Comparative analysis of hospitalizations among patients treated with hemodialysis and peritoneal dialysis in European pediatric nephrology centers: results from a prospective EPDWG/ESPN Dialysis Working Group study.

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

Genetic atypical hemolytic uremic syndrome in children: a 20-year experience from a tertiary center / Síndrome hemolítica urêmica atípica genética em crianças: uma experiência de 20 anos a partir de um centro terciário

Abstract Introduction: Atypical hemolytic uremic syndrome (aHUS) is a rare disorder characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, which primarily affects preschool-aged children. This study's aim was to describe the clinical profile, management, and long-term outcome of the genetic aHUS patients admitted to a tertiary care pediatric nephrology center during 20 years. Methods: We performed a retrospective analysis of the clinical records of all aHUS patients younger than 18 years with identified genetic mutations. Data on clinical features, genetic study, therapeutic interventions, and long-term outcomes were reviewed. Results: Five cases of aHUS with an identified genetic mutation were included; all were inaugural cases with the youngest being 4 months old. Complement factor H gene mutation was identified in four patients. Therapeutic plasma exchange was performed for acute management in 4 patients, one of whom also needed acute renal replacement therapy (peritoneal dialysis). All patients went on complete remission, 2 had more than one relapse but only 1 of these progressed to chronic kidney disease during the follow-up period (median (25th-75th percentile), 136 (43.5-200.5) months). Conclusion: In children, the prognosis of renal function seems to be strongly dependent on the genetic background, thus being crucial to perform genetic study in all aHUS cases. In our cohort, 2 patients presented genetic mutations not previously described. Recent innovations on the genetic field leading to the identification of new mutations has lead to a better understanding of aHUS pathogenesis, but further studies, focusing on the genotype-phenotype correlation, with longer follow-up periods, are needed.

Resumo Introdução: A síndrome hemolítica urêmica atípica (SHUa) é um distúrbio raro caracterizado pela tríade de anemia hemolítica microangiopática, trombocitopenia e lesão renal aguda, afetando principalmente crianças em idade pré-escolar. O objetivo deste estudo foi descrever perfil clínico, manejo e desfecho em longo prazo dos pacientes com SHUa genética admitidos em um centro terciário de nefrologia pediátrica durante 20 anos. Métodos: Realizamos análise retrospectiva dos registros clínicos de todos os pacientes com SHUa menores de 18 anos com mutações genéticas identificadas. Revisaram-se dados sobre características clínicas, estudo genético, intervenções terapêuticas e desfechos em longo prazo. Resultados: Incluíram-se cinco casos de SHUa com uma mutação genética identificada; sendo todos casos inaugurais, o mais jovem tendo 4 meses de idade. A mutação no gene do fator H do complemento foi identificada em quatro pacientes. Plasmaférese terapêutica foi realizada para tratamento agudo em 4 pacientes, um dos quais também necessitou terapia renal substitutiva aguda (diálise peritoneal). Todos os pacientes tiveram remissão completa, 2 mais de uma recidiva, mas apenas 1 evoluiu para doença renal crônica durante acompanhamento (mediana (percentil 25°-75°), 136 (43,5-200,5) meses). Conclusão: Em crianças, o prognóstico da função renal parece ser fortemente dependente do histórico genético, sendo crucial realizar estudo genético em todos os casos de SHUa. Em nossa coorte, 2 pacientes apresentaram mutações genéticas não descritas anteriormente. Inovações recentes no campo genético que levaram à identificação de novas mutações conduziram a um melhor entendimento da patogênese SHUa, mas são necessários mais estudos, focando na correlação genótipo-fenótipo, com períodos de acompanhamento mais longos.

Genetic atypical hemolytic uremic syndrome in children: a 20-year experience from a tertiary center.

INTRODUCTION: Atypical hemolytic uremic syndrome (aHUS) is a rare disorder characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, which primarily affects preschool-aged children. This study's aim was to describe the clinical profile, management, and long-term outcome of the genetic aHUS patients admitted to a tertiary care pediatric nephrology center during 20 years. METHODS: We performed a retrospective analysis of the clinical records of all aHUS patients younger than 18 years with identified genetic mutations. Data on clinical features, genetic study, therapeutic interventions, and long-term outcomes were reviewed. RESULTS: Five cases of aHUS with an identified genetic mutation were included; all were inaugural cases with the youngest being 4 months old. Complement factor H gene mutation was identified in four patients. Therapeutic plasma exchange was performed for acute management in 4 patients, one of whom also needed acute renal replacement therapy (peritoneal dialysis). All patients went on complete remission, 2 had more than one relapse but only 1 of these progressed to chronic kidney disease during the follow-up period (median (25th-75th percentile), 136 (43.5-200.5) months). CONCLUSION: In children, the prognosis of renal function seems to be strongly dependent on the genetic background, thus being crucial to perform genetic study in all aHUS cases. In our cohort, 2 patients presented genetic mutations not previously described. Recent innovations on the genetic field leading to the identification of new mutations has lead to a better understanding of aHUS pathogenesis, but further studies, focusing on the genotype-phenotype correlation, with longer follow-up periods, are needed.

Identifiable relatives in the family history: not without individual consent.

The family history is a traditional section of the clinical record. Data on family members in the clinical record may be anonymous but yet these may be easily identifiable; therefore, exposing the relatives of the patient to the fact that a written record is produced, mentioning them, without their consent. This is in direct contradiction with European data protection and other regulations and in contradiction with a reasonable ethical perspective. For the purpose of obtaining an image of the present state of affairs, we used as a convenience sample, the series of Case Records published in 2019 in The New England Journal of Medicine (January to December). From a total number of 40 reports, identifiable relatives were present in 30. The number of identifiable relatives varied between none and 6. It is not the right of each individual to disclose sensitive clinical information regarding other persons, without consent from these latter. Family history should no longer include identifiable relatives, unless consent is obtained from each identifiable person. The authors offer the following guidelines on this topic: (1) Do not mention any identifiable relative of the patient in the medical history without consent from the said relative; (2) Do not mention in the family history clinical conditions seemingly unrelated to the present clinical situation; (3) Do not mention in the family history clinical conditions that the patient does not (him/) herself have and that may be seen as social stigmata; (4) Consult the institutional Ethics committee in case of reasonable doubt.

Oxidized low-density lipoprotein and lipoprotein(a) levels in chronic kidney disease patients under hemodialysis: influence of adiponectin and of a polymorphism in the apolipoprotein(a) gene.

Chronic kidney disease (CKD) has been associated with an abnormal lipid profile. Our aim was to study the interplay between oxidized low-density lipoprotein (ox-LDL), adiponectin, and blood lipids and lipoproteins in Portuguese patients with CKD under hemodialysis (HD); the influence of the pentanucleotide repeat polymorphism in the apolipoprotein(a) (apo [a]) gene upon lipoprotein(a) (Lp[a]) levels in these patients. We studied 187 HD patients and 25 healthy individuals. ox-LDL and adiponectin were measured using enzyme-linked immunoassays. Apo(a) genotyping was performed by polymerase chain reaction, followed by electrophoresis in polyacrylamide gel. Compared with controls, patients presented with significantly higher levels of adiponectin, Lp(a), and ox-LDL/low-density lipoprotein cholesterol (LDLc) ratio; significantly lower levels of total cholesterol (TC), LDLc, apo A-I, apo B, ox-LDL, and TC/high-density lipoprotein cholesterol (HDLc) ratio were also observed. Similar changes were observed for patients with or without statin therapy, as compared with controls, except for Lp(a). Multiple linear regression analysis showed that body mass index, HDLc, time on HD, and triglycerides (TG) were independent determinants of adiponectin levels, and that apo B, TG and LDLc were independent determinants of ox-LDL concentration. Concerning the apo(a) genotype, the homozygous (TTTTA)8/8 repeats was the most prevalent (50.8%). A raised proportion of LDL particles that are oxidized was observed. Adiponectin almost doubled its values in patients and seems to be an important determinant in HDLc and TG levels, improving the lipid profile in these patients. Apo(a) alleles with a lower number of repetitions are more frequent in patients with higher Lp(a).

Changes in red blood cells membrane protein composition during hemodialysis procedure.

Our aim was to evaluate the influence of the hemodialysis (HD) procedure in red blood cells (RBC) membrane protein composition. We evaluated hematological data (RBC count, hemoglobin concentration, and hematimetric indices) and RBC membrane protein composition (linear and exponential gradient polyacrylamide gel electrophoresis in the presence of sodium dodecylsulfate [SDS-PAGE] followed by densitometry analysis of RBC membrane proteins) before and immediately after the HD procedure in 20 patients (10 responders and 10 non-responders to recombinant human erythropoietin therapy [rhEPO]) and 26 healthy controls. Before HD, patients presented anaemia and significant changes in membrane protein composition, namely, a statistically significant reduction in spectrin associated with a significant increase in bands 6, as well as an altered membrane protein interaction (protein 4.1/spectrin, protein 4.1/band 3, protein 4.2/band 3 and spectrin/band 3). After HD, we found that patients showed a statistically significant increase in RBC count and hemoglobin, a further and statistically significant decrease in spectrin, an increase in band 3, and an altered spectrin/band 3 ratio. When comparing responders and non-responders patients after HD, we found that the non-responders presented a trend to a higher reduction in spectrin. Our data suggest that HD procedure seems to contribute to a reduction in spectrin, which is normally associated with a reduction in RBC deformability, being that reduction in spectrin is higher in non-responder patients.

Neutrophil activation and resistance to recombinant human erythropoietin therapy in hemodialysis patients.

AIM: The aim of this work was to evaluate the neutrophil activation state in chronic kidney disease (CKD) patients under hemodialysis, and its linkage with resistance to recombinant human erythropoietin (rhEPO) therapy. METHODS: We studied 63 CKD patients under hemodialysis and rhEPO treatment (32 responders and 31 non-responders to rhEPO therapy). In 20 of the CKD patients (10 responders and 10 non-responders to rhEPO therapy), blood samples were also collected immediately after dialysis. Twenty-six healthy volunteers were included in a control group. Hemoglobin levels, total and differential leukocyte counts, and circulating levels of C-reactive protein (CRP), elastase and lactoferrin were measured in all patients and controls. RESULTS: Compared with controls, CKD patients presented with significantly higher CRP, neutrophil and elastase levels. When we compared the 2 groups of patients, we found that non-responders presented statistically significantly higher elastase plasma levels. A positive significant correlation was found between elastase levels and weekly rhEPO dose and CRP serum levels. After the hemodialysis procedure, a statistically significant rise in elastase, lactoferrin and, elastase/neutrophil and lactoferrin/neutrophil ratios were found. CONCLUSIONS: Our data show that CKD patients under hemodialysis present higher elastase levels (particularly in non-responding patients), which could be related to the rise in neutrophils, and to be part of the enhanced inflammatory process found in these patients.

Cardiac Fabry's disease: an unusual cause of left ventricular hypertrophy.

BACKGROUND: A 64-year-old male was observed as an outpatient with atypical, non-exercise-induced chest pain and palpitations. He had arterial hypertension and marked concentric left ventricular hypertrophy. After 2.5 years of antihypertensive drug therapy the patient's blood pressure had returned to normal, but his left ventricular hypertrophy was unchanged. INVESTIGATIONS: Electrocardiography, transthoracic echocardiography, myocardial perfusion scintigraphic imaging, measurement of alpha-galactosidase A activity, gene sequencing, brain MRI, carotid artery ultrasonography, biochemical renal evaluation and cardiac Doppler tissue imaging. DIAGNOSIS: Cardiac Fabry's disease. MANAGEMENT: Losartan, hydrochlorothiazide, low-dose aspirin and bisoprolol. The patient is expected to begin enzyme replacement therapy.

Glomerular filtration rate and coronary artery disease burden in patients with acute coronary syndrome.

BACKGROUND: Mild renal dysfunction may be associated with increased cardiovascular morbidity and mortality. METHODS: The relation between estimated glomerular filtration rate (eGFR), as calculated from plasma creatinine at admission, and coronary artery disease burden (CADB), was studied in a cohort of 110 patients with acute coronary syndrome and coronary atherosclerosis. RESULTS: A relatively weak but significant negative correlation was found between eGFR and CADB as measured by angiography (coefficient correlation of - 0.26, probability value of 0.006); a similar association was seen in multiple regression analysis, taking CADB as dependent variable, and eGFR, age, plasma calcium and plasma phosphorus as independent variables. After dividing the 110 patients into eGFR tertiles (with mean values of 102.9 +/- 22.8, n = 37, 75.7 + or - 5.6, n = 36, and 53.1 +/- 13.4, n = 37, all in mL/min per 1.73 m(2)), mean CADB values of the lower and higher eGFR tertiles were found to be significantly different (270.6 +/- 176.4 and 192.9 +/- 78.5, respectively). Similar mean values for CADB and for eGFR were noted when patients with elevated ST segment/new left bundle branch block and patients with nonelevated ST segment acute coronary syndrome were compared. CONCLUSIONS: We conclude that renal function of patients with acute coronary syndromes and coronary atherosclerosis, as estimated at admission, is negatively correlated with coronary artery disease burden. It is unknown whether renal dysfunction acts as a cause for accelerated coronary artery disease or if it merely acts as a surrogate marker for the overall systemic vascular system status.

Apnea/hypopnea index and benzodiazepine use in patients with arterial hypertension and excessive weight.

Sleep apnea may be associated to psychological symptoms and to increase use of antidepressant drugs. It is unknown if the use of benzodiazepines, psychoactive drugs with a depressant effect on the brain, is similar, in this regard, to antidepressant drugs use. Thirty patients with treated arterial hypertension and excessive weight (body mass index >25), either regularly using (13 patients) or not using (17 patients) benzodiazepines, were studied, by comparing the apnea/hypopnea index measured in a sleep study in both groups. Cardiac left chamber dimensions, corrected QT interval, body weight, height and mass index, as well as cervical and abdominal circumferences, were additional parameters under study. The mean apnea/hypopnea index was found to be significantly greater in patients not under chronic benzodiazepine use, when compared to the other group of patients (21.8+/-12.4, n=17 versus 9.7+/-11.3, n=13, p<0.05). Mean cervical and abdominal diameters were also greater in patients not treated with benzodiazepines. We conclude that, in this small group of patients with treated arterial hypertension and excessive weight, chronic benzodiazepine therapy was not associated with a greater mean apnea/hypopnea index. Further studies are needed to establish if, in fact, an inverse association might exist.