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Background Sodium (Na) balance is unexplored in dialyzed children. We assessed a simplified sodium balance (sNaB) and its correlates in pediatric patients receiving maintenance dialysis. Methods 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). Results Forty-one patients (31 HD), with a median age of 13.3 (IQR 5.2) years, were enrolled. Twelve patients (29.3%) received Na-containing drugs, accounting for 0.6 (0.7) mEq/kg/day. Median total Na intake was 1.5 (1.1) mEq/kg/day, corresponding to 60.6% of the maximum recommended daily intake for healthy children. Median uNa and sNaB were 0.6 (1.8) mEq/kg/day and 0.9 (1.7) mEq/kg/day, respectively. The strongest independent predictor of sNaB in the cohort was urine output. In patients receiving HD, sNaB correlated with IDWG, pre-HD DBP, and first-hour refill index, a volume index based on blood volume monitoring. sNaB was the strongest predictor of IDWG in multiple regression analysis ([beta] = 0.63; p = 0.005). Neither SBP SDS nor DBP SDS correlated with sNaB. Conclusions Na intake is higher than uNa in children on dialysis, and medications may be an important source of Na. sNaB is best predicted by urine output in the population, and it is a significant independent predictor of IDWG in children on HD. Graphical abstract, Author(s): Fabio Paglialonga [sup.1] , Rukshana Shroff [sup.2] , Ilona Zagozdzon [sup.3] , Sevcan A. Bakkaloglu [sup.4] , Ariane Zaloszyc [sup.5] , Augustina Jankauskiene [sup.6] , Alejandro Cruz Gual [sup.7] [...]

Background Associations between anthropometric measures and patient outcomes in children are inconsistent and mainly based on data at kidney replacement therapy (KRT) initiation. We studied associations of height and body mass index (BMI) with access to kidney transplantation, graft failure, and death during childhood KRT. Methods We included patients < 20 years starting KRT in 33 European countries from 1995-2019 with height and weight data recorded to the ESPN/ERA Registry. We defined short stature as height standard deviation scores (SDS) 1.88. Underweight, overweight and obesity were calculated using age and sex-specific BMI for height-age criteria. Associations with outcomes were assessed using multivariable Cox models with time-dependent covariates. Results We included 11,873 patients. Likelihood of transplantation was lower for short (aHR: 0.82, 95% CI: 0.78-0.86), tall (aHR: 0.65, 95% CI: 0.56-0.75), and underweight patients (aHR: 0.79, 95%CI: 0.71-0.87). Compared with normal height, patients with short and tall statures showed higher graft failure risk. All-cause mortality risk was higher in short (aHR: 2.30, 95% CI: 1.92-2.74), but not in tall stature. Underweight (aHR: 1.76, 95% CI: 1.38-2.23) and obese (aHR: 1.49, 95% CI: 1.11-1.99) patients showed higher all-cause mortality risk than normal weight subjects. Conclusions Short and tall stature and being underweight were associated with a lower likelihood of receiving a kidney allograft. Mortality risk was higher among pediatric KRT patients with a short stature or those being underweight or obese. Our results highlight the need for careful nutritional management and multidisciplinary approach for these patients. Graphical abstract, Author(s): Marjolein Bonthuis [sup.1] [sup.2] , Sevcan A. Bakkaloglu [sup.3] , Enrico Vidal [sup.4] , Sergey Baiko [sup.5] , Fiona Braddon [sup.6] , Carmela Errichiello [sup.7] , Telma Francisco [sup.8] [...]

Background Infants with chronic kidney disease (CKD) form a vulnerable population who are highly prone to mineral and bone disorders (MBD) including biochemical abnormalities, growth retardation, bone deformities, and fractures. We present a position paper on the diagnosis and management of CKD-MBD in infants based on available evidence and the opinion of experts from the European Society for Paediatric Nephrology (ESPN) CKD-MBD and Dialysis working groups and the Pediatric Renal Nutrition Taskforce. Methods PICO (Patient, Intervention, Comparator, Outcomes) questions were generated, and relevant literature searches performed covering a population of infants below 2 years of age with CKD stages 2-5 or on dialysis. Clinical practice points (CPPs) were developed and leveled using the American Academy of Pediatrics grading matrix. A Delphi consensus approach was followed. Results We present 34 CPPs for diagnosis and management of CKD-MBD in infants, including dietary control of calcium and phosphate, and medications to prevent and treat CKD-MBD (native and active vitamin D, calcium supplementation, phosphate binders). Conclusion As there are few high-quality studies in this field, the strength of most statements is weak to moderate, and may need to be adapted to individual patient needs by the treating physician. Research recommendations to study key outcome measures in this unique population are suggested. Graphical Abstract, Author(s): Justine Bacchetta [sup.1] [sup.2] [sup.3] , Claus Peter Schmitt [sup.4] , Sevcan A. Bakkaloglu [sup.5] , Shelley Cleghorn [sup.6] , Maren Leifheit-Nestler [sup.7] , Agnieszka Prytula [sup.8] , Bruno [...]

Serum osmolality is the sum of the osmolalities of every single dissolved particle in the blood such as sodium and associated anions, potassium, glucose, and urea. Under normal conditions, serum sodium concentration is the major determinant of serum osmolality. Effective blood osmolality, so-called blood tonicity, is created by the endogenous (e.g., sodium and glucose) and exogenous (e.g., mannitol) solutes that are capable of creating an osmotic gradient across the membranes. In case of change in effective blood osmolality, water shifts from the compartment with low osmolality into the compartment with high osmolarity in order to restore serum osmolality. The difference between measured osmolality and calculated osmolarity forms the osmolal gap. An increase in serum osmolal gap can stem from the presence of solutes that are not included in the osmolarity calculation, such as hypertonic treatments or toxic alcoholic ingestions. In clinical practice, determination of serum osmolality and osmolal gap is important in the diagnosis of disorders related to sodium, glucose and water balance, kidney diseases, and small molecule poisonings. As blood hypertonicity exerts its main effects on the brain cells, neurologic symptoms varying from mild neurologic signs and symptoms to life-threatening outcomes such as convulsions or even death may occur. Therefore, hypertonic states should be promptly diagnosed and cautiously managed. In this review, the causes and treatment strategies of hyperosmolar conditions including hypernatremia, diabetic ketoacidosis, hyperglycemic hyperosmolar syndrome, hypertonic treatments, or intoxications are discussed in detail to increase awareness of this important topic with significant clinical consequences., Author(s): Bahar Büyükkaragöz [sup.1] , Sevcan A. Bakkaloglu [sup.1] Author Affiliations: (1) grid.25769.3f, 0000 0001 2169 7132, Department of Pediatric Nephrology, Gazi University, , 06560, Besevler, Ankara, Turkey Introduction Maintenance [...]

Background Automated peritoneal dialysis (APD) is increasingly preferred worldwide. By using a software application (Homechoice with Claria sharesource system (CSS)) with a mod-M added to the APD device, details of the home dialysis treatment become visible for PD nurses and physicians, allowing for close supervision. We aimed to evaluate the perceptions of patients/caregivers, PD nurses, and physicians about the advantages and disadvantages of CSS. Methods Three different web-based questionnaires for patients/caregivers, nurses, and physicians were sent to 15 pediatric nephrology centers with more than 1 year of experience with CSS. Results Respective questionnaires were answered by 30 patients/caregivers, 22 pediatric nephrologists, and 15 PD nurses. Most of the nurses and physicians (87% and 73%) reported that CSS improved patient monitoring. A total of 73% of nurses suggested that CCS is not well known by physicians, while half of them reported reviewing CSS data for all patients every morning. Sixty-eight percent of physicians thought that CSS helps save time for both patients/caregivers and healthcare providers by reducing visits. However, only 20% of patients/caregivers reported reduced hospital visits. A total of 90% of patients/caregivers reported that being under constant monitoring made them feel safe, and 83% stated that the patient's sleep quality improved. Conclusions A remote monitoring APD system, CSS, can be successfully applied with children for increased adherence to dialysis prescription by giving shared responsibility and may help increase the patient's quality of life. This platform is more commonly used by nurses than physicians. Its potential benefits should be evaluated in further well-designed clinical studies with larger patient groups. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information., Author(s): Bahriye Uzun Kenan [sup.1] , Beltinge Demircioglu Kilic [sup.2] , Mehtap Akbalik Kara [sup.3] , Aysel Taktak [sup.4] , Aysun Karabay Bayazit [sup.5] , Zeynep Nagehan Yuruk Yildirim [sup.6] [...]

Background Coronavirus disease-2019 (COVID-19) has been challenging for patients and medical staff. Radical changes have been needed to prevent disruptions in patient care and medical education. Methods A web-based survey was sent to European Society for Pediatric Nephrology (ESPN) members via the ESPN mailing list to evaluate the effects of the COVID-19 pandemic on delivery of pediatric nephrology (PN) care and educational activities. There were ten questions with subheadings. Results Seventy-six centers from 24 countries completed the survey. The time period was between the beginning of the pandemic and May 30, 2020. The number of patients admitted in PN wards and outpatient clinics were significantly decreased (2.2 and 4.5 times, respectively). Telemedicine tools, electronic prescriptions, online applications for off-label drugs, and remote access to laboratory/imaging results were used in almost half of the centers. Despite staff training and protective measures, 33% of centers reported COVID-19 infected staff, and 29% infected patients. Difficulties in receiving pharmaceuticals were reported in 25% of centers. Sixty percent of centers suspended living-related kidney transplantation, and one-third deceased-donor kidney transplantation. Hands-on education was suspended in 91% of medical schools, and face-to-face teaching was replaced by online systems in 85%. Multidisciplinary training in PN was affected in 54% of the centers. Conclusions This survey showed a sharp decline in patient admissions and a significant decrease in kidney transplantation. Telemedicine and online teaching became essential tools, requiring integration into the current system. The prolonged and fluctuating course of the pandemic may pose additional challenges necessitating urgent and rational solutions. Graphical abstract, Author(s): Burcu Yazicioglu [sup.1] , Sevcan A. Bakkaloglu [sup.1] , M. Abranches, S. Akman, H. Alpay, G. Ariceta, B. Atmis, A. Bael, S. A. Bakkaloglu, U. S. Bayrakçi, R. Bhimma, [...]

Author(s): Emre Leventoglu [sup.1] , Bahar Büyükkaragöz [sup.1] , Ipek Isik Gönül [sup.2] , Kibriya Fidan [sup.1] , Betül Ögüt [sup.2] , Oguz Söylemezoglu [sup.1] , Sevcan A. Bakkaloglu [sup.1] [...]

Author(s): Emre Leventoglu [sup.1] , Bahar Büyükkaragöz [sup.1] , Bahriye Uzun Kenan [sup.1] , Arzu Okur [sup.2] , Esra Döger [sup.3] , Sevcan A. Bakkaloglu [sup.1] Author Affiliations: (1) grid.25769.3f, [...]

Author(s): Emre Leventoglu [sup.1] , Bahar Büyükkaragöz [sup.1] , Bahriye Uzun Kenan [sup.1] , Sinan Sari [sup.2] , Sevcan A. Bakkaloglu [sup.1] Author Affiliations: (1) grid.25769.3f, 0000 0001 2169 7132, [...]

Author(s): Emre Leventoglu [sup.1] , Bahar Büyükkaragöz [sup.1] , Zühre Kaya [sup.2] , Kibriya Fidan [sup.1] , Oguz Söylemezoglu [sup.1] , Sevcan A. Bakkaloglu [sup.1] Author Affiliations: (1) grid.25769.3f, 0000 [...]

Background Hypertension is prevalent in children on dialysis and associated with cardiovascular disease. We studied the blood pressure (BP) trends and the evolution of BP over 1 year in children on conventional hemodialysis (HD) vs. hemodiafiltration (HDF). Methods This is a post hoc analysis of the '3H - HDF-Hearts-Height' dataset, a multicenter, parallel-arm observational study. Seventy-eight children on HD and 55 on HDF who had three 24-h ambulatory BP monitoring (ABPM) measures over 1 year were included. Mean arterial pressure (MAP) was calculated and hypertension defined as 24-h MAP standard deviation score (SDS) [greater than or equal to]95th percentile. Results Poor agreement between pre-dialysis systolic BP-SDS and 24-h MAP was found (mean difference - 0.6; 95% limits of agreement -4.9-3.8). At baseline, 82% on HD and 44% on HDF were hypertensive, with uncontrolled hypertension in 88% vs. 25% respectively; p < 0.001. At 12 months, children on HDF had consistently lower MAP-SDS compared to those on HD (p < 0.001). Over 1-year follow-up, the HD group had mean MAP-SDS increase of +0.98 (95%CI 0.77-1.20; p < 0.0001), whereas the HDF group had a non-significant increase of +0.15 (95%CI -0.10-0.40; p = 0.23). Significant predictors of MAP-SDS were dialysis modality ([beta] = +0.83 [95%CI +0.51 - +1.15] HD vs. HDF, p < 0.0001) and higher inter-dialytic-weight-gain (IDWG)% ([beta] = 0.13 [95%CI 0.06-0.19]; p = 0.0003). Conclusions Children on HD had a significant and sustained increase in BP over 1 year compared to a stable BP in those on HDF, despite an equivalent dialysis dose. Higher IDWG% was associated with higher 24-h MAP-SDS in both groups., Author(s): Francesca De Zan [sup.1] , Colette Smith [sup.2] , Ali Duzova [sup.3] , Aysun Bayazit [sup.4] , Constantinos J Stefanidis [sup.5] , Varvara Askiti [sup.5] , Karolis Azukaitis [sup.6] [...]

Author(s): Emre Leventoglu [sup.1] , Bahar Büyükkaragöz [sup.1] , Ipek Isik Gönül [sup.2] , Kibriya Fidan [sup.1] , Betül Ögüt [sup.2] , Oguz Söylemezoglu [sup.1] , Sevcan A. Bakkaloglu [sup.1] [...]

Background Peritoneal dialysis (PD) is the most common kidney replacement therapy in children. Complications associated with PD affect treatment success and sustainability. The aim of this study was to investigate the frequency of PD-related non-infectious complications and the predisposing factors. Methods Retrospective data from 11 centers in Turkey between 1998 and 2018 was collected. Non-infectious complications of peritoneal dialysis (NICPD), except metabolic ones, in pediatric patients with regular follow-up of at least 3 months were evaluated. Results A total of 275 patients were included. The median age at onset of PD and median duration of PD were 9.1 (IQR, 2.5-13.2) and 7.6 (IQR, 2.8-11.9) years, respectively. A total of 159 (57.8%) patients encountered 302 NICPD within the observation period of 862 patient-years. The most common NIPCD was catheter dysfunction (n = 71, 23.5%). At least one catheter revision was performed in 77 patients (28.0%). Longer PD duration and presence of swan neck tunnel were associated with the development of NICPD (OR 1.191; 95% CI 1.079-1.315, p = 0.001 and OR 1.580; 95% CI 0.660-0.883, p = 0.048, respectively). Peritoneal dialysis was discontinued in 145 patients; 46 of whom (16.7%) switched to hemodialysis. The frequency of patients who were transferred to hemodialysis due to NICPD was 15.2%. Conclusions Peritoneal dialysis-related non-infectious complications may lead to discontinuation of therapy. Presence of swan neck tunnel and long duration of PD increased the rate of NICPD. Careful monitoring of patients is necessary to ensure that PD treatment can be maintained safely., Author(s): Gulsah Kaya Aksoy [sup.1] , Mesiha Ekim [sup.2] , Sevcan A. Bakkaloglu [sup.3] , Seda Coskun [sup.4] , Ali Delibas [sup.5] , Seçil Conkar [sup.6] , Dilek Yilmaz [sup.7] [...]

Author(s): Sevcan A. Bakkaloglu [sup.1] Author Affiliations: (1) grid.25769.3f, 0000 0001 2169 7132, Divisions of Pediatric Nephrology and Rheumatology, Department of Pediatrics, Faculty of Medicine, Gazi University, , Besevler, Ankara, [...]

Author(s): Emre Leventoglu [sup.1] , Bahar Büyükkaragöz [sup.1] , Bahriye Uzun Kenan [sup.1] , Sinan Sari [sup.2] , Sevcan A. Bakkaloglu [sup.1] Author Affiliations: (1) grid.25769.3f, 0000 0001 2169 7132, [...]

Author(s): Burcu Yazicioglu [sup.1] , Sevcan A. Bakkaloglu [sup.1] , M. Abranches, S. Akman, H. Alpay, G. Ariceta, B. Atmis, A. Bael, S. A. Bakkaloglu, U. S. Bayrakçi, R. Bhimma, [...]

Background During erythropoietin-stimulating agent (ESA) treatment, hemoglobin (Hb) levels usually fluctuate; this phenomenon is known as 'Hb cycling (HC).' In this study, we aimed to evaluate the predictors of HC and its impact on left ventricular hypertrophy (LVH) as a patient-important outcome parameter in pediatric dialysis patients. Methods Records of patients followed up in nine pediatric nephrology centers between 2008 and 2013 were reviewed. More than 1 g/dL decrease or increase in Hb level was considered as HC. Patients were divided into two groups according to 12-month Hb trajectory as rare cycling (RC) ([less than or equal to] 3) and frequent cycling (FC) (> 3 fluctuation) as well as three groups based on T-A-Hb levels: 11 g/dL. Results Two hundred forty-five dialysis (160 peritoneal dialysis (PD) and 85 hemodialysis (HD)) patients aged 12.3 ± 5.1 (range 0.5-21) years were enrolled in this study. Fifty-two percent of the patients had RC, 45% had FC, and only 3% had no cycling. There were no differences between HC groups with respect to age, dialysis modality, having anemia, hospitalization rate, residual urine volume, and mortality. Although left ventricular mass index (LVMI) tended to be higher in RC than FC group (65 ± 37 vs 52 ± 23 g/m.sup.2.7, p = 0.056), prevalence of LVH was not different between the groups (p = 0.920). In regression analysis, FC was not a risk factor for LVH, but low T-A Hb level (< 10 g/dL) was a significant risk for LVH (OR = 0.414, 95% CI 0.177-0.966, p = 0.04). The target Hb levels were more often achieved in PD patients, and the number of deaths was significantly lower in non-anemic patients (Hb level > 11 g/dL). Conclusion Hb cycling is common among dialysis patients. Severity of anemia rather than its cycling has more significant impact on the prevalence of LVH and on inflammatory state., Author(s): Sevcan A. Bakkaloglu [sup.1] , Yasar Kandur [sup.1] , Erkin Serdaroglu [sup.2] , Aytül Noyan [sup.3] , Aysun Karabay Bayazit [sup.4] , Mehmet Tasdemir [sup.5] , Sare Gülfem Özlü [...]

Background The optimal time for dialysis initiation in adults and children with chronic kidney disease remains unclear. The aim of this study was to evaluate the impact of dialysis timing on different outcome parameters, in particular left ventricular (LV) morphology and inflammation, in pediatric patients receiving peritoneal dialysis and hemodialysis. Methods The medical records of pediatric dialysis patients who were followed-up in nine pediatric nephrology centers in Turkey between 2008 and 2013 were retrospectively reviewed. In addition to demographic data, we retrieved anthropometric measurements, data on dialysis treatment modalities, routine biochemical parameters, complete blood count, serum ferritin, parathormone, C-reactive protein (CRP), and albumin levels, as well as echocardiographic data and hospitalization records. The patients were divided into two groups based on their estimated glomerular filtration rate (eGFR) levels at dialysis initiation, namely, an early-start group, characterized by an eGFR of >10 ml/min/1.73 m.sup.2, and a late-start group, with an eGFR of < 7 ml/min/1.73 m.sup.2. The collected data were compared between these groups. Results A total of 245 pediatric dialysis patients (mean age ± standard deviation 12.3 ± 5.1 years, range 0.5-21 years) were enrolled in this study. Echocardiographic data were available for 137 patients, and the mean LV mass index (LVMI) was 58 ± 31 (range 21-215) g/m.sup.2.7. The LVMI was 75 ± 30 g/m.sup.2.7(n = 81) and 34 ± 6 g/m.sup.2.7(n = 56) in patients with or without LV hypertrophy (LVH) (p 10 ml/min/1.73 m.sup.2) versus late-start dialysis (eGFR < 7 ml/min/1.73 m.sup.2) groups did not significantly differ in LVMI and LVH status (p > 0.05) nor in number of hospitalizations. Serum albumin levels were significantly higher in the early-dialysis group compared with the late-dialysis group (3.3 ± 0.7 vs. 3.1 ± 0.7 g/dl, respectively; p < 0.05). The early-start group had relatively higher time-averaged albumin levels (3.2 ± 0.5 vs. 3.1 ± 0.5 g/dl; p = > 0.05) and relatively lower CRP levels (3.64 ± 2.00 vs. 4.37 ± 3.28 mg/L, p > 0.05) than the late-start group, but these differences did not reach statistical significance. Conclusion Although early dialysis initiation did not have a significant effect on important clinical outcome parameters, including LVH, inflammatory state, and hospitalization, in our pediatric dialysis patients, this area of study deserves further attention., Author(s): Sevcan A. Bakkaloglu [sup.1] , Yasar Kandur [sup.1] , Erkin Serdaroglu [sup.2] , Aytül Noyan [sup.3] , Aysun Karabay Bayazit [sup.4] , Lale Sever [sup.5] , Sare Gülfem Özlü [...]

Author(s): Emre Leventoglu [sup.1] , Bahar Büyükkaragöz [sup.1] , Bahriye Uzun Kenan [sup.1] , Arzu Okur [sup.2] , Esra Döger [sup.3] , Sevcan A. Bakkaloglu [sup.1] Author Affiliations: (1) grid.25769.3f, [...]

Author(s): Emre Leventoglu [sup.1] , Bahar Büyükkaragöz [sup.1] , Zühre Kaya [sup.2] , Kibriya Fidan [sup.1] , Oguz Söylemezoglu [sup.1] , Sevcan A. Bakkaloglu [sup.1] Author Affiliations: (1) grid.25769.3f, 0000 [...]

Author(s): Burcu Yazicioglu [sup.1] , Sevcan A. Bakkaloglu [sup.1] Author Affiliations: (1) grid.25769.3f, 0000 0001 2169 7132, Department of Pediatric Nephrology, Gazi University School of Medicine, , Ankara, Turkey Correction [...]

Tularemia is a disease caused primarily by 2 subspecies of Francisella tularensis: F. tularensis subsp. tularensis, which is restricted to North America; and F. tularensis subsp. holarctica, which is found [...]

Background Pleural or pericardial effusions secondary to pleuro-peritoneal fistula (PPF) and pericardio-peritoneal fistula (PcPF) are rare but serious complications of peritoneal dialysis (PD). Methods We conducted a 10-year survey across all participating centres in the European Paediatric Dialysis Working Group to review the incidence, diagnostic techniques, therapeutic options and outcome of children on chronic PD with PPF and/or PcPF. Results Of 1506 children on PD there were ten cases (8 of PPF, 1 each of PcPF and PPF + PcPF), with a prevalence of 0.66 %. The median age at presentation was 1.5 [inter-quartile range (IQR) 0.4-2.4] years, and nine children were Conclusion In conclusion, PPF and PcPF are rare in children on chronic PD, but are associated with significant morbidity, requiring a change of dialysis modality in all cases. Risk factors for PPF development include age of, Author(s): Stephanie Dufek[sup.1] , Tuula Holtta[sup.2] , Michel Fischbach[sup.3] , Gema Ariceta[sup.4] , Augustina Jankauskiene[sup.5] , Rimante Cerkauskiene[sup.5] , Claus Peter Schmitt[sup.6] , Betti Schaefer[sup.6] , Christoph Aufricht[sup.7] , Elizabeth [...]

Despite technological improvements in dialysis connectology and dialysis technique, peritonitis remains the most common and most significant complication of peritoneal dialysis (PD) in children. Most children undergoing chronic PD experience none or only one peritonitis episode, while others have multiple episodes or episodes secondary to unusual organisms. Knowledge of potential risk factors and likely patient outcome is imperative if treatment is to be optimized. In this review we will, in turn, describe episodes of peritonitis that are characterized as either relapsing, recurrent, repeat or zoonosis-related to highlight the clinical issues that are commonly encountered by clinicians treating these infections., Author(s): Sevcan A. Bakkaloglu[sup.1] , Bradley A. Warady[sup.2] Author Affiliations: (1) Department of Pediatrics, Division of Pediatric Nephrology, Gazi University School of Medicine, Ankara, Turkey (2) Division of Pediatric Nephrology, [...]

Background Few observations on apheresis in pediatric nephrology units have been published. Methods This retrospective study involved children [less than or equal to] 18 years undergoing plasma exchange (PE), immunoadsorption (IA), or double filtration plasmapheresis (DFPP) in 12 European pediatric nephrology units during 2012. Results Sixty-seven children underwent PE, ten IA, and three DFPP, for a total of 738 PE and 349IA/DFPP sessions; 67.2 % of PE and 69.2 % of IA/DFPP patients were treated for renal diseases, in particular focal segmental glomerulosclerosis (FSGS), hemolytic-uremic syndrome (HUS), and human leukocyte antigen (HLA) desensitization prior to renal transplantation; 20.9 % of PE and 23.1 % of IA/DFPP patients had neurological diseases. Membrane filtration was the most common technique, albumin the most frequently used substitution fluid, and heparin the preferred anticoagulant. PE achieved full disease remission in 25 patients (37.3 %), partial remission in 22 (32.8 %), and had no effect in 20 (29.9 %). The response to IA/ DFPP was complete in seven patients (53.8 %), partial in five (38.5 %), and absent in one (7.7 %). Minor adverse events occurred during 6.9 % of PE and 9.7 % of IA/DFPP sessions. Conclusions PE, IA, and DFPP are safe apheresis methods in children. Efficacy is high in pediatric patients with recurrent focal segmental glomerulosclerosis (FSGS), atypical hemolytic uremic syndrome (HUS), human leukocyte antigen (HLA) sensitization, and neurological autoimmune diseases. Keywords Pediatric apheresis * Therapeutic apheresis * Plasma exchange * Immunoadsorption * Double filtration plasmapheresis, Introduction Apheresis is a widely recognized therapeutic option in pediatric patients, even though the literature on the various forms of pediatric apheresis is mostly limited to single-center, retrospective studies [1-6]. [...]

Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of end-stage renal failure. Identification of single-gene causes of SRNS has generated some insights into its pathogenesis; however, additional genes and disease [...]

Background There is increasing focus on the problems involved in the transition and transfer of young adult patients from paediatric to adult renal units. This situation was addressed by the 2011 International Pediatric Nephrology Association/International Society of Nephrology (IPNA/ISN) Consensus Statement on transition. Methods We performed a survey of transition practices of 15 paediatric nephrology units across Europe 2 years after publication of the consensus statement. Results Two thirds of units were aware of the guidelines, and one third had integrated them into their transition practice. Forty-seven per cent of units transfer five or fewer patients with chronic kidney disease (CKD) stage 5 per year to a median of five adult centres, with higher numbers of CKD stages 2-4 patients. Seventy-three per cent of units were required by the hospital or government to transfer patients by a certain age. Eighty per cent of units commenced transition planning after the patient turned 15 years of age and usually within 1-2 years of the compulsory transfer age. Forty-seven per cent of units used a transition or transfer clinic. Prominent barriers to effective transition were patient and parent attachment to the paediatric unit and difficulty in allowing the young person to perform self-care. Conclusions Whereas awareness of the consensus statement is suboptimal, it has had some impact on practice. Adult nephrologists receive transferred patients infrequently, and the process of transition is introduced too late by paediatricians. Government- and hospital-driven age-based transfer policies distract focus from the achievement of competencies in self care. Variable use of transition clinics, written patient information and support groups is probably due to economic and human-resource limitations. The consensus statement provides a standard for evolving and evaluating transitionpolicies jointly agreed upon by paediatric and adult units. Keywords Adolescence * Chronic kidney disease * Guidelines * Survey * Transition * Young adult, Introduction Increasing numbers of children with chronic illness, including chronic kidney disease (CKD), are surviving into young adulthood and requiring transition to adult services [1]. Numbers transferring within localities may [...]

A series of thin films of CoNiCu and NiCu produced using the electrodeposition method have been examined using X-ray fluorescence (XRF), X-ray diffraction (XRD), and scanning electron microscopy (SEM). Energy dispersive XRF spectroscopy was used to determine the concentrations of the atomic percentage in these films. CoNiCu and NiCu thin film samples were excited by gamma rays with 59.5 keV energy photons from 100 mCi [sup.241]]Am radioisotope source. K X-rays emitted by samples were counted by an Ultra-LEGe detector having a resolution of 150 eV at 5.9 keV. Structural analyses of these films have been done using the XRD technique and thin films were found to have a face-centred cubic (fcc) structure. In addition, surface morphologies of the films have been analysed by SEM. If one examines the SEM images of thin film samples, it can be seen that these elements have been homogeneously distributed in the samples of the thin films. PACS Nos.: 32.30.Rj, 61.05.cp, 68.37.Hk. Resume: Nous preparons une serie de films minces de CoNiCu et de NiCu. Les films sont examines par fluorescence X (XRF), par diffraction X (XRD) et a l'aide d'un microscope electronique a balayage (SEM). Nous utilisons l'analyse XRF dispersive en energie pour determiner la concentration des pourcentages atomiques dans ces films. Les films minces de CoNiCu et de NiCu sont excites par rayons gamma de 59.5 keV a partir d'une source de [sup.241]Am de 100 mCi. Les rayons X emis par les echantillons sont comptes par un detecteur Ultra-LEGe d'une resolution de 150 eV a 5.9 keV. Nous utilisons la XRD sur ces films et nous trouvons une structure cubique a face centree (fcc). Nous etudions aussi leur morphologie de surface a l'aide du SEM. Les images obtenues indiquent que les elements sont distribues de facon homogene dans ces echantillons. [Traduit par la Redaction], 1. Introduction Thin films are thin material layers ranging from a fraction of a nanometre to several micrometres in thickness. Thin film technology and the investigation of the properties of [...]

Background Many factors may impact upon choice of renal replacement therapy (RRT) for children and adolescents, including patient and family choice, patient size and distance from the renal centre as well as logistic issues such as facilities and staffing at the unit. We report a survey of factors influencing treatment choice in 14 European paediatric nephrology units. Methods A questionnaire was developed by consensus and completed by 14 members of the European Paediatric Dialysis Working Group on facilities, staffing and family assessments impacting on choice of therapy as well as choice of therapy for 97 patients commencing initial RRT in 2011. Results All units offered all modalities of RRT, but there were limitations for pre-emptive transplantation (PET) and largely adult surgical dependence for creation of arteriovenous fistulae and transplantation. The average waiting time for a deceased donor kidney was 18.5 (range 3-36) months. Full time dietetic support was available in six of the 14 units. There was no social worker, psychology, play therapy or teaching support in three, two, seven and four units, respectively. Assessment by other members of the multidisciplinary team and home visits before choice of therapy was carried out in 50 % of units, and although all patients were discussed at team meetings, the medical opinion predominated. In terms of types of RRT, 50 % of patients were commenced on chronic peritoneal dialysis (PD), 34 % on haemodialysis (HD) and 16 % underwent pre-emptive transplantation (PET). Chronic PD predominated in patients aged 10 years. Patient and family choice and age or size of patient were predominant factors in choice of therapy with a predictable decline in renal function favouring PET and social factors HD. Conclusions Chronic peritoneal dialysis predominated as primary choice of RRT, especially in younger children. The PET rates remain low. The influence of surgeons predominanted, and national transplant rules may be significant. Most units had insufficient multiprofessional support, which may impact upon initial choice of therapy as well as sustaining families through RRT. Keywords Choice of therapy * Renal replacement therapy * Dialysis * Pre-emptive transplantation * Psychosocial * Pediatric, Introduction The choice of chronic renal replacement therapy (RRT) for each individual child and family can be a complex issue. It involves consideration of the facilities and expertise available at [...]

Abstract Chronic peritoneal dialysis (CPD) has been utilized in the treatment of children since 1989 in Turkey. The aims of this study were to summarize our experience with CPD in [...]

We report the molecular findings for the CTNS gene in 12 Turkish cystinosis patients aged 7-29 years. All presented initially with severe failure to thrive, polyuria, and polydipsia. Cystinosis was diagnosed at age 1 month to 9 years. Seven patients reached end-stage renal failure at ages ranging from 6.5 to 15 years. Whereas three of the remaining five have renal Fanconi syndrome with proteinuria, two have had kidney failure of varying degrees. Molecular analyses involved an initial multiplex polymerase chain reaction (PCR) to determine the presence or absence of the 57-kb northern European founder deletion in CTNS, followed by sequencing of the ten coding exons of CTNS. Comprehensive mutation analysis verified that none of the 12 patients carried the common 57-kb deletion. We identified four previously reported nucleotide variations associated with cystinosis and five new variants: a 10-kb deletion, three missense variants, and a nucleotide substitution in a potential branch point site of intron 4. This study is the first molecular analysis of Turkish cystinosis patients and provides guidance for the molecular diagnosis of cystinosis in this population. Keywords Cystinosis * CTNS gene * Turkish patients * Genetic basis * New mutations, Introduction Cystinosis (CTNS; OMIM 219800) is an autosomal recessive disease caused by mutations of the CTNS gene (OMIM 606272; GenBank NM_004937.2) located on chromosome 17p13. CTNS codes for cystinosin, a [...]

The purpose of this article is to provide recommendations on the choice of peritoneal dialysis (PD) fluids in children by the European Pediatric Dialysis Working Group. The literature on experimental and clinical studies with PD solutions in children and adults was analyzed together with consensus discussions within the group. A grading was performed based on the international KDIGO nomenclature and methods. The lowest glucose concentration possible should be used. Icodextrin may be applied once daily during the long dwell, in particular in children with insufficient ultrafiltration. Infants on PD are at risk of ultrafiltration-associated sodium depletion, while anuric adolescents may have water and salt overload. Hence, the sodium chloride balance needs to be closely monitored. In growing children, the calcium balance should be positive and dialysate calcium adapted according to individual needs. Limited clinical experience with amino acid-based PD fluids in children suggests good tolerability. The anabolic effect, however, is small; adequate enteral nutrition is preferred. CPD fluids with reduced glucose degradation products (GDP) content reduce local and systemic toxicity and should be preferred whenever possible. Correction of metabolic acidosis is superior with pH neutral bicarbonate-based fluids compared with single-chamber, acidic, lactate-based solutions. Prospective comparisons of low GDP solutions with different buffer compositions are still few, and firm recommendations cannot yet be given, except when hepatic lactate metabolism is severely compromised., Author(s): Claus Peter Schmitt [sup.1] , Sevcan A. Bakkaloglu [sup.2] , Günter Klaus [sup.3] , Cornelis Schröder [sup.4] , Michel Fischbach [sup.5] Author Affiliations: (1) Division of Pediatric Nephrology, Center [...]

The purpose of this article is to provide recommendations on the choice of peritoneal dialysis (PD) fluids in children by the European Pediatric Dialysis Working Group. The literature on experimental and clinical studies with PD solutions in children and adults was analyzed together with consensus discussions within the group. A grading was performed based on the international KDIGO nomenclature and methods. The lowest glucose concentration possible should be used. Icodextrin may be applied once daily during the long dwell, in particular in children with insufficient ultrafiltration. Infants on PD are at risk of ultrafiltration-associated sodium depletion, while anuric adolescents may have water and salt overload. Hence, the sodium chloride balance needs to be closely monitored. In growing children, the calcium balance should be positive On behalf of the European Pediatric Dialysis Working Group and dialysate calcium adapted according to individual needs. Limited clinical experience with amino acid-based PD fluids in children suggests good tolerability. The anabolic effect, however, is small; adequate enteral nutrition is preferred. CPD fluids with reduced glucose degradation products (GDP) content reduce local and systemic toxicity and should be preferred whenever possible. Correction of metabolic acidosis is superior with pH neutral bicarbonate-based fluids compared with single-chamber, acidic, lactate-based solutions. Prospective comparisons of low GDP solutions with different buffer compositions are still few, and firm recommendations cannot yet be given, except when hepatic lactate metabolism is severely compromised. Keywords Peritoneal dialysis fluids * Pediatrics * Biocompatible * Icodextrin * Amino acid * Consensus * Glucose degradation products, Introduction Peritoneal dialysis (PD) is the preferred renal replacement therapy in children until renal transplantation can be realized. The choice of PD solution has gained particular importance, in the light [...]

The aim of this prospective, multicenter study was to define the etiology and clinical features of acute kidney injury (AKI) in a pediatric patient cohort and to determine prognostic factors. Pediatric-modified RIFLE (pRIFLE) criteria were used to classify AKI. The patient cohort comprised 472 pediatric patients (264 males, 208 females), of whom 32.6% were newborns (median age 3 days, range 1-24 days), and 67.4% were children aged >1 month (median 2.99 years, range 1 month-18 years). The most common medical conditions were prematurity (42.2%) and congenital heart disease (CHD, 11.7%) in newborns, and malignancy (12.9%) and CHD (12.3%) in children aged>1 month. Hypoxic/ischemic injury and sepsis were the leading causes of AKI in both age groups. Dialysis was performed in 30.3% of newborns and 33.6% of children aged>1 month. Mortality was higher in the newborns (42.6 vs. 27.9%; p1 month. Keywords Epidemiology * Mortality * pRIFLE * Prognosis, Introduction Acute kidney injury (AKI) is a medical condition commonly encountered by pediatricians, nephrologists, and intensivists. However, only a limited number of studies on the epidemiology of AKI in children [...]

Conflicting results have been reported in small non-homogenous groups of children with chronic renal failure in terms of casual blood pressure and ambulatory blood pressure monitoring (ABPM) parameters and left ventricular hypertrophy (LVH). The aim of our study was to assess the value of ABPM and hematological and biochemical parameters in predicting LVH in children on chronic peritoneal dialysis (CPD). Echocardiography and 24-h ABPM were performed in addition to routine biochemical and hematological evaluations in 47 children on CPD (26 male, 21 female; mean age 14.74 [+ or -] 3.52 years). Mean daytime systolic blood pressure (SBP) and mean daytime diastolic blood pressure (DBP) values were found to be higher than the mean casual SBP and DBP (p=0.001) values. Thirty-three (70.2%) children had LVH. The correlations between the left ventricular mass index and ABPM variables were good. Stepwise multiple regression analysis revealed daytime SBP load ([beta]=0.652; /K0.01) and hematocrit ([beta] = -0.282; p15% and hematocrit value 31% and daytime SBP load Keywords Blood pressure load * Children * Chronic peritoneal dialysis * Hematocrit * Left ventricular hypertrophy, Introduction Ambulatory blood pressure monitoring (ABPM) can be used to precisely characterize the variations in blood pressure (BP) that occur during daily activities [1]. It is also superior to casual [...]

In this study, risk factors were investigated in children with community-acquired urinary tract infections (UTI) caused by extended-spectrum beta-lactamases (ESBL)-producing E. coli or Klebsiella spp. One hundred and fifty-five patients were diagnosed with ESBL-positive UTI (case group) in the outpatient clinics of Hacettepe University Children's Hospital between 1 January 2004 and 31 December 2006. A control group, 155 out of 4,105 children, was matched by age and sex among children with ESBL-negative UTI. A total of 310 patients' files were evaluated retrospectively. As regards the symptoms of UTI, no statistical differences were seen between the two groups. Although the most frequently isolated microorganism was E. coli in both groups, Klebsiella spp. was found to be more frequent in those diagnosed with ESBL(+) UTI (p < 0.001). Having an underlying disease and hospitalization, infections, and use of antibiotics within the last 3 months were found to be potential risk factors (p < 0.001). With conditional logistic regression analysis, having an underlying disease and hospitalization within the last 3 months were identified as independent risk factors for ESBL(+) UTI. In conclusion, the recognition of risk factors for UTI, caused by ESBL(+) bacteria in children, may aid in the identification of high-risk cases and may enable proper management of these patients. Keywords Extended-spectrum beta-lactamases (ESBL)producing bacteria * Urinary tract infection * Community-acquired infection * Risk factors * Children, Introduction Extended-spectrum beta-lactamases (ESBL) are plasmid-mediated enzymes that cause resistance to various types of the newer [beta]-lactam antibiotics, including the expanded-spectrum cephalosporins and monobactams [1-4]. Initially reported in the mid-1980s [...]

Cyclophosphamide (CYC) has been the landmark in the treatment of lupus nephritis. However, long-term treatment with CYC is associated with significant side effects. We aimed to evaluate the efficacy of short-term intravenous (IV) CYC treatment as a remission induction treatment followed by azathioprine (AZA) or mycophenolate mofetil (MMF) as a maintenance treatment. Twenty patients (18 girls) with biopsy-proven class III (5) and IV (15) lupus nephritis were included in to the study. Detailed clinical and laboratory data and patient outcomes were evaluated. All patients received three methylprednisolone (MP) IV pulses, followed by oral prednisone 0.5-1 mg/kg per day and one IV pulse of CYC per month for 6 months. Azathioprine was started as a remission-maintaining treatment. In ten of 20 patients, treatment was switched to MMF. The mean age at the time of diagnosis was 16.11 ± 3.49 years, and the mean duration of follow-up was 49.6 ± 27 months. Fourteen patients (70%) had complete remission, three (15%) had partial remission, one (5%) continued to have active disease, and two (10%) progressed to end-stage renal disease. Nine of the patients (45%) with complete remission had received AZA, and switching to MMF increased complete remission rate (additional five patients; 25%). In conclusion, short-term (6-month) IV bolus CYC treatment followed by AZA is a safe and effective treatment in children with severe lupus nephritis, and using MMF increases remission rate in resistant cases., Author(s): Esra Baskin [sup.1] , Seza Ozen [sup.2] , Nilgun Çakar [sup.3] , Umut S. Bayrakci [sup.1] , Erkan Demirkaya [sup.4] , Aysin Bakkaloglu [sup.2] Author Affiliations: (1) grid.411548.d, 0000000114571144, [...]

Cyclophosphamide (CYC) has been the landmark in the treatment of lupus nephritis. However, long-term treatment with CYC is associated with significant side effects. We aimed to evaluate the efficacy of short-term intravenous (IV) CYC treatment as a remission induction treatment followed by azathioprine (AZA) or mycophenolate mofetil (MMF) as a maintenance treatment. Twenty patients (18 girls) with biopsy-proven class III (5) and IV (15) lupus nephritis were included in to the study. Detailed clinical and laboratory data and patient outcomes were evaluated. All patients received three methylprednisolone (MP) IV pulses, followed by oral prednisone 0.5-1 mg/kg per day and one IV pulse of CYC per month for 6 months. Azathioprine was started as a remission-maintaining treatment. In ten of 20 patients, treatment was switched to MMF. The mean age at the time of diagnosis was 16.11 [+ or -] 3.49 years, and the mean duration of follow-up was 49.6 [+ or -] 27 months. Fourteen patients (70%) had complete remission, three (15%) had partial remission, one (5%) continued to have active disease, and two (10%) progressed to end-stage renal disease. Nine of the patients (45%) with complete remission had received AZA, and switching to MMF increased complete remission rate (additional five patients; 25%). In conclusion, short-term (6-month) IV bolus CYC treatment followed by AZA is a safe and effective treatment in children with severe lupus nephritis, and using MMF increases remission rate in resistant cases. Keywords Lupus nephritis * Children * Treatment * Cyclophosphamide * MMF, Introduction Renal involvement is frequent in children with systemic lupus erythematosus (SLE). SLE tends to be severe and to have a variable response in childhood. The risk of progression to [...]

Answers 1--Angiographic findings showing occlusion of a middle-sized artery and tissue biopsy findings demonstrating necrotizing non-granulomatous inflammation of the wall ofa middle-sized artery confirm the diagnosis of polyarteritis nodosa (PAN) [...]

Protein coding genes constitute only approximately 1% of the human genome but harbor 85% of the mutations with large effects on disease-related traits. Therefore, efficient strategies for selectively sequencing complete coding regions (i.e., 'whole exome') have the potential to contribute to the understanding of rare and common human diseases. Here we report a method for whole-exome sequencing coupling Roche/NimbleGen whole exome arrays to the Illumina DNA sequencing platform. We demonstrate the ability to capture approximately 95% of the targeted coding sequences with high sensitivity and specificity for detection of homozygous and heterozygous variants. We illustrate the utility of this approach by making an unanticipated genetic diagnosis of congenital chloride diarrhea in a patient referred with a suspected diagnosis of Bartter syndrome, a renal salt-wasting disease. The molecular diagnosis was based on the finding of a homozygous missense D652N mutation at a position in SLC26A3 (the known congenital chloride diarrhea locus) that is virtually completely conserved in orthologues and paralogues from invertebrates to humans, and clinical follow-up confirmed the diagnosis. To our knowledge, whole-exome (or genome) sequencing has not previously been used to make a genetic diagnosis. Five additional patients suspected to have Bartter syndrome but who did not have mutations in known genes for this disease had homozygous deleterious mutations in SLC26A3. These results demonstrate the clinical utility of whole-exome sequencing and have implications for disease gene discovery and clinical diagnosis. Bartter syndrome | congenital chloride diarrhea | next-generation sequencing | whole-exome sequencing | personal genomes www.pnas.org/cgi/doi/10.1073/pnas.0910672106

Low 1/f noise, low-dropout (LDO) regulators are becoming critical for the supply regulation of deep-submicron analog baseband and RF system-on-chip designs. A low-noise, high accuracy LDO regulator (LN-LDO) utilizing a chopper stabilized error amplifier is presented. In order to achieve fast response during load transients, a current-mode feedback amplifier (CFA) is designed as a second stage driving the regulation FET. In order to reduce clock feed-through and 1/f noise accumulation at the chopping frequency, a first-order digital [SIGMA][DELTA] noise-shaper is used for chopping clock spectral spreading. With up to 1 MHz noise-shaped modulation clock, the LN-LDO achieves a noise spectral density of 32 nV/ [square root of Hz] and a PSR of 38 dB at 100 kHz. The proposed LDO is shown to reduce the phase noise of an integrated 32 MHz temperature compensated crystal oscillator (TCXO) at 10 kHz offset by 15 dB. Due to reduced 1/f noise requirements, the error amplifier silicon area is reduced by 75%, and the overall regulator area is reduced by 50% with respect to an equivalent noise static regulator. The current-mode feedback second stage buffer reduces regulator settling time by 60% in comparison to an equivalent power consumption voltage mode buffer, achieving 0.6 [micro]s settling time for a 25-mA load step. The LN-LDO is designed and fabricated on a 0.25 [micro]m CMOS process with five layers of metal, occupying 0.88 [mm.sup.2]. Index Terms--Chopper stabilization, current feedback amplifier, low-dropout regulators, power supply rejection.

Systematic design of low-dropout-regulator (LDO) regulated low-phase-noise LC-tank voltage controlled oscillators (VCOs) is presented. Low-frequency sensitivity profile of power supply induced phase noise of a typical cross-coupled LC-tank VCO is investigated. The relationship between frequency pushing and power supply-induced phase noise is derived. Systematic codesign of VCO sensitivity to low-frequency supply noise with respect to an LDO output noise and power supply rejection profile is introduced. To demonstrate the design approach experimentally, two 2.4-GHz LC-tank VCOs with pMOS and nMOS switching devices powered by PFET LDOs are designed and fabricated on an 0.18-ftm, 7-layer metal CMOS process. By using an integrated LDO, it is shown that the VCO phase-noise sensitivity to low frequency improves by 55 dB at 100-kHz offset. Index Terms--DC-DC power conversion, voltage regulators, phase noise, power supply rejection (PSR), voltage-controlled oscillators (VCOs).

A de novo chromosome 7q inversion disrupting Autism susceptibility candidate 2 (AUTS2) and Contactin Associated Protein-Like 2 (CNTNAP2) in a child with congitive and social delay is identified. It is suggested that rare variants contribute to the pathophysiology of autism spectrum disorders (ASD).

The design and analysis of a fully integrated multistage interleaved synchronous buck dc-dc converter with on-chip filter inductor and capacitor is presented. The dc-dc converter is designed and fabricated in 0.18 [micro]m SiGe RFBiCMOS process technology and generates 1.5 V-2.0 V programmable output voltage supporting a maximum output current of 200 mA. High switching frequency of 45 MHz, multiphase interleaved operation, and fast hysteretic controller reduce the filter inductor and capacitor sizes by two orders of magnitude compared to state-of-the-art converters and enable a fully integrated converter. The fully integrated interleaved converter does not require off-chip decoupling and filtering and enables direct battery connection for integrated applications. This design is the first reported fully integrated multistage interleaved, zero voltage switching synchronous buck converter with monolithic output filters. The fully integrated buck regulator achieves 64% efficiency while providing an output current of 200 mA. Index Terms--Fully integrated switched-mode (SM) dc-dc converter, interleaved synchronous buck converter, zero voltage switching (ZVS).

[SIGMA][DELTA] frequency discriminators ([SIGMA][DELTA]AFDs) convert instantaneous frequency deviations of a carrier signal to digital. They are used for decoding narrowband phase or frequency modulated signals in communication receivers, self calibration of RF frequency synthesizers and in digital phase locked loops. In this paper, the impact of reference (sampling) clock phase noise on a [SIGMA][DELTA]AFD's spurious-free dynamic range (SFDR) is derived. It is shown that for [SIGMA][DELTA]FDs with jittered sampling clock, in addition to FM sidebands, a high baseband tonal content is generated degrading overall SFDR. The reference clock phase noise impact is derived mathematically, and two commonly used [SIGMA][DELTA]FDs circuits are designed and implemented to verify the results experimentally. Experimental results are shown to match the theoretical prediction of SFDR within 3 dB. Index Terms--Clock Jitter, frequency discriminators, [SIGMA][DELTA]modulators.

Current feedback amplifiers (CFAs) provide fast response and high slew rate with Class-AB operation. Fast response, low-dropout regulators (LDRs) are critical for supply regulation of deep-submicron analog baseband and RF system-on-chip designs. An LDR with an CFA-based second stage driving the regulation field-effect transistor is presented. The low dropout (LDO) achieves an output noise spectral density of 67.7 nV/[square root of Hz], and PSR of 38 dB, both at 100 kHz. In comparison to an equivalent power consumption voltage feedback buffer LDO, the proposed CFA-based LDO settles 60% faster, achieving 0.6-[micro]s settling time for a 25-mA load step. The LDO with CFA buffer is designed and fabricated on a 0.25-[micro]m CMOS process with five layers of metal, occupying 0.23-[mm.sup.2] silicon area. Index Terms--Current feedback amplifier (CFA), low-dropout regulators (LDRs), power supply rejection.

Two integrated polar supply-modulated class E and F power amplifiers (PAs) in 0.18-[micro]m SiGe BiCMOS process are presented. The amplifiers are used to transmit GSM-EDGE signals with an envelope dynamic range of 11 dB and a frequency range of 880-915 MHz. The amplifiers use switch-mode dc--dc buck converters for supply modulation, where sigma--delta ([SUMMATION][DELTA]M), delta ([DELTA]M), and pulsewidth modulation are used to modulate the PA amplitude signal. A framework has been developed for comparing the three switching techniques for EDGE implementation. The measurement results show that [DELTA]M gives the highest efficiency and lowest adjacent channel power, providing class E and F PA efficiencies of 33% and 31%, respectively, at maximum EDGE output power. The corresponding class E and F finearized amplifiers' output spectra at 400-kHz offset are -54 and -57 dBc, respectively. Index Terms--EDGE, polar modulation, power amplifiers (PAs), switching amplifiers. Digital Object Identifier 10.1109/TMTT.2007.895407

Pulsewidth modulation (PWM) and sigma-delta modulation (SDM) have been used in several high linearity, high accuracy power delivery applications such as dc-dc power converters, audio, and radio frequency power amplifiers and data converters. While PWM can generate high linearity signals with high efficiency, it suffers from discrete tonal output spectrums. SDM, on the other hand, can generate high linearity output spectrums with shaped quantization noise spectrums and lower efficiencies due to oversampling requirements. In this paper we present a particular class of carrier frequency modulated PWM (CFMPWM), which spreads the tonal content of regular PWM uniformly in frequency and reduces the baseband noise with respect to SDM by up to 15 dB. The new modulation scheme preserves the high efficiency properties of PWM. An approximate method to estimate the spectrum of CFMPWM signals with both deterministic and random modulation is also presented. Simulation results and experimental data are reported to analyze the spectral spreading properties of the proposed CFMPWM scheme. Index Terms--Carrier frequency modulated pulsewidth modulation (CFMPWM), electromagnetic interference (EMI), pulse density modulation (PDM), sigma--delta modulation (SDM).

A bandpass (BP) sigma-delta modulator ([SIGMA][DELTA]M)-based direct digital frequency synthesizer (DDS) architecture is presented. The DDS output is passed through a single-bit, second-order BP[SIGMA][DELTA]M, shaping quantization noise out of the signal band. The single-bit BP[SIGMA][DELTA]M is then injection locked to an LC-tank oscillator, which provides a tracking BP filter response within its locking range, suppressing the BP[SIGMA][DELTA]M out of band quantization noise. The instantaneous digital frequency control word input of the DDS is used to tune the noise shaper center frequency, achieving up to 20% tuning range around the fundamental. The BP[SIGMA][DELTA]M-based synthesizer is fabricated in a 0.25-[micro]m digital CMOS process with four layers of metal. With a second-order BP noise shaper and a 44-MHz LC tank oscillator, an SFDR of 73 dB at a 2-MHz bandwidth and phase noise lower than--105 dBc/Hz at a 10-kHz offset is achieved. Index Terms--Direct digital frequency synthesizer (DDS), injection locking, oscillator, phase noise, sigma-delta modulator ([SIGMA][DELTA]M).