Intensified hemodialysis regimens: neglected treatment options for children and adolescents

During recent years, the importance of intensified dialysis regimens has gathered increasing interest, especially after the Hemodialysis (HEMO) Study Group reported that a higher dose of thrice-weekly hemodialysis failed to improve clinical outcomes. Long nocturnal hemodialysis (three to six times per week) or short daily hemodialysis are the currently used forms of intensified dialysis. There is substantial evidence for cardiovascular and quality-of-life improvements as well as financial benefits with intensified hemodialysis. Preliminary experience with daily hemodialysis and hemodiafiltration in children has been reported. Given the continuing shortage of donor organs for kidney transplantation, the increasing incidence of end-stage renal disease (ESRD) and recognition of the deleterious effects of long-lasting ESRD, growth retardation, and poor social rehabilitation, more intensified dialysis regimens are a much-needed therapeutical option in both adults and children.     

Growth and height in children after liver transplantation

Abstract  To assess the linear growth after liver transplantation, height curves were constructed for 45 children who underwent liver transplantation at the Children's Hospital 19 La Pa 9, Madrid, and were followed for more than 2 years. The prednisolone dose was progressively tapered and switched to alternate-day administration at 12 months. Growth was severely impaired during daily steroid therapy but the mean growth rate normalized in the second year and a significant improvement was observed in successive years. Observations over a long period revealed flucting growth rates under stable or decreasing doses of prednisolone on alternate-day administration. Beyond the first year, some annual periods of abnormal growth rate occurred in 57 % of the children. Marginally better posttransplantation growth was observed in children transplanted for intrahepatic chole-static diseases. The prednisolone dose did not correlate with growth rate. In the long term, short stature was highly prevalent due to an accumulation of factors: previous disease, daily prednisolone period, inconstant growth rate under alternate-day steroid therapy, and puber-tal delay.     

Comparison of growth retarding effects induced by two different glucocorticoids in prepubertal sick children: An interim long-term analysis

Summary The low interference with growth expected in child for a cortisol analogue, deflazacort (DFZ), prompted us to verify if DFZ could affect growth less than prednisone (PDN). An interim analysis relative to 27 girls and 38 boys (out of 100 expected) age 3–12 yrs, after a median period of 14 mo.s is reported. Children with connective tissues (CTD) and glomerular disorders (KD) were randomly allocated to DFZ or PDN. Anthropometric measurements and maturity ratings were performed. Mean daily doses of PDN (or DFZ equivalent), from 0.57 to 0.64 mg/kg (DFZ 0.92 to 0.94 mg/kg) to induce control and from 0.19 to 0.93 mg/kg (DFZ 0.34 to 0.36 mg/kg) to maintain disease under control were given in CTD and KD, respectively. The increase in bone age delay over time was significantly>for PDN(-4.0 mo/yr) than DFZ (-1.8 mo/yr) in the overall group. The increases in statural age delay and loss over time were significantly> for PDN (-5.9 and-5.9 mo/yr) than DFZ (-2.4 and-2.4 mo/yr), only in children with “taller” midparents. Although doses of DFZ 1.1–1.8 times those of PDN were given, growth retardation in PDN-treated children was nevertheless 2.3–2.5 times that in DFZ-ones.     

Protein Z and natural anticoagulants in children on peritoneal dialysis and hemodialysis

Hemostatic alterations due to abnormalities in the coagulation and fibrinolytic system may occur in dialysis patients. Protein Z (PZ) is a vitamin K-dependent coagulation protein promoting assembly of thrombin with phospholipid vesicles. The aim of this study was to investigate PZ and natural anticoagulants in children on hemodialysis (HD) and peritoneal dialysis (PD). Protein Z, protein C (PC), protein S (PS), antithrombin III (AT III), and fibrinogen levels were studied in 24 PD, 13 HD patients and 23 controls. Plasma PZ levels in patients on HD were significantly higher than those on PD and control group (p = 0.04, p = 0.03). We observed elevated PC, PS and AT III activities in children on PD when compared to controls (p = 0.011, p = 0.003, p < 0.001). In HD patients, only PS activity was increased compared to controls (p = 0.016). PC and PS activities did not differ between PD and HD patients whereas AT III activity was higher in PD patients compared to HD patients (p < 0.001). Normal/high levels of PC, PS and AT III suggest that children on PD or HD treatment do not seem to have an increased risk of thrombogenesis due to reduction of these proteins. Increased PZ levels, however, might contribute to the hemostatic alterations in children on HD treatment along with other well known abnormalities.     

Kidney growth and renal functions under the growth hormone replacement therapy in children

Objective: The aim of this study was to investigate the kidney growth and renal functions in children receiving recombinant human growth hormone (rhGH) treatment. Materials and methods: A total of 37 children who received rhGH for 1.5 years before the study was started and 48 healthy controls were included at first evaluation. Hormone levels were determined and kidney sizes were measured by ultrasound. Kidney functions were assessed by serum creatinine and estimated glomerular filtration rate (eGFR). After 3 years of first evaluation, 23 patients were re-assessed. Results: Kidney sizes were found to be lower in rhGH received children compared with controls at first evaluation (p?0.05). Significant positive correlations were found between anthropometric measurements and kidney length and kidney volume (p?0.05). Height was the most significant predictor of kidney volume in rhGH received children (p?0.001). After 3-years of follow-up significantly increases were found in kidney length and volume compared with the first measurements (p?0.05). Increase percentage of body height was similar to increasing percent of kidney length and liver long axis (14.2%, 11.7.1% and 7.7%, respectively, p?>?0.05). Although no abnormal renal function test results were found at first and second evaluations; rhGH received children had significantly lower eGFR, at first evaluation, compared with controls; however, renal functions significantly increased after 3 years of follow-up (p?0.05). Conclusions: In conclusion, effect rhGH treatment on kidney growth is parallel to growth in body height and other visceral organs. A 3-years rhGH treatment resulted in significant increases in renal functions.     

Impact of parathyroidectomy on the fibroblast growth factor-23 in hemodialysis patients

Objective To study the effcts of total parathyroidectomy with autotransplantation (tPTX+AT) on fibroblast growth factor -23 (FGF - 23) in maintenance hemodialysis (MHD) patients with severe secondary hyperparathyroidism (SPTH). Methods Maintenance hemodialysis patients with severe SPTH treated in our hospital from 2014 to 2016 were enrolled and divided into two groups: tPTX+AT group and non-surgical group. Two groups' biochemical indexes and FGF-23 level before and after 6 months treatment were compared. Results A total of 48 patients were included in the study, including 22 in the tPTX+AT group and 26 in the non-surgical group. Age, duration of dialysis, primary disease, rate of hypertension, parathyroid hormone (iPTH), FGF-23, cholesterol (TCH), triglyceride (TG), albumin (ALB), and hemoglobin (HGB) level showed no significant difference between the two groups (P＞0.05); but serum calcium and alkaline phosphatase (ALP) of that tPTX+AT group were significantly higher than those of the non-surgical group (P＜0.01). After 6 months the blood iPTH, calcium, phosphorus and the calcium-phosphorus product level of tPTX+AT group were significantly lower than those of non-surgical group (P＜0.05). Blood lipids, propagated, HGB, and ALP level had no statistical differences in the two groups (P＞0.05); serum FGF-23 progressive declined after 1 week, 1 month, 3 month and 6 month in tPTX+AT patients, and after 6 months, the level of FGF-23 was significantly lower than that of non-surgical patients[1462.9(903.7, 5826.9) ng/L vs 12 627.9(5488.9, 16 844.4) ng/L, P＜0.01]. Conclusion tPTX+AT can significantly alleviate calcium and phosphorus metabolism disorders and in 6 months gradually reduce FGF-23 level in patients receiving MHD.     

成纤维细胞生长因子23在血液透析患者磷和维生素D代谢中的作用

目的 探讨成纤维细胞生长因子23（FGF-23）在维持性血液透析（MHD）患者磷和维生素D代谢中的作用及相关调控机制。 方法 采用酶联免疫分析法（ELISA）对59例MHD患者（血透组）及20例健康志愿者（对照组）进行血清全段FGF-23测定，同时应用放免法测定血清1，25-二羟维生素D（1,25(OH)2VitD）水平。血透组患者测定血清白蛋白（Alb）、血红蛋白（Hb）、血肌酐（Scr）、尿素氮（BUN）、钙（Ca）、磷（P）及全段甲状旁腺激素（iPTH）等指标。 结果 血透组血清FGF-23水平明显高于对照组[（215.23±123.55）比（28.72±11.49） ng/L，P < 0.01]，而血清1,25(OH)2VitD水平明显低于对照组[（13.25±8.73）比（42.24±12.45） μg/L，P < 0.01]。Pearson相关分析显示，血透组血清FGF-23水平与血清P、Scr、Ca、iPTH及透析疗程时间呈正相关（P < 0.05）；与血清1,25(OH)2VitD水平和年龄呈负相关（P < 0.05）；而与性别、血压、血清Alb、Hb、BUN等指标无相关。多元回归分析显示，血清P、Ca、Scr、iPTH和1,25(OH)2VitD是影响血清FGF-23的主要变量，5者组成的模型解释了总变异的约62%（R2=0.623，P < 0.01）。 结论 MHD患者血清全段FGF-23水平明显增高，而1,25(OH)2VitD水平明显降低。FGF-23的调控是由复杂的多种因素共同作用的结果，血清P、Ca、Scr、iPTH和1,25(OH)2VitD是影响血清FGF-23水平的主要调控因子。     

Kidney growth in children with congenital hypothyroidism

The effect of hypothyroidism on kidney size has not been studied in children. The aim of this study was to examine the role of congenital hypothyroidism and levothyroxine (L-thyroxine) treatment on renal growth. Forty children with congenital hypothyroidism and 37 healthy controls were prospectively included. The mean age of patients was 8.2+/-4.7 years. Patients had lower height and weight standard deviation scores compared with controls. The mean L-thyroxine initial age and treatment duration were 37.0 and 60.5 months, respectively. In 62.5% of patients, L-thyroxine was initiated after 6 months of age, and 60.0% of patients had severe hypothyroidism. Patients had lower kidney length and total kidney volume compared with controls (P < 0.05). No significant differences were found in kidney volume/body weight and kidney volume/ body height ratios between patients and controls (P > 0.05). Multiple regression analysis showed significant relationship between relative kidney volume and average free thyroxine level (P < 0.05). No significant differences in kidney sizes were found between patients who had L-thyroxine initiated before and after 6 months of age or between mild/moderate and severe hypothyroidism at diagnosis (P > 0.05). In conclusion, normal renal growth can be accomplished with L-thyroxine replacement despite considerable delay in treatment initiation and/or severe hypothyroidism.     

Meropenem pharmacokinetics in children and adolescents receiving hemodialysis

The emergence of multi-drug-resistant bacteria is of great concern to the care of pediatric end-stage renal disease (ESRD) patients who receive either hemodialysis or peritoneal dialysis via a catheter. Infections with gram-negative organisms, especially Pseudomonas aeruginosa, are difficult to eradicate and often necessitate catheter removal. Meropenem, a broad-spectrum antibiotic of the carbapenem class of beta-lactams, is effective against most gram-positive and gram-negative bacteria and has enhanced activity against P. aeruginosa. We studied the pharmacokinetics of meropenem during and between hemodialysis treatments in seven pediatric patients. Meropenem was given as a single dose of 20 mg/kg (maximum 500 mg) before and after two separate hemodialysis treatments. Meropenem administration was tolerated without any adverse effects. Hemodialysis effectively cleared meropenem in a manner that correlated with percent urea reduction. Median drug half-life was 7.3 h off dialysis (range 4.9-11.7 h). The dose of 20 mg/kg was not sufficient to produce an acceptable interdialytic pharmacodynamic profile of 70% duration with a meropenem concentration >4 microg/ml, the MIC90 of meropenem for P. aeruginosa. Dosing simulations revealed that a daily dose of 25 mg/kg or an alternate day dose of 40 mg/kg would result in an acceptable pharmacodynamic profile. Both simulated doses achieved acceptable peak concentrations.     

Risk factors for early peritoneal dialysis catheter failure in children

Background

There is uncertainty regarding the optimal approach for surgical placement of peritoneal dialysis (PD) catheters in children. Operative technique, catheter selection, and patient variables (eg, age or prior surgical history) may influence catheter lifespan.

Methods

A retrospective review of all PD catheters placed at a tertiary children's medical center during a 6-year period was performed. Our primary outcome was catheter function 2 months after placement. Data were analyzed using Student 2-tailed t test or χ² analysis.

Results

There were 121 PD catheters placed in 81 patients. The median primary functional catheter lifetime was 109 days. Primary PD catheter failure (within 2 months) occurred in 36 catheters (30%). Patients with primary catheter failure (8 ± 7 years) were younger than patients with a functioning catheter at 2 months (12 ± 5 years; P = .002). Catheters placed without simultaneous omentectomy were more likely to fail (P = .042). Catheter failure rate was not significantly different based upon operative technique or catheter type.

Conclusion

Omentectomy at the time of catheter placement decreased the risk of early catheter failure. In contrast, type of catheter or laparoscopic placement did not influence the likelihood of early catheter failure.     

Laminin and transforming growth factor beta-1 in children with vesicoureteric reflux

High-grade vesicoureteric reflux (VUR) promotes the development of renal nephropathy (RN) due to scar formation. This process involves transforming growth factor beta-1 (TGF beta₁), which stimulates production of the extracellular matrix proteins, including laminin (LN). The aim of the study was to assess LN and TGF beta₁ concentration according to VUR grade. The study group (1) consisted of 54 patients aged 6.23 ± 4.15 years with VUR, including: A, 19 with grade II; B, 19 with grade III; and C, 16 with grades IV or V reflux. The control group (2) contained 27 healthy patients aged 6.76 ± 4.02 years. LN and total TGF beta₁ concentrations in serum and urine were determined by the immunoenzymatic (EIA) method. To assess total serum TGF beta₁ levels, we used a solid-phase enzyme-linked immunosorbent assay (ELISA). Both serum and urinary levels of LN and TGF beta₁ in VUR patients were higher compared with controls (p < 0.05). The highest urinary concentration of LN and TGF beta₁ was found in subgroup C. A positive correlation was noted between urinary TGF beta₁ and LN. Increased TGF-beta₁ and LN levels in urine of high-grade VUR children suggests a potential role in fibrogenesis. Further trials are needed to investigate the role of serum and urinary LN level in VUR children.     

A pilot study of twice-weekly exercise during hemodialysis in children

Few published studies have assessed the exercise capacity and/or the effect of exercise in children receiving maintenance hemodialysis (HD). The aim of this study was to determine if twice-weekly exercise for 1 h during HD could improve exercise capacity in children receiving HD. We assessed lower extremity strength (Biodex; dominant extension peak torque in 60° per second, Newton-meters), grip strength (dynanometer, kilogram) and 6-min walk capacity (yards) in ten children (median age 13.6 years, range 8–25 years) at baseline and after 3 months of twice weekly exercise for 1 h during HD. Baseline assessment revealed a mean (1) Biodex of 70 ± 32 N-m/s, (2) 6-m walk test of 589 ± 90 yards and (3) grip strength of 23.2 ± 10 kg, which were 50% lower than the normal value for healthy controls. Patients demonstrated significant improvements in lower extremity strength and 6-min walk test after 3 months of exercise. Our data show that twice-weekly exercise of a moderate intensity during HD can lead to exercise capacity improvement in 3 months. We identified barriers to and strategies for the successful implementation of intradialytic exercise. We suggest that intradialytic exercise intervention may be effective to improve exercise capacity in children receiving maintenance HD.     

Recombinant human erythropoietin dosage in children undergoing hemodialysis and continuous ambulatory peritoneal dialysis

The efficacy of erythropoietin (EPO) in 11 children on hemodialysis (HD) and 8 on continuous ambulatory peritoneal dialysis (CAPD) (mean age 11.8 years) was compared. The initial EPO dose was 50 U/kg s.c. once a week; the time of observation was 24 weeks. In the CAPD group, the mean hemoglobin (Hb) level increased from 7.7±0.2 to 11.2±0.6 g/dl (P< 0.001) and hematocrit (Hct) from 22.3±1.0 to 32.6±1.4% (P<0.001), while in the HD group the mean Hb rose from 7.7±0.6 to 9.3±0.8 g/dl (P<0.001) and mean Hct from 22.7±2.3 to 27.6±2.8% (P<0.001) after 12 weeks of observation. An increase in Hb to over 10 g/dl was obtained in 87.5% of children on CAPD but in only 10% on HD after 8 weeks of EPO treatment. After 12 weeks of treatment, all children on CAPD had the target Hb level of more than 10 g/dl, while 7 children on HD required increased doses of EPO (100 U/kg per week). We conclude that the EPO dose of 50 U/kg given s.c. once a week is effective for children with anemia on CAPD but is insufficient for children on HD. Received June 17, 1996; received in revised form January 24, 1997; accepted March 4, 1997     

Analysis of growth in children after orthotopic liver transplantation

Growth after pediatric liver transplantation is an important factor in determining the quality of life. We collected data on height, skeletal age, and liver function of 45 consecutive pediatric transplant recipients and assessed the influence of primary diagnosis, liver function, and immunosuppressive regimen on their growth. Height and skeletal age were plotted as median standard deviation scores versus years post-transplantation. Growth, in terms of both height and skeletal age, were continuous without catch-up growth. Primary diagnosis was found to have no influence on height and poor liver function had a negative effect on both height and skeletal growth. A higher alternate day prednisolone maintenance dose also had a negative effect on skeletal growth. Thus, it can be concluded that a pretransplant lack of growth will not be restored and is an indication for early transplantation in endstage liver disease, especially in younger children.     

缓慢低效透析滤过对维持性血液透析患者低血压状态的影响

目的探讨应用持续缓慢低效每日透析滤过（SLEDI）-f）对于维持性血液透析（MHD）患者合并低血压状态的临床治疗效果。方法选择我院血液净化中心合并低血压状态的MHD患者36例,应用SLEDI）-f治疗,观察每次治疗过程中患者生命体征指标（血压、脉搏、心率、体温）、血氧饱和度,记录总超滤量、尿素氮和血肌酐变化并计算尿素清除指数（Kt／V）;整个疗程治疗前、后行彩色多普勒超声检测心功能指标,同时监测C反应蛋白（CRP）。结果治疗过程中,患者生命体征稳定,并发症少,透析充分性好。治疗后,患者左心室舒张末期内径（LVDd）较治疗前降低（P〈0．05）,心脏指数（CI）及左心室射血分数（LVEF）较治疗前升高（P〈0．05）,CRP较治疗前降低（P〈0．01）。结论采用SLEDI）-f治疗可提高MHD合并低血压状态患者对治疗的适应性,显著改善心功能指标,有助于提高患者治疗效果。     

Recombinant human growth hormone in infants and young children with chronic renal insufficiency

Children with chronic renal insufficiency (CRI) secondary to congenital structural abnormalities frequently have significant growth retardation by 2 years of age. In a multicenter placebo-controlled study of the use of recombinant human growth hormone (rhGH), 30 of 125 (24%) participants were<2.5 years of age at enrollment. Since the treatment arms of the study were balanced for age at randomization, data for these patients were examined for efficacy and safety. During the first 2 years of the study, approximately two-thirds of the patients (n=19) received rhGH 0.05 mg/kg per day subcutaneously and one-third (n=11) received placebo injections. At entry into the study, the mean (± SD) calculated creatinine clearance was 29.2±14.3 (range 12.0–63.7) ml/min per 1.73 m² in the rhGH-treated group and 23.3±15.1 (range 8.0–59.4) ml/min per 1.73 m² in the placebo-treated group. The 1st year growth rate was 14.1±2.6 cm/year for the rhGH-treated group and 9.3±1.5 cm/year in the placebo-treated group (P<0.00005). During the 2nd year of the study, the growth rate was 8.6±1.2 cm/year in the rhGH-treated group compared with 6.9±1.0 in the placebo groupP=0.025). The height standard deviation score was +2.0±0.7 for the rhGH-treated group compared with –0.2±1.1 in the placebo-treated group (P<0.00005) during the 2 years of the study. Minor adverse events occurred with similar frequency in both groups. These data suggest that rhGH is efficacious and safe in children with CRI under age 2.5 years. rhGH therapy may correct significant loss of growth at this age when used in conjunction with optimal medical management.     

Leptin and plasminogen activator inhibitor-1 levels in children on chronic dialysis

Abstract

Purpose: In this study, it is aimed to compare the serum leptin and PAI-1 levels and evaluate their relationship in children on hemodialysis (HD) and peritoneal dialysis (PD). Method: Thirty-six patients on HD (mean age: 15.0?±?2.8 years), 19 patients on PD (mean age: 13.0?±?3.5 years) and 15 healthy subjects (mean age: 14.5?±?2.7 years) were included in the study. Laboratory investigations included blood count, biochemical parameters, serum iron, iron binding capacity, parathormone, erythrocyte sedimentation rate, C-reactive protein (CRP), prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, serum leptin and PAI-1 levels. Results: Serum leptin levels were significantly higher in HD group than in control group when the effects of BMI and sex were controlled, while PD and control groups had similar leptin levels. PAI-1 levels were also significantly higher in HD group than in control group, while there was no statistically significant difference in PAI-1 levels of PD and control group. PAI-1 levels and leptin levels were significantly correlated, which was independent of the effect of BMI in both HD and PD groups when they are evaluated separately. Conclusion: Results of our study showed that HD patients had higher leptin and PAI-1 levels and leptin and PAI-1 levels were correlated significantly in both patient groups. The effect of elevated serum leptin and PAI-1 levels on the cardiovascular complications remains to be established.     

Chronic peritoneal dialysis in Turkish children: a multicenter study

Chronic peritoneal dialysis (CPD) has been utilized in the treatment of children since 1989 in Turkey. The aims of this study were to summarize our experience with CPD in children and to establish a pediatric registry data system in Turkey. Standard questionnaires were sent to all pediatric CPD centers. 514 patients treated between 1989 and 2002 in 12 pediatric centers were enrolled in the study. Reflux nephropathy was the most common (18.1%) cause of renal failure. Mean age at dialysis initiation was 10.1±4.6 years. Mean duration of dialysis was 24.1±20.5 months. Continuous ambulatory peritoneal dialysis (CAPD) was the first CPD modality for 476 (92.6%) patients, 142 of whom switched to automated peritoneal dialysis (APD) during follow-up. Currently, 47.3% of the patients are still on CPD, 15.4% were transplanted, 13.2% switched to hemodialysis, 16.7% died. The patient and technique survivals were 90% and 95% at one year and 70% and 69% at five years, respectively. The survival was significantly shorter in the youngest age group (0–24 months) compared to those in older age groups (p=0.000). We herein report the first results of the TUPEPD study providing information on demographic data and survival of pediatric CPD patients. As opposed to clear recommendations in favor of APD, there is a clear preponderance of CAPD in our pediatric CPD population. That vesicoureteral reflux (VUR) is still the leading cause of renal failure is a distressing finding. Remarkably lower survival rates and transplantation ratios are as striking and distressing as the high incidence of VUR among the causes of ESRD. We conclude that we must make a great effort to achieve better results and to change these undesirable events.     

Clinical characteristics and prognosis of peritoneal dialysis treatment in children with acute kidney injury

Objective To investigate the efficiency and safety of peritoneal dialysis (PD) in pediatric patients with acute kidney injury (AKI). Method A retrospective study of children who underwent PD for AKI in the First Affiliated Hospital of Xi’an Jiaotong University from 2003 to 2013 was performed, and the laboratory examinations, the causes, the complication, the prognosis and the risk factors were evaluated. Results The study included 48 children, with the age of (67.6±51.7) months (ranging from 3 months to 15 years old), including 31 males (64.6%) and 34 co-infections (70.8%). Primary glomerulonephritis (27.1%) was the most common cause of AKI, followed by the hemolytic uremic syndrome (18.7%) and drug induced AKI (18.7%). Peritoneal dialysis was performed manually using percutaneous or adapted catheters. The duration of PD during hospitalization was 11(7,14) days. PD treatment was highly effective in attenuation of toxics retention and correction of electrolyte disturbances (all P＜0.05). There were 3 cases of PD-related complications, including 1 case of peritonitis, 1 case of catheter outflow obstruction, 1 case of catheter exit site hematoma, and no child patient died of PD complications. Among the AKI children, 37 cases (77.1%) recovered with the PD treatment and had the catheter successfully removed till discharge, 7 cases (14.6%) needed further peritoneal dialysis and 4 cases (8.3%) died. The serum albumin level was significantly higher in patients who got recovered with PD treatment than other unrecovered cases [(32.6±6.7) g/L vs (23.2±4.3) g/L, t=-3.994, P＜0.001]. Conclusions PD can be safely and efficiently performed for the treatment of pediatric AKI. Low albumin level may be related to poor prognosis of AKI.