Effects of Hydroxychloroquine on Proteinuria in IgA Nephropathy: A Randomized Controlled Trial.

RATIONALE & OBJECTIVE: Despite optimization of renin-angiotensin-aldosterone system (RAAS) inhibition, patients with immunoglobulin A nephropathy (IgAN) and persistent proteinuria remain at risk for kidney failure. We evaluated the efficacy and safety of hydroxychloroquine (HCQ), an immunomodulator, when added to the treatment regimen of patients with IgAN. STUDY DESIGN: Double-blind, randomized, placebo-controlled, phase 2 clinical trial. SETTING & PARTICIPANTS: Participants had IgAN (proteinuria with protein excretion of 0.75-3.5g/d and estimated glomerular filtration rate>30mL/min/1.73m2) and were receiving optimized RAAS inhibitor therapy. INTERVENTIONS: Patients were randomly assigned 1:1 to receive daily oral HCQ or a placebo for 6 months. OUTCOMES: The primary outcome was percentage change in proteinuria between baseline and 6 months. RESULTS: 60 participants (mean estimated glomerular filtration rate, 53.8mL/min/1.73m2; median urine protein excretion, 1.7g/d) were recruited and randomly assigned to receive HCQ (n=30) or placebo (n=30). Percentage change in proteinuria at 6 months was significantly different between the HCQ group and the placebo group (-48.4% [IQR, -64.2%, -30.5%] vs 10.0% [IQR, -38.7%, 30.6%]; P<0.001, respectively). At 6 months, median proteinuria level was significantly lower in the HCQ group than in the placebo group (0.9 [IQR, 0.6, 1.0] g/d vs 1.9 [IQR, 0.9, 2.6] g/d; P=0.002, respectively). No serious adverse events were recorded during the study in either study group. LIMITATIONS: The short treatment period and lack of postwithdrawal observations limit conclusions about long-term renoprotective efficacy and safety. CONCLUSIONS: HCQ in addition to optimized RAAS inhibition significantly reduced proteinuria in patients with IgAN over 6 months without evidence of adverse events. These findings require confirmation in larger treatment trials. FUNDING: This study was supported by grants from a government entity, the Capital of Clinical Characteristics, and the Applied Research Fund. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT02942381.

Comparison of the effects of hydroxychloroquine and corticosteroid treatment on proteinuria in IgA nephropathy: a case-control study.

BACKGROUND: Hydroxychloroquine (HCQ), a well-known immunomodulator, has recently been found to be a promising and safe anti-proteinuric agent for treating IgA nephropathy (IgAN). We aimed to compare the efficacy and safety of HCQ and corticosteroid treatment in patients with IgAN. METHODS: This is a case-control study. Ninety-two patients with IgAN who received HCQ in addition to routine renin-angiotensin-aldosterone system inhibitors (RAASi) therapy were included. Ninety-two matched historical controls who received corticosteroids were selected by propensity score matching. The clinical data over 6 months were compared. RESULTS: Baseline proteinuria levels were comparable between the HCQ and corticosteroid groups (1.7 [1.2, 2.3] vs. 1.8 [1.3, 2.5] g/d, p = 0.96). The percentage reduction in proteinuria at 6 months was smaller in the HCQ group than in the corticosteroid group (- 48.5% [- 62.6, - 31.4] vs. -62.9% [- 81.1, - 34.9], p = 0.006). The time averaged proteinuria within the 6 months of observation was comparable for the HCQ and corticosteroid groups (1.1 [0.8, 1.5] vs. 1.1 [0.5, 1.8] g/d, p = 0.48). The cumulative frequency of patients with a 50% reduction in proteinuria during the study was also comparable between the two groups (52.2% vs. 62.0%, p = 0.25). However, six of the 92 (6.5%) patients suffered from severe adverse events (SAEs) in the corticosteroid group, while no SAEs were observed in the HCQ group (6.5% vs. 0%, p = 0.03). CONCLUSIONS: The antiproteinuric effect of HCQ might be slightly inferior to that of corticosteroids over 6 months in patients with IgAN who were deemed to be candidates for HCQ and not corticosteroids treatment. However, HCQ treatment was safer than corticosteroid treatment.

Effects of Hydroxychloroquine on Proteinuria in Immunoglobulin A Nephropathy.

BACKGROUND: Hydroxychloroquine (HCQ) is a well-known immunomodulator that is useful as in the treatment for lupus because of its inhibitory effect on toll-like receptors and cytokines, which are speculated to play a role in the pathogenesis of Immunoglobulin A (IgA) nephropathy (IgAN). However, there was only one study that investigated the effect of HCQ on proteinuria in patients with IgAN. METHODS: Ninety patients with IgAN who received HCQ in addition to optimized dosage of renin-angiotensin-aldosterone system inhibitors (RAASi) were recruited for this study, and 90 matched historical controls who received RAASi alone were selected from our registry by the propensity score matching method. Their clinical data were compared at baseline and during follow-up till the termination of HCQ or addition of immunosuppressive agents. RESULTS: The median baseline proteinuria level of the 90 patients who received HCQ was comparable with the RAASi-alone group (1.5 [1.2, 2.1] vs. 1.5 [1.2, 1.9] g/day, p = 0.74). At 6 months post-study initiation, the median proteinuria level in the HCQ group was lower than that in the RAASi-alone group (0.8 [0.7, 1.2] vs. 1.2 [0.8, 1.8] g/day, p = 0.02). The percentage by which proteinuria was reduced in the HCQ group was significantly higher than that in the RAASi-alone group (-43% [-57, -12] vs. -19% [-46, 17], p = 0.01). No serious adverse effects were documented during treatment with HCQ. CONCLUSION: The addition of HCQ to RAASi resulted in a significant and safe reduction in proteinuria in patients with IgAN.

Validation and modification of simplified Geriatric Assessment and Elderly Prognostic Index: Effective tools for older patients with diffuse large B-cell lymphoma.

Geriatric assessment can aid in optimizing treatment strategies and supportive interventions for older patients with diffuse large B-cell lymphoma (DLBCL). Fondazione Italiana Linformi has recently introduced novel geriatric assessment tools, simplified Geriatric Assessment (sGA) and Elderly Prognostic Index (EPI), aimed at tailoring the treatment and predicting the outcomes for older patients with DLBCL. The objectives of this study are the validation and possible modification of the sGA and EPI in China. In the study, both sGA and EPI demonstrated the predictive capabilities for overall survival (OS) and early mortality (both p < 0.05) in older individuals with DLBCL. Albumin, serving as an independent predictive biomarker for OS (p = 0.006), was utilized to adjust the measurements, resulting in the establishment of sGA-A and EPI-A. The sGA-A effectively addressed the shortcomings of the sGA and EPI in predicting PFS and surpassed them in predicting OS and early mortality. Nevertheless, there is insufficient evidence to support the use of sGA and EPI as treatment guidance tools. In conclusion, the modified sGA-A model proved to be a successful instrument for geriatric assessment of older patients with DLBCL.

Clinical Outcomes of BCMA CAR-T Cells in a Multiple Myeloma Patient With Central Nervous System Invasion.

Background: Multiple myeloma (MM) is the second most common hematological malignancy that still lacks effective clinical treatments. In particular, MM with central nervous system (CNS) invasion occurs rarely. Although B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor-T (CAR-T) cell therapy has shown great promise for the treatment of relapsed/refractory MM, few studies have reported whether BCMA CAR-T could inhibit MM with CNS invasion. Case Presentation: In this study, we report a special case of a 63-year-old male patient who suffered MM with CNS invasion and presented rapid extramedullary disease (EMD) progression into multiple organs. Before CAR-T cell infusion, this patient received five cycles of bortezomib, Adriamycin, and dexamethasone (PAD) and an autologous transplant as the front-line treatment, followed by two cycles of bortezomib, lenalidomide, and dexamethasone (VRD) as the second-line regimen, and daratumumab, bortezomib, dexamethasone (DVD) as the third-line regimen. Since the patient still showed rapid progressive disease (PD), BCMA CAR-T cells were infused, and 1 month later, a stringent complete response (sCR) was achieved, and the response lasted for 4 months. Meanwhile, only grade 1 cytokine release syndrome (CRS) was observed. Conclusion: This case report demonstrated that BCMA CAR-T could effectively eradicate CNS-involved MM with low adverse events, suggesting that CAR-T cell therapy could be a feasible therapeutic option for this kind of refractory disease. Clinical Trial Registration: https://ClinicalTrials.gov, identifier: NCT04537442.a.

Clinical features of IgA nephropathy with serum ANCA positivity: a retrospective case-control study.

BACKGROUND: The coexistence of IgA nephropathy (IgAN) and antineutrophil cytoplasmic autoantibodies (ANCAs) is relatively rare. Only a few studies have reported the features of these patients. METHODS: We studied the clinical and histological features of 20 ANCA-positive IgAN patients. They were compared with ANCA-negative IgAN patients (n = 40) and ANCA-associated systemic vasculitis (AASV) patients (n = 40) with a randomly selected and matched proportion of crescentic glomeruli. Furthermore, 9 ANCA-positive crescentic IgAN patients out of the 20 cases were compared with two control groups with crescentic nephritis. RESULTS: ANCA-positive IgAN patients showed older age, lower haemoglobin and higher inflammatory indicator levels at baseline, and a higher percentage of general symptoms and pulmonary involvement, compared with ANCA-negative IgAN patients, and were comparable to AASV patients. Histologically, there was a significantly higher percentage of fibrinoid necrosis in glomeruli in ANCA-positive IgAN patients and in AASV patients compared with ANCA-negative IgAN patients (35, 25 and 0%, respectively, P = 0.003). After immunosuppressive therapy, ANCA-positive crescentic IgAN patients were more likely to withdraw from dialysis (75 versus 9.1%, P = 0.03) and not to reach end-stage renal disease within 6 months (11.1 versus 66.7%, P = 0.01) compared with ANCA-negative crescentic IgAN patients. CONCLUSIONS: IgAN patients with ANCA positivity showed more severe clinical and histological features when compared with ANCA-negative IgAN patients and were comparable to AASV patients. However, renal prognosis was relatively better in ANCA-positive crescentic IgAN patients after aggressive immunosuppressive therapy in the short term, compared with ANCA-negative patients.