Center for Pediatric and Adolescent Medicine

Heidelberg, Germany

Center for Pediatric and Adolescent Medicine

Heidelberg, Germany
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PubMed | Institute of Medical Biometry and Informatics, Pediatric Nephrology, University of Strasbourg and Center for Pediatric and Adolescent Medicine
Type: Journal Article | Journal: Pediatric nephrology (Berlin, Germany) | Year: 2016

Modern hemodialysis (HD) machines are able to measure ionic dialysance online and thereby continuously monitor Kt/V. The accuracy of measurement depends on the input of the correct urea distribution volume (V), available from anthropometric equations and body composition monitoring (BCM). The latter method, however, has not been validated in children.We compared V determined by BCM to that calculated using four different anthropometric formulas (Morgenstern, Mellits and Cheek, Hume-Weyers and Watson equations) in 23 pediatric HD patients. We also compared online Kt/V using BCM-derived V with the Kt/V calculated from pre- and post-dialytic urea concentrations using the single-pool second-generation Daugirdas equation.The V calculated by the Morgenstern equation was similar to that derived by BCM, with a mean difference of -0.7% (95% limits of agreement -11.7 to 10.3%). In contrast, the V calculated by the other equations was 5.4, 6.2 and 18%, respectively higher than the BCM-derived V. The mean difference between Kt/V calculated using the Daugirdas equation and online Kt/V determination based on BCM-derived V data was 0.10 (95% limits of agreement -0.50 to 0.70%).In our pediatric HD patients the V measured by BCM was in agreement with that calculated using the Morgenstern equation, which is the only equation which has been validated to date in children on dialysis. Online determination of Kt/V using a BCM-derived V largely agreed with that calculated by the Daugirdas equation. We therefore conclude that the former approach is suitable for frequent online assessment of dialytic small solute clearance.

Schaefer B.,Center for Pediatric and Adolescent Medicine | Tonshoff B.,Center for Pediatric and Adolescent Medicine | Schmidt J.,University of Heidelberg | Golriz M.,University of Heidelberg | And 6 more authors.
Pediatric Nephrology | Year: 2013

Background: ABO-incompatible renal transplantation (ABOi-RTx) following preconditioning with immunoadsorption (IA) and rituximab is a promising approach to facilitate living-related RTx. However, clinical experience is limited in pediatric patients. Methods: Three patients underwent living-related ABOi-RTx in our center. Preoperative IA was performed six, ten and 11 times in patient one, two and three, respectively, to achieve isoagglutinin titers of ≤1:8 on the day of transplantation; rituximab was administered once. The immunosuppressive regimen further comprised tacrolimus, mycophenolate, methylprednisolone and basiliximab; immunoglobulin G (IgG) was infused on the day of ABOi-RTx. Results: All three patients achieved normal renal function within 2-6 days post-RTx. Major postoperative bleeding occurred in two patients, with one requiring repeated blood transfusions and the other a surgical revision 4 h after RTx, despite local citrate anticoagulation use during the preoperative IA procedures in the latter patient. A pyelonephritis-associated increase of the isoagglutinin IgG/IgM titers to 1:64/1:128 led to a biopsy-proven acute humoral rejection in the third patient, which was treated successfully with plasma exchange and methylprednisolone pulses. The estimated glomerular filtration rate at 18, 8 and 23 months post-RTx was 96, 52 and 74 ml/min/1.73 m2, respectively. Conclusions: ABOi-RTx can successfully be performed in pediatric patients after preconditioning with quadruple immunosuppression, rituximab and IA. Caution is required regarding bleeding complications, which are most likely due to the unspecific binding of coagulation factors during repeated IA. © 2012 IPNA.

Schaefer B.,University of Heidelberg | Schaefer F.,University of Heidelberg | Wittmer D.,University of Heidelberg | Engelmann G.,University of Heidelberg | And 3 more authors.
Pediatric Nephrology | Year: 2012

Background Cholestatic pruritus may severely compromise quality of life. The Molecular Adsorbents Recirculating System (MARS) allows removal of pruritogenic substances without exposure to foreign proteins. Pediatric data, however, are scant. Methods We retrospectively analyzed the efficacy of MARS in three boys with severe cholestatic pruritus. They received a total of 135 MARS sessions during 8, 4, and 13 months prior to liver transplantation. Total serum bilirubin and bile acids were monitored, and pruritus was assessed by a numerical rating scale (NRS 0 = no pruritus, 10 = maximal pruritus). Results MARS sessions were initially performed three times weekly at a mean duration of 6.3±1.4 h. Sessions could be reduced to once weekly and once every other week in two patients. Pre-MARS plasma bile acid concentrations averaged 207±67 μmol/l. They declined to 67± 9%, 48±3%, 38±14%, and 37±5% of baseline within 2, 4, 6 and 8 h of therapy, respectively (all p<0.05). The average interdialytic increase of plasma bile acids was 34±33 μmol/ l per day. Mean NRS score decreased from 6.5±2.3 to 3.3± 2.9 (p<0.01). Skin lesions from itching disappeared. All MARS treatments were well tolerated. Conclusion MARS dialysis substantially reduces cholestatic pruritus in children refractory to pharmacological treatment. © IPNA 2012.

Thimm E.,Heinrich Heine University Düsseldorf | Schmidt L.E.,Heinrich Heine University Düsseldorf | Heldt K.,Center for Pediatric and Adolescent Medicine | Spiekerkoetter U.,University Hospital Freiburg
Journal of Inherited Metabolic Disease | Year: 2013

Aim of the study was the evaluation of health-related quality of life (HRQoL) and the detection of deviant behavior in early-treated children and adolescents with PKU in comparison with healthy peers. Special focus was laid on the impact of compliance with treatment as defined by the national recommendations on HRQoL. Our investigation in 50 children and adolescents and their parents for the first time demonstrates that despite an overall normal HRQoL in our PKU patient collective, parents are concerned about performance in school especially when phenylalanine concentrations in their children are mainly above the therapeutic range. Adherence to target phenylalanine concentrations ameliorated markedly in patients above 10 years in comparison to younger patients due to relaxed treatment recommendations. Interestingly, this alleged improvement in metabolic control has an impact on the parent assessed but not on the patient assessed appraisal of HRQoL. However, a positive correlation between poor metabolic control and conduct problems was identified by patients' self-assessment. In conclusion, lacking adherence to the strict treatment recommendations in infancy results in significant concern about school success and success in life in parents of PKU patients. With relaxation of dietary phenylalanine restriction at 10 years of age, these concerns diminish. © 2012 SSIEM and Springer Science+Business Media Dordrecht.

Ansurudeen I.,Karolinska Institutet | Sunkari V.G.,Karolinska Institutet | Grunler J.,Karolinska Institutet | Peters V.,Center for Pediatric and Adolescent Medicine | And 4 more authors.
Amino Acids | Year: 2012

Diabetes mellitus (DM) is a progressive disorder with severe late complications. Normal wound healing involves a series of complex and well-orchestrated molecular events dictated by multiple factors. In diabetes, wound healing is grossly impaired due to defective, and dysregulated cellular and molecular events at all phases of wound healing resulting in chronic wounds that fail to heal. Carnosine, a dipeptide of alanine and histidine and an endogenous antioxidant is documented to accelerate healing of wounds and ulcers. However, not much is known about its role in wound healing in diabetes. Therefore, we studied the effect of carnosine in wound healing in db/db mice, a mice model of Type 2 DM. Six millimeter circular wounds were made in db/db mice and analyzed for wound healing every other day. Carnosine (100 mg/kg) was injected (I.P.) every day and also applied locally. Treatment with carnosine enhanced wound healing significantly, and wound tissue analysis showed increased expression of growth factors and cytokines genes involved in wound healing. In vitro studies with human dermal fibroblasts and microvascular-endothelial cells showed that carnosine increases cell viability in presence of high glucose. These effects, in addition to its known role as an antioxidant and a precursor for histamine synthesis, provide evidence for a possible therapeutic use of carnosine in diabetic wound healing. © 2012 Springer-Verlag.

Peters V.,Center for Pediatric and Adolescent Medicine | Schmitt C.P.,Center for Pediatric and Adolescent Medicine | Zschocke J.,Innsbruck Medical University | Gross M.-L.,Institute of Pathology | And 2 more authors.
Amino Acids | Year: 2012

Recently, we identified an allelic variant of human carnosinase 1 (CN1) that results in increased enzyme activity and is associated with susceptibility for diabetic nephropathy in humans. Investigations in diabetic (db/db) mice showed that carnosine ameliorates glucose metabolism effectively. We now investigated the renal carnosinase metabolism in db/db mice. Kidney CN1 activity increased with age and was significantly higher in diabetic mice compared to controls. Increased CN1 activity did not affect renal carnosine levels, but anserine concentrations were tenfold lower in db/db mice compared to controls (0.24 ± 0.2 vs. 2.28 ± 0.3 nmol/mg protein in controls; p < 0.001). Homocarnosine concentrations in kidney tissue were low in both control and db/db mice (below 0.1 nmol/mg protein, p = n.s.). Carnosine treatment for 4 weeks substantially decreased renal CN1 activity in diabetic mice (0.32 ± 0.3 in non-treated db/db vs. 0.05 ± 0.05 μmol/mg/h in treated db/db mice; p < 0.01) close to normal activities. Renal anserine concentrations increased significantly (0.24 ± 0.2 in non-treated db/db vs. 5.7 ± 1.2 μmol/mg/h in treated db/db mice; p < 0.01), while carnosine concentrations remained unaltered (53 ± 6.4 in non-treated vs. 61 ± 15 nmol/mg protein in treated db/db mice; p = n.s.). Further, carnosine treatment halved proteinuria and reduced vascular permeability to one-fifth in db/db mice. In renal tissue of diabetic mice carnosinase activity is significantly increased and anserine concentrations are significantly reduced compared to controls. Carnosine treatment largely prevents the alterations of renal carnosine metabolism. © 2011 Springer-Verlag.

Schmitt C.P.,Center for Pediatric and Adolescent Medicine | Bakkaloglu S.A.,Gazi University | Klaus G.,diatric Kidney Center | Schroder C.,Gelre Hospital | Fischbach M.,Hopital de Hautepierre
Pediatric Nephrology | Year: 2011

The purpose of this article is to provide recommendations on the choice of peritoneal dialysis (PD) fluids in children by the European Pediatric Dialysis Working Group. The literature on experimental and clinical studies with PD solutions in children and adults was analyzed together with consensus discussions within the group. A grading was performed based on the international KDIGO nomenclature and methods. The lowest glucose concentration possible should be used. Icodextrin may be applied once daily during the long dwell, in particular in children with insufficient ultrafiltration. Infants on PD are at risk of ultrafiltration-associated sodium depletion, while anuric adolescents may have water and salt overload. Hence, the sodium chloride balance needs to be closely monitored. In growing children, the calcium balance should be positive and dialysate calcium adapted according to individual needs. Limited clinical experience with amino acid-based PD fluids in children suggests good tolerability. The anabolic effect, however, is small; adequate enteral nutrition is preferred. CPD fluids with reduced glucose degradation products (GDP) content reduce local and systemic toxicity and should be preferred whenever possible. Correction of metabolic acidosis is superior with pH neutral bicarbonate-based fluids compared with singlechamber, acidic, lactate-based solutions. Prospective comparisons of low GDP solutions with different buffer compositions are still few, and firm recommendations cannot yet be given, except when hepatic lactate metabolism is severely compromised. © IPNA 2010.

Schaefer B.,Center for Pediatric and Adolescent Medicine | Schmitt C.P.,Center for Pediatric and Adolescent Medicine
Pediatric Nephrology | Year: 2013

The majority of children with acute, acute-on-chronic, and progressive chronic liver failure require liver transplantation. Since organ availability is limited, extracorporeal liver support systems are increasingly applied to bridge the time until transplantation. At present, four different devices are available: The molecular adsorbent recirculating system (MARS), Prometheus dialysis, plasma exchange combined with hemodialysis (PE/HD), and single-pass albumin dialysis (SPAD). Randomized trials in adults have demonstrated efficient toxin removal, improved portal hypertension, hemodynamic stability, and improved hepatic encephalopathy compared with standard medical therapy. None of the liver support systems has yet been evaluated systematically in children. Knowledge of the specific indications and technical features of the different devices is essential if applied in children. MARS combines albumin dialysis with conventional hemodialysis and allows for efficient removal of water and protein-bound toxins without exogenous protein delivery and the associated infectious and allergic risks. It has successfully been applied in children with otherwise intractable cholestatic pruritus and with liver failure. The benefits, however, need to be balanced against the costs and the risk of volume and nitrogen overload if repeated plasma infusion is required. In cases of active bleeding, plasma exchange in combination with hemodialysis should be preferred. © 2012 IPNA.

Schmitt C.P.,Center for Pediatric and Adolescent Medicine | Aufricht C.,Medical University of Vienna
Pediatric Nephrology | Year: 2016

Introduction of the so-called biocompatible peritoneal dialysis (PD) fluids was based on a large body of experimental evidence and various clinical trials suggesting important clinical benefits. Of these, until now, only preservation of residual renal function—likely due to lower glucose degradation product load and, in case of icodextrin, improved fluid and blood pressure control—have consistently been proven, whereas the impact on important clinical endpoints such as infectious complications, preservation of PD membrane transport function, and patient outcome, are still debated. In view of the high morbidity and mortality rates of PD patients, novel approaches are warranted and comprise the search for alternative osmotic agents and enrichment of PD fluids with specific pharmacologic agents, such as alanyl-glutamine, potentially counteracting local but also systemic sequelae of uremia and PD. © 2016 The Author(s)

Verrina E.E.,G Gaslini Children Hospital | Cannav R.,G Gaslini Children Hospital | Schaefer B.,Center for Pediatric and Adolescent Medicine | Schmitt C.P.,Center for Pediatric and Adolescent Medicine
Contributions to Nephrology | Year: 2012

Peritoneal dialysis (PD) is the treatment modality of choice in pediatric CKD5D patients awaiting renal transplantation. Facing many decades of renal replacement therapy long term preservation of peritoneal membrane function is of particular importance in this patient group. Whereas conventional PD fluids induce severe morphological and functional alterations of the peritoneal membrane within a few years, reduction of glucose degradation product content by multichamber systems, replacement of glucose by icodextrin and amino acids, and of lactate by bicarbonate at a neutral to physiological pH are expected to preserve peritoneal membrane integrity. Based on numerous in vitro, experimental and clinical studies, the European Pediatric Dialysis Working Group recommended the use of low glucose degradation product solutions whenever possible. Icodextrin is considered a useful option, in particular in children with sodium and water overload, even though infants may absorb higher amounts of icodextrin and achieve less ultrafiltration. The concept of amino acid- based PD fluids is intriguing, but pediatric benefits are insufficiently described and cannot replace tube feeding in malnourished children. Bicarbonatebased PD fluids better control metabolic acidosis and have been recommended in children with acute kidney injury and impaired lactate metabolism. This review discusses the scientific evidence and potential advantages of PD solutions with an improved biocompatibility profile, with a particular focus on pediatric studies. Copyright © 2012 S. Karger AG.

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