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1.
目的探讨环孢素A治疗儿童难治性肾病综合征的临床疗效。方法 26例难治性肾病综合征患儿入院后口服环孢素A,剂量为2~4mg(/kg·d),同时联合激素治疗,疗程3个月。治疗前及治疗后检测24h尿蛋白定量、血浆白蛋白、血浆胆固醇、尿素氮、血肌酐等指标。结果 26例患儿经治疗后,完全缓解14例,占53.85%;部分缓解10例,占38.46%;未缓解2例,占7.69%。结论环孢素A联合激素能有效治疗难治性肾病综合征。  相似文献   

2.
Acquired deficiency of anticoagulant proteins, due to loss in the urine, has been proposed as one of the major thrombogenic alterations in nephrotic syndrome (NS). Protein Z (PZ) is a single-chain vitamin K-dependent glycoprotein. Low PZ levels are reported to be a risk factor for thrombosis. The aim of this study was to investigate protein Z and other natural anticoagulant levels in children with NS. Thirty children aged between 1.5 and 12 years with NS (Groups I and II) and 19 age-and-sex-matched healthy controls (Group III) were enrolled into the study. Patients were divided into two groups: Group I (proteinuria >40 mg/m2/hr) and Group II (patients in remission). Plasma PZ levels in Group I were significantly lower than Group II (p=0.009) and group III (p=0.018). Plasma levels of AT III for Group I were significantly lower than for Groups II and III (p=0.009, p=0.005, respectively). Protein C levels in Group I were higher than in Group II and Group III (p=0.002, p=0.000, respectively). Protein Z levels positively correlated with serum total protein and albumin levels (p=0.003, p=0.003, respectively) and negatively with the degree of proteinuria (p=0.000). Protein Z levels were positively correlated with AT III (r=0.037, p=0.04). Along with the other coagulation abnormalities, decreased protein Z may contribute to increased risk of thromboembolic complications in children with NS. The negative correlation between proteinuria and PZ level suggests the possibility of renal PZ loss. Further studies are needed to investigate the mechanism and role of decreased PZ in NS.  相似文献   

3.
In this paper, we report the pharmacokinetics changes observed in seven children with steroid-resistant nephrotic syndrome (SRNS). They received cyclosporine A (CsA) microemulsion 6 mg/kg/day and, one week later, they were admitted to perform a 12-h pharmacokinetic profile with eight time sample points. The pharmacokinetic profile was repeated at 24 weeks of treatment, when all patients achieved remission. Blood concentration against time curves were constructed for each patient at weeks 1 and 24 of CsA treatment. Peak concentrations (C max) and the time needed to reach peak concentrations (t max) were directly determined from these plots. The area under the curve (AUC) was estimated by the trapezoidal rule. There was a statistically significant difference of the AUC, trough levels, and t max between weeks 1 and 24, with a decrease of AUC from 5,211 ng*h/ml in week 1 to 3,289 ng*h/ml in week 24, the trough levels decreased from 157 ng/ml to 96 ng/ml, and the t max decreased from 1.85 h to 1.00 h. The higher CsA bioavailability during the nephrotic state has to be considered when managing patients, since the target AUC cannot be the same throughout the treatment.  相似文献   

4.
The podocin (NPHS2) gene encodes podocin protein, which has an important role in glomerular ultrafiltration and controlling slit membrane permeability. The detection of an NPHS2 mutation affects the treatment plan for children with nephritic syndrome (NS). The frequency and spectrum of podocin mutations in the Turkish population have remained largely unknown. The aim of this study was to screen for podocin mutations in Turkish patients with steroid-resistant NS (SRNS) and to compare it with other published series. There were 295 children with SRNS, originating from Turkey, included in this study. Forty-one patients (13.8%) had familial NS and 254 patients (86.2%) had sporadic NS. Mutation analysis was performed in all eight exons of the NPHS2 gene with the direct DNA sequencing method. There were 53 different pathogenetic NPHS2 mutations detected, including 37 novel mutations. The mutation detection rate was 24.7% for all patients, 29.2% for familial, and 24% for sporadic SRNS. The most common mutated exon was exon 5 (52 allele). The presence of mutations in exon 4 was found to increase the risk of end-stage renal disease (ESRD). Among patients with mutations, the rates of renal failure and/or ESRD (26%) were significantly higher than in those without mutations (12.6%). The mean time of progression to renal failure and ESRD in patients with mutations (1.8 ± 2.5 years) was significantly shorter than in patients without mutations (3.7 ± 4.0 years). Additionally, in patients with heterozygote mutations, fewer cases (13.6%) progressed to renal failure and/or ESRD than in with patients who had homozygote/compound heterozygote mutations (31.3%). In conclusion, podocin mutations are responsible for some of both familial and sporadic SRNS cases in Turkey. The mutations in this gene should be searched for in every child after presentation with the first episode of NS.  相似文献   

5.
他克莫司在儿童原发性肾病综合征中的应用   总被引:5,自引:1,他引:4  
目的 研究他克莫司(TAC,FK506)在儿童原发性肾病综合征中的临床应用。 方法 65例患儿入院后根据不同的临床类型联合激素或逐渐减用激素,同时给予口服他克莫司,剂量0.1~0.15 mg/kg,每12小时1次,疗程6~24个月,并监测血药浓度。 结果 65例患儿经他克莫司治疗1~2个月后,尿蛋白逐渐减少;血清白蛋白迅速增加并恢复正常;胆固醇、三酰甘油均有不同程度的改善;总缓解率83.1%;显效时间为7~54 d。随访中12例出现复发。细胞亚群CD4增高时缓解率高。他克莫司药物代谢基因型为3/3型或3/1型缓解率高。微小病变型肾病(MCN)缓解率为96.4%;系膜增生性肾炎(MsPGN)为90.0%;膜性肾病(MN)为2/3;膜增生性肾炎(MPGN)为3/5;局灶节段性肾小球硬化症(FSGS)为4/9。他克莫司起始剂量为0.1~0.15 mg/kg,每12小时1次,治疗浓度控制在5~10 g/L时,本组患儿可获得缓解。12例出现厌食、恶心、呕吐;1例腹痛;2例头痛;1例震颤;3例失眠;4例出现一过性Scr上升;8例N-乙酰氨基葡萄糖苷酶(NAG)轻微增加;6例C3与α-2巨球蛋白增加。部分患儿在1周内恢复正常,其他患儿在他克莫司减药后症状消失。 结论 他克莫司对原发性肾病综合征患儿有良好的疗效,即使患儿肝功能异常、并发结核感染或有严重激素不良反应。他克莫司可替代环孢素A作为新的治疗用药。  相似文献   

6.
Cyclosporin A absorption profiles in children with nephrotic syndrome   总被引:1,自引:0,他引:1  
A single blood concentration measurement of Neoral 2 h after administration (C2) is a new concept in therapeutic drug monitoring (TDM). In most adult patients, the concentration of cyclosporin A (CyA) peaks within 2 h after Neoral administration. Therefore, monitoring the area under the concentration-time curve over the first 4 h post-dose (AUC0–4) is considered to be the most reliable strategy for Neoral TDM. In addition, C2 is considered to be the most accurate predictor of AUC0–4, with which C2 correlates best. Thus, in adult patients, C2 monitoring is recommended as the best single-point TDM method for Neoral. However, in paediatric patients, the effectiveness of C2 monitoring is still unclear. We examined the trough concentration (C0), C1, C2, C3, and C4 of CyA in 60 patients (1 to 20 years old, mean age 7.42±0.67 years) who had nephrotic syndrome treated with Neoral. The peak concentration of C0-C4 was C1 or C2 in 38 patients (early peak group) and C3 or C4 in 22 patients (late peak group). C2 in the late peak group was significantly lower than that in the early peak group (422±50.1 vs. 665 ±53.8 ng/ml, P =0.0008), although the administered doses of Neoral and C0 were similar between these groups. Therefore, TDM by C2 using the same standard as in the early peak group might result in an overdose of CyA in the late peak group. As the concentration peaked at 3 h or more after Neoral administration in the late peak group, AUC0–4 does not necessarily reflect the Neoral absorption profile. As more than 33% of the paediatric patients were in the late peak group, TDM by AUC0–4 or C2 should be used carefully in paediatric patients treated with Neoral.  相似文献   

7.
To better understand the role of nitric oxide (NO) in pediatric nephrotic syndrome, we measured nitrite/nitrate (NOx) in serum obtained from patients with several pediatric kidney diseases and investigated the locations of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS). NOx in serum showed significantly higher levels than those in healthy controls (mean ± SE: 297 ± 55.7 vs. 158 ± 13.1 pmol/10 μl). There was no significant difference between six patients with frequent relapse and five patients with nonfrequent relapse. The studies with immunostaining of iNOS and nitrotyrosine were negative for glomerulus in patients with nephrotic syndrome. Those findings suggest that NOx might indirectly influence disease progression in nephrotic syndrome.  相似文献   

8.
Serum and urine leptin concentration in children with nephrotic syndrome   总被引:3,自引:0,他引:3  
Literature data point to the relationship between leptin concentration and certain markers of the metabolic syndrome, including cholesterol, triglycerides and apolipoproteins. A substantial lipid metabolism disturbance occurs in children with idiopathic nephrotic syndrome (NS). The aim of the study was to find out whether in NS children, serum and urine leptin levels change proportionally to lipid metabolism disturbances. The study was performed on two groups: (I) 30 children with NS (A) before, (B) during, prednisone therapy after proteinuria regression; (II) 25 healthy children. Serum and urine leptin levels were determined by the immunoenzymatic ELISA method. Serum leptin level in NS children before and after treatment was similar to that in the control group ( p >0.05). Leptin urinary excretion in group A was approximately 60 times and in group B 24 times higher than in the controls ( p <0.01). Before treatment, children with NS had increased concentrations of TC, TG, LDL, -lipoprotein, apolipoprotein B (apo B) ( p <0.01) and reduced HDL and apolipoprotein A (apo A) ( p <0.01). The conclusions were that: (1) in NS children leptin urinary excretion increases but its level is unchanged in serum; (2) serum leptin level is correlated with lipid parameters.  相似文献   

9.
Background. Recent studies suggested the possible benefits of cyclosporine (CsA) therapy in patients with membranous nephropathy, although most of these studies were short-term. An uncontrolled retrospective study was undertaken to evaluate the long-term effect of CsA therapy on idiopathic membranous nephropathy presented with refractory nephrotic syndrome. Methods. The subjects were eight patients with idiopathic membranous nephropathy presenting with refractory nephrotic syndrome. All patients had received a course of corticosteroid therapy before CsA therapy, and had not responded to the corticosteroid, including one or two administrations of intravenous methylprednisolone pulse therapy. The CsA doses were adjusted to maintain trough blood level at 100 ng/ml during the first 3 months and then reduced to maintain the level at 50 ng/ml in patients who had responded to partial remission. Results. CsA therapy induced a marked decrease in proteinuria from the first month, and a significant decrease from month 3 and thereafter. The mean serum total protein and albumin levels rose, and total cholesterol fell significantly with CsA therapy. The serum creatinine level was unchanged during CsA therapy. Three patients showed complete remission and two were in partial remission, while three were nephrotic at 12 months of CsA therapy. From 18 to 24 months of CsA therapy, three patients were in complete remission, four were in partial remission, and one patient was nephrotic. There were no side effects of CsA, except for gum hyperplasia and hypertrichosis in one patient. Conclusion. These results suggest that long-term CsA therapy at a low or moderate dose is potentially effective and safe in most nephrotic patients with idiopathic membranous nephropathy refractory to corticosteroid therapy. Received: February 22, 1999 / Accepted: July 30, 1999  相似文献   

10.
Cyclosporin A (CsA) is an effective therapy for children with long-lasting nephrotic syndrome (NS). Long-term treatment can result in chronic CsA nephropathy (CsAN) and there is controversy concerning its incidence and severity. Trough levels are commonly used to monitor the drug concentration. We report a retrospective clinical and histological analysis of 18 children (12 males, 6 females) with steroid-dependent nephrotic syndrome (15 patients) and partially steroid-sensitive nephrotic syndrome (3 patients) treated with CsA for a long-term period (mean 4.9 years, range 2.2–6.9). Before CsA treatment all patients had normal creatinine clearance. CsA was started at a dose of 5 mg/kg per day administered orally in two divided doses and adjusted to maintain the mean CsA blood concentration between 250 and 350 ng/ml obtained from abbreviated area under the curve (AUC). A renal biopsy was performed after a mean period of 3.9 years (range 2.2–6.2) from the start of CsA treatment. Tubular, interstitial, and arteriolar lesions were evaluated in order to assess CsAN. The mean CsA dose and the mean CsA blood concentration were 4.4 mg/kg per day (range 3.6–5.8) and 276.6 ng/ml (range 162–346), respectively. No child had a worsening creatinine clearance during CsA treatment and follow-up after CsA discontinuation. If compared with the year before the start of CsA treatment, NS relapses and prednisone (PDN) dose significantly decreased during CsA treatment, 4/year versus 0.8/year (P <0.0001) and 0.9 mg/kg per day versus 0.2 mg/kg per day (P <0.0001), respectively. Histological analysis showed 15 patients with minimal change disease and 3 with focal segmental glomerulosclerosis. Clear-cut lesions diagnostic of CsAN were never found and only mild lesions were observed in 5 children (suggestive of CsAN in 2 patients and consistent with CsAN in 3 patients). Long-term CsA treatment is confirmed to be effective in preventing NS relapses and reducing PDN dose. Renal function is not a reliable indicator of CsAN. With the mean CsA blood concentrations used in our patients CsAN presented a low incidence (28%) and was generally mild. Renal biopsy should be performed 2–3 years from the start of long-term CsA treatment, especially if the mean CsA blood concentrations are not regularly monitored.  相似文献   

11.
We conducted a retrospective analysis of infections in 154 children (114 boys, 40 girls) with nephrotic syndrome who satisfied the International Study of Kidney Disease in Children criteria. Their mean age at onset of symptoms was 6.2 years (range 6 months to 16 years) and the mean duration of follow-up was 32 months (range 6–55 months). One or more infectious complications were observed in 59 of the 154 children (38%), with urinary tract infection being the commonest (13.7%), followed by pulmonary tuberculosis (10.4%), peritonitis (9.1%), skin infections (5.2%), upper respiratory infections (5.2%), lower respiratory tract infections (3.9%) and pyomeningitis (0.6%). There were 3 deaths, the mortality in 2 patients being attributable to infections. There was no significant difference between children who developed infection and those who didn't in terms of age of onset, sex, duration of disease, serum creatinine, blood urea nitrogen and 24-h proteinuria. However, the children who developed infectious complications had significantly higher serum cholesterol levels (P<0.01) and lower serum albumin levels (P<0.02). The frequency of infections was higher inchildren who were frequent relapsers, steroid dependent and subsequent non-responders (28/60) compared with infrequent relapsers and initial non-responders (29/94).  相似文献   

12.
The aim of this study was to examine the expression of P-glycoprotein (P-gp) in CD3 lymphocytes of children with nephrotic syndrome (NS) in relation to their clinical response to glucocorticoid (GC) treatment. The examinations were performed on two groups. The study group (I) consisted of 88 children aged 2.0–20.0 years with NS, divided according to their clinical response to GC: NFR—non-frequent relapse NS; FR—frequent relapse NS; SD—steroid-dependent NS. The control group (II) consisted of 18 healthy children never treated with GC. We measured P-gp expression on CD3 lymphocytes of patients with NS using a flow cytometry assay. The CD3/P-gp was significantly higher than in controls. The difference was higher in SD (P=0.0001) and FR - (P=0.0002) group. The difference in NFR was smaller. Mean CD3/P-gp (in percent) was twice as high in SD children than in NFR, and the difference, as between FR and NFR, was statistically significant (P<0.01). Worse response to GC or dependency may be due to overexpression of P-gp. Further examinations are necessary to establish whether increased P-gp activity is a result of MDR-1 polymorphism and to determine GC response, or to ascertain if such activity is only a result of GC therapy.  相似文献   

13.
Four children with steroid-sensitive nephrotic syndrome (SSNS) coexisting with type 1 diabetes are presented. This number is higher than expected according to the estimated prevalence rates for each disease separately. In three, diabetes preceded nephrotic syndrome (NS), and in one it developed almost simultaneously. None of the patients had hypertension or retinopathy. Two had a renal biopsy: in one it was compatible with minimal change histology (MCH), and the other had MCH and early diabetic nephropathy changes. In addition to the two presented here, in 11 of 12 previously reported cases with biopsy proven SSNS coexisting with type 1 diabetes, the biopsy showed MCH. In none was treatment influenced by biopsy results. However, our experience suggests that daily steroid taper allows easier glycaemic control than alternate day steroids. We conclude that the indications for a renal biopsy in nephrotic children with and without insulin-dependent diabetes mellitus (IDDM) should be similar. Received: 27 July 2001 / Revised: 15 January 2002 / Accepted: 15 January 2002  相似文献   

14.
目的分析儿童激素敏感性肾病综合征复发的原因,为合理治疗肾病综合征复发提供依据。方法对激素敏感性肾病综合征患儿进行定期随访检查,复发时进行详细病史询问、体检和血尿常规、血生化、血皮质醇测定,分析肾病复发的原因。结果纳入儿童激素敏感性肾病综合征93例,未复发28例(未复发组);复发65例,共计116例次复发,其中频复发31例(频复发组),非频复发34例(非频复发组)。复发原因最多为激素依赖和(或)免疫抑制剂依赖(占49.1%),之后依次为感染(占36.2%),激素停用(占1.7%),过敏和接种(占1.7%),外伤(占1.7%),10.3%原因不明。血清皮质醇水平减低在频复发组中的比例显著高于非频复发组和未复发组(P〈0.05和P〈0.01),而严重低血清白蛋白血症和低IgG血症在各组中无显著差别。结论糖皮质激素依赖和感染是儿童激素敏感性肾病综合征复发的主要原因,而血皮质醇水平低下可能是儿童激素敏感性肾病综合征出现频繁复发和激素依赖的重要机制。  相似文献   

15.
小儿原发性肾病综合征脂质紊乱与蛋白代谢异常的关系   总被引:12,自引:0,他引:12  
目的研究小儿原发性肾病综合征(INS)与蛋白代谢异常的关系。方法检测68例小儿INS7项脂质指标及5项蛋白代谢参数。采用SDSPAGE电泳检测其尿蛋白类型。结果INS小儿存在明显脂质紊乱,具有动脉粥样硬化、冠心病及进行性肾脏损害的危险因素结论尿白蛋白排泄率增加或中分子尿蛋白是脂质紊乱重要原因。尿白蛋白排泄率与脂质紊乱关系密切。  相似文献   

16.
Cyclosporine A (CsA) has relieved children with steroid-dependent nephrotic syndrome (NS) from steroid toxicity. However, most patients frequently relapse again when CsA is withdrawn, resulting in the development of CsA nephropathy for its long-term use. In order to assess the efficacy of mycophenolate mofetil (MMF) therapy, we prospectively analyzed 12 children with idiopathic steroid-dependent NS requiring long-term CsA therapy with MMF for at least 6 months. Mean follow-up after starting MMF was 11 months (range 6–42). The mean MMF dose required was 610±95 mg/m2/12 h, which maintained mean predose mycophenolic acid (C0-MPA) levels of 2.4±1.1 mcg/ml. Treatment with MMF resulted in CsA and/or prednisolone (PSL) sparing, with a reduction in mean CsA dose from 3.5±1.3 to 1.5±2.4 mg/kg/day (p<0.01), and mean PSL dose from 0.29±0.16 to 0.21±0.11 mg/kg/day (p<0.05). Nine of 12 patients (75%) were finally able to be weaned off CsA. Mean relapse rates decreased from 2.7±1.6 to 0.6±0.9 episodes/year (p<0.01). Relapse-free ratio on MMF therapy was lower in patients whose average C0-MPA levels were less than 2 mcg/ml (p<0.05). Our experience demonstrates that MMF therapy results in significant CsA and/or steroid sparing and reduction in relapse rates in children with CsA-dependent NS.  相似文献   

17.
Therapeutic guidelines are not available for children with minimal change nephrotic syndrome (MCNS) who experience frequent relapses or develop steroid resistance after a course of cytotoxic therapy. The records of nine children with biopsy-proven MCNS who received two courses of cytotoxic therapy with either chlorambucil or cyclophosphamide were reviewed to evaluate the length of remission, associated side-effects and long-term outcome. Initial cytotoxic therapy was given to five frequent-relapsing patients and four steroid-resistant patients 2–48 months (mean 16 months) following diagnosis of nephrotic syndrome. The second drug was given 4–85 months (mean 27 months) after the first. Steroid-resistant patients attained remissions of 0–81 months (mean 23 months) following the first agent and 13–67 months (mean 32 months) following the second. Frequent-relapsing patients experienced remissions of 0.5–24 months (mean 7.4 months) following the first cytotoxic drug and 3–72 months (mean 22 months) after the second. Remissions following the second agent were equal to or longer than those following the first in the seven patients who received both chlorambucil and cyclophosphamide. In the 19- to 128-month follow-up (mean 66 months), all four steroid-resistant patients experienced infrequent relapses which responded to prednisone. One frequent-relapsing patient remains in remission, three have chronic proteinuria and one still has a frequent-relapsing course. For the select group of patients who become frequent relapsing or steroid resistant after one course of cytotoxic therapy, a second course of cytotoxic therapy may allow time for catch-up growth, as well as improve steroid responsiveness once relapses occur.  相似文献   

18.
Forty-eight Arab patients with steroid-responsive childhood nephrotic syndrome were studied for the frequency of HLA-A,-B,-C and-DR antigens. HLA-DR7 was significantly increased in the patient group (63% vs. 28%,P=0.0002) confirming reports of a DR7 association in other ethnic groups and indicating a universal association with this antigen. HLA-CW6 was also significantly increased (44% vs. 21%,P corr.=0.042). HLA-DQW1 was significantly reduced in the patients (29% vs. 57%,P corr.=0.012) as was HLA-CW4 (6% vs. 24%,P corr.=0.042).  相似文献   

19.
Attempts to minimize the effects of prolonged steroid use in steroid-dependent nephrotic syndrome (SDNS) and the need to overcome steroid resistance (SRNS) justifies immunosuppressant therapy. We report our experience in a cohort of patients with SD/SRNS during the administration of mycophenolate mofetil (MMF) in a prospective protocol initiated in January 2001. Twenty-six children with idiopathic nephrotic syndrome were included (21 steroid dependent and 5 steroid resistant), whose response did not change after sequential treatment with cyclophosphamide (CPM) and cyclosporine (CsA). Histopathologic patterns were: 11 minimal change disease (MCD), 1 diffuse mesangial proliferation (DMP), 13 focal segmental glomerulosclerosis (FSGS) and membranous 1 glomerulonephritis (MGN). The median age of onset of NS was 2.8 years (range 1.2–12.5), and treatment with MMF was performed at a median age of 11.4 years (range 5–17) with an initial dose of 600 mg/m2/12 h, adjusted to maintain levels of mycophenolic acid (MPA) at 2.5–5 mcg/ml. The planned duration of study to assess treatment efficacy was 6 months. The mean MMF dose required was 624 (SD=136) mg/m2/12 h (range 415–970), which maintained mean C0-MPA levels of 2.9 (SD=1.17) mcg/ml (range 1.2–5.9 mcg/ml). In the five patients with SRNS, only one achieved complete remission. In the patients with SDNS, steroid sparing was achieved in 15 and 9 remained in remission on MMF monotherapy. Withdrawal of MMF resulted in immediate relapse in 47%. In our study, MMF was a useful immunosuppressant due to its fewer undesirable effects and similar efficacy to other drugs used. It appears effective for the maintenance of remission in SDNS patients, with a response similar to that of CsA.  相似文献   

20.
目的 通过测定。肾病综合征患儿激素不同治疗阶段的血清骨钙蛋白及血清碱性磷酸酶,探讨二者在泼尼松治疗时的内在关系及变化规律。方法 实验分3组:激素治疗前组,激素治疗和对照组。结果 肾病综合征患儿在激素治疗前血清骨钙蛋白水平明显低于对照组(P<0.05),而碱性磷酸酶与对照组相比差异无显著性(P>0.05);应用激素治疗后二者均明显低于激素治疗前组(P<0.05),血清骨钙蛋白水平和血清碱性磷酸酶水平呈正相关(P<0.05)。结论 血清骨钙蛋白和血清碱性磷酸酶都是反映成骨细胞功能活性的指标,激素治疗后患儿的成骨细胞功能受到显著抑制,导致血清骨钙蛋白和碱性磷酸酶水平降低。  相似文献   

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