Central venous lines for chronic hemodialysis: survey of the Midwest Pediatric Nephrology Consortium

Central venous lines (CVL) continue to be the most commonly used vascular access device for children on hemodialysis (HD). Despite their frequent use, little is known regarding the frequency of CVL-related intradialytic complications that could interfere with delivery of effective dialysis. To better assess this, we conducted a cross-sectional study of ten HD centers within the Midwest Pediatric Nephrology Consortium. Vascular access was provided by CVL in 61 of the 83 patients (73%) included. CVL dysfunction (defined as reduced blood flows, need for reversed lines, or frequent intradialytic alarms) occurred in 46% in the prior month. Treatment for suspected clots occurred in 16 patients. Intraluminal tissue plasminogen activator (tPA) was the preferred treatment for a suspected clot. The survey also inquired about the preferred treatment for documented clots, and intraluminal tPA was most preferred, followed by CVL stripping, CVL removal, CVL brushing, and systemic tPA. As for preventative strategies, most HD centers locked the CVL with intraluminal heparin in concentrations ranging from 1,000 to 5,000 U/ml. In conclusion, catheter usage rates and complications were highly prevalent in pediatric HD units in this study. As treatment strategies varied greatly, future prospective studies are needed to determine the effectiveness of each individual therapy.     

Influenza vaccine after pediatric kidney transplant: a Midwest Pediatric Nephrology Consortium study

The main aim of this study was to compare the response to trivalent inactivated influenza vaccine in children who received a kidney transplant and were on steroid-free versus steroid-based immunosuppression. Groups: 1. Kidney transplant recipients on steroid-free immunosuppression (n = 27); 2. Kidney transplant recipients on steroid-based immunosuppression (n = 39); 3. Healthy controls (n = 21). Hemagglutination inhibition titers against 2007–2008 A/H1N1 and A/H3N2 and B strains were measured before and 8 weeks postvaccination. Postvaccination geometric mean titers to A/H1N1 were significantly lower among both transplant groups than controls (p = 0.025 and 0.015, respectively). Postvaccination titers to H3N2 and B strains were not statistically different between groups. Proportions of participants developing seroprotection were not different among groups. Both kidney transplant groups seroconverted less than controls for A/H1N1 (p = 0.0002) and were no different from controls for B. For A/H3N2, the steroid-free group had the weakest seroconversion (p = 0.008), possibly due to mycophenolate-enhanced exposure and a younger age. Overall, children after kidney transplantation demonstrated a good serologic response to the inactivated influenza vaccine although somewhat lower than controls. Steroid-free immunosuppression did not seem to present an advantage in antibody response. Data on inactivated influenza vaccine safety and efficacy was collected and demonstrated absence of acute rejection or laboratory-proven influenza for 6 months postvaccination.     

Vitamin D in incident nephrotic syndrome: a Midwest Pediatric Nephrology Consortium study

Background

Cross-sectional studies of children with prevalent nephrotic syndrome (NS) have shown 25-vitamin D (25(OH)D) deficiency rates of 20–100 %. Information on 25(OH)D status in incident patients or following remission is limited. This study aimed to assess 25(OH)D status of incident idiopathic NS children at presentation and longitudinally with short-term observation.

Methods

Multicenter longitudinal study of children (2–18 years old) from 14 centers across the Midwest Pediatric Nephrology Consortium with incident idiopathic NS. 25(OH)D levels were assessed at diagnosis and 3 months later.

Results

Sixty-one children, median age 5 (3, 11) years, completed baseline visit and 51 completed second visit labs. All 61 (100 %) had 25(OH)D?<?20 ng/ml at diagnosis. Twenty-seven (53 %) had 25(OH)D?<?20 ng/ml at follow-up. Fourteen (28 %) children were steroid resistant. Univariate analysis showed that children prescribed vitamin D supplements were less likely to have 25(OH)D deficiency at follow-up (OR 0.2, 95 % CI 0.04, 0.6). Steroid response, age, and season did not predict 25(OH)D deficiency. Multivariable linear regression modeling showed higher 25(OH)D levels at follow-up by 13.2 ng/ml (SE 4.6, p?<?0.01) in children supplemented with vitamin D.

Conclusions

In this incident idiopathic NS cohort, all children at diagnosis had 25(OH)D deficiency and the majority continued to have a deficiency at 2–4 months. Supplemental vitamin D decreased the odds of 25(OH)D deficiency at follow-up, supporting a role for supplementation in incident NS.

     

Blood pressure and total peripheral resistance in children with chronic kidney disease

We performed a study to assess cardiac output (CO) and total peripheral resistance (TPR) at rest and during peak exercise with the goal to better define the role of these parameters in the development of hypertension in children with chronic kidney disease (CKD) stage 2–4. Fifty-two pediatric patients with CKD (mean age 12.7±3.7 years) and 28 healthy individuals of comparable age and sex participated in the study. At rest, children with CKD had a significantly higher systolic and diastolic blood pressure (BP) and calculated mean arterial pressure (MAP) than healthy controls. Total peripheral resistance was significantly higher in children with CKD than in controls (1627.7±534.6 vs 1354.6±338.9 dyne×s×cm^–5, p =0.02). There was no significant difference in heart rate or CO between the two groups. Children taking antihypertensive medications had lower TPR than children without BP medications (1514.6±439.6 vs 1788.2±505.4 dyne×s×cm^–5, respectively, p =0.06). At peak exercise, children with CKD had a significant increase in MAP, heart rate and CO and had a significant decrease in TPR (difference between rest and peak exercise: –782.4±375.9 dyne×s×cm^–5, p <0.001). Children taking BP medications had blunted MAP and CO responses when compared to controls ( CO: 6.2±2.8 l/min vs 9.8±4.5 l/min, respectively, p =0.01; MAP: 13.9±10.2 mmHg vs 21.5±11.7 mmHg, respectively, p =0.01). Children without BP medications had a similar to controls response to exercise in respect to CO, MAP and TPR. We conclude that increased TPR is a major contributor to elevated blood pressure in children with CKD and suggest that BP medications decreasing vascular resistance should be used as a first line of antihypertensive therapy in these patients.     

Severe cardiac hypertrophy and long-term dialysis: the Midwest Pediatric Nephrolgy Consortium study

Cross-sectional studies have demonstrated that left ventricular hypertrophy (LVH) is common in children on maintenance dialysis. We report the echocardiogram results of 17 children from seven centers in the Midwest Pediatric Nephrology Consortium who have spent at least 2 years on maintenance dialysis and had three consecutive echocardiograms: at initiation of dialysis therapy and 1 and 2 years later. The results indicate that LVH is prevalent at the initiation of dialysis (82%) and remains both frequent (82%) and severe (59%) after 2 years of maintenance dialysis. Normalization of LV geometry was unlikely: the prevalence of concentric LVH increased and the prevalence of eccentric LVH did not change over time, indicating poor blood pressure and volume status control in these patients. We conclude that children on maintenance dialysis are at high risk for future cardiovascular disease.     

Treatment outcome of late steroid-resistant nephrotic syndrome: a study by the Midwest Pediatric Nephrology Consortium

Background

Idiopathic nephrotic syndrome (NS) in children is classified as steroid sensitive or steroid resistant. Steroid sensitivity typically portends a low risk of permanent renal failure. However, some initially steroid-sensitive patients later develop steroid resistance. These patients with late steroid resistance (LSR) are often treated with immunosuppressant medications, but the effect of these additional drugs on the long-term prognosis of LSR is still unknown.

Methods

A retrospective chart review was performed on patients diagnosed with idiopathic NS and subsequent LSR during the 8-year study period from 2002 up to and including 2009, with a minimum of 2 years of follow-up. Primary outcome measures were proteinuria and renal function.

Results

A total of 29 patients were classified as having LSRNS. The majority of patients received treatment with calcineurin inhibitors and/or mycophenolate mofetil. Seven patients received three or more non-steroid immunosuppressant medications. Sustained complete or partial remission was achieved in 69 % of patients. Three developed end-stage renal disease, and all others maintained normal renal function. There were 13 episodes of serious adverse events, none of which were fatal or irreversible.

Conclusion

Most patients with LSRNS responded to immunosuppressive therapy by reduction or resolution of proteinuria and preservation of renal function. The results suggest that immunosuppressive treatment is a viable option in NS patients who develop LSR.     

Iron therapy in the pediatric hemodialysis population

Iron therapy maintains iron stores and optimizes the response to recombinant human erythropoietin (r-HuEPO) in patients with end-stage renal failure. Information is limited, however, regarding the preferential route of iron administration in pediatric patients receiving hemodialysis. Therefore, we prospectively randomized 35 iron-replete patients (aged >1 to <20 years) to receive up to 16 weeks of maintenance IV (n=17) or daily oral (n=18) iron. Eligible patients had received hemodialysis for >2 months, had a baseline transferrin saturation [TSAT] >20%, and were receiving maintenance r-HuEPO. Treatment arms were evenly distributed with respect to baseline demographic and clinical characteristics, with no statistically significant differences in baseline hemoglobin (Hb), hematocrit (Hct), reticulocyte Hb content (CHr), serum ferritin (SF), TSAT, or r-HuEPO dose. In the 35 patients, IV iron dextran and not oral iron was associated with a significant increase (138.5 to 259.1 ng/ml, P=0.003) in SF. A comparison of the change in SF between the IV iron group and the oral iron group was also significant (P=0.001). Whereas only IV iron was associated with a significant decrease in the dose of r-HuEPO (234.0 to 157.6 U/kg per week, P=0.046) and an increase of the CHr (29.2 to 30.1 pg, P=0.049), these changes were not significantly different from those experienced by patients in the oral iron group. In both groups, the Hct remained stable and in neither group was there a significant change in the TSAT. In summary, although both oral and IV iron maintained patients in an iron-replete state in this short-term study, only IV therapy allowed for a significant improvement in iron stores.     

Blood pressure measurements and left ventricular mass index in hemodialysis patients

Left ventricular hypertrophy (LVH) is the most frequent cardiac abnormality in hemodialysis (HD) patients. It is related to cardiovascular diseases and is an important risk factor for mortality in HD patients. Arterial hypertension is an established risk factor for LVH in HD patients. Inferior vena cava (IVC) diameter is a good indicator of circulating fluid volume; hypervolemia is an important pathogenetic factor of hypertension in HD patients. The purpose of our study was to evaluate possible association between LVH, IVC diameter, and different blood pressure (BP) measurements in HD patients. In the present study, 85 HD patients were included. BP was measured with a standard mercury sphygmomanometer before and after the HD session; the average 1‐monthly values of the routine BP measurements were also analyzed. 24‐ and 48‐h ambulatory blood pressure measurements (ABPMs) were performed after the end of HD sessions using a noninvasive ABPM. Average values of systolic and diastolic BP were analyzed separately for the first (HD) and second (interdialytic) day ABPM and for both days together. Using echocardiography, left ventricular mass was measured and left ventricular mass index (LVMI) was calculated. Using ultrasonography, IVC diameter was measured on the interdialytic day. Using multiple regression analysis, we found statistically significant correlations between LVMI and mean monthly postdialysis systolic BP (P < 0.05) and mean 48‐h diastolic BP (P < 0.05). Only longer BP measurements (average 1‐month post‐HD and 48‐h ABPM) were associated with LVMI in HD patients.     

自我管理教育对维持性血液透析者血压及容量状况的影响

目的 探讨自我管理教育在维持性血液透析者血压及容量控制中的作用.方法 选择2012年2月至2013年2月在我院行维持性血液透析且合并高血压的患者56例,其中男31例,女25例,年龄29 ～ 75岁,平均（59±6）岁.在常规护理的基础上,以自我管理模式理论为指导,对患者进行疾病知识和管理技能培训,观察患者干预前与干预后3个月时血压及容量变化.采用t检验进行数据统计.结果 进行自我管理教育3个月后,患者血压及容量控制水平较干预前显著提高,体质量增长量及降压药物应用均有所下降,差异统计学意义（均P＜0.05）.结论 自我管理教育能有效提高维持性血液透析者的健康行为和自我管理能力,有效控制患者血压,改善患者容量状况.     

血液透析患者血压控制目标与药物选择

高血压是维持性血液透析患者的常见并发症。长期高血压与血液透析患者增加的死亡率密切相关。因此,血液透析患者的降压治疗在整体治疗中占有重要地位。目前血液透析患者高血压治疗的靶目标尚有争议,作者建议降压的靶目标应该个体化。选择合适的透析方式是降压治疗的重要手段,但多数血液透析患者需要服用两种或两种以上不同类别的降压药联合控制血压,合理选择降压药物至关重要。     

Masked hypertension is prevalent in children with sickle cell disease: a Midwest Pediatric Nephrology Consortium study

Background

The prevalence of hypertension and abnormal blood pressure (BP) patterns on 24-h ambulatory BP monitoring (ABPM) remains unknown in children with sickle cell disease (SCD).

Methods

Thirty-eight asymptomatic children with sickle cell disease (SCD) (12 HbSS receiving routine care, 13 HbSC, and 13 HbSS receiving chronic transfusion therapy) underwent 24-h ABPM. Average clinic BP, demographic and biochemical characteristics were collected.

Results

Median age was 13?years (range 11?C16), body mass index (BMI) 19.1 kg/m² (range 18.2?C21.1), and 50% were male. Seventeen subjects (43.6%) had ambulatory hypertension, while 4 (10.3%) were hypertensive based on their clinic BP. Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) dip were 8.3?±?5.9% and 14.7?±?7.6% respectively. Twenty-three subjects (59%) had impaired SBP dipping, 7 (18%) had impaired DBP dipping, and 5 (13%) had reversed dipping. Clinic and ABP classification were modestly correlated (rho?=?0.38, P?=?0.02).

Conclusion

Abnormalities in ABP measurements and patterns in children with SCD are prevalent and require more attention from heath care providers. ABPM is a valuable tool in identifying masked hypertension and abnormalities in circadian BP.     

Pylorus-preserving pancreaticoduodenectomy in patients undergoing chronic hemodialysis

This report describes three patients who underwent a pylorus-preserving pancreaticoduodenectomy (PpPD) and received maintenance hemodialysis due to chronic renal failure. The three cases were diagnosed to have bile duct cancer, intraductal papillary mucinous neoplasm, and carcinoma of the ampulla of Vater, respectively. They underwent chronic hemodialysis for 7.7 years. They all underwent a PpPD with lymph node dissection. The mean operation time was 373 min and mean blood loss was 647 ml. During the postoperative courses, hemodialysis was restarted on postoperative day 1 in all three cases. In the three patients, only minor complications were experienced and these were treated conservatively. The mean postoperative hospital stay was 48 days. Two patients are still alive 135 and 21 months after the operation, respectively, but the other patient died of another disease 21 months after the PpPD. A PpPD may therefore be safe and feasible even in patients receiving chronic hemodialysis.     

Long-term results of rhGH treatment in children with renal failure: experience of the French Society of Pediatric Nephrology

Few publications have described the long-term effects of recombinant human growth hormone (rhGH) in uremic patients. This study reports the results of rhGH therapy at the end of treatment and at adult age in 178 French patients. At enrollment, 63 patients were under conservative treatment (CT), 40 under hemodialysis (HD), and 75 had a functioning renal transplant (RT). Under rhGH treatment, height velocities (HV) significantly increased in all patients, but the effect was significantly better in the CT group. The HV gain (HV under rhGH-HV before treatment) was similar in all three groups. Increases in HV allowed height standard deviation scores (SDS) catch up, and this effect persisted over a 5-year period. SDS height at the completion of treatment was significantly related to group (best in CT) and response to treatment during the first year. Data on adult height was available for 102 patients. Mean adult height was 162.2 cm in men and 152.9 cm in women, and 46% were > −2 SDS for height. Adult height SDS was correlated with height SDS and spontaneous HV before treatment and effect of treatment. Analysis of adult height in the 49 patients who entered the protocol with a height SDS between −2 and −3 (the current recommendation for rhGH use) revealed that 65% had an adult-height SDS >−2. These adult heights were significantly better if compared with historical cohorts of patients not treated by rhGH; rhGH significantly improves the adult-height prognosis of uremic patients suffering from growth retardation. Early rhGH administration during CT gives better height SDS at both the end of rhGH therapy and in adulthood. Members of the French Society of Pediatric Nephrology: J.L. André, A. Bensman, E. Bérard, J.P. Bertheleme, F. Bouissou, B. Boudailliez, F. Brou, M. Broyer, A. Burguet, G. Champion, P. Cochat, M. Dehennault, G. Deschênes, P. Desprez, R. Dumas, M. Fischbach, M. Foulard, M.T. Freycon, M.F. Gagnadoux, S. Gié, G. Guest, C. Guyot, G. Landthaler, M.P. Lavocat, C. Loirat, M.A. Macher, D. Morin, C. Mousson, P. Niaudet, H. Nivet, J.B. Palcoux, G. Picon, B. Roussel, M. Tsimaratos     

维持性血液透析患者皮肤瘙痒情况的调查

目的 分析维持性血液透析患者皮肤瘙痒的部位、程度及治疗情况.方法 对我院血液净化中心63例维持性血液透析患者的皮肤瘙痒发生部位、以视觉模拟评分法评估瘙痒程度并调查其治疗情况.结果 63例维持性血液透析患者常见的瘙痒部位依次为背部、下肢、胸部、上肢、头颈部;轻度、中度、重度瘙痒分别为22例(34.9%)、25例(39.6%)、16例(25.4%);合并皮肤感染5例.63例患者中有40例患者接受血液灌流和(或)血液透析滤过治疗,经规律血液灌流和(或)血液透析滤过治疗后症状缓解.单纯行血液透析治疗的23例瘙痒患者中有14例去皮肤科就诊,经局部对症治疗效果不明显.结论 维持性血液透析患者皮肤瘙痒多为中、重度并可能发生皮肤感染.规律血液灌流和(或)血液透析滤过治疗能有效地缓解维持性血液透析患者皮肤瘙痒,而单纯局部对症治疗无效.     

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.     

Paricalcitol versus calcitriol treatment for hyperparathyroidism in pediatric hemodialysis patients

Secondary hyperparathyroidism (SHPT) remains a treatment dilemma in pediatric dialysis patients. Recent experience with paricalcitol (P), a vitamin D analogue, in adults with SHPT has shown equal efficacy and improved survival compared to traditional treatment with calcitriol (C). We present our experience with (C) compared to (P) treatment in our pediatric dialysis patients with SHPT. Twenty-one patients (mean age 11.5±5 years) with SHPT (intact parathyroid hormone (iPTH) averaging 1,228±496 pg/ml) were studied. Seventeen received (C) followed by (P); while an additional four were treated with either (C=1) or (P=3) alone. After 26±8 weeks, average percent (%) decrease in iPTH was similar with (C) and (P) (−60.4±34% versus −65.4±28%, respectively; p=0.6). In the (P) group, the effective dose in children was greater than in adult trials based on kilogram weight. Episodes of hypercalcemia between the treatment groups were not different. However, episodes of elevated calcium × phosphorus product (Ca×P)≥70 mg²/dl² occurred more frequently in the (C) group (odds ratio=1.5; p=0.01). Paricalcitol appears to be safe and effective in pediatric patients. Data suggest that dosing should be gauged according to degree of SHPT. This should serve as impetus for future pharmacokinetic studies in pediatric dialysis patients.     

Gaining the Patient Reported Outcomes Measurement Information System (PROMIS) perspective in chronic kidney disease: a Midwest Pediatric Nephrology Consortium study

Background and objectives

Chronic kidney disease is a persistent chronic health condition commonly seen in pediatric nephrology programs. Our study aims to evaluate the sensitivity of the Patient Reported Outcomes Measurement Information System (PROMIS) pediatric instrument to indicators of disease severity and activity in pediatric chronic kidney disease.

Methods

This cross sectional study included 233 children 8–17 years old, with chronic kidney disease from 16 participating institutions in North America. Disease activity indicators, including hospitalization in the previous 6 months, edema, and number of medications consumed daily, as well as disease severity indicators of kidney function and coexisting medical conditions were captured. PROMIS domains, including depression, anxiety, social-peer relationships, pain interference, fatigue, mobility, and upper extremity function, were administered via web-based questionnaires. Absolute effect sizes (AES) were generated to demonstrate the impact of disease on domain scores. Four children were excluded because of missing glomerular filtration rate (GFR) estimations.

Results

Of the 229 children included in the final analysis, 221 completed the entire PROMIS questionnaire. Unadjusted PROMIS domains were responsive to chronic kidney disease activity indicators and number of coexisting conditions. PROMIS domain scores were worse in the presence of recent hospitalizations (depression AES 0.33, anxiety AES 0.42, pain interference AES 0.46, fatigue AES 0.50, mobility AES 0.49), edema (depression AES 0.50, anxiety AES 0.60, pain interference AES 0.77, mobility AES 0.54) and coexisting medical conditions (social peer-relationships AES 0.66, fatigue AES 0.83, mobility AES 0.60, upper extremity function AES 0.48).

Conclusions

The PROMIS pediatric domains of depression, anxiety, social-peer relationships, pain interference, and mobility were sensitive to the clinical status of children with chronic kidney disease in this multi-center cross sectional study. We demonstrated that a number of important clinical characteristics including recent history of hospitalization and edema, affected patient perceptions of depression, anxiety, pain interference, fatigue and mobility. The PROMIS instruments provide a potentially valuable tool to study the impact of chronic kidney disease. Additional studies will be required to assess responsiveness in PROMIS score with changes in disease status over time.     

单中心维持性血液透析患者临床分析

目的：调查深圳市中医院维持性血液透析（maintenance hemodialysis,MHD）患者的现状。方法选择2013年3月至6月在本中心透析的147例 MHD 患者为研究对象,进行横断面调查,统计患者血管通路的种类和人数、每次透析的超滤情况,检测患者血红蛋白、血电解质、甲状旁腺素及透析前、透析后肾功能,并进行统计学分析,评价其透析状况。结果147例 MHD患者中,男女比例为1.58∶1,平均年龄（50.1±14.9）岁,原发病前2位分别为慢性肾小球肾炎和糖尿病肾脏疾病,血管通路以自体动静脉内瘘为主（140例,占95.23%）;本组147例 MHD 患者中,配合采血者122例,采血依从性为82.99%;血红蛋白为（103.03±15.32）g/L,达到贫血治疗目标的患者有33例,达标率为27.04%,半数以上的患者存在轻度贫血;血钾为（5.32±0.79）mmol/L,高血钾症（＆gt;5.3 mmol/L）的患者49例（占40.16%）;血钙为（2.15±0.22）mmol/L（未用血白蛋白校正）,血磷（1.98±0.51）mmol/L,甲状旁腺素为359.2（163.35,825.2）ng/L（四分位分析法）,贫血、血钾和钙磷代谢紊乱控制较差;透析充分性方面,尿素清除指数（Kt/V）值达标率为90.16%;乙型病毒性肝炎患者9例（占6.12%）,无院内新增传染病患者。结论本中心患者大部分透析充分,传染病控制好,但部分患者慢性并发症控制欠佳,有待于加强对患者的管理和治疗。