Anemia in children following renal transplantation-results from the ESPN/ERA-EDTA Registry.

BACKGROUND: Our aim was to determine the prevalence of sub-target hemoglobin (Hb) levels in children with a renal allograft and to identify potential determinants associated with these Hb levels. METHODS: Data from 3669 children with a functioning renal allograft, aged <18 years between 1 January 2000 and 31 December 2012, from 20 European countries were retrieved from the ESPN/ERA-EDTA Registry, providing 16,170 Hb measurements. RESULTS: According to the NKF/KDOQI classification and the UK-NICE guidelines, 49.8 and 7.8% of the patients, respectively, were anemic. Hb levels were strongly associated with graft function, with Hb levels of 12.6 g/dl in children with chronic kidney disease (CKD) stage 1, declining to 10.7 g/dl in children with CKD stage 5 (P < 0.001). Higher Hb levels were associated with the use of tacrolimus compared to ciclosporin (0.14 g/dl; 95% confidence interval 0.02-0.27; P = 0.002). Low Hb levels were associated with an increased risk of graft failure (P = 0.01) or combined graft failure and death (P < 0.01), but not with death alone (not significant). CONCLUSIONS: Anemia is present in a significant proportion of European pediatric kidney transplant recipients and is associated with renal allograft dysfunction and type of immunosuppressants used. In our patient cohort, higher Hb levels were associated with better graft and patient survival and less hypertension.

Prognostic value of plasma von Willebrand factor and its cleaving protease ADAMTS13 in patients with atrial fibrillation.

BACKGROUND: The von Willebrand factor (vWF) is essential for platelet adhesion and arterial thrombosis. It is degraded into less active multimers by ADAMTS13. Patients with atrial fibrillation (AF) exhibit higher plasma vWF and lower ADAMTS13 antigen levels. The vWF/ADAMTS13-ratio might help to estimate the pro-thrombotic risk of patients with AF. We therefore investigated whether a high ratio of vWF/ADAMTS13, independently of clinical risk scores, predicts major adverse cardiovascular events (MACE) in patients with AF. METHODS: This prospective longitudinal single center study included 269 patients with AF. Blood samples were analyzed for vWF and ADAMTS13-antigen concentration by means of enzyme-linked immunoassay kits. RESULTS: After adjustment for all univariable predictors for MACE (p ≤ 0.1), ADAMTS13≤49.77% (HR 1.833 (95% CI 1.089-3.086); p=0.023) and vWF/ADAMTS13-ratio>27.57 (HR 2.174 (95% CI 1.238-3.817); p=0.007) remained independently associated with outcome. vWF>1434.92 mU/ml (HR 1.539 (95% CI 0.883-2.682); p=0.128) alone failed to independently predict MACE. In patients with low and intermediate risk for MACE according to the CHADS2-score the addition of high vWF/ADAMTS13-ratio levels (>27.57) had significant impact on the patients' outcome. CONCLUSION: A high ratio of vWF/ADAMTS13 independently predicts MACE in patients with AF. Therefore, vWF and its cleaving protease ADAMTS13 might play an important role in the development and perpetuation of vascular disease in AF patients. This might be a novel target for future treatment strategies or an additional help for risk stratification in AF patients.

A rare case: childhood-onset C3 glomerulonephritis due to homozygous factor H deficiency.

C3 glomerulopathy is a recently described pathological entity including dense deposit disease and C3 glomerulonephritis (C3GN). In some cases, C3 glomerulopathy is associated with defects or even complete deficiency of factor H. However, complete factor H deficiency among patients with C3GN is rare, and paediatric cases have not yet been described. Here, we report a child with homozygous factor H deficiency who presented with haematuria and minor proteinuria, together with undetectable plasma C3 levels, at the age of 10 years. Kidney biopsy demonstrated C3GN. Detailed complement analysis revealed complete factor H deficiency due to a homozygous CFH mutation. Furthermore, there was a complete deletion of CFHR-1/-3. During follow-up, the patient has had recurrent episodes of macro-haematuria and minor proteinuria, but during 4 years of follow-up, no deterioration of renal function has been observed. Mutations of factor H in C3GN have been described; however, complete CFH deficiency is rare in these patients. Furthermore, clinical presentation usually occurs in adulthood. Therefore, this case presents a rare manifestation of the disease and might contribute to the early detection of similar cases also in childhood.

Neuromuscular electrical stimulation reduces skeletal muscle protein degradation and stimulates insulin-like growth factors in an age- and current-dependent manner: a randomized, controlled clinical trial in major abdominal surgical patients.

OBJECTIVE: To investigate the effect of neuromuscular electrical stimulation (NMES) on skeletal muscle metabolism after major abdominal surgery. SUMMARY BACKGROUND DATA: Protein catabolism associated with surgical interventions leads to reduced muscle strength, increased clinical complications and prolonged convalescence. Immobilization is suggested as a major stimulus for muscle wasting. This study investigates the potency of NMES on skeletal muscle growth factors and degradation processes in surgical patients. METHODS: This observer blind study included 26 patients after major abdominal surgery mainly due to cancer aged 60 +/- 10 years. Starting on the first postoperative day, 1 randomly assigned thigh of each patient was treated on 4 consecutive days with NMES, whereas the other leg was used as sham-stimulated control. Thereafter, muscle biopsies from both legs were performed. Differences in mRNA level, protein expression, and enzyme activity between legs were analyzed by cross-over analysis of variance (Clinical Trial Registration Number: NCT00635440). RESULTS: NMES significantly increased total RNA content and total sarcoplasmatic protein content. NMES significantly reduced ubiquitin-conjugated sarcoplasmatic proteins and proteasome activity. The mechano growth factor mRNA level correlated positively with the applied current and negatively with the body mass index of the patients. The increase in insulin like growth factor-1Ea mRNA after NMES correlated negatively with the age of the patients. CONCLUSIONS: This study shows that NMES significantly increases total RNA content and reduces protein degradation in postoperative patients. Moreover, the induction of growth factors by NMES reveals dependency on body mass index, age, and applied current. We conclude that NMES is a useful clinical tool to reduce protein catabolism in postoperative patients.