【作者】 王楠；

【导师】 胡昭；

【作者基本信息】 山东大学 ， 内科学（肾内科）（专业学位）， 2022， 硕士

【摘要】 研究背景及目的:原发性肾小球肾炎(primary glomerulonephritis,PGN)患者妊娠是临床面临的巨大挑战,原发性肾小球肾炎女性患者可能与妊娠不良结局的风险增加有关,包括早产、先兆子痫、低出生体重儿等,而妊娠则可能会影响原发性肾小球肾炎的进展。因此,了解原发性肾小球肾炎与妊娠之间的关系很重要,但目前关于这方面的临床研究较少。本研究通过回顾性分析,总结我中心诊治的经活检证实的原发性肾小球肾炎患者的临床特征及妊娠结局,探究母体及胎儿不良结局的危险因素及妊娠对肾脏疾病的影响,为预防或减少原发性肾小球肾炎患者的不良妊娠结局提供更好的指导。研究方法:通过病历检索系统筛选出2014年1月1日至2021年12月31日在山东大学齐鲁医院经活检证实为原发性肾小球肾炎的患者,并纳入原发性肾小球肾炎诊断或随访期间的所有妊娠病例。从病历中收集患者的年龄、性别等基本资料、病理类型、实验室数据、药物应用、妊娠结局和肾脏结局。应用相关性分析探究原发性肾小球肾炎患者妊娠不良结局的危险因素。研究结果:1.本次研究纳入的17例原发性肾小球肾炎妊娠患者,平均年龄为29.4±4.1岁,范围在22-37岁;发病时的平均孕周为16.4±6.0周,范围在5-25周。发病时所有患者血清肌酐<1.5 mg/dL(血清平均肌酐为0.78 mg/dL),平均蛋白尿为9.30 g/g;其中4例(24%)有高血压病史,12例有血尿(71%),14例(82%)表现为肾病综合征。17例患者均进行了肾活检,10例是妊娠期间新诊断的原发性肾小球肾炎,并且在分娩后1年内接受了肾活检;其中膜性肾病6例,局灶性节段性肾小球硬化4例,微小病变肾病3例,IgA肾病3例,系膜增生性肾小球肾炎1例。2.17例原发性肾小球肾炎妊娠,6例(35%)出现母体不良结局包括妊娠期高血压(18%)、先兆子痫(18%)。活产率为76%,分娩时的平均孕周为36.0±2.8周,范围为29-39周。7例(41%)出现早产(35%)、低出生体重(35%)、先天性畸形(12%)等胎儿不良结局。3例(18%)在妊娠期间出现急性肾损伤,其中2例在随访期间发生肾功能进展,1例最终进展到终末期肾病。3.蛋白尿与先兆子痫(P=0.016)、重度先兆子痫(P=0.016)、早产(P=0.035)和低出生体重(P=0.035)等不良妊娠结局显著相关。发病时尿蛋白<3.5 g/g的3例妊娠无不良妊娠结局发生,而在尿蛋白≥3.5 g/g的14例妊娠中,发生不良妊娠结局的共11例,包括先兆子痫、流产、早产、低出生体重、先天性畸形、新生儿重症监护室。研究结论:1.原发性肾小球肾炎妊娠患者发病时常表现为肾病综合征,且伴有血尿。2.原发性肾小球肾炎患者发生妊娠不良结局风险较高,包括妊娠期高血压、先兆子痫、早产、低出生体重、先天性畸形,但远期肾功能相对稳定。3.蛋白尿与不良妊娠结局的发生显著相关,而尿蛋白≥3.5 g/g的患者妊娠不良事件的发生率可能更高。更多还原

【Abstract】 Background and Objective:Primary glomerulonephritis(PGN)patients are at higher risks of adverse maternal and fetal outcomes and face several challenges during pregnancy due to their increased physiologic demands on the kidney:increased risk of complications such as preeclampsia,preterm delivery and low birth weight,and progression of kidney disease.There are a few studies about pregnancy and renal outcomes in patients with primary glomerulonephritis.We aimed to investigate the risk factors for maternal and fetal outcomes,the effect of pregnancy on renal disease in patients with biopsy-proven primary glomerulonephritis to provide better guidance for preventing or reducing adverse pregnancy outcomes.Methods:We performed a retrospective study of the pregnant patient with biopsy-proven primary glomerulonephritis diagnosed at Qilu Hospital of Shandong University from 2014 to 2021.All cases of pregnancy during primary glomerulonephritis diagnosis or follow-up were included.Clinical manifestations,pathology subtypes,laboratory data,medication,pregnancy outcomes,and renal outcome were collected from medical records.Pearson’s correlation was used to test correlation between preeclampsia,severe preeclampsia,preterm birth,low birth weight and acute kidney injury and several risk factors including maternal age,hypertension,serum creatinine,serum albumin and proteinuria.Results:1.Among 17 patients,mean maternal age at onset of pregnancy was 29.4 ± 4.1 years(range,22-37 years)and mean gestational age at presentation was 16.4±6.0 weeks(range,5-25 weeks).The mean serum creatinine was 0.78 mg/dl and proteinuria was 9.30 g/g at presentation.All patients had a serum creatinine level<1.5 mg/dl.Four patients(24%)had a history of hypertension,12 patients had hematuria(71%),and 14 patients(82%)had nephrotic-range proteinuria at presentation.All 17 patients underwent renal biopsy,including membranous nephropathy(n=6).focal segmental glomerulosclerosis(n=4),minimal change nephropathy(n=3),IgA nephropathy(n=3),and mesangial proliferative glomerulonephritis(n=1).Ten patients were newly diagnosed with primary glomerulonephritis during pregnancy and underwent renal biopsy within one year of delivery.2.During pregnancy,6 pregnancies(35%)complicated by adverse maternal events including gestational new-onset hypertension(1 8%),preeclampsia(18%).The live birth rate was 76%(13/17)and the mean gestational week at delivery was 36.0 ± 2.8 weeks(range,25-40 weeks).Seven pregnancies(41%)complicated by adverse fatal events including preterm deliveries(35%),low birth weight(35%),fetal malformation(12%),etc.Three patients(18%)developed acute kidney injury during pregnancy,2 of 3 patients had renal disease progression at final follow-up after delivery,including 1 reaching end-stage renal disease and performing renal transplantation at final follow-up.3.Proteinuria was significantly correlated with adverse pregnancy events of preeclampsia(P=0.016),severe preeclampsia(P=0.016),preterm delivery(P=0.035)and low birth weight(P=0.035).In the 17 cases whose urinary protein-creatinine ratio at presentation<3.5 g/g,there were 3 cases with no adverse maternal-fetal events,while in the 14 cases with urinary protein-creatinine ratio≥3.5 g/g,there altogether 11 maternal-fetal events including preeclampsia,fetal loss,preterm delivery,low birth weight,fetal malformations and neonatal intensive care unit.Conclusion:1.Primary glomerulonephritis pregnant patients often presented with nephrotic syndrome and hematuria at onset.2.Primary glomerulonephritis patients showed a higher risk of adverse pregnancy outcomes but had relatively stable kidney processes.3.Proteinuria was significantly correlated with adverse maternal-fetal events and heavy proteinuria(urinary protein-creatinine ratio≥3.5 g/g)may predict a higher rate of adverse materno-fetal events.Further studies of larger subjects in the future are urgently needed.更多还原