Kerstin Froede

Patterns of Growth after Kidney Transplantation among Children with ESRD

BACKGROUND AND OBJECTIVES Poor linear growth is a frequent complication of CKD. This study evaluated the effect of kidney transplantation on age-related growth of linear body segments in pediatric renal transplant recipients who were enrolled from May 1998 until August 2013 in the CKD Growth and Development observational cohort study. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Linear growth (height, sitting height, arm and leg lengths) was prospectively investigated during 1639 annual visits in a cohort of 389 pediatric renal transplant recipients ages 2-18 years with a median follow-up of 3.4 years (interquartile range, 1.9-5.9 years). Linear mixed-effects models were used to assess age-related changes and predictors of linear body segments. RESULTS During early childhood, patients showed lower mean SD scores (SDS) for height (-1.7) and a markedly elevated sitting height index (ratio of sitting height to total body height) compared with healthy children (1.6 SDS), indicating disproportionate stunting (each P<0.001). After early childhood a sustained increase in standardized leg length and a constant decrease in standardized sitting height were noted (each P<0.001), resulting in significant catch-up growth and almost complete normalization of sitting height index by adult age (0.4 SDS; P<0.01 versus age 2-4 years). Time after transplantation, congenital renal disease, bone maturation, steroid exposure, degree of metabolic acidosis and anemia, intrauterine growth restriction, and parental height were significant predictors of linear body dimensions and body proportions (each P<0.05). CONCLUSIONS Children with ESRD present with disproportionate stunting. In pediatric renal transplant recipients, a sustained increase in standardized leg length and total body height is observed from preschool until adult age, resulting in restoration of body proportions in most patients. Reduction of steroid exposure and optimal metabolic control before and after transplantation are promising measures to further improve growth outcome.

Protocol biopsy‐driven interventions after pediatric renal transplantation

Kanzelmeyer NK, Ahlenstiel T, Drube J, Froede K, Kreuzer M, Broecker V, Ehrich JHH, Melk A, Pape L. Protocol biopsy‐driven interventions after pediatric renal transplantation.
Pediatr Transplantation 2010: 14:1012–1018

Alterations of cyclosporin A metabolism induced by mycophenolate mofetil

Unexpectedly lower CsA 2‐h levels were found in patients who received additional immunosuppression by MMF in our center. The aim of this study is to prove whether there are differences in CsA metabolization when MMF is added to treatment. In 33 children who received an immunosuppression of prednisolone and CsA as well as in 15 children who were treated with additional MMF, C2 and C0 were taken. In 11 children, full AUC of CsA were obtained. C2 levelsdiffered significantly (p < 0.05) between patients treated with (617 ± 230 ng/mL) and without MMF (750 ± 271 ng/mL) but with similar CsA dosages. C2 correlated better with the AUC than CsA levels at other time points with r = 0.95. The equation AUC = 139 + 6.17 × C2 was calculated to match best in a C2‐limited sampling strategy. This formula proved to be safer than equations that had been published before. According to our findings, we suspect that MMF alters the CsA metabolism. When MMF is used in pediatric transplant recipients, either target values of CsA have to be changed or patients may require higher doses of CsA.

ABO-incompatible kidney transplantation of an 8-yr-old girl with donor/recipient-constellation A1B/B

Abstract: Background: Antigen‐specific immunoadsorption combined with rituximab offers the possibility for ABO‐incompatible kidney transplantation without splenectomy.

Comprehensive analysis of glomerular mRNA expression of pro- and antithrombotic genes in atypical haemolytic-uremic syndrome (aHUS)

Atypical haemolytic–uremic syndrome (aHUS) is, in most cases, due to hereditary or acquired defects in complement regulation and a life-threatening disease. Despite the rapidly grown knowledge about the primary defects in aHUS, the pathogenesis that links complement dysregulation with microthrombus formation in aHUS is still unknown. Thus, we examined the glomerular microvascular expression of pro- and antithrombotic genes. Glomeruli were microdissected from 12 archival paraffin-embedded biopsies with aHUS and from seven control biopsies. Glomerular mRNA expression was quantified by single real-time PCR reactions after preamplification. In addition immunostains were performed for plasminogen activator inhibitor 1 (PAI-1) and for tissue plasminogen activator (tPA). Results were compared between cases and controls and with clinical data. Glomeruli in aHUS had increased mRNA expression of antifibrinolytic, prothrombotic PAI-1, antithrombotic thrombomodulin (THBD) and CD73 and decreased expression of profibrinolytic, antithrombotic tPA compared to controls. Impaired fibrinolysis due to increased microvascular expression of the antifibrinolytic PAI-1 in combination with the decreased expression of the profibrinolytic tPA seems to be a final common pathway in renal thrombotic microangiopathy that is also effective in aHUS. The concomitant induction of antithrombotic transcripts likely indicates counterregulatory efforts, demonstrating that the capillary bed is not a passive victim of complement attack. Future research should investigate if and how complement activation could induce the reported shift in the expression of PAI-1 and tPA.

Belatacept after kidney transplantation in adolescents: a retrospective study.

Regardless of recipient age at kidney transplantation (KTx), patients are at greatest risk for graft loss in adolescence, partly due to nonadherence to an oral immunosuppressive regimen. Belatacept, a non‐nephrotoxic, first‐in‐class immunosuppressant that inhibits costimulation of T cells requires intravenous application only every 4 weeks, potentially leading to better adherence. However, it is only approved for use in adults. We report here the findings of the first study of belatacept in adolescents, comprising all patients in our department switched to belatacept post‐KTx. Six patients (median age 15.5 years) were switched after a median of 7.5 months (range 23 days to 12 years), treatment range 3–28 months (cumulative 83 months): Three patients switched early (<3 months after KTx) had increased estimated glomerular filtration rate (GFR); one patient switched 12 years post‐KTx has stable GFR; two patients were switched following rapid decline of and with markedly impaired GFR, changing slope in one patient. One patient had one acute rejection. In addition of two patients who received belatacept for other conditions, the only relevant adverse event was neutropenia (after a cumulative 109 months). Belatacept as primary immunosuppression is an option in Epstein–Barr virus‐seropositive nonadherent adolescents if administered sufficiently early before deterioration of graft function.

Correction to: Rabbit anti-human thymocyte immunoglobulin for the rescue treatment of chronic antibody-mediated rejection after pediatric kidney transplantation

The article “Rabbit anti-human thymocyte immunoglobulin for the rescue treatment of chronic antibody-mediated rejection after pediatric kidney transplantation”, written by Yasemen Cihan, Nele Kanzelmeyer, Jens Drube, Martin Kreuzer, Christian Lerch, Imke Hennies, Kerstin Froede, Murielle Verboom.