.29 years (SE=0.01). The median time to death was 0.82 years (95% CI: 0.79-0.85) for those who did not receive a HSCT and was not reached among those who received a HSCT. Those who had a HSCT had a lower risk of death (HR=0.54 95% CI: 0.50-0.58) during the observation period than those who did not, controlling for demographic characteristics and clinical diagnoses. Demographic and clinical diagnoses that were associated with a decreased odds of receiving a HSCT included increasing age, black or other race, hypertension, diabetes, coronary artery disease (CAD), congestive heart failure (CHF), arrhythmias, inflammatory bowel disease (IBD), cerebrovascular disease (CVD), liver disease, obesity, peptic ulcer disease (PUD), and chronic obstructive pulmonary disease (COPD). Of the patients that received a HSCT, factors that led to an increased risk of death included, increasing age, CHF, liver disease, and COPD. Variables that were significant in the final model and were associated with a decreased risk of death included black or other race, Hispanic ethnicity, hypertension, diabetes, and obesity. Obesity is known to have a survival benefit among ESRD patients. In our study, obese patients with MM and ESRD had a lower risk of death post HSCT compared to those who were non-obese. Conclusions: There is very low utilization of HSCT in patients with MM and ESRD. In our study, those who underwent a HSCT had a lower risk of death compared to those without a HSCT. A strong emphasis on early referral might improve the odds of transplantation and survival advantage in this population. Black race patients with MM and ESRD had lower odds of receiving a HSCT. Further studies accruing diverse patient populations to reduce racial disparities among patients eligible for HSCT should be encouraged. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Procollagen C-proteinase enhancer-1 and renal failure in multiple myeloma.

Renal involvement is present in approximately 50% of multiple myeloma (MM) cases and is associated with a poor prognosis. Procollagen C-Proteinase Enhancer1 (PCPE-1) is an extracellular matrix glycoprotein that has been shown to increase collagen production by enhancing the activity of Procollagen C-Proteinase (PCP) involved in collagen fibrillogenesis and contribute to the fibrotic process. This study investigates the relationship between PCPE-1 and renal function in myeloma patients. Eighty-one adults, consisting of 61 patients diagnosed with MM and 20 healthy controls, were included in this cross-sectional study. The MM patients with renal injury (RI) were classified as "MM-RI( +)" and those with no RI as "MM-RI(-)". The median serum PCPE-1 level was 10.7 (5.0-39.4) ng/mL for the entire study population, 9.9 (5.0-13.6) ng/mL for the control group, 10.0 (6.4-22.5) ng/mL for the MM-RI(-) group, and 11.4 (8.1-39.4) ng/mL for the MM-RI( +) group. The difference between the control group and MM-RI( +) group was statistically significant (p < 0.013). PCPE-1 levels negatively correlated with estimated glomerular filtration rate (eGFR), serum albumin, and hemoglobin levels but positively correlated with serum creatinine and CRP levels in the entire study population. Among MM patients, only serum phosphorus and beta-2-microglobulin (β2M) were positively correlated with PCPE-1. PCPE-1 levels was not affected by other parameters in the entire study population and in the MM group. Although serum PCPE-1 was higher in the MM-RI( +) group, it was thought to be associated with low GFR reflecting non-specific kidney injury rather than myeloma-related kidney injury.

P-154: Incidence and prognosis of renal failure in multiple myeloma: 50-years experience from an academic institution

P-154: Incidence and prognosis of renal failure in multiple myeloma: 50-years experience from an academic institution

Multiple Myeloma and Renal Failure: Mechanisms, Diagnosis, and Management.

Multiple myeloma (MM) is the second most common hematologic malignancy that involves monoclonal immunoglobulin (Ig)-producing plasma cells. Due to its multifaceted clinical manifestations and complications, it draws attention to various medical specialties like neurology, nephrology, orthopedics, cardiology, etc. Renal failure (RF) is one of the most common and most serious complications of MM that can be caused either by excess immunoglobulins that are nephrotoxic or some other causes like hypercalcemia, infection, etc. In this review article, we have discussed the pathogenesis of RF in MM, described the different diagnostic tools to diagnose RF in MM, and explained different treatment modalities to treat RF in MM, including certain general measures (i.e., hydration, withholding any nephrotoxic agents), renal replacement therapy, serum free light chain (SFLC) removal by plasma exchange and high cut-off dialyzer (HCO-HD), chemotherapy, hematopoietic stem cell transplantation (HSCT), and renal transplantation.

Multiple Myeloma as a rare cause of membranoproliferative glomerular nephritis

Multiple myeloma (MM) is a relatively uncommon cancer characterized by the neoplastic proliferation of plasma cells producing a monoclonal immunoglobulin(Ig). Renal failure in multiple myeloma is around 48% and it may be the presenting manifestation of MM.[1] Renal involvement is multifactorial including light chain cast nephropathy amyloidosis, monoclonal Ig deposition disease and less frequently cryoglobulinaemic glomerulonephritis and proliferative glomerulonephritis.[2-5] Hence membrano proliferative glomerulonephritis (MPGN) is a rare form in MM. Here we report a case of multiple myeloma with MPGN in a 60-year-old male who succumbed to death while on chemotherapy.

P0745URINE TIMP-2 AND IGFBP-7- NEW BIOMARKERS OF KIDNEY INJURY IN MULTIPLE MYELOMA PATIENTS

Abstract Background and Aims Urine tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) seem to be novel kidney injury related biomarkers, especially in tubular cells damage. Free light chains (FLCs) are associated with renal failure in multiple myeloma (MM) and appear to have a prognostic value and indicate stages in MM. The aim of the study was to investigate the correlation between new biomarkers and acclaimed parameters of renal failure and markers of MM stages and prognosis. Method The study included 124 patients with MM in the mean age of 66 +/- 10 years, with median time from MM diagnosis of 30 (lower; upper quartile 14; 63) months. There were 7(6%) patients with smoldering MM, 80(65%) with ISS stage 1, 22 (18%)with stage 2 and 15 (12%) with stage 3 MM. Mean eGFR was 71 +/- 25 ml/min/1.73 m2 and 30 (24%) patients had eGFR &amp;lt;60 ml/min/1.73 m2. The examined parameters included creatinine, urine NGAL, urine and serum cystatin-C, urine and serum FLC kappa and lambda, serum monoclonal protein, IGFBP-7 and TIMP-2 in serum and urine, WBC count, IL-6, NT-proBNP, serum albumin and β2-microglobulin. IGFBP-7 and TIMP-2 in serum were measured in a subgroup of 73 patients, including 26 (36%) with eGFR &amp;lt;60 ml/min/1.73 m2. The association between between these parameters were determined by multivariate stepwise regression analysis. The p-value &amp;lt;0.05 was considered statistically significant. Results Except for urine cystatin C and urine TIMP-2, all the studied markers were higher among patients with eGFR &amp;lt;60 ml/min/1.73m2: urine NGAL: 23.3 (9.2; 68.4) vs. 7.8 (3.9; 16.8) ng/ml; p&amp;lt;0.001; urine IGFBP-7: ; serum IGFBP-7: 86.2 (29.3; 125.0) vs. 33.7 (13.2; 61.5) ng/ml; p=0.003; and serum TIMP-2: 628 (498; 663) vs. 431 (360; 614) ng/ml; p=0.011, respectively. Serum and urine IGFBP-7 and urine NGAL were also higher among patients with ISS grade 3 comparing to the rest of the group (p=0.008, p&amp;lt;0.001 and p=0.033, respectively). Patients with smoldering myeloma did not differ from those with symptomatic disease. No differences in studied markers were observed between patients with newly diagnosed MM in comparison to those who had been treated with one or more schemes. Only urinary IGFBP-7 differed between patients who were on treatment at the time of samples’ collection (median ng/ml) in comparison to untreated (median ng/ml; p=0.009). No differences in TIMP-2 and IGFBP-7 levels in patients divided according to MM state were observed (remission vs stable vs progressive disease). In whole studied group, urinary markers of tubular injury were interrelated: cystatin C correlated positively with NGAL monomer (R=0.22; p=0.016), IGFBP-7 (R=0.26; p=0.004) and TIMP-2 (R=0.22; p=0.016), NGAL correlated positively with IGFBP-7 (R=0.39; p&amp;lt;0.001) and TIMP-2 (R=0.25; p=0.005), and IGFBP-7 correlated positively with TIMP-2 (R=0.31; p&amp;lt;0.001). In multiple linear regression, the negative correlation between urinary IGFBP-7 and eGFR was independent of other studied urinary markers of tubular injury. However, after adjustment for confounders (age, smoldering versus symptomatic MM, ISS, LDH, remission versus stable or progressive disease, and the concentrations of involved urine light chains), only urinary NGAL was independently associated with eGFR. Conclusion Urine TIMP-2 and IGFBP-7 may be useful in investigating tubular renal damage in patients with chronic kidney injury among patients with MM. This can lead to noninvasive biomarker-targeted diagnostic interventions and contribute to early beginning of treatment that may improve life expectancy quality of life in MM.

P1114HA-130 HEMOPERFUSION CARTRIDGE IN THE TREATMENT OF CAST NEPHROPATHY IN A 58-YEAR-OLD MALE WITH MULTIPLE MYELOMA: A CASE REPORT

Abstract Background and Aims Multiple myeloma is a plasma cell neoplasm that results in the production of monoclonal immunoglobulin. Renal failure is a common complication of multiple myeloma, occurring in approximately one-half of patients on initial presentation and is associated with increased mortality. Cast nephropathy in particular, is considered to be one of the major mechanisms of renal failure in multiple myeloma, and is characterized by precipitation of free light chains in the distal nephron, leading to intratubular obstruction, inflammation and fibrosis. Recent studies have demonstrated the use of extracorporeal methods such as plasmapheresis and high-cutoff membrane dialysis as an adjunctive therapy to chemotherapy in the management of cast nephropathy, however currently there are no existing guidelines in the use of extracorporeal therapies in the management of complications of multiple myeloma. Hemoperfusion is an extracorporeal treatment technique which utilizes adsorption in the removal of specific toxins. The HA 130 cartridge in particular has a resin pore size distribution of 500Da- 40 KDa and is able to remove molecules at 5-30kDa. In this case report we describe the use of HA 130 hemoperfusion cartridge in the treatment of cast nephropathy in Multiple Myeloma. Method A 58-year-old male, diabetic, non-hypertensive came in for 5-day history of generalized body weakness, associated with myalgia, lumbar pain and undocumented fever, with 1-day history of loose stools and vomiting. Upon admission blood tests done revealed anemia with a hemoglobin of 7.8g/dl, creatinine of 9.97mg/dL and potassium of 5.5mmol/L. He was diagnosed with acute renal failure and underwent hemodialysis on the second hospital day. On workup he had lytic bone lesions in the spine, pelvis and cranium on CT scan and x-ray. Serum Protein Electrophoresis (SPEP) and Serum Free Light Chain (sFLC) tests showed a monoclonal gammopathy. Serum beta 2 microglobulin was elevated at 12,618ng/ml. Free kappa and lambda light chains were also elevated at 19,250mg/L and 25.7mg/L, respectively. Bone marrow biopsy was done, with findings of markedly hypercellular marrow with 80% plasma cells confirming the diagnosis of Multiple Myeloma. Combined hemodialysis with hemoperfusion were done using HA 130 filter and hi flux dialyzer for 2.5 hours then hemodialysis for three times a week. Patient was also started on chemotherapy using Bortezomib with Dexamethasone for 2 cycles. Results Patient had a total of 14 sessions of combined hemoperfusion with hemodialysis. On repeat free kappa light chains decreased to 212.5mg/L. Patient was maintained on hemodialysis three times a week and was discharged after 55 hospital days. Outpatient hemodialysis was continued three times a week, and after 2 weeks, patient showed signs of renal recovery with a repeat creatinine of 2.1mg/dL. Four weeks after discharge, patient was independent of hemodialysis with a repeat creatinine of 1.3mg/dL. Conclusion This report highlights the use of hemoperfusion using HA 130 cartridge in combination with chemotherapy using Bortezomib in reducing free light chain levels in a 58-year-old male that developed renal failure secondary to cast nephropathy. Patient was able to achieve reduction in free light chain levels, improvement in renal function and eventually independence from hemodialysis four weeks after the last hemoperfusion treatment. Further studies using a randomized control trial on the use of hemoperfusion in directly reducing serum free light chain levels is recommended. The value of hemoperfusion on the rate of independence from hemodialysis, as well as survival rates among patients with renal failure secondary to multiple myeloma may also be worth investigating using larger studies.

New Markers of Renal Failure in Multiple Myeloma and Monoclonal Gammopathies.

Multiple myeloma (MM) is a common plasma cell malignancy, which is responsible for significant mortality, often related to severe renal impairment (RI). Kidney injury can limit therapeutic choices and may often translate into poor outcomes, but it remains potentially reversible in a proportion of patients. The most accessible, conventional markers of RI are subject to several shortfalls, among which are the delayed onset following kidney insult, multiple interfering factors, and lesser sensitivity to mild changes in glomerular filtration. Neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C have accumulated large interest in MM-RI due to being very sensitive markers of renal injury, as well as indicators of tubular-glomerular axis impairment. Of interest, recent data suggest that prediction of acute kidney injury may be aided by urinary tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), which both act to induce G1 cell cycle arrest, reflective of a state of pre-injury, and thus may be superior to other measures of kidney insult (NGAL, kidney injury molecule ((KIM-1)). Moreover, TIMP-2 seems to be a biomarker dedicated to distal tubular cells, whereas insulin-like growth factor-binding protein 7 (IGFBP7) secretion has been found in proximal tubule cells. IGFBP7 can also identify a subsection of the normal proximal nephron, even, maybe the one that is responding to insult. They may be adopted into a conceptual screening panel for MM-RI. Unfortunately, no biomarker is ideal (influence of non-renal, biologic factors), and novel measures are limited by economic constraints, availability, lack of standardization. With the emergence of more advanced diagnostic and prognostic MM models, markers reflective of disease processes (including RI) are of high interest. Candidate molecules also include peptidome markers.

Clinically Suspected Cast Nephropathy: A Retrospective, Multi-Center, Real-World Study

INTRODUCTION Myeloma cast nephropathy (CN) is the most common form of monoclonal immunoglobulin-mediated kidney disease, resulting from the precipitation of excessive amounts of monoclonal serum free light chains (sFLC) and causing around 70% of the cases of dialysis-dependent renal failure in multiple myeloma (MM)(Heher et al. 2013; Nasr et al. 2012; Sanders et al. 1991). In patients with acute renal failure, the finding of a high sFLC concentration with an abnormal sFLC ratio raises the clinical suspicion of CN (Hutchison et al. 2011). Although the histopathologic diagnosis of CN is established by renal biopsy, in routine clinical practice, the diagnostic yield of this procedure is often outweighed by the urgent need of anti-myeloma treatment and the risk of procedure-related complications. Recruitment of patients with CN into clinical trials is challenging and therefore real-world data on clinically suspected CN are necessary to understand the clinical characteristics, treatment and prognosis of these patients (Bridoux et al. 2017; Hutchison et al. 2019). METHODS We searched the population-based Danish Multiple Myeloma Registry for patients diagnosed with MM according to the International Myeloma Working Group criteria between 1st of January 2013 and 31st of December 2017 with a serum creatinine concentration of 200 µg/L or higher and a sFLC concentration of 1000 mg/L or higher at diagnosis. We conducted a retrospective patient chart review in eight Danish centers and assessed baseline characteristics, biopsy results, and overall survival. Anti-myeloma treatment, sFLC levels and renal function were registered during the first 12 months after MM diagnosis. RESULTS We identified 181 patients (176 with accessible clinical records). The median age was 72 years, the median serum creatinine was 384 µg/L, the median involved sFLC concentration was 5960 mg/L and dialysis dependent renal failure was present in 35%. Pre-myeloma estimated glomerular filtration rate (eGFR) was available in 80%, the median eGFR was 66 ml/min/1.73 m2. A kidney biopsy was carried out in 21% of patients and showed CN in 70% of cases. The median time from first sFLC measurement to initiation of therapy was 4 days. The number of lines of therapy ranged between zero and six. 173 patients received one, 35 patients received two and 14 patients received three lines of therapy during the first 12 months from diagnosis. High-dose melphalan with autologous stem cell transplantation (HDT-ASCT) was carried out in 45 (26%) patients. Bortezomib was administered as part of the first-line regimen in 163 (94%) patients. The most common first-line regimens were bortezomib-dexamethasone (n=67) and cyclophosphamide-bortezomib-dexamethasone (n=46). The first line of therapy resulted in very good partial response or better in 50% (Figure 1A), but was discontinued due to death, toxicity or progressive disease in 38% of patients. Dialysis dependency, eGFR and involved sFLC concentration were assessed at the end of the first cycle, at three months, six months and 12 months after initiation of therapy. At all these time points, achievement of renal recovery was associated with the magnitude of reduction of involved sFLC (Figure 1B). The median overall survival was 3.3 years (Figure 1C). At 12 months after diagnosis, 68% of patients were alive and 15% were dialysis dependent. Reduction of the initial involved sFLC concentration to ≤ 10% at three months was strongly associated with longer OS in a multivariate cox regression analysis adjusted for age and HDT-ASCT; hazard ratio 0.42, p=0.003. CONCLUSION In conclusion, we assessed a population-based cohort of newly diagnosed MM patients presenting with a serum creatinine of 200 µg/L or higher together with a sFLC of 1000 mg/L or higher. Although CN could have been clinically suspected in these cases, a kidney biopsy was only performed in one fifth of the population. Bortezomib-based therapy was initiated quickly and resulted in deep responses in most patients. Approximately one third of patients died within a year from MM diagnosis. Achievement of early and deep reduction in involved sFLC resulted in longer OS. Figure 1 Disclosures Szabo: Janssen: Consultancy. Vangsted:Takeda: Membership on an entity's Board of Directors or advisory committees; Jansen: Honoraria; Celgene: Honoraria; Sanofi: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees. Plesner:Celgene: Consultancy; AbbVie: Consultancy; Genmab: Consultancy; Oncopeptides: Consultancy; Takeda: Consultancy; Janssen: Consultancy, Research Funding.

Zoledronic Acid-Induced Acute Renal Failure in Multiple Myeloma

Zoledronic Acid-Induced Acute Renal Failure in Multiple Myeloma

Prognostic value of kidney biopsy in myeloma cast nephropathy: a retrospective study of 70 patients.

BACKGROUND Light chain myeloma cast nephropathy (MCN) is the major cause of renal failure in multiple myeloma and strongly impacts patient survival. The role of kidney biopsy in the management of MCN is unclear. METHODS Renal pathological findings were retrospectively studied in 70 patients with multiple myeloma and MCN. Patients were categorized according to the achievement or not of renal response, as defined by estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m(2) and/or dialysis independence at 3 months. RESULTS Thirty-two patients (46%) achieved a renal response. In the whole study population, the following parameters differed significantly between patients with and without renal response, respectively: baseline median eGFR (13.3 versus 9.3 mL/min/1.73 m(2), P = 0.017), Acute Kidney Injury Network Stage 3 (68.8 versus 92.1%, P = 0.019), haematological response rate (94 versus 34%, P < 0.0001), median percentage of free light chain (FLC) reduction at Day 21 (92 versus 24%, P = 0.006) and median number of casts/10 fields (14 versus 25, P = 0.005). The extent of interstitial fibrosis and tubular atrophy was similar. In multivariate analysis, only FLC reduction at Day 21 was significantly associated with renal response. However, when considering only the subgroup of haematological responders, both median number of casts [odds ratio (OR) = 0.93, 95% confidence interval (95% CI): 0.88-0.98, P = 0.01] and extent of tubular atrophy (OR = 0.03, 95% CI: 0.00-0.52, P = 0.02) were independent predictors of renal response. CONCLUSIONS In MCN, the presence of numerous casts and diffuse tubular atrophy is associated with poor renal prognosis. These data suggest that additional strategies to reduce FLC burden should be considered in patients with extensive cast formation.

Prognostic value of kidney biopsy in myeloma cast nephropathy: a retrospective study of 70 patients.

Light chain myeloma cast nephropathy (MCN) is the major cause of renal failure in multiple myeloma and strongly impacts patient survival. The role of kidney biopsy in the management of MCN is unclear. Renal pathological findings were retrospectively studied in 70 patients with multiple myeloma and MCN. Patients were categorized according to the achievement or not of renal response, as defined by estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m(2) and/or dialysis independence at 3 months. Thirty-two patients (46%) achieved a renal response. In the whole study population, the following parameters differed significantly between patients with and without renal response, respectively: baseline median eGFR (13.3 versus 9.3 mL/min/1.73 m(2), P = 0.017), Acute Kidney Injury Network Stage 3 (68.8 versus 92.1%, P = 0.019), haematological response rate (94 versus 34%, P < 0.0001), median percentage of free light chain (FLC) reduction at Day 21 (92 versus 24%, P = 0.006) and median number of casts/10 fields (14 versus 25, P = 0.005). The extent of interstitial fibrosis and tubular atrophy was similar. In multivariate analysis, only FLC reduction at Day 21 was significantly associated with renal response. However, when considering only the subgroup of haematological responders, both median number of casts [odds ratio (OR) = 0.93, 95% confidence interval (95% CI): 0.88-0.98, P = 0.01] and extent of tubular atrophy (OR = 0.03, 95% CI: 0.00-0.52, P = 0.02) were independent predictors of renal response. In MCN, the presence of numerous casts and diffuse tubular atrophy is associated with poor renal prognosis. These data suggest that additional strategies to reduce FLC burden should be considered in patients with extensive cast formation.

Aggressive presentation of multiple myeloma as renal failure and pathological fracture of dorsal vertebra in a young patient: a rare case report

Multiple myeloma presenting with acute renal failure with dorsal vertebral fracture is extremely rare phenomenon. Renal failure in multiple myeloma is associated with Light chain myeloma, serum creatinine more than 4mg/dL, extensive proteinuria and early infections. Our patient was a 29 -year-old male with multiple poor prognostic factors for renal failure. He presented with sudden onset pain in the backbone with weakness of lower extremities and loss of bowel and bladder control. On neurological examination – power of lower extremities was 4/5 with sign of sensory deficit at below umbilicus. He was diagnosed as lamda type nonsecretory multiple myeloma. He was started with malphalalan-prednisolone regimen but succumb to his disease process after one week.

Renal failure in patients with multiple myeloma.

Renal dysfunction is encountered in 20-25% of patients with multiple myeloma (MM) at the time of diagnosis. There is often a precipitating event. Several biochemical and clinical correlations with renal failure in MM have been reported. Renal failure in MM is associated with worse outcome of the disease. We retrospectively analyzed the medical records of 64 patients with MM admitted to our institution during the period January 1992 to December 2012. Abnormal renal function was observed in 24 (37.5%) patients and 17 (26.6%) of them had renal failure; 14 of the 17 (82.4%) of patients with renal failure had Stage III MM. Urine Bence- Jones protein was positive in ten (58.8%) patients with renal failure versus ten (21.3%) patients without renal failure (P = 0.004). Potential precipitating factors of renal failure were determined in nine patients. Renal function normalized in 11 patients with simple measures, while six patients required hemodialysis; one remained dialysis dependent till time of death. Early mortality occurred in five (29.4%) patients with renal failure as compared with two (4.3%) patients in the group without renal failure (P = 0.005). In conclusion, renal failure is associated with a higher tumor burden and Bence-Jones proteinuria in patients with MM. It is reversible in the majority of patients; however, early mortality tends to be higher in patients with persistent renal failure.

Pathogenesis of Renal Failure in Multiple Myeloma: Any Role of Contrast Media?

The spectrum of kidney disease-associated monoclonal immunoglobulin and plasma cell malignancies is remarkably broad and encompasses nearly all nephropathologic entities. Multiple myeloma with kidney impairment at presentation is a medical emergency since the recovery of kidney function is associated with survival benefits. In most cases, kidney impairment may be the first clinical manifestation of malignant plasma cell dyscrasias like multiple myeloma and light chain amyloidosis. Multiple myeloma per se cannot be considered a main risk factor for developing acute kidney injury following intravascular administration of iodinated contrast media. The risk is increased by comorbidities such as chronic kidney disease, diabetes, hypercalcemia, dehydration, and use of nephrotoxic drugs. Before the administration of contrast media, the current recommended laboratory tests for assessing kidney function are serum creatinine measurement and the estimation of glomerular filtration rate by using the CKD-EPI equation. The assessment of Bence Jones proteinuria is unnecessary for evaluating the risk of kidney failure in patients with multiple myeloma, since this test cannot be considered a surrogate biomarker of kidney function.

Renal failure in multiple myeloma

Renal failure in multiple myeloma

Plasmapheresis in myeloma cast nephropathy

Renal failure in multiple myeloma is frequent, and portends a dismal prognosis. Precipitation of free light chains in tubules contributes to development of cast nephropathy and renal failure. Treatment with plasmapheresis is reported as an adjunct to chemotherapy in these patients, but evidence regarding its efficacy in the literature is conflicting. In this article, we report the case of a 63-year-old man who presented with severe acute renal failure due to myeloma cast nephropathy and whose kidney function improved significantly following treatment with dexamethasone and a course of 8 plasma exchanges. We then provide a review of the technical aspects of plasmapheresis, followed by an analysis of the randomized trials that have been published to date on the efficacy of plasmapheresis for myeloma cast nephropathy.

Haemodialysis using high cut-off dialysers for treating acute renal failure in multiple myeloma.

Acute renal failure (ARF) occurs in 12%-20% of all multiple myeloma (MM) cases, and the survival of these patients depends on renal function recovery. Renal function is not recovered in 75% of dialysis-dependent patients, and their mean survival with replacement therapy is less than one year. Renal tubular disease is the most frequent cause of renal failure. It is present in more than 55% of renal failure cases and in 75% of those requiring dialysis. Rapid reduction of free light chain levels in the blood is necessary in order to recover renal function. One coadjuvant measure in treating the disease is reducing light chain levels with plasmapheresis, but its efficacy has not yet been clearly proven. Our proposal was therefore to use extended haemodialysis sessions with high cut-off dialysers (HCO-HD), obtaining a recovery rate of more than 60%. We present the progress of 6 patients with myeloma and acute renal failure who were treated with HCO-HD and the complications associated with using this type of haemodialysis. Then, we review the pros and cons of this technique. Six patients diagnosed with MM and ARF requiring dialysis and with serum free light chain levels above 500 mg/l were treated with 8-hour haemodialysis sessions with an HCO-HD filter. Before and after each session, serum free light chain levels were measured by nephelometry; other parameters were recorded as well. At the same time, patients underwent chemotherapy according to protocols. The symptom onset times of the 3 men and 3 women diagnosed with MM and ARF were highly variable, from 7 days to more than 1 year. We performed 90 extended sessions with HCO-HD filters, and each patient underwent between 6 and 40 sessions. Free light chain levels decreased by a mean of 65% between treatment onset and completion, except in one patient who experienced a 12.6% reduction. The mean percentage of reduction of light chain levels per session was 54.98% ± 17.27%. A complication occurred during 28% of the sessions. Of these complications, 48% were due to system coagulation. There were no major changes in pre-dialysis albumin, calcium, phosphorous or magnesium levels, although lower values that were not clinically relevant were recorded in one case. Renal function was recovered in 3 patients, they are alive and dialysis-free. In biopsied cases that recovered renal function, the specimen showed tubular nephropathy only. Those patients who took longer to be diagnosed did not recover their renal function, and when biopsied, they were diagnosed with renal tubular disease and light chain deposition disease. We found extended haemodialysis with HCO-HD filters to be a reasonable alternative in ARF caused by renal tubular disease, and achieved a recovery rate of 50% in our cases. Function recovery was influenced by the elapsed time between symptom onset and myeloma diagnosis, histological findings, promptness of starting chemotherapy, response to chemotherapy, and effectiveness of light chain extraction. In any case, further studies are needed to examine new chemotherapy agents and new direct free light chain removal techniques.

Actualités dans le traitement du myélome avec insuffisance rénale

Renal failure, mostly related to myeloma cast nephropathy (MCN), is a frequent complication of multiple myeloma (MM), which occurs in up to 50% of patients during the course of the disease. Persistent renal failure in MM is associated with poor survival. Treatment of MCN relies on urgent symptomatic measures (alkalinisation, rehydration, correction of hypercalcemia, and withdrawal of nephrotoxic drugs), with rapid introduction of chemotherapy to efficiently reduce the production of monoclonal light chains (LC). Recent studies suggest that, in patients with MM and severe renal failure due to MCN, rapid removal of circulating LC, through intensive hemodialysis sessions using a new generation high cut-off dialysis membrane, might result in dialysis withdrawal in most patients. If the development of intensive therapy and new efficient chemotherapy agents (thalidomide, bortezomib, lenalidomide) has transformed the care and prognosis of MM, the modalities and safety of these therapeutic regimens in patients with renal failure remain to be defined. The association of bortezomib with dexamethasone should be considered currently as first-line treatment in patients with MM and impaired renal function.

100 Long Term Outcome of Renal Failure in Multiple Myeloma Following Autologous Stem Cell Transplant

100 Long Term Outcome of Renal Failure in Multiple Myeloma Following Autologous Stem Cell Transplant