Multimodal lipid-lowering treatment in pediatric patients with homozygous familial hypercholesterolemia-target attainment requires further increase of intensity

Background Familial hypercholesterolemia (FH) causes premature cardiovascular disease (CVD). Lipoprotein apheresis (LA) is recommended as first-line lipid-lowering treatment (LLT) for homozygous (ho) FH. Methods Efficacy of multimodal LLT including lifestyle counseling, drug treatment, and LAwas analyzed in 17 pediatric hoFH or compound heterozygous (c-het) FH patients, who commenced chronic LA in Germany before the age of 18. Results At time of diagnosis, mean low-density lipoprotein cholesterol (LDL-C) concentration was 19.6 mmol/ l (756 mg/ dl). Multimodal LLT resulted in 73% reduction of mean LDL-C concentration including a 62% contribution of LA. Only three children (18%) achieved mean LDL-C concentrations below the recommended pediatric target of 3.5 mmol/ l (135 mg/ dl). In 13 patients (76%) during chronic LA, neither cardiovascular events occurred nor was CVD progression detected clinically or by routine imaging techniques. In four patients (24%), cardiovascular events documented progression of CVD despite weekly LA, including one death due to coronary and cerebrovascular CVD which was not stabilized after commencing LA. Based on the mutational status, only 6 out of the 17 children were candidates for proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibition. Two already responded with further LDL-C decrease by 40%. Conclusions Next to drug therapy, regular LA is an essential component of LLT for approaching LDL-C targets in children with hoFH or c-hetFH, which was successful only in a minority of children. Progression of CVD morbidity and resulting mortality remain unresolved issues. Early and intensified multimodal LLT guided by risk factors beyond LDL-C concentration is needed to improve outcome

Automated Greulich-Pyle bone age determination in children with chronic kidney disease

Growth restriction and retarded bone age are common findings in children with chronic kidney disease (CKD). We compared the automated BoneXpert (TM) method with the manual assessment of an X-ray of the non-dominant hand. In this retrospective multicenter study, 359 patients with CKD stages 2-5, aged 2-14.5 (girls) or 2.5-17 years (boys) were included. Bone age was determined manually by three experts (according to Greulich and Pyle). Automated determination of bone age was performed using the image analysis software BoneXpert (TM). There was a strong correlation between the automatic and the manual method (r = 0.983, p < 0.001). The automatic method tended to generate higher bone age values (0.64 +/- 0.73 years) in the younger patients (4-5 years) and to underestimate retardation or acceleration of bone age. The so-called bone health index (BHI) was reduced in comparison to the reference population. Bone health index standard deviation score (BHI-SDS) was not related to the stage of CKD, but weakly negatively correlated with plasma PTH concentrations (r = 0.12, p = 0.019). BoneXpert (TM) allows an objective, time-saving, and in general valid bone age assessment in children with CKD. Possible underestimation of retarded or accelerated bone age should be taken into account. Validation of the BHI needs further study

Endurance-oriented training program with children and adolescents on maintenance hemodialysis to enhance dialysis efficacy-DiaSport (Jun, 10.1007/s00467-021-05114-8, 2021)

A Correction to this paper has been published

Cardiovascular Outcome of Pediatric Patients With Bi- Allelic (Homozygous) Familial Hypercholesterolemia Before and After Initiation of Multimodal Lipid Lowering Therapy Including Lipoprotein Apheresis

Twenty-four patients with bi-allelic familial hypercholesterolemia commencing chronic lipoprotein apheresis (LA) at a mean age of 8.5 +/- 3.1 years were analysed retrospectively and in part prospectively with a mean follow-up of 17.2 +/- 5.6 years. Mean age at diagnosis was 6.3 +/- 3.4 years. Untreated mean LDL-C concentrations were 752 mg/di +/- 193 mg/di (19.5 mmol/l +/- 5.0 mmol/l). Multimodal lipid lowering therapy including LA resulted in a mean LDL-C concentration of 184 mg/di (4.8 mmol/l), which represents a 75.5% mean reduction. Proprotein convertase subtilisin/kexin type 9-antibodies contributed in 3 patients to LDL-C lowering with 5 patients remaining to be tested. After commencing chronic LA, 16 patients (67%) remained clinically stable with only subclinical findings of atherosclerotic cardiovascular disease (ASCVD), and neither cardiovascular events, nor need for vascular interventions or surgery. In 19 patients (79%), pathologic findings were detected at the aortic valve (AV), which in the majority were mild. AV replacement was required in 2 patients. Mean Lipoprotein(a) concentration was 42.4 mg/dl, 38% had >50 mg/dl. There was no overt correlation of AV pathologies with other ASCVD complications, or Lipoprotein(a) concentration. Physicochemical elimination of LDL particles by LA appears indispensable for patients with bi-allelic familial hypercholesterolemia and severe hypercholesterolemia to maximize the reduction of LDL-C. In conclusion, in this rare patient group regular assessment of both the AV, as well as all arteries accessible by ultrasound should be performed to adjust the intensity of multimodal lipid lowering therapy with the goal to prevent ASCVD events and aortic surgery. (C) 2020 Elsevier Inc. All rights reserved

HOSPITALIZATION BURDEN IN CHILDREN WITH CHRONIC KIDNEY DISEASE (CKD): FINDINGS FROM THE 4C STUDY

WOS: 00040841890045

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