Steroid sensitive nephrotic syndrome

Nephrotic syndrome in children is a common recurrent disease. Most of the cases are due to minimal change disease with a favourable outcome. More than 90% of children with minimal change disease respond to corticosteroid therapy (steroid sensitive nephrotic syndrome). 40-60% experience frequent relapses or have steroid dependence. These children require frequent corticosteroid therapy and/or immunomodulators or treatment with immunosuppressants, and are at high risk of cumulative steroid toxicity and side effects of cytotoxic therapy. Children with frequent relapses or steroid dependence should be managed in consultation with a pediatric nephrologist. Despite relapsing course, progression of minimal change nephrotic syndrome to end stage renal disease is extremely rare.     

Steroid sensitive nephrotic syndrome

Nephrotic syndrome in children is a common recurrent disease. Most of the cases are due to minimal change disease with a favourable outcome. More than 90% of children with minimal change disease respond to corticosteroid therapy (steroid sensitive nephrotic syndrome). 40–60% experience frequent relapses or have steroid dependence. These children require frequent corticosteroid therapy andJor immunomodulators or treatment with immunosuppressants, and are at high risk of cumulative steroid toxicity and side effects of cytotoxic therapy. Children with frequent relapses or steroid dependence should be managed in consultation with a pediatric nephrologist. Despite relapsing course, progression of minimal change nephrotic syndrome to end stage renal disease is extremely rare.     

Nonsteroidal antiinflammatory drugs. Renal toxicity. Review of pediatric issues

Nonsteroidal antiinflammatory drugs (NSAIDs) are an important part of therapy for childhood rheumatic disease and for the symptomatic management of clinical problems such as fever, musculoskeletal pain, and dysmenorrhea. Overall, there is a low incidence of significant complications resulting from NSAID therapy in children, but serious adverse effects on renal function have occurred. The physician should be aware of the potential renal toxicity of these drugs and monitor patients accordingly.     

Hepatitis B surface antigen associated nephrotic syndrome

Hepatitis B virus (HBV) has been reported in association with the nephrotic syndrome from different parts of the world, but its role as a cause of the pathological findings of nephrotic syndrome is still controversial. We report seven nephrotic children with positive hepatitis B markers in which members of their families were also positive for the markers but without clinical, renal or hepatic involvement. Four showed haematuria at onset and three developed hypertension later in the course of the disease. Only two were responsive to steroid therapy. Renal biopsy was performed in four, of whom three showed membranous nephropathy and the other showed mesangioproliferative glomerulonephritis. Four patients developed end-stage renal disease. We conclude that in our environment HBV, when detected in children with nephrotic syndrome, should not be considered as a chance finding, but may have a definite role in its pathogenesis. Moreover, the prognosis of HBV-associated nephrotic syndrome appears poor.     

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.     

Nephrotisches Syndrom im Kindesalter

Nephrotic syndrome is defined by severe proteinuria and hypoalbuminemia and is one of the most common renal diseases in the pediatric population. Nephrotic syndrome in children is classified by the criteria etiology, age at onset, response to glucocorticoids and histomorphology. Due to its etiology the common primary nephrotic syndrome has to be distinguished from secondary forms within the scope of other underlying diseases. The rare congenital forms have mostly a genetic background. Response to steroid therapy is highly relevant in terms of clinical course and prognosis. Primary steroid resistance affects about 10% of patients with idiopathic nephrotic syndrome. In these patients focal-segmental glomerulosclerosis is the leading histological finding, whereas in steroid-sensitive nephrotic syndrome minimal change glomerulonephritis is mostly found. In cases of frequent relapse or steroid dependency alternative immunosuppressive treatment options with e.g. cytostatic drugs, calcineurin inhibitors or mycophenolic acid should be considered to avoid steroid-associated side effects.     

Immunity and immunosuppression in childhood idiopathic nephrotic syndrome]

Steroid sensitive idiopathic nephrotic syndrome is a T-cell disorder characterized by a functional renal impairment. Concluding a still relevant demonstration involving cellular immunity in the pathogenesis of the disease, R. Shalhoub in 1974 suggested a "special role for the thymus" based on the efficiency of steroids and alkylating agents, dramatic recoveries following measles, sensibility to bacterial infection due to a lack of cooperation between T and B cell and association to Hodgkin disease. As a matter of fact, the selected drugs based on medical empirism somehow enhance thymocytes apoptosis and negative selection of T cell, except cyclosporin. Steroids have been the first historical treatment of idiopathic nephrotic syndrome and have steadily been the first-line treatment for 50 years. Their unavoidable ability to induce rapid recovery of proteinuria and long-lasting or definite remission are dependent to a strict compliance to treatment. Indications of steroids-sparing treatments are not that clearcut in patients with steroids intoxication. Objectively, efficiency of levamisole and cyclophosphamide are much more limited than previously reported and cyclosporin nephrotoxicity might severely impair renal function following long-lasting treatment as well as it may paradoxically increase the activity of the disease. An alternate strategy to those currently adopted would use cyclosporin as the first-line steroids-sparing treatment during a very limited period, awaiting favourable ageing of patients and natural dampening activity of the disease to a full efficiency of alkylating agents. Compared to cyclophosphamide and cyclosporin, the relative safety of levamisole is encouraging to a more frequent uses. Its association to a full dose of prednisone in the treatment of the inaugural episode should be investigated. According to the limitations of those therapies, emerging drugs as mycophenolate might be worthwhile in the treatment of nephrotic patients.     

初诊为原发性肾炎型肾病综合征患儿的病因构成分析——对国内儿童原发性肾病综合征临床分型的商榷

目的总结初诊为原发性肾炎型肾病综合征患儿的病因构成情况,探讨国内儿童原发性肾病综合征临床分型的价值。方法纳入2013年1月1日至2017年12月31日北京大学第一医院儿科收治的病初临床诊断为原发性肾炎型肾病综合征患儿,且经肾脏病理检查或基因突变分析明确最终诊断者,排除继发性、遗传性肾病综合征及伴有明显肉眼血尿者。原发性肾病综合征的临床分型参照中华医学会儿科学分会肾脏病学组标准。截取患儿入院时一般情况、入院时诊断和临床分型、肾脏穿刺活检病理检查结果、基因检测结果和最终诊断。结果 28例临床分型为原发性肾炎型肾病综合征的患儿进入本文分析,占同期收治的原发性肾病综合征的10.6%(28/265)。分型依据:25例(89.3%)为镜下血尿,2例为高血压(7.2%),1例为肾功能异常(3.6%)。28例均进行了肾穿刺活检,11例行基因检测,最终诊断:原发性肾炎型肾病综合征5例(17.9%),Ig A肾病10例(35.7%),Alport综合征8例(28.6%),遗传性肾病综合征3例(10.7%),急性感染后肾小球肾炎和纤维素性肾小球肾炎各1例(3.6%)。结论儿童原发性肾炎型肾病综合征临床分型诊断的主要依据为镜下血尿,通过肾脏病理检查和基因检测明确病因,以Ig A肾病、遗传性肾脏疾病等居多,因此,临床诊断儿童原发性肾炎型肾病综合征应该慎重。     

Steroid-responsive nephrotic syndrome and allergy: immunological studies.

Immunological studies were performed on 84 children with steroid-sensitive nephrotic syndrome as part of an investigation of the relationship between steroid-responsive nephrotic syndrome and allergy. Serum total IgE levels tended to be raised, particularly in children who had frequent relapses of nephrotic syndrome. Ten children had extremely high levels (greater than 1500 IU/ml) and several of them had neither a history of atopy nor any other identifiable cause. 25% of the children had at least one positive test for specific IgE antibody. IgE was not detected by immunofluorescence in renal biopsy tissue from 25 children, regardless of whether the child was in remission or relapse at the time of biopsy. Serum IgG and IgA levels were depressed particularly at the time of a relapse. Serum IgM tended to be raised and to remain so, even in children who had been in remission for more than a year. No clinically useful relationship was found between the frequency of HLA antigens and the occurrence or course of the syndrome, whether or not accompanied by atopy. Clinical and immunological features of atopy are more common in children with idiopathic nephrotic syndrome. This may be a causal or non-causal association. Pollen sensitivity is a rare cause of nephrotic syndrome; careful search for provocative agents may show other causes.     

Risk of long term renal impairment and duration of follow up recommended for Henoch-Schonlein purpura with normal or minimal urinary findings: a systematic review.

BACKGROUND: The duration of follow up to assess the risk of long term renal impairment in Henoch-Sch?nlein purpura (HSP) without nephritic or nephrotic syndrome or renal failure on diagnosis remains undetermined. AIMS: To undertake a systematic review of the literature to assess whether the risk of long term renal impairment without renal involvement on diagnosis could be estimated and to determine the time period when renal involvement is very unlikely after the diagnosis of HSP. METHODS: Search of studies of unselected children with HSP, and available information on urinary findings, renal involvement, and long term renal function follow up. Studies of selected children with HSP nephropathy at diagnosis were excluded. RESULTS: Twelve studies of 1133 children were reviewed. The follow up period ranged from 6 weeks to 36 years. Proteinuria and/or haematuria, which occurred in 34.2%, of which only one fifth were in association with nephritic or nephrotic syndrome, developed in 85% of cases within 4 weeks of the diagnosis of HSP, in 91% within 6 weeks, and in 97% within 6 months. Permanent renal impairment never developed after normal urinalysis; it occurred in 1.6% of those with isolated urinary abnormalities, and in 19.5% of those who developed nephritic or nephrotic syndrome. CONCLUSION: No long term renal impairment occurred after normal urinalysis. Even if urinalysis is normal at presentation, the testing should be continued for six months. There is no need to follow up after the first six months those whose urinalysis remains normal.     

The role of immunosuppressive agents in the treatment of nephrosis in children

Good clinical results are well known with the use of immunosuppressive therapy in children with idiopathic nephrotic syndrome; more recently, biological data have enhanced immunological anomalies, concerning mainly T helper lymphocytes. The need for steroids may decrease when relapsing nephrotic syndrome is associated with steroid intoxication and is absent when corticoresistance occurs. In these cases, the use of immunosuppressive agents is justified, but limited by side effects and toxicity. In patients treated with alkylating agents and now cyclosporine, good responses are often seen in frequently relapsing children whereas the course of steroid-resistant nephrotic syndrome is not significantly modified. However, the definite appreciation of such therapeutic results has to be further precised by both histological data and multicentric studies concerning new protocols.     

Safety concerns of angiotensin II receptor blockers in preschool children

Two recent trials of angiotensin II receptor blockers (ARBs) were performed in children 0-5 years of age. Data from the published reports of these trials together with additional information from the sponsoring drug companies were obtained. Three deaths occurred in the 183 (1.6%) hypertensive children participating in the two trials. At least two of these deaths occurred in children known to be susceptible to drugs acting on the renin-angiotensin system, that is, children with ongoing nephrotic syndrome and acute gastroenteritis. Clinicians who prescribe ARBs in preschool children need to be aware of the risk of drug toxicity especially in children susceptible to intravascular dehydration. Clinicians should consider discontinuing the drugs in the presence of acute diarrhoea.     

Immunosuppressive agents in the treatment of the nephrotic syndrome and glomerulonephritis in children.

There is good, controlled evidence which suggests that cyclophosphamide, and perhaps related drugs, have a definite role in the treatment of nephrotic children with the minimal change lesion. This role is one of secondary treatment, and the drugs should not be used as a first line of attack; they should be employed only when corticosteroid resistance or toxicity is a problem. In a few patients, azathioprine or 6-mercaptopurine may have a role in minimising corticosteroid toxicity, but the remission induced in relapsing children is no more durable than that after corticosteroids. Chlorambucil must be given in doses, and for periods long enough to run the risk of neoplasia, particularly leukaemia; there does not appear to be a place for its use in nephrotic children unless the duration of remission can be shown to be longer than that obtainable with cyclophosphamide. There is no evidence that any immunosuppressive agent has a place in the management of children with idiopathic glomerular disease showing structural alterations in the glomeruli. Children with systemic lupus erythematosus and nephritis may benefit from the addition of cytotoxic agents to their corticosteroid regime, although the indications for this are not clear, and controlled evidence is lacking.     

Left atrial atheromatosis in childhood nephrotic syndrome

Three male children who had onset, at approximately age 2 years, of nephrotic syndrome, which progressed to renal insufficiency had left atrial atheromatosis at autopsy disproportionate to the degree of aortic or vascular atheromatosis found. The atrial atheromatous process was distributed in elongated nodules, which had a ridged or corduroy-like appearance on gross examination. Two of the patients showed renal lesions of advanced focal glomerulosclerosis, but one had membranoproliferative glomerulopathy, suggesting that the "syndrome" of early onset nephrotic syndrome progressing to renal insufficiency, hyperlipidemia, and exaggerated left atrial atheromatosis, of which association we have not found a specific report, is etiologically heterogeneous. The patients reported died in 1943, 1952, and 1963. Whether more recent methods of treatment of nephrotic syndrome, hyperlipidemia, or chronic renal insufficiency in children have altered the incidence of such disproportionate left atrial atheromatosis is not known.     

Ifosfamide in the treatment of nephrotic syndrome (author's transl)

Ifosfamide, an alkylating agent was used successfully in the treatment of children with steroid sensitive nephrotic syndrome with minimal changes. Remissions have persisted for about 6 years. Toxicity was very minor, and the regimen constitutes a useful advance in management of these patients. Ifosfamide had no significant effect on children with steroid resistence nephrotic syndrome or other morphological changes. Because the potential gonadal dysfunction Ifosfamide should be given only in patients with steroid toxicity or frequent relapsers.     

Kidney transplantation in a child with Pierson syndrome

Congenital nephrotic syndrome is commonly associated with mutations in genes that encode podocyte and slit diaphragm proteins or the structural and regulatory proteins of the GBM. These mutations lead to the formation of dysfunctional proteins, which account for the resistance of the renal manifestations to conventional treatment methods. Consequently, patients become renal replacement therapy dependent. Mutation of the LAMB2 gene is associated with Pierson syndrome, which is an autosomal recessive disorder characterized by congenital nephrotic syndrome and ocular abnormalities. In this report, a 2‐year‐old male patient who was diagnosed with Pierson syndrome is presented. He had bilateral microcoria and developmental delay in addition to nephrotic syndrome. His renal function deteriorated rapidly, and he underwent a deceased donor kidney transplantation. He showed dramatic improvement after kidney transplantation; in addition to having good renal function, he started to catch up to his peers in terms of growth. Pierson syndrome should be considered during the diagnostic investigations of children with renal manifestations and ocular abnormalities. Children with Pierson syndrome must be evaluated in terms of kidney transplantation as soon as they are diagnosed.     

Cyclophosphamide treatment of steroid dependent nephrotic syndrome: comparison of eight week with 12 week course. Report of Arbeitsgemeinschaft für P?diatrische Nephrologie.

In a prospective study (Cytotoxic Drug Study II), 18 children with steroid dependent nephrotic syndrome and steroid toxicity were treated with cyclophosphamide (2 mg/kg body weight/day) for 12 weeks in combination with reducing doses of prednisone (group A). This group was compared retrospectively with 18 children with steroid dependent nephrotic syndrome, studied as part of the Cytotoxic Drug Study I, and who had received cyclophosphamide for eight weeks (group B). There were no differences between the groups in age at the onset of the nephrotic syndrome, age at entry into the study, and duration of the nephrotic syndrome before entry into the study. The number of relapses during the six months before the treatment was the same in both groups. Two years after treatment 12 of 18 children treated with cyclophosphamide for 12 weeks were still in remission. By contrast, only four of of 18 children treated with cyclophosphamide for eight weeks were still in remission. The cumulative rates of sustained remissions were significantly higher (67% and 22%, respectively) in group A. All relapses were observed within 400 days of stopping cytotoxic treatment. No severe side effects of cyclophosphamide occurred up to two years after treatment had been stopped. We conclude that for children with steroid dependent nephrotic syndrome and steroid toxicity cyclophosphamide treatment should be prolonged to 12 weeks to increase the likelihood of a prolonged remission.     

Management of steroid sensitive nephrotic syndrome: revised guidelines

JUSTIFICATION: In 2001, the Indian Pediatric Nephrology Group formulated guidelines for management of patients with steroid sensitive nephrotic syndrome. In view of emerging scientific evidence, it was felt necessary to review the existing recommendations. PROCESS: Following a preliminary meeting in March 2007, a draft statement was prepared and circulated among pediatric nephrologists in the country to arrive at a consensus on the evaluation and management of these patients. OBJECTIVES: To revise and formulate recommendations for management of steroid sensitive nephrotic syndrome. RECOMMENDATIONS: The need for adequate cortico-steroid therapy at the initial episode is emphasized. Guidelines regarding the initial evaluation, indications for renal biopsy and referral to a pediatric nephrologist are updated. It is proposed that patients with frequently relapsing nephrotic syndrome should, at the first instance, be treated with long-term, alternate-day prednisolone. The indications for use of alternative immunosuppressive agents, including levamisole, cyclophosphamide, mycophenolate mofetil and cyclosporin are outlined. The principles of dietary therapy, management of edema, and prevention and management of complications related to nephrotic syndrome are described. These guidelines, formulated on basis of current best practice, are aimed to familiarize physicians regarding management of children with steroid sensitive nephrotic syndrome.     

Prevention of serious bacterial infection in children with nephrotic syndrome

Although nephrotic syndrome is well known as a predisposing factor to bacterial infection in children, especially peritonitis due to Streptococcus pneumoniae , data on the incidence of infection and the effectiveness of preventative measures are limited. With particular reference to pneumococcal disease, this review summarises the available data on the pattern and incidence of invasive bacterial infection in children with nephrotic syndrome, and the level of evidence for the use of penicillin chemoprophylaxis and pneumococcal immunisation. Although data on the effectiveness of pneumococcal immunisation in children with nephrotic syndrome are limited, the safety profile of this vaccine makes the risk–benefit ratio favourable to use of the current polysaccharide vaccine in those over 2 years of age. Conjugate pneumococcal vaccines are likely to be more effective, particularly in children under 2 years of age and should be available by the year 2000. Although penicillin prophylaxis against pneumococcal infection is not of proven benefit for nephrotic syndrome, it is beneficial in sickle cell disease without appreciable risk. Subgroups of patients with nephrotic sydrome most likely to benefit from twice daily phenoxymethyl penicillin prophylaxis include children under 2 years of age, with unresponsive or frequently relapsing disease, or who have had a previous episode of pneumococcal infection.     

婴幼儿期肾病综合征临床特点分析

目的　探讨婴幼儿期原发性肾病综合征 (简称婴幼儿肾病 )的临床特点 ;分析婴幼儿肾病临床特点、免疫功能、病理分型和糖皮质激素 (简称激素 )疗效的关系。方法　对 31例婴幼儿肾病患儿进行临床观察 ;进行体液免疫和细胞免疫功能测定 ;14例接受肾穿刺活检 ;31例均采用激素中长程疗法 ,18例予以免疫抑制剂如环磷酰胺 (CTX)等联合治疗。结果　婴幼儿肾病临床以肾炎型肾病为主 ;体液免疫和细胞免疫功能下降 ;病理以非微小病变型为主 ;约 6 0 %患儿对激素治疗不敏感 ,需用激素与免疫抑制剂联合治疗。结论　婴幼儿肾病具有与其它儿童肾病综合征不同的特点 ,应当引起临床重视。