A young woman presented with a 17-year history of proteinuria, hematuria with persistent hypocomplementemia. She has been followed up for 2 years. The patient underwent comprehensive diagnostic evaluation, including two renal biopsies. The initial biopsy indicated membranoproliferative glomerulonephritis (MPGN), while the subsequent biopsy revealed concurrent thrombotic microangiopathy (TMA) kidney injury, suggesting a complement-mediated disorder. Genetic testing identified two heterozygous missense variants, c.848A > G (p.Asp283Gly) and c.1339C > T (p.Pro447Ser), in the Complement factor I (CFI) gene. Both are classified as variants of uncertain significance, suggestive of potential susceptibility to complement dysregulation. The clinical diagnosis was MPGN with overlapping TMA. Treatment with mycophenolate mofetil and losartan potassium resulted in reduced urinary protein, improved complement levels, and stabilized renal function; traditional Chinese herbal medicine was administered as supportive therapy. This case highlights the diagnostic challenges, when renal pathology indicates membranoproliferative-like lesions that cannot be explained by Ig-mediated or C3 glomerulopathy, especially accompanied by TMA lesions or persistent hypocomplementemia, complement system-related tests including complement regulatory gene mutation may helpful to establish the etiological diagnosis and guide management.

IgA nephropathy (IgAN), the most common form of glomerulonephritis worldwide, often progresses to chronic kidney failure within 10 to 15 years. Despite its clinical importance, effective disease-modifying therapies for IgAN remain limited. Proteinuria is well recognized as both a prognostic biomarker and a modifiable therapeutic target in IgAN. Several randomized controlled trials conducted among Chinese patients with IgAN have demonstrated the efficacy of hydroxychloroquine (HCQ) in reducing proteinuria. The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines also suggest that HCQ may exert potential therapeutic effects in IgAN. However, the molecular mechanisms underlying the renoprotective effects of HCQ remain incompletely understood. This review synthesises current evidence on HCQ's therapeutic mechanisms in IgAN, highlighting its multifaceted roles in: (1) suppressing pathogenic galactose-deficient IgA1 synthesis through modulation of mucosal immunity, Toll-like receptor (TLR) signaling, IL-6 pathways, and complement activation; (2) inhibiting autophagy-mediated antigen presentation via major histocompatibility complex class II (MHC-II) molecules; (3) modulating non-canonical autophagy pathways to attenuate human mesangial cells (HMCs) proliferation and protect podocytes; and (4) demonstrating antithrombotic effects. Collectively, HCQ demonstrates multifaceted mechanisms for proteinuria reduction in IgAN while maintaining a favorable safety profile.

We report the case of a 31-year-old male who presented with repeated episodes of nephritic-nephrotic syndrome in concomitance with infection. IgA was diagnosed and was initially responsive to treatment with immunosuppressors but further disease flare did not respond to treatment. Based on three consecutive renal biopsies over 8 years, a pattern switch from endocapillary proliferative IgA nephropathy to membranous proliferative glomerulonephritis with monoclonal IgAκ deposits was observed. Bortezomib-dexamethasone combination therapy finally led to a favorable renal response. This case provides new insights into the pathophysiological mechanisms of proliferative glomerulonephritis with monoclonal immunoglobin deposits (PGNMID), highlighting the importance of repeat renal biopsies and routine evaluation of monoclonal immunoglobin deposits in proliferative glomerulonephritis with refractory nephrotic syndrome.

Antiviral drugs are commonly used in clinical practice, and may lead to acute kidney injury through a variety of mechanisms, including renal hypoperfusion, direct renal tubular toxicity, crystal nephropathy, and thrombotic microangiopathy, etc. The pandemic of COVID-19 has brought antiviral drug-associated kidney injury to extensive clinical focus. This article reviewed the performances of antiviral drugs in COVID-19 treatment and their effect on the kidney, and summarized the clinical manifestations and pathological mechanisms of antiviral drug-associated acute kidney injury.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, with varied clinical and histopathological features between individuals, particularly across races. As an autoimmune disease, IgAN arises from consequences of increased circulating levels of galactose-deficient IgA1 and mesangial deposition of IgA-containing immune complexes, which are recognized as key events in the widely accepted "multi-hit" pathogenesis of IgAN. The emerging evidence further provides insights into the role of genes, environment, mucosal immunity and complement system. These developments are paralleled by the increasing availability of diagnostic tools, potential biomarkers and therapeutic agents. In this review, we summarize current evidence and outline novel findings in the prognosis, clinical trials and translational research from the updated perspectives of IgAN pathogenesis.

血栓性微血管病是以微血管性溶血性贫血、血小板减少及器官损伤为特征的一组急性临床综合征,病因繁复,症状多样,而合理的中医辨治可减轻重症临床表现,并有效改善疾病转归.本文基于温病理论,结合临床实践,就血栓性微血管病中医辨治策略进行阐述,为临床治疗提供借鉴.

Monoclonal gammopathy of renal significance (MGRS) is a pathological state which presents with a spectrum of renal lesions. MGRS is characterized by pathogenic monoclonal immunoglobulins or light chains produced by a premalignant plasma cell or B cell clone. In view of inadequate understanding in the past, the low detection rate of MGRS often results in poor outcomes and reduces quality of life of patients. Thus, MGRS stands for a group of clinical refractory renal diseases. To date, no standard treatment strategy for MGRS is available. Current consensus suggests a clone-directed approach that aims to eradicate the offending clone, but its long-term prognosis is not clear. In this article, we discuss the diagnostic methods, highlight treatment advances, and introduce integrated Chinese and Western medicine in the management of MGRS.

Additional file 4. Sample size calculation.

Background: IgA nephropathy (IgAN) is the most common glomerular disease worldwide. It has a high incidence in Asians and is more likely to progress to end-stage renal disease (ESRD). For high-risk IgAN, which is clinically characterized by massive proteinuria and renal dysfunction, however, there has been no international consensus on treatment options. Compared with other developed countries, IgAN patients in China are often found to have severe kidney function loss at initial diagnosis. Yi-Qi-Qing-Jie Formula Granule (a compound recipe of Chinese medicinal herbs, YQF) has shown potential renal protection in our previous clinical studies. To further confirm the efficacy and safety of YQF in the treatment of high-risk IgAN, we design a prospective double-blind randomized placebo-controlled trial. Methods/Design: The TCM-WINE study is a single-center, prospective, double-blind randomized placebo-controlled trial. We plan to randomize 60 participants with biopsy-proven IgAN to YQF combined group (YQF compound, combined with prednisolone, and cyclophosphamide if necessary) and immunosuppression group (placebo-YQF, combined with prednisolone, and cyclophosphamide if necessary). The two groups will enter 48-week in-trial treatment phase and receive post-trial follow-up till study completion (3-year). All patients will receive optimal supportive care. The primary composite outcome is defined as the first occurrence of 40% decrease in estimated glomerular filtration rate (eGFR) from the baseline lasting for 3 months, initiating continuous renal replacement treatment or death due to chronic kidney disease (CKD), during the 3-year study phase. The secondary endpoint events are defined as the mean annual eGFR decline rate (eGFR-Slope, ml/min per 1.73 m2 per year) which is calculated by the eGFR regression curve for each eligible patient, and proteinuria remission (prescribed as proteinuria<0.5g/day) at week 24, 36, 48 during the in-trial phase. The remission rate of symptoms and inflammation status will be evaluated respectively at week 48. Safety monitoring and assessment will be undertaken during the study. Discussion: TCM-WINE study will evaluate effects and safety of YQF combined therapy compared with immunosuppression monotherapy on basis of optimal supportive treatment in high-risk IgAN. The evidence from this study will provide a novel, effective and safe Chinese characteristic therapy for high-risk IgAN patients. Trial registration: Clinicaltrials.gov, identifier: NCT03418779. Registered on 18 June 2018. https://clinicaltrials.gov/show/NCT03418779

目的 评价益气清解方(YQF)联合免疫抑制剂对高危IgA肾病患者的疗效.方法 采用倾向性评分匹配法,选择广安门医院接受YQF联合糖皮质激素加环磷酰胺(CTX)治疗的高危IgA肾病患者作为治疗组,北京大学第一医院IgA肾病随访队列中接受同样免疫抑制剂治疗但未服中药的患者作为对照组,两组1∶1匹配,形成治疗组和对照组各34例.比较两组患者启动治疗后6、12个月后的24 h尿蛋白定量(24 h UTP)、估算肾小球滤过率(eGFR)变化值,比较两组启动治疗方案后12个月内月平均eGFR变化速率(eGFR-Slope),观察随访至2016年12月31日进入终末期肾脏病(ESRD)的情况,记录与治疗相关的严重不良反应.结果 与本组治疗前比较,治疗组6、12个月eGFR升高(P＜0.01).与对照组同期比较,治疗组6、12个月eGFR及△eGFR升高(P＜0.01),eGFR-Slope升高(P＜0.01).随访中治疗组5例、对照组9例进入ESRD,2组累计肾脏存活率比较,差异无统计学意义(P=0.058).对照组5例患者发生与治疗相关严重不良反应,治疗组无严重不良反应报告.结论 免疫抑制剂治疗联合YQF治疗高危IgA肾病,对改善患者肾功能和降低免疫抑制治疗相关不良事件风险可能有益.