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.
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.
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.
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).
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.
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.
Abstract
Background and Aims
Attainment of a normal adult height remains a great challenge in the care of children with end stage kidney disease. Moreover, the incidence of overweight and obesity ...increases post kidney transplantation (KT). We aimed to describe growth parameters and predictive factors in children post KT.
Method
We retrospectively reviewed the records of 28 children who underwent KT in our center between 2002-2022. Height (hSDS) and body mass index (BMISDS) z-scores at various time points and possible predictors were assessed.
Results
Median age at KT was 11.2 years (5.3-14), 20 were male, mean time on dialysis was 5.95 years. KT from a living donor (LRD) was performed in 18 patients. Mean follow-up time was 4.88 (1-10) years. rhGH was administered pre-KT in 15/28 patients and in 3 post KT. Following the first year post KT, steroid free, alternate day and daily steroid regimes were adopted for 9, 11 and 8 patients, respectively. Mean hSDS at the time of KT, one year after and at last visit were -1.76, -1.87, and -1.77 (p>0.05). Mean BMISDS at the respective time points were 0.13, 0.65 and 0.05 respectively (p>0.05). At last visit, 29% and 17% of children showed moderate and severe height deficit. hSDS at last visit was associated with preoperative hSDS, whereas difference between hSDS pre and last visit post KT (ΔhSDS) was associated with the type of KT mean ΔhSDS for LRD and DDT -1.45 (95%CI -1.87, -1.03) and -2.66 (95%CI -3.4, -1.93) respectively, p = 0.002 and steroid regime mean ΔhSDS for daily and alternate day steroid treatment -0.39 (95%CI -0.77, -0.003) and 0.55 (95%CI -0.07, 1.17) respectively, p = 0.037. Τhere was no association between ΔhSDS and rejection episodes or rhGH administration pre-KT. At the time of KT and at last visit 25% and 10.7% were overweight, respectively, whereas only 1 patient was obese preoperatively but none at last visit. The overall incidence of overweight and obesity had reduced at last visit compared to pre-KT (p = 0.01).
Conclusion
Linear growth post KT remained limited, resulting in short stature in nearly half of children. Strategies to improve height post pediatric KT could include height optimization pre-KT, steroid withdrawal/avoidance protocols, and LRD KT.
Abstract
Background and Aims
Bartter syndrome is an autosomal recessive renal tubular disorder. Clinical diagnosis can be challenging due to rarity and phenotypic overlap. Little information is ...available on a long term follow-up in Bartter syndrome. Our aim was to describe clinical -genetic correlations as well as our experience from the long term follow up of these patients.
Method
Clinical and genetic characteristics of patients with Bartter syndrome at diagnosis and long term follow up are reported in 19 children. Genetic testing (whole exome sequencing, WES) was done in 14/19 patients. The study period was 17 years (January 1, 2006 to December 31, 2022).
Results
16 Caucasian and 3 of gipsy origin (13 boys, 68%) were included. The median age at diagnosis was 0,52 yrs. Median follow up time was 9.8yrs (IQR 6.86-13.8). WES revealed 6 mutations in KCNJ1 genes, 5 in SLC12A1 and 3 in CLCNKB genes. 4 new mutations were identified (3 in KCNJ1 genes and 1 in SLC12A1. 18/19 children were born pre-term (including 2/3 patients with CLCNKB). Nephrocalcinosis was present in 18/19 patients (included the 3 patients with CLCKNB mutations). 4/6 patients with KCNJ1 mutations presented initially with hyperkalemia. Medical treatment in the last follow up included supplementation with potassium in 18, non -steroidal anti-inflammatory agents in 15 and gastroprotective drugs in 13, ramipril in 2. 2/19 received recombinant growth hormone. At last follow up body weight and height were within normal ranges in 16/19 (84%) patients. Hyperparathyroidism (median time of PTH 151.5 pg/ml) have 6/11 (56%) of patients with Bartter I (ΚCNJ1mutation) and Bartter II (SLC12A1 mutation) and only 1/3 with Bartter III (CLCNKB mutation). 2/19 patients have proteinuria. Chronic kidney disease (CKD) occurred in 7/19 (37%) suggesting that the long term prognosis can be unfavorable (4 CKD stage II, 3 CKD stage III). Of note 2 patients with CKD had impaired renal function since diagnosis while the remaining 5 progressed gradually during followup.
Conclusion
WES is useful in dealing with the phenotypic heterogeneity of Bartter syndrome. Our results emphasize the need for early diagnosis, regular followup and appropriate treatment in order to maintain normal renal function and achieve normal final height and weight.
Abstract
Background and Aims
The determination of dry weight (DW) in children on chronic hemodialysis (HD) remains problematic. No method has been shown superior for DW assessment in the few ...pediatric studies exploring the utility of inferior vena cava expiratory and inspiratory diameter diameter (IVCDe, IVCDi) and BIS against clinical criteria. We aimed to compare the performance of IVCD, BIS and clinical judgement in DW prediction in hemodialyzed children.
Method
IVCD and BIS were measured serially pre and post the midweek HD session. IVCDi, IVCDe and IVC contractility index (IVCCI) associations with: (1) BIS estimated (BIS-relOH) and (2) clinically assessed hydration status (OHc) based on deviation from DW were explored. The interpretation of IVC measurements was based on previously published pediatric reference values. The level of agreement between the three tools in fluid overload recognition was studied.
Results
Fifty-two sets of measurements were undertaken in 13 patients (median age 11 years). OHc and BIS-relOH were positively associated to each other (r=0,5, p<0,05) and to IVCDi (r=0,4, r=0,5, p<0,05) and IVCDe (r=0,4, r=0,6, p<0,05). A negative association between IVCCI and relOH-BIS was observed (r= -0,4, p<0,05). There was a poor agreement between the three methods in identification of fluid overload; out of 28 clinically overloaded patients, BIS identified only 7 whereas IVCD none (Cohen’s k <0).
Conclusion
IVCD measurements alone are not reliable for accurate fluid status prediction in hemodialyzed children as they seem to underestimate fluid overload compared to BIS and clinical criteria. Further studies are warranted to explore the applicability of new technologies for DW assessment of dialysis patients.
Abstract
Background and Aims
Cardiovascular disease is highly prevalent in the chronic kidney disease population and associates with higher morbidity and mortality even in young ages. The aim of the ...present study was to assess data from 24h ambulatory blood pressure monitoring (ABPM) and 24h pulse wave analysis (PWA) in dialyzed children and investigate their association with left ventricular mass as a marker of increased cardiovascular risk.
Method
Children and adolescents aged 6 to 18 years, on dialysis for more than 12 months, 16 on peritoneal dialysis (PD) and 12 on hemodialysis (HD), underwent 24h ABPM, 24h PWA, and echocardiography.
Results
Peripheral and central blood pressures (BPs), mean pulse wave velocity (PWV) and left ventricular mass index (LVMI) were similar between PD and HD patients (figure 1a,b). Among PWA hemodynamic parameters, augmentation index (AIx75), cardiac index (CI), and heart rate were higher in the HD group (p<0.05) (figure 1c,d). LVMI was associated with hemoglobin (Hb) (R2=0.19, p<0.05)mean arterial pressure (MAP) (R2=0.34, p<0.005), central systolic BP (cSBP) (R2=0.39, p<0.001), AIx75 (R2=0.26, p<0.005), CI (R2=0.14 p<0.05) and PWV (R2=0.26, p<0.005), but not with weight, body mass index or relative overhydration. CI and AIx75 were higher in the HD group compared to PD both in patients with normal LVMI and those with left ventricular hypertrophy (LVH). CI remained higher in HD patients after adjustment for Hb, MAP, cSBP, PWV, AIx75, and LVMI (estimated marginal means 4.17, 95%CI 3.80-4.53 versus 3.40, 95%CI 3.11-369 in PD patients, p<0.05). Similarly, AIx75 remained higher in HD patients after adjustment for Hb, MAP, cSBP, PWV, CI, and LVMI (estimated marginal means 28.89, 95%CI 24.49-33.30 versus 22.62, 95%CI 19.15-26.08 in PD patients, p=0.05).
Conclusion
HD pediatric patients demonstrate higher AIx75 and CI compared to PD patients even in the absence of LVH. These results suggest distinct patterns of vascular and cardiac functional changes in HD patients that may increase cardiovascular risk beyond LVH.
Abstract Anamnestic 13-valent pneumococcal conjugate vaccine immunization did not affect the relapse risk in pediatric idiopathic nephrotic syndrome. Pneumococcal serotype (PS)-specific antibody ...titers increased significantly in all groups. Children receiving immunomodulatory treatments (IMTs) displayed significantly lower levels of PS-specific antibodies for 3/8 serotypes tested. PS-specific B-cell counts significantly increased only in healthy controls and patients receiving corticosteroids.
Abstract
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.
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