Hepatitis B Virus Status and Clinical Outcomes in IgA Nephropathy.

Introduction: Immunoglobulin A nephropathy (IgAN) has been reported to coexist with hepatitis B virus (HBV) infection. Despite the clinical significance of this association, there is a lack of comprehensive research investigating the impact of various common conditions following HBV infection and the potential influence of anti-HBV therapy on the progression of IgAN. Methods: We investigated 3 distinct states of HBV infection, including chronic HBV infection, resolved HBV infection, and the deposition of hepatitis B antigens in renal tissue, in a follow-up database of 1961 patients with IgAN. IgAN progression was defined as a loss of estimated glomerular filtration rate (eGFR) >40%. Multivariable cause-specific hazards models to analyze the relationship between HBV states and IgAN progression. Results: Chronic HBV infection was identified as an independent risk factor for IgAN progression, supported by both prematching analysis (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.06-2.44; P = 0.024) and propensity-score matching analysis (HR, 1.74; 95% CI 1.28-2.37; P < 0.001). Conversely, resolved HBV infection showed no significant association with IgAN progression (HR, 1.01; 95% CI 0.67-1.52; P = 0.969). Moreover, the presence of HBV deposition in the kidneys and the utilization of anti-HBV therapy did not appear to be significant risk factors for renal outcomes (P > 0.05). Conclusion: Chronic HBV infection is an independent risk factor for IgAN progression, whereas resolved HBV infection is not. In patients with IgAN, management of concurrent chronic HBV infection should be enhanced. The presence of HBV deposition in the kidneys and the use of anti-HBV medications do not impact the kidney disease progression in patients with IgAN with concurrent HBV infection.

Circulating Proteins and IgA Nephropathy.

BACKGROUND: The therapeutic options for IgA nephropathy are rapidly evolving, but early diagnosis and targeted treatment remain challenging. We aimed to identify circulating plasma proteins associated with IgA nephropathy by proteome-wide mendelian randomization studies across multiple ancestry populations. METHODS: In this study, we applied Mendelian randomization and colocalization analyses to estimate the putative causal effects of 2615 proteins on IgA nephropathy in Europeans and 235 proteins in East Asians. Following two-stage network Mendelian randomization, multi-trait colocalization analysis and protein-altering variant annotation were performed to strengthen the reliability of the results. A protein-protein interaction network was constructed to investigate the interactions between the identified proteins and the targets of existing medications. RESULTS: Putative causal effects of 184 and 13 protein-disease pairs in European and East Asian ancestries were identified, respectively. Two protein-disease pairs showed shared causal effects across them (CFHR1 and FCRL2). Supported by the evidence from colocalization analysis, potential therapeutic targets were prioritized and four drug-repurposing opportunities were suggested. The protein-protein interaction network further provided strong evidence for existing medications and pathways that are known to be therapeutically important. CONCLUSIONS: Our study identified a number of circulating proteins associated with IgA nephropathy and prioritized several potential drug targets that require further investigation.

A cluster of type I interferon-regulated genes associates with disease activity and prognosis in patients with IgA nephropathy.

The exact pathogenesis of IgA nephropathy (IgAN) is complex and so far, not well defined. Since it has been shown that microbial infections could induce high levels of type I interferon (IFN-I) and there is an evident link between mucosal infection and gross hematuria in IgAN, we hypothesized that IFN-I may play a role in the pathogenic process. In this study, we investigated the type I interferon status in IgAN based on the expression of 17 IFN-regulated genes (IRGs) in whole blood from 59 IgAN patients in a cross-sectional study, of which 34 patients followed longitudinally. Analysis of the IFN-score showed that there was a significant elevated IFN-score in the IgAN patients compared with healthy controls (n = 28, p = 9.80 × 10-3), and we observed an elevated IFN-score in the group with less tubular atrophy/interstitial fibrosis (p = 1.07 × 10-2) and with a lower proportion of mesangial hypercellularity (p = 1.23 × 10-2). In the longitudinal analysis, Cox regression analysis revealed that a higher IFN level was associated with a better renal outcome in IgAN after adjustments for gender and age (hazard ratio, 0.90; 95 % confidence interval, 0.81 to 0.97; p = 4.20 × 10-2). In conclusion, our finding suggested that IFN score may represent a novel type of biomarker in IgAN, which requires further exploration on its mechanism and therapeutic targeting.

Unveiling biomarkers and therapeutic targets in IgA nephropathy through large-scale blood transcriptome analysis.

INTRODUCTION: IgA nephropathy (IgAN) is the most prevalent form of glomerulonephritis. Unfortunately, molecular biomarkers for IgAN derived from omics studies are still lacking. This research aims to identify critical genes associated with IgAN through large-scale blood transcriptome analysis. METHODS: We constructed novel blood transcriptome profiles from peripheral blood mononuclear cells (PBMCs) of 53 Chinese IgAN patients and 28 healthy individuals. Our analysis included GO, KEGG, and GSEA for biological pathways. We analyzed immune cell profiles with CIBERSORT and constructed PPI networks with STRING, visualized in Cytoscape. Key differentially expressed genes (DEGs) were identified using CytoHubba and MCODE. We assessed the correlation between gene expressions and clinical data to evaluate clinical significance and identified hub genes through machine learning, validated with an open-access dataset. Potential drugs were explored using the CMap database. RESULTS: We identified 333 DEGs between IgAN patients and healthy controls, mainly related to immune response and inflammation. Key pathways included NK cell mediated cytotoxicity, complement and coagulation cascades, antigen processing, and B cell receptor signaling. Cytoscape revealed 16 clinically significant genes (including KIR2DL1, KIR2DL3, VISIG4, C1QB, and C1QC, associated with sub-phenotype and prognosis). Machine learning identified two hub genes (KLRC1 and C1QB) for a diagnostic model of IgAN with 0.92 accuracy, validated at 1.00 against the GSE125818 dataset. Sirolimus, calcifediol, and efaproxiral were suggested as potential therapeutic agents. CONCLUSION: Key DEGs, particularly VISIG4, KLRC1, and C1QB, emerge as potential specific markers for IgAN, paving the way for future targeted personalized treatment options.

Time-Varying Proteinuria and Progression of IgA Nephropathy: A Cohort Study.

RATIONALE & OBJECTIVE: Proteinuria is a surrogate end point for predicting long-term kidney outcomes in IgA nephropathy (IgAN) with levels<1g/day identified as a therapeutic target. However, this threshold has not been sufficiently studied. We quantified the associations of progression of IgAN with various levels of proteinuria. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: 1,530 patients with IgAN and at least 12 months of follow-up at Peking University First Hospital. EXPOSURE: Proteinuria levels updated over time (time-varying proteinuria, TVP). OUTCOME: A composite kidney outcome of a 50% reduction in the estimated glomerular filtration rate or end-stage kidney disease. ANALYTICAL APPROACH: Marginal structural models. RESULTS: After a median follow-up period of 43.5 (IQR, 27.2-72.8) months, 254 patients (16.6%) developed the composite kidney outcome. A graded association was observed between TVP and composite kidney outcomes with higher risk among those with proteinuria of≥0.5g/day. Compared with TVP<0.3g/day, the HRs for proteinuria levels of 0.3 to<0.5g/day, 0.5 to<1.0g/day, 1.0 to<2.0g/day, and≥2.0g/day were 2.22 (95% CI, 0.88-5.58), 4.04 (95% CI, 1.93-8.46), 8.46 (95% CI, 3.80-18.83), and 38.00 (95% CI, 17.62-81.95), respectively. The trend was more pronounced in patients with baseline proteinuria of≥1.0g/day, among whom a higher risk was observed with TVP of 0.3 to<0.5g/day compared with TVP<0.3g/day (HR, 3.26 [95% CI, 1.07-9.92], P=0.04). However, in patients with baseline proteinuria levels of<1g/day, the risk of composite kidney outcome only began to increase when TVP was≥1.0g/day (HR, 3.25 [95% CI, 1.06-9.90]). LIMITATIONS: Single-center observational study, selection bias, and unmeasured confounders. CONCLUSIONS: This study showed that patients with IgAN and proteinuria levels of>0.5g/day, have an elevated risk of kidney failure especially among patients with proteinuria levels≥1.0g/day before initiating treatment. These data may serve to inform the selection of proteinuria targets in the treatment of IgAN. PLAIN-LANGUAGE SUMMARY: The presence of proteinuria has often been considered a surrogate end point and a possible therapeutic target in clinical trials in IgA nephropathy (IgAN). Some guidelines recommend a reduction in proteinuria to<1g/day as a treatment goal based on the results of previous longitudinal studies. However, these findings may have been biased because they did not properly adjust for time-dependent confounders. Using marginal structural models to appropriately account for these confounding influences, we observed that patients with IgAN and proteinuria levels≥0.5g/day have an elevated risk of kidney failure, especially among patients who had proteinuria levels of≥1.0g/day before initiating treatment. These data may serve to inform the selection of proteinuria targets in the treatment of IgAN.

Machine learning in predicting T-score in the Oxford classification system of IgA nephropathy.

Background: Immunoglobulin A nephropathy (IgAN) is one of the leading causes of end-stage kidney disease (ESKD). Many studies have shown the significance of pathological manifestations in predicting the outcome of patients with IgAN, especially T-score of Oxford classification. Evaluating prognosis may be hampered in patients without renal biopsy. Methods: A baseline dataset of 690 patients with IgAN and an independent follow-up dataset of 1,168 patients were used as training and testing sets to develop the pathology T-score prediction (T pre) model based on the stacking algorithm, respectively. The 5-year ESKD prediction models using clinical variables (base model), clinical variables and real pathological T-score (base model plus T bio), and clinical variables and T pre (base model plus T pre) were developed separately in 1,168 patients with regular follow-up to evaluate whether T pre could assist in predicting ESKD. In addition, an external validation set consisting of 355 patients was used to evaluate the performance of the 5-year ESKD prediction model using T pre. Results: The features selected by AUCRF for the T pre model included age, systolic arterial pressure, diastolic arterial pressure, proteinuria, eGFR, serum IgA, and uric acid. The AUC of the T pre was 0.82 (95% CI: 0.80-0.85) in an independent testing set. For the 5-year ESKD prediction model, the AUC of the base model was 0.86 (95% CI: 0.75-0.97). When the T bio was added to the base model, there was an increase in AUC [from 0.86 (95% CI: 0.75-0.97) to 0.92 (95% CI: 0.85-0.98); P = 0.03]. There was no difference in AUC between the base model plus T pre and the base model plus T bio [0.90 (95% CI: 0.82-0.99) vs. 0.92 (95% CI: 0.85-0.98), P = 0.52]. The AUC of the 5-year ESKD prediction model using T pre was 0.93 (95% CI: 0.87-0.99) in the external validation set. Conclusion: A pathology T-score prediction (T pre) model using routine clinical characteristics was constructed, which could predict the pathological severity and assist clinicians to predict the prognosis of IgAN patients lacking kidney pathology scores.

MTMR3 risk alleles enhance Toll Like Receptor 9-induced IgA immunity in IgA nephropathy.

Multiple genome-wide association studies (GWASs) have reproducibly identified the MTMR3/HORMAD2/LIF/OSM locus to be associated with IgA nephropathy (IgAN). However, the causal variant(s), implicated gene(s), and altered mechanisms remain poorly understood. Here, we performed fine-mapping analyses based on GWAS datasets encompassing 2762 IgAN cases and 5803 control individuals, and identified rs4823074 as the candidate causal variant that intersects the MTMR3 promoter in B-lymphoblastoid cells. Mendelian randomization studies suggested the risk allele may modulate disease susceptibility by affecting serum IgA levels through increased MTMR3 expression. Consistently, elevated MTMR3 expression in peripheral blood mononuclear cells was observed in patients with IgAN. Further mechanistic studies in vitro demonstrated that MTMR3 increased IgA production dependent upon its phosphatidylinositol 3-phosphate binding domain. Moreover, our study provided the in vivo functional evidence that Mtmr3-/- mice exhibited defective Toll Like Receptor 9-induced IgA production, glomerular IgA deposition, as well as mesangial cell proliferation. RNA-seq and pathway analyses showed that MTMR3 deficiency resulted in an impaired intestinal immune network for IgA production. Thus, our results support the role of MTMR3 in IgAN pathogenesis by enhancing Toll Like Receptor 9-induced IgA immunity.

Clinicopathological and immunological features of new onset kidney disease: a rare event after SARS-CoV-2 vaccination.

The onset of various kidney diseases has been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. However, detailed clinical and pathological features are lacking. We screened and analyzed patients with newly diagnosed kidney diseases after inactivated SARS-CoV-2 vaccination in Peking University First Hospital from January 2021 to August 2021, and compared them with the reported cases in the literature. We obtained samples of blood, urine and renal biopsy tissues. Clinical and laboratory information, as well as light microscopy, immunostaining and ultrastructural observations, were described. The SARS-CoV-2 spike protein and nucleoprotein were stained using the immunofluorescence technique in the kidney biopsy samples. SARS-CoV-2 specific antibodies were tested using magnetic particle chemiluminescence immunoassay. The study group included 17 patients with a range of conditions including immune-complex-mediated kidney diseases (IgA nephropathy, membranous nephropathy and lupus nephritis), podocytopathy (minimal change disease and focal segmental glomerulosclerosis) and others (antineutrophil-cytoplasmic-antibody-associated vasculitis, anti-glomerular basement membrane nephritis, acute tubulointerstitial nephritis and thrombotic microangiopathy). Seven patients (41.18%) developed renal disease after the first dose and ten (58.82%) after the second dose. The kidney disease spectrum as well as clinicopathological features are similar across different types of SARS-CoV-2 vaccines. We found no definitive evidence of SARS-CoV-2 spike protein or nucleoprotein deposition in the kidney biopsy samples. Seropositive markers implicated abnormal immune responses in predisposed individuals. Treatment and follow-up (median = 86 days) showed that biopsy diagnosis informed treatment and prognosis in all patients. In conclusion, we observed various kidney diseases following SARS-CoV-2 vaccine administration, which show a high consistency across different types of SARS-CoV-2 vaccines. Our findings provide evidence against direct vaccine protein deposition as the major pathomechanism, but implicate abnormal immune responses in predisposed individuals. These findings expand our understanding of SARS-CoV-2 vaccine renal safety.

Intensive blood pressure control and the progression of IgA nephropathy: a cohort study using marginal structural models.

BACKGROUND: In chronic kidney disease, current guidelines recommend systolic blood pressure (SBP) below 120 mmHg. However, the renoprotective effect of intensive blood-pressure (BP) lowering on immunoglobulin A nephropathy (IgAN) remains undetermined. We aimed to determine the effect of intensive BP control on the progression of IgAN. METHODS: At Peking University First Hospital, 1530 patients with IgAN were enrolled. An examination of the relationship between baseline and time-updated BP and composite kidney outcomes, defined as development of end-stage kidney disease (ESKD) or a 30% decline in estimated glomerular filtration rate (eGFR), was conducted. Baseline and time-updated BPs were modeled using multivariate causal hazards models and marginal structural models (MSMs). RESULTS: In a median follow-up of 43.5 (interquartile range 27.2, 72.7) months, 367 (24.0%) patients experienced the composite kidney outcomes. No significant associations were found between baseline BP and the composite outcomes. Using MSMs with time-updated SBP for analysis, a U-shaped association was found. In reference to SBP 110-119 mmHg, hazard ratios (95% confidence intervals) for the SBP categories <110, 120-129, 130-139 and ≥140 mmHg were 1.48 (1.02-2.17), 1.13 (0.80-1.60), 2.21 (1.54-3.16) and 2.91 (1.94-4.35), respectively. The trend was more prominent in patients with proteinuria ≥1 g/day and eGFR ≥60 mL/min/1.73 m2. After analyzing time-updated diastolic BP, no similar trend was observed. CONCLUSIONS: In patients with IgAN, intensive BP control during the treatment period may retard the kidney disease progression, but the potential risk of hypotension still needs to be considered.

Comparison between hydroxychloroquine and systemic corticosteroids in IgA nephropathy: a two-year follow-up study.

BACKGROUND: Hydroxychloroquine (HCQ) is recommended as a treatment for IgA nephropathy (IgAN) to control proteinuria. The long-term effects of HCQ compared to systemic corticosteroid therapy remain unclear. METHODS: We conducted a retrospective case‒control study at Peking University First Hospital. Thirty-nine patients with IgAN who received HCQ for at least 24 months without corticosteroids (CSs) or other immunosuppressive agents were included. Thirty-nine matched patients who received systemic CS therapy were selected using propensity score matching. Clinical data over a 24-month period were compared. RESULTS: In the HCQ group, the level of proteinuria decreased from 1.72 [1.44, 2.35] to 0.97 [0.51, 1.37] g/d (-50.5 [-74.0, -3.4] %, P < 0.001) at 24 months. A significant decline in proteinuria was also found in the CS group, but no significant differences were found between the HCQ group and CS group in the levels of proteinuria (0.97 [0.51, 1.37] vs. 0.53 [0.25, 1.81] g/d, P = 0.707) and change rates (-50.5% [-74.0%, -3.4%] vs. -63.7% [-78.5%, -24.2%], P = 0.385) at 24 months. In addition, the decline rates of eGFR between the HCQ and CS groups were comparable (-7.9% [-16.1%, 5.8%] vs. -6.6% [-14.9%, 5.3%], P = 0.758). More adverse events were observed in the CS group. CONCLUSIONS: Long-term use of HCQ can maintain stable renal function with minimal side effects. In patients who cannot tolerate corticosteroids, HCQ might be an effective and safe supportive therapy for IgAN.

Corrigendum: Concurrent IgA nephropathy and membranous nephropathy, is it an overlap syndrome?

[This corrects the article DOI: 10.3389/fimmu.2022.846323.].

Discontinuation of Renin-Angiotensin System Inhibitors and Clinical Outcomes in Chronic Kidney Disease: A Systemic Review and Meta-Analysis.

BACKGROUND: Discontinuation of renin-angiotensin system (RAS) inhibitors is common in patients with chronic kidney disease (CKD), and the potential danger has been reported in several studies. However, a comprehensive analysis has not been conducted. OBJECTIVES: This study sought to evaluate the effects of discontinuation of RAS inhibitors in CKD. METHOD: Relevant studies up to November 30, 2022, were identified in the PubMed, Embase, Web of Science, and Cochrane Library databases. Efficacy outcomes included the composite of all-cause mortality, cardiovascular events, and end-stage kidney disease (ESKD). Results were combined using a random-effects or fixed-effects model, and sensitivity analysis used the leave-one-out method. RESULTS: Six observational studies and one randomized clinical trial including 244,979 patients met the inclusion criteria. Pooled data demonstrated that discontinuation of RAS inhibitors was associated with an increased risk of all-cause mortality (HR 1.42, 95% CI 1.23-1.63), cardiovascular event risk (HR 1.25, 95% CI 1.17-1.22), and ESKD (HR 1.23, 95% CI 1.02-1.49). In sensitivity analyses, the risk for ESKD was reduced. Subgroup analysis showed that the risk of mortality was more pronounced in patients with eGFR above 30 mL/min/m2 and in patients with hyperkalemia-related discontinuation. In contrast, patients with eGFR below 30 mL/min/m2 were at great risk of cardiovascular events. CONCLUSIONS: The discontinuation of RAS inhibitors in patients with CKD was associated with a significantly increased risk of all-cause mortality and cardiovascular events. These data suggest that RAS inhibitors should be continued in CKD if the clinical situation allows.

Corticosteroids in the treatment of IgA nephropathy: lessons from the TESTING trial.

IgA nephropathy (IgAN), the most common form of primary glomerulonephritis, is mainly observed in young adults and children. Clinical and basic studies indicate the role of immunity in IgAN pathogenesis; however, corticosteroid therapy has been controversial in past decades. The TESTING study, initiated in 2012, is an international, multicenter, double-blinded, randomized, placebo-controlled trial that aimed to evaluate oral methylprednisolone's safety and long-term efficacy under conditions of optimized supportive treatment in patients with IgAN whose risk of progression is high. After a decade of effort, the successful completion of the TESTING study showed that a 6- to 9-month course of oral methylprednisolone is an effective regimen to protect kidney function in high-risk patients with IgAN, but also demonstrated safety concerns. Compared with the full-dose regimen, the reduced-dose regimen was reported to be beneficial, with successfully increased safety. Overall, the TESTING trial provided more data regarding the treatment dosage and safety of corticosteroids, a cost-effective therapy, in IgAN, which have important implications for pediatric patients with IgAN. With a deeper understanding of the disease pathogenesis of IgAN, ongoing studies of novel therapeutic regimens would help further optimize the benefit-risk ratio.

Visit-to-visit variability in blood pressure and kidney disease progression in IgA nephropathy.

Background: The visit-to-visit variability (VVV) in blood pressure (BP) is an important risk factor for stroke and coronary heart disease and may also be associated with kidney damage and the development of chronic kidney disease (CKD). Data on the association between VVV in BP and the risk of CKD progression among patients with immunoglobulin A nephropathy (IgAN) are limited. We aimed to evaluate the relationships of VVV in BP with the progression of IgAN. Methods: We assessed 1376 patients with IgAN at Peking University First Hospital. The main VVV in BP was expressed as the standard deviation (SD), coefficient of variation (CV) and average real variability (ARV). The associations of variability in BP with composite kidney disease progression events, defined as a 50% decline in estimated glomerular filtration rate (eGFR) and kidney failure, were examined using Cox models. Results: During a median follow-up of 44.1 months (interquartile range 23.0-76.7), 247 (18.0%) patients experienced composite kidney disease progression events. With a higher SD in systolic BP (SBP) values, the risk of kidney disease progression events increased {hazard ratio [HR] 1.07 [95% confidence interval (CI) 1.03-1.11]; P < .001} after maximal adjustment, including baseline SBP and mean SBP during the first 12-month period. Using the first quartile of SD SBP values as the reference, the risk of composite kidney disease progression events was higher among patients with higher SD SBP values; the HR was 2.12 (95% CI 1.31-3.44) in the highest quartile (P for trend < .001). A similar trend could be observed when analysing the SD of diastolic BP, but the risk was not significantly increased. The associations were similar when analysed with the CV and ARV. Conclusion: SBP variability was significantly associated with kidney disease progression in IgAN.

Concurrent IgA Nephropathy and Membranous Nephropathy, Is It an Overlap Syndrome?

IgA nephropathy (IgAN) and membranous nephropathy (MN) are common glomerulonephritis, the presence of which in the same patient- concurrent of IgAN and MN (cIgAN/MN) has been described occasionally. This study aims to show clinical-pathological features of cIgAN/MN and attempts to suggest underlying pathogenesis using disease-specific biomarkers and a genomics approach. This retrospective cohort study described the clinical and pathological data from 137 patients with cIgAN/MN diagnosed in Peking University First Hospital from 2005 to 2019. One hundred primary IgAN and 100 MN cases were randomly selected as disease controls between the same time interval. Moreover, disease-specific biomarkers and polygenic risk score models were conducted to reveal the underlying pathogenesis. The median age of the cIgAN/MN cases was 45-year-old, and 46% were women. Compared to IgAN, patients with cIgAN/MN had a higher level of 24-hour proteinuria excretion but lower microscopic hematuria. They had a lower median level of galactose-deficient IgA1 (Gd-IgA1, 4.00 versus 5.45 µg/ml, P=0.002) as well as the standardized genetic risk scores of developing IgAN (GRSs: 0.05 versus 0.68, P<0.001). Compared to MN, patients with cIgAN/MN had a lower proportion of nephrotic syndrome and a lower level of albumin-to-creatinine ratio. However, the 24-hour proteinuria levels, serum lipid profiles, proportion of hypertension, and pathology classification were similar. Patients with cIgAN/MN had lower levels of plasma autoantibodies against the M-type transmembrane phospholipase A2 receptor (PLA2R) (11.23 versus 36.59 U/ml, P=0.005). Intriguingly, there were no statistical differences in standardized GRSs of developing MN between them (2.77 versus 3.02, P=0.326). Compared to IgAN, cIgAN/MN may lean towards MN more according to clinical-pathological features, disease-specific biomarker levels, and disease-specific genetic risk scores.

The efficacy and safety of hydroxychloroquine in pregnant patients with IgA nephropathy: A retrospective cohort study.

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.

Long-term safety and efficacy of hydroxychloroquine in patients with IgA nephropathy: a single-center experience.

BACKGROUND: Hydroxychloroquine (HCQ) has been used as a supportive therapy for IgA nephropathy (IgAN). We aimed to determine the long-term efficacy and safety of HCQ therapy in patients with IgAN. METHODS: A total of 180 patients with IgAN who had received HCQ therapy for at least 1 year were enrolled in this study. The changes in proteinuria and the estimated glomerular filtration rate (eGFR) were analyzed during the follow-up period. RESULTS: The level of proteinuria decreased from 1.69 [1.24, 2.30] to 1.01 [0.59, 1.74] g/day (- 37.58 [- 57.52, 8.24] %, P < 0.001) at 12 months and to 1.00 [0.59, 1.60] g/day (- 55.30 [- 71.09, - 3.44] %, P < 0.001) at 24 months. There was no significant change in the eGFR of these patients at 12 months (65.82 ± 25.22 vs. 63.93 ± 25.96 ml/min/1.73 m2, P = 0.411); however, the eGFR decreased from 65.82 ± 25.22 to 62.15 ± 25.81 ml/min/1.73 m2 at 24 months (P = 0.003). The cumulative frequency of all patients with a 50% decrease in proteinuria was 72.78% at 12 months. Sixty (33.3%) patients changed to corticosteroid therapy during the follow-up period. No serious adverse effects were documented during HCQ treatment. CONCLUSIONS: HCQ effectively and safely reduces proteinuria in IgAN patients with different levels of eGFR, supporting the maintenance of stable kidney function in the long term.