Noninvasive diagnosis of tubular damage by the use of the urinary chondroitin-4-sulfate/heparan sulfate ratio

20 healthy children, 20 children with tubulointerstitial nephritis (TIN) and 20 children with glomerulonephritis in the active state were examined. Polyacrylamide gel electrophoresis of urinary proteins, beta-2-microglobulin excretion and acid glycosaminoglycan electrophoresis were performed. Polyacrylamide-gel electrophoresis showed in all the cases with TIN low molecular weight proteinuria, no bands were observed in healthy children and in all the cases of glomerulonephritis high molecular weight proteinuria. Beta-2-microglobulin determination showed no differences between healthy children and children with glomerulonephritis, but showed high levels in the group of children with TIN. Acid glycosaminoglycan electrophoresis showed in the group of children with healthy children a mean chondroitin-4-sulfate-/heparan sulfate ratio (CS/HS) of 3.8 +/- 0.4. Children with TIN presented a low ratio of 1.5 +/- 0.5. Patients with glomerulonephritis showed a mean ratio of 3.7 +/- 0.3. Our results clearly show that tubular damage can be revealed by a low quotient of chondroitin-4-sulfate to heparan sulfate.     

Tamm-Horsfall蛋白诱导肾小管间质性肾炎发病机理探讨

目的探讨Ｔａｍｍ－Ｈｏｒｓｆａｌ蛋白（ＴＨＰ）致肾小管间质性肾炎（ＴＩＮ）的发病机理。方法采用流式细胞仪测定了１９只经肾内注射ＴＨＰ建立的大鼠ＴＩＮ模型的外周血Ｔ淋巴细胞免疫表型（ＣＤ４，ＣＤ８，ＣＤ２５，Ｉａ抗原）的表达，并应用免疫荧光技术定性观察了５只大鼠肾脏ＴＩＮ病灶局部浸润的Ｔ淋巴细胞亚群。结果于肾脏注射ＴＨＰ第１４天，模型组外周血ＣＤ＋４，ＣＤ＋８－ＣＤ＋２５，ＣＤ＋８－Ｉａ＋细胞及ＣＤ４／ＣＤ８比值较对照组升高（Ｐ＜０．０５），此时肾脏ＴＩＮ病灶局部浸润的Ｔ淋巴细胞表型大多数显示ＣＤ＋８。结论效应杀伤性Ｔ细胞介导的细胞毒作用在ＴＨＰ致肾脏免疫损伤过程中可能起重要作用     

Management of urinary tract infections

Urinary tract infection (UTI) is common in childhood. It may result in long-term complications due to renal scaring. Younger children are at higher risk of renal scarring. The diagnosis of UTI is based on urine culture. The bacterial count for diagnosis of UTI depends on the method of urine collection. Urinalysis is useful for making a presumptive diagnosis of UTI and allows initiation of empirical treatment in high-risk patients, after urine culture has been obtained. The treatment of UTI is guided by the severity of illness and age of the patient. Following a UTI, investigation should be performed to identify an underlying urinary tract anomaly. Recurrence of UTI occurs in 30–50% children. Important predisposing factors include VUR, urinary tract obstruction, voiding dysfunction and constipation. Vesicoureteric reflux (VUR) is seen in 30–50% children with UTI. The cornerstone of management of VUR is long-term antibiotic prophylaxis, which has been found to be as effective as surgical reimplantation.     

Transient erythroblastopenia of childhood: prospective study of 10 patients with special reference to viral infections

PURPOSE: It has been proposed that human parvovirus B19 or human herpesvirus 6 (HHV-6) causes transient erythroblastopenia of childhood (TEC). This study was performed prospectively and accurately in a sufficiently large population to confirm or reject these suggestions, or possibly to find another causative agent for TEC. PATIENTS AND METHODS: The authors studied prospectively the causative aspects of 10 consecutive children with TEC presenting at five Swedish pediatric clinics from 1994 to 1998 using serologic assays and polymerase chain reaction assays for B19, HHV-6, cytomegalovirus, and Epstein-Barr virus (EBV). The authors also performed isolation investigations of virus from bone marrow, stools, and aspirate from the nasopharynx. RESULTS: The authors found acute EBV infection in one child. There were no other instances of IgM positivity for any viruses at presentation, but a few children did show IgG positivity to HHV-6 (n = 2), EBV (n = 1), and cytomegalovirus (n = 1). No children were positive with respect to IgG for B19. However, it could not be determined when these children had been infected, and thus, a connection to TEC cannot be proved or excluded. No child showed B19 or HHV-6 DNA in serum or bone marrow collected at presentation. Isolation of virus from bone marrow, stools, and aspirate from nasopharynx culture was negative in all children but one, who had rotavirus in stool. CONCLUSIONS: HHV-6, B19, EBV, and cytomegalovirus are not common causative agents of TEC. The authors found no proof of any single agent causing TEC.     

Etiology of community-acquired pneumonia in hospitalized children based on WHO clinical guidelines

Community-acquired pneumonia (CAP) is a major cause of death in developing countries and of morbidity in developed countries. The objective of the study was to define the causative agents among children hospitalized for CAP defined by WHO guidelines and to correlate etiology with clinical severity and surrogate markers. Investigations included an extensive etiological workup. A potential causative agent was detected in 86% of the 99 enrolled patients, with evidence of bacterial (53%), viral (67%), and mixed (33%) infections. Streptococcus pneumoniae was accounted for in 46% of CAP. Dehydration was the only clinical sign associated with bacterial pneumonia. CRP and PCT were significantly higher in bacterial infections. Increasing the number of diagnostic tests identifies potential causes of CAP in up to 86% of children, indicating a high prevalence of viruses and frequent co-infections. The high proportion of pneumococcal infections re-emphasizes the importance of pneumococcal immunization.     

Bacterial coinfection in children hospitalized with respiratory syncytial virus infections

Clinical and bacterial findings were prospectively studied in 90 children hospitalized because of middle or lower respiratory tract infection caused by respiratory syncytial virus (RSV) during a surveillance period of 12 months. The results were compared with those of RSV-negative children hospitalized with identical indications during the 3 peak months of the RSV epidemic (N = 91) or for the 3 months after the outbreak (N = 99). A high frequency of pneumonia and acute otitis media were found in both RSV-positive and RSV-negative children during the epidemic, but not in control patients after the epidemic. Bacterial infection, based on a significant rise of antibody titer and/or on detection of pneumococcal antigen in serum or urine, was observed in 39% of the children with RSV infection. The respective figures were 24% in RSV-negative children hospitalized during the epidemic and 8% after the epidemic. Our observations stress the role of RSV as a predisposing agent for secondary bacterial infection in the airways of children. The most common bacteria involved in the mixed RSV-bacterial infections were Streptococcus pneumoniae and Haemophilus influenzae, the latter being found only in pneumonic patients. The presence or absence of pneumonia or acute otitis media was not significantly correlated with evidence of pneumococcal infection. We conclude that a bacterial pathogen should be actively sought when managing patients with lower respiratory tract syndromes, especially in those who have evidence of RSV infection.     

Clinical features of acute kidney injury in patients with Kawasaki disease

Although acute kidney injury (AKI) is a common complication in hospitalized children, AKI has rarely been reported in patients with Kawasaki disease (KD). Herein, we review the clinical trajectories of AKI in patients with KD. A total of 39 patients with KD who developed AKI have been reported in 28 publications as case reports. The causes of AKI include prerenal AKI associated with acute heart failure (AHF), intrinsic AKI caused by tubulointerstitial nephritis (TIN), acute nephritic syndrome (ANS), hemolytic uremic syndrome (HUS), immune complex-mediated nephropathy, rhabdomyolysis, and KD shock syndrome (KDSS). Six of the 39 patients (15.4%) underwent renal replacement therapy. While AHF and multiple organ dysfunction syndrome developed in 41% and 68% of KD patients with AKI, respectively, all patients recovered without any renal sequelae. Although the precise pathogenic mechanism underlying the development of AKI in patients with KD is unknown, several possible mechanisms have been proposed, including T-cell-mediated immunologic abnormalities for TIN, renal and glomerular endothelial injury resulting from vasculitis for HUS, immune complex-mediated kidney injury for immune complex-mediated nephropathy and ASN, and capillary leak and an increased release of cytokines with myocardial dysfunction for KDSS.     

Combined therapy of enalapril and losartan attenuates histologic progression in immunoglobulin A nephropathy

BACKGROUND: It has been reported that combined therapy of angiotensin converting enzyme inhibitor and angiotensin receptor blocker significantly decreases proteinuria in immunoglobulin A (IgA) nephropathy. However, histologic alterations following the therapy have not been reported. METHODS: A total of nine Japanese children with severe proteinuric IgA nephropathy who received a prompt immunosuppressive therapy were enrolled the study, four of whom received a combined therapy of angiotensin converting enzyme inhibitor, enalapril and angiotensin receptor blocker, losartan (Group A), while the remaining five did not (Group B). All underwent renal biopsy before and approximately 12 months after the first renal biopsy. RESULTS: At presentation, urine protein excretion and the histologic indices of mean activity index, mean chronicity index and tubulointerstitial scores did not show a statistical difference between the two groups: Group A (2.6 +/- 0.6 g/day; mean activity index, 5.0 +/- 1.0; mean chronicity index, 5.0 +/- 1.0; tubulointerstitial scores, 4.3 +/- 1.0) and Group B (2.2 +/- 0.6 g/day; mean activity index, 4.8 +/- 0.8; mean chronicity index, 4.8 +/- 1.3; tubulointerstitial scores, 3.6 +/- 0.5, respectively). All had normal blood pressure and renal function. Urine protein excretion and the activity index decreased at the second renal biopsy, while the chronicity index and the tubulointerstitial scores slightly increased or remained unchanged. In comparison with Group B, a significant suppression in increasing the chronicity index and the tubulointerstitial scores obtained at the second renal biopsy were observed in Group A [Group A: 4.3 +/- 1.2 and 3.0 +/- 0.0, respectively, vs Group B: 6.0 +/- 0.7 and 4.4 +/- 0.9, respectively (P < 0.05)]. One patient in Group B developed chronic renal insufficiency thereafter. CONCLUSIONS: Although only a small number of patients were examined, these clinical findings suggest that a combined therapy of enalapril and losartan may attenuate histologic progression in at least a proportion of patients with severe proteinuric IgA nephropathy.     

What is the role of autoimmune processes in nephropathies?

Classical autoimmune nephropathies rarely occur during childhood. They include the glomerulonephritis and tubulointerstitial nephritis caused by antibasement membrane antibodies and the systemic lupus erythematosus. The autoimmune pathogenesis of glomerulopathies such as minimal change disease and different forms of tubulointerstitial nephritis which are more frequent in children is not proven yet. The possible mechanisms of autoimmune disorders affecting the kidneys are 1. the genetic predisposition, 2. a defect in the immune system, 3. exogenous agents leading to cross-reactivity or polyclonal B cell stimulation, and 4. endogenous agents leading to immunogenic autoantigens. This review summarizes the current knowledge on the autoimmune pathogenesis of nephropathies derived from investigations in humans and animal experiments.     

特发性塌陷性肾小球病二例分析

目的分析和认识小儿特发性塌陷性肾小球病(ICG)的临床特征及病理特点。方法回顾性总结分析二例小儿特发性塌陷性肾小球病的临床资料、病理资料、治疗反应及随访结果。结果二例临床表现为典型的肾病综合征;化验结果有大量蛋白尿、高脂血症、低蛋白血症;病理可见肾小球毛细血管丛节段／全球性塌陷伴上皮细胞增生肥大变性及严重肾小管间质病变;治疗转归二例对激素耐药,其中1例用甲泼尼松和环磷酰胺冲击无效,迅速发展为肾衰竭,半年内死亡;另一例激素耐药。用环孢素A无改善,追踪8个月,持续高血压,蛋白尿无改善。结论小儿特发性塌陷性肾小球病临床以严重的肾病综合征伴迅速进展肾衰竭为特点;病理以肾小球的塌陷、上皮细胞增生肥大变性及严重肾小管间质病变为特点;本病治疗困难,预后不良。     

Bacterial septicemias in children with homozygous sickle cell anemia. Analysis of 69 cases

A retrospective analysis of 69 case-reports of children with homozygous sickle cell anemia hospitalized from 1964 through 1985 at the Kinshasa University Pediatric Hospital highlights these patient's high susceptibility to bacterial septicemia. Among causative organisms, the most prevalent were salmonellae (20 cases), pneumococci (15 cases), and klebsiella (12 cases). Clinical features of bacterial septicemia are identical in children with and without sickle cell anemia. Bone and/or joint infections are usually found in salmonella septicemia and meningeal or pleuropulmonary localizations in pneumococcal septicemia. Eighteen children (26%) died, including 10 with pneumococcal septicemia (5 cases) and 10 with Salmonella septicemia (5 cases). Poor prognosis factors include resistance to commonly used antimicrobial agents, frequently found with Salmonella organisms, and concomitant meningeal infection.     

Etiology of community-acquired pneumonia in 254 hospitalized children

BACKGROUND: Childhood community-acquired pneumonia is a common illness, but there have been relatively few comprehensive studies of the viral and bacterial etiology in developed countries. The aim of the present investigation was to determine the etiology of community-acquired pneumonia in hospitalized children by several laboratory methods. METHODS: In a 3-year prospective study a nasopharyngeal aspirate for viral studies and acute and convalescent serum samples for viral and bacterial serology were taken from 254 children with symptoms of acute infection and infiltrates compatible with pneumonia in the chest radiograph. The role of 17 microbes was investigated. RESULTS: A potential causative agent was detected in 215 (85%) of the 254 patients. Sixty-two percent of the patients had viral infection, 53% had bacterial infection and 30% had evidence of concomitant viral-bacterial infection. Streptococcus pneumoniae (37%), respiratory syncytial virus (29%) and rhinovirus (24%) were the most common agents associated with community-acquired pneumonia. Only one patient had a positive blood culture (S. pneumoniae) of 125 cultured. A dual viral infection was detected in 35 patients, and a dual bacterial infection was detected in 19 patients. CONCLUSIONS: The possible causative agent of childhood community-acquired pneumonia can be detected in most cases. Further studies are warranted to determine what etiologic investigations would aid in the management of pneumonia. With effective immunization for S. pneumoniae and respiratory syncytial virus infections, more than one-half of the pneumonia cases in this study could have been prevented.     

Treatment of pediatric outpatients with complicated urinary tract infections

In an open and prospective study involving outpatient children with complicated urinary tract infections (UTI), we evaluated the therapeutic efficacy of ceftriaxone administered intramuscularly, once-daily--50 to 70 mg/kg, during 8 to 10 days. Initially, the selected patients exhibited at least two of the following clinical criteria: age below 6 months, any degree of toxicity, fever, strong suspicion or proved abnormalities of their urinary tracts and lumbar pain in children older than 4 years. Significant bacteriuria was demonstrated by urine culture in 40 patients (21 boys, 19 girls), whose ages ranged from 15 days to 6 years 9 months (median 3 months). The radiological studies revealed vesicoureteral reflux in 6 patients, urethral posterior valve in 1, and neurogenic bladder in 4. The main causative agents were Escherichia coli isolated in 30 patients, Klebsiella (4) and Proteus (4). The treatment was found to be effective in 38 patients (95%). There was failure of treatment in 1 patient and a symptomatic reinfection in another one. It was concluded that children with complicated UTI could be treated alternatively by once daily ceftriaxone.     

过敏性紫癜患儿尿中中性粒细胞明胶酶相关脂质运载蛋白、尿胱抑素C水平测定及其意义

目的 检测过敏性紫癜(HSP)患儿尿中中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、尿胱抑素C(Cys C)、尿β<,2>-微球蛋白(β<,2>-MG)水平及24 h尿蛋白定量,探讨尿NGAL、Cys C在检测HSP患儿肾小管间质损伤中的临床意义.方法 选择临床诊断为HSP的患儿60例.根据24 h尿蛋白定量将患儿分为尿检末见异常组(A组,20例)、尿检轻度异常组(B组,20例)、尿检重度异常组(C组,20例)、治疗后病情好转组(D组,15例,均为C组治疗后患儿).选取在本院儿童保健门诊体榆健康儿章20例为健康对照组.其中15例患儿(B组5例,C组10例)行肾脏病理检查,并对肾小管间质进行病理评分.30例患儿(B组10例,C组20例)行尿蛋白电泳检查.设立尿NGAL、Cys C、β<,2>-MG的正常参考值上限,高于此值者视为异常,并计算异常率.结果 1.A、B、C组尿NGAL及Cys C水平升高,且呈递增趋势;D组尿NGAL水平与健康对照组比较无明显差异,尿Cys C水平较B组降低,但高于健康对照组.2.B组尿NGAL的异常率高于尿β<,2>-MG,尿Cys C的异常率与尿β<,2>-MG比较无明显差异;D组尿β<,2>-MG的异常率高于尿NGAL.3.尿NGAL、Cys C、β<,2>-MG水平与肾小管间质病理评分、尿蛋白电泳结果均呈正相关(r=0.638、0.471;0.661、0.321;0.405、0.342,P<,a><0.05).C组患儿小管间质病例评分、尿蛋白电泳(小管性)结果均高于 B组(P<,a><0.05).结论 尿NGAL、Cys C可作为监测HSP患儿早期肾小管间质损伤的指标,具有较高的灵敏度和特异性,优于传统指标尿β<,2>-MG.     

Aetiological agents, interleukin-6, interleukin-8 and CRP concentrations in children with community- and hospital-acquired pneumonia

OBJECTIVE: To determine the pathogens causing pneumonia in community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP) and to investigate serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8) and CRP in pneumonia caused by different aetiological agents. STUDY DESIGN: Eighty-seven children (mostly < 5 years of age) were recruited in a prospective study, 55 of them with CAP without prior antibiotic treatment and 32 with HAP. Thirty healthy outpatient children served as controls. RESULTS: The causative micro-organisms were determined by serological and microbiological methods in 40 cases with CAP (72.7%) and 30 with HAP (93.7%). In CAP, M. pneumoniae was the most common causative agent (43.6%), followed by S. pneumoniae (20%) and C. pneumoniae (18.1%). Bacteria alone were the sole causative agents in only 21.8% of cases with HAP. Pseudomonas aeruginosa (34.3%) and K. pneumoniae (32.5%) were the most frequently isolated. Although IL-6 and IL-8 levels were raised, there was no statistical difference between the CAP and HAP groups, or between bacterial and mycoplasma infections; neither was there a difference in CRP levels between these two groups. CONCLUSION: The causes of pneumonia differ between CAP and HAP. Levels of IL-6, IL-8 and CRP are raised in pneumonia but are unhelpful in differentiating the various aetiologies.     

New insights into pediatric rhinosinusitis

Rhinosinusitis is a common children's disease. Most cases are acute, follow an episode of common cold, and are the consequence of a superimposed bacterial infection. If mild, they are characterized by the persistence of signs and symptoms of upper respiratory tract disease for more than 10 days; if severe, they involve fever and a purulent nasal discharge, and can cause a substantial decline in general health. Recurrent acute or chronic cases are usually diagnosed in children with predisposing factors, such as recurrent respiratory tract infections, allergic rhinitis, cystic fibrosis, immunodeficiency, ciliary dyskinesia, anatomic abnormalities or reflux. Therapy is based on antibiotics, administered orally in mild, and intravenously in severe cases. On the basis of recently highlighted antibiotic resistances and the possibility of spontaneous resolution, experts agree in considering amoxicillin the drug of choice for mild cases, and an antibiotic capable of overcoming all possible resistance for severe cases.     

Factor V 1691 G-A mutation in children with intracardiac thrombosis: a prospective study

The objective of this study was to determine the association between intracardiac thrombosis and hereditary causes of thrombophilia, including factor V 1691 G-A (factor V Leiden, FVL) and prothrombin 20210 G-A mutations. Over a period of 3 y, genetic risk factors were evaluated in 13 consecutive children (mean age 6.27 ±5.44 y) with intracardiac thrombosis, diagnosed by cross-sectional echocardiography. Thrombi were localized in the left heart in four patients and the right heart in nine patients. All children had predisposing factors for thrombus formation: ventriculoatrial shunt for hydrocephalus ( n = 3), indwelling catheter for chemotherapy ( n = 5), cardiomyopathy ( n = 2), sepsis ( n = 1), homocystinuria ( n = 1) and tetralogy of Fallot ( n = 1). Six of the 13 children with intracardiac thrombosis were heterozygotes for FVL mutation. Three of these six children with FVL mutation had ventriculoatrial shunt for hydrocephalus, two children had cardiomyopathy and one had sepsis. None of the patients carried the prothrombin 20210 G-A mutation.

Conclusion : It is recommended that FVL mutations should be investigated in all cases of intracardiac thrombosis irrespective of whether or not a predisposing factor is identified. When a predisposing factor is found antithrombotic prophylaxis may be considered in patients carrying the FVL mutation.     

Clinical response to antibiotic therapy for community-acquired pneumonia

Childhood community-acquired pneumonia is a common and potentially serious problem worldwide. Unless the patient has bacteraemia or pleural empyema, aetiological diagnostics are limited and antibiotic treatment is empirical. Published data on expected response to therapy are scarce. To determine the clinical response to antibiotic treatment in a developed country in otherwise healthy children with community-acquired pneumonia, we conducted a prospective study of 153 hospitalised children with pneumonia. The role of 17 microbes as potential causative agents was evaluated. The duration of fever (>37.5°C) and hospitalisation were studied as objective measures of recovery. A potential aetiology was found in 83% of 153 patients: 29% of the patients had sole viral and 26% sole bacterial and 29% mixed viral-bacterial infections. The median duration of fever after the onset of antibiotic treatment (mainly penicillin G) was 14 h and the median duration of hospitalisation was 48 h. Patients with mixed viral-bacterial infection became afebrile more slowly than those with either sole viral or sole bacterial infections. Conclusion: the findings indicate that in a developed country, children with pneumonia make a rapid, uneventful recovery needing only a short hospital stay. Expensive and time-consuming microbiological investigations are not required once bacterial sepsis has been excluded.Abbreviations CAP community-acquired pneumonia - RSV respiratory syncytial virus     

The number of podocyte slit diaphragms is decreased in minimal change nephrotic syndrome

The pathophysiology of proteinuria in acquired kidney diseases is mostly unknown. Recent findings in genetic renal diseases suggest that glomerular epithelial cells (podocytes) and the slit diaphragm connecting the podocyte foot processes play an important role in the development of proteinuria. In this work we systematically evaluated the podocyte slit pores by transmission electron microscopy in two important nephrotic diseases, minimal change nephrotic syndrome (MCNS) and membranous nephropathy (MN). As controls, we used kidneys with tubulointerstitial nephritis (TIN). Effacement of podocyte foot processes was evident in proteinuric kidneys. However, quite normal looking foot processes and slit pores with varying width were also observed. Careful analysis of slit pores revealed, that the proportion of the pores spanned by the linear image of slit diaphragm, was reduced by 39% in kidneys from MCNS patients (1265 pores analyzed) compared with TIN samples (902 pores analyzed, p = 0.0003). To enhance the detection rate of the slit diaphragms, the "empty" podocyte pores were further analyzed with tilting series from -45 to +45. This revealed the linear diaphragm image in 71% and 26% of the slits in TIN and MCNS kidneys, respectively (p = 0.0003). In contrast to findings in MCNS, no significant reduction of the slit diaphragms were seen in MN kidneys compared with the controls. The results suggest that MCNS is associated with disruption of glomerular slit diaphragms.