CV disease is the major cause of death in patients with CKD. Recently, CMR imaging emerges as a complementary method providing advantages in cardiac assessment; however, data on CMR in pediatric CKD are scarce. We performed CMR in 15 children: two with CKD, six on peritoneal dialysis, seven on hemodialysis, and in 18 children 5.1 (0.4-15.4) yr after kidney Tx. Eight children underwent CMR six months before and after Tx. Results are presented as mean z score ± SD. LV EF was higher and in the normal range in Tx patients compared with CKD (-0.3 ± 1 vs. -2.1 ± 1.6, respectively, p < 0.05), whereas RV EF was similar (-0.9 ± 1.4 vs. -0.9 ± 1.8, p = n.s.). End-diastolic and end-systolic LV volume index (0 ± 1.7 vs. 2.1 ± 3.1; 0.2 ± 1.2 vs. 3.1 ± 3.7, both p < 0.05) and LV mass index (1.4 ± 1.5 vs. 3.4 ± 2.9, p < 0.05) were lower in Tx children. All parameters improved in the eight children after Tx. In conclusion, our CMR analysis suggests marked improvement of cardiac function and morphology in children after kidney Tx. CMR might be an appropriate complementary method for measuring detailed cardiac status in children with CKD.

Chronic kidney disease (CKD) greatly increases the risk for cardiovascular disease (CVD). However, molecular mechanisms underlying CKD-induced arterial remodeling are largely unknown. We performed a systematic analysis of arterial biopsies from children with stage 5 predialysis CKD participating in the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4 C) study. For comparison, we studied biopsies from children without CKD, coronary bypass vessels from adults with atherosclerotic coronary heart disease without CKD and aortic sections of subtotally nephrectomized rats. In pediatric CKD patients, gene expression was correlated to the cardiovascular phenotype assessed by surrogate end-points. The arterial calcium content correlated with the intima-media thickness (IMT) of biopsied vessels from pediatric CKD patients, was markedly increased compared to biopsies from children without CKD and comparable to adult coronary bypass patients. Significant transcriptional changes included ECM components, pro-calcifying factors, and physiological calcification inhibitors; most were highly accordant with changes observed in adults with atherosclerosis and in uremic rats. Individual gene expression levels were significantly associated with the left ventricular mass index and carotid intima media thickness. Thus, inflammatory processes (TNF, IL-10), calcification inhibitors (CA2), the Wnt-pathway (FGF-2) and foremost, ECM components (HMGA1, VNN1, VCAN), impact pathobiological responses in arteries from children with CKD.

This case documents a potent beneficial effect of rituximab on renal manifestation of GPA even in long-established ESRD.

Background and Aims Due to the unphysiological composition of PD fluids, chronic peritoneal dialysis (PD) induces progressive peritoneal fibrosis, hypervascularization, and vasculopathy. The evolution of the PD membrane and vasculopathy following kidney transplantation (KTx) is largely unknown. Method Arteriolar and peritoneal tissues were obtained from 107 children with chronic kidney disease (CKD5), 72 children on PD (treated with neutral pH PD fluids, with low glucose degradation product content, GDP) and 21 children, who underwent KTx 4-5 weeks after a median 21 months of PD. Specimen underwent standardized digital quantitative histomorphometry. Molecular mechanisms were studied in omental arterioles microdissected from surrounding fat by multi-omics followed by Gene Set Enrichment Analysis (GSEA); key findings were validated in parietal tissues of independent, matched cohorts by quantitative immunohistochemistry (n=15/group). Results Arteriolar transcriptome and proteome GSEA revealed suppression of leucocyte migration and T-cell activation / secretory pathways regulation, of sprouting angiogenesis biological processes and of epithelial proliferation and cell cycle after KTx as compared to PD. Lipid / fatty acid metabolism, autophagy and ATP synthesis pathways were activated. Transcriptome analysis including KTx, PD and CKD5 specifically attributed regulation of arteriolar lipid and fatty acid metabolism to transplantation and comprised 140 transcripts; their regulation was confirmed on the proteome level. Hub gene fatty acid synthase was identified by protein interaction analysis (string-db.org). 15 arteriolar genes activated by PD were inactivated after KTx and included glucose metabolisms and cytoskeleton related transcripts. 24 transcripts and 10 corresponding proteins induced by PD were still active after KTx and associated with biological processes related to TGF-ß signaling, fibrosis and mineral absorption. In line with arteriolar multi-omics findings, peritoneal hypervascularization induced by chronic PD was reversed after Tx to CKD5 level. CD45 positive tissue infiltrating leucocytes count was reduced by 40% and was independently associated with microvessel density in multivariable analysis including PD vintage, daily GDP exposure and recent KTx. Peritoneal lymphatic vessel density, submesothelial thickness, activated fibroblast, fibrin deposit, macrophage and EMT cell counts remained unchanged after KTx compared to PD. Arteriolar lumen to vessel ratios (a marker of vasculopathy) were similar in both groups. Vessel-homeostasis-related proteins in independent, matched cohorts demonstrated increased caspase-3 abundance in peritoneal arterioles after KTx. Arteriolar VEGF-A, thrombospondin, angiopoietin1/2, and hypoxia-inducible factor-1 (HIF-1a) were unchanged, while submesothelial HIF-1a and angiopoietin1/2 were decreased after Tx, favoring vessel maturation. The abundance of the key driver of fibrosis, TGF-ß-effector pSMAD2/3, was unchanged in the peritoneum and arterioles after Tx. Conclusion Our multi-omics analyses of fat covered omental arterioles, not directly exposed to PD fluids, demonstrate inhibition of PD induced immune response and angiogenesis pathways, of glucose metabolism and cytoskeleton regulation to levels similar as seen in children with CKD5. Arteriolar lipid and fatty acid metabolism is selectively altered after KTx. Reversal of low GDP PD induced hypervascularization and inflammation of the parietal peritoneum after KTx, mirror molecular changes in omental arterioles, while profibrotic activity persists after KTx in omental arterioles and in the parietal peritoneum.

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