Treatment of Patients with Multiple Myeloma Complicated by Renal Failure with Bortezomib - Based Regimens.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2739-2739 ◽  
Author(s):  
Maria Roussou ◽  
Efstathios Kastritis ◽  
Athanasios Anagnostopoulos ◽  
Erasmia Psimenou ◽  
Irini Grapsa ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
Renal Function ◽  
Serum Creatinine ◽  
Median Time ◽  
Objective Response ◽  
Elevated Serum ◽  
Management Problem ◽  
Newly Diagnosed ◽  
Kinetics Of

Abstract Introduction: Renal failure is a common feature of multiple myeloma and a major management problem. There is limited data regarding the reversibility of renal failure, the kinetics of serum creatinine and the safety of novel agents, such as bortezomib, when administered to newly diagnosed or relapsed/refractory patients with renal failure. The purpose of our analysis was to assess the frequency of renal failure improvement and kinetics of serum creatinine in patients who received bortezomib-based regimens. Patients and methods: We evaluated 20 consecutive patients with newly diagnosed (n=7) or relapsed/refractory (n=13) multiple myeloma and renal failure, defined as a serum creatinine ≥ 2mg/dl. Patients’ median age was 66 years (range 43–88 years). Median serum creatinine was 3.8 mg/dl (range 2–11.9 mg/dl) and median creatinine clearance was 15.3 ml/min (range 6.4–33.3). Other features included hemoglobin <10gr/dl in 12 patients, platelets <100 × 109/l in 3 patients and elevated serum LDH in 9 patients. All patients received bortezomib plus dexamethasone alone or in combination with other agents, such as thalidomide, doxorubicin or melphalan. Reversibility of renal failure was defined as a sustained decrease of serum creatinine to <1.5 mg/dl and renal response was defined as ≥50% decrease of serum creatinine from its peak value. Results: Reversal of renal failure was documented in 35% of all patients and the median time to reversal was 23 days. Moreover, 9 patients (45%) had 50% decrease in serum creatinine and the median time to decrease was 34 days. Some decrease of creatinine was documented in 88% of patients. Among four patients who were on renal dialysis, 2 became independent of this procedure after the second and the third cycle of treatment. The objective response rate was 61% and the median progression free survival for responders was 12 months. Toxicities were similar to those seen in myeloma patients without renal failure who were treated with bortezomib-based regimens. Grade 3–4 neutropenia and thrombocytopenia were seen in 28% and 22% of patients respectively. One patient died of infection and bortezomib had to be discontinued in 4 patients due to grade III neurotoxicity. Conclusions: When bortezomib-based regimens are administered to myeloma patients with renal impairment their toxicity and efficacy are similar to those observed in patients with normal renal function. Moreover, these regimens are associated with rapid improvement of renal function in most patients and with reversal of renal failure in one-third of them.

Reversibility of Renal Impairment of Multiple Myeloma Patients Treated with Bortezomib-Based Regimens: Identification of Predictive Factors.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1725-1725 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Maria Roussou ◽  
Efstathios Kastritis ◽  
Maria Gavriatopoulou ◽  
Flora Zagouri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
Renal Function ◽  
Partial Response ◽  
Renal Impairment ◽  
Creatinine Clearance ◽  
Light Chain ◽  
Management Problem ◽  
Newly Diagnosed ◽  
Renal Response

Abstract Renal impairment (RI) is a frequent complication of multiple myeloma (MM) and a major management problem. Previous studies have shown that bortezomib is active and well tolerated in MM patients with RI and can be associated with improvement of renal function. The purpose of our analysis was to identify factors that may predict for renal impairment reversal in patients treated with bortezomib-based regimens. Over the last 5 years, 149 either newly diagnosed or relapsed/refractory MM patients received bortezomib-based regimens in our center. Our analysis is based on 46 consecutive patients with newly diagnosed (n=10) or relapsed/refractory (n=36) MM who presented with RI defined as creatinine clearance (CrCl) &lt; 50 mL/min. Median CrCl was 23 mL/min (range 6 to 48), 34 (74%) had a CrCl&lt;30 ml/min and 9 patients required renal dialysis. Sixteen patients (35%) had light chain only myeloma, elevated LDH&gt;300 IU/L was found in 24%, more than 2 gr/day of Bence Jones protein in 20 (44%) and kappa to lambda free light chain ratio was ≥8 or ≤0.125 in 25%. Patients received bortezomib (B) at standard dose and schedule, plus dexamethasone (D) (16 patients, 35%), or BD in combination with other agents such as thalidomide, doxorubicin or melphalan (30 patients, 65%). Renal complete response (RCR) was defined as a sustained increase of CrCl to &gt;60 mL/min after treatment. Renal partial response (RPR) was defined as an increase of CrCl by 50% and with improvement of renal function by at least one stage (stage IV: &lt;30 mL/min, stage III 30–59 mL/min) but with a post treatment CrCl &lt; 60 mL/min. RCR was documented in 22% of patients and RPR in 22% of patients. Thus, renal response (RCR + RPR) occurred in 20 patients (44%). The median time to renal response was 11 days (range 8 to 41). Among 9 patients who required dialysis 2 patients became independent of this procedure after the second cycle of treatment. The objective response rate (at least partial response) of the myeloma was 63%. Toxicities were similar to those seen in myeloma patients without renal failure who were treated with bortezomib-based regimens. Previously untreated patients (80% vs 33% for pretreated patients, p=0.012) and those with light chain only myeloma (69% vs 30%, p=0.012) had a higher probability to achieve renal response. Response of MM to treatment was also associated with higher rate of renal response (55% vs. 24% for non-responders, p=0.037). Creatinine clearance &lt;30 ml/min (47% vs. 33% for ClCr 330 ml/min, p=0.410), age&gt;75 years (p=0.309), corrected serum calcium ≥10,5 mg/dl (p=0.428), Bence Jones proteinuria ≥2g/day (p=0.167) or type of bortezomib regimen (BD or BD plus other agents, p=0.222) did not significantly affect the probability of renal response. Seventeen percent of patients presenting with RI died within the first 3 months after initiation of treatment. Patients with renal response had a trend for longer survival compared to those who did not achieve a renal response (79% vs 54% alive at 1 year, p=0.150). We conclude that when bortezomib-based regimens are administered to MM patients with RI, they are associated with a clinically meaningful renal response in 44% of them. Renal response is very rapid and occurred within 2 months in all patients. Previously untreated patients and those with light chain only myeloma may have a higher probability of renal response. Moreover, patients who achieved at least a partial response of their myeloma reversed RI more frequently than non-responders. Our data were derived from an unselected patient population with severe renal failure in more than two-thirds and with 20% of patients on dialysis. They provide further evidence that bortezomib-based regimens have a unique role in patients with RI.

Recovery of Renal Function and Independence from Dialysis in Newly Diagnosed and Relapsed Multiple Myeloma Patients - A Single Instituition Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4847-4847
Author(s):  
Girish Ravindranathan ◽  
Tanya Indrakumar ◽  
Sohail Ahmad ◽  
Moez Dungarwalla ◽  
Pamela Kanagasabapathy ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
Renal Function ◽  
Renal Impairment ◽  
Current Therapy ◽  
High Dose ◽  
Newly Diagnosed ◽  
Female Ratio ◽  
Male To Female ◽  
Relapsed Myeloma

Abstract Background: Renal impairment occurs in up to 30% of patients who present with multiple myeloma and in up tp 50% of patients at some stage of the illness. It is known that renal impairment can be reversed in a significant number of such patients by correction of precipitating factors and rehydration but that 3–12% patients will require dialysis or other major intervention. These patient have a worse prognosis largely due to an excess of early deaths, renal failure being the major cause of death in 14% of myeloma patients and contributing factor in a further 14%. (Drayson et al UK MRC MM trials 1980–2002) We have conducted a study to look into the clinical course and outcome of all patients with renal impairment sufficiently severe to be referred to the regional renal unit in South East England between 2000 and 2007 with either newly diagnosed multiple myeloma (MM) or relapsed disease to try to identify features which predict for better outcomes. Methods: 62 patients with MM and renal failure received treatment in our hospital over the last 8 years. Patients have been assessed for recovery of renal function and dialysis independence in two groups - newly diagnosed (n=47) and relapsed patients (n=15). They were analysed separately as the disease tends to be biologically different at presentation and relapse, and therapeutic options may be different. In addition relatively little data on relapsed myeloma with renal failure is available. Results: 14 patients in the newly diagnosed group and 4 in the relapsed group were deemed unsuitable for an active treatment approach and have been excluded from statistical analysis in this paper but will be analysed separately to try to identify factors which could improve the outcome for this group. The patients with newly diagnosed MM and actively treated had a mean age of 65.3±1.7 years (range 41.9–83.3), male to female ratio of 1.7:1 and a mean peak creatinine at presentation of 684.5±60.9 mmol/l (range 107–1820). Light chain myeloma was overrepresented and was seen in 57.5% of patients (n=19). 12 (36.3%) of 33 the new patients avoided dialysis. 21 required dialysis, of whom 8 patients (38.1%) recovered function to dialysis independence at 6 months. There were only 3 deaths at 6 months follow-up. The mean age of the relapsed patients was 61.8±3.5 years (range 34.9–80.7), male to female ratio of 2.6:1 and a mean peak creatinine at presentation of 824±118.4 mmol/l (range 231–1591). Majority of myeloma was IgA in 36.3% (n = 4). Among the 11 relapsed, 82% (n=9) required dialysis but a significant proportion, 88% (n=8), were dialysis independent at 6 months There was only one death within 6 months of a relapse. Treatments in the 2 groups varied but involved the use of regimes containing high dose steroids in most patients. Conclusions: Our data suggest that renal failure and dialysis dependence can be avoided or is reversible in a large number of newly diagnosed and relapsed myeloma patients. This study of an unselected group of patients receiving current therapy provides an important baseline against which to compare the effect of approaches involving the newer biological agents.

The Role of Novel Agents on Reversibility of Renal Impairment in Newly Diagnosed Patients with Multiple Myeloma; a Single Center Experience on 112 Patients,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3961-3961
Author(s):  
Meletios A Dimopoulos ◽  
Maria Roussou ◽  
Maria Gkotzamanidou ◽  
Erasmia Psimenou ◽  
Despoina Mparmparoussi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Multivariate Analysis ◽  
Renal Impairment ◽  
Median Time ◽  
Novel Agents ◽  
Newly Diagnosed ◽  
Renal Response ◽  
Group B

Abstract Abstract 3961 Renal impairment (RI) is a frequent complication of multiple myeloma (MM). Proteasome inhibitors and immunomodulatory drugs (IMiDs) are used as frontline therapy for MM but their effect on renal function recovery has not been clearly defined. To address this issue we studied 112 patients with newly diagnosed MM and RI who were treated in the Department of Clinical Therapeutics of the University of Athens, over the last decade. RI was defined as an estimated glomelural filtration rate (eGFR) ≤60 ml/min, using the simplified MDRD formula. Patients were divided into three groups; group T included 53 patients who received thalidomide-based regimens (with dexamethasone alone, with dexamethasone and melphalan or cyclophosphamide, or with VAD); group B included 30 patients who received bortezomib-based regimens (with dexamethasone alone, with dexamethasone and thalidomide or with cyclophosphamide) and group L included 29 patients who received lenalidomide-based regimens (with dexamethasone or with melphalan and prednisone). Lenalidomide dose was adjusted for the degree of RI according to current recommendations. Renal complete response (CRrenal) was defined as a sustained increase of baseline eGFR to >60 ml/min, renal partial response (PRrenal) as an increase of eGFR from <15 to 30–50 ml/min and renal minor response (MRrenal) as sustained improvement of baseline eGFR of <15 ml/min to 15–29 ml/min, or, if baseline eGFR was 15–29 ml/min, improvement to 30–59 ml/min. Patients in groups T and L were older than those of group B (p=0.0001). Anemia (Hb <10 g/dl) was more frequent in patients of group L (p=0.007). There were no significant differences in the severity of RI, or other clinical and laboratory parameters among the three groups. An improvement of renal function, recorded as MRrenal or better, was achieved more frequently in patients treated with bortezomib-(83%) or thalidomide-based regimens (77%) than in patients treated with lenalidomide-based regimens (55%, p=0.033). We subsequently focused our analysis in major renal responses (at least PRrenal) since this endpoint is clinically more relevant. CRrenal was achieved in 53% of patients in group T, in 70% in group B and in 34% in group L (p=0.014), while CRrenal+PRrenal rates were 55%, 80% and 38% for groups T, B and L, respectively (p=0.004). eGFR <30 ml/min was associated with a significantly lower probability of at least PRrenal (p=0.016). In multivariate analysis bortezomib-based regimens (OR: 8.8, 95% CI: 2–37, p=0.003) and thalidomide-based regimens (OR: 2.85, 95% CI: 1.01–8, p=0.046) were associated with higher probability at least PRrenal than lenalidomide-based regimens. Other factors that were independently associated with higher probability of at least PRrenal, were baseline eGFR >30 ml/min (OR: 4.85, 95% CI: 1.9–12.5, p=0.001) and age ≤65 years (OR: 3.8, 95% CI: 1.07–13.5, p=0.038). The median time to first renal response was longer for patients of group L compared to those of group T (5.5 months vs. 1.5 months, p=0.038) and it was significantly shorter for patients of group B (0.85 months, p=0.001). The median time to major renal response was 1.1 months for bortezomib-based and 2.7 months for thalidomide-based regimens, and exceeds 6 months for lenalidomide-based regimens (p=0.002). In multivariate analysis bortezomib-based regimens (OR: 3.12, 95% CI: 1.35–7.2, p=0.008) and baseline eGFR >30 ml/min (OR: 1.93, 95% CI: 1.13–3.3, p=0.015) were independently associated with a shorter time to ≥PRrenal. Myeloma response to treatment was 61%, 83% and 83% for the three treatment groups, respectively and was associated with any renal response (≥MRrenal; p=0.008) and with a major renal response (CRrenal+PRrenal; p=0.001). Among 8 patients who required dialysis (group T 4 patients, group B 4 patients), 4 patients (2 in each group) became independent of this procedure. This is the first analysis which compared the role of the three novel agents in MM patients presenting with RI. Our data indicate that novel agent-based regimens can improve renal function in the majority of patients with RI. However, bortezomib- and thalidomide-based regimens are more efficacious than lenalidomide-based regimens in this setting. Furthermore, bortezomib-based regimens act more rapidly than IMiD-based regimens even in patients with severe RI. We conclude that bortezomib-based regimens are the preferred therapy for newly diagnosed myeloma patients with RI. Disclosures: Dimopoulos: Janssen-Cilag: Honoraria; Celgene: Honoraria; Millenium: Honoraria. Terpos:Janssen-Cilag: Honoraria; Celgene: Honoraria.

scholarly journals The elevated serum urea : creatinine ratio in canine babesiosis in South Africa is not of renal origin

2006 ◽  
Vol 77 (4) ◽  
Author(s):  
M.P. De Scally ◽  
A.L. Leisewitz ◽  
R.G. Lobetti ◽  
P.N. Thompson
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Serum Creatinine ◽  
Cystatin C ◽  
Elevated Serum ◽  
Serum Urea ◽  
Canine Babesiosis ◽  
Serum Cystatin C ◽  
Serum Cystatin ◽  
Renal Origin

Pigmented serum, usually due to free haemoglobin and/or bilirubin, is a common finding in dogs with babesiosis, resulting in interference with all biochemical tests that rely on photochemistry. This is particularly true of urea and creatinine determinations, complicating the diagnosis of acute renal failure, which is a serious complication of babesiosis. A disproportionately raised serum urea concentration of unknown origin occurs in severely anaemic canine babesiosis patients and gives rise to an increased serum urea:creatinine ratio. The assay for cystatin-C, an excellent measure of glomerular filtration rate, is unaffected by free serum haemoglobin, and due to its different intrinsic origins, is free of influence by the metabolic derangements and organ pathology, other than renal disease, encountered in canine babesiosis. Serum cystatin-C was used to compare the concentrations of serum urea and serum creatinine in dogs with the severely anaemic form of canine babesiosis as well as a canine babesiosis-free reference group. Mean serum urea and mean serum urea:creatinine ratio were significantly elevated in the babesia-infected group relative to the reference population in this study. Mean serum creatinine and mean serum cystatin-C were within the reference ranges. Therefore an elevated urea:creatinine ratio in canine babesiosis in the presence of a normal serum creatinine concentration is considered to be caused by an elevated serum urea concentration and is most likely of non-renal origin. Serum creatinine was therefore as specific a measure of renal function as serum cystatin-C in canine babesiosis in this study. The sensitivity of serum creatinine as a measure of renal function was not established by this study. Serum urea, however, proved to be of little use compared to serum cystatin-C and serum creatinine. Serum urea should therefore not be used to diagnose renal failure in canine babesiosis.

Autotransplantation in Patients with Multiple Myeloma and Concurrent Renal Failure Is Safe and Feasible and Associated with Recovery of Renal Function in > 30% of Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5126-5126
Author(s):  
Gaurav C. Parikh ◽  
Rima M. Saliba ◽  
Amit Lahoti ◽  
Chitra Hosing ◽  
Floralyn Mendoza ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Renal Failure ◽  
Renal Function ◽  
Serum Creatinine ◽  
Hazard Ratio ◽  
P Value ◽  
High Dose ◽  
Post Transplant ◽  
Relapsed Disease

Abstract Background: About 20% of patients with multiple myeloma (MM) have renal impairment at diagnosis and 2–3% are dialysis-dependent (DD). These patients may potentially benefit from high-dose therapy (HDT) and autotransplants. Method: We analyzed the outcome in 48 patient who received an autotransplant for MM while in renal failure at our institution between 8/1991 and 9/2006. Renal failure was defined as serum creatinine ≥ 2 mg/dl sustained for > 1 month. 9 patients (18%) were DD. Median age was 56 (29–72) years. 26 patients (54%) had at least a PR to induction therapy, 16 had primary refractory disease (33%) and 6 patients (12%) had relapsed disease. Median serum Cr was 2.9 mg/dl (2.0 – 12.5) and creatinine clearance (CrCl) at transplant was 33 ml/min (8.7 – 63). A CrCl of <20 ml/min was seen in 15 patients (31%). PBSC mobilization was performed with G-CSF alone in 37 patients (77%) and chemotherapy + G-CSF in the rest. Median CD34 cell dose was 4.47 x 106 /kg (1.4 – 9.7). Forty-six patients received HD melphalan as preparative regimen, while 2 patients received a combination of thiotepa, busulfan and cyclophosphamide. Results: 9 patients achieved a CR (19%), with a total response rate (CR + PR) of 67% (32 patients). 2 patients (4%) died within 100 days of autotransplant. Median times to neutrophil and platelet engraftment were 10 (9–18) and 12 (8–81) days, respectively. Grade ≥ 1 mucositis was seen in 21 patients (43%), with 3 patients (6%) experiencing grade ≥3 mucositis. After a median follow up of 34 months, the estimated median PFS and OS were 21 and 87 months, respectively. Kaplan-Meier estimates of 5-year PFS and OS probabilities were 21% and 54%, respectively. Significant improvement in renal function, defined as an increase in Glomerular Filtration Rate by 25% above baseline by 1 year post-transplant, was seen in 17 patients (35%). None of the 9 DD patients became dialysis independent. A pre-transplant creatinine level of ≥ 3mg/dl was associated with a significantly shorter overall survival (p = 0.05, HR 2.8), but did not adversely impact the improvement in renal function (p = 0.6). Conclusion: Autotransplant after HDT is safe and feasible in patients with multiple myeloma and renal failure. Response rates and outcomes were similar to those observed in other patients. Approximately 35% of patients had a significant improvement in renal function post-transplant. Analysis Results Ref= Reference N Event Free Survival Overall Survival 48 Hazard Ratio at 3 years 95% CI p value Hazard ratio at 3 years 95% CI p value Age ≤ 55 23 Ref Ref > 55 25 1.2 0.6–2.7 0.6 1.2 0.4–3.1 0.8 Cytogenetics Abnormal 10 0.9 0.4–2.5 0.9 1.7 0.5–6.1 0.4 Normal 27 Ref Ref Pretransplant Dialysis Dependent Yes 9 1.1 0.4–3.4 0.8 1.1 0.4–4.7 0.6 No 39 Ref Ref Serum Creatinine ≥ 3 23 1.6 0.7–3.4 0.2 2.8 1–7.9 0.05 <3 25 Ref Ref

Comparison of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Modification of Diet in Renal Disease (MDRD) Study Equations and A Formula Based on Cystatin-C and Serum Creatinine for the Estimation of Glomerular Filtration Rate in Patients with Multiple Myeloma; Is It Time to Change From MDRD to CKD-EPI Equation?

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5091-5091
Author(s):  
Meletios Athanasios Dimopoulos ◽  
Efstathios Kastritis ◽  
Eirini Katodritou ◽  
Anastasia Pouli ◽  
Eurydiki Michalis ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Serum Creatinine ◽  
Filtration Rate ◽  
Newly Diagnosed ◽  
Mdrd Equation ◽  
Ckd Stage ◽  
Stage 1

Abstract Abstract 5091 Renal impairment (RI) is a frequent complication in multiple myeloma (MM). The IMWG has recommended the use of the MDRD formula for the estimation of glomerular filtration rate (GFR) in MM patients with stabilized serum creatinine (sCr) and the classification of these patients in the 5 stages of RI, according to the KDIGO classification (Dimopoulos et al, JCO 2010;28:4976–84). Because MDRD equation has limitations, especially in the normal or near-normal GFR range, other prediction equations based on serum cystatin-C (cys-C), a very sensitive GFR surrogate marker, have been suggested for use in patients with CKD. Furthermore, the CKD-EPI has proposed a new formula for the estimation of GFR, which is based on age, race and sCr, and it seems to be more accurate than the MDRD equation in the estimation of GFR in CKD and in kidney transplant patients (Levey et al, Ann Intern Med 2009;150:604–12). The aim of this study was to evaluate the renal function of newly diagnosed patients with symptomatic MM using the MDRD, the CKD-EPI equations and an equation based on Cys-C/age/sCr (Stevens et al, Am J Kidney Dis 2008;51:395–406) and explore their prognostic value on survival. We studied 204 newly-diagnosed, previously untreated, symptomatic MM patients. The median age was 69 years (range: 36–94 years); 62% of patients were >65 years of age, 57% were males and 16% had sCr ≥2 mg/dl. Serum Cys-C was measured using a latex particle-enhanced nephelometric immunoassay (Dade Behring, Liederbach, Germany). Serum Cys-C was increased in MM patients compared to 52 age- and gender-matched controls [median: 1.07 mg/l vs. 0.72 mg/l, p<0.0001]. The median values for eGFR calculated by the MDRD, the Cys-C/age/sCr and the CKD-EPI equations were 63.95 ml/min/1.73m2, 68.08 ml/min/1.73m2 and 56.5 ml/min/1.73 m2, respectively (p<0.01 for all comparisons between equations). Patients were divided in the 5 CKD stages of KDIGO classification, according to eGFR (stage 1: eGFR >90 ml/min/1.73 m2; stage 2: 60–89 ml/min/1.73m2; stage 3: 30–59 ml/min/1.73 m2; stage 4: 15–29 ml/min/1.73 m2; stage 5: <15 ml/min/1.73 m2 or on dialysis). For each studied equation, the number of patients with RI stage 3–5 (i.e. eGFR <60 ml/min/1.732) was 43% for MDRD vs. 42% for Cys-C/age/sCr vs. 53% for CKD-EPI (p<0.001; see also the table). Concordance for CKD stage allocation for the three equations of estimating eGFR was 68% for MDRD vs. CKD-EPI, 68% for MDRD vs. Cys-C/age/creatinine and 61% for CKD-EPI vs. Cys-C/age/sCr (see also the table). A significant correlation was found between ISS stage and MDRD, Cys/age/creatinine and CKD-EPI calculated eGFR (p<0.001 for all). The median survival for all patients was 49 months. Overall survival was significantly shorter for patients with CKD stage 3, 4 or 5, calculated by the different studied equations, compared to those with CKD stage 1 or 2 (p<0.01 for all equations). Thus, we pooled patients with CKD stages 1 and 2 and CKD stages 3–5 for survival analysis. By using the eGFR of 60 ml/min/1.73 m2 as a cut-off, patients with eGFR <60 ml/min/1.73 m2, assessed by each of the 3 studied equations, had a significantly shorter median overall survival: 24 months vs. 98 months (χ2=9.8, p=0.002) for MDRD equation, 27 months vs. 98 months (χ2=12.8, p<0.001) for Cys-C/age/sCr equation and 38 months vs. not reached (χ2=13.3, p<0.001) for CKD-EPI equation. When we adjusted for ISS stage, the allocation to RI of stage 3–5, using the CKD-EPI equation, was significantly associated with survival (p=0.041); this was not observed for the allocation to stage 3–5 RI using the other formulas (p=0.357 for MDRD equation and p=0.235 for Cys-C/age/sCr equation). Our data suggest that CKD-EPI equation for the estimation of GFR detects more MM patients with stage 3–5 RI than MDRD or Cys-C/age/sCr equations. Furthermore, CKD-EPI was the only equation that could predict for overall survival adjusted for ISS stage. The confirmation of these data may lead to the broader use of CKD-EPI formula for the evaluation of RI in patients with MM, as it has been suggested for patients with several renal disorders.Table.Evaluation of Renal Function Stage by Different EquationsCKD stageMDRD equationEquation based on Cys-C/age/sCrCKD-EPI equationp-value147 (23%)51 (25%)30 (15%)270 (34%)68 (33%)66 (32%)Friedman-test354 (26%)54 (26%)68 (33%)p<0.001422 (11%)23 (11%)23 (11)511 (5%)8 (4%)17 (8%) Disclosures: No relevant conflicts of interest to declare.

scholarly journals Kinetics of Renal Function during Induction in Newly Diagnosed Multiple Myeloma: Results of Two Prospective Studies by the German Myeloma Study Group DSMM

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1322
Author(s):  
Friederike Bachmann ◽  
Martin Schreder ◽  
Monika Engelhardt ◽  
Christian Langer ◽  
Denise Wolleschak ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Complete Response ◽  
Study Group ◽  
Newly Diagnosed ◽  
Percent Change ◽  
Prospective Trials ◽  
Kinetics Of

Background: Preservation of kidney function in newly diagnosed (ND) multiple myeloma (MM) helps to prevent excess toxicity. Patients (pts) from two prospective trials were analyzed, provided postinduction (PInd) restaging was performed. Pts received three cycles with bortezomib (btz), cyclophosphamide, and dexamethasone (dex; VCD) or btz, lenalidomide (len), and dex (VRd) or len, adriamycin, and dex (RAD). The minimum required estimated glomerular filtration rate (eGFR) was >30 mL/min. We analyzed the percent change of the renal function using the International Myeloma Working Group (IMWG) criteria and Kidney Disease: Improving Global Outcomes (KDIGO)-defined categories. Results: Seven hundred and seventy-two patients were eligible. Three hundred and fifty-six received VCD, 214 VRd, and 202 RAD. VCD patients had the best baseline eGFR. The proportion of pts with eGFR <45 mL/min decreased from 7.3% at baseline to 1.9% PInd (p < 0.0001). Thirty-seven point one percent of VCD versus 49% of VRd patients had a decrease of GFR (p = 0.0872). IMWG-defined “renal complete response (CRrenal)” was achieved in 17/25 (68%) pts after VCD, 12/19 (63%) after RAD, and 14/27 (52%) after VRd (p = 0.4747). Conclusions: Analyzing a large and representative newly diagnosed myeloma (NDMM) group, we found no difference in CRrenal that occurred independently from the myeloma response across the three regimens. A trend towards deterioration of the renal function with VRd versus VCD may be explained by a better pretreatment “renal fitness” in the latter group.

Thalidomide-Dexamethasone as Induction Therapy Prior to Autologous Stem-Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma and Renal Failure.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4934-4934
Author(s):  
Patrizia Tosi ◽  
Elena Zamagni ◽  
Paola Tacchetti ◽  
Michela Ceccolini ◽  
Giulia Perrone ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
Renal Function ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Creatinine Clearance ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
High Dose ◽  
Newly Diagnosed

Abstract Abstract 4934 Multiple myeloma (MM) patients presenting with renal feature at disease onset should not be excluded from high-dose therapy programs; seeking novel effective and non-nephrotoxic induction regimens is thus mandatory in order to maximize the reduction of tumor burden prior to transplant. From May 2002 to February 2008, 31 newly diagnosed MM patients (18 male, 13 female, median age 60 years) with symptomatic MM and renal failure, defined as creatinine clearance '50ml/min, were enrolled in a clinical trial aimed at evaluating the efficacy and the feasibility of a thalidomide-based regimen as induction therapy in preparation to autologous stem cell transplantation. Sixteen patients had a more severe renal impairment (creatinine clearance '30ml/min) and 7 of them were in chronic hemodyalisis. After informed consent, patients received four months of combined oral thalidomide (thal) (100mg/day for two weeks and 200mg/day thereafter) and dexamethasone (dex) (40mg/day on day 1-4, 9-11, 17-20/28 days on odd cycles and on day 1-4 on even cycles); peripheral blood stem cell collection was thus to be performed after priming with high-dose cyclophosphamide + G-CSF or G-CSF alone; a single or double autologous stem cell transplantation was then to follow, upon preparation with high-dose melphalan. After induction, a PR or better was obtained in 23 patients (74%), with 8 patients (26%) achieving a VGPR or better. No difference in response rate was observed in patients with a baseline creatinine clearance ≥30ml/min (86%) or < 30ml/min (62%). An improvement in renal function was more frequently observed in patients achieving ≥ PR (82% vs. 37% in patients obtaining < PR, p =0.04). Twenty-six patients underwent peripheral blood stem cell mobilization; in 17 of them (65%) the procedure was successful resulting in the collection of > 4 × 106 CD34+ cells/kg. Fifteen patients received a double autologous stem cell transplantation while a single transplant was performed in four patients. Overall, median event-free survival was 30 months, and median survival has not been reached, upon 32 months median follow-up. Toxicity profile of thal-dex was comparable to that observed in patients with a normal renal function. In conclusion, our data show that thal-dex can be safely administered in patients with newly diagnosed MM and renal failure. given the relationship between recovery of renal function and response to induction treatment, more intensive thal + bortezomib-including regimens could be potentially useful in order to rescue a higher number of patients. Disclosures Off Label Use: Thalidomide plus dexamethasone in newly diagnosed multiple myeloma.

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

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5553-5553
Author(s):  
Agoston Gyula Szabo ◽  
Jonathan Thorsen ◽  
Charlotte Toftmann Hansen ◽  
Maja Ølholm Vase ◽  
Manuela Teodorescu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
Serum Creatinine ◽  
Board Of Directors ◽  
Kidney Biopsy ◽  
Population Based ◽  
First Line ◽  
Advisory Committees ◽  
Cast Nephropathy ◽  
Initiation Of Therapy

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.

Dialytic Support in Patients with Acute Renal Failure with Implantable Left Ventricular Assist Devices

1997 ◽  
Vol 12 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Luz Moreno ◽  
Martine Leblanc ◽  
Melisa Gurley ◽  
Patrick Mccarthy ◽  
Emil P. Paganini
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Renal Replacement Therapy ◽  
Serum Creatinine ◽  
Heart Transplantation ◽  
Replacement Therapy ◽  
Metabolic Control ◽  
Left Ventricular ◽  
Ventricular Assist ◽  
Left Ventricular Assist

The left ventricular assist device (LVAD), used thus far as a bridge to heart transplantation, may offer an alternative to heart transplantation. Because patients receiving LVADs are in cardiogenic shock, many experience acute ischemic renal failure in the peri-implantation period. We describe 10 patients who underwent dialysis after receiving LVADs for end-stage heart disease. Among 37 patients who received an LVAD, 10 required dialytic support (8 men, 2 women; mean age, 47.3 ± 11.3 yr; mean APACHE II score at ICU admission, 18.0 ± 4.7). Renal replacement therapy was started for fluid removal within 48 hours of LVAD implantation in 8 patients. Continuous renal replacement therapy (CRRT) was the first-line modality for 9 patients, including 3 slow continuous ultrafiltrations (SCUF), 4 continuous venovenous hemofiltrations (CWH), 5 continuous venovenous hemodiafiltrations (CWHD), 2 continuous arteriovenous hemofiltrations (CAVH), and 1 continuous arteriovenous hemodiafiltration (CAVHD). Patients remained on CRRT for a mean of 14.4 ± 6.1 days, and 5 were eventually changed to intermittent hemodialysis. The mean time on renal replacement therapy was 27.8 ± 19.7 days. During CRRT, despite daily average ultrafiltration of 3,445 ± 623 mL, net fluid loss was only 358 ± 507 mL/day. Metabolic control achieved with CRRT, expressed as mean ± SD, was: BUN 75.5 ± 13.0 mg/dL (26.9 ± mmol/L), serum creatinine 4.0 ± 0.7 mg/dL (354 ± 62 mmol/L), carbon dioxide content (bicarbonate plus dissolved CO2) 21.5 ± 1.7 mEq/L, and serum electrolytes within normal limits. Survival for patients with LVADs who did not require dialysis was 93% compared with 40% for the group with combined LVADs and dialytic support. The 4 patients who survived in the dialysis group all recovered renal function, and their need for dialysis ceased within 18 to 33 days. Mean serum creatinine levels at follow-up after transplantation were 2.0 ± 1.0 mg/dL (177 ± 88 mmol/L). In conclusion, CRRT provides good metabolic control and allows large ultrafiltration volume in patients supported by an implantable LVAD. We observed a 40% survival rate in patients with combined LVADS and dialytic support, and the survivors all recovered renal function.

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