The choice of vascular access (VA) plays a key role in the success of hemodialysis (HD). Despite their widespread use, central venous catheters (CVCs) are associated with higher rates of dysfunction, thrombosis, and catheter-related bloodstream infections (CRBSI). We investigated current practices in pediatric HD across European pediatric nephrology centers, focusing on VA choices, infection control measures, and CRBSI management. An online questionnaire was e-mailed to 119 members of the European Society for Pediatric Nephrology (ESPN) Dialysis Working Group and European Pediatric Dialysis Working Group (EPDWG). Descriptive statistics were used to summarize practices across centers, comparative analyses between centers in countries with Human Development Index (HDI) > 0.90 and < 0.90. Thirty-one centers across Europe participated in the survey. CVCs were the primary VA in 73.1

Prescribing an adequate intraperitoneal dialysate volume is essential in peritoneal dialysis (PD) to balance optimal solute and fluid removal against the risk of increased intraperitoneal pressure (IPP) and to prevent increased reabsorption and mechanical complications. Since the description of manual hydrostatic IPP measurement (IPPM) in children in 1996, a few small observational studies in children and adults have provided limited evidence on the acceptable upper limit of IPP and associated complications. We conducted a practice survey across European pediatric dialysis centers, which showed that of the responding 47 centers, 68

Background:Children with steroid-dependent nephrotic syndrome (SDNS) require long-term immunosuppressive (IS) treatment, significantly impacting their quality of life. Cord-blood-derived mesenchymal stromal cells (CB-MSCs) are multipotent stem cells with proven immunomodulatory properties. Methods:We conducted an adaptive, open-label, single-arm, phase II trial with an adaptive second part to evaluate the efficacy of CB-MSCs in children aged 3-18 years with SDNS in remission for ≥6 months on IS therapy. In Part 1, patients received three intravenous infusions of CB-MSCs (1.5 × 10⁶/kg) at 1-2-week intervals, with rapid IS tapering and discontinuation after the third infusion. The primary endpoint was relapse-free survival at 6 months post-IS withdrawal, with a threshold of <4/11 relapsing patients. In the adaptive Part 2, IS was discontinued before the first infusion to enhance CB-MSCs activity, and the dose was increased to 2 × 10⁶/kg, with a booster fourth infusion. A historical cohort of SDNS children tapering IS under standard care served as a post-hoc control. Results:In Part 1, 9 patients were enrolled, and 7/9 (78%) relapsed, failing to meet the prespecified efficacy threshold. In Part 2, 11 patients were enrolled; 9 (82%) were in remission at 2 weeks post-third infusion and received the boosted dose. However, 6/11 (55%) relapsed within 6 months, with no significant difference in relapse-free survival compared to Part 1 (P = .25). Historical controls had significantly better relapse-free survival (P = .0007). Conclusion:In children with SDNS, this novel therapy with CB-MSCs was safe but failed to improve relapse-free survival 6 months after IS withdrawal.

The pathogenesis of idiopathic nephrotic syndrome (INS) in most pediatric cases involves immune cell dysfunction, mediated, among other factors, by biologically active polyunsaturated fatty acids -dependent compounds in the blood and cell membranes. The immunosuppressive drug mycophenolate mofetil (MMF) is commonly used to maintain remission in patients with steroid-dependent nephrotic syndrome. The aim of this pilot study was to investigate the effect of trough blood mycophenolic acid (MPA) levels on the endoleukocyte fatty acid omega-3 and omega-6 series. Eighteen pediatric subjects with INS were enrolled, including 12 steroid-sensitive and 6 steroid-resistant children. Fatty acid (FA) profile was analyzed by gas-chromatography, and MPA blood level was evaluated by immunometric assay. Among steroid-sensitive patients, a positive correlation was observed between endoleukocyte omega-3 FA (n-3) and trough blood MPA levels, and a negative correlation was found between endoleukocyte omega-6 FA (n-6) and trough blood MPA levels. In addition, a positive correlation was found between endoleukocyte anti-inflammatory DHA and trough blood MPA levels. In contrast, in steroid-resistant subjects no correlation between endoleukocyte n-6/n-3 ratio and trough blood MPA levels was observed. In conclusion, adequate trough MPA drug levels may have contributed to switch the FA pathway to a more favorable endoleukocyte n-6/n-3 ratio and DHA levels, possibly supporting the natural anti-inflammatory activities of n-3 FA. In steroid-resistant NS, despite adequate MPA levels, no promotion of the anti-inflammatory activity of the n-3 series was found.

Automated peritoneal dialysis (APD) consists of dwells with the same dwell volume and time. New cyclers allow modification of time and volume to prescribe adapted APD (AAPD), i.e., a series of short, small dwells followed by long, large dwells. Safety, efficacy, and underlying mechanisms of AAPD in children are uncertain. Two double mini-PET were performed in randomized sequence. The standard test consisted of two identical cycles (fill volume 1000 ml/m2, 75 min) and the adapted test of a short, small cycle (600 ml/m2 BSA, 30 min) followed by a long, large cycle (1400 ml/m2, 120 min). Solute and water fluxes were quantified together with intraperitoneal pressure (IPP). Nine pediatric PD patients (5–21 years) were treated per protocol. Residual dialysate volume was 422 ± 190 ml/m2 BSA. There were no differences in ultrafiltration rates, glucose uptake, and creatinine, urea, and electrolyte clearances with the adapted and standard double mini-PET, despite identical cumulative dialysate volume and time. IPP varied by 1.7 ± 3.4 (range −2 to 9) cm H2O with a drained volume of 1123 ± 386 and 1159 ± 210 ml/m2 BSA for each standard dwell. IPP decreased from 1.9 with small volume to 1.0 cm H2O /m2/100 ml with large volume dwells (p < 0.001) and was above 14 cm H2O in 21 out of 63 measurements. Within the limitation of small patient numbers, this proof-of-concept study suggests similar ultrafiltration and clearance rates with a single adapted versus standard double mini-PET. High residual dialysate volumes and high IPPs highlight the challenges of AAPD prescription in children.

Hyperkalemia is an important issue in kidney failure. The aim of the study was to investigate the predictors of hyperkalemia in children receiving maintenance dialysis. This was an international prospective cross-sectional observational study involving patients < 18 years receiving chronic hemodialysis or peritoneal dialysis. Hyperkalemia was defined as serum potassium (sK+) ≥ 5 mEq/L based on the Pediatric Renal Nutrition Taskforce recommendations. We recorded age, dialysis vintage, urine output (24-h urine collection); dietary K+, energy, protein and sodium intake (three-day diaries); office blood pressure (BP) in children < 5 years and 24-h ABPM in older patients; biochemistry (creatinine, urea, sodium, bicarbonate, hemoglobin, phosphate, albumin) and antihypertensive drugs. Forty-one patients were enrolled (10 peritoneal dialysis, 31 hemodialysis), median age 13.3 (IQR 10.6–15.8) years; 15 of them (36.6

Background:Limited data exist on rehospitalization in paediatric dialysis patients. The objective of this study was to identify indications, rates and risk factors for 30-day readmissions in this population. Methods:We used a prospective multinational, multicentre cohort study of haemodialysis (HD) and peritoneal dialysis (PD) patients discharged between July 2017 and July 2018. Readmission was identified as repeat hospitalization within 30 days of a prior (index) admission. Potentially preventable readmissions were clinically related to the initial admission. Early readmissions were those occurring within 7 days of discharge. The primary outcome was 30-day readmission. Secondary outcomes included potentially avoidable and early readmissions. Results:A total of 54 (31%) of 176 patients (102 PD, 74 HD) had at least one readmission; 84 (18%) discharges were followed by readmission. PD and HD patients had similar readmission rates {30.4% versus 31.1%; hazard ratio [HR] 1.06 [95% confidence interval (CI) 0.61-1.81]}. Compared with PD, HD patients had a significantly shorter time to readmission (8 versus 14 days; P = .019), higher early readmission rates (46% versus 18%; P = .010) and risk [odds ratio (OR) 3.87 (95% CI 1.35-11.11)]. Main readmission causes were dialysis access-related non-infectious complications (31%) and access infections (22.7%); 47% of readmissions were potentially avoidable. Lower haemoglobin levels were linked to readmission [HR 0.78 (95% CI 0.64-0.95)]. Bicarbonate use was associated with a 51% lower readmission risk [HR 0.49 (95% CI 0.24-0.99)]. Neurological comorbidity [OR 7.00 (95% CI 1.04-47.22)] and partial recovery [OR 56.45 (95% CI 3.02-1053.10)] were risk factors for avoidable readmission. Risk of avoidable and early readmission decreased with age [OR 0.98 (95% CI 0.97-0.99) and OR 0.99(95%CI 0.98-0.99), respectively]. Conclusions:Readmissions are common in paediatric dialysis patients, with a substantial proportion being potentially preventable. To reduce rehospitalizations, interventions should target modifiable factors such as access complications, anaemia and incomplete recovery at discharge, while recognizing non-modifiable risks like HD and younger age to identify high-risk patients.

Time to remission (TTR) has been largely considered one of the predictive factors for the risk of relapse and steroid dependency in childhood steroid-sensitive nephrotic syndrome, yet conflicting opinions exist. However, the factors influencing TTR have never been studied. We performed a post-hoc analysis of the prospective pediatric cohort enrolled in a previous multicenter study (ClinicalTrials.gov Id: NCT01386957) to evaluate the possible influence of some clinical and laboratory parameters at INS onset on the timing of TTR. A total of 136 children were evaluated. In simple linear regression models, TTR was directly correlated with serum uric acid, urea, potassium, and urinary protein levels at onset. TTR showed a non-linear inverse correlation with age at onset. A multiple linear regression model of TTR showed that hyperuricemia (p = 0.0000007), non linear age ( p = 0.0006) and proteinuria (especially in binary form) ( p = 0.02) were significant predictors of TTR, and that there was a significant positive interaction between uricemia and proteinuria as predictors of TTR ( p = 0.004). Conclusions : In our analysis, TTR appears to be associated to a nephrotic status at clinical diagnosis characterized by more severe proteinuria and hyperuricemia. Moreover, younger age at onset, notably associated with prognosis, is also associated with a longer TTR. What is Known: • Corticosteroids are the first-line treatment in childhood nephrotic syndrome. • Over the years, time to remission has been considered a potential predictive factor for the risk of relapse and steroid dependency in childhood nephrotic syndrome, with conflicting results. What is New: • Clinical and laboratory parameters at nephrotic syndrome onset are associated with prolonged time to remission in children.

BACKGROUND:The effectiveness of therapeutic drug monitoring (TDM) of mycophenolic acid (MPA) trough levels in children with steroid-dependent or frequently relapsing nephrotic syndrome (SDNS/FRNS) treated with mycophenolate mofetil (MMF) has not been adequately assessed. METHODS:We performed an international, retrospective study including children with SDNS/FRNS, treated with MMF as the first-line steroid-sparing agent, and a follow-up of more than six months. Patients were categorized into two groups: TDM, if MPA trough levels were monitored, and No-TDM, if not. In the TDM group, MMF doses were adjusted to maintain MPA trough levels of more than 3 µg/ml, unless toxicity occurred. The primary outcome was relapse-free survival. RESULTS:A total of 167 patients were observed, 90 in the TDM and 77 in the No-TDM group. Relapse-free survival over the total follow-up was significantly longer in the TDM group (p=0.001, log-rank test) with an estimated relapse-free survival at six months of 73% for the TDM and 55% for the No-TDM group. After correcting for potential confounders, the association remained statistically significant (p<0.001). TDM patients also received lower doses of prednisone after MMF introduction. In the TDM group, children were more likely to modify their initial dose (90% vs 9%; p<0.001). While MMF dose was not associated with relapse (median 1186 vs 1298 mg/m 2 ; p=0.14), MPA trough levels were significantly higher in children who did not relapse (4.0 vs 2.7 µg/ml, p=0.001). Among children maintaining mean MPA levels more than 2.9 µg/ml, relapse-free survival at 6 months was 86%. Reported side effects were similar in both groups. CONCLUSIONS:Monitoring MPA trough levels was associated with an approximately 20% higher MMF effectiveness in maintaining remission at six months in children with SDNS/FRNS. Personalized MMF dosing, adjusted to maintain MPA levels more than 2.9 µg/ml, was both safe and effective. We recommend including MPA trough level monitoring in future studies comparing MMF with other steroid-sparing agents in SDNS/FRNS children.

Previous studies investigating hospitalizations in dialysis patients have focused primarily on patient-centered factors. We analyzed the impact of hospital and dialysis unit characteristics on pediatric dialysis patients’ hospitalizations for access-related complications (ARCs). This cross-sectional study involved 102 hemodialysis (HD) and 163 peritoneal dialysis (PD) patients. Data between July 2017 and July 2018 were analyzed. Children’s hospitals (CHs) had more pediatric nephrologists and longer PD experience (years) than general hospitals (GHs) (p = 0.026 and p = 0.023, respectively). A total of 53

Kidney transplantation is the preferred therapeutic option for end-stage kidney disease, but, despite major therapeutic advancements, allograft rejection continues to endanger graft survival. Every patient is unique due to his or her clinical history, drug metabolism, genetic background, and epigenetics. For this reason, examples of "personalized medicine" and "precision medicine" have steadily increased in recent decades. The final target of precision medicine is to maximize drug efficacy and minimize toxicity for each individual patient. Immunosuppressive drugs, in the setting of kidney transplantation, require a precise dosage to avoid either adverse events (overdosage) or a lack of efficacy (underdosage). In this review, we will explore the knowledge regarding the pharmacogenomics of the main immunosuppressive medications currently utilized in kidney transplantation. We will focus on clinically relevant pharmacogenomic data, that is, the polymorphisms of the genes that metabolize immunosuppressive drugs.

Background and hypothesis. Hospital admissions in pediatric dialysis patients need to be better studied, and most existing studies are retrospective and based on registry data. This study aimed to analyse and compare hospital admission rates, causes, length of stay (LOS), and outcomes in children treated with peritoneal dialysis (PD) and hemodialysis (HD).Methods. Data from 236 maintenance PD and 138 HD patients across 16 European dialysis centers were collected between 1 July 2017 and 30 June 2018. A total of 178 hospitalized patients (103 PD, 75 HD) were included for further analyses.Results. There were 465 hospitalization events (268 PD, 197 HD) with a rate of 0.39 admissions per 100 patient-days at risk (PDAR) and 2.4 hospital days per 100 PDAR. The admission rates were not significantly different between HD and PD patients. The most common causes of hospitalization were access-related infections (ARI) (17%), non-infectious complications of access (NIAC) (14%), and infections unrelated to access (12%). ARI was the leading cause in PD patients (24%), while NIAC was more common in HD patients (19%). PD patients had more ARIs, diagnostic procedures, and treatment adjustments (P < .05), while HD patients had more NIACs, infections unrelated to access, access placement procedures, and interventional/surgical procedures (P < .001). LOS was longer with acute admissions than non-acute admissions (P < .001). Overall LOS and LOS in the intensive care unit were similar between HD and PD patients. High serum uric acid and low albumin levels were significant predictors of longer LOS (P = .022 and P = .045, respectively). Young age, more significant height deficit, and older age at the start of dialysis were predictors of longer cumulative hospital days (P = .002, P = .001, and P = .031, respectively).Conclusion. Access-related complications are the main drivers of hospitalization in pediatric dialysis patients, and growth and nutrition parameters are significant predictors of more extended hospital stays.

Sodium (Na) balance is unexplored in dialyzed children. We assessed a simplified sodium balance (sNaB) and its correlates in pediatric patients receiving maintenance dialysis. Patients < 18 years old on hemodialysis (HD) or peritoneal dialysis (PD) in six European Pediatric Dialysis Working Group centers were recruited. sNaB was calculated from enteral Na, obtained by a 3-day diet diary, Na intake from medications, and 24-h urinary Na (uNa). Primary outcomes were systolic blood pressure and diastolic blood pressure standard deviation scores (SBP and DBP SDS), obtained by 24-h ambulatory blood pressure monitoring or office BP according to age, and interdialytic weight gain (IDWG). Forty-one patients (31 HD), with a median age of 13.3 (IQR 5.2) years, were enrolled. Twelve patients (29.3

Background: The ''HDF-Heart-Height'' study showed that haemodiafiltration (HDF) is associated with improved growth compared to conventional haemodialysis (HD). We report a post-hoc analysis of this study assessing the effect of extracorporeal dialysis therapies on nutritional indices. Methods: 107 children were included in the baseline cross-sectional analysis, of whom 79 (43 HD, 36 HDF) completed the 12-month follow-up. Height (Ht), optimal 'dry' weight (Wt), and body mass index (BMI) standard deviations scores (SDS), waist-to-hip ratio, des-acyl ghrelin (DAG), adiponectin, leptin, insulin-like growth factor-1 (IGF-1)-SDS and insulin were measured. Results: The levels of nutritional indices were comparable between HDF and HD patients at baseline and 12-month. On univariable analyses Wt-SDS positively correlated with leptin and IGF-1-SDS, and negatively with DAG, while Ht-SDS of the overall cohort positively correlated with IGF1-SDS and inversely with DAG and adiponectin. On multivariable analyses, higher 12-month Ht-SDS was inversely associated with baseline DAG (beta= -0.13 per 500 higher; 95%CI-0.22,-0.04; P=.004). Higher Wt-SDS at 12-month was positively associated with HDF modality (beta 5 0.47 vs HD; 95%CI 0.12-0.83; P =.01) and inversely with baseline DAG (beta=-0.18 per 500 higher; 95%CI -0.32, -0.05; P =.006). Growth Hormone (GH) treated patients receiving HDF had higher annualized increase in Ht SDS compared to those on HD. Conclusions: In children on HD and HDF both Wt- and Ht-SDS independently correlated with lower baseline levels of the anorexygenic hormone DAG. HDF may attenuate the resistance to GH, but further studies are required to examine the mechanisms linking HDF to improved growth.