16 research outputs found
Plasma Urotensin II levels in children and adolescents with chronic kidney disease: a single-centre study
The immunopathogenesis of idiopathic nephrotic syndrome: a narrative review of the literature
Idiopathic nephrotic syndrome (INS) is a common glomerular disease in
childhood, and the immunological involvement in the pathogenesis of
non-genetic INS, although not fully elucidated, is evident. This
narrative review aims to offer a concise and in-depth view of the
current knowledge on the immunological mechanisms of the development of
INS as well as the role of the immunological components of the disease
in the responsiveness to treatment. T cell immunity appears to play a
major role in the INS immunopathogenesis and has been the first to be
linked to the disease. Various T cell immunophenotypes are implicated in
INS, including T-helper-1, T-helper-2, T-helper-17, and T regulatory
cells, and various cytokines have been proposed as surrogate biomarkers
of the disease; however, no distinct T helper or cytokine profile has
been conclusively linked to the disease. More recently, the recognition
of the role of B cell mediated immunity and the various B cell subsets
that are dysregulated in patients with INS have led to new hypotheses on
the underlying immunological causes of INS. Finally, the disambiguation
of the exact mechanisms of the INS development in the future may be the
key to the development of more targeted personalized approaches in
managing INS.
Conclusions: INS demonstrates particularly interesting
immunopathogenetic pathways, in which multiple interactions between T
cell and B cell immunity and the podocyte are involved. The
disambiguation of these pathways will provide promising novel
therapeutic targets in INS.
What is Known:
INS is the most common glomerular disease in the paediatric population,
and its onset and relapses have been linked to various immunological
triggers.
Multiple immunological mechanisms have been implicated in the
pathogenesis of INS; however, no single distinct immunological profile
has been recognized.
What is New:
Th17 cells and Treg cells play an important role in the immune
dysregulation in INS.
Transitional B cell levels as well as the transitional/memory B cell
ratio have been correlated to nephrotic relapses and have been proposed
as biomarkers of INS relapses in SSNS patients
Nucleotide variations in the NPHS2 gene in Greek children with steroid-resistant nephrotic syndrome.
Safety and immunogenicity of booster immunization with 7-valent pneumococcal conjugate vaccine in children with idiopathic nephrotic syndrome
Safety and immunogenicity of a booster dose of 7-valent pneumococcal
conjugate vaccine (PCV7) were evaluated in 29 patients with idiopathic
nephrotic syndrome (INS), who had been primed 12 months earlier with one
dose of PCV7. PCV7 was not associated with increased risk of INS relapse
(RR = 0.77, p = 0.8) and serotype-specific antibodies increased in all
subjects at 1 month (p < 0.01). The quantitative characteristics of
immune response and the effect of treatment with mycophenolate mofetil
and/or cyclosporine A following booster PCV7 were similar with primary
response. Additional PCV7 doses could be safely given in children with
INS to increase circulating antibodies above the protective threshold.
(C) 2014 Elsevier Ltd. All rights reserved
Broad and unexpected phenotypic expression in Greek children with steroid-resistant nephrotic syndrome due to mutations in the Wilms' tumor 1 (WT1) gene
Plasma Brain Natriuretic Peptide Levels in Children with Chronic Kidney Disease and Renal Transplant Recipients: A Single Center Study
Pediatric chronic kidney disease (CKD) patients, as well as kidney transplant patients, are at an increased risk of developing cardiovascular disease. BNP measurement, as a biomarker of cardiovascular risk, has been recommended to this high-risk population. Plasma BNP levels were measured in 56 CKD children in either pre-dialysis stage, hemodialysis (HD) or renal transplant recipients (RTRs) and in 76 sex- and age-matched healthy controls. BNP levels were investigated in HD children, before and after the completion of their HD session. BNP levels in total CKD population, in pre-dialysis stage patients and on HD were significantly higher, compared to the respective controls. HD children had higher BNP levels compared to CKD patients in the pre-dialysis stage. Moreover, post-HD BNP concentration was slightly higher than pre-HD, with the difference being marginally statistically significant. BNP was positively correlated with eGFR, creatinine, cystatin-C and parathormone and negatively with albumin and 25-hydroxyvitamin D. A positive correlation between BNP concentration and the ratio of E/A in pulse-wave Doppler echocardiography was also observed. In conclusion, CKD pediatric patients, mainly those undergoing HD, have high plasma BNP levels which do not decrease after the HD session. This is indicative of a greater risk for future cardiovascular disease
Plasma Urotensin II levels in children and adolescents with chronic kidney disease: a single-centre study
Abstract Background Increased plasma Urotensin II (UII) levels have been found in adults with renal diseases. Studies in children are scarce. The objective of the study is to estimate plasma UII levels in subjects with chronic kidney disease (CKD) stages 3 to 5 and renal transplant recipients (RTR). In addition, the correlation of UII with anthropometric features and biochemical parameters was assessed. Methods Fifty-four subjects, aged 3 to 20 years old, 23 with CKD, 13 with end-stage kidney disease (ESKD) undergoing hemodialysis (HD) and 18 RTR were enrolled. A detailed clinical evaluation was performed. Biochemical parameters of renal and liver function were measured. Plasma UII levels were measured in all patients and in 117 healthy controls, using a high sensitive enzyme immunoassay (EIA) kit. All data were analyzed using STATA™ (Version 10.1). Results Median UII and mean log-transformed UII levels were significantly higher in CKD and RTR patients compared to healthy subjects (p < 0.001). HD patients had higher but not statistically significant UII and log-UII levels than controls. UII levels increased significantly at the end of the HD session and were higher than controls and in line to those of other patients. The geometric scores of UII in HD (before dialysis), CKD and RTR patients increased respectively by 42, 136 and 164% in comparison with controls. Metabolic acidosis was associated with statistical significant change in log-UII levels (p = 0.001). Patients with metabolic acidosis had an increase in UII concentration by 76% compared to those without acidosis. Conclusions Children and adolescents with CKD, particularly those who are not on HD and RTR, have significantly higher levels of UII than healthy subjects. UII levels increase significantly at the end of the HD session. The presence of metabolic acidosis affects significantly plasma UII levels
Novel and known nephrin gene (NPHS1) mutations in two Greek cases with congenital nephrotic syndrome including a complex genotype
The burden of subclinical cardiovascular disease in children and young adults with chronic kidney disease and on dialysis.
Background
Cardiovascular disease (CVD) is a common cause of morbidity and mortality even in young people with chronic kidney disease (CKD). We examined structural and functional CV changes in patients ˂30 years of age with CKD Stages 4 and 5 and on dialysis.
Methods
A total of 79 children and 21 young adults underwent cardiac computed tomography for coronary artery calcification (CAC), ultrasound for carotid intima-media thickness (cIMT), carotid-femoral pulse wave velocity (cfPWV) and echocardiography. Differences in structural (CAC, cIMT -score, left ventricular mass index) and functional (carotid distensibility -score and cfPWV -score) measures were examined between CKD Stages 4 and 5 and dialysis patients.
Results
Overall, the cIMT -score was elevated [median 2.17 (interquartile range 1.14-2.86)] and 10 (10%) had CAC. A total of 16/23 (69.5%) patients with CKD Stages 4 and 5 and 68/77 (88.3%) on dialysis had at least one structural or functional CV abnormality. There was no difference in the prevalence of structural abnormalities in CKD or dialysis cohorts, but functional abnormalities were more prevalent in patients on dialysis (P 2 standard deviation (SD) or distensibility <-2 SD) had less carotid dilatation (lumen:wall cross-sectional area ratio) compared with those with normal cIMT and distensibility.
Conclusions
There is a high burden of subclinical CVD in young CKD patients, with a greater prevalence of functional abnormalities in dialysis compared with CKD patients. Longitudinal studies are required to test these hypothesis-generating data and define the trajectory of CV changes in CKD
Routine serum biomarkers, but not dual-energy X-ray absorptiometry, correlate with cortical bone mineral density in children and young adults with chronic kidney disease.
BACKGROUND
Biomarkers and dual-energy X-ray absorptiometry (DXA) are thought to be poor predictors of bone mineral density (BMD). The Kidney Disease: Improving Global Outcomes guidelines suggest using DXA if the results will affect patient management, but this has not been studied in children or young adults in whom bone mineral accretion continues to 30 years of age. We studied the clinical utility of DXA and serum biomarkers against tibial cortical BMD (CortBMD) measured by peripheral quantitative computed tomography, expressed as Z-score CortBMD, which predicts fracture risk.
METHODS
This was a cross-sectional multicentre study in 26 patients with CKD4 and 5 and 77 on dialysis.
RESULTS
Significant bone pain that hindered activities of daily living was present in 58%, and 10% had at least one low-trauma fracture. CortBMD and cortical mineral content Z-scores were lower in dialysis compared with CKD patients (P = 0.004 and P = 0.02). DXA BMD hip and lumbar spine Z-scores did not correlate with CortBMD or biomarkers. CortBMD was negatively associated with parathyroid hormone (PTH; r = -0.44, P < 0.0001) and alkaline phosphatase (ALP; r = -0.22, P = 0.03) and positively with calcium (Ca; r = 0.33, P = 0.001). At PTH <3 times upper limit of normal, none of the patients had a CortBMD below -2 SD (odds ratio 95% confidence interval 7.331 to infinity). On multivariable linear regression PTH (β = -0.43 , P < 0.0001), ALP (β = -0.36, P < 0.0001) and Ca (β = 0.21, P = 0.005) together predicted 57% of variability in CortBMD. DXA measures did not improve this model.
CONCLUSIONS
Taken together, routinely used biomarkers, PTH, ALP and Ca, but not DXA, are moderate predictors of cortical BMD. DXA is not clinically useful and should not be routinely performed in children and young adults with CKD 4-5D