Exploring systemic inflammation in children with chronic kidney disease: correlates of interleukin 6.

BACKGROUND: Systemic inflammation (SI) is linked to chronic kidney disease (CKD) progression and multiple complications. Data regarding SI biomarkers in pediatric patients are scarce. This case-control and cross-sectional study investigates the correlation of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), total iron binding capacity (TIBC) and serum albumin to serum interleukin-6 (IL-6). METHODS: NLR and PLR were measured in 53 patients (median age: 12.9 years), including 17 on dialysis and 36 with a median glomerular filtration rate of 39 ml/min/1.73m2, and in 25 age and sex-matched healthy controls. Iron profile, serum albumin and IL-6 were measured in the patient group. IL-6 levels > 3rd quartile were classified as high. RESULTS: Patients presented higher NLR and PLR and particularly those on dialysis (p < 0.001 and p = 0.001). We observed a significant correlation between natural logarithm (ln) of IL-6 (lnIL-6) and NLR (rs = 0.344, p = 0.014), serum albumin (rs = -0.350, p = 0.011) and TIBC (rs = -0.345, p = 0.012) after adjustment for CKD stage, while the correlation between lnIL-6 and PLR was not significant (rs = 0.206, p = 0.151). Combination of NLR, serum albumin and TIBC predicted high IL-6 (13 patients) with an AUC of 0.771 (95% CI 0.608-0.943). Pairing of NLR ≥ 1.7 and TIBC ≤ 300 µg/dL exhibited the highest sensitivity (76.9%), while incorporating serum albumin ≤ 3.8 g/dL along with them achieved the highest specificity (95%) for detecting high IL-6 levels. CONCLUSION: Both NLR and PLR levels increase in CKD, especially in patients on chronic dialysis. NLR, rather than PLR, along with TIBC and serum albumin, are associated with IL-6 in pediatric CKD.

Sources of error in direct radionuclide cystography in children and the need for a standardized, manometric apparatus.

Direct radionuclide cystography (DRC) is a safe and reliable method for the detection and follow-up of vesico-ureteral reflux (VUR). Since the first DRC was performed, during the early 60s, the method has undergone many refinements. Themanometric approach, which was first introduced in 1984, provides a correlation between the bladder pressure and VUR visualization. In this study the sources of error that may alter the results of DRC are discussed and a novel, standardized low costmanometric apparatus is suggested.

Association Between Adipokine Profile, Systemic Inflammation, Muscle and Protein Energy Wasting in Children With Chronic Kidney Disease.

OBJECTIVES: This cross-sectional study explores the association of adipokines and interleukin-6 (IL-6) with muscle and protein energy wasting (PEW) in children with chronic kidney disease (CKD). METHODS: We measured serum adiponectin, leptin, resistin and IL-6 in 53 patients with CKD stage 3-5. Lean tissue (LTI) and fat tissue index (FTI) were estimated by bioimpedance analysis spectroscopy. PEW was defined as muscle wasting [LTI adjusted to height age (LTI HA) z-score < -1.65 SD) and at least 2 of the following: reduced body mass [body mass index adjusted to height age (BMI HA) z-score < -1.65 SD), poor growth [height z-score < -1.88 SD], questionnaire-based decreased appetite, and serum albumin ≤3.8 g/dL. RESULTS: PEW, observed in 8 (15.1%) patients, was more prevalent in CKD stage 5 (P = .010). Among the adipokines, adiponectin, and resistin levels were significantly higher in CKD stage 5 (P < .001, P = .005). Adiponectin was correlated to LTI HA z-score (Rs = -0.417, P = .002), leptin to FTI z-score (Rs = 0.620, P < .001), while no correlation was observed between resistin and body composition parameters. Resistin was the only adipokine correlated to IL-6 (Rs = 0.513, P < .001). After adjustment for CKD stage and patient age, PEW was associated with adiponectin and IL-6 rise by 1 µg/mL and 10 pg/mL respectively (odds ratio (OR) 1.240, 95% confidence interval (CI) 1.040, 1.478 and OR 1.405, 95% CI 1.075-1.836) but not with leptin, while resistin association with PEW lost its significance. CONCLUSIONS: In pediatric CKD, adiponectin is associated with muscle wasting, leptin with adiposity and resistin with systemic inflammation. Adiponectin and cytokine IL-6 may serve as PEW biomarkers.

Fibroblast growth-factor 23 and vitamin D are associated with iron deficiency and anemia in children with chronic kidney disease.

BACKGROUND: This cross-sectional study investigates the association of fibroblast growth-factor 23 (FGF23) and other bone mineral parameters with iron status and anemia in pediatric chronic kidney disease (CKD). METHODS: Serum calcium, phosphorus, 25-hydroxyvitamin D (25(OH)D), intact parathormone, c-terminal FGF23, a-Klotho, iron (Fe), ferritin, unsaturated iron-binding capacity, and hemoglobin (Hb) were measured in 53 patients from 5 to 19 years old with GFR < 60 mL/min/1.73 m2. Transferrin saturation (TSAT) was calculated. RESULTS: Absolute (ferritin ≤ 100 ng/mL, TSAT ≤ 20%) and functional iron deficiency (ferritin > 100 ng/mL, TSAT ≤ 20%) were observed in 32% and 7.5% of patients, respectively. In CKD stages 3-4 (36 patients), lnFGF23 and 25(OH)D were correlated with Fe (rs = - 0.418, p = 0.012 and rs = 0.467, p = 0.005) and TSAT (rs = - 0.357, p = 0.035 and rs = 0.487, p = 0.003) but not to ferritin. In this patient group, lnFGF23 and 25(OH)D were correlated with Hb z-score (rs = - 0.649, p < 0.001 and rs = 0.358, p = 0.035). No correlation was detected between lnKlotho and iron parameters. In CKD stages 3-4, in multivariate backward logistic regression analysis, including bone mineral parameters, CKD stage, patient age, and daily alphacalcidol dose as covariates, lnFGF23 and 25(OH)D were associated with low TSΑΤ (15 patients) (OR 6.348, 95% CI 1.106-36.419, and OR 0.619, 95% CI 0.429-0.894, respectively); lnFGF23 was associated with low Hb (10 patients) (OR 5.747, 95% CI 1.270-26.005); while the association between 25(OH)D and low Hb did not reach statistical significance (OR 0.818, 95% CI 0.637-1.050). CONCLUSIONS: In pediatric CKD stages 3-4, iron deficiency and anemia are associated with increased FGF23, independently of Klotho. Vitamin D deficiency might contribute to iron deficiency in this population. A higher resolution version of the Graphical abstract is available as Supplementary information.

Surgical management of Encapsulating Peritoneal Sclerosis (EPS) in children: international case series and literature review.

BACKGROUND: Encapsulating Peritoneal Sclerosis (EPS) is a rare phenomenon in paediatric patients with kidney failure treated with peritoneal dialysis (PD). This study highlights clinical challenges in the management of EPS, with particular emphasis on peri-operative considerations and surgical technique. METHODS: Retrospective analysis of all paediatric patients with EPS treated at the Manchester Centre for Transplantation. RESULTS: Four patients were included with a median duration of 78 months on PD. All patients had recurrent peritonitis (> 3 episodes), and all had symptoms within three months of a change of dialysis modality from PD to haemodialysis or transplant. In Manchester, care was delivered by a multi-disciplinary team, including surgeons delivering the adult EPS surgical service with a particular focus on nutritional optimisation, sepsis control, and wound management. The surgery involved laparotomy, lavage, and enterolysis of the small bowel + / - stoma formation, depending on intra-abdominal contamination. Two patients had a formal stoma, which were reversed at three and six months, respectively. Two patients underwent primary closure of the abdomen, whereas two patients had re-look procedures at 48 h with secondary closure. One patient had a post-operative wound infection, which was managed medically. One patient's stoma became detached, leading to an intra-abdominal collection requiring re-laparotomy. The median length of stay was 25 days, and patients were discharged once enteral feeding was established. All patients remained free of recurrence with normal gut function and currently two out of four have functioning transplants. CONCLUSIONS: This series demonstrates 100% survival and parenteral feed independence following EPS surgery. Post-operative morbidity was common; however, with individualised experience-based decision-making and relevant additional interventions, patients made full recoveries. Health and development post-surgery continued, allowing the potential for transplantation. A higher resolution version of the Graphical abstract is available as Supplementary information.

Diminished Systemic Amino Acids Metabolome and Lipid Peroxidation in Ureteropelvic Junction Obstruction (UPJO) Infants Requiring Surgery.

Congenital anomalies of the urinary tract, and particularly of obstructive nephropathy such as ureteropelvic junction obstruction (UPJO) in infants, can later lead to chronic kidney disease and hypertension. Fundamental questions regarding underlying mechanisms remain unanswered. The aim of the present study was to quantitate the systemic amino acids metabolome in 21 UPJO infants requiring surgery (Group A) and 21 UPJO infants under conservative treatment (Group B). Nineteen healthy age-matched infants served as controls (Group C). Serum amino acids involved in several pathways and representative metabolites, including the L-arginine-derived nitric oxide (NO) metabolites nitrite and nitrate and the lipid peroxidation biomarker malondialdehyde (MDA) were measured by gas chromatography-mass spectrometry (GC-MS) methods using their stable-isotope labeled analogs as internal standards after derivatization to their methyl esters N-pentafluoropropionic amides (amino acids) and to their pentafluorobenzyl derivatives (nitrite, nitrate, MDA). The concentrations of the majority of the biomarkers were found to be lower in Group A compared to Group B. Statistical analysis revealed clear differentiation between the examined study groups. Univariate statistical analysis highlighted serum homoarginine (q = 0.006), asymmetric dimethylarginine (q = 0.05) and malondialdehyde (q = 0.022) as potential biomarkers for UPJO infants requiring surgery. Group A also differed from Group B with respect to the diameter of the preoperative anterior-posterior renal pelvis (AP) as well as regarding the number and extent of inverse correlations between AP and the serum concentrations of the biomarkers. In Group A, but not in Group B, the AP diameter strongly correlated with hydroxy-proline (r = -0.746, p = 0.0002) and MDA (r = -0.754, p = 0.002). Our results indicate a diminished amino acids metabolome in the serum of UPJO infants requiring surgery comparing to a conservative group.

Association between insulin growth factor-1, bone mineral density, and frailty phenotype in children with chronic kidney disease.

BACKGROUND: This cohort study investigates the association between insulin growth factor-1 (IGF-1), bone mineral density, and frailty phenotype in children with chronic kidney disease (CKD). METHODS: Forty-six patients (median age 14.5 years) were prospectively enrolled. Frailty phenotype was defined as the presence ≥ 3 of the following indicators: suboptimal growth/weight gain (body mass index height age < 5th percentile or height < 3rd percentile or loss of ≥ 10 percentiles/year in at least one parameter), low muscle mass (lean tissue mass height age < 5th percentile or loss of ≥ 10 percentiles/year), general fatigue reported by parent or child, and C-reactive protein > 3 mg/l. Lumbar bone mineral apparent density (LBMAD) was measured by dual-energy X-ray absorptiometry, body composition by bioimpedance spectroscopy, and IGF-1 by enzyme-labeled chemiluminescent immunometric assay. RESULTS: Frailty phenotype (seven patients) was more frequent in advanced CKD (estimated glomerular filtration rate < 30 ml/min/1.73m2) (p = 0.014). IGF-1 and LBMAD z-scores were lower in patients with suboptimal growth/weight gain (14 patients) (p = 0.013, p = 0.012), low muscle mass (nine patients) (p = 0.001, p = 0.009), and general fatigue (eight patients) (p < 0.001, p = 0.004). IFG-1 and LBMAD z-scores were associated with frailty phenotype (OR 0.109, 95% CI 0.015-0.798 and OR 0.277, 95% CI 0.085-0.903) after adjustment for CKD stage. IGF-1 z-score was associated with LBMAD < 5th percentile (six patients) (OR 0.020, 95% CI 0.001-0.450) after adjustment for CKD stage. The association between LBMAD and frailty phenotype lost significance after adjustment for IGF-1. CONCLUSION: Frailty phenotype is more frequent in advanced pediatric CKD. IGF-1 is negatively associated with frailty phenotype and interferes in the association between frailty and LBMAD.

Radionuclide techniques for the detection of vesicoureteral reflux and their clinical significance.

We discuss and try to evaluate the detection of vesicoureteral reflux (VUR) by radionuclide techniques and especially direct radionuclide cystography (DRC). Direct radionuclide cystography is applied for more than half a century mainly in children. Vesicoureteral reflux has a complex pathology not yet completely understood and is often related to urinary tract infection (UTI) and renal parenchyma scarring that can lead to long-term renal function impairment. Since there is no consensus on the optimal imaging algorithm after the first febrile urinary tract infection, many imaging strategies have been proposed for VUR detection in the last decade, including or not DRC. Views opposing or accepting its use are also presented.

Serum-Targeted HILIC-MS Metabolomics-Based Analysis in Infants with Ureteropelvic Junction Obstruction.

Ureteropelvic junction obstruction (UPJO) constitutes the predominant cause of obstructive nephropathy in both neonates and infants. Fundamental questions regarding UPJO's mechanism, assessment, and treatment still remain unanswered. The aim of the present study was to elucidate potential differences through serum metabolic profiling of surgical cases of infants with UPJO compared to both nonsurgical cases and healthy age-matched controls. Early diagnosis of renal dysfunction in this cohort based on highlighted biomarkers was the ultimate goal. Thus, serum samples were collected from 20 patients preoperatively, 19 patients with mild stenosis treated conservatively, and 17 healthy controls. All samples were subjected to targeted metabolomics analysis by hydrophilic interaction liquid chromatography coupled to mass spectrometry (HILIC LC-MS/MS). Both univariate and multivariate statistical analyses were performed. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) score plots showed that the studied groups differed significantly, with a panel of metabolites, including creatinine, tryptophan, choline, and aspartate, distinguishing patients who required surgery from those followed by systematical monitoring as well as from healthy controls, showing high performance as indicators of UPJO disease.

The role of urinary NGAL and serum cystatin C in assessing the severity of ureteropelvic junction obstruction in infants.

BACKGROUND: The ideal management of ureteropelvic junction obstruction (UPJO) remains debatable. This prospective case-control study aimed to investigate if urinary levels of Neutrophil Gelatinase-Associated Lipocalin (NGAL) and serum levels of cystatin C could distinguish surgical from non-surgical cases of UPJO and if they could detect earlier impairment of renal function. METHODS: Biomarkers were measured in the following age-matched groups: (a) 22 infants with surgical UPJO, at initial diagnosis and 12 months postoperatively (groups A1 and A2, respectively); (b) 19 infants with non-surgical UPJO (group B); and (c) 17 controls (group C). Based on serum cystatin C levels, estimated glomerular filtration rate (eGFR) was calculated. RESULTS: Urinary NGAL (uNGAL) was significantly higher in group A1 vs. group A2 (p = 0.02) and in group A1 vs. group C (p = 0.03), whereas there was no statistically significant difference between groups A2 and C (p = 0.77). Likewise, cystatin C levels were significantly higher in group A1 vs. group A2 and in group A1 vs. group C (p = 0.004 and p = 0.02, respectively), but no statistically significant difference between groups A2 and C (p = 0.82). uNGAL and serum cystatin C did not differ between groups B and A, nor did they differ between groups B and C. Cystatin C levels and eGFR of group A1 were significantly higher than those of group A2 and group C (p = 0.0001 and p = 0.02, respectively). CONCLUSION: It seems that NGAL and cystatin C are able to distinguish patients who were treated surgically from healthy controls, and their levels appear to improve significantly following surgery.

Epidemiology of and Risk Factors for BK Polyomavirus Replication and Nephropathy in Pediatric Renal Transplant Recipients: An International CERTAIN Registry Study.

BACKGROUND: BK polyomavirus-associated nephropathy (BKPyVAN) constitutes a serious cause of kidney allograft failure, but large-scale data in pediatric renal transplant recipients and a comprehensive analysis of specific risk factors are lacking. METHODS: We analyzed the data of 313 patients in the Cooperative European Pediatric Renal Transplant Initiative Registry, with an observation period of 3.3 years (range, 1-5). The net state of immunosuppressive therapy was assessed by the modified Vasudev score. RESULTS: Presumptive BKPyVAN (defined as sustained [>3 wk] high-level BK viremia >10 copies/mL) within 5 years posttransplant occurred in 49 (15.8%) of 311 patients, and biopsy-proven BKPyVAN in 14 (4.5%) of 313. BKPyV viremia was observed in 115 (36.7%) of 311 patients, of whom 11 (9.6%) of 115 developed viremia late, that is, after the second year posttransplant. In 6 (12.5%) of 48 patients with high-level viremia and in 3 (21.4%) of 14 with BKPyVAN, this respective event occurred late. According to multivariable analysis, BKPyV viremia and/or BKPyVAN were associated not only with a higher net state of immunosuppression (odds ratio [OR], 1.3; P < 0.01) and with tacrolimus-based versus ciclosporin-based immunosuppression (OR, 3.6; P < 0.01) but also with younger recipient age (OR, 1.1 per y younger; P < 0.001) and obstructive uropathy (OR, 12.4; P < 0.01) as primary renal disease. CONCLUSIONS: Uncontrolled BKPyV replication affects a significant proportion of pediatric renal transplant recipients and is associated with unique features of epidemiology and risk factors, such as young recipient age, obstructive uropathy, and overall intensity of immunosuppressive therapy. BKPyV surveillance should be considered beyond 2 years posttransplant in pediatric patients at higher risk.

Arterial Stiffness in a Toddler with Neurofibromatosis Type 1 and Refractory Hypertension.

Arterial hypertension is a common finding in patients with neurofibromatosis (NF) type 1. Renovascular hypertension due to renal artery stenosis or midaortic syndrome could be the underlying cause. We report the case of a 4-year-old girl with NF type 1 and midaortic syndrome whose changes in blood pressure and pulse wave velocity suggested the evolution of vasculopathy, diagnosis of renovascular hypertension, and provided insights of response to treatment. Hypertension persisted after percutaneous transluminal angioplasty in the abdominal aorta, requiring escalation of antihypertensive treatment, while arterial stiffness demonstrated a mild decrease. Regular assessment of blood pressure using ambulatory blood pressure monitoring and noninvasive assessment of arterial stiffness may enhance the medical care of patients with NF type 1.

JC polyomavirus replication and associated disease in pediatric renal transplantation: an international CERTAIN Registry study.

BACKGROUND: JC polyomavirus (JCPyV)-associated nephropathy (JCPyVAN) is a severe, but rare complication in adult renal transplant (RTx) recipients. Related data in pediatric patients are scarce. METHODS: Based on the CERTAIN Registry, we therefore performed a multi-center, retrospective study on the JCPyV antibody status, prevalence of JCPyV replication, and its associated disease in 139 pediatric RTx recipients (mean age, 8.5 ± 5.3 years). JCPyV DNA in plasma and/or urine was measured by quantitative PCR at a median time of 3.2 (IQR, 0.3-8.1) years post-transplant. RESULTS: 53.2% of patients were JCPyV-seronegative prior to transplantation; younger age was associated with JCPyV seronegativity. 34/139 (24.5%) patients post-transplant showed active JCPyV replication in either urine (22.0%), plasma (13.4%), or both (7.6%). JCPyV viremia occurred significantly (p < 0.001) more often in patients with viruria (34.6%) than in those without (7.6%), but 7/118 (5.9%) had isolated viremia. High-level viruria (> 107 copies/mL) was found in 29.6% of viruric patients. A higher net state of immunosuppression constituted an independent risk factor for JCPyV replication both in urine and plasma (OR 1.2, p < 0.02). Male patients tended to have a higher risk of JCPyV viremia than females (OR 4.3, p = 0.057). There was one male patient (0.7%) with JCPyVAN 7 years post-transplant, which resolved after reduction of immunosuppressive therapy. No patient exhibited progressive multifocal leukoencephalopathy. CONCLUSIONS: This first multi-center study on JCPyV in pediatric renal transplant recipients shows that JCPyV replication is common (24.5%), with strong immunosuppression being a significant risk factor, but associated nephropathy is rare.

Long-Term Outcome of Steroid-Resistant Nephrotic Syndrome in Children.

We investigated the value of genetic, histopathologic, and early treatment response information in prognosing long-term renal outcome in children with primary steroid-resistant nephrotic syndrome. From the PodoNet Registry, we obtained longitudinal clinical information for 1354 patients (disease onset at >3 months and <20 years of age): 612 had documented responsiveness to intensified immunosuppression (IIS), 1155 had kidney biopsy results, and 212 had an established genetic diagnosis. We assessed risk factors for ESRD using multivariate Cox regression models. Complete and partial remission of proteinuria within 12 months of disease onset occurred in 24.5% and 16.5% of children, respectively, with the highest remission rates achieved with calcineurin inhibitor-based protocols. Ten-year ESRD-free survival rates were 43%, 94%, and 72% in children with IIS resistance, complete remission, and partial remission, respectively; 27% in children with a genetic diagnosis; and 79% and 52% in children with histopathologic findings of minimal change glomerulopathy and FSGS, respectively. Five-year ESRD-free survival rate was 21% for diffuse mesangial sclerosis. IIS responsiveness, presence of a genetic diagnosis, and FSGS or diffuse mesangial sclerosis on initial biopsy as well as age, serum albumin concentration, and CKD stage at onset affected ESRD risk. Our findings suggest that responsiveness to initial IIS and detection of a hereditary podocytopathy are prognostic indicators of favorable and poor long-term outcome, respectively, in children with steroid-resistant nephrotic syndrome. Children with multidrug-resistant sporadic disease show better renal survival than those with genetic disease. Furthermore, histopathologic findings may retain prognostic relevance when a genetic diagnosis is established.

Hypertension screening during healthcare pediatric visits.

BACKGROUND: Guidelines in both Europe and the United States recommend screening for hypertension during child care pediatric visits in children above 3 years old. The aims of the study were to assess the frequency of blood pressure (BP) measurement during preventive or chronic care pediatric visits and determine the factors that may associate with screening. METHOD: We prospectively included in the study consecutive children hospitalized in our department. Anthropometric measurements were performed in all children. Office BP was measured in children above 5 years old and mothers and/or fathers. Personal and family history, and self-reported BP screening during pediatric visits were recorded. RESULTS: Hypertension screening had been performed at least once in 45.3% of the children during pediatric visits. Fifty per cent of the children with elevated BP levels had never been screened for hypertension. Low birth weight, history of prematurity, or chronic disease was not associated with increased frequency of screening, whereas screening was more likely in children above 3 years old with positive personal history (odds ratio 2.35, 95% confidence interval 1.07-5.15, P < 0.05). Obesity tended to increase the frequency of hypertension screening in all ages (odds ratio 2.60, 95% confidence interval 0.93-7.28, P = 0.06). Moreover, 37.5% of children without positive personal history exhibited BP levels above the 90th percentile, and 13.5% of mothers and 31.1% of fathers were not aware of their own elevated BP levels. CONCLUSION: These findings suggest that hypertension screening does not occur during pediatric visits for a considerable percentage of children, although a significant number of children and adolescents without positive history of hypertension or chronic disease may have elevated office BP levels.

Urinary and serum biomarkers in ureteropelvic junction obstruction: a systematic review.

CONTEXT: Ureteropelvic junction obstruction (UPJO) constitutes a predominant cause of obstructive hydronephrosis. Fundamental questions regarding the assessment and treatment of infants and children with obstructive nephropathy remain unanswered. OBJECTIVE: Several studies have investigated the usefulness of substances that could serve as potential diagnostic and prognostic biomarkers in children with UPJO. Aim of the present study is to systematically review the literature on biomarkers that have been studied to date in patients with UPJO. METHODS: The main search was conducted in the electronic databases MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL) from inception through March 2014 using various combinations of Medical Subject Headings (MeSH). RESULTS: The 14 included studies reported data on 380 UPJO patients who underwent surgery, 174 who were treated conservatively and 213 controls. CONCLUSION: Some biomarkers offer promising results however more multicenter, prospective carefully designed studies are needed to evaluate their diagnostic and prognostic value.

Management of anemia in children receiving chronic peritoneal dialysis.

Little information exists regarding the efficacy, modifiers, and outcomes of anemia management in children with CKD or ESRD. We assessed practices, effectors, and outcomes of anemia management in 1394 pediatric patients undergoing peritoneal dialysis (PD) who were prospectively followed in 30 countries. We noted that 25% of patients had hemoglobin levels below target (<10 g/dl or <9.5 g/dl in children older or younger than 2 years, respectively), with significant regional variation; levels were highest in North America and Europe and lowest in Asia and Turkey. Low hemoglobin levels were associated with low urine output, low serum albumin, high parathyroid hormone, high ferritin, and the use of bioincompatible PD fluid. Erythropoiesis-stimulating agents (ESAs) were prescribed to 92% of patients, and neither the type of ESA nor the dosing interval appeared to affect efficacy. The weekly ESA dose inversely correlated with age when scaled to weight but did not correlate with age when normalized to body surface area. ESA sensitivity was positively associated with residual diuresis and serum albumin and inversely associated with serum parathyroid hormone and ferritin. The prevalence of hypertension and left ventricular hypertrophy increased with the degree of anemia. Patient survival was positively associated with achieved hemoglobin and serum albumin and was inversely associated with ESA dose. In conclusion, control of anemia in children receiving long-term PD varies by region. ESA requirements are independent of age when dose is scaled to body surface area, and ESA resistance is associated with inflammation, fluid retention, and hyperparathyroidism. Anemia and high ESA dose requirements independently predict mortality.

Short- and middle-term continuous use of cinacalcet in children on peritoneal dialysis.

BACKGROUND: Secondary hyperparathyroidism (HPT) constitute a high-turnover bone disease, manifested by elevated parathyroid hormone. Cinacalcet, belonging to calcimimetics, has been shown to be promising in the control of secondary HPT with limited data in children. OBJECTIVE: To evaluate the safety and efficacy of cinacalcet in children on peritoneal dialysis (PD) with secondary HPT. METHODS: Four patients on PD with severe secondary HPT, uncontrolled with phosphorus dietary restrictions combined with phosphate binders and analog of 1,25 vitamin D3 received cinacalcet. RESULTS: After cinacalcet treatment, in two of four patients, we found a serum intact parathyroid hormone (iPTH) level reduction by more than 70% at 4 weeks and more than 60% at 3 or more than 6 months. Nevertheless, in the other two patients, a transient reduction of iPTH was found in 4 weeks and an increase in 3 or more months, who were finally treated with surgical parathyroidectomy. During cinacalcet treatment, no adverse events were noted. CONCLUSION: Cinacalcet may be a safe and effective treatment for PD patients with secondary HPT, although surgical parathyroidectomy cannot be avoided in certain cases.

Safety and efficacy of rituximab in refractory pediatric systemic lupus erythematosus nephritis: a single-center experience of Northern Greece.

Lupus nephritis (LN) is the major determinant of outcome in pediatric systemic lupus erythematosus (pSLE), and its treatment remains a challenge. The aim of this study was to report the experience of our center in treating with rituximab (RTX) SLE patients with severe LN. Four pSLE patients with biopsy-proven LN, who are refractory to conventional immunosuppressive treatment, received four doses of 375-500 mg/m(2) RTX, 2-3 weeks apart. All patients were concurrently receiving corticosteroids (CSs) and mycophenolate mofetil. Patients' clinical and laboratory findings were recorded at RTX initiation, after each infusion and at 3.4 ± 2.1 month intervals thereafter. pSLE activity was assessed using the European Consensus Lupus Activity Measurement (ECLAM), while LN activity using 24-hour urine protein excretion and serum cystatin C. Patients were followed up for 6-21 months (median: 16 months). Full Β-cell depletion was noticed 2-4 weeks after RTX initiation and lasted 4-7 months. All patients achieved complete LN remission 3.5 months (range: 2-4) after RTX initiation, which was retained in 3 patients through the follow-up period. One patient relapsed 15 months after RTX initiation and received one additional RTX dose. ECLAM scores and CSs doses were markedly reduced in all patients, while complement levels were increased. No side effects or infections were observed. In conclusion, RTX is an alternative, safe and efficient treatment for refractory LN.