Renal Recovery In Patients Research Articles

635 - Impact of race on renal recovery in patients with new diagnosis of multiple myeloma and acute kidney injury requiring dialysis

635 - Impact of race on renal recovery in patients with new diagnosis of multiple myeloma and acute kidney injury requiring dialysis

Impact of Race on Renal Recovery in Patients with New Diagnosis of Multiple Myeloma and AKI Requiring Dialysis

Impact of Race on Renal Recovery in Patients with New Diagnosis of Multiple Myeloma and AKI Requiring Dialysis

The effect of cytosorb® application on kidney recovery in critically ill patients with severe rhabdomyolysis: a propensity score matching analysis

Severe rhabdomyolysis frequently results in acute kidney injury (AKI) due to myoglobin accumulation with the need of kidney replacement therapy (KRT). The present study investigated whether the application of Cytosorb® (CS) led to an increased rate of kidney recovery in patients with KRT due to severe rhabdomyolysis. Adult patients with a myoglobin-concentration >10,000 ng/ml and KRT were included from 2014 to 2021. Exclusion criteria were chronic kidney disease and CS-treatment before study inclusion. Groups 1 and 2 were defined as KRT with and without CS, respectively. The primary outcome parameter was independence from KRT after 30 days. Propensity score (PS) matching was performed (predictors: myoglobin, SAPS-II, and age), and the chi2-test was used. 35 pairings could be matched (mean age: 57 vs. 56 years; mean myoglobin: 27,218 vs. 26,872 ng/ml; mean SAPS-II: 77 vs. 76). The probability of kidney recovery was significantly (p = .04) higher in group 1 (31.4 vs. 11.4%, mean difference: 20.0%, odds ratio (OR): 3.6). Considering patients who survived 30 days, kidney recovery was also significantly (p = .03) higher in patients treated with CS (61.1 vs. 23.5%, mean difference: 37.6%, OR: 5.1). In conclusion, the use of CS might positively affect renal recovery in patients with severe rhabdomyolysis. A prospective randomized controlled trial is needed to confirm this hypothesis.

Bicarbonate-Based Solution for the Management of Established Acute Kidney Injury: A Pilot Open-Label Observation Study.

Background Administration of intravenous (IV) solutions constitutes a key component of acute kidney injury (AKI) management. However, the optimal IV fluid solution in the setting of AKI remains uncertain. In this study, we assessed whether the use of bicarbonate-containing solution in patients with established AKI is associated with early renal recovery as compared to bicarbonate-free solutions. Methods We performed an open-label observational pilot study in 59 patients with established AKI. IV fluid solutions that were used include bicarbonate-based solution with low chloride content (80 mEq/L of 8% sodium bicarbonate in a solution that contains 77 mEq/L of sodium, 77 mEq/L of chloride and 25 g/L of glucose) or solutions without bicarbonate with high chloride content (0.9% normal saline, 0.45% half-saline, normal ringer, or 4% succinylated gelatine). We evaluated the association of IV fluids type with renal recovery. Results The median age of study participants was 66 years (inter-quartile range (IQR) 37-85), and 59% (n=35) were men. The prevalence of diabetes and chronic kidney disease (CKD) stages 1-3 were 34% (n=20) and 39% (n=23), respectively. Patients who received bicarbonate-based IV solutions had a greater reduction of serum creatinine (sCr) per day (delta sCr) as compared with patients who received bicarbonate-free solutions (-0.29±0.47 vs. 0.07±0.42; p=0.007). The renal recovery was faster in patients who received bicarbonate-based solutions as compared to the bicarbonate-free group (days from peak sCr to baseline sCr: 5.6±2.1 vs. 7.6±2.8; p < 0.001, respectively). Conclusions We observed faster renal recovery in patients with established AKI who received the bicarbonate-based solution with low chloride content. Our study findings require confirmation in larger cohorts.

Risk nomogram for assessing renal recovery in patients with newly diagnosed multiple myeloma-related renal impairment

To determine risk factors affecting renal recovery in newly diagnosed multiple myeloma (NDMM) patients with renal impairment (RI) and establish a risk nomogram. This multi-center, retrospective cohort study included 187 NDMM patients with RI, 127 of whom were admitted to Huashan Hospital and assigned to the training cohort and 60 were admitted to Changzheng Hospital and assigned to the external validation cohort. The baseline data of the 2 cohorts were compared, and survival and renal recovery rates were analyzed. Independent risk factors affecting renal recovery were determined by binary logistic regression analysis, and a risk nomogram was established and subsequently tested in the external validation cohort. Results: The median overall survival (OS) improved in patients who achieved renal recovery etc within 6 courses of MM directed treatment compared with patients without renal recovery. Median time to renal recovery was 2.65 courses, and the cumulative renal recovery rate during the first 3 courses was 75.05%. Involved serum free light chain (sFLC) ratio of >120 at diagnosis, time from renal impairment to treatment > 60 days, and a hematologic response without a very good partial remission (VGPR) or better resulted as independent risk factors for renal recovery during the first 3 courses. The established risk nomogram had good discriminative ability and accuracy. Involved sFLC was a key factor affecting renal recovery. Starting treatment as soon as possible after detecting RI and achieving deep hematologic remission during the first 3 courses of treatment helped achieve renal recovery and improve prognosis.

Analysis of urinary C–C motif chemokine ligand 14 (CCL14) and first-generation urinary biomarkers for predicting renal recovery from acute kidney injury: a prospective exploratory study

BackgroundAcute kidney injury (AKI) is a frequent syndrome in the intensive care unit (ICU). AKI patients with kidney function recovery have better short-term and long-term prognoses compared with those with non-recovery. Numerous studies focus on biomarkers to distinguish them. To better understand the predictive performance of urinary biomarkers of renal recovery in patients with AKI, we evaluated C–C motif chemokine ligand 14 (CCL14) and two first-generation biomarkers (cell cycle arrest biomarkers and neutrophil gelatinase-associated lipocalin) in two ICU settings.MethodsWe performed a prospective study to analyze urinary biomarkers for predicting renal recovery from AKI. Patients who developed AKI after ICU admission were enrolled and urinary biomarkers including tissue inhibitor of metalloproteinase-2 (TIMP-2), insulin-like growth factor-binding protein 7 (IGFBP7), CCL14, and neutrophil gelatinase-associated lipocalin (NGAL) were detected on the day of AKI diagnosis. The primary endpoint was non-recovery from AKI within 7 days. The individual discriminative ability of CCL14, [TIMP-2] × [IGFBP7] and NGAL to predict renal non-recovery were evaluated by the area under receiver operating characteristics curve (AUC).ResultsOf 164 AKI patients, 64 (39.0%) failed to recover from AKI onset. CCL14 showed a fair prediction ability for renal non-recovery with an AUC of 0.71 (95% CI 0.63–0.77, p < 0.001). [TIMP-2] × [IGFBP7] showed the best prediction for renal non-recovery with an AUC of 0.78 (95% CI 0.71–0.84, p < 0.001). However, NGAL had no use in predicting non-recovery with an AUC of 0.53 (95% CI 0.45–0.60, p = 0.562). A two-parameter model (non-renal SOFA score and AKI stage) predicted renal non-recovery with an AUC of 0.77 (95% CI 0.77–0.83, p = 0.004). When [TIMP-2] × [IGFBP7] was combined with the clinical factors, the AUC was significantly improved to 0.82 (95% CI 0.74–0.87, p = 0.049).ConclusionsUrinary CCL14 and [TIMP-2] × [IGFBP7] were fair predictors of renal non-recovery from AKI. Combing urinary [TIMP-2] × [IGFBP7] with a clinical model consisting of non-renal SOFA score and AKI stage enhanced the predictive power for renal non-recovery. Urinary CCL14 showed no significant advantage in predicting renal non-recovery compared to [TIMP-2] × [IGFBP7].

Prognostic value of serum levels of multiple adhesion factors in patients with sepsis-induced acute kidney injury

BackgroundAcute kidney injury (AKI) is common in patients with sepsis and septic shock. Urine output and serum creatinine (SCr) levels are the criteria for diagnosing AKI. However, the application of these levels in the diagnosis of AKI has limitations.ObjectiveTo detect the expression of various adhesion factors in different stages of AKI as defined by Kidney Disease: Improving Global Outcomes (KDIGO) and to analyse their relationship with the prognosis of patients with sepsis-induced AKI (S-AKI).MethodsAdult patients with sepsis who were admitted to the hospital between June 2019 and May 2020 were included. Of 90 adult patients with sepsis, 58 had S-AKI. Sixty-seven subjects without sepsis were used as controls. Enzyme-linked immunosorbent assay kits were used to measure E-selectin (CD62E), L-selectin (CD62L), P-selectin, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and their relationship with the prognosis of patients with S-AKI patients was analysed. Receiver operating characteristic curves were used to analyse the predictive value of different adhesion factors on renal resistance index and renal function recovery. Multivariate logistic regression analysis was used to identify factors associated with renal recovery.ResultsThe expression of CD62L was significantly higher in S-AKI patients than in non-AKI patients with sepsis. Compared with the non-AKI group, Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores were significantly higher in the AKI group than in the non-AKI group (P < 0.05). Mean blood pressure, SCr levels and procalcitonin levels were higher in the AKI group than in the non-AKI group (P < 0.05 for all). The CD62L levels decreased with increasing S-AKI stage. The CD62E levels were highest in S-AKI stage 2, and the VCAM-1 levels were highest in S-AKI stage 3. All patients with S-AKI were followed up with for 28 days. The results found that VCAM-1 was the best predictor of renal recovery in patients with S-AKI.ConclusionCD62L is an indicator of S-AKI stage1, and CD62E is an indicator of S-AKI stage 2. In addition, VCAM-I demonstrated satisfactory performance in predicting early recovery of renal function in patients with S-AKI.

Reduction of Intra-Operative Nephrotoxic Antimicrobial Exposure Can Improve Renal Recovery in Patients Undergoing Heart Transplantation

Reduction of Intra-Operative Nephrotoxic Antimicrobial Exposure Can Improve Renal Recovery in Patients Undergoing Heart Transplantation

Effect of angiotensin receptor neprilysin inhibitor in patients of heart failure with reduced ejection fraction with reduced ejection fraction with cardiorenal syndrome type-1

Background: Heart failure is recognized as one of the most common indications for hospitalization. The dysfunction of either the heart or the kidneys affect the functioning of each other and thus play an important role in the quality of life.Methods: This study is a Prospective interventional Cohort study over a period of 18 months in 125 patients. The patients were divided into two broad treatment groups. The primary end point of the study was to quantify the response of ARNI for renal recovery in patients of cardio-renal syndrome and improvement in cardiovascular parameters by measuring the change in urine output, estimated glomerular filtration rate, serum creatinine, change in weight of the patients, control of blood pressure and change in left ventricular ejection fraction. The secondary end-points were evaluated during the 60 days follow up period post admissions.Results: Cardio-renal syndrome was seen in 39% of the patients. On screening e-GFR was 91±14 and 49±8 for group 1and 2 respectively, the median age, UACR was 59 years ,1.0 mg/mmol respectively for both the groups and 19% had micro albuminuria. ACEIs had more reports of hyperkalemia (8/32, 25%), and greater deterioration of renal parameters (10/32, 34%) needing discontinuation of the drug in some patients. Patients also developed cough (6/32, 20%) needing replacement with ARBs. ARNI group developed more hypotension (6/31, 20%). In all cardiovascular and renal end points except UACR, ARNI showed better recovery profile in CRS-1patients including diabetics.Conclusions: This study showed beneficial effects of ARNI in heart failure patients with cardio-renal syndrome.

Renal Recovery In Patients With Type B Aortic Dissections Who Underwent Aortic Stent Placement: A Retrospective Review

Renal Recovery In Patients With Type B Aortic Dissections Who Underwent Aortic Stent Placement: A Retrospective Review

MO322: Utility of Contrast-Enhanced Ultrasound to Predict Renal Recovery in Patients With Sepsis-Associated Acute Kidney Injury Receiving Renal Replacement Therapy

Abstract BACKGROUND AND AIMS Microcirculation plays a critical role in the development of sepsis-associated acute kidney injury (S-AKI); however, it remains uncertain whether microcirculatory dysfunction influences recovery. We investigated the association of contrast-enhanced ultrasound (CEUS)-assessed microcirculatory parameters with dialysis dependence in patients with S-AKI receiving renal replacement therapy. METHOD This study included 23 patients who underwent renal replacement therapy due to S-AKI, in addition to 17 healthy individuals and 18 subjects with chronic kidney disease (CKD). Parameters obtained from CEUS were compared. RESULTS Of the CEUS-derived parameters, patients with S-AKI had delayed rise time, time to peak and fall time, compared with healthy individuals (P = .039, .045 and .072), but they had similar values of peak enhancement, wash-in/out area under the curve (AUC), and wash-in perfusion index. Parameters did not differ between the S-AKI and CKD groups. Among patients with S-AKI, 10 (43.5%) patients did not experience renal recovery and required the lifelong dialysis treatment. They had lower values of peak enhancement, wash-in/out AUC, and wash-in perfusion index than in those with recovered renal function (P = .049, .021, .036 and .049). In addition, these values were slightly related to renal recovery after the adjustment with age, sex and disease severity (P = .096, .065, .094 and .072, respectively). We further evaluated the receiver operating characteristic curve and observed that CEUS-derived peak enhancement, wash-in/out AUC, and wash-in perfusion index predicted renal recovery (P = .047, .022, .035 and .047). CONCLUSION Assessment of microcirculatory alterations using CEUS may help to predict the probability of renal recovery in patients with S-AKI receiving renal replacement therapy. Further studies are needed to confirm the utility of CEUS, in consideration with baseline renal function and pathologic findings.

Intravenous Administration of Vitamin B Complex Improves Renal Recovery in Patients with AKI

Intravenous Administration of Vitamin B Complex Improves Renal Recovery in Patients with AKI

Reduction of Intraoperative Nephrotoxic Antimicrobial Exposure Can Decrease the Severity of Stage of AKI and Improve Renal Recovery in Patients Undergoing Heart Transplantation

Reduction of Intraoperative Nephrotoxic Antimicrobial Exposure Can Decrease the Severity of Stage of AKI and Improve Renal Recovery in Patients Undergoing Heart Transplantation

Modalities of renal replacement therapy and clinical outcomes of patients with acute kidney injury in a resource-limited setting: Results from a SEA-AKI study.

To determine the effects of modalities of renal replacement therapy (RRT) on the 30-d mortality and renal recovery in patients with acute kidney injury (AKI). A multicenter cohort study was conducted in 17 hospitals from Thailand and Indonesia. We recruited patients who were admitted to the Intensive care unit and diagnosed with AKI. Relevant mode of RRT, as intermittent hemodialysis (IHD), continuous renal replacement therapy (CRRT), peritoneal dialysis (PD), or sustained low efficiency dialysis (SLED), was initiated as indicated. From 2844 patients with AKI, 449 cases (8.1%) received RRT. There were no significant differences in the 30-d mortality between those initially treated with CRRT, PD, and SLED compared to those treated with IHD. The renal recovery was similar for each RRT mode. The three independent factors of death were the primary diagnosis of kidney disease, higher APACHE II score, and non-renal SOFA score. Only 48 (10.7%) patients had been switched to another mode of RRT. All four modes of RRT (IHD, CRRT, PD, and SLED) are acceptable treatments for severe AKI and gave a similar survival rate.

Intermittent Convective Therapies in Patients with Acute Kidney Injury: A Systematic Review with Meta-Analysis

Introduction: In critically ill patients requiring intermittent renal replacement therapy (RRT), the benefits of convective versus diffusive clearance remain uncertain. We conducted a systematic review and meta-analysis to determine the safety, clinical efficacy, and clearance efficiency of hemofiltration (HF) and hemodiafiltration (HDF) compared to hemodialysis (HD) in patients with acute kidney injury (AKI) receiving intermittent RRT. Method: We searched Medline, Embase, Cochrane Library, and PROSPERO. We included clinical trials and observational studies that reported the use of intermittent HF or HDF in adult patients with AKI. The following outcomes were included: mortality, renal recovery, clearance efficacy, intradialytic hemodynamic stability, circuit loss, and inflammation modulation. Results: A total of 3,169 studies were retrieved and screened. Four randomized controlled trials and 4 observational studies were included (n: 615 patients). Compared with conventional HD, intermittent convective therapies had no effect on in-hospital mortality (relative risk, 1.23; 95% confidence interval (CI), 0.76–1.99), renal recovery at 30 days (RR, 0.98; 95% CI, 0.82–1.16), time-to-renal recovery (mean difference [MD], 0.77; 95% CI, −6.56 to 8.10), and number of dialysis sessions until renal recovery (MD, −1.34; 95% CI, −3.39 to 0.72). The overall quality of included studies was low, and dialysis parameters were suboptimal for all included studies. Conclusion: This meta-analysis suggests that there is no significant difference in short-term mortality and renal recovery in patients with severe AKI when treated with intermittent HF or HDF compared to conventional HD. This systematic review emphasizes the need for further trials evaluating optimal convective parameters in AKI patients treated with intermittent dialysis.

Histopathological Findings Predict Renal Recovery in Severe ANCA-Associated Vasculitis Requiring Intensive Care Treatment.

Renal involvement is a common and severe complication of AAV as it can cause ESRD. Histopathological subgrouping and ARRS are helpful to predict long-term ESRD in patients with AAV. Because a subgroup of critically ill patients with severe AAV present with deterioration of kidney function requiring RRT at admission, we here aimed to evaluate histopathological findings and predictive value of Berden's histopathological subgrouping and ARRS for severity of AKI and requirement of RRT during the short-term clinical course in critically ill patients requiring intensive care treatment and predictors for short-term renal recovery in patients requiring RRT. A subgroup of 15/46 (32. 6%) AAV patients with biopsy-proven AAV required RRT during the short-term course of disease, associated with requirement of critical care treatment. While histopathological subgrouping and ARRS were associated with requirement of acute RRT, presence of global glomerular scarring was the strongest predictor of failure to recover from RRT after initiation of remission induction therapy. This new aspect requires further investigation in a prospective controlled setting for therapeutic decision making especially in this subgroup.

Higher Plasma KIM-1 Is Associated with Increased Mortality and Decreased Renal Recovery in Patients with AKI Requiring Renal Replacement Therapy

Higher Plasma KIM-1 Is Associated with Increased Mortality and Decreased Renal Recovery in Patients with AKI Requiring Renal Replacement Therapy

PF635 SERUM ERYTHROPOIETIN IS A PREDICTIVE FACTOR OF RENAL REVERSIBILITY IN RENAL IMPAIRMENT IN MULTIPLE MYELOMA PATIENTS

Background:Renal impairment (RI) is a common complication of multiple myeloma (MM) that contributes to its morbidity and mortality. Previous studies have shown that early reduction of serum‐free light chains (FLC) is associated with renal recovery. Some patients, however, developed irreversible RI, although they received novel agents and achieved early reduction of FLC. In the era of novel agents, the other factors of RI reversibility remain unclear.Aims:The purpose of this study was to extend and update our previous research and determine the clinical variables that affect renal recovery in patients with RI who receive novel agents.Methods:We retrospectively analyzed the medical records of patients with newly diagnosed MM with concurrent RI at the Kameda Medical Center (Chiba, Japan) between January 2008 and December 2018. RI was defined as an estimated glomerular filtration rate (eGFR) &lt;50 ml/min per 1.73m2 that was measured before treatment by the simplified Modification of Diet in Renal Disease formula. Maximum renal response was evaluated according to the International Myeloma Working Group criteria. We defined major renal response as the achievement of CRrenal and PRrenal.Results:A total of 110 patients with RI and median age of 72 years, were included in this study; 56 (50.9%) achieved major renal response, including PRrenal (4.5%) and CRrenal (46.4%). There were significant differences in median percentage of urinary albumin and serum erythropoietin levels between the patients with and without major renal response, but the baseline involved FLC (iFLC) and percentage of iFLC reduction at day 12 and 21 was not significantly different. As the level of circulating erythropoietin is increased by the presence of anemia, 6 patients who did not have anemia (male, Hb &lt; 12.0 g/dl; female, Hb &lt; 11.0 g/dl) were excluded from the analysis associated with erythropoietin. The baseline of erythropoietin &gt; 25 mIU/ml was associated with shorter time to rapid major response (2.4 months vs not estimated [NE] for erythropoietin ≤ 25 mIU/ml, P &lt;0.001). Percentage of urinary albumin excretion was also associated with more rapid major response (3.0 months vs NE for percentage of urinary albumin &gt; 25%, P &lt; 0.001). Reduction of iFLC on days 12 and 21 tended to be associated with shorter time to major renal response, but the relation was not statistically significant. When we adjusted for age, baseline serum calcium, and baseline eGFR by multivariate analysis, erythropoietin &gt; 25 mIU/ml (hazard ratio [HR], 5.99; 95% CI, 2.38–15.1; P &lt; 0.001) and percentage of urinary albumin excretion ≤ 25% (HR, 6.67; 95% CI, 1.91–23.3; P = 0.003) were independent predictive factors for shorter time to major renal response.We assigned a score of 1 to each of the two predictive variables (erythropoietin &gt; 25 mIU/ml and percentage of urinary albumin excretion ≤ 25%). The median time to major renal response of patients with scores of 2, 1, and 0 points differed significantly (2.0 months vs NE vs NE, P &lt; 0.001). The estimated rates of major renal response at 6 months of patients with scores of 2, 1, and 0 points were 78.6%, 30.6%, and 0%, respectively (Figure)Summary/Conclusion:Our analysis, for the first time, indicated that the level of erythropoietin &gt; 25 mIU/ml showed an independent positive predictive value for shorter time to major renal response. When the level of erythropoietin &gt; 25 mIU/ml was combined with a percentage of urinary albumin excretion ≤ 25%, renal reversibility was predicted more accurately and patients with irreversible renal impairment could be detected.image

High cutoff versus high-flux haemodialysis for myeloma cast nephropathy in patients receiving bortezomib-based chemotherapy (EuLITE): a phase 2 randomised controlled trial

In multiple myeloma, severe acute kidney injury due to myeloma cast nephropathy is caused by pathogenic free light chain immunoglobulin in serum. High cutoff haemodialysis (HCO-HD) can remove large quantities of free light chain immunoglobulin from serum, but its effect on clinical outcomes is uncertain. We therefore aimed to assess whether HCO-HD could increase the frequency of renal recovery in patients with de novo multiple myeloma, severe acute kidney injury, and myeloma cast nephropathy relative to treatment with standard high-flux haemodialysis (HF-HD). In this open-label, phase 2, multicentre, randomised controlled trial (EuLITE), we recruited patients with newly diagnosed multiple myeloma, biopsy-confirmed cast nephropathy, and acute kidney injury that required dialysis from renal services in 16 hospitals in the UK and Germany. Patients were randomly assigned (1:1) by random number generation to receive intensive HCO-HD (in sessions lasting 6-8 h) or standard HF-HD and they were stratified by age and centre. Patients and the medical staff treating them were not masked to treatment allocation. Patients received bortezomib, doxorubicin, and dexamethasone chemotherapy, and were then followed up for 2 years. The primary outcome was independence from dialysis at 90 days after random allocation to groups, which was assessed in an intention-to-treat population. The trial has completed follow-up, and is registered at the ISRCTN registry, number ISRCTN45967602. Between June 7, 2008, and Sept 18, 2013, we recruited 90 patients, of whom 43 (48%) were randomly assigned to receive HCO-HD and 47 (52%) were randomly assigned to receive HF-HD. All 90 patients were included in the analysis of the primary outcome. One (2%) patient from the HF-HD group withdrew consent before receiving treatment. During treatment, nine (21%) patients from the HCO-HD group and two (4%) patients in the HF-HD group discontinued trial treatment. After 90 days, 24 (56%) patients in the HCO-HD group and 24 (51%) patients in the HF-HD group were independent from dialysis (relative risk 1·09, 95% CI 0·74-1·61; p=0·81). During the 2-year follow-up, 98 serious adverse events were reported in the HCO-HD group and 82 serious adverse events were reported in the HF-HD group. The most common serious adverse events were infections and adverse events related to the cardiovascular and thrombotic and musculoskeletal systems. During the first 90 days, 26 infections were reported in the HCO-HD group and 13 infections were reported in the HF-HD group, including 14 lung infections in the HCO-HD group and three lung infections in the HF-HD group. In this phase 2 study, HCO-HD did not improve clinical outcomes for patients with de novo multiple myeloma and myeloma cast nephropathy who required haemodialysis for acute kidney injury and who received a bortezomib-based chemotherapy regimen relative to those receiving HF-HD. These results do not support proceeding to a phase 3 study for HCO-HD in these patients. Gambro, Janssen, and Binding Site.

Erythropoietin Level and Percentage of Urinary Albumin Are Important for Renal Recovery in Patients with Multiple Myeloma Receiving Novel Agents

BackgroundRenal impairment (RI) is one of the most common complications of multiple myeloma (MM), and is a major cause of morbidity and mortality. Monoclonal free light chain (FLC) is associated with most RI in patients with MM, and previous reports showed that early reduction of FLC is associated with renal recovery. Novel agents including bortezomib and immunomodulatory drugs (IMiDs) contribute to early reduction of FLC, leading to renal recovery. However, some patients developed irreversible RI despite the use of novel agents, and the factors that predict renal recovery other than early reduction of FLC remain unclear. This study retrospectively analyzed the clinical variables that affect renal recovery in patients with RI receiving novel agents.Patients and MethodsThe study population consisted of 235 consecutive patients with newly diagnosed MM (NDMM) between January 2008 and April 2018 at Kameda Medical Center, Japan. All patients were treated with bortezomib or IMiD-based combined chemotherapy in the frontline setting. Nine patients who received less than 2 courses of chemotherapy were excluded because it was difficult to assess renal recovery. RI was defined as an estimated pretreatment glomerular filtration rate (eGFR) of <50 ml/min/1.73 m2. We used the simplified Modification of Diet in Renal Disease formula to calculate eGFR. Maximum renal response was evaluated according to International Myeloma Working Group (IMWG) renal response criteria. Major renal response was defined as achieving PRrenal and CRrenal. Erythropoietin (EPO) was measured, if a patient had anemia (male: hemoglobin [Hb] <12.0 g/dl, female Hb <11.0 g/dl). Statistical analyses were performed with EZR, which is a graphical user interface for R ver. 3.2.2.Ethical considerationsThis study was approved by the institutional review board of Kameda Medical Center and conducted in accordance with the principles of the Declaration of Helsinki.ResultsThe median patient age was 72.2 years and the median observation period was 40.8 months. Moderate-to-severe RI (eGFR <50 mL/min/1.73 m2) was identified in 104 patients (46.5%). The median eGFR was 27.9 ml/min/1.73 m2. The percentage of patients with light-chain only isotype was 28.8%, and 57.7% of the patients had kappa light chain. According to IMWG renal response criteria, 54.8% of patients achieved major renal response, including PRrenal 4.8% and CRrenal 49.0%. Baseline involved FLC, reduction of FLC, light chain-only isotype, and kappa light chain type were not statistically significant between patients with or without major renal response. There were significant differences in age, calcium, EPO, and percentage of urinary albumin excretion between responders and non-responders (Table). Receiver operating characteristic curve analysis showed that the best cutoff values were 24.6 mIU/ml for EPO and 24.7% for the percentage of urinary albumin (Figure). The factors associated with major renal response included age <75 years, calcium, percentage of urinary albumin <25%, and EPO ≥25 mIU/ml. The multivariate logistic regression analysis showed that age <75 years [Odds ratio (OR)=9.86; p=0.005], calcium (OR=8.94; p=0.010), percentage of urinary albumin <25% (OR=15.5; p=0.002), and EPO ≥25 mIU/ml (OR=18.4; p<0.001) were independent predictive factors for renal recovery. When patients were divided based on the percentage of urinary albumin <25% and level of EPO ≥25 mIU/ml, the proportion of those who achieved major renal recovery was significantly different among 3 groups (both urinary albumin <25% and EPO ≥25 mIU/ml vs. either urinary albumin <25% or EPO ≥25 mIU/ml vs. neither urinary albumin <25% nor EPO ≥25 mIU/ml: 84.2% vs 32.3% vs. 6.0%, p<0.001).ConclusionOur results indicate that early reduction of FLC could have less predictive value for renal recovery compared to that in previous reports because early FLC reduction could be obtained in almost all patients irrespective of improvement in renal function. However, the level of serum EPO and the percentage of urinary albumin emerged as positive predictive factors for renal recovery in patients with RI receiving novel agents. The combination of these 2 variables could predict renal recovery more precisely. DisclosuresNo relevant conflicts of interest to declare.