Mycophenolate Mofetil versus Cyclosporin A in Children with Frequently Relapsing Nephrotic Syndrome

The severe side effects of long-term corticosteroid or cyclosporin A (CsA) therapy complicate the treatment of children with frequently relapsing steroid-sensitive nephrotic syndrome (FR-SSNS). We conducted a randomized, multicenter, open-label, crossover study comparing the efficacy and safety of a 1-year treatment with mycophenolate mofetil (MMF; target plasma mycophenolic acid trough level of 1.5–2.5 µg/ml) or CsA (target trough level of 80–100 ng/ml) in 60 pediatric patients with FR-SSNS. We assessed the frequency of relapse as the primary endpoint and evaluated pharmacokinetic profiles (area under the curve [AUC]) after 3 and 6 months of treatment. More relapses per patient per year occurred with MMF than with CsA during the first year (P=0.03), but not during the second year (P=0.14). No relapses occurred in 85% of patients during CsA therapy and in 64% of patients during MMF therapy (P=0.06). However, the time without relapse was significantly longer with CsA than with MMF during the first year (P<0.05), but not during the second year (P=0.36). In post hoc analysis, patients with low mycophenolic acid exposure (AUC <50 µg⋅h/ml) experienced 1.4 relapses per year compared with 0.27 relapses per year in those with high exposure (AUC>50 µg⋅h/ml; P<0.05). There were no significant differences between groups with respect to BP, growth, lipid levels, or adverse events. However, cystatin clearance, estimated GFR, and hemoglobin levels increased significantly with MMF compared with CsA. These results indicate that MMF is inferior to CsA in preventing relapses in pediatric patients with FR-SSNS, but may be a less nephrotoxic treatment option

FS7BJ Multiple prevalent fractures in relation to macroscopic bone architecture in patients with cystic fibrosis

Background: The relative risk for bone fractures in patients with cystic fibrosis (CF) and its relationship to macroscopic bone architecture assessed by pQCT and DXA are incompletely defined. Methods: In a cross-sectional study of 43 CF patients (age, 17.8 +/- 6.2 years), rate and location of fractures, bone mass, density, geometry, and strength of the radius as well as forearm muscle size were investigated. Results: The fracture rate in CF was 9.2-fold higher compared to an age-matched German control population. The probability of remaining free of any fracture in CF patients at 25 years was reduced to 39.8% compared to 84.6% in controls (P < 0.001). Assessment of macroscopic bone architecture by DXA and pQCT allowed the differentiation of patients with multiple prevalent fractures with a high sensitivity (up to 100%) and specificity (up to 94.3%). Conclusions: Bone densitometry is a useful tool for noninvasive assessment of fracture risk in CF patients. (C) 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved

Kidney re-transplantation in a child across the barrier of persisting angiotensin II type I receptor antibodies

Background!#!Approximately 20% of antibody-mediated rejection (ABMR) episodes in the absence of donor-specific antibodies against human leucocyte antigens (HLA-DSA) in pediatric and adult kidney transplant recipients are associated with, and presumably caused by, antibodies against the angiotensin type 1 receptor (AT!##!Case!#!We report on a male patient with kidney failure in infancy due to obstructive uropathy who had lost his first kidney transplant due to AT!##!Conclusion!#!This case highlights the difficulty of persistently decreasing elevated A

Analysis of the functional muscle-bone unit of the forearm in patients with phenylketonuria by peripheral quantitative computed tomography

Bone disease in patients with phenylketonuria (PKU) is incompletely characterized. We therefore analyzed, in a cross-sectional study radius macroscopic bone architecture and forearm muscle size by peripheral quantitative computed tomography (pQCT) and muscle strength by hand dynamometry in a large cohort (n = 56) of adolescent and adult patients with PKU aged 26.0 +/- 8.9 (range, 11.8-41.5) years. Data were compared with a reference population (n = 700) from the DONALD study using identical methodology. We observed a significant reduction of cortical thickness (z-score -1.01 +/- 0.79), Strength-Strain Index (SSI) (z-score -0.81 +/- 1.03), and total bone mineral density (BMD) of the distal radius (z-score -1.05 +/- 1.00). Mean muscle cross-sectional area (z-score -0.98 +/- 1.19) and muscle grip force (z-score -0.64 +/- 1.26) were also significantly reduced, indicating an impaired muscular system as part of the clinical phenotype of PKU. SSI positively correlated (r = 0.53, P < 0.001) with the corresponding muscle cross-sectional area in the reference population; however, the regression line slope in PKU patients was less steep (P < 0.001), indicating that bone strength is not adequately adapted to muscle force. In conclusion, the radial bone in PKU patients is characterized by reduced bone strength in relation to muscular force, decreased cortical thickness, and impaired total BMD at the metaphyseal site. These alterations indicate a mixed bone defect in PKU, both of which are due to primary alterations of bone metabolism and to secondary alterations in response to neuromuscular abnormalities

Steroid withdrawal improves blood pressure control and nocturnal dipping in pediatric renal transplant recipients: analysis of a prospective, randomized, controlled trial

BackgroundVariable effects of steroid minimization strategies on blood pressure in pediatric renal transplant recipients have been reported, but data on the effect of steroid withdrawal on ambulatory blood pressure and circadian blood pressure rhythm have not been published so far.MethodsIn a prospective, randomized, multicenter study on steroid withdrawal in pediatric renal transplant recipients (n=42) on cyclosporine, mycophenolate mofetil, and methylprednisolone, we performed a substudy in 28 patients, aged 11.23.8years, for whom ambulatory blood pressure monitoring (ABPM) data were available.ResultsIn the steroid-withdrawal group, the percentage of patients with arterial hypertension, defined as systolic and/or diastolic blood pressure values recorded by ABPM >1.64 SDS and/or antihypertensive medication, at month 15 was significantly lower (35.7%, p=0.002) than in controls (92.9%). The need of antihypertensive medication dropped significantly by 61.2% (p<0.000 vs. control), while in controls, it even rose by 69.3%. One year after steroid withdrawal, no patient exhibited hypertensive blood pressure values above the 95th percentile, compared to 35.7% at baseline (p=0.014) and to 14.3% of control (p=0.142). The beneficial impact of steroid withdrawal was especially pronounced for nocturnal blood pressure, leading to a recovered circadian rhythm in 71.4% of patients vs. 14.3% at baseline (p=0.002), while the percentage of controls with an abnormal circadian rhythm (35.7%) did not change.Conclusions Steroid withdrawal in pediatric renal transplant recipients with well-preserved allograft function is associated with less arterial hypertension recorded by ABPM and recovery of circadian blood pressure rhythm by restoration of nocturnal blood pressure dipping