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Objective: Cast nephropathy (CN) is the leading cause of acute kidney injury (AKI) in multiple myeloma (MM). Since it is sparsely documented why some patients with CN do achieve a renal response while others do not, we describe a single-center cohort of patients with multiple myeloma and biopsy-confirmed CN to evaluate potential markers of renal response., Methods: The data was collected as a retrospective, single-center analysis of CN-patients treated at the Medical University Vienna between 01/01/2004 and 01/01/2022. Baseline parameters and clinical outcome was compared between renal responders and non-responders., Results: Among 28 patients with CN, n  = 23 were assessed for renal response (14 responders; 9 non-responders). Renal responders were younger (median age: 61 years; 77 years, p  = 0.039), showed higher overall survival (153months; 58months, p  = 0.044) and achieved hematologic response (≥PR) to first-line therapy ( p  = 0.029), and complete hematologic response (CR) at any time ( p  = 0.025) significantly more often. Further, we could show that rapid initiation of anti-myeloma therapy after initial presentation correlated significantly with renal response (median 9 days; 27 days, p  = 0.016). Analyses of kidney biopsy specimens revealed that patients with a high IF/TA score showed end stage renal disease (dialysis ≥ 3 months) significantly more often ( p  = <0.001)., Discussion: In summary, our data suggests, that a rapid start with systemic hematologic treatment in patients with MM and CN is crucial and achieving an early hematologic response is important for renal recovery. Moreover, achieving a deep hematologic response and subsequent renal recovery improves clinical outcome as reflected by an overall survival benefit.

Background: Lupus nephritis (LN) is associated with poor outcomes and a significant risk of progression to end-stage renal disease (ESRD). Some patients with resistant LN do not respond adequately to current treatment options and need alternative strategies or therapies., Objective: The objective is to evaluate the efficacy and safety of rituximab as a re-induction therapy (Re-RTX) followed by maintenance therapy for patients with resistant LN., Methods: Twenty-four patients with resistant LN (failed initial induction therapy or severe relapse after remission) were analyzed. Re-RTX was co-administered with other immunosuppressants. The primary KDIGO criteria outcomes included renal response (complete and partial), disease progression, relapses, and infections., Results: The median age was 28 years (IQR 24.5-42), and the female-to-male ratio was 11:1. All patients had active LN, and 91.3% had proliferative LN. Baseline creatinine was 1.075 mg% (IQR 0.7-1.38), and mean urine protein-to-creatinine ratio (UPCR) was 4.9 (IQR 2.8-6.65). Of the patients receiving RTX as re-induction therapy, 66.6% (16/24) had failed initial induction therapy with other immunosuppressants, whereas 33.3% (8/24) had severe relapse during maintenance therapy.Re-RTX had a favorable renal response at 6 months, with 91.7% of the patients responding (20.8% complete response and 70.8% partial response). At 12 months, 58.3% of the patients maintained a renal response (25% complete response and 33.3% partial response). Approximately one-third of patients relapsed within a year.Fourteen patients (58.3%) continued RTX maintenance therapy with two different treatment regimens. At 6 months, Regimen-1 (500 mg every 6 months) resulted in a partial response in 43% (3/7) and relapse in 57% (4/7) of patients. Regimen 2 (1 g dose per year) achieved a complete response in 28.5% (2/7) and a partial response in 71.5% (5/7) with no relapses at 6 months.At a median follow-up of 29 months, adverse renal outcomes were observed in 29.16% of the patients with progression to advanced chronic kidney disease (CKD) or end-stage renal disease (ESRD). The overall use of Re-RTX was considered safe, with a reported infection prevalence of 16%, which is comparable to the existing data., Conclusion: Re-RTX demonstrated efficacy and safety as an induction therapy for resistant LN. However, the response waned after 1 year, underscoring the need for optimized maintenance therapy., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: To assess the efficacy of autologous hematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM) patients with acute renal failure. Materials and Methods: A retrospective single-center study included 64 patients (30 men, 34 women) with MM and kidney damage at the onset of the disease, aged 19 to 65 years (median 54), who underwent auto-HSCT from 2013 to 2019. 23 patients (36%) were dialysis-dependent at the time of diagnosis. The analysis was carried out in two groups: the "HD-" group (patients who were independent of hemodialysis during auto-HSCT, n = 54), and the "HD +" group (patients who underwent auto-HSCT while treated with programmed hemodialysis, n = 10). Research results were statistically processed using the Statistica software (version 10.0); the data obtained were presented graphically. Statistical analysis was performed using survival analysis (using the Kaplan-Meier method, with a Log-Rank Test) and frequency analysis (using contingency tables and Fisher's test). Results : The patients dependent on hemodialysis were significantly more likely to require red blood cell transfusions compared to the dialysis-independent patients (100% versus 35%, p = 0.0001). Reactivation of a herpes viral infection and reversible toxic encephalopathy developed significantly more often in the patients from the "HD +" group compared with the patients from the "HD-" group (30% versus 6%, p = 0.04 and 20% versus 0%, p = 0.02, respectively). As a result of the treatment (induction + auto-HSCT), 14 patients (61%) became hemodialysis-independent. There was no transplant-related mortality. With a median follow-up of 48 months, the 5-year overall survival (OS) and progression-free survival (PFS) were 70% and 42%, respectively. Conclusion : Auto-HSCT is a safe and effective treatment for patients with MM complicated by acute kidney injury. Fourteen of 23 (61%) patients became dialysis-independent., Competing Interests: The authors declare no conflicts of interest in this work., (Copyright © 2024 Tehran University of Medical Sciences.)

Cytokines contribute to the pathogenesis of lupus nephritis (LN), yet their value as prognostic biomarkers is still debated. We aimed to describe the serum cytokines' profiles and prospectively assess correlations with disease features and renal response in a multicentric cohort of consecutive adult patients with biopsy-proven active LN. Cytokine associations with clinical and serological data were performed at LN diagnosis (T0), and at 3 (T3) and 6 months (T6) of follow up. Renal response according to EULAR definition was assessed at T3, T6 and T12. BAFF and interleukin (IL)-37 were measured by ELISA; IL-2, IL-10, IL-17A and IL-18 by a bead-based multiplex cytokine assay (Luminex). Thirty-nine patients with active LN (age 40.5 ± 15.6 years; F 71.8%; 84.6% proliferative LN) were enrolled, of whom twenty-nine displayed complete longitudinal records. At T0, we observed higher levels of IL-37 and IL-17 in proliferative vs. non-proliferative LN (IL-37: 0.0510 (0.0110-0.2300) vs. 0.0000 (0.0000-0.0397) ng/mL, p = 0.0441; IL-17: 2.0920 (0.5125-17.9400) vs. 0.0000 (0.0000-0.6025) pg/mL, p = 0.0026, respectively), and positive correlations between IL-10 and 24 h proteinuria (r = 0.416, p = 0.0249) and anti-dsDNA levels (r = 0.639, p = 0.0003). BAFF was higher in patients with low complement ( p < 0.0001). We observed a sustained correlation between BAFF and IL-10 throughout T6 (r = 0.654, p = 0.0210). Higher baseline IL-37 and BAFF levels were associated with renal response at T3 and T6, respectively, while baseline IL-18 levels were higher in patients achieving response at T12. Our study highlights the complexity of the cytokine network and its potential value as a marker of active LN and renal response.

Avoiding end-stage kidney disease in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) has a high therapeutic priority. Although renal response is a crucial measure to capture clinically relevant changes, clinal trials have used various definitions and no well-studied key surrogate markers to predict renal outcome in AAV exist. Differences in clinical features and histopathologic and therapeutic approaches will influence the course of kidney function. Its assessment through traditional surrogates (i.e. serum creatinine, glomerular filtration rate, proteinuria, hematuria and disease activity scores) has limitations. Refinement of these markers and the incorporation of novel approaches such as the assessment of histopathological changes using cutting-edge molecular and machine learning mechanisms or new biomarkers could significantly improve prognostication. The timing is favourable since large datasets of trials conducted in AAV are available and provide a valuable resource to establish renal surrogate markers and, likely, aim to investigate optimized and tailored treatment approaches according to a renal response score. In this review we discuss important points missed in the assessment of kidney function in patients with AAV and point towards the importance of defining renal response and clinically important short- and long-term predictors of renal outcome., Competing Interests: B.O. has received speaker fees and travel support from Otsuka. A.B. is member of the CKJ editorial board and has received consulting and speaker fees from AstraZeneca, Bayer, ChemoCentryx, Fresenius, Merck/MSD and Vifor. D.G. has received consulting fees from ChemoCentryx, GlaxoSmithKline and Aurinia. D.J. has received consultancy or lecture fees from Amgen, AstraZeneca, Bristol-Myers Squibb, ChemoCentryx, CSL Vifor, Novartis, Otsuka, Roche and Takeda. A.K. is member of the CKJ editorial board and has received consulting fees from Vifor Pharma, Otsuka, Delta 4, UriSalt and Catalyst Biosciences. The other authors declared no conflicts of interest related to this work., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Objective: To define predictors of response, time to response, flares, and long-term renal outcome in an inception cohort of proliferative lupus nephritis (PLN). Methods: We included 100 patients (80% female; mean age 31 ± 13 years) with biopsy-proven PLN (III, IV, III/IV + V). Clinical, laboratory, histological and therapeutical parameters were recorded at baseline, 6, 9, 12, 18, 24, 36, 72 months, time of flare, and last follow-up visit. Logistic and Cox-regression models were applied. Results: After induction treatment (69% received cyclophosphamide (CYC) and 27% mycophenolic acid (MPA)), partial (PR) or complete (CR) response was achieved in 59% (26% CR, 33% PR) and 67% (43% CR, 24% PR) of patients at 3 and 6 months, respectively; median time to PR was 3 months (IQR 5) and median time to CR was 6 months (IQR 9). Baseline proteinuria <1.5 g/day correlated with a shorter time to CR (HR 1.77) and with CR at 3, 6, and 9 months (OR 9.4, OR 5.3 and OR 3.7, respectively). During 100-month median follow-up, 33% of patients had ≥1 renal flares (median time: 38 months). Proteinuria >0.8 g/day at 12 months was associated with a higher risk of flares (OR 4.12), while MPA and mixed classes with lower risk (OR 0.14 and OR 0.13, respectively). Baseline proteinuria >2 g/day and 12-month proteinuria >0.8 g/day correlated with a shorter time to flare (HR 2.56 and HR 2.57, respectively). At the end of follow-up, 10% developed stage 3-4 chronic kidney disease (CKD), and 12% end-stage renal disease (ESRD). Twelve-month proteinuria >0.8 g/day (OR 10.8) and interstitial fibrosis/tubular atrophy >25% (OR 7.7) predicted CKD or ESRD at last visit. Conclusions: Baseline proteinuria <1.5 g/day predicted time to CR. Twelve-month proteinuria >0.8 g/day correlated with flares (ever) and time to flare and, along with baseline interstitial fibrosis/tubular atrophy >25%, predicted CKD or ESRD at the last visit.

Renal impairment (RI) is a relatively common complication of multiple myeloma, which increases in frequency as disease becomes more advanced and recovery of renal function becomes less likely as patients progress through lines of therapy. Clinical trials in the relapsed/refractory multiple myeloma (RRMM) setting have not uniformly included patients with RI or robustly reported their outcomes. Here, we review existing data among patients with RI and RRMM across drug classes (including immunomodulatory agents, proteasome inhibitors, monoclonal antibodies, antibody-drug conjugates, chimeric antigen receptor T-cell therapies, and exportin-1 inhibitor) to provide an improved understanding of available treatment options for this important population. We highlight data from pivotal clinical trials, including data relating to renal response (as defined by the International Myeloma Working Group) and discuss real-world experiences in patients with RI, where applicable. Despite substantial advances in RRMM treatment, the presence of RI remains associated with reduced overall survival. Consistent inclusion of patients with RI, and uniform reporting of their outcomes, should be encouraged in future prospective trials of treatments for RRMM., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MAD reports honoraria from participation in Advisory Boards from Amgen, Beigene, Bristol Myers Squibb, Janssen, and Takeda. JM reports consulting fees from Amgen, Bristol Myers Squibb, Glaxo Smith Kline, Janssen, Karyopharm, and Sanofi and a leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid for the American Society of Hematology. ET reports research funding from Amgen, Celgene, Genesis, Glaxo Smith Kline, Janssen, Sanofi, and Takeda; and honoraria from Amgen, Bristol Myers Squibb, Celgene, Genesis, Glaxo Smith Kline, Janssen, Novartis, Sanofi, and Takeda. PM reports honoraria for Abbvie, Amgen, Celgene, Janssen, Sanofi, and Oncopeptides. JB reports honoraria from Amgen, Celgene, Janssen, Takeda, and Oncopeptides; and participation in other board, society, committee, or advocacy group, paid or unpaid for Karyopharm and Sanofi. KSG reports research funding from Caelum Biosciences, Ionis, Janssen, Sanofi and Takeda; and honoraria from GSK and Janssen. PGR reports research funding from Bristol Myers Squibb, Celgene, Karyopharm, Oncopeptides and Takeda; Participation on a Data Safety Monitoring Board or Advisory Board for AstraZeneca, Bristol Myers Squibb/Celgene, Glaxo Smith Kline, Janssen, Karyopharm, Oncopeptides, Protocol Intelligence, Regeneron, Sanofi, Secura Bio, and Takeda. XL and JSK have nothing to disclosure., (© The Author(s), 2022.)

Background: Belimumab was recently approved for treatment of lupus glomerulonephritis (LN)., Aim: To evaluate renal response and its predictors in LN patients receiving belimumab in real-life., Patients and Methods: We considered all patients fulfilling the SLEDAI-2K renal items and/or having estimated glomerular filtration rate (eGFR)≤60 ml/min/1.73 m 2 , with positive anti-dsDNA and/or low C3/C4 enrolled in the multicentre Italian lupus cohort BeRLiSS (BElimumab in Real LIfe Setting Study), treated with monthly IV Belimumab 10 mg/kg over standard treatment. Primary efficacy renal response (PERR), defined as proteinuria ≤0.7 g/24 h, eGFR≥60 ml/min/1.73 m 2 without rescue therapy, was considered as primary outcome. Complete renal response (CRR; proteinuria <0.5 g/24 h, eGFR≥90 ml/min/1.73 m 2 ) was considered as secondary outcome. Prevalence and predictors of PERR were evaluated at 6, 12, 24 months by multivariate logistic regression., Results: Among the 466 SLE patients of BeRLiSS, 91 fulfilled the inclusion criteria, 79 females, median age 41.0 (33.0-47.0) years, median follow-up 22.0 (12.0-36.0) months. Sixty-four (70.3%) achieved PERR, of whom 38.4% reached CRR. Among patients achieving PERR at 6 months, 86.7% maintained response throughout the follow-up. At multivariable analysis, hypertension (OR [95%CI]: 0.28 [0.09-0.89], p = 0.032), high baseline serum creatinine (0.97 [0.95-0.99], p = 0.01) and high baseline proteinuria (0.37, [0.19-0.74], p = 0.005) negatively predicted PERR. Positive predictors of PERR at 12 and 24 months were baseline anti-Sm positivity (OR [95%CI]: 6.2 [1.21-31.7], p = 0.029; 19.8 [2.01-186.7], p = 0.009, respectively) and having achieved PERR at 6 months (14.4 [3.28-63.6]; 11.7 [2.7-48.7], p = 0.001 for both)., Conclusions: Add-on therapy with belimumab led to durable renal response in patients with LN in a real-life setting., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Renal impairment (RI) is associated with poor survival in newly diagnosed multiple myeloma (MM) patients. Renal function recovery has been one of the main therapeutic goals in those patients., Methods: The records from 393 newly diagnosed MM patients in our hospital between January 2012 and December 2016 were retrospectively analyzed. RI was defined as an eGFR < 40 mL/min according to the novel IMWG criteria. RI patients were categorized based on their renal function at diagnosis: severe RI: eGFR < 30 mL/min, and mild RI: 30 mL/min ≤ eGFR <40 mL/min. We explored whether RI, and particularly severe RI, was an adverse prognostic factor for survival, and investigated the impact of renal function recovery on survival., Results: Severe RI, hemoglobin <100 g/L, LDH ≥ 245 U/L, hyperuricemia, 1q21 amplification, and lack of novel agent treatment were associated with decreased overall survival (OS). Severe RI patients with renal response had a median OS of 27 months compared with 18 months for those patients without renal response (P = .030), but their median OS was still significantly lower than that for patients without severe RI, which was 51 months. In severe RI patients, the overall renal response rate in bortezomib-based regimens was significantly higher than that in nonbortezomib-based regimens., Conclusion: Our results suggest that severe RI is an adverse prognostic factor for survival in newly diagnosed MM patients, restoration of renal function may improve survival, and bortezomib-based regimens may be the preferred treatment in patients with severe RI., (© 2020 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals LLC.)

Background and Objectives: Incomplete peripheral blood B cell depletion after rituximab in lupus nephritis might correlate with inability to reduce tubulointerstitial lymphoid aggregates in the kidney, which together could be responsible for inadequate response to treatment. We utilized data from the Lupus Nephritis Assessment with Rituximab (LUNAR) study to characterize the variability of peripheral blood B cell depletion after rituximab and assess its association with complete response in patients with lupus nephritis., Design, Setting, Participants, & Measurements: We analyzed 68 participants treated with rituximab. Peripheral blood B cell depletion was defined as 0 cells/ µ l, termed "complete peripheral depletion," assessed over 78 weeks. Logistic regression was used to estimate the association between characteristics of complete peripheral depletion and complete response (defined as urine protein-to-creatinine ratio <0.5 mg/mg, and normal serum creatinine or an increase in creatinine <15%, if normal at baseline), assessed at week 78., Results: A total of 53 (78%) participants achieved complete peripheral depletion (0 cells/ µ l) in a median time of 182 days (interquartile range, 80-339).The median duration of complete peripheral depletion was 71 days (interquartile range, 14-158). Twenty-five (47%) participants with complete peripheral depletion achieved complete response, compared with two (13%) without. Complete peripheral depletion was associated with complete response (unadjusted odds ratio [OR], 5.8; 95% confidence interval [95% CI], 1.2 to 28; P =0.03). Longer time to achieving complete peripheral depletion was associated with a lower likelihood of complete response (unadjusted OR, 0.89; 95% CI, 0.81 to 0.98; P =0.02). Complete peripheral depletion lasting >71 days (the median) was associated with complete response (unadjusted OR, 4.1; 95% CI, 1.5 to 11; P =0.008)., Conclusions: There was substantial variability in peripheral blood B cell depletion in patients with lupus nephritis treated with rituximab from the LUNAR trial. Achievement of complete peripheral depletion, as well as the rapidity and duration of complete peripheral depletion, were associated with complete response at week 78., Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018&#95;09&#95;06&#95;CJASNPodcast&#95;18&#95;10&#95;.mp3., (Copyright © 2018 by the American Society of Nephrology.)

Background: Intensive haemodialysis (IHD) in addition to bortezomib-based chemotherapy might be efficient to rapidly decrease serum immunoglobulin-free light chains removal in patients with multiple myeloma (MM) and to improve renal prognosis and survival., Methods: The aim of this retrospective multi-centre study was to compare the efficacy (renal recovery rate) of IHD and of standard haemodialysis (SHD) in patients with MM and dialysis-dependent acute kidney injury (AKI), concomitantly treated with bortezomib-based chemotherapy., Results: We selected 41 patients with MM and dialysis-dependent AKI, most likely due to myeloma cast nephropathy (MCN), and who were treated in eight French hospitals between January 2007 and June 2011. Patients were classified in two groups according to dialysis regimen: IHD [ n  = 21, with a mean of 11.3 dialysis sessions all with poly(methyl methacrylate) (PMMA) membranes for 13.2 days] and SHD ( n  = 20 patients, mostly three times per week, 31% with PMMA membrane). The main outcome was dialysis-independence at 3 months. At 3 months, 15 patients could stop dialysis: 8 (38.1%) in the IHD and 7 (35%) in the SHD group (P = 1). Moreover, 14 (56%) of the 25 patients who did show haematological response and only one of the 16 patients who did not were dialysis-independent (P = 0.002) at 3 months., Conclusions: The results of this retrospective study did not show any clear renal benefit of IHD in patients with MM and MCN compared with SHD. Conversely, they underline the importance of the haematological response to chemotherapy for the renal response and patient prognosis.

Renal impairment (RI) in patients with multiple myeloma (MM) is associated with poor prognosis. In this population-based cohort study, we assessed the effects of renal response, evaluated according to the IMWG-criteria, on overall survival (OS) in patients with newly diagnosed MM with RI at presentation. All included patients were diagnosed between January 2005 and January 2014 with MM and RI in Friesland, a province of the Netherlands. Of the 131 included patients, 61% achieved renal response. Using a time-varying exposure Cox model, no difference in OS between renal response and non-response was observed (HR = 1.08, 95% CI = 0.67-1.74, p = .76). In multivariable analysis, baseline eGFR <30 ml/min (HR = 1.71), age >70 yrs (HR = 1.77), hypercalcemia (HR = 2.73), lambda Bence-Jones (HR= 1.76), and initial treatment regimen (HR = 0.89 for thalidomide, HR = 1.95 in treatment regimens without novel agents and HR = 3.60 for no chemotherapy, all vs. bortezomib) were associated with decreased OS. In conclusion, achieving renal response was not associated with improved OS.

Monoclonal immunoglobulin deposition disease (MIDD) is characterized by non-organized immunoglobulin-fragments along renal basement membranes with subsequent organ deterioration. Treatment is directed against the immunoglobulin-producing clone. We treated 18 MIDD patients with bortezomib-based regimens (12 received bortezomib-dexamethasone, 6 bortezomib-dexamethasone with cyclophosphamide). Eleven (61%) patients achieved a hematologic response, but only 6 (33.3%) reached to a complete (CR) or very good partial response (VGPR). Regarding renal outcomes 77.8 and 55.6% had ≥30 and ≥50% reduction of proteinuria, respectively, but 33.3% ended up in end-stage renal disease (ESRD). Among patients with CR or VGPR, median eGFR improvement was 7.7 ml/min/1.73 m 2 and none progressed to ESRD, but no significant renal recovery was observed in patients achieving a partial response or less, with 50% progressing to dialysis. Pretreatment eGFR seems to influence renal prognosis. Bortezomib-based treatment is considered an effective approach in MIDD and reaching to a deep hematologic response (≥VGPR) conditionally controls further renal declining.

Background: Lupus nephritis class III or IV is associated with a poor prognosis for both patient and renal survival. Recommendations for the management of lupus nephritis have recently been established, and changing therapies is recommended for patients who do not respond adequately to induction therapy. However, it remains a major challenge to determine when to switch the treatment. In this study, we identified early prognostic factors capable of predicting poor renal outcome as well as overall damage accrual in patients with lupus nephritis class III or IV., Methods: Eighty patients with biopsy-proven lupus nephritis class III or IV were retrospectively recruited and divided into two groups: those with complete renal response (CR) or non-CR at 3 years after induction therapy. We investigated when clinical responses were obtained at each observational period from baseline to year 3. Clinical responses were divided into three groups: CR, partial renal response (PR), and non-PR. Furthermore, patients were assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) and cumulative dose of corticosteroid for 3 years., Results: Forty-four patients with CR and thirty-six with non-CR were enrolled. The cumulative CR rate was 85.0%. PR rates of patients with CR were significantly higher than those with non-CR from week 12 (p < 0.01). We identified the achievement of PR at 12 weeks as an independent predictor (OR 3.57, p = 0.03) by multivariate analysis. We next divided all patients into two groups according to PR achievement at week 12. The cumulative CR rate of the patients who achieved PR at week 12 was significantly higher than that of those who did not (96.5% vs 69.2%, p < 0.001). Furthermore, a significantly higher SDI and cumulative dose of corticosteroid were seen in the patients who did not achieve PR at week 12 than in those who did, regardless of their CR status, at year 3., Conclusions: Lack of PR at week 12 predicts a lower likelihood of achieving CR at 3 years and a higher SDI.

Background: Kidney diseases associated with immunoglobulin M (IgM) monoclonal gammopathy are poorly described, with few data for patient outcomes and renal response., Study Design: Case series., Setting & Participants: 35 patients from 8 French departments of nephrology were retrospectively studied. Inclusion criteria were: (1) detectable serum monoclonal IgM, (2) estimated glomerular filtration rate (eGFR) < 60mL/min/1.73m(2) and/or proteinuria with protein excretion > 0.5g/d and/or microscopic hematuria, and (3) kidney biopsy showing monoclonal immunoglobulin deposits and/or lymphomatous B-cell renal infiltration. All patients received chemotherapy, including rituximab-based regimens in 8 cases., Predictors: Patients were classified into 3 groups according to renal pathology: glomerular AL amyloidosis (group 1; n=11), nonamyloid glomerulopathies (group 2; n=15, including 9 patients with membranoproliferative glomerulonephritis), and tubulointerstitial nephropathies (group 3; n=9, including cast nephropathy in 5, light-chain Fanconi syndrome in 3, and isolated tumor infiltration in 1)., Outcomes: Posttreatment hematologic response (≥50% reduction in serum monoclonal IgM and/or free light chain level) and renal response (≥50% reduction in 24-hour proteinuria or eGFR≥30mL/min/1.73m(2) in patients with glomerular and tubulointerstitial disorders, respectively)., Results: Nephrotic syndrome was observed in 11 and 6 patients in groups 1 and 2, respectively. Patients in group 3 presented with acute kidney injury (n=7) and/or proximal tubular dysfunction (n=3). Waldenström macroglobulinemia was present in 26 patients (8, 12, and 6 in groups 1, 2, and 3, respectively). Significant lymphomatous interstitial infiltration was observed in 18 patients (4, 9, and 5 patients, respectively). Only 9 of 29 evaluable patients had systemic signs of symptomatic hematologic disease (2, 5, and 2, respectively). In groups 1, 2, and 3, respectively, hematologic response was achieved after first-line treatment in 3 of 9, 9 of 10, and 5 of 6 evaluable patients, while renal response occurred in 5 of 10, 9 of 15, and 5 of 8 evaluable patients., Limitations: Retrospective study; insufficient population to establish the impact of chemotherapy., Conclusions: IgM monoclonal gammopathy is associated with a wide spectrum of renal manifestations, with an under-recognized frequency of tubulointerstitial disorders., (Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Renal impairment (RI) is one of the key clinical manifestations of symptomatic multiple myeloma. However, the incidence of RI and renal response to treatment are variable depending on their definition. A total of 379 patients newly-diagnosed and treated for symptomatic myeloma at the Samsung Medical Center between January 2000 and December 2011 were retrospectively reviewed. RI and renal response were assessed according to the recent International working group (IMWG) recommendations. Out of the 379 patients, renal insufficiency was present in 117 (30.8%) and was associated with adverse clinical parameters such as anemia, elevated beta-2 microglobulin (B2M), elevated lactate dehydrogenase (LDH), hypercalcemia, and more advanced disease by the International Staging System (ISS). Out of the 85 patients who were evaluable for renal response, 58 (68.2%) showed renal response and 46 (54%) had major renal response. Less advanced disease by the International Staging System and inclusion of high-dose dexamethasone as first-line treatment were independently predictive for major renal response. Median time-to-renal response was 5.5 months, and bortezomib-containing regimen, high-dose dexamethasone, and less advanced stage disease were associated with a more rapid renal response., Conclusion: The incidence of RI in patients with newly-diagnosed multiple myeloma was 31%, and renal response was affected by the treatment and staging by the International Staging System., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: The duration of maintenance therapy after induction therapy for lupus nephritis has not been rigorously established. A common practice is to maintain immunosuppression for 1-2 years after complete remission, and longer for partial remission. The present work addresses whether a repeat kidney biopsy might be informative in deciding who should continue immunosuppression after complete or partial remission., Methods: The practice in a large Buenos Aires nephrology unit is to repeat a kidney biopsy before finalizing the decision to withdraw or continue immunosuppression. This work reports on a cohort of 25 Hispanic patients that had two or more kidney biopsies, the last occurring after at least 24 months of clinically quiescent disease., Results: Despite normalization of serum creatinine and reduction of proteinuria to <500 mg/d, 30% of patients still had significant activity at the last biopsy. Conversely, 60% of patients with ongoing proteinuria (500-1000 mg/d), or stable but abnormal serum creatinine, had no activity by biopsy. Univariate association analyses demonstrated that improvement in the activity index (AI) of the last biopsy was associated with choice of induction therapy (cyclophosphamide or mycophenolate), improvement in serum creatinine over the first six months of treatment, and improvement in complement component C4. By multivariate regression analyses, two AI prediction models emerged. Cyclophosphamide plus change in serum creatinine or cyclophosphamide plus change in C4 accounted for 50% of the improvement in AI., Conclusion: These data suggest that a repeat biopsy may be useful in making the decision to withdraw or continue maintenance immunosuppression., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)