Publications by authors named "Gyorgy Reusz"

51 Publications

De novo inflammatory bowel disease in children after solid organ transplantation

Orv Hetil 2021 05 2;162(18):720-726. Epub 2021 May 2.

1 Semmelweis Egyetem, Általános Orvostudományi Kar, I. Gyermekgyógyászati Klinika, Budapest, Bókay J. u. 53., 1083.

Összefoglaló. A gyulladásos bélbetegség (inflammatory bowel disease, IBD) incidenciája folyamatosan nő, etiológiája egyelőre ismeretlen. Kezelésében gyakran alkalmazunk immunszuppresszív, illetve immunmoduláns szereket. Egyes esetekben azonban szolidszerv-transzplantációt követően, folyamatos immunszuppresszív kezelés mellett is megfigyelhető de novo IBD kialakulása. Célunk az volt, hogy Klinikánk beteganyagából összesítsük azon eseteket, amelyekben szolid szerv (máj, vese, tüdő) transzplantációját követően de novo IBD alakult ki. A transzplantációt megelőzően szklerotizáló cholangitis miatt gondozott betegeket kizártuk. A Klinikánkon gondozott, szolid szerv transzplantációján (179 máj, 197 vese, 29 tüdő) átesett betegek közül 4 (2 máj- és 2 vesetranszplantált) gyermeknél alakult ki de novo IBD. A transzplantációhoz vezető alapbetegségek biliaris atresia, polycystás vese és Denys-Drash-szindróma voltak. A transzplantációt követő immunszuppresszív terápia mind a 4 esetben tartalmazott szisztémásszteroid- és takrolimuszkezelést, emellett 3 esetben mikofenolát-mofetil (MMF)-terápiát is. A kivizsgálást indikáló főbb tünetek a haematochesia, hasmenés, fáradékonyság és fogyás voltak. A családi anamnézis 1 esetben volt pozitív. A de novo IBD diagnózisának felállítását követően mind a 4 betegnél az addigi immunszuppressziós terápia módosításra került. Összességében elmondható, hogy a szolidszerv-transzplantációt követő de novo IBD kialakulása ritka, etiológiája tisztázatlan. Az irodalom felveti az alkalmazott immunszuppresszív szerek (takrolimusz és MMF), illetve infekciók etiológiai szerepét, de az is felmerül, hogy a de novo IBD olyan önálló entitás, mely elkülönül a klasszikus IBD kategóriáitól. Klinikai szempontból fontos a tünetek hátterében álló betegség tisztázása, hiszen a prezentációs tüneteknek megfelelő, a differenciáldiagnosztika során felmerülő egyéb betegségek terápiája merőben eltér. A megfelelő terápia hozzájárulhat a transzplantált betegek morbiditásának és mortalitásának csökkentéséhez. Orv Hetil. 2021; 162(18): 720-726. Summary. The incidence of inflammatory bowel disease (IBD) is increasing, however, the aetiology is still unknown. The therapy consists of immunosuppressants and immunomodulators. In some cases, despite the continuous immunosuppressant therapy, de novo IBD develops. Our aim was to evaluate patients diagnosed with de novo IBD after solid organ (liver, kidney, or lung) transplantation. Patients treated with sclerosing cholangitis prior to liver transplantation were excluded. 4 patients (two kidney and two liver transplants) were diagnosed with de novo IBD. The underlying diseases leading to transplantation were biliary atresia, polycystic kidney, and Denys-Drash syndrome. All patients received systemic steroid and tacrolimus treatment, and 3 patients (2 kidney and 1 liver transplant) also received mycophenolate mofetil (MMF). The main symptoms indicative of de novo IBD were haematochezia, diarrhoea, fatigue, and weight loss. Family history for IBD was positive in 1 case. Following the diagnosis of IBD, immunosuppressive therapy was modified. Overall, the development of de novo IBD following solid organ transplantation is quite rare, and its aetiology is unknown. According to the literature, immunosuppressants (tacrolimus and MMF) and infections play a role in the pathomechanism, but it seems that de novo IBD is a separate entity from the classical IBD categories. From a clinical point of view, it is important to elucidate the underlying disease of the symptoms, as the treatment of other diseases that arise during differential diagnosis according to the presentation symptoms is very different. Appropriate therapy can help reduce morbidity and mortality in transplant patients. Orv Hetil. 2021; 162(18): 720-726.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1556/650.2021.32070DOI Listing
May 2021

Prognostic Value of Early Risk Stratification in Pediatric Pulmonary Arterial Hypertension.

Transplant Proc 2021 Feb 20. Epub 2021 Feb 20.

Gottsegen György National Institute of Cardiology, Pediatric Heart Center, Budapest, Hungary.

Background: Pulmonary arterial hypertension (PAH) is a life-threatening disease with risk stratification-based treatment strategy in adults. Although the risk factors have been studied individually in children, effective risk stratification is still lacking. We have tested the prognostic accuracy of pediatric PAH risk factors in our patient group.

Patients And Methods: Records of 58 PAH patients treated between 1995 and 2019 were reviewed retrospectively. Median age at diagnosis was 4.2 years (range, 0.1-16.1 years), and follow-up was 5.4 years (range, 0.01-24.1 years). Data collected at diagnosis were demographics, World Health Organization functional class, evidence of right ventricular failure, and parameters of echocardiography and cardiac catheterization.

Results: Mortality was 29% and 33% reached the composite endpoint. Patients with idiopathic PAH (n = 12) had increased risk of mortality compared with the congenital heart disease-associated PAH group (n = 32) (P = .0024). Neither the initial World Health Organization functional class staging nor the echocardiographic parameters significantly predicted the prognosis. The number of risk factors had no significant prognostic value either. In contrast, patients with higher pulmonary vascular resistance index (PVRI) had significantly increased risk (each 10 Wood units ⋅ m increase in PVRI being associated with 49.1% higher hazard, P = .0048).

Conclusions: Survival analysis showed that PAH etiology might be an important determinant in pediatric PAH risk stratification. We confirmed that PVRI has predictive value in prognostic assessment. We could not establish the prognostic value of nonweighted single risk factors or their combination to predict pediatric PAH outcome due to the low sample size, but these results indicate that such studies are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.transproceed.2021.01.047DOI Listing
February 2021

Distance measurement for pulse wave velocity estimation in pediatric age: Comparison with intra-arterial path length.

Atherosclerosis 2020 06 18;303:15-20. Epub 2020 May 18.

Istituto Auxologico Italiano, IRCCS, Cardiology Unit, Milan, Italy.

Background And Aims: Central pulse wave velocity (PWV) is a marker of arterial stiffness and is calculated by dividing the pulse wave travel distance by the transit time. However, there is no consensus as to the ideal distance measurement in children. The aim of our study was to identify the more reliable method to assess the distance measurement in the pediatric age.

Methods: Carotid-femoral PWV was measured by applanation tonometry in 988 healthy children aged 6.5-19.9 years. Two different surface distances were assessed: the subtraction method, representing the distance from the suprasternal notch to the femoral artery minus the distance from the carotid artery to the suprasternal notch, and the direct method, consisting of 80% of the distance from the carotid artery to the femoral artery. Both these methods were compared with the actual path length determined by magnetic resonance imaging (MRI) in 31 children.

Results: Subtraction and direct methods were significantly correlated in patients aged <14 years and the corresponding PWV values showed a good agreement. In children aged ≥14 years, a significant difference between the two methods was found: subtraction - direct distance = -45 ± 28 mm, with a significant difference in the resulting PWV values = -0.57 ± 0.35 m/s (p < 0.0001). This result was confirmed by MRI, showing a 10% overestimation in distance measurement by the direct method in subjects aged ≥14 years, resulting in a significantly higher PWV.

Conclusions: These data suggest a greater reliability of the subtractive method of distance measurement compared to the direct method in children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atherosclerosis.2020.04.026DOI Listing
June 2020

Validation of distinct pathogenic patterns in a cohort of membranoproliferative glomerulonephritis patients by cluster analysis.

Clin Kidney J 2020 Apr 21;13(2):225-234. Epub 2019 Jun 21.

FMC Center of Dialysis, Miskolc, Hungary.

Background: A novel data-driven cluster analysis identified distinct pathogenic patterns in C3-glomerulopathies and immune complex-mediated membranoproliferative glomerulonephritis. Our aim was to replicate these observations in an independent cohort and elucidate disease pathophysiology with detailed analysis of functional complement markers.

Methods: A total of 92 patients with clinical, histological, complement and genetic data were involved in the study, and hierarchical cluster analysis was done by Ward method, where four clusters were generated.

Results: High levels of sC5b-9 (soluble membrane attack complex), low serum C3 levels and young age at onset (13 years) were characteristic for Cluster 1 with a high prevalence of likely pathogenic variations (LPVs) and C3 nephritic factor, whereas for Cluster 2-which is not reliable because of the small number of cases-strong immunoglobulin G staining, low C3 levels and high prevalence of nephritic syndrome at disease onset were observed. Low plasma sC5b-9 levels, decreased C3 levels and high prevalence of LPV and sclerotic glomeruli were present in Cluster 3, and patients with late onset of the disease (median: 39.5 years) and near-normal C3 levels in Cluster 4. A significant difference was observed in the incidence of end-stage renal disease during follow-up between the different clusters. Patients in Clusters 3-4 had worse renal survival than patients in Clusters 1-2.

Conclusions: Our results confirm the main findings of the original cluster analysis and indicate that the observed, distinct pathogenic patterns are replicated in our cohort. Further investigations are necessary to analyse the distinct biological and pathogenic processes in these patient groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ckj/sfz073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147314PMC
April 2020

C4 nephritic factor in patients with immune-complex-mediated membranoproliferative glomerulonephritis and C3-glomerulopathy.

Orphanet J Rare Dis 2019 11 8;14(1):247. Epub 2019 Nov 8.

FMC Center of Dialysis, Miskolc, Hungary.

Background: Acquired or genetic abnormalities of the complement alternative pathway are the primary cause of C3glomerulopathy(C3G) but may occur in immune-complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) as well. Less is known about the presence and role of C4nephritic factor(C4NeF) which may stabilize the classical pathway C3-convertase. Our aim was to examine the presence of C4NeF and its connection with clinical features and with other pathogenic factors.

Results: One hunfe IC-MPGN/C3G patients were enrolled in the study. C4NeF activity was determined by hemolytic assay utilizing sensitized sheep erythrocytes. Seventeen patients were positive for C4NeF with lower prevalence of renal impairment and lower C4d level, and higher C3 nephritic factor (C3NeF) prevalence at time of diagnosis compared to C4NeF negative patients. Patients positive for both C3NeF and C4NeF had the lowest C3 levels and highest terminal pathway activation. End-stage renal disease did not develop in any of the C4NeF positive patients during follow-up period. Positivity to other complement autoantibodies (anti-C1q, anti-C3) was also linked to the presence of nephritic factors. Unsupervised, data-driven cluster analysis identified a group of patients with high prevalence of multiple complement autoantibodies, including C4NeF.

Conclusions: In conclusion, C4NeF may be a possible cause of complement dysregulation in approximately 10-15% of IC-MPGN/C3G patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13023-019-1237-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839100PMC
November 2019

Growth Patterns After Kidney Transplantation in European Children Over the Past 25 Years: An ESPN/ERA-EDTA Registry Study.

Transplantation 2020 01;104(1):137-144

Pediatric Nephrology Unit, Bordeaux University Hospital, Bordeaux, France.

Background: Improved management of growth impairment might have resulted in less growth retardation after pediatric kidney transplantation (KT) over time. We aimed to analyze recent longitudinal growth data after KT in comparison to previous eras, its determinants, and the association with transplant outcome in a large cohort of transplanted children using data from the European Society for Paediatric Nephrology/European Renal Association and European Dialysis and Transplant Association Registry.

Methods: A total of 3492 patients transplanted before 18 years from 1990 to 2012 were included. Height SD scores (SDS) were calculated using recent national or European growth charts. We used generalized equation models to estimate the prevalence of growth deficit and linear mixed models to calculate adjusted mean height SDS.

Results: Mean adjusted height post-KT was -1.77 SDS. Height SDS was within normal range in 55%, whereas 28% showed moderate, and 17% severe growth deficit. Girls were significantly shorter than boys, but catch-up growth by 5 years post-KT was observed in both boys and girls. Children <6 years were shortest at KT and showed the greatest increase in height, whereas there was no catch-up growth in children transplanted >12.

Conclusions: Catch-up growth post-KT remains limited, height SDS did not improve over time, resulting in short stature in nearly half of transplanted children in Europe.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TP.0000000000002726DOI Listing
January 2020

Cardiovascular Risk Assessment in Pediatric Liver Transplant Patients.

J Pediatr Gastroenterol Nutr 2019 03;68(3):377-383

First Department of Pediatrics, Semmelweis University, Budapest, Hungary.

Objectives: Cardiovascular (CV) diseases play a leading role in the mortality of adult liver transplant (LT) recipients. However, data regarding CV risk factors in children after LT remain sparse. The present study assessed the presence of CV risk factors and signs of CV impairment in LT children.

Methods: A total of 42 LT recipients (21 men, age 9.93 ± 3.57 years) were studied. Body composition [body mass index standard deviation score, percentage of body fat (by bioimpedance analysis)], lipid profiles, glycemic control, blood pressure, and arterial stiffness [assessed by aortic pulse wave velocity (PWV)] were evaluated. The effect of different treatment modalities [tacrolimus (TAC) (n = 30) or cyclosporine (CyA) (n = 11)] was also analyzed.

Results: Almost 18% of children were overweight or obese. Patients on TAC had a significantly higher body fat mass and percentage of body fat compared with the CyA group (P < 0.02). Borderline to high lipid values were present in 40% of patients. Children on CyA had higher serum cholesterol levels compared to TAC (P < 0.004). Nineteen percent of patients had hypertension. Half of the patients had glomerular filtration rate values <90 mL/min/1.73 m, whereas PWV values were above the 95th percentile in 12%.

Conclusions: Increased body fat, chronic kidney disease, high lipid content, hypertension, and increased arterial stiffness are already present and are in part related to the type of immunosuppression regimen in LT children >5 years following transplantation. Long-term follow-up is needed to evaluate their impact on CV health and survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPG.0000000000002196DOI Listing
March 2019

[Solid organ transplantation in childhood].

Orv Hetil 2018 11;159(46):1948-1956

I. Gyermekgyógyászati Klinika, Semmelweis Egyetem, Általános Orvostudományi Kar Budapest, Bókay J. u. 53., 1083.

Paediatric organ transplantation today is considered and accepted and widely available therapy in children with end-stage organ failure. It is important to know that in childhood, diseases leading to end-stage organ failure differ from those in adults. Beside this, in children there are different surgical and paediatric challenges before and after transplantation (size differences of the patient and donor organ, special and paediatric infections, different pharmacokinetics and pharmacodynamics of immunosuppressive drugs, noncompliance). However, paediatric organ transplantation in the last decades became a success story of the Hungarian health care owing to several working groups in Hungary and outside the country. Orv Hetil. 2018; 159(46): 1948-1956.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1556/650.2018.31284DOI Listing
November 2018

[Atypical hemolytic uremic syndrome caused by primary complement defects].

Authors:
György Reusz

Orv Hetil 2018 Jun;159(23):929-936

I. Gyermekgyógyászati Klinika, Semmelweis Egyetem, Általános Orvostudományi Kar Budapest, Bókay J. u. 53-54., 1083.

Complement is one of the most archaic parts of the innate immune system, which enhances the ability of antibodies and phagocytic cells to clear cell debris, and microorganisms. The complement system promotes inflammation and attacks the pathogen's plasma membrane. Malfunction of the system may lead to the development of autoimmunity or uncontrolled infections. Further, dysregulation of the tightly controlled complement activation process may lead to thrombotic microangiopathies with consequent multiorgan involvement. The present paper gives a short overview of the different pathways of complement activation. It focuses on primary genetic defects of components of the alternative pathway that result in dysregulation as well as on pathomechanism, classification, diagnostics and treatment of atypical hemolytic uremic syndrome (aHUS) based on the most recent international recommendations and guidelines. Finally the critical role of complement in host immunity and genetic diagnostics of complement deficiencies are illustrated with two cases of aHUS. Orv Hetil. 2018; 159(23): 929-936.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1556/650.2018.31044DOI Listing
June 2018

Cardiac Magnetic Resonance Imaging of the Myocardium in Chronic Kidney Disease.

Kidney Blood Press Res 2018 8;43(1):134-142. Epub 2018 Feb 8.

1st Department of Pediatrics, Semmelweis University, Budapest, Hungary.

Early stages of chronic kidney disease (CKD) are often underdiagnosed, while their deleterious effects on the cardiovascular (CV) system are already at work. Thus, the assessment of early CV damage is of crucial importance in preventing major CV events. Myocardial fibrosis is one of the major consequences of progressive CKD, as it may lead to reentry arrhythmias and long-term myocardial dysfunction predisposing to sudden death and/or congestive heart failure. Subclinical myocardial fibrosis, with a potential key role in the development of uraemic cardiac disease, can be measured and characterised by appropriate cardiac magnetic resonance (CMR) techniques. Fibrosis detection was initially based on the contrast agent gadolinium, due to the superiority in sensitivity and accuracy of contrast-based methods in fibrosis assessment relative to native techniques. However, the severe consequences of gadolinium administration in uraemia (nephrogenic systemic fibrosis) have forced practitioners to re-evaluate the methodology. In the present overview, we review the possible contrast-based and contrast agent-free CMR techniques, including native T1 relaxation time, extracellular volume and global longitudinal strain measurement. The review also summarises their potential clinical relevance in CKD patients based on recently published studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000487367DOI Listing
September 2018

Analysis of Linear Antibody Epitopes on Factor H and CFHR1 Using Sera of Patients with Autoimmune Atypical Hemolytic Uremic Syndrome.

Front Immunol 2017 30;8:302. Epub 2017 Mar 30.

3rd Department of Internal Medicine, Research Laboratory, Semmelweis University, Budapest, Hungary.

Introduction: In autoimmune atypical hemolytic uremic syndrome (aHUS), the complement regulator factor H (FH) is blocked by FH autoantibodies, while 90% of the patients carry a homozygous deletion of its homolog complement FH-related protein 1 (CFHR1). The functional consequence of FH-blockade is widely established; however, the molecular basis of autoantibody binding and the role of CFHR1 deficiency in disease pathogenesis are still unknown. We performed epitope mapping of FH to provide structural insight in the autoantibody recruitment on FH and potentially CFHR1.

Methods: Eight anti-FH positive aHUS patients were enrolled in this study. With overlapping synthetic FH and CFHR1 peptides, we located the amino acids (aa) involved in binding of acute and convalescence stage autoantibodies. We confirmed the location of the mapped epitopes using recombinant FH domains 19-20 that carried single-aa substitutions at the suspected antibody binding sites in three of our patients. Location of the linear epitopes and the introduced point mutations was visualized using crystal structures of the corresponding domains of FH and CFHR1.

Results: We identified three linear epitopes on FH (aa1157-1171; aa1177-1191; and aa1207-1226) and one on CFHR1 (aa276-290) that are recognized both in the acute and convalescence stages of aHUS. We observed a similar extent of autoantibody binding to the aHUS-specific epitope aa1177-1191 on FH and aa276-290 on CFHR1, despite seven of our patients being deficient for CFHR1. Epitope mapping with the domain constructs validated the location of the linear epitopes on FH with a distinct autoantibody binding motif within aa1183-1198 in line with published observations.

Summary: According to the results, the linear epitopes we identified are located close to each other on the crystal structure of FH domains 19-20. This tertiary configuration contains the amino acids reported to be involved in C3b and sialic acid binding on the regulator, which may explain the functional deficiency of FH in the presence of autoantibodies. The data we provide identify the exact structures involved in autoantibody recruitment on FH and confirm the presence of an autoantibody binding epitope on CFHR1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2017.00302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5371605PMC
March 2017

Microarray Analysis Reveals Increased Expression of Matrix Metalloproteases and Cytokines of Interleukin-20 Subfamily in the Kidneys of Neonate Rats Underwent Unilateral Ureteral Obstruction: A Potential Role of IL-24 in the Regulation of Inflammation and Tissue Remodeling.

Kidney Blood Press Res 2017 28;42(1):16-32. Epub 2017 Feb 28.

MTA-SE, Pediatrics and Nephrology Research Group, Budapest, Hungary.

Background/aims: Congenital obstructive nephropathy (CON) is the main cause of pediatric chronic kidney diseases leading to renal fibrosis. High morbidity and limited treatment opportunities of CON urge the better understanding of the underlying molecular mechanisms.

Methods: To identify the differentially expressed genes, microarray analysis was performed on the kidney samples of neonatal rats underwent unilateral ureteral obstruction (UUO). Microarray results were then validated by real-time RT-PCR and bioinformatics analysis was carried out to identify the relevant genes, functional groups and pathways involved in the pathomechanism of CON. Renal expression of matrix metalloproteinase (MMP)-12 and interleukin (IL)-24 were evaluated by real-time RT-PCR, flow cytometry and immunohistochemical analysis. Effect of the main profibrotic factors on the expression of MMP-12 and IL-24 was investigated on HK-2 and HEK-293 cell lines. Finally, the effect of IL-24 treatment on the expression of pro-inflammatory cytokines and MMPs were tested in vitro.

Results: Microarray analysis revealed 880 transcripts showing >2.0-fold change following UUO, enriched mainly in immune response related processes. The most up-regulated genes were MMPs and members of IL-20 cytokine subfamily, including MMP-3, MMP-7, MMP-12, IL-19 and IL-24. We found that while TGF-β treatment inhibits the expression of MMP-12 and IL-24, H2O2 or PDGF-B treatment induce the epithelial expression of MMP-12. We demonstrated that IL-24 treatment decreases the expression of IL-6 and MMP-3 in the renal epithelial cells.

Conclusions: This study provides an extensive view of UUO induced changes in the gene expression profile of the developing kidney and describes novel molecules, which may play significant role in the pathomechanism of CON.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000464317DOI Listing
March 2018

Decreased Neutrophil Extracellular Trap Degradation in Shiga Toxin-Associated Haemolytic Uraemic Syndrome.

J Innate Immun 2017 27;9(1):12-21. Epub 2016 Oct 27.

Section of Medical Protein Chemistry, Department of Translational Medicine, Lund University, Malmö, Sweden.

Background: Neutrophil extracellular traps (NETs) can stimulate thrombosis, and their degradation is decreased in several autoimmune disorders. It was recently reported that some patients with haemolytic uraemic syndrome (HUS) also fail to degrade NETs and that neutrophils from Shiga toxin-associated HUS are primed to form NETs.

Method: We used a well-characterized cohort of 74 thrombotic microangiopathy (TMA) patients, with a subset also providing follow-up samples, and 112 age-matched controls to investigate NET degradation and serum nuclease activity in TMA before, during and after treatment.

Results: We identified that in the cohort of TMA patients, 50% of patients with Shiga toxin-associated HUS displayed a decreased ability to degrade NETs. NET degradation correlated with serum nuclease activity, but not with autoantibodies against double-stranded DNA, which has been previously observed in some autoimmune disorders. Further, NET degradation negatively correlated with serum creatinine levels, suggesting that kidney function was negatively impacted by the low NET degradation ability.

Conclusions: We revealed that decreased NET degradation is a common feature of Shiga toxin-associated HUS and that it is associated with decreased kidney function in these patients. It remains to be clarified whether improving NET degradation would be beneficial for the patient.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000450609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738868PMC
October 2017

Association of affective temperaments with blood pressure and arterial stiffness in hypertensive patients: a cross-sectional study.

BMC Cardiovasc Disord 2016 08 8;16(1):158. Epub 2016 Aug 8.

Department of Family Medicine, Semmelweis University, Budapest, Hungary.

Background: Affective temperaments (anxious, depressive, cyclothymic, irritable and hyperthymic) measure subclinical manifestations of major mood disorders. Furthermore, cumulating evidence suggests their involvement in somatic disorders as well. We aimed to assess associations between affective temperament scores and blood pressure and arterial stiffness parameters in hypertensive patients.

Methods: In this cross-sectional study, 173 patients with well-controlled or grade 1 chronic hypertension, with no history of depression, completed the TEMPS-A, Beck Depression Inventory (BDI) and Hamilton Anxiety Scale (HAM-A) questionnaires in three GP practices. Arterial stiffness was measured with tonometry (PulsePen).

Results: According to multiple linear regression analysis, cyclothymic temperament score was positively associated with brachial systolic blood pressure independently of age, sex, total cholesterol, brachial diastolic blood pressure, BDI, HAM-A and the use of alprazolam (β = 0.529, p = 0.042), while hyperthymic temperament score was negatively related to augmentation index independent of age, sex, smoking, heart rate, BDI, HAM-A and the use of alprazolam (β = -0.612, p = 0.013). A significant interaction was found between cyclothymic temperament score and sex in predicting brachial systolic blood pressure (p = 0.025), between irritable and anxious temperament scores and sex in predicting pulse wave velocity (p = 0.021, p = 0.023, respectively) and an interaction with borderline significance between hyperthymic temperament score and sex in predicting augmentation index (p = 0.052).

Conclusions: The present findings highlight elevated blood pressure among subjects with high cyclothymic temperament as well as an increased level of arterial stiffening in subjects with low hyperthymic scores suggesting that affective temperaments may play a role in the development of hypertension and arterial stiffening and may thus represent markers of cardiovascular risk. Sex differences were also present in these associations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12872-016-0337-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4977892PMC
August 2016

Mortality risk in European children with end-stage renal disease on dialysis.

Kidney Int 2016 06 13;89(6):1355-62. Epub 2016 Apr 13.

ESPN/ERA-EDTA Registry and ERA-EDTA Registry, Amsterdam, the Netherlands.

We aimed to describe survival in European pediatric dialysis patients and compare the differential mortality risk between patients starting on hemodialysis (HD) and peritoneal dialysis (PD). Data for 6473 patients under 19 years of age or younger were extracted from the European Society of Pediatric Nephrology, the European Renal Association, and European Dialysis and Transplant Association Registry for 36 countries for the years 2000 through 2013. Hazard ratios (HRs) were adjusted for age at start of dialysis, sex, primary renal disease, and country. A secondary analysis was performed on a propensity score-matched (PSM) cohort. The overall 5-year survival rate in European children starting on dialysis was 89.5% (95% confidence interval [CI] 87.7%-91.0%). The mortality rate was 28.0 deaths per 1000 patient years overall. This was highest (36.0/1000) during the first year of dialysis and in the 0- to 5-year age group (49.4/1000). Cardiovascular events (18.3%) and infections (17.0%) were the main causes of death. Children selected to start on HD had an increased mortality risk compared with those on PD (adjusted HR 1.39, 95% CI 1.06-1.82, PSM HR 1.46, 95% CI 1.06-2.00), especially during the first year of dialysis (HD/PD adjusted HR 1.70, 95% CI 1.22-2.38, PSM HR 1.79, 95% CI 1.20-2.66), when starting at older than 5 years of age (HD/PD: adjusted HR 1.58, 95% CI 1.03-2.43, PSM HR 1.87, 95% CI 1.17-2.98) and when children have been seen by a nephrologist for only a short time before starting dialysis (HD/PD adjusted HR 6.55, 95% CI 2.35-18.28, PSM HR 2.93, 95% CI 1.04-8.23). Because unmeasured case-mix differences and selection bias may explain the higher mortality risk in the HD population, these results should be interpreted with caution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.kint.2016.02.016DOI Listing
June 2016

Neurocognitive functions of pediatric kidney transplant recipients.

Pediatr Nephrol 2016 09 12;31(9):1531-8. Epub 2016 Apr 12.

First Department of Pediatrics, Semmelweis University, Budapest, Hungary.

Background: End-stage renal disease (ESRD) in children is associated with impaired neurocognitive function and development. However, data on factors associated with neurocognitive dysfunctions in children with kidney transplants are limited.

Methods: We conducted a cross-sectional analysis comparing cognitive functions (using the Woodcock-Johnson International Edition, WJIE) in 35 kidney transplant and 35 healthy control children. Data on laboratory measurements, comorbidities, and social characteristics were collected.

Results: Transplant children had significantly worse scores on the intelligence quotient (IQ) test compared with controls [Full Scale IQ score 85 (26) vs 107 (10), p <0.001]. Lower maternal education level was significantly associated with lower WJIE cognitive test scores; however, no association was found between laboratory values and WJIE scores. Among children with kidney transplants, those with medical comorbid conditions had significantly lower Verbal Ability and Full Scale IQ scores. Earlier age of dialysis onset and a longer total time on dialysis (>9 months) were associated with lower test scores. Age-standardized duration of hospitalization was inversely correlated with IQ (r = -0.46, p <0.01) and was an independent significant predictor (Beta = -0.38, p = 0.02) of IQ scores in transplanted children.

Conclusions: Child kidney transplant recipients have neurocognitive function impairments that are associated with markers of socioeconomic status (SES) and factors related to disease severity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-016-3380-yDOI Listing
September 2016

Genetic analysis and functional characterization of novel mutations in a series of patients with atypical hemolytic uremic syndrome.

Mol Immunol 2016 Mar 27;71:10-22. Epub 2016 Jan 27.

3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary. Electronic address:

Atypical hemolytic uremic syndrome (aHUS) is a rare disorder caused by dysregulation of the complement alternative pathway, and associated with mutations in genes of complement components and regulators. In the recent years several studies have been published describing these mutations, however, no data is available from the Central and Eastern European region. In this study we present a detailed genetic analysis of our 30 patients, hospitalized with the diagnosis of aHUS in the past 7 years. We analyzed the genetic variants of genes CFH, CFI, CD46, THBD, CFB and C3; furthermore the possible effect of mutations that may alter the function or level of factor H protein was also investigated. We identified 27 (12 novel and 15 previously described) potentially disease-causing mutations in the candidate genes in 23 patients. Genetic analysis of family members revealed that in most cases the disease develops in individuals with multiple genetic risk factors, which may explain the low penetrance of the mutations. Here we showed that two novel mutations (p.W198R, p.P1161T) and a previously reported one (p.R1215Q) in CFH caused impaired regulation as indicated by increased lysis in hemolytic test, while four CFH mutations (p.V609D, p.S722X, p.T1216del and p.C448Y) were associated with decreased factor H protein level in serum as determined by allele-specific immunoassay. These results further point to the necessity of complete genetic workup of patients with aHUS and to the importance of functional characterization of novel variations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.molimm.2016.01.003DOI Listing
March 2016

Ambulatory arterial stiffness in chronic kidney disease: a methodological review.

Hypertens Res 2016 Apr 3;39(4):192-8. Epub 2015 Dec 3.

Department of Family Medicine Semmelweis University Budapest, Budapest, Hungary.

Cardiovascular mortality is the leading cause of death in chronic kidney disease (CKD) and end-stage renal disease (ESRD). This can be explained in part by an increased and progressive calcification of the medial layer of the large arteries leading to arterial stiffening. The prognostic value of measurements of arterial stiffness, especially pulse wave velocity (PWV), in the general population and in CKD and ESRD patients is high, and is above that of traditional risk factors with respect to cardiovascular outcome. In recent years, as an alternative to office measurements, methods for monitoring ambulatory arterial stiffness have been developed. The ambulatory arterial stiffness index (AASI) allows derivation of a parameter from ambulatory blood pressure measurements; however, doubts have emerged about the usefulness of this parameter. Recently, new oscillometric methodologies using simple brachial cuffs, such as Mobil-O-Graph, Vasotens or Arteriograph 24, have been introduced. They measure parameters of 24-h arterial stiffness including PWV, augmentation index and central blood pressure. This enables study of the 24-h variability of these parameters, which will hopefully lead to better cardiovascular risk stratification and improved cardiovascular outcomes of patients. Our review summarizes the present data and future directions of AASI and the methods for monitoring oscillometric 24-h stiffness in different patient populations and especially in CKD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/hr.2015.137DOI Listing
April 2016

Anemia in children following renal transplantation-results from the ESPN/ERA-EDTA Registry.

Pediatr Nephrol 2016 Feb 18;31(2):325-33. Epub 2015 Sep 18.

University of Heidelberg Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany.

Background: Our aim was to determine the prevalence of sub-target hemoglobin (Hb) levels in children with a renal allograft and to identify potential determinants associated with these Hb levels.

Methods: Data from 3669 children with a functioning renal allograft, aged <18 years between 1 January 2000 and 31 December 2012, from 20 European countries were retrieved from the ESPN/ERA-EDTA Registry, providing 16,170 Hb measurements.

Results: According to the NKF/KDOQI classification and the UK-NICE guidelines, 49.8 and 7.8% of the patients, respectively, were anemic. Hb levels were strongly associated with graft function, with Hb levels of 12.6 g/dl in children with chronic kidney disease (CKD) stage 1, declining to 10.7 g/dl in children with CKD stage 5 (P < 0.001). Higher Hb levels were associated with the use of tacrolimus compared to ciclosporin (0.14 g/dl; 95% confidence interval 0.02-0.27; P = 0.002). Low Hb levels were associated with an increased risk of graft failure (P = 0.01) or combined graft failure and death (P < 0.01), but not with death alone (not significant).

Conclusions: Anemia is present in a significant proportion of European pediatric kidney transplant recipients and is associated with renal allograft dysfunction and type of immunosuppressants used. In our patient cohort, higher Hb levels were associated with better graft and patient survival and less hypertension.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-015-3201-8DOI Listing
February 2016

Mineral metabolism in European children living with a renal transplant: a European society for paediatric nephrology/european renal association-European dialysis and transplant association registry study.

Clin J Am Soc Nephrol 2015 May 20;10(5):767-75. Epub 2015 Feb 20.

Due to the number of contributing authors,the affiliations are provided in the Supplemental Material.

Background And Objectives: Data on mineral metabolism in pediatric renal transplant recipients largely arise from small single-center studies. In adult patients, abnormal mineral levels are related to a higher risk of graft failure. This study used data from the European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association Registry to study the prevalence and potential determinants of mineral abnormalities, as well as the predictive value of a disturbed mineral level on graft survival in a large cohort of European pediatric renal transplant recipients.

Design, Setting, Participants, & Measurements: This study included 1237 children (0-17 years) from 10 European countries, who had serum calcium, phosphorus, and parathyroid hormone measurements from 2000 onward. Abnormalities of mineral metabolism were defined according to European guidelines on prevention and treatment of renal osteodystrophy in children on chronic renal failure.

Results: Abnormal serum phosphorus levels were observed in 25% (14% hypophosphatemia and 11% hyperphosphatemia), altered serum calcium in 30% (19% hypocalcemia, 11% hypercalcemia), and hyperparathyroidism in 41% of the patients. A longer time since transplantation was associated with a lower risk of having mineral levels above target range. Serum phosphorus levels were inversely associated with eGFR, and levels above the recommended targets were associated with a higher risk of graft failure independently of eGFR.

Conclusions: Abnormalities in mineral metabolism are common after pediatric renal transplantation in Europe and are associated with graft dysfunction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2215/CJN.06200614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422235PMC
May 2015

Bone metabolism and arterial stiffness after renal transplantation.

Kidney Blood Press Res 2014 28;39(6):507-15. Epub 2014 Nov 28.

1st Department of Pediatrics, Semmelweis University, Budapest, Hungary.

Background/aims: To assess the relationship between bone and vascular disease and its changes over time after renal transplantation. Metabolic bone disease (MBD) is common in chronic kidney disease (CKD) and is associated with cardiovascular (CV) disease. Following transplantation (Tx), improvement in CV disease has been reported; however, data regarding changes in bone disease remain controversial.

Methods: Bone turnover and arterial stiffness (pulse wave velocity (PWV)) were assessed in 47 Tx patients (38 (3-191) months after Tx).

Results: Bone alkaline phosphatase (BALP), osteocalcin (OC) and beta-crosslaps were significantly higher in Tx patients, and decreased significantly after one year. There was a negative correlation between BALP, OC and steroid administered (r = -0.35; r = -0.36 respectively). PWV increased in the Tx group (1.15 SD). In patients with a follow up of <24 months, PWV was correlated with BALP and beta-crosslaps (r=0.53; r = 0.69 respectively) while in the ≥24 months group, PWV was correlated with cholesterol (r=0.38).

Conclusions: Increased bone turnover and arterial stiffness are present following kidney transplantation. While bone turnover decreases with time, arterial stiffness correlates initially with bone turnover, after which the influence of cholesterol becomes significant. Non-invasive estimation of bone metabolism and arterial stiffness may help to assess CKD-MBD following renal transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000368461DOI Listing
September 2015

First-line therapy in atypical hemolytic uremic syndrome: consideration on infants with a poor prognosis.

Ital J Pediatr 2014 Dec 11;40:101. Epub 2014 Dec 11.

3rd Department of Internal Medicine, Semmelweis University, Kútvölgyi st. 4, H-1125, Budapest, Hungary.

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare and heterogeneous disorder. The first line treatment of aHUS is plasma therapy, but in the past few years, the recommendations have changed greatly with the advent of eculizumab, a humanized monoclonal anti C5-antibody. Although recent recommendations suggest using it as a primary treatment for aHUS, important questions have arisen about the necessity of immediate use of eculizumab in all cases. We aimed to draw attention to a specific subgroup of aHUS patients with rapid disease progression and high mortality, in whom plasma therapy may not be feasible.

Methods: We present three pediatric patients of acute complement-mediated HUS with a fatal outcome. Classical and alternative complement pathway activity, levels of complement factors C3, C4, H, B and I, as well as of anti-factor H autoantibody and of ADAMTS13 activity were determined. The coding regions of CFH, CFI, CD46, THBD, CFB and C3 genes were sequenced and the copy number of CFI, CD46, CFH and related genes were analyzed.

Results: We found severe activation and consumption of complement components in these patients, furthermore, in one patient we identified a previously not reported mutation in CFH (Ser722Stop), supporting the diagnosis of complement-mediated HUS. These patients were not responsive to the FFP therapy, and all cases had fatal outcome.

Conclusion: Taking the heterogeneity and the variable prognosis of atypical HUS into account, we suggest that the immediate use of eculizumab should be considered as first-line therapy in certain small children with complement dysregulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13052-014-0101-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295478PMC
December 2014

[Post-transplantation lymphoproliferative disorder in childhood].

Orv Hetil 2014 Feb;155(8):313-8

Semmelweis Egyetem, Általános Orvostudományi Kar I. Gyermekgyógyászati Klinika Budapest Bókay J. u. 53. 1083.

Introduction: Among possible complications of transplantation the post-transplant lymphoproliferative disease due to immunosuppressive therapy is of paramount importance. In most cases the direct modulating effect of Epstein-Barr virus on immune cells can be documented.

Aim: The aim of the authors was to evaluate the incidence os post-transplant lymphoproliferative diseases in pediatric transplant patients in Hungary.

Method: The study group included kidney, liver and lung transplant children followed up at the 1st Department of Pediatrics, Semmelweis University, Budapest and stem cell transplant children at Szent László Hospital, Budapest. Data were collected from 78 kidney, 109 liver and 17 lung transplant children as well as from 243 children who underwent allogenic stem cell transplantation.

Results: Between 1998 and 2012, 13 children developed post-transplant lymphoproliferative disorder (8 solid organ transplanted and 5 stem cell transplanted children). The diagnosis was based on histological findings in all cases. Mortality was 3 out of the 8 solid organ transplant children and 4 out of the 5 stem cell transplant children. The highest incidence was observed among lung transplant children (17.6%).

Conclusions: These data indicate that post-transplant lymphoproliferative disease is a rare but devastating complication of transplantation in children. The most important therapeutic approaches are reduction of immunosuppressive therapy, chemotherapy and rituximab. Early diagnosis may improve clinical outcome and, therefore, routine polymerase chain reaction screening for Epstein-Barr virus of high risk patients is recommended.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1556/OH.2014.29796DOI Listing
February 2014

Adult height in patients with advanced CKD requiring renal replacement therapy during childhood.

Clin J Am Soc Nephrol 2014 Jan 31;9(1):92-9. Epub 2013 Oct 31.

Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.

Background And Objectives: Growth and final height are of major concern in children with ESRD. This study sought to describe the distribution of adult height of patients who started renal replacement therapy (RRT) during childhood and to identify determinants of final height in a large cohort of RRT children.

Design, Setting, Participants, & Measurements: A total of 1612 patients from 20 European countries who started RRT before 19 years of age and reached final height between 1990 and 2011 were included. Linear regression analyses were performed to calculate adjusted mean final height SD score (SDS) and to investigate its potential determinants.

Results: The median final height SDS was -1.65 (median of 168 cm in boys and 155 cm in girls). Fifty-five percent of patients attained an adult height within the normal range. Adjusted for age at start of RRT and primary renal diseases, final height increased significantly over time from -2.06 SDS in children who reached adulthood in 1990-1995 to -1.33 SDS among those reaching adulthood in 2006-2011. Older age at start of RRT, more recent period of start of RRT, cumulative percentage time on a functioning graft, and greater height SDS at initiation of RRT were independently associated with a higher final height SDS. Patients with congenital anomalies of the kidney and urinary tract and metabolic disorders had a lower final height than those with other primary renal diseases.

Conclusions: Although final height remains suboptimal in children with ESRD, it has consistently improved over time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2215/CJN.00890113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3878688PMC
January 2014

Williams syndrome predisposes to vascular stiffness modified by antihypertensive use and copy number changes in NCF1.

Hypertension 2014 Jan 14;63(1):74-9. Epub 2013 Oct 14.

Washington University School of Medicine, 660 S Euclid, Campus Box 8208, St. Louis, MO 63110.

Williams syndrome is caused by the deletion of 26 to 28 genes, including elastin, on human chromosome 7. Elastin insufficiency leads to the cardiovascular hallmarks of this condition, namely focal stenosis and hypertension. Extrapolation from the Eln(+/-) mouse suggests that affected people may also have stiff vasculature, a risk factor for stroke, myocardial infarction, and cardiac death. NCF1, one of the variably deleted Williams genes, is a component of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex and is involved in the generation of oxidative stress, making it an interesting candidate modifier for vascular stiffness. Using a case-control design, vascular stiffness was evaluated by pulse wave velocity in 77 Williams cases and matched controls. Cases had stiffer conducting vessels than controls (P<0.001), with increased stiffness observed in even the youngest children with Williams syndrome. Pulse wave velocity increased with age at comparable rates in cases and controls, and although the degree of vascular stiffness varied, it was seen in both hypertensive and normotensive Williams participants. Use of antihypertensive medication and extension of the Williams deletion to include NCF1 were associated with protection from vascular stiffness. These findings demonstrate that vascular stiffness is a primary vascular phenotype in Williams syndrome and that treatment with antihypertensives or agents inhibiting oxidative stress may be important in managing patients with this condition, potentially even those who are not overtly hypertensive.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/HYPERTENSIONAHA.113.02087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932371PMC
January 2014

Continuous glucose monitoring system (CGMS) in kidney-transplanted children.

Pediatr Transplant 2013 Aug;17(5):454-60

First Department of Pediatrics and Nephrology, Research Laboratory of the Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary.

NODAT and IGT are well-known complications of immunosuppressive therapy after transplantation being a risk factor for cardiovascular disease affecting patient and graft survival. Therefore, early identification and treatment are of high importance. In this study, we examined the glycemic homeostasis of 20 renal-transplanted children using routine laboratory tests and the continuous glucose monitoring system (CGMS). Six patients (30%) had IGT, and one patient had NODAT (5%). The HOMA index was in an abnormal range in 35% of all patients and was abnormal in 67% of the IGT patients. CGMS analysis showed that IGT patients had higher "lowest glucose" level, and the incidence of hypoglycemic episodes was significantly lower compared with patients with normal OGTT result. In IGT patients, glucose variability tended to be lower. Furthermore, in the whole patient cohort, glucose variability significantly decreased with time after transplantation. Summarizing, these novel data show that "lowest glucose" level and hypoglycemic episodes are significantly influenced and altered in renal-transplanted patients with IGT. Furthermore, there is a decrease in glucose variability with time after transplantation. The mechanism and relevance of these data need further investigations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/petr.12106DOI Listing
August 2013

The role of complement in Streptococcus pneumoniae-associated haemolytic uraemic syndrome.

Nephrol Dial Transplant 2013 Sep 19;28(9):2237-45. Epub 2013 Jun 19.

3rd Department of Medicine, Research Laboratory, Faculty of Medicine, Semmelweis University, Budapest, Hungary.

Background: Atypical forms of haemolytic uraemic syndrome (aHUS) include HUS caused by defects in the regulation of alternative complement pathway and HUS linked to neuraminidase-producing pathogens, such as Streptococcus pneumoniae. Increasing data support a pathogenic role of neuraminidase in the development of S. pneumoniae-associated haemolytic uraemic syndrome (SP-HUS), but the role of complement has never been clarified in detail. Therefore, we aimed to investigate whether the pathologic complement profile and genetic risk factors of aHUS are present in patients with SP-HUS.

Methods: Enrolling five patients with SP-HUS classical and alternative pathway activity, besides C3, C4, factors H, B, I and anti-factor H autoantibody levels were determined. The coding regions of CFH, CFI, CD46 (MCP), THBD, C3 and CFB genes were sequenced and the copy number of CFI, CD46, CFH and related genes were also analyzed.

Results: We found that in the acute phase samples of SP-HUS patients, complement components C4, C3 and activity of the classical and alternative pathways were decreased, indicating severe activation and complement consumption, but most of these alterations normalized later in remission. Three of the patients carried mutations and risk haplotypes in complement-mediated aHUS associated genes. The identified mutations include a previously published CFI variant (P50A) and two novel ones in CFH (R1149X) and THBD (T44I) genes.

Conclusions: Our results suggest that severe complement dysregulation and consumption accompany the progress of invasive pneumococcal disease (IPD)-associated SP-HUS and genetic variations of complement genes may contribute to the development of this complication in a proportion of the affected patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ndt/gft198DOI Listing
September 2013

Aldosterone antagonists in monotherapy are protective against streptozotocin-induced diabetic nephropathy in rats.

PLoS One 2012 28;7(6):e39938. Epub 2012 Jun 28.

1st Department of Pediatrics, Semmelweis University, Budapest, Hungary.

Angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) are the standard clinical therapy of diabetic nephropathy (DN), while aldosterone antagonists are only used as adjuncts. Previously in experimental DN we showed that Na/K ATPase (NKA) is mislocated and angiotensin II leads to superimposed renal progression. Here we investigated the monotherapeutic effect of aldosterone blockers on the progression of DN and renal NKA alteration in comparison to ACEi and ARBs. Streptozotocin-diabetic rats developing DN were treated with aldosterone antagonists; ACEi and ARB. Renal function, morphology, protein level and tubular localization of NKA were analyzed. To evaluate the effect of high glucose per se; HK-2 proximal tubular cells were cultured in normal or high concentration of glucose and treated with the same agents. Aldosterone antagonists were the most effective in ameliorating functional and structural kidney damage and they normalized diabetes induced bradycardia and weight loss. Aldosterone blockers also prevented hyperglycemia and diabetes induced increase in NKA protein level and enzyme mislocation. A monotherapy with aldosterone antagonists might be as, or more effective than ACEi or ARBs in the prevention of STZ-induced DN. Furthermore the alteration of the NKA could represent a novel pathophysiological feature of DN and might serve as an additional target of aldosterone blockers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0039938PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3386228PMC
January 2013

Prevalence and predictors of the sub-target Hb level in children on dialysis.

Nephrol Dial Transplant 2012 Oct 27;27(10):3950-7. Epub 2012 Jun 27.

Department of Medical Informatics, University of Amsterdam, Amsterdam, The Netherlands.

Background: Anaemia is a common and potentially treatable co-morbidity of end-stage renal disease. We aimed to determine the prevalence of the sub-target haemoglobin (Hb) level among European children on dialysis and to identify factors associated with a low Hb level.

Methods: From the European Society for Paediatric Nephrology (ESPN)/European Renal Association-European Dialysis Transplant Association (ERA-EDTA) registry, data were available on 2351 children between 1 month and 18 years of age, totalling 5546 measurements from 19 countries.

Results: The mean Hb level was 10.8 g/dL (5th-95th percentiles, 7.4-13.9). Among those above 2 years of age, the mean Hb level was 10.9 g/dL (11.4% below 8.5 g/dL), while it was 10.3 g/dL among those below 2 years (11.2% below 8.0 g/dL). A total of 91.2% of the patients were on an erythropoiesis-stimulating agent (ESA). Hb levels increased with age and were higher in peritoneal dialysis compared with haemodialysis patients. Patients with congenital anomalies of the kidney and urinary tract showed the highest Hb levels, and those with cystic kidney diseases or metabolic disorders the lowest ones. Ferritin levels between 25 and 50 ng/mL were associated with the highest Hb levels. We found a weak inverse association between parathyroid hormone (PTH) and Hb. Whereas standardized blood pressure (BP) was not elevated in patients with above-target Hb, elevated systolic BP z-score was noted in those with sub-target Hb levels.

Conclusions: Sub-target Hb levels remain common in children on dialysis, in spite of virtually all children being treated with ESA; although we cannot exclude under-dosing. Optimal ferritin levels seemed to be slightly lower in children (25-50 ng/mL) than those in adults. Other risk factors for sub-target Hb are dialysis modality and a high PTH level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ndt/gfs178DOI Listing
October 2012