Therapy of Rituximab in Idiopathic Membranous Nephropathy with Nephrotic Syndrome: A Systematic Review and Meta-analysis

Objective To investigate the efficacy and safety of rituximab(RTX) in the treatment of idiopathic membranous nephropathy(IMN) with nephrotic syndrome with a systematic review and meta-analysis.Methods Pub Med, Embase, Cochrane Library and Clinical Trials(December 2016) were searched to identify researches investigating the treatment of RTX in adult patients with biopsy-proven IMN. Complete remission(CR) or partial remission was regarded as effective therapy, and the cumulated remission rate was calculated.Results Seven studies involved 120 patients(73% were men) were included in our systematic review and metaanalysis. All were prospective observation cohort studies or matched-cohort studies, mainly came from two medical centers, and one study was multi-centric(four nephrology units in northern Italy). The creatinine clearance was more than 20 ml/(min·1.73 m2) and persistent proteinuria higher than 3.5 g/d for at least 6 months. All patients received treatment previously [44(36.7%) had immunosuppressive treatment]. In 12-and 24-month, 56%(95%CI, 0.47-0.65) and 68%(95%CI, 0.41-0.87) patients could reach remission, while 15%(95%CI, 0.09-0.23) and 20%(95%CI, 0.12-0.32) patients could reach CR. The reduction in proteinuria was gradual and obvious, paralleled with upward trend of serum albumin level and decreasing serum cholesterol level. Renal functions were stable. Relapses happened in 24 months were around 8%. RTX related adverse events were mild and were mostly infusion-related reactions.Conclusions RTX treatment in IMN was efficient, well tolerated and safe. More than 60% patients can reach partial remission or CR in 24 months, and relapse is rare. Adverse events of RTX are mostly infusion-related reactions and generally mild.

Primary membranous nephrotic syndrome with chylothorax as first presentation:A case report and literature review

BACKGROUND Primary membranous nephrotic syndrome with chylothorax as the first manifestation is an unusual condition.To date,only a few cases have been reported in clinical practice.CASE SUMMARY The clinical data of a 48-year-old man with primary nephrotic syndrome combined with chylothorax admitted to the Department of Respiratory and Critical Care Medicine of Shaanxi Provincial People's Hospital were retrospec-tively analysed.The patient was admitted to the hospital for 12 d due to shortness of breath.Imaging showed pleural effusion,laboratory tests confirmed true chylothorax,and renal biopsy revealed membranous nephropathy.After primary disease treatment and early active symptom treatment,the prognosis of the patient was good.This case suggests that chylothorax is a rare complication of primary membranous nephrotic syndrome in adults,and early lymphan-giography and renal biopsy can assist in the diagnosis when there are no contrain-dications.CONCLUSION Primary membranous nephrotic syndrome combined with chylothorax is rare in clinical practice.We report a relevant case to provide case information for clinicians and to improve diagnosis and treatment.

Successful treatment of patients with refractory idiopathic membranous nephropathy with low-dose Rituximab:A single-center experience

BACKGROUND The recognition of idiopathic membranous nephropathy(IMN)as an autoimmune disease has paved the way for the use of B-cell-depleting agents,such as Rituximab(RTX),which is now a first-line drug for treating IMN with proven safety and efficacy.Nevertheless,the usage of RTX for the treatment of refractory IMN remains controversial and challenging.AIM To evaluate the efficacy and safety of a new low-dose RTX regimen for the treatment of patients with refractory IMN.METHODS A retrospective study was performed on refractory IMN patients that accepted a low-dose RTX regimen(RTX,200 mg,once a month for five months)in the Xiyuan Hospital of Chinese Academy of Chinese Medical Sciences’Department of Nephrology from October 2019 to December 2021.To assess the clinical and immune remission data,we performed a 24 h urinary protein quantification(UTP)test and measured the serum albumin(ALB)and serum creatinine(SCr)levels,phospholipase A2 receptor(PLA2R)antibody titer,and CD19+B-cell count every three months.RESULTS A total of nine refractory IMN patients were analyzed.During follow-up conducted twelve months later,the results from the 24 h UTP decreased from baseline[8.14±6.05 g/d to 1.24±1.34 g/d(P<0.05)]and the ALB levels increased from baseline[28.06±8.42 g/L to 40.93±5.85 g/L(P<0.01)].Notably,after administering RTX for six months,the SCr decreased from 78.13±16.49μmol/L to 109.67±40.87μmol/L(P<0.05).All of the nine patients were positive for serum anti-PLA2R at the beginning,and four patients had normal anti-PLA2R titer levels at six months.The level of CD19+B-cells decreased to 0 at three months,and CD19+B-cell count remained at 0 up until six months of follow-up.CONCLUSION Our low-dose RTX regimen appears to be a promising treatment strategy for refractory IMN.

A Discussion on TCM Treatment and the Pathogenesis of Membranous Nephropathy in Primary Nephrotic Syndrome

Objective:To investigate the TCM treatment principle of membranous nephropathy and its effect.Methods:A total of 56 patients were selected from the Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine.They were then divided into the control group(western medicine standard therapy)and the study group(Qidi Gushen prescription),with 28 patients in each group.The treatment effect,treatment safety,and patients’satisfaction were observed and compared between the two groups.Results:The results showed that the treatment effect of the study group was 96.43%,which was significantly better compared with the control group(75.00%)(p<0.05);in terms of safety,the probability of adverse events was 7.14%in the study group and 32.14%in the control group,in which the difference was statistically significant(p<0.05);in addition,the study group’s satisfaction with the treatment measures was significantly higher than that of the control group(p<0.05).Conclusion:In treating membranous nephropathy,traditional Chinese medicine can be tailored to its pathogenesis,which is not only beneficial to the treatment effect,but also has a high safety profile.

Idiopathic Adult Nephrotic Syndrome: A Clinicopathological Study and Response to Steroid in a Sub-Saharan African Country

Introduction: Idiopathic nephrotic syndrome represents 25% to 30% of glomerulonephritis in adults. These glomerulonephritides are responsible of about the half of chronic kidney failure examined as well in United States as in Europe or Africa. The aim of this study was to determine the anatomoclinic, therapeutic and progression patterns of idiopathic nephritic syndrome in Dakar. Patients and Methods: It is a retrospective ten-year study in the nephrology department of Aristide Le Dantec Hospital. Patients with idiopathic nephrotic syndrome were included. We analyzed anatomoclinic, therapeutic and progression data of idiopathic nephrotic syndrome. Results: On 202 patients with nephrotic syndrome, 156 (77%) were primitive. The mean age was 29.7 ± 12 years with a sex ratio of 2.4. Edema was found in 98 patients (62.8%) and hypertension in 63 patients (40%). The mean proteinuria was 6.8 ± 4.8 g/24h. Histologic lesions found at renal biopsy were focal segmental glomerulosclerosis in 71 patients (45.5%), minimal change disease in 68 patients (43.5%) and membranous nephropathy in 8 patients (5%). 134 patients (85.8%) received steroids alone, 12 patients (7.6%) received cyclophosphamide and 4 patients (2.5%) azathioprine in association with steroids. 44 patients (28.2%) reached remission. The factors of poor prognosis were: age, above 40 years, proteinuria above 10 g/24h, existence of renal failure at admission, absence of use of steroids therapy. Conclusion: This study shows that idiopathic nephrotic syndrome is frequent in our country with a prevalence of 77%. The most common lesion found at the renal biopsy is the focal segmental glomerulosclerosis. Remission is found only in 28% which is very low. 33% of patients progress towards chronic kidney disease due to the lack of early diagnosis and the use of traditional medicine.

Acute myocardial infarction in patients of nephrotic syndrome： a case series

Thromboembolic complications have been frequently re- ported in patients with long-lasting nephrotic syndrome （NS）. Although thrombotic complications in the venous system are common in patients with NS, arterial thromboses associated with NS are much less common. However, coronary thromboses are extremely rarely observed. So, NS is a rare cause of acute coronary syndrome （ACS）. As such, the incidence, pathogenesis, and treatment of these patients have yet to be clearly defined. In the current litera- ture, publications contain less than 15 patients, most of whom are young children.

Unusual Case of Idiopathic Membranous Later Developing Non-Hodgkin’s Lymphoma

A 30-year-old male presented to nephrology services as a case of nephrotic syndrome and membranous nephropathy was found on renal biopsy. He was treated for this pathology with steroid and cytotoxic drugs and remained in remission for 3 years and then presented with non Hodgkin’s lymphoma.

Cyclosporine treatment in idiopathic membranous nephropathy nephrotic syndrome in adults： a retrospective study spanning 15 years

Background Cyclosporine is effective in treating nephrotic syndrome （NS） with idiopathic membranous nephropathy （IMN） in adults. But high relapse rate remains a major concern. The way to manipulate cyclosporine is inconclusive. The aim of this study was to introduce the way how to titrate the cyclosporine to maintain complete remission without relapse. Methods Patients with biopsy-proven IMN with NS treated with cyclosporine for at least 1 month from 1996 to 2011 at Peking Union Medical College Hospital were reviewed. Results Mean age of the 51 eligible patients was 52 years, with 39 men. Mean proteinuria was （7.47±3.14） g/d, serum albumin （24.50±6.29） g/L, and serum creatinine （82.62±21.18） μmol/L. Cyclosporine was commenced at a mean dose of （3.46±0.63） mg·kg^-1·d^-1. Oral prednisone （0.40±0.29） mg·kg^-1·d^-1 was given concomitantly in 38 patients. Cyclosporine was administered for a median of 16 months （range 1-93 months） and stopped in non-responders by month six. By month 3 （n=47）, the number in complete remission （CR） and partial remission （PR） was 3 and 24, which shifted to 12 and 17 by month 6 （n=41）. Male gender, heavy proteinuria, low serum albumin level, and high serum creatinine level were significant determinants in poor response by month six （P 〈0.05 in all variables compared with responders）. There was a significant reversible serum creatinine increase within 25% during month 3 to 12 （P 〈0.05 in all variables compared with baseline value）. Eleven patients maintained cyclosporine for more than 24 months with a cyclosporine dose of （1.04±1.06） mg·kg^-1·d^-1. Nine patients were in CR. Renal function, systolic and diastolic blood pressure remained stable. Renal impairment （〉30% rise of serum creatinine）, secondary infection, hypertension, gingival hyperplasia and liver impairment occurred in 6, 4, 10, 4, and 1 patients, respectively. Conclusions The observation time for cyclosporine to effectively induce CR of NS in IMN adults should be at least six months. Long-term and low-dose of cyclosporine therapy is safe and effective to maintain CR in those responders.

Is de novo membranous nephropathy suggestive of alloimmunity in renal transplantation?A case report

BACKGROUND Post-transplant nephrotic syndrome(PTNS)in a renal allograft carries a 48%to 77%risk of graft failure at 5 years if proteinuria persists.PTNS can be due to either recurrence of native renal disease or de novo glomerular disease.Its prognosis depends upon the underlying pathophysiology.We describe a case of post-transplant membranous nephropathy(MN)that developed 3 mo after kidney transplant.The patient was properly evaluated for pathophysiology,which helped in the management of the case.CASE SUMMARY This 22-year-old patient had chronic pyelonephritis.He received a living donor kidney,and human leukocyte antigen-DR(HLA-DR)mismatching was zero.PTNS was discovered at the follow-up visit 3 mo after the transplant.Graft histopathology was suggestive of MN.In the past antibody-mediated rejection(ABMR)might have been misinterpreted as de novo MN due to the lack of technologies available to make an accurate diagnosis.Some researchers have observed that HLA-DR is present on podocytes causing an anti-DR antibody deposition and development of de novo MN.They also reported poor prognosis in their series.Here,we excluded the secondary causes of MN.Immunohistochemistry was suggestive of IgG1 deposits that favoured the diagnosis of de novo MN.The patient responded well to an increase in the dose of tacrolimus and angiotensin converting enzyme inhibitor.CONCLUSION Exposure of hidden antigens on the podocytes in allografts may have led to subepithelial antibody deposition causing de novo MN.

奥妥珠单抗治疗膜性肾病的研究进展

膜性肾病是成人肾病综合征的常见原因之一。Ⅰ型抗CD20单克隆抗体利妥昔单抗是治疗膜性肾病的有效药物,然而其使用后的完全或部分缓解率(随访至24个月)仅为60%。奥妥珠单抗是经糖基化改造的Ⅱ型人源化抗CD20单克隆抗体,与利妥昔单抗相比,它能引起更加严重的B淋巴细胞耗竭,因此其在治疗某些血液系统恶性肿瘤方面表现出更好的效果。在狼疮肾炎、肾移植等的治疗中奥妥珠单抗也展现出了良好的治疗效果,基于此一些中心已在膜性肾病中尝试使用奥妥珠单抗,本文就奥妥珠单抗在膜性肾病中的应用做一综述。

413例成人特发性膜性肾病(IMN)临床及病理分析

目的 总结成人特发性膜性肾病（idiopathic membranous nephropathy,IMN）的临床病理特征。方法 对1983年3月至2011年6月于复旦大学附属中山医院住院并经肾穿刺活检确诊的413例IMN患者的临床和病理资料进行回顾性分析。结果 413例IMN患者中,活检前病程0.1~336个月（中位数2.0个月）。男性236例（57.1%）,女性177例（42.9%）;年龄50.2±15.5 （14~83）岁,≥30岁者占88.9%;蛋白尿0.15~40.37 g/24 h,其中〉3.5 g/24 h者 250例（60.5%）;血清白蛋白8~48 g/L,其中〈30 g/L者285例（69.0%）,肾病综合征218例（52.8%）;血尿150例（36.3%）,其中肉眼血尿3例;高血压199例（48.2%）。肾小球滤过率（estimated glomerular filtration rate,eGFR）≥90 mL·min-1·1.73 m-2者238例（57.6%）,〈60 mL·min-1·1.73 m-2者61例（14.8%）。与女性比较,男性患者年龄大,24 h尿蛋白定量高,肾病综合征比例高,血清白蛋白浓度低,血肌酐高,eGFR低,肾小管间质损伤积分高,差异均有统计学意义。随年龄增长和蛋白尿量增加,IMN患者临床表现加重、肾功能下降及肾小管间质损伤程度加重。肾小球病理分期以Ⅰ、Ⅱ期为主,占81.4%。结论 男性、年龄大、高血压、尿蛋白量多者肾小球病变分期高,肾小管间质病变重,肾功能减退多见,故宜尽早就诊并行穿刺活检。

小剂量利妥昔单抗改善早期中高风险膜性肾病疾病进展:一项探索性研究

膜性肾病(membranous nephropathy,MN)是成人原发性肾病综合征(nephrotic syndrome,NS)最常见的病因,近年来研究发现PLA2R是MN的关键致病靶抗原,且其发现给利妥昔单抗(rituximab,RTX)等靶向B细胞的治疗提供了理论基础,然而针对抗体的早期干预是否能有效地阻止MN的进展仍有待进一步探索。我们系统分析了2019年10月至2023年3月在我中心接受RTX治疗的13例PLA2R抗体相关早期中高危MN患者的临床特征和随访。早期中高危MN定义为基线或入院时抗PLA2R抗体滴度超过50 RU/mL,但尚未出现NS状态。患者在基线评估中位时间4.1个月(IQR 1-7.7)启动RTX治疗,此后中位随访时间为27个月(IQR 23-45),期间均未发展至NS,12例(92.3%)在随访2年或末次随访时评估为完全或部分缓解。随访期间未发生死亡、严重感染或其他严重不良反应。RTX对早期中高危MN患者具有良好的疗效和安全性,适时启动抗体清除治疗可能有利于长期疾病控制和远期肾脏预后。

低分子肝素钙/磺达肝癸钠序贯联合双嘧达莫预防性抗凝在肾病综合征中的应用效果及安全性

目的探讨低分子肝素钙/磺达肝癸钠序贯联合双嘧达莫预防性抗凝在原发性肾病综合征(PNS)中的应用效果及安全性。方法回顾性选取2020年3月至2022年12月期间四川省凉山彝族自治州第一人民医院收治的188例PNS患者,根据肾穿刺活检病理结果及磷脂酶A2受体抗体分为膜性肾病组(n=73)与非膜性肾病组(n=115)。两组患者均根据血清白蛋白水平,采用低分子肝素钙或磺达肝癸钠序贯联合双嘧达莫抗凝。比较两组患者治疗前及治疗后4周、治疗后6个月的肾功能指标[白蛋白、尿素氮、血肌酐、肾小球滤过率(eGFR)和24 h尿蛋白定量(24 h PRO)],治疗前及治疗后4周的血栓弹力图指标[反应指数(R时间)、凝血时间(K时间)、血栓最大弹力度(MA)、凝血指数(CI)和α角],以及随访6个月记录血栓事件、出血事件。结果治疗后4周、6个月,两组的白蛋白、eGFR均较治疗前明显升高,尿素氮、血肌酐、24 h PRO均较治疗前明显降低,差异均有统计学意义(P<0.05),但两组治疗后各肾功能指标比较,差异均无统计学意义(P>0.05)。治疗后4周,两组患者的R时间、K时间均较治疗前明显延长,MA、CI值和α角均较治疗前明显降低,差异均有统计学意义(P<0.05),但两组患者治疗后4周的R时间、K时间、MA、CI值和α角比较,差异均无统计学意义(P>0.05)。膜性肾病组患者的血栓、出血事件发生率分别为6.85%、10.96%,均高于非膜性肾病组(0.87%、3.48%),但两组间血栓事件总发生率、出血事件发生率比较,差异均无统计学意义(P>0.05)。结论低分子肝素钙/磺达肝癸钠序贯联合双嘧达莫预防性抗凝有利于改善PNS患者的肾功能,缓解高凝状态,降低血栓栓塞事件发生率,且非膜性肾病患者获益较膜性肾病患者更明显,安全性更高。

健脾逐瘀方联合中药穴位敷熨治疗老年特发性膜性肾病脾虚肾瘀证的效果

目的探讨健脾逐瘀方联合中药穴位敷熨治疗老年特发性膜性肾病脾虚肾瘀证的临床效果。方法本研究为前瞻性随机对照研究,依据随机数字表法将2021年2月至2022年6月新密市中医院收治的100例老年特发性膜性肾病脾虚肾瘀证患者分为对照组(50例,常规基础治疗+中药穴位敷熨)和观察组(50例,常规基础治疗+中药穴位敷熨+健脾逐瘀方治疗),均持续治疗3个月。比较治疗3个月时临床疗效,以及治疗前和治疗3个月时肾功能指标、血液流变学水平;并统计治疗期间不良反应发生情况。结果对照组治疗总有效率低于观察组(P<0.05);治疗3个月后,对照组血尿素氮、24 h尿蛋白定量、血肌酐高于观察组(P<0.05);治疗3个月后,对照组纤维蛋白原、D-二聚体、血浆黏度水平高于观察组(P<0.05);两组治疗期间不良反应率比较,差异无统计学意义(P>0.05)。结论健脾逐瘀方联合中药穴位敷熨治疗老年特发性膜性肾病脾虚肾瘀证的临床效果显著,有助于缓解患者症状,改善肾功能水平和血液流变学指标,且未明显增加不良反应。

免疫抑制治疗和利妥昔单抗靶向治疗在特发性膜性肾病中有效性及安全性比较

目的评价中风险及以上特发性膜性肾病(IMN)3种治疗方案[利妥昔单抗(RTX)靶向B细胞疗法、钙调磷酸酶抑制剂(CNI)联合小剂量糖皮质激素、足量激素联合环磷酰胺(CTX)]的有效性及安全性,同时分析影响IMN缓解率的因素。方法采用回顾性队列研究的方法分析我院肾病科经肾穿刺活检诊断为IMN的患者,其中中风险及以上的患者共148例。按以上治疗方案分组,RTX组60例,CNI组42例,CTX组46例。记录随访开始患者基线24 h尿蛋白定量(24 h UTP)、血清白蛋白、血肌酐、尿酸、估算的肾小球滤过率(eGFR)、抗血清磷脂酶A2受体(PLA2R)抗体水平;比较3组患者治疗6、12、18个月后,24 h UTP、eGFR变化以及患者的缓解率、不良事件发生情况,并利用COX回归分析影响IMN缓解率的因素。结果随访开始时,患者基线性别、年龄、24 h UTP、血清白蛋白、血肌酐、尿酸、eGFR、血清抗PLA2R抗体水平、体质量指数(BMI)、收缩压无明显差别,具有可比性。随访6个月时,3组24 h UTP与eGFR无明显变化;RTX组与CTX组缓解率均低于CNI组。随访12个月时,RTX组24 h UTP显著低于CNI组,3组患者总缓解率差异不明显。随访18个月时,RTX组24 h UTP显著低于CNI组,eGFR水平显著高于CNI组,CTX组24 h UTP低于CNI组,RTX组与CTX组缓解率均高于CNI组。RTX主要不良反应是输液反应和感染;CNI主要不良反应是代谢综合征和血肌酐升高;CTX组主要不良反应为肝功能不全。多因素COX回归分析结果显示,基线抗PLA2R抗体与IMN缓解率存在关联(HR=1.162,95%CI:1.078~1.249)。结论RTX治疗IMN起效慢,在18个月诱导疾病缓解率高于CNI,等同于CTX,且维持缓解时间较长;CNI起效快,但易导致患者肾功能进展;高滴度血清抗PLA2R抗体水平是影响IMN缓解的独立危险因素。

635例特发性膜性肾病患者的中医证型与肾脏病理相关性研究

目的探讨特发性膜性肾病(IMN)患者的中医证型分布情况及与肾脏病理的相关性。方法回顾性分析2008—2022年于陕西省中医医院住院行肾穿刺活检术确诊为IMN的635例患者资料,收集患者的中医证型、病理分期、病理特征,比较各证型、病理分期及特征之间的异同。结果中医证型分为6类,以脾肾亏虚、风湿扰络证最多(39.84%),然后依次为脾虚水泛证(36.38%)、阳虚癥积证(10.24%)、脾虚湿热证(9.13%)、气阴两虚证(2.68%)、瘀水互结证(1.73%)。膜性肾病Ⅰ期213例(33.70%),Ⅱ期408例(64.25%),Ⅲ期12例(1.89%),Ⅳ期2例(0.32%)。膜性肾病Ⅰ期、Ⅲ期以脾虚水泛证多见,膜性肾病Ⅱ期以脾肾亏虚、风湿扰络证多见;气阴两虚证及瘀水互结证不见于膜性肾病Ⅲ期,膜性肾病Ⅳ期患者中1例为气阴两虚证,1例为瘀水互结证。中医证型与肾小球硬化、肾小管萎缩相关(P均<0.05),与增生、肥大、水肿、淋巴单核、泡沫细胞、空泡变性、管型的分布情况相关(P均<0.05),与球囊粘连、重度空泡变性、颗粒变性、再生、浆细胞、球周纤维化的分布情况无相关性(P均>0.05)。结论IMN患者的中医证型与肾脏病理分期及部分病理特征存在相关性,可为中医辨证用药提供依据。

基于“水郁折之”辨治特发性膜性肾病

特发性膜性肾病(IMN)是临床上较为常见的一种原发性肾小球疾病,相当于中医的水肿病,中医药治疗该病有其独特的优势。该病临床常见水肿、蛋白尿、小便不利、倦怠乏力等症。基于《黄帝内经》“水郁折之”的理论内涵,认为“水郁”是IMN发病的中心环节,总结出“疏散行水”“实土夺水”“扶阳利水”“祛瘀消水”四大法用于治疗IMN,使体内郁结之水或宣、或燥、或温、或消。为IMN的治疗提供新思路。

特发性膜性肾病患者抗磷脂酶A2受体抗体、幽门螺杆菌与中医证型的关系研究

目的:探讨抗磷脂酶A2受体(PLA2R)抗体、幽门螺杆菌(Helicobacter pylori,Hp)和中医证型在特发性膜性肾病(idiopathic membranous nephropathy,IMN)患者的临床特点。方法:收集57例IMN患者的抗PLA2R抗体、Hp检测、中医证型分布的临床资料,进行数据处理和分析。结果:57例IMN患者的中医证型分别为肺肾气虚证、脾肾气虚证、脾肾阳虚证、肝肾阴虚证;其中脾肾气虚证可见于IMN的不同病理分期;在肺肾气虚证、脾肾气虚证、脾肾阳虚证、肝肾阴虚证的患者中,抗PLA2R抗体阳性率分别为73.7%、72%、75%、80%;在膜性肾病(MN)Ⅱ期、MN Ⅲ期患者中,抗PLA2R抗体阳性率分别为77.3%,70%;在肺肾气虚证、脾肾气虚证、脾肾阳虚证的患者中,Hp阳性率分别为63.2%、68%、75%;在MN Ⅱ期、MN Ⅲ期患者中Hp阳性率分别为63.6%、60%。结论:脾肾气虚证是IMN的主要中医证型;抗PLA2R抗体阳性可见于IMN的不同病理分期和各个中医证型;抗PLA2R抗体阳性率随着中医证型的演变而升高,抗PLA2R抗体检测联合中医证型可进行IMN的病情评估;HP阳性率在IMN不同病理分期阶段及不同的中医证型中均较高,且HP感染率随中医证型演变有明显升高趋势,在IMN的中西医治疗过程中需提高对抗Hp治疗地位重要性的认识。

原发性肾病综合征儿童尿液CD80表达水平对临床预后价值研究

目的探讨尿CD80在原发性肾病综合征(primary nephrotic syndrome,PNS)患儿中的表达水平及其对预后的影响。方法选择2016年1月~2017年12月宜宾市第一人民医院收治的73例PNS患儿为病例组,根据病理类型分为膜性肾病组(MN组,n=41)、微小病变肾病组(MCD组,n=32),并于同期随机选取40例健康体检儿童为对照组。检测并比较各组尿CD80,24h尿蛋白、血肌酐(SCr)和血尿素氮(BUN)水平,计算并比较肾小球滤过率估计值(eGFR)。采用Pearson积矩相关分析法分析尿CD80与SCr,BUN,24h尿蛋白和eGFR的相关性。受试者工作特征(ROC)曲线分析尿CD80对MN组和MCD组的鉴别诊断价值。采用Kaplan-Meier生存曲线分析尿CD80与MN组和MCD组患儿肾损伤进展的关系。结果病例组SCr(135.72±25.86μmol/L),BUN(8.52±3.19mmol/L),24h尿蛋白(3.79±1.24g/24h)和尿CD80(503.75±86.24ng/g)水平高于对照组(49.18±23.04μmol/L,3.51±2.67mmol/L,1.12±0.95g/24h,129.22±77.13ng/g),差异均有统计学意义(t=17.662,8.416,11.823,22.901,均P<0.05);eGFR水平低于对照组(92.39±18.51ml/min/1.73m^(2)vs 145.72±20.41ml/min/1.73m^(2)),差异有统计学意义(t=14.129,P<0.05)。MCD组患儿SCr(167.25±28.61μmol/L),BUN(9.82±3.64mmol/L),24h尿蛋白(6.21±1.38g/24h)和尿CD80(623.50±92.31ng/g)水平高于MN组(105.49±24.17μmol/L,7.51±4.02mmol/L,2.43±1.19g/24h,358.12±85.46ng/g),差异均有统计学意义(t=9.993,2.546,12.556,12.715,均P<0.05);eGFR水平低于MN组(78.05±22.90ml/min/1.73m^(2)vs 118.67±18.03ml/min/1.73m^(2)),差异有统计学意义(t=8.483,P<0.05)。Pearson积矩相关分析,MN组、MCD组尿CD80与SCr,BUN和24h尿蛋白均呈正相关性(r=0.392~0.649,均P<0.05),与eGFR呈负相关性(r=-0.579,-0.593,均P<0.05)。ROC曲线结果显示,尿CD80鉴别诊断MN组和MCD组的AUC为0.811(95%CI:0.785~0.839),截断值为492.65ng/g,约登指数为0.59,敏感度和特异度分别为81.25%,78.05%。尿CD80<352.76ng/g的MN组患儿未发生慢性肾病综合征(chronic kidney disease,CKD)的中位生存时间长于尿CD80≥352.76ng/g的MN组患儿(2.37年vs 2.01年),差异有统计学意义(χ^(2)=12.531,P<0.05)。尿CD80<631.50ng/g的MCD组患儿未发生CKD的中位生存时间长于尿CD80≥631.50ng/g的MCD组患儿(1.92年vs 1.55年),差异有统计学意义(χ^(2)=9.286,P<0.05)。结论PNS患儿尿CD80表达上调,有助于鉴别诊断PNS病理类型和预测预后不良。

预防性抗凝治疗在特发性膜性肾病中的疗效分析

目的探讨预防性抗凝治疗在特发性膜性肾病(idiopathic membranous nephropathy,IMN)患者中的疗效及安全性。方法回顾性收集2019年12月~2021年12月在武汉大学人民医院就诊且病理确诊的197例IMN患者的临床资料,根据是否进行预防性抗凝治疗分为预防性抗凝组(n=99)与未预防性抗凝组(n=98),根据抗凝方案差异,预防性抗凝组分为低分子肝素组、低分子肝素+直接口服抗凝剂(direct oral anticoagulants,DOACs)组及华法林组。比较组间实验室检查及病理资料的差异,以及使用抗凝药物6个月后,组间患者的疗效、血栓及出血事件的差异。结果与未预防性抗凝组比较,预防性抗凝组男性比例、年龄、24h尿总蛋白、D-二聚体、血总胆固醇较高,白蛋白(albumin,ALB)、凝血酶Ⅲ活性较低(P<0.05)。两组患者在肾脏病理方面比较,差异无统计学意义。未预防性抗凝组患者的血栓事件比例高于预防性抗凝组(12.2%vs 3.0%,P=0.030),血栓部位以下肢静脉血栓为主;预防性抗凝组出血事件比例高于未预防性抗凝组(15.1%vs 2.0%,P=0.003),出血部位以皮肤黏膜及牙龈出血为主。血栓高风险组(ALB<25g/L)中,未预防性抗凝组血栓事件比例高于预防性抗凝组(9.2%vs 1.0%,P=0.022)。3组比较,华法林组出血比例高于低分子肝素组和低分子肝素+DOACs组(33.3%vs 5.7%vs 16.3%,P=0.042)。结论无论何种预防性抗凝治疗方案(低分子肝素、华法林或DOACs)均可以安全有效地降低IMN患者发生血栓事件风险。