小儿急进性肾炎和新月体肾炎的再认识:附43例临床与病理分析

目的 探讨小儿急进性肾炎和新月体肾炎的病因、临床以及病理特点及两者之间的关系。方法 回顾总结1987年至2002年临床诊断急进性肾炎或病理诊断新月体肾炎的43例住院患儿的临床资料。结果 患儿以学龄儿童多见，60．5％为原发性肾脏疾病，绝大多数表现为浮肿、少尿、高血压、肉眼血尿及肾病水平蛋白尿。部分(24．0％)急进性肾炎的肾脏病理为非新月体肾炎，包括毛细血管内增生性肾小球肾炎、Ⅳ型膜增殖性狼疮性肾炎、增生硬化性肾小球肾炎及局灶节段性肾小球硬化：而部分(32．1％)新月体肾炎的临床表现为非急进性肾炎，包括肾病综合征(肾炎型)、急性肾炎综合征及慢性肾脏疾病。予正规治疗的25例患儿中，44．0％的患儿肾功能恢复，44．0％的患儿肾功能好转。结论 急进性肾炎是临床诊断，新月体肾炎是病理诊断，两者并非完全一致；积极行肾穿刺活检，有助于明确肾脏病理类型，指导治疗；早期诊断、及时治疗有助于改善急进性肾炎或新月体肾炎患儿的预后。     

急进性肾小球肾炎100例临床分析

目的：RPGN是一组病理发展快的疾病,近年来该病治疗上进展较大,疗效明显提高.本文对100例RPGN患者进行了临床分析.结果：患者住院天数平均25天,临床症状消失,实验室检查正常,痊愈者41例（42%）,好转50例（54%）,后者离院时仍有微量蛋白尿及镜下红细胞,补体3（C3）在2个月内基本恢复正常.3例因年龄太大,转为肾衰,5年间死亡.结论：RPGN是一组临床表现和病理改变相似,但病因各异的临床综合征,因此在诊断RPGN时应作出病因诊断.只有确定了病因、免疫类型、疾病的发展阶段、活动性后,方可选择合理治疗,权衡治疗的利弊与风险,并作出预后评价.     

Anti-glomerular Basement Membrane Glomerulonephritis During the First Trimester of Pregnancy

A 28-year-old woman was admitted during the eighth week of her pregnancy because her clinical course was consistent with rapid progressive glomerulonephritis (RPGN). Anti-glomerular basement membrane antibody (anti-GBM Ab) and myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) were positive, and the anti-GBM Ab titer being extremely high. She was treated with hemodialysis, plasma exchange and prednisolone. She survived the illness; however, neither the fetus nor her kidney function could be rescued. She had human leukocyte antigen (HLA)-DRB1*1502:01, which differs from the DRB1*1501 associated with anti-GBM GN. When patients have particular symptoms, we should check the urine and serum creatinine to exclude RPGN, even in cases of pregnancy.     

Endocarditis-associated rapidly progressive glomerulonephritis mimicking vasculitis: a diagnostic and treatment challenge

BackgroundInfective endocarditis (IE)-associated rapidly progressive glomerulonephritis (RPGN) is rarely reported. Sporadic case reports have noted the diagnostic and therapeutic challenge in IE-associated glomerulonephritis because it may masquerade as idiopathic vasculitis.MethodsPatients with clinical diagnosis of IE-related RPGN in a tertiary hospital in China between January 2004 and May 2021 were identified and retrospectively reviewed.ResultsTwenty-four patients with IE-associated RPGN were identified. All patients presented with fever and multiorgan system involvement on top of heart and kidneys, spleen (79%, 19/24), skin (63%, 15/24), lung (33%, 8/24) and nervous system (17%, 4/24). Six of the 24 patients (25%) were initially suspected to have ANCA-associated or IgA vasculitis. Forty-five percent of patients are seropositive for ANCA. Renal histology showed mesangial and/or endocapillary hypercellularity with extensive crescents in most patients. C3-dominant deposition was the predominant pattern on immunofluorescence and pauci-immune necrotising crescentic glomerulonephritis was observed in one case. All patients received antibiotics with or without surgery. Six patients received immunosuppressive therapy before antibiotics due to misdiagnosis and seven patients received immunosuppressive therapy after antibiotics due to persistence of renal failure. Three of the 24 patients died due to severe infection. All the surviving patients had partial or complete recovery of renal function.ConclusionIE-associated RPGN is rare and the differential diagnosis from idiopathic vasculitis can be challenging due to overlaps in clinical manifestations, ANCA positivity and absence of typical presentations of IE. The prognosis is generally good if antibiotics and surgery are not delayed. The decision on introducing immunoruppressive treatment should be made carefully on a case by case basis when kidney function does not improve appropriately after proper anti-infective therapy.

Key messages

• Infective endocarditis associated RPGN is rare and differentiating it from idiopathic vasculitis can be challenging due to overlap in clinical manifestations, ANCA positivity and occasional absence of typical manifestations of infective endocarditis.
• Kidney function usually responds to antibiotic therapy alone.
• Immunosuppressive therapy may be beneficial in carefully selected patients whose kidney function does not improve with antibiotics alone.

     

Pauci-immune rapidly progressive glomerulonephritis after nephrectomy in a renal donor

Idiopathic rapidly progressive glomerulonephritis (RPGN) is a clinicopathologic syndrome in which glomerular damage is accompanied by a rapid and progressive decline in renal function, usually resulting in irreversible renal failure in weeks or months. We report the occurrence of pauci-immune RPGN, more specifically microscopic polyarteritis nodosa (PAN), in a 60-year-old woman 15 months after donor nephrectomy, and 3 months after documentation of intact, residual renal function. The transplanted kidney continues to function well in the recipient, 6 years posttransplantation, and 4.5 years beyond destruction of the donor's contralateral kidney by RPGN. The donor underwent cadaveric renal transplantation after 2 years on dialysis, and at the 3-year mark has intact renal function. These intriguing observations strongly argue that host environmental factors, rather than intrarenal factors, play a major causative role in the pathogenesis of RPGN.     

Improvements in treatment strategies for patients with antineutrophil cytoplasmic antibody-associated rapidly progressive glomerulonephritis

The course of rapidly progressive glomerulonephritis (RPGN) caused by antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is often life-threatening, especially in the elderly when pulmonary involvement and/or severely impaired renal function are present. Corticosteroids and cyclophosphamide are the first-line treatment, but ironically infection, not vascular events such as hemorrhage, caused by the vasculitis itself, is the most common cause of death of RPGN patients. Several new treatment strategies, such as leukocytapheresis (LCAP) and intravenous immunoglobulin (IVIg), have become available during the past decade and these treatments have made it possible to treat high-risk RPGN patients without inducing serious immunosuppressive states. In the present paper we review recent clinical trials of LCAP and IVIg therapy in patients with pauci-immune/ANCA-associated RPGN, and show improved clinical outcomes after using these new treatment strategies in our institution.     

Renal Expression of Adhesion Molecules in Anca-Associated Disease

INTRODUCTION: Anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated disease among other manifestations can underlie rapidly progressive glomerulonephritis (RPGN), with crescentic and necrotizing GN. Differences in pathogenic immune mechanisms in RPGN may provide differences in the renal expression of adhesion molecules mediating these lesions. METHODS: Renal intercellular adhesion molecule 1 (ICAM-1; CD54) and vascular cell adhesion molecule 1 (VCAM-1; CD106) were assessed in 40 patients with type I RPGN (anti-glomerular basement membrane antibodies, n = 4), type II (immune complexes, n = 17), and type III (ANCA, n = 19). Enzyme-linked immunosorbent assay (ELISA) for detection of immunoglobulin G antibodies against the Goodpasture's antigen and indirect immunofluorescence and ELISA for myeloperoxidase (MPO) and proteinase 3 (PR3) were performed for ANCA testing. Ten normal renal tissues were used as controls. Relationships between ICAM-1 and VCAM-1, histopathologic features, and CD18, CD14, and CD3 cells were analyzed. RESULTS: Abnormal ICAM-1 and VCAM-1 in tubule was seen in >80% of biopsies with RPGN. Abnormal VCAM-1 in glomerular tuft was seen in >60% of biopsies with RPGN. Glomerular ICAM-1 was associated with less glomerulosclerosis (chi (2) = 6.719, p = 0.01), less interstitial fibrosis (chi (2) = 4.322, p < 0.05), and less tubular atrophy (chi (2) = 8.547, p < 0.005). Glomerular VCAM-1 was associated with glomerular leukocyte infiltration (chi (2) = 4.698, p < 0.05). Glomerular tuft stains of ++/+++ for VCAM-1 was observed in 10% from MPO-ANCA-GN patients but in 60% from PR3-ANCA-GN (Fi = 8.538, p = 0.03). CONCLUSIONS: The following conclusions can be made from this study. (1) The renal expression of ICAM-1 and VCAM-1 is upregulated in RPGN, and this is associated with the histological activity. (2) De novo expression of VCAM-1 on glomerular tuft suggests that endothelial cells play a role in RPGN. (3) De novo tubular expression of ICAM-1 and VCAM-1 suggests that epithelial cells may participate in adhesive interactions in RPGN. (4) De novo expression of VCAM-1 at the glomerular tuft in PR3-ANCA positive patients seems greater than in MPO-ANCA positive patients, which suggests that testing specific immune activation mechanisms may play a role in ANCA-associated GN.