促皮质素在肾病综合征中的作用机制北大核心CSCD

促皮质素(ACTH)治疗某些激素抵抗型肾病综合征有一定疗效,包括膜性肾病、局灶节段性肾小球硬化、微小病变型肾病等,可有效缓解蛋白尿和保护肾功能,提示其除了促皮质素效应外,可能存在其他作用机制。现主要介绍ACTH的生物学特性,结合ACTH治疗肾病综合征的临床及基础研究,阐明其可能的作用机制,为临床应用提供依据。     

Nephrotic syndrome complicating alpha-glucosidase replacement therapy for Pompe disease

We report a patient with Pompe disease who developed reversible nephrotic syndrome during prolonged, high-dose, experimental, enzyme replacement therapy with recombinant human acid alpha-glucosidase (rhGAA). Because of the development of antibodies to rhGAA and concomitant clinical decline, escalating doses of rhGAA were administered as part of an experimental immune tolerance regimen. Histologic evaluation of kidney tissue revealed glomerular deposition of immune complexes containing rhGAA itself, in a pattern of membranous nephropathy. To our knowledge, this is the first reported case of nephrotic syndrome occurring during enzyme replacement therapy. The nephrotic syndrome gradually resolved after the rhGAA dose was decreased, indicating that decreasing the antigenic load can ameliorate glomerular immune complex deposition associated with enzyme replacement in a highly sensitized patient.     

Membranous nephropathy associated with ovarian tumour in a young girl: recovery after removal

We report a 7-year-old girl who presented with membranous glomerulonephritis and steroid-resistant nephrotic syndrome in association with a benign ovarian tumour. Surgical excision of the tumor led to complete disappearance of the proteinuria within 2 weeks. Tumour-associated membranous nephropathy in children is rare, as a review of the literature shows.Abbreviations CEA carcino embryonic antigen - NCA non-specific cross-reacting antigen     

Dramatic response to corticosteroid therapy of nephrotic syndrome associated with IgA nephropathy

We report a dramatic response of the nephrotic syndrome to prednisolone therapy (2 mg per kg per day) in a 6-year-old boy with IgA nephropathy. He had developed massive proteinuria (22.1 gm per day) and microscopic hematuria shortly after an episode of tonsillitis. Renal biopsy two months after onset showed mild mesangial hypercellularity with typical mesangial deposition of IgA. Corticosteroid therapy resulted in a sharp cessation of proteinuria and complete resolution of the urinary abnormalities. We suggest that massive proteinuria associated with IgA nephropathy may be responsive to corticosteroid therapy when there are minimal glomerular changes.     

Extramembranous nephropathy in black South African children

Membranous nephropathy is the most frequent histological category among black children with nephrotic syndrome. In this study 31 African children with this condition are described. There were more boys than girls and the peak age was four to 11 years. The incidence of this histological category and clinical outcome in the African children were similar to these features in adults with membranous nephropathy. During a follow-up period of up to six years there was spontaneous remission in a third of patients, persistent proteinuria in just over a third (37.5%) and persistent relapse in under a third (29.2%). Hypertension occurred more frequently (19.3%) and spontaneous remission less often (33.3%) than in children with membranous nephropathy elsewhere. Hypertension, the lower remission rate and persistence of proteinuria during the course of the disease were similar to the disease seen in adults. Renal failure was not encountered in any patients. Steroids were of little value in the treatment of these children. Five children (16.2%) had associated infections. HBsAg was present in three of six children tested.     

Rituximab followed by mycophenolate mofetil in children with IgM nephropathy

IgM nephropathy presents with refractory nephrotic syndrome and its treatment is a significant challenge for pediatricians. We present two patients with IgM nephropathy and frequently relapsing nephrotic syndrome treated with rituximab and subsequently mycophenolate mofetil. Both showed complete remission, which 24 to 30 months later, was still maintained. The role of mycophenolate mofetil therapy in maintaining remission after successful treatment of rituximab in IgM nephropathy needs to be examined.     

Systemic lupus erythematosus (SLE) presenting with nephrotic syndrome and membranous glomerulopathy in a 10-year-old girl

The authors report the case of a 10-y-old girl with clinical diagnosis of systemic lupus erythematosus (SLE), made at the age of 6 y, based upon arthritis, serositis, haematological disorder and positive antinuclear antibody. The first manifestation of disease--Raynaud's phenomenon--appeared at the age of 4 y. Seven months after the diagnosis, she developed nephrotic proteinuria with haematuria. Percutaneous renal biopsy showed membranous glomerulonephritis, the least common form of lupus nephritis. CONCLUSION: Intravenous cyclophosphamide therapy associated with oral prednisolone proved effective in inducing complete remission of nephrotic syndrome.     

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??Abstract?? Objective To investigate the children with idiopathic membranous nephropathy??IMN?? about the clinical and pathological characteristics?? efficacy and prognosis?? providing the reference for the clinical diagnosis and treatment.Methods Summarize and analyze the clinical manifestation?? pathological features?? treatment and prognosis of 20 cases of IMN patients in Paediatric Nephrology of Shengjing Hospital of China Medical University between 2006.2 and 2014.2. Results ??1??In 20 cases of children with IMN??there were 13 male cases and 7 female cases, male to female ratio 1.86??1. The age ranged from 4 to 14 years?? the mean age being 10.65 ± 3.18 years??from onset to renal biopsy the was 7 to 190 days??with an average of 59.1 ± 55.9 days.There were 5 cases of below nephrotic proteinuria in clinical manifestations?? ??including simple proteinuria in 1 case?? hematuria and proteinuria in 4 cases????and 15 cases of nephrotic proteinuria?? of which 1 case with acute renal insufficiency.??2??Renal pathology:light microscopy showed that there were 2 cases of stage I membranous nephropathy??17 cases of stage II membranous nephropathy and 1 cases of stage III membranous nephropathy??among which 16 cases were with mild mesangial cells proliferation and mesangial matrix increase??4 cases with partial glomerular sclerosis??percentage of glomerular sclerosis was 2.4%??3.4%??3.7% and 5.5%??respectively????and 7 cases with focal tubular atrophy and interstitial fibrosis.Immunofluorescence showed there was IgG and C3 deposition?? partly with IgM??Fg??C1q??and IgA deposition.??3??According to the level of proteinuria the patients were treated with glucocorticoid and renin angiotensin converting enzyme inhibitor??ACEI?? or combined with immunosuppressive therapy with a result of 12 cases completely relieved and 8 parthy relieved.??4??In the 19 cases followed up for 2-7 years??12 cases obtained complete remission?? of which 2 cases replased in 1.5 year and 2 years after drug withdrawal. Eight cases had partial remission??of which 7 cases were still receiving sequential treatment??while 1 case lost follow-up because of refusing the use of immunosuppressant. Conclusion The onset of IMN is mainly in elder children and male is more than female.Nephrotic syndrome is the major clinical manifestations of IMN. Glucocorticoids combined withimmunosuppressive drugs can achieve satisfactory therapeutic effect.     

HBV associated nephrotic syndrome: resolution with oral lamivudine

A 6 year old boy presenting with a five month history of fever, lethargy, and anorexia, was found to have hepatitis B associated membranous glomerulonephropathy and nephrotic syndrome. After two months treatment with oral lamivudine, his proteinuria cleared and serum albumin and aminotransferases normalised, associated with disappearance of hepatitis B e antigen (HBeAg) and appearance of anti-HBeAg antibodies. After 12 months, without side effects, lamivudine was discontinued. He remains well 11 months off treatment.     

HBV associated nephrotic syndrome: resolution with oral lamivudine.

A 6 year old boy presenting with a five month history of fever, lethargy, and anorexia, was found to have hepatitis B associated membranous glomerulonephropathy and nephrotic syndrome. After two months treatment with oral lamivudine, his proteinuria cleared and serum albumin and aminotransferases normalised, associated with disappearance of hepatitis B e antigen (HBeAg) and appearance of anti-HBeAg antibodies. After 12 months, without side effects, lamivudine was discontinued. He remains well 11 months off treatment.     

儿童特发性膜性肾病临床病理特点及治疗探讨

目的 了解儿童特发性膜性肾病(IMN)的临床病理特点,探讨其治疗方案.方法 回顾性分析25例病理确诊的IMN患儿的临床病理特点,总结其不同治疗方法 的疗效.结果 儿童IMN占同期所有肾穿刺活检(简称肾穿)患儿的3.81%.25例IMN中男9例,女16例;起病年龄2～14岁,平均(9.4±3.4)岁;肾穿时病程0.4～11.0个月,中位数2.5个月.临床表现为肾病综合征肾炎型21例(84%),肾小球肾炎4例(16%).全部患儿均伴血尿,其中肉眼血尿7例,高血压4例,并发血栓2例,肾功能不全1例.病理分期IMNⅡ期21例(84%).伴中重度小管间质损害者6例,伴局灶节段硬化2例.22例肾病综合征及肾病水平蛋白尿患儿中,21例首选糖皮质激素治疗,其中20例符合评价激素疗效标准:激素敏感1例(复发后转为激素耐药),19例为激素耐药(95%).后续治疗包括继续单纯激素减量隔日治疗8例,其中完全缓解5例,部分缓解3例;激素联合免疫抑制剂治疗12例,该12例连同首选联合免疫抑制剂治疗1例、激素治疗5周联合免疫抑制剂治疗1例,共14例.结论 本组患儿IMN临床表现以肾病综合征为主,均伴有不同程度血尿.绝大多数初治激素耐药,但部分病例减量隔日治疗过程中获缓解,联合免疫抑制剂治疗及疗效尚需进一步临床验证.

Abstract：

Objective To investigate the clinicopathological feature and treatment of idiopathic membranous nephropathy(IMN)in children.Method A retrospective analysis of 25 cases of biopsyproven IMN seen between January 2004 and December 2009.Result The incidence of IMN was 3.81% in all the children patients who underwent renal biopsy.Of 25 patients with IMN,nine were boys and sixteen were girls.The mean age at onset was(9.4±3.4)years with a range of 2-14 years.Renal biopsies were performed at a median 2.5 months(range 0.4-11 months)after onset.The clinical manifestations included nephrotic syndrome(NS)nephritic type in 21 cases(84%)and glomerulonephritis in 4 cases.All patients presented with hematuria,and 7 had macroscopic hematuria.Hypertension was noted in 4 patients.Two patients were complicated with thrombosis.One patient was in a chronic renal insufficiency(CRI)state.According to the MN staging criteria,21 cases were in stage Ⅱ IMN(84%).Six patients showed moderate or severe tubulointerstitial lesion.Focal segmental glomerulosclerosis(FSGS)was found in two patients.Of the 22 patients with NS and nephrotic proteinuria,21 cases were treated with prednisone initially and in 20 of them the efficacy of corticosteroid therapy was evaluated:one of them was steroid sensitive(became steroidresistant after relapse)and all the others were steroid-resistant(95%).The subsequent treatment:eight of them were treated with prednisone followed by a taper to alternate-day therapy.Five of them had complete remission and three partial remission.Twelve cases were treated with combined therapy of prednisone and immunosuppressive agents. Of these 12 cases together with one case who received initially combined treatment with prednisone and immunosuppressive agent and one case treated with prednisone initially for five weeks then with combined therapy contained another immunosuppressive agent,totally 14 cases,5 had complete remission,2 partial remission,3 did not achieve remission,and 3 had unknown response.Conclusion Of the patient cohort,the predominant presenting feature was nephrotic syndrome,and with different degree hematuria.Almost all of them were steroid resistant,but followed by a taper to alternate-day therapy,some could achieve remission.The effect of a combination of prednisone and immunosuppressive agent is needed to be further proven in children.     

儿童特发性膜性肾病的临床病理特点及治疗转归（附22例报告）

目的　总结儿童特发性膜性肾病（IMN）的临床病理特点、治疗及预后转归。方法　回顾性分析2005年1月至2017年2月山东大学附属省立医院小儿肾脏风湿免疫科经病理证实的22例IMN患儿的临床表现、病理特征、治疗及预后等资料。结果　22例患儿中男12例,女10例,发病年龄3～15岁。临床表现：血尿蛋白尿4例（18.18%）;原发性肾病综合征18例（81.82%）。初次肾活检结果：膜性肾病Ⅰ期8例（36.36%）、Ⅰ～Ⅱ期5例（22.73%）,Ⅱ期5例（22.73%）、Ⅱ～Ⅲ期1例（4.54%）、不典型膜性肾病3例（13.64%）。22例患儿肾组织M型磷脂酶A2受体（PLA2R）阳性者12例（54.54%）,83.33%（10/12）PLA2R阳性的患儿起病年龄≥10岁。治疗方案：4例血尿蛋白尿患儿中2例给予激素及血管紧张素转化酶抑制剂（ACEI）治疗,2例仅给予ACEI治疗,均获得完全缓解。18例肾病综合征患儿全部予以激素、ACEI治疗,激素耐药者加用免疫抑制剂治疗。随访发现22例患儿中18例（81.82%）获完全缓解,3例（13.64%）获部分缓解,1例（4.54%）失访。结论　儿童IMN临床多表现为肾炎型肾病综合征,以激素耐药型为主。病理表现以Ⅰ～Ⅱ期多见。儿童IMN的PLA2R阳性以青少年为主,小年龄儿童阳性率较低。激素联合ACEI、免疫抑制剂治疗缓解率较高。     

Nephrotic syndrome in Hodgkins disease

A case of nephrotic syndrome due to minimal lesion glomerulonephritis associated with Hodgkins disease is described. The course of the nephrotic syndrome was relapsing, preceeding the development of lymphoma by eighteen months. Treatment of this nephrotic syndrome with repeated courses of Prednisone and Cyclophosphamide resulted only in partial improvement of his proteinuria. However, complete absence of proteinuria only occurred with successful therapy of Hodgkins disease.     

他克莫司在儿童肾脏疾病中的临床应用及作用机制

儿童肾小球疾病的发病机制中免疫因素是主要致病因素之一。他克莫司作为继环孢菌素A之后临床应用的一种强而有效的免疫抑制剂,近年来在儿童肾脏疾病治疗中的地位与作用日渐被重视。他克莫司在针对难治性肾病综合征包括激素依赖型、激素耐药型和频繁复发型等肾小球疾病治疗中取得了良好的效果。该文从作用机制入手,综述他克莫司在肾病综合征、局灶节段性肾小球硬化、系膜增生性肾小球肾炎、膜性肾病、狼疮性肾炎等儿童肾脏疾病中的应用。     

Enalapril and hydroxyurea therapy for children with sickle nephropathy

Proteinuria in children with sickle cell anemia (SCA) is an early sign of sickle nephropathy, and portends the development of nephrotic syndrome and chronic renal failure. Enalapril has been shown to reduce proteinuria in adult patients with SCA, but the potential benefits of hydroxyurea in this clinical setting have not been reported. A single institution retrospective analysis was performed. Children with sickle nephropathy were identified, and the laboratory effects of enalapril and hydroxyurea therapy were evaluated in children with substantial proteinuria. Three children developed proteinuria at 8 +/- 1 years of age. Pre-treatment laboratory studies included a low serum albumin (2.8 +/- 0.8 g/dl) and a highly elevated urine protein/creatinine ratio (6.9 +/- 3.7, normal <0.2). Enalapril treatment for 3.0 +/- 1.3 years normalized serum albumin (3.9 +/- 0.3 g/dl) without significant changes in serum potassium, serum creatinine, or systolic blood pressure. However, urine protein/creatinine remained elevated in the nephrotic range (1.6 +/- 0.7). The addition of hydroxyurea therapy for 3.5 +/- 1.2 years increased fetal hemoglobin levels (7.0 +/- 3.6% to 21.0 +/- 3.2%) and was associated with a near-normal urine protein/creatinine ratio (0.5 +/- 0.1). Enalapril therapy for children with sickle nephropathy reduces urinary protein excretion and normalizes serum albumin. Hydroxyurea therapy may further normalize the urine protein/creatinine ratio. Combination therapy should be tested prospectively in children with sickle nephropathy.     

Hepatitis B-associated nephrotic syndrome in Jamaican children

Between December 1984 and November 1996, 171 children under 12 years old presented to the University Hospital of the West Indies with nephrotic syndrome. Hepatitis B surface antigen (HBsAg) was found in ten (6%) of these children, eight of whom had membranous nephropathy (MN), and one each had mesangial proliferative glomerulonephritis (MesN) and minimal change nephrotic syndrome (MCNS). Only those children with MesN and MCNS were steroid-sensitive. The HBsAg-positive status was identified incidentally on screening. At a mean follow-up of 34 months, seven of ten children had experienced complete or partial remission and three had persistent nephrotic syndrome, although none was in renal failure. Six of the ten had biochemical hepatitis. All the children were still HBsAg-positive. Hepatitis B virus (HBV) is a factor contributory to nephrotic syndrome in Jamaican children. As diagnostic clinical markers for HBV-associated nephropathy are usually absent, all children presenting with nephrotic syndrome should be screened for HBsAg. A policy should be implemented in Jamaica for screening pregnant women and at-risk groups for HBsAg, as well as for immunising susceptible neonates, in order to reduce the incidence of HBV-associated pathology.     

Nephrotic syndrome associated with acquired immunodeficiency syndrome in children

We report here the cases of 15 children in whom nephrotic syndrome developed, from among 164 children (55% male, 90% black) followed in our acquired immunodeficiency syndrome clinic from 1984 through 1990. Mean age at onset of nephrotic syndrome was 4.9 +/- 2.6 years. Fourteen patients were black and one was Hispanic. Seventy-three percent of our patients with nephrotic syndrome were girls. The mean duration of clinical acquired immunodeficiency syndrome before development of nephrotic syndrome was 1.7 +/- 1.1 years. In eight patients, nephrotic syndrome appeared between 3 and 11 months after intravenous infusions of immune globulin or albumin were administered as part of a research protocol; this incidence (8/47) was higher than the incidence of nephrotic syndrome among those who did not receive intravenous infusions (7/117, p less than 0.05). Tissue for histologic examination was available for 80% of the patients, and histologic examination demonstrated mesangial hypercellularity (5 patients), focal segmental glomerulosclerosis (4 patients), minimal change disease (2 patients), and IgM nephropathy (1 patient). Deposition of one or more immunoglobulins was noted in all but one patient studied with immunofluorescence. Corresponding electron-dense deposits were seen by electron microscopy in 78% of specimens. Prednisone did not induce a remission of nephrotic syndrome in the 13 patients treated, whereas cyclosporine did so in the 3 patients to whom it was administered. Five patients were in the end stage of renal disease within 8 months. Successful maintenance peritoneal dialysis was performed in three patients, but 80% of patients have died of human immunodeficiency virus-related complications; one patient was lost to follow-up. We conclude that immune-complex deposition is consistently seen in children with human immunodeficiency virus-associated nephrotic syndrome. This nephrotic syndrome is resistant to steroid therapy, but we observed a remission of the proteinuria with cyclosporine therapy in three patients. For patients with end-stage renal disease, maintenance peritoneal dialysis may improve the quality of life.     

Nephrotic syndrome in indian children.

A clinicopathological study of 206 Indian children with nephrotic syndrome showed a primary renal cause in 195 (96%), of which 77% were boys. In 126 children (96 boys, 30 girls) onset of the disorder occurred before the age of 5 years. Renal biopsy showed minimal lesions in 150 patients (77%); in 85 of these biopsy was done 3 months to 16 years after onset of the nephrotic syndrome. Significant renal histological abnormalities in 45 cases were labelled as mesangiocapillary 8, mesangioproliferative 4, proliferative with extensive crescents 2, membranous 3, focal segmental glomerulosclerosis 9, focal global glomerulosclerosis 2, advanced nonspecific 8, and mild proliferative 9. Nephritic manifestations were mainly associated with significant renal lesions, which were more frequently encountered when the onset of disease was after the age of 5 years. Clearance of proteinuria with corticosteroid therapy was practically confined to patients with minimal or mild renal histological changes. Our findings suggest that the pattern of idiopathic nephrotic syndrome in Indian children is similar to that reported from Western countries.     

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??Objective??To summarize the clinicopathological features??treatment and prognosis of childhood idiopathic membranous nephropathy??IMN??. Methods??The clinical manifestations??pathologic features??treatment and prognosis of 22 IMN children who were diagnosed by pathology from January 2005 to February 2017 were retrospectively analyzed. Results??Twenty-two children??12 males and 10 females?? had an onset age range of 3 to 15 years. Clinical manifestations??hematuria and proteinuria in 4 cases??18.18%????nephrotic syndrome??NS?? in 18 cases??81.82%??. Renal biopsy results??8 cases??36.36%?? in stage??5 cases??22.73%?? in stage ??-??5 cases??22.73%?? in stage ??1 case??4.54%?? in stage ??-??atypical membranous nephropathy in 3 cases??13.64%??. Among them??12 cases??54.54%?? of M-type phospholipase A2 receptor??PLA2R?? positive were detected and 83.33%??10/12?? PLA2R positive children with an onset age older than 10 years old. Immunofluorescence showed predominantly IgG and C3 deposition. Treatment programs??in the 4 cases whose clinical manifestations were hematuria and proteinuria??2 cases were given glucocorticoid and ACEI drug treatment??the other 2 cases were given ACEI drugs alone??and they had complete remission. The 18 patients with NS all were treated with glucocorticoid and ACEI??and immunosuppressive agents were given to steroid-resistant patients. During the follow-up??18 cases??81.82%?? were completely relieved??3 cases??13.64%?? were partially relieved??and 1 patient??4.54%?? was lost of follow-up. Conclusion??Clinical manifestations of IMN are mostly nephritis nephrotic syndrome??mainly steroid-resistant nephrotic syndrome. Pathological performance mainly is??-??stage. The positive rate of PLA2R in junior age was lower than adolescence. Glucocorticoid combined with immunosuppressive agents has a higher response rate.     

Nephropathy gonadal dysgenesis--or incomplete Drash syndrome?]

This is a report about a phenotypical normal girl with nephropathy and gonadal dysgenesis. At the age of 2 years 8 months she presented with steroid resistant nephrotic syndrome. Focal segmental glomerulosclerosis was found by biopsy. Because of delayed puberty karyotyping was performed, which revealed 46 XY. Thirteen years after onset of proteinuria she reached end stage renal failure. Gonadal dysgenesis and nephropathy are often indistinguishable from incomplete Drash syndrome. Children with early nephropathy of unknown origin or gonadal dysgenesis should be observed for development of Wilms tumor. When chronic nephropathies are present in girls, karyotyping should be considered.