Use of intravenous iron and risk of anaphylaxis: A multinational observational post-authorisation safety study in Europe.

PURPOSE: This post-authorisation safety study estimated the risk of anaphylaxis in patients receiving intravenous (IV) iron in Europe, with interest in iron dextran and iron non-dextrans. Studies conducted in the United States have reported risk of anaphylaxis to IV iron ranging from 2.0 to 6.8 per 10 000 first treatments. METHODS: Cohort study of IV iron new users, captured mostly through pharmacy ambulatory dispensing, from populations covered by health and administrative data sources in five European countries from 1999 to 2017. Anaphylaxis events were identified through an algorithm that used parenteral penicillin as a positive control. RESULTS: A total of 304 210 patients with a first IV iron treatment (6367 iron dextran), among whom 13-16 anaphylaxis cases were identified and reported as a range to comply with data protection regulations. The pooled unadjusted incidence proportion (IP) ranged from 0.4 (95% confidence interval [CI], 0.2-0.9) to 0.5 (95% CI, 0.3-1.0) per 10 000 first treatments. No events were identified at first dextran treatments. There were 231 294 first penicillin treatments with 30 potential cases of anaphylaxis (IP = 1.2; 95% CI, 0.8-1.7 per 10 000 treatments). CONCLUSION: We found an IP of anaphylaxis from 0.4 to 0.5 per 10 000 first IV iron treatments. The study captured only a fraction of IV iron treatments administered in hospitals, where most first treatments are likely to happen. Due to this limitation, the study could not exclude a differential risk of anaphylaxis between iron dextran and iron non-dextrans. The IP of anaphylaxis in users of penicillin was consistent with incidences reported in the literature.

Glomerular disease patients have higher odds not to reach quality targets in chronic dialysis compared with CAKUT patients: analyses from a nationwide German paediatric dialysis registry.

BACKGROUND: Paediatric dialysis patients still suffer from high morbidity rates. To improve this, quality assurance programs like the German QiNKid (Quality in Nephrology for Children)-Registry have been developed. In our study, the significance of underlying renal disease on a range of clinical and laboratory parameters impacting morbidity and mortality was analysed. Our aim was to evaluate whether or not disease-specific dialysis strategies should be considered in planning dialysis for a patient. METHODS: Inclusion criteria were defined as follows: (1) CAKUT (congenital anomalies of the kidney and urinary tract) or glomerular disease patient, (2) < 18 years of age, (3) haemodialysis or peritoneal dialysis patient. Only measurements obtained from day 90 to 365 after the date of the first dialysis in the registry were analysed. Laboratory (serum albumin, haemoglobin, ferritin, calcium, phosphate, parathyroid hormone) and clinical parameters (height, blood pressure) were analysed using mixed effects models accounting for the correlation of repeated measures in individual patients. RESULTS: The study cohort comprised n = 167 CAKUT and n = 55 glomerular disease patients. Glomerular disease patients had significantly higher odds of hypoalbuminemia (OR 13.90, 95% CI 1.35-159.99; p = 0.0274), anaemia (OR 3.31, 95% CI 1.22-9.13; p = 0.0197), hyperphosphatemia (OR 9.69, 95% CI 2.65-37.26; p = 0.0006) and diastolic hypertension (OR 3.38, 95% CI 1.20-9.79; p = 0.0212). CONCLUSIONS: Glomerular disease patients might require more intensive dialysis regimens. The evaluation of hydration status should be given more attention, since conditions differing between the cohorts can be linked to overhydration. The QiNKid-Registry allows monitoring of the quality of paediatric dialysis in a nationwide cohort.

Burden of multimorbidity and outcome in ambulatory geriatric hemodialysis patients : Report from the QiN registry in Germany.

BACKGROUND: Patients with end-stage renal disease (ESRD) requiring hemodialysis are typically characterized by multimorbidity and increasingly by advanced age; however, there are few data on their geriatric needs. OBJECTIVE: The aim of the study was to evaluate the clinical characteristics of a large cohort of incident patients in ambulatory hemodialysis units with a particular focus on those aged over 80 years in Germany. METHODS: The electronic patient registry of the Board of Trustees (Kuratorium) for Dialysis and Kidney Transplantation (KfH) was searched for all patients who began hemodialysis in 1 of the 191 units between 2007 and 2013 and were 65 years and older. Patients were analyzed by age (65-79 years and ≥80 years) for clinical and biochemical characteristics, mortality, quality of life and hospitalizations. RESULTS: Of the 21,355 incident patients, a total of 13,872 (65%) were over 65 years old, with 9998 (46.8%) aged between 65 and 79 years and 3874 (18.1%) patients 80 years or older (oldest old). The spectrum of morbidity was comparable between the two age groups but there was a significantly higher prevalence of anemia, hypoalbuminemia and multimorbidity (>four comorbidities) in the older age group. Median survival was 4.5 years (1638 days) in the younger age group and 2.7 years (978 days) in the older group. Almost half of the patients experienced at least one episode of hospitalization during the first year but there were no significant differences between the age groups (45.9% in younger vs. 47% in older patients). In the older age group 463 (12%) patients survived more than 5 years after initiation of hemodialysis despite the presence of multiple risk factors for adverse clinical outcome. CONCLUSION: More than half of the chronic ambulatory hemodialysis patients were of advanced age and had a very high burden of multimorbidity. Nevertheless, a subgroup of ERSD patients over 80 years old survived at least 5 years on hemodialysis despite the presence of multiple risk factors for adverse clinical outcome. Identification of these patients as well as optimized care for frail hemodialysis patients will require application of geriatric assessment tools in addition to traditional parameters in nephrology. The development and validation of such tools should be the subject of further clinical studies.

[Current insights into anemia in old age : Summary of the symposium "Anemia in old age" on the occasion of the annual congress of the German Society for Geriatrics (DGG) 2016 in Stuttgart]. / Aktuelle Einblicke in die Anämie im Alter : Zusammenfassung zum Symposium "Anämie im Alter" anlässlich der DGG-Jahrestagung 2016 in Stuttgart.

Anemia in advanced age is often a multifactorial condition requiring an interdisciplinary approach. The contributions to the opening interdisciplinary symposium on anemia in older subjects focused on physiological and histopathological as well as on nephrological and neurogeriatric aspects and on the therapeutic implications of this underdiagnosed, yet highly frequent disease. The symposium was the kick-off event for the founding of the German Geriatric Society special interest group on anemia in advanced age.

Associations between global population health indicators and dialysis variables in the Monitoring Dialysis Outcomes (MONDO) consortium.

BACKGROUND: The number of patients receiving renal replacement therapy (RRT) increases annually and worldwide. Differences in the RRT incidence, prevalence, and modality vary between regions and countries for reasons yet to be clarified. AIMS: Gain a better understanding of the association between hemodialysis (HD)-related variables and general population global health indicators. METHODS: The present study included prevalent HD patients from 27 countries/regions from the monitoring dialysis outcomes (MONDO) database from 2006-2011. Global population health indicators were obtained from the 2014 World Health Organization report and the Human Development Index from the Human Development Report Office 2014. The Spearman rank test was used to assess the correlations between population social economic indicators and HD variables. RESULTS: A total of 84,796 prevalent HD patients were included. Their mean age was 63 (country mean 52-71), and 60% were males (country mean 52-85%). Significant correlations were found between HD demographic clusters and population education, wealth, mortality, and health indicators. The cluster of nutrition and inflammation variables were also highly correlated with population mortality, wealth, and health indicators. Finally, cardiovascular, fluid management, and dialysis adequacy clusters were associated with education, wealth, and health care resource indicators. CONCLUSION: We identified socioeconomic indicators that were correlated with dialysis variables. This hypothesis-generating study may be helpful in the analysis of how global health indicators may interfere with access to HD, treatment provision, dialytic treatment characteristics, and outcomes.

Interdialytic weight gain, systolic blood pressure, serum albumin, and C-reactive protein levels change in chronic dialysis patients prior to death.

Reports from a United States cohort of chronic hemodialysis patients suggested that weight loss, a decline in pre-dialysis systolic blood pressure, and decreased serum albumin may precede death. However, no comparative studies have been reported in such patients from other countries. Here we analyzed dynamic changes in these parameters in hemodialysis patients and included 3593 individuals from 5 Asian countries; 35,146 from 18 European countries; 8649 from Argentina; and 4742 from the United States. In surviving prevalent patients, these variables appeared to have notably different dynamics than in patients who died. While in all populations the interdialytic weight gain, systolic blood pressure, and serum albumin levels were stable in surviving patients, these indicators declined starting more than a year ahead in those who died with the dynamics similar irrespective of gender and geographic region. In European patients, C-reactive protein levels were available on a routine basis and indicated that levels of this acute-phase protein were low and stable in surviving patients but rose sharply before death. Thus, relevant fundamental biological processes start many months before death in the majority of chronic hemodialysis patients. Longitudinal monitoring of these dynamics may help to identify patients at risk and aid the development of an alert system to initiate timely interventions to improve outcomes.

Monitoring dialysis outcomes across the world--the MONDO Global Database Consortium.

BACKGROUND/AIMS: Dialysis providers frequently collect detailed longitudinal and standardized patient data, providing valuable registries of routine care. However, even large organizations are restricted to certain regions, limiting their ability to separate effects of local practice from the pathophysiology shared by most dialysis patients. To overcome this limitation, the MONDO (MONitoring Dialysis Outcomes) research consortium has created a platform for the joint analysis of data from almost 200,000 dialysis patients worldwide. METHODS: We examined design and operation of MONDO as well as its methodology with respect to patient inclusion, descriptive data and other study parameters. RESULTS: MONDO partners contribute primary databases of anonymized patient data and collaboratively analyze populations across national and regional boundaries. To that end, datasets from different electronic health record systems are converted into a uniform structure. Patients are enrolled without systematic exclusions into open cohorts representing the diversity of patients. A large number of patient level treatment and outcome data is recorded frequently and can be analyzed with little delay. Detailed variable definitions are used to determine if a parameter can be studied in a subset or all databases. CONCLUSION: MONDO has created a large repository of validated dialysis data, expanding the opportunities for outcome studies in dialysis patients. The density of longitudinal information facilitates in particular trend analysis. Limitations include the paucity of uniform definitions and standards regarding descriptive information (e.g. comorbidities), which limits the identification of patient subsets. Through its global outreach, depth, breadth and size, MONDO advances the observational study of dialysis patients and care.

Duration of Protection From Pneumonia After Pneumococcal Vaccination in Hemodialysis Patients (DOPPIO): Protocol for a Prospective Multicenter Study.

BACKGROUND: Pneumonia is a leading cause of death in patients with end-stage chronic kidney disease treated with dialysis. Current vaccination schedules recommend pneumococcal vaccination. However, this schedule disregards findings of rapid titer decline in adult hemodialysis patients after 12 months. OBJECTIVE: The primary objective is to compare pneumonia rates between recently vaccinated patients and patients vaccinated more than 2 years ago. As an exploratory objective, antipneumococcal antibody titers in hemodialysis patients will be determined as a function. Factors influencing antibody kinetics will be identified. METHODS: Within this prospective multicenter study, we aim to compare 2 strata of vaccinated patients: those recently vaccinated and those vaccinated more than 2 years ago. A total of 792 patients will be enrolled. Twelve partner sites (within the German Centre for Infection Research [DZIF]) with allocated dialysis practices participate in this study. All dialysis patients who are vaccinated against pneumococcal infection in accordance with Robert Koch Institute guidelines prior to enrollment will be eligible. Data on baseline demographics, vaccination history, and underlying disease will be assessed. Pneumococcal antibody titers will be determined at baseline and every 3 months for 2 years. DZIF clinical trial units coordinate titer assessment schedules and actively follow-up on study patients for 2-5 years after enrollment, including validation of end points of hospitalization, pneumonia, and death. RESULTS: The study has enrolled 792 patients and the last follow-up has been completed. Currently, the statistical and laboratory analyses are ongoing. CONCLUSIONS: Results will increase physician adherence to current recommendations. Establishing a framework for the efficient evaluation of guideline recommendations through a combination of routine and study data will inform the evidence base for future guidelines. TRIAL REGISTRATION: ClinicalTrials.gov NCT03350425; https://clinicaltrials.gov/ct2/show/NCT03350425. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/45712.

Exercise during Hemodialysis in Patients with Chronic Kidney Failure.

BACKGROUND: Patients with kidney failure undergoing hemodialysis experience physical deconditioning and multimorbidity. Exercise interventions may mitigate this outcome, but their clinical role is unclear. METHODS: This multicenter, cluster randomized controlled trial evaluated combined endurance and resistance exercise training during hemodialysis versus usual care in chronic kidney failure. It assessed physical functioning, quality of life, hospitalizations, and overall survival. The primary outcome was the change in the 60-second sit-to-stand test (STS60) between baseline and 12 months. RESULTS: A total of 1211 patients underwent randomization, 917 (65.9±14.4 years; 38.9% female) of whom were included in the full analysis (exercise intervention, n=446; usual care, n=471). At 12 months, the STS60 repetitions improved from 16.2±7.6 to 19.2±9.1 in the exercise group but declined from 16.2±7.1 to 14.7±7.9 in the usual care group (group difference, 3.85 repetitions; 95% confidence interval [CI], 2.22 to 5.48; P<0.0001). The timed up-and-go test (−1.1 seconds; 95% CI, −1.9 to −0.3) and the 6-minute walk test (37.5 m; 95% CI, 14.7 to 60.4) also differed in the exercise group versus usual care group. The physical summary score and vitality subscale of the quality of life questionnaire (i.e., the 36-item Short Form Health Survey) differed in the exercise group versus usual care group, but the other subscales did not change. Adverse events during dialysis sessions were similar in both groups. Median days spent in the hospital annually were 2 in the exercise group and 5 in the usual care group. Mortality and dialysis-specific adverse events were not affected. CONCLUSIONS: Twelve months of intradialytic exercise in patients with kidney failure significantly improved the STS60 compared with usual care. (Funded by the Innovation Fund, Federal Joint Committee; ClinicalTrials.gov number, NCT03885102.)

The influence of gender and sexual hormones on incidence and outcome of chronic kidney disease.

It has long been known that the female sex is associated with a better clinical outcome in chronic renal diseases. Although many experimental, clinical, and epidemiological studies in adults have attempted to explain the difference in disease progression between females and males, a definitive understanding of the underlying mechanisms is still lacking. Hormone-modulating therapies are being increasingly used for various indications (such as post-menopausal hormone replacement, estrogen- or androgen-receptor antagonists for cancer therapy). Therefore, a deeper knowledge of the interaction between sexual hormones and progression of kidney disease is important, as hormone-modulating therapy for non-renal indication may influence both kidney structure and function. In addition, specific modulation of the sexual hormone system, such as the use of selective estrogen receptor modulators, may represent a therapeutic option for patients with renal diseases. Although conclusive data on this topic in the pediatric population are still lacking, the aim of this review is to familiarize pediatric nephrologists with gender-specific differences in renal physiology, pathophysiology, and the progression of kidney diseases. Experimental models that analyze the effects of sexual hormones on renal structure and function are discussed. It is hoped that this review will stimulate researchers to focus on pediatric studies that will provide a deeper insight into the interaction of gender hormones and the kidney both before and during puberty.

Diminished Short- and Long-Term Antibody Response after SARS-CoV-2 Vaccination in Hemodialysis Patients.

Short-term studies have shown an attenuated immune response in hemodialysis patients after COVID-19-vaccination. The present study examines how antibody response is maintained after vaccination against SARS-CoV-2 in a large population of hemodialysis patients from six outpatient dialysis centers. We retrospectively assessed serum antibody levels against SARS-CoV-2 spike protein and nucleocapsid protein (electrochemiluminescence immunoassays, Roche Diagnostics) after COVID-19-vaccination in 298 hemodialysis and 103 non-dialysis patients (controls), comparing early and late antibody response. Compared to a non-dialysis cohort hemodialysis patients showed a favorable but profoundly lower early antibody response, which decreased substantially during follow-up measurement (median 6 months after vaccination). Significantly more hemodialysis patients had anti-SARS-CoV-2-S antibody titers below 100 U/mL (p < 0.001), which increased during follow-up from 23% to 45% but remained low in the control group (3% vs. 7%). In multivariate analysis, previous COVID-19 infections (p < 0.001) and female gender (p < 0.05) were significantly associated with higher early as well as late antibody vaccine response in hemodialysis patients, while there was a significant inverse correlation between patient age and systemic immunosuppression (p < 0.001). The early and late antibody responses were significantly higher in patients receiving vaccination after a SARS-CoV-2 infection compared to uninfected patients in both groups (p < 0.05). We also note that a higher titer after complete immunization positively affected late antibody response. The observation, that hemodialysis patients showed a significantly stronger decline of SARS-CoV-2 vaccination antibody titers within 6 months, compared to controls, supports the need for booster vaccinations to foster a stronger and more persistent antibody response.

Antibody response to mRNA SARS-CoV-2 vaccines in haemodialysis patients.

BACKGROUND: Some studies have shown an attenuated immune response in haemodialysis patients after vaccination. The present study examines the humoral response after mRNA vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a large population of haemodialysis patients from different outpatient dialysis centres. METHODS: We retrospectively assessed antibodies against SARS-CoV-2 spike protein and nucleocapsid protein (chemiluminescence immunoassays, Roche diagnostics) 3-6 weeks after the second mRNA vaccine dose in 179 maintenance haemodialysis and 70 non-dialysis patients (control cohort). Differences in anti-SARS-CoV-2 spike protein titers were statistically analysed with respect to patient-relevant factors, including age, gender, previous coronavirus disease 2019 (COVID-19) infection, systemic immunosuppressive therapy and time on dialysis. RESULTS: We found a favourable, but profoundly lower SARS-CoV-2 spike protein antibody response in comparison with a non-dialysis cohort (median 253.5 versus 1756 U/mL, P < 0.001). In multivariate analysis, previous COVID-19 infection (P < 0.001) and female gender were associated with a significantly higher vaccine response (P = 0.006) in haemodialysis patients, while there was a significant inverse correlation with increasing patient age and systemic immunosuppression (P < 0.001). There was no statistically significant correlation between the antibody titer and time on dialysis. Immune response in haemodialysis patients with a previous COVID-19 infection led to substantially higher antibody titers that were equal to those of vaccinated non-dialysis individuals with previous infection. CONCLUSION: We strongly argue in favour of regular antibody testing after COVID-19 vaccination in haemodialysis patients. Further studies should elucidate the utility of booster vaccinations to foster a stronger and persistent antibody response.

Cluster Randomized Controlled Trial on the Effects of 12 Months of Combined Exercise Training during Hemodialysis in Patients with Chronic Kidney Disease-Study Protocol of the Dialysis Training Therapy (DiaTT) Trial.

Patients with chronic kidney disease (CKD) on hemodialysis (HD) experience treatment-related immobility and physical deconditioning, which is responsible for an increased risk of frailty and a high burden of multi-morbidity. Exercise has been shown to counteract this vicious cycle; however, its effectiveness has only been investigated in small cohorts. Therefore, the objective of the Dialysis Training Therapy (DiaTT) trial will be to assess the effects of a 12-month intradialytic exercise program on physical functioning, frailty and health economics in a large cohort of HD patients in a real-world setting. DiaTT will be a prospective, cluster-randomized (1:1), controlled, multi-center, interventional clinical trial across 28 dialysis units, aiming at the recruitment of >1100 CKD patients on HD. The intervention group will receive 12 months' intradialytic exercise (combined aerobic and resistance training), whereas the usual care group will not receive intervention. The primary endpoint will be a change on the sit-to-stand test (STS60) result between baseline and 12 months. Secondary endpoints will include physical functioning, frailty, quality of life, 3-point MACE, hospitalizations, survival, quality of HD, health literacy and health care costs. By including almost as many patients as previously investigated in smaller trials, DiaTT will be the largest randomized, controlled trial assessing frailty, quality of life and mortality in the field of nephrology.

The subcellular localization of TRPP2 modulates its function.

TRPP2, also known as polycystin-2, is a calcium permeable nonselective cation channel that is mutated in autosomal dominant polycystic kidney disease but has also been implicated in the regulation of cardiac development, renal tubular differentiation, and left-to-right (L-R) axis determination. For obtaining further insight into how TRPP2 exerts tissue-specific functions, this study took advantage of PACS-dependent trafficking of TRPP2 in zebrafish larvae. PACS proteins recognize an acidic cluster within the carboxy-terminal domain of TRPP2 that undergoes phosphorylation and mediate retrieval of TRPP2 to the Golgi and endoplasmic reticulum (ER). The interaction of human TRPP2 with PACS proteins can be inhibited by a Ser812Ala mutation (TRPP2(S812A)), thereby allowing TRPP2 to reach other subcellular compartments, and enhanced by a Ser812Asp mutation (TRPP2(S812D)), thereby trapping TRPP2 in the ER. It was found that the TRPP2(S812A) mutant rescued cyst formation of TRPP2-deficient zebrafish larvae to the same degree as wild-type TRPP2, whereas the TRPP2(S812D) mutant was significantly more effective in normalizing the distorted body axis of TRPP2-deficient fish. Surprisingly, the TRPP2(S812D) mutant rescued the abnormalities of L-R asymmetry more effectively than either wild-type or TRPP2(S812A), suggesting that the ER localization of TRPP2 plays an important role in the development of normal L-R asymmetry. Taken together, these findings support the hypothesis that TRPP2 assumes distinct subcellular localizations to exert tissue-specific functions.

Multidimensional analysis of factors responsible for the low prevalence of ambulatory peritoneal dialysis in Germany (MAU-PD): a cross-sectional Mixed-Methods Study Protocol.

INTRODUCTION: Patients with end-stage kidney failure can be treated either by transplant or by dialysis, which can be administered as haemodialysis (HD) or peritoneal dialysis (PD). Although they are equivalent therapeutic options in terms of mortality, the percentage of patients in Germany treated with PD is currently very low (∼6%) compared with other countries. The aim of our study is to analyse the factors behind this percentage and their relevance to the choice of dialysis treatment in Germany. This includes analyses of regional disparities in the provision of care for dialysis patients as well as the evaluations of costs and the influence of reimbursement structures. This approach should provide further insights to explain the variation in the usage of PD and HD and will help to define starting points for future interventions. METHODS AND ANALYSIS: A mixed-methods approach will be applied to several data sources, including administrative data (ambulatory physicians' claim data, statutory health insurance claim data), quality assurance data from one of the largest German dialysis providers Kuratorium für Dialyse (KfH) and qualitative and quantitative survey data (patients, nephrologists and dialysis nurses). Qualitative data will be analysed content-analytically. Based on the quantitative data, multivariable analyses will be performed and, where possible, hierarchical models will be tested. This multidimensional approach will enable us to account for the different factors influencing the penetration of PD in Germany. ETHICS AND DISSEMINATION: Ethics approval (17-299) has been obtained from the Ethics Committee of the Medical Faculty of the University of Cologne on 25 April 2018. National and international dissemination will be accomplished by informing healthcare practitioners, patients and professional organisations and other stakeholders via conferences, scientific and non-scientific publications and seminars. TRIAL REGISTRATION NUMBER: DRKS00012555; Pre-Results.

Induction of B7-1 in podocytes is associated with nephrotic syndrome.

Kidney podocytes and their slit diaphragms form the final barrier to urinary protein loss. This explains why podocyte injury is typically associated with nephrotic syndrome. The present study uncovered an unanticipated novel role for costimulatory molecule B7-1 in podocytes as an inducible modifier of glomerular permselectivity. B7-1 in podocytes was found in genetic, drug-induced, immune-mediated, and bacterial toxin-induced experimental kidney diseases with nephrotic syndrome. The clinical significance of our results is underscored by the observation that podocyte expression of B7-1 correlated with the severity of human lupus nephritis. In vivo, exposure to low-dose LPS rapidly upregulates B7-1 in podocytes of WT and SCID mice, leading to nephrotic-range proteinuria. Mice lacking B7-1 are protected from LPS-induced nephrotic syndrome, suggesting a link between podocyte B7-1 expression and proteinuria. LPS signaling through toll-like receptor-4 reorganized the podocyte actin cytoskeleton in vitro, and activation of B7-1 in cultured podocytes led to reorganization of vital slit diaphragm proteins. In summary, upregulation of B7-1 in podocytes may contribute to the pathogenesis of proteinuria by disrupting the glomerular filter and provides a novel molecular target to tackle proteinuric kidney diseases. Our findings suggest a novel function for B7-1 in danger signaling by nonimmune cells.

Hemodialysis outcomes in a global sample of children and young adult hemodialysis patients: the PICCOLO MONDO cohort.

BACKGROUND: The aim of this study was to describe the experience of pediatric and young adult hemodialysis (HD) patients from a global cohort. METHODS: The Pediatric Investigation and Close Collaborative Consortium for Ongoing Life Outcomes for MONitoring Dialysis Outcomes (PICCOLO MONDO) study provided de-identified electronic information of 3244 patients, ages 0-30 years from 2000 to 2012 in four regions: Asia, Europe, North America and South America. The study sample was categorized into pediatric (≤18 years old) and young adult (19-30 years old) groups based on the age at dialysis initiation. RESULTS: For those with known end-stage renal disease etiology, glomerular disease was the most common diagnosis in children and young adults. Using Europe as a reference group, North America [odds ratio (OR) 2.69; CI 1.29, 5.63] and South America (OR 4.21; CI 2.32, 7.63) had the greatest mortality among young adults. North America also had higher rates of overweight, obesity, hypertension, cardiovascular disease, hospitalizations and secondary diabetes compared with all other regions. Initial catheter use was greater for North American (86.4% in pediatric patients and 75.2% in young adults) and South America (80.6% in pediatric patients and 75.9% in young adults). Catheter use at 1-year follow-up was most common in North American children (77.3%) and young adults (62.9%). Asia had the lowest rate of catheter use. For both age groups, dialysis adequacy (equilibrated Kt/V) ranged between 1.4 and 1.5. In Asia, patients in both age groups had significantly longer treatment times than in any other region. CONCLUSIONS: The PICCOLO MONDO study has provided unique baseline and 1-year follow-up information on children and young adults receiving HD around the globe. This cohort has brought to light aspects of care in these age groups that warrant further investigation.

LIS1-associated classic lissencephaly: A retrospective, multicenter survey of the epileptogenic phenotype and response to antiepileptic drugs.

BACKGROUND: Patients with LIS1-associated classic lissencephaly typically present with severe psychomotor retardation and drug-resistant epilepsy within the first year. AIM: To analyze the epileptogenic phenotype and response to antiepileptic therapy in LIS1-associated classic lissencephaly. METHOD: Retrospective evaluation of 22 patients (8 months-24 years) with genetically and radiologically confirmed LIS1-associated classic lissencephaly in 16 study centers. RESULTS: All patients in our cohort developed drug-resistant epilepsy. In 82% onset of seizures was noted within the first six months of life, most frequently with infantile spasms. Later in infancy the epileptogentic phenotype became more variable and included different forms of focal seizures as well generalized as tonic-clonic seizures, with generalized tonic-clonic seizures being the predominant type. Lamotrigine and valproate were rated most successful with good or partial response rates in 88-100% of the patients. Both were evaluated significantly better than levetiracetam (p<0.05) and sulthiame (p<0.01) in the neuropediatric assessment and better than levetiracetam, sulthiame (p<0.05) and topiramate (p<0.01) in the family survey. Phenobarbital and vigabatrin achieved good or partial response in 62-83% of the patients. CONCLUSION: Our findings suggest that patients with LIS1-associated lissencephaly might benefit most from lamotrigine, valproate, vigabatrin or phenobarbital.

Vitamin D status and cancer prevalence of hemodialysis patients in Germany.

AIM: To describe Vitamin D (VitD) status and prevalence of cancer in a large cohort of ambulatory hemodialysis patients in Germany. PATIENTS AND METHODS: In a registry study adult patients starting dialysis between 2006 and 2012 were analyzed for VitD blood levels and International classification of diseases (ICD)-10 cancer diagnoses. RESULTS: Almost one third (32.7%) of patients initiating dialysis, had VitD levels<12.5 ng/ml and 79.7% had levels<30 ng/ml (n=8,377). Average VitD at dialysis initiation increased from 18.0 to 23.2 ng/ml between 2006 and 2012. Prevalence of cancer in this cohort was 22.1% with genital, renal and gastro-intestinal cancers being most common. Cancer frequencies were similar in patients with high and low vitamin D levels. CONCLUSION: Most chronic hemodialysis patients were vitamin D-deficient in spite of concurrent vitamin D supplementation. The burden of cancer was high in these patients. Future studies should address the role of vitamin D treatment on the course and progression of cancer in chronic kidney disease (CKD) patients.