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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.

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/1.73m 2 ) 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/1.73m 2 ; 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., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

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., (© 2018 S. Karger AG, Basel.)

Background: Tacrolimus has been reported to be effective in refractory nephrotic syndrome, such as focal segmental glomerulosclerosis and membranous nephropathy. Some IgA nephropathy (IgAN) patients with massive proteinuria showed resistance to steroids and/or cytotoxic immunosuppressants based on the supportive therapy with renin- angiotensin system blockade. The efficacy and safety of tacrolimus in such refractory IgAN patients are extremely ambiguous, and the mechanism of tacrolimus improving proteinuria remission needs to be investigated., Methods: 14 refractory IgAN patients were enrolled. The patients received tacrolimus (0.05-0.1 mg/kg/day) and prednisone (0.5 mg/kg/day) for at least 6 months. Synaptopodin and calcineurin expression were detected in renal tissues of patients who received re-biopsy. A puromycin aminonucleoside (PAN)-induced human podocyte injury model was applied to investigate the possible role of tacrolimus in proteinuria remission., Results: Of the 14 patients enrolled, 3 were withdrawn because serum creatinine increased over 30% baseline. In 11 patients treated with tacrolimus over 6 months, 9 showed complete or partial remission and 7 achieved remission within 1 month. In renal tissues, the expression of calcineurin increased while synaptopodin decreased and recovered partially after tacrolimus therapy. In an in vitro study, F-actin disrupted in human podocytes after stimulation of PAN, while calcineurin increased and synaptopodin decreased. After co-treatment with tacrolimus the reorganization of F-actin and the expression of calcineurin and synaptopodin recovered., Conclusions: Tacrolimus showed a rapid proteinuria remission in refractory IgAN patients. The possible mechanism of tacrolimus to proteinuria remission might be podocyte cytoskeleton stabilization through inhibition of calcineurin expression., (Copyright © 2012 S. Karger AG, Basel.)

Background: Vitamin D has shown efficacy in the reduction of proteinuria in patients with chronic kidney disease. This study aimed to determine the effect of calcitriol on urinary protein excretion in patients with immunoglobulin A (IgA) nephropathy., Study Design: Open-label, non-placebo-controlled, randomized study., Setting & Participants: 50 patients with IgA nephropathy were enrolled. The main criterion for inclusion was urinary protein excretion >0.8 g/d after renin-angiotensin system-inhibitor treatment for at least 3 months., Intervention: Patients were randomly assigned (1:1) to receive 2 doses (0.5 μg) of calcitriol per week or no treatment for 48 weeks., Outcomes: The primary end point was to compare change in 24-hour urinary protein excretion from baseline to last measurement during treatment., Measurements: Every 8 weeks, there was measurement of 24-hour urinary protein excretion, serum calcium, serum phosphorus, serum creatinine, and intact parathyroid hormone., Results: Measurement of the primary end point showed changes in urinary protein excretion of +21% (from 1.29 to 1.58 g/24 h; 95% CI, -9% to +52%) in the control group and -19% (from 1.60 to 1.30 g/24 h; 95% CI, -42% to +4%) in the calcitriol-treated group. There was a significant decrease in proteinuria in the calcitriol-treated group compared with the control group (difference between groups, 41%; 95% CI, 5%-79%; P = 0.03). The secondary end point of achieving at least a 15% decrease in proteinuria was attained by 7 of 24 (29%) controls and 17 of 26 (65%) of those treated with calcitriol (P = 0.02). No significant differences were observed in decrease in estimated glomerular filtration rate and change in blood pressure between the 2 groups. The incidence of recorded adverse events was similar between the 2 groups., Limitations: Small and non-placebo-controlled study., Conclusions: The addition of calcitriol to a renin-angiotensin system inhibitor resulted in a safe decrease in proteinuria in patients with IgA nephropathy., (Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate whether combination of urine sediment and urine protein can predict the renal pathological changes., Methods: We prepared 146 specimens of routine fresh fasting morning urine. Sediment analysis was performed with phase-contrast microscopy and 24-hour urine protein was measured. Both urine protein and sediment data were integrated to form three urine analysis groups. Urine group I: proteinuria, hematuira, urine white blood cells, red/white cell casts. Urine group II: proteinuria, few cell hyaline/fine granular casts. Urine group III: minor proteinuira, epithelial cells of tubule, granular/cell casts. The renal pathological lesions were predicted before and then confirmed by renal biopsy. Statistical analyses were performed using kappa test, chi-square test, and significance was accepted at P<0.05., Results: After renal biopsy, we identified 95 cases of glomerular lesion with proliferation, 46 cases of glomerular disease without obvious proliferation and 5 cases of tubular interstitial lesion. According to the sediment analysis, only 67 cases (46%) could be attributed to urine group I. When combined with urine protein, we could pick out another 75 cases from urine groups I and II, and 8 cases from urine group III. The combined urine analysis could predict glomerular disease (77.7%)., Conclusion: Clinically we can take advantage of the combined urine analysis to predict the pathological lesion of kidney disease, which is especially suitable for primary care doctor, who can not perform renal biopsy.

Aim: Hydroxychloroquine (HCQ) is used to control proteinuria in IgA Nephropathy (IgAN) However, its efficacy and safety in pregnant IgAN patients remains unknown. This study aimed to verify the safety of HCQ in pregnant IgAN patients and compare renal function and pregnancy outcomes with those of patients not treated with HCQ. Methods: We retrospectively reviewed medical records of all pregnant IgAN patients and singleton gestations at Peking University First Hospital from 2003–2021. Patients who did and did not receive HCQ treatment during pregnancy were compared. Results: We found no significant pre‐ or post‐pregnancy differences in proteinuria or renal function between the two groups. However, the HCQ (+) group had higher proteinuria at the time of kidney biopsy (2.04 [1.26, 2.56] g/d vs. 0.80 [0.44, 1.11] g/d, P <.001); the proteinuria level at HCQ therapy initiation was also higher than that at the beginning of pregnancy (1.87 [1.30, 2.59] g/d vs. 1.08 [0.75, 1.50] g/d, P =.001). Despite no difference in preterm birth, birth weight, preeclampsia or postpartum haemorrhage, the proportion of patients with a previous history of spontaneous abortion was higher in the HCQ (+) group than in the HCQ (−) group (48.0% vs. 20.6%, P =.010). The eGFR (regression coefficient, 0.981; 95%CI 0.964–0.998) was a predictive factor for obstetrical complications. Conclusion: HCQ is safe for IgAN treatment during pregnancy with effective reduction of proteinuria. HCQ might also be helpful in patients with a history of spontaneous abortion. SUMMARY AT A GLANCE: In this retrospective comparison of 25 pregnant patients with IgA nephropathy treated with hydroxychloroquine (HCQ) versus 65 other pregnant IgAN patients who were not given HCQ, it was found that HCQ is safe and effective in reducing proteinuria. Multivariate regression shows that baseline eGFR is a predictor of obstetric complications. [ABSTRACT FROM AUTHOR]

We report a 41-year-old Chinese female with Fabry disease and diffuse thinning of the glomerular basement membrane (GBM). The patient presented with peripheral edema, mild proteinuria, microscopic hematuria, normal renal function, hypertension and tinnitus. Family screening showed that her daughter had microscopic hematuria, tinnitus and neuropathic pain. Renal biopsy of the proband showed focal segmental glomerulosclerosis with cytoplasmic vacuolization of the glomerular visceral epithelial cells by light microscopy. Laminated myelin inclusions in some of the glomerular podocytes, parietal epithelia, distal tubular epithelial cells and vascular endothelial cells along with diffuse thinning of the GBM (mean thickness of GBM: 216 ± 31 nm) were identified by electron microscopy. Genetic analysis detected a de novo novel GLA mutation, 1208 ins 21 bp, while a new variant of COL4A3 SNP M1209I was carried by mother and daughter as well as the proband’s father (I-1) and one sister (II-4). The coexistence of thinned GBM should be considered in patients with Fabry disease-manifested familial hematuria. [ABSTRACT FROM AUTHOR]