Christina Taylan

Ultrasound-Guided Percutaneous Renal Biopsy in 295 Children and Adolescents: Role of Ultrasound and Analysis of Complications

Introduction Percutaneous renal biopsy (PRB) is a decisive diagnostic procedure for children and adolescents with renal diseases. Aim of this study was to evaluate retrospectively the complication rates of percutaneous kidney biopsies and their therapeutic consequences to assess the role of ultrasound-guidance including Doppler ultrasound examinations in preparation, execution and follow-up care and to present a recommended protocol. Patients and Methods Institutional review board approved this retrospective study; informed consent was waived. Between 1997 and 2011 a total of 438 ultrasound-guided biopsies were performed in 295 patients, 169 of the biopsies were performed on kidney transplants. Average age of patients was 10.2+/−5.2 years (range of 15 days until age of 23). Before and post biopsy ultrasound examination including Doppler examination was carried out. Biopsy itself was ultrasound monitored. Complications were analysed with regard to age of patient, kidney transplants, year of occurrence, number of punctures, performing physician and time interval of occurrence to develop an optimized protocol for ultrasound-guidance. Results In 99% of cases successful PRB were performed, i.e. enough kidney parenchyma for histological analysis was obtained. No lethal or major complication that required surgical intervention occurred. Eighteen relevant complications were observed (complication rate: 4.1%). Except in one case in which additional MRI diagnostic was necessary, ultrasound examination after 4 hours post biopsy or even earlier when symptoms occurred, was able to detect complications and determine indications for intervention. Conclusion Ultrasound-guided PRB is an established and effective method in children and adolescents, but shows a certain rate of complications and therefore should not be indicated without diligence. Ultrasound including Doppler ultrasound is a valuable tool in preparation, guidance of biopsy, detection of complications and in follow-up care. Ultrasound examinations (including Doppler) pre-, during and 4 hours post kidney biopsy and, depending from case, a few days until weeks after biopsy is recommended.

Mycophenolate Mofetil Therapy in Children With Idiopathic Nephrotic Syndrome: Does Therapeutic Drug Monitoring Make a Difference?

Background: Idiopathic nephrotic syndrome (INS) necessitates administration of corticosteroids or corticoid-sparing agents in 60% of the cases for prolonged periods resulting in serious adverse effects. Methods: To avoid these complications, we investigated the efficacy and safety of mycophenolate mofetil (MMF) in our retrospective single-center study with 15 patients presenting with complicated courses of INS and aspired to estimate a cutoff level for mycophenolic acid–area under the curve (MPA-AUC) values, which can predict relapses with high sensitivity. Results: Seven of 15 patients stayed in remission while receiving MMF. Average frequency of relapses was 1.39 (0.28–2.5) per year. In case of relapses, patients had lower predose and estimated AUC0–12 levels of MPA (P = 0.02 and 0.001, respectively). Based on the results of receiver operating characteristic analysis, we consider an estimated MPA-AUC0–12 lower than 44.6 mg·h·L−1 as a risk factor for future relapses (91% sensitivity, 57% specificity, P = 0.06) because the prevalence of relapse is significantly lower (0.07 versus 0.5, P = 0.02), if the estimated MPA-AUC0–12 is >44.6 mg·h·L−1. During MMF administration, we did not detect any adverse event requiring discontinuation of treatment. Conclusions: In conclusion, we demonstrate MMF as an alternative treatment for children with complicated INS to maintain remission without serious side effects. Furthermore, we propose a higher therapeutic target range of MPA-AUC0–12 (>45 mg·h·L−1) than used in transplanted children underlining the crucial role of therapeutic drug monitoring.

Transitional Care and Adherence of Adolescents and Young Adults After Kidney Transplantation in Germany and Austria: A Binational Observatory Census Within the TRANSNephro Trial

AbstractTransition from child to adult-oriented care is widely regarded a challenging period for young people with kidney transplants and is associated with a high risk of graft failure.We analyzed the existing transition structures in Germany and Austria using a questionnaire and retrospective data of 119 patients transferred in 2011 to 2012.Most centers (73%) confirmed agreements on the transition procedure. Patients’ age at transfer was subject to regulation in 73% (18 years). Median age at transition was 18.3 years (16.5–36.7). Median serum creatinine increased from 123 to 132 &mgr;mol/L over the 12 month observation period before transfer (P = 0.002). A total of 25/119 patients showed increased creatinine ≥20% just before transfer. Biopsy proven rejection was found in 10/119 patients. Three patients lost their graft due to chronic graft nephropathy.Mean coefficient of variation (CoV%) of immunosuppression levels was 0.20 ± 0.1. Increased creatinine levels ≥20% just before transfer were less frequently seen in patients with CoV < 0.20 (P = 0.007).The majority of pediatric nephrology centers have internal agreements on transitional care. More than half of the patients had CoV of immunosuppression trough levels consistent with good adherence. Although, 20% of the patients showed increase in serum creatinine close to transfer.

Dyslipidemia after pediatric renal transplantation—The impact of immunosuppressive regimens

Dyslipidemia contributes to cardiovascular morbidity and mortality in pediatric transplant recipients. Data on prevalence and risk factors in pediatric cohorts are, however, scarce. We therefore determined the prevalence of dyslipidemia in 386 pediatric renal transplant recipients enrolled in the CERTAIN registry. Data were obtained before and during the first year after RTx to analyze possible non‐modifiable and modifiable risk factors. The prevalence of dyslipidemia was 95% before engraftment and 88% at 1 year post‐transplant. Low estimated glomerular filtration rate at 1 year post‐transplant was associated with elevated serum triglyceride levels. The use of TAC and of MPA was associated with significantly lower concentrations of all lipid parameters compared to regimens containing CsA and mTORi. Immunosuppressive regimens consisting of CsA, MPA, and steroids as well as of CsA, mTORi, and steroids were associated with a three‐ and 25‐fold (P<.001) increased risk of having more than one pathologic lipid parameter as compared to the use of TAC, MPA, and steroids. Thus, amelioration of the cardiovascular risk profile after pediatric RTx may be attained by adaption of the immunosuppressive regimen according to the individual risk profile.

Children of non-Western origin with end-stage renal disease in the Netherlands, Belgium and a part of Germany have impaired health-related quality of life compared with Western children

BACKGROUND Many children with end-stage renal disease (ESRD) living in Western Europe are of non-Western European origin. They have unfavourable somatic outcomes compared with ESRD children of Western origin. In this study, we compared the Health-related Quality of Life (HRQoL) of both groups. METHODS All children (5-18 years) with ESRD included in the RICH-Q project (Renal Insufficiency therapy in Children-Quality assessment and improvement) or their parents were asked to complete the generic version of the Paediatric Quality-of-Life Inventory 4.0 (PedsQL). RICH-Q comprises the Netherlands, Belgium and a part of Germany. Children were considered to be of non-Western origin if they or at least one parent was born outside Western-European countries. Impaired HRQoL for children with ESRD of Western or non-Western origin was defined as a PedsQL score less than fifth percentile for healthy Dutch children of Western or non-Western origin, respectively. RESULTS Of the 259 eligible children, 230 agreed to participate. One hundred and seventy-four children responded (response rate 67%) and 55 (32%) were of non-Western origin. Overall, 31 (56%) of the ESRD children of non-Western origin, and 58 (49%) of Western origin had an impaired total HRQoL score. Total HRQoL scores of children with ESRD of Western origin and non-Western origin were comparable, but scores on emotional functioning and school functioning were lower in non-Western origin (P=0.004 and 0.01, respectively). The adjusted odds ratios (95% confidence interval) for ESRD children of non-Western origin to have impaired emotional functioning and school functioning, compared with Western origin, were 3.3(1.5-7.1) and 2.2(1.1-4.2), respectively. CONCLUSION Children with ESRD of non-Western origin in three Western countries were found to be at risk for impaired HRQoL on emotional and school functioning. These children warrant special attention.

AV fistula creation in paediatric patients: outcome is independent of demographics and fistula type reducing usage of venous catheters

Purpose Even though early transplantation is still the first-line therapy in paediatric patients with end-stage renal disease (ESRD), up to 30% of these patients still require haemodialysis (HD). Creating an arteriovenous fistula (AVF) is quite challenging, particularly in children, leading to disproportional use of catheters. In this paper, we describe our experience in the creation of AVF with currently no in-dwelling catheters in children and adolescents on HD. Methods From January 2009 to December 2013, there were 34 patients rated as unfit for transplantation for at least the next 6 months or who had already been on HD through a central venous catheter (CVC). Three patients aged between 12 months and 3 years and weighing 9-12 kg were not suitable for AVF. Finally 31 patients, from 6 to 19 years of age with a mean weight of 43.3 ± 14.5 kg (19-80 kg), were assigned to the alternative of AVF. Results During the above-mentioned time period, 31 patients were provided with 32 AVFs; 26 received a distal radiocephalic fistula, five a Gracz-type fistula and one a brachio-basilic fistula. All but two fistulae matured primarily, within an average time of 45 (range: 16-191) days until the first dialysis. The fistulas 1-year primary and primary assisted patency rates were 78% and 94%, respectively. Conclusions The creation of a native vascular access is an effective and durable procedure in paediatric and adolescent patients. It reduces using of CVCs and is appropriate both for long-term treatment and as a bridging procedure until renal transplantation.

Neutral pH and low–glucose degradation product dialysis fluids induce major early alterations of the peritoneal membrane in children on peritoneal dialysis

The effect of peritoneal dialysates with low-glucose degradation products on peritoneal membrane morphology is largely unknown, with functional relevancy predominantly derived from experimental studies. To investigate this, we performed automated quantitative histomorphometry and molecular analyses on 256 standardized peritoneal and 172 omental specimens from 56 children with normal renal function, 90 children with end-stage kidney disease at time of catheter insertion, and 82 children undergoing peritoneal dialysis using dialysates with low-glucose degradation products. Follow-up biopsies were obtained from 24 children after a median peritoneal dialysis of 13 months. Prior to dialysis, mild parietal peritoneal inflammation, epithelial-mesenchymal transition and vasculopathy were present. After up to six and 12 months of peritoneal dialysis, blood microvessel density was 110 and 93% higher, endothelial surface area per peritoneal volume 137 and 95% greater, and submesothelial thickness 23 and 58% greater, respectively. Subsequent peritoneal changes were less pronounced. Mesothelial cell coverage was lower and vasculopathy advanced, whereas lymphatic vessel density was unchanged. Morphological changes were accompanied by early fibroblast activation, leukocyte and macrophage infiltration, diffuse podoplanin presence, epithelial mesenchymal transdifferentiation, and by increased proangiogenic and profibrotic cytokine abundance. These transformative changes were confirmed by intraindividual comparisons. Peritoneal microvascular density correlated with peritoneal small-molecular transport function by uni- and multivariate analysis. Thus, in children on peritoneal dialysis neutral pH dialysates containing low-glucose degradation products induce early peritoneal inflammation, fibroblast activation, epithelial-mesenchymal transition and marked angiogenesis, which determines the PD membrane transport function.

Transition structures and timing of transfer from paediatric to adult-based care after kidney transplantation in Germany: a qualitative study

Objectives It is known that transition, as a shift of care, marks a vulnerable phase in the adolescents’ lives with an increased risk for non-adherence and allograft failure. Still, the transition process of adolescents and young adults living with a kidney transplant in Germany is not well defined. The present research aims to assess transition-relevant structures for this group of young people. Special attention is paid to the timing of the process. Setting In an observational study, we visited 21 departments of paediatric nephrology in Germany. Participants were doctors (n=19), nurses (n=14) and psychosocial staff (n=16) who were responsible for transition in the relevant centres. Structural elements were surveyed using a short questionnaire. The experiential viewpoint was collected by interviews which were transcribedverbatim before thematic analysis was performed. Results This study highlights that professionals working within paediatric nephrology in Germany are well aware of the importance of successful transition. Key elements of transitional care are well understood and mutually agreed on. Nonetheless, implementation within daily routine seems challenging, and the absence of written, structured procedures may hamper successful transition. Conclusions While professionals aim for an individual timing of transfer based on medical, social, emotional and structural aspects, rigid regulations on transfer age as given by the relevant health authorities add on to the challenge. Trial registration number ISRCTN Registry no 22988897; results (phase I) and pre-results (phase II).