Publications by authors named "Matthias Galiano"

20 Publications

  • Page 1 of 1

Blunt renal trauma-induced hypertension in pediatric patients: a single-center experience.

J Pediatr Urol 2021 Jun 30. Epub 2021 Jun 30.

Clinic of Urology and Pediatric Urology, University Hospital Erlangen, Germany. Electronic address:

Purpose: Children have a greater chance of sustaining a renal injury than adults and higher odds of having a high-grade renal injury. Hypertension is a rare complication of blunt renal trauma, with risk being higher in cases of major renal trauma. We reviewed the cases of pediatric blunt renal trauma-induced hypertension in our tertiary referral center in an attempt to better understand this rare condition.

Study Design: A retrospective evaluation of children under the age of 18 who were admitted to our department during the last 20 years and were diagnosed with blunt renal trauma.

Results: Twenty-three children presented with blunt renal trauma, one of whom was treated with emergency nephrectomy. Four children (18%) developed post-traumatic hypertension. All four cases were associated with a reduction in blood flow to the kidney, either through injury to the renal artery (in three cases) or through extrinsic compression of the kidney by a large perirenal hematoma (Page kidney; in one case). The Page kidney case developed hypertension during the initial hospitalization, and it resolved spontaneously after five months through the gradual resorption of the perirenal hematoma. Among the three cases of renal artery injury, hypertension during the initial hospitalization was only observed in one case, with hypertension in the other two cases manifesting after two months and four years, respectively. All three cases of renal artery injury resulted in a complete loss of function of the injured kidney, and two cases were treated with nephrectomy. Following nephrectomy, the blood pressure level returned to normal within a few days.

Discussion: Development of hypertension following a blunt renal trauma can be heterogenous, with the time of manifestation stretching between days after the accident and years thereafter. Children have a higher risk of renal trauma and, according to published data out of the National Trauma Data Bank, a 20-times higher risk of renal artery injury in comparison to the adult population. Large multicenter studies are required to answer the question of whether children are therefore more prone to blunt renal trauma-induced hypertension than adults.

Conclusions: Our study highlights the importance of blood pressure monitoring in children following blunt renal trauma, as post-traumatic hypertension can develop even years after the accident. In cases of a poorly functioning kidney, nephrectomy may be regarded as a curative therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpurol.2021.06.026DOI Listing
June 2021

Precise variant interpretation, phenotype ascertainment, and genotype-phenotype correlation of children in the EARLY PRO-TECT Alport trial.

Clin Genet 2021 01 25;99(1):143-156. Epub 2020 Oct 25.

Clinic for Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany.

Early initiation of therapy in patients with Alport syndrome (AS) slows down renal failure by many years. Genotype-phenotype correlations propose that the location and character of the individual's variant correlate with the renal outcome and any extra renal manifestations. In-depth clinical and genetic data of 60/62 children who participated in the EARLY PRO-TECT Alport trial were analyzed. Genetic variants were interpreted according to current guidelines and criteria. Genetically solved patients with X-linked inheritance were then classified according to the severity of their COL4A5 variant into less-severe, intermediate, and severe groups and disease progress was compared. Almost 90% of patients were found to carry (likely) pathogenic variants and classified as genetically solved cases. Patients in the less-severe group demonstrated a borderline significant difference in disease progress compared to those in the severe group (p = 0.05). While having only limited power according to its sample size, an obvious strength is the precise clinical and genetic data of this well ascertained cohort. As in published data differences in clinical progress were shown between patients with COL4A5 less-severe and severe variants. Therefore, clinical and segregational data are important for variant (re)classification. Genetic testing should be mandatory allowing early diagnosis and therapy of AS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cge.13861DOI Listing
January 2021

Cardiovascular Outcome of Pediatric Patients With Bi-Allelic (Homozygous) Familial Hypercholesterolemia Before and After Initiation of Multimodal Lipid Lowering Therapy Including Lipoprotein Apheresis.

Am J Cardiol 2020 12 16;136:38-48. Epub 2020 Sep 16.

Renal Unit, KfH Pediatric Kidney Centre, and Centre for Undiagnosed and Rare Diseases, University Hospital Marburg, Germany.

Twenty-four patients with bi-allelic familial hypercholesterolemia commencing chronic lipoprotein apheresis (LA) at a mean age of 8.5 ± 3.1 years were analysed retrospectively and in part prospectively with a mean follow-up of 17.2 ± 5.6 years. Mean age at diagnosis was 6.3 ± 3.4 years. Untreated mean LDL-C concentrations were 752 mg/dl ± 193 mg/dl (19.5 mmol/l ± 5.0 mmol/l). Multimodal lipid lowering therapy including LA resulted in a mean LDL-C concentration of 184 mg/dl (4.8 mmol/l), which represents a 75.5% mean reduction. Proprotein convertase subtilisin/kexin type 9-antibodies contributed in 3 patients to LDL-C lowering with 5 patients remaining to be tested. After commencing chronic LA, 16 patients (67%) remained clinically stable with only subclinical findings of atherosclerotic cardiovascular disease (ASCVD), and neither cardiovascular events, nor need for vascular interventions or surgery. In 19 patients (79%), pathologic findings were detected at the aortic valve (AV), which in the majority were mild. AV replacement was required in 2 patients. Mean Lipoprotein(a) concentration was 42.4 mg/dl, 38% had >50 mg/dl. There was no overt correlation of AV pathologies with other ASCVD complications, or Lipoprotein(a) concentration. Physicochemical elimination of LDL particles by LA appears indispensable for patients with bi-allelic familial hypercholesterolemia and severe hypercholesterolemia to maximize the reduction of LDL-C. In conclusion, in this rare patient group regular assessment of both the AV, as well as all arteries accessible by ultrasound should be performed to adjust the intensity of multimodal lipid lowering therapy with the goal to prevent ASCVD events and aortic surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjcard.2020.09.015DOI Listing
December 2020

A multicenter, randomized, placebo-controlled, double-blind phase 3 trial with open-arm comparison indicates safety and efficacy of nephroprotective therapy with ramipril in children with Alport's syndrome.

Kidney Int 2020 06 17;97(6):1275-1286. Epub 2020 Jan 17.

Department of Medical Statistics, University Medical Center Göttingen, Göttingen, Germany.

Children with Alport syndrome develop renal failure early in life. Since the safety and efficacy of preemptive nephroprotective therapy are uncertain we conducted a randomized, placebo-controlled, double-blind trial in 14 German sites of pediatric patients with ramipril for three to six years plus six months follow-up to determine these parameters. Pretreated children and those whose parents refused randomization became an open-arm control, which were compared to prospective real-world data from untreated children. The co-primary endpoints were safety (adverse drug reactions) and efficacy (time to progression). Out of 66 oligosymptomatic children, 22 were randomized and 44 joined the open-arm comparison. Ramipril therapy showed no safety issues (total of 216.4 patient-years on ramipril; adverse event rate-ratio 1.00; 95% confidence interval 0.66-1.53). Although not significant, our results cautiously showed that ramipril therapy was effective: in the randomized arm, Ramipril decreased the risk of disease progression by almost half (hazard ratio 0.51 (0.12-2.20)), diminished the slope of albuminuria progression and the decline in glomerular filtration. In adjusted analysis, indications of efficacy were supported by prospective data from participants treated open label compared with untreated children, in whom ramipril again seemed to reduce progression by almost half (0.53 (0.22-1.29)). Incorporating these results into the randomized data by Bayesian evidence synthesis resulted in a more precise estimate of the hazard-ratio of 0.52 (0.19-1.39). Thus, our study shows the safety of early initiation of therapy and supports the hope to slow renal failure by many years, emphasizing the value of preemptive therapy. Hence, screening programs for glomerular hematuria in children and young adults could benefit from inclusion of genetic testing for Alport-related gene-variants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.kint.2019.12.015DOI Listing
June 2020

Homozygous familial hypercholesterolemia with severe involvement of the aortic valve-A sibling-controlled case study on the efficacy of lipoprotein apheresis.

J Clin Apher 2020 Jun 12;35(3):163-171. Epub 2020 Mar 12.

Apheresis Research Institute, Cologne, Germany.

Background: Homozygous familial hypercholesterolemia (hoFH) can cause severe atherosclerotic cardiovascular disease (ASCVD) in early infancy. Diagnosis and initiation of effective lipid-lowering therapy (LLT) are recommended as early as possible to prevent ASCVD-related morbidity and mortality.

Methods: The clinical courses of a pair of siblings with an identical hoFH genotype, who exhibited major similarities of their clinical phenotype were analyzed in a case-control fashion including the family.

Results: The older sibling was diagnosed with hoFH at the age of 4. Untreated LDL-cholesterol (LDL-C) was 17 mmol/L (660 mg/dL). LLT including lipoprotein apheresis (LA) was initiated and has been successful for 8 years now. A reduction of estimated cholesterol burden by 74% was achieved by LA and combined drug therapy including statins and ezetimibe. The efficacy of escalation of drug therapy was limited because the underlying LDL receptor (LDLR) mutation in the family resulted in substantially reduced receptor function. Treatment with proprotein convertase subtilisin-kexin type 9 (PCSK9)-antibodies failed. His younger brother died at the age of 2 years shortly after the hoFH diagnosis of the elder sibling. Postmortem examination revealed advanced aortic root atheroma and aortic valve stenosis. In the older sibling, aortic valve stenosis and insufficiency were treated at the age of 9 years with mechanical aortic valve replacement.

Conclusions: LLT including LA should be initiated as early as possible following the diagnosis of hoFH with very high LDL-C levels. With the same genotype, the phenotype of hoFH can exhibit similar patterns but outcome is substantially related to treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jca.21772DOI Listing
June 2020

Isolated nocturnal and isolated daytime hypertension associate with altered cardiovascular morphology and function in children with chronic kidney disease: findings from the Cardiovascular Comorbidity in Children with Chronic Kidney Disease study.

J Hypertens 2019 11;37(11):2247-2255

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

Introduction: Prevalence of isolated nocturnal hypertension (INH) and isolated daytime hypertension (IDH) is around 10% in adults. Data in children, especially in chronic kidney disease (CKD), are lacking. The aim of this cross-sectional multicenter cohort study was to define the prevalence of INH and IDH and its association with cardiovascular morphology and function, that is, pulse wave velocity (PWV), carotid intima-media thickness (cIMT), or left ventricular mass index (LVMI) in children with CKD.

Methods: Ambulatory blood pressure (BP) monitoring profiles were analyzed in 456 children with CKD stages III-V participating in the Cardiovascular Comorbidity in Children with Chronic Kidney Disease Study (64.3% males, 71.3% congenital anomaly of the kidney and urinary tract, age 12.5 ± 3.2 years, estimated glomerular filtration rate 29 ± 12 ml/min per 1.73 m). Baseline PWV, cIMT, and LVMI were compared in normotension, INH, IDH, or sustained 24-h hypertension.

Results: Prevalence of sustained hypertension was 18.4%, of INH 13.4%, and of IDH 3.7%. PWV SDS (SD score) and cIMT SDS were significantly higher in sustained hypertension and INH, and PWV SDS was significantly higher in IDH, compared with normotension. LVMI was significantly increased in sustained hypertension, but not in INH or IDH. Determinants of INH were smallness for gestational age, older age, higher height SDS and parathyroid hormone, and shorter duration of CKD. In logistic regression analysis, day/night-time hypertension or ambulatory BP monitoring pattern (normal, INH, IDH, sustained hypertension) were independently associated with cardiovascular outcome measures: elevated night-time BP was associated with increased cIMT, PWV, and left ventricular hypertrophy; INH was associated with cIMT.

Conclusion: INH is present in almost one out of seven children with predialysis CKD; INH and nocturnal hypertension in general are associated with alterations of arterial morphology and function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/HJH.0000000000002160DOI Listing
November 2019

Clinical courses and complications of young adults with Autosomal Recessive Polycystic Kidney Disease (ARPKD).

Sci Rep 2019 05 28;9(1):7919. Epub 2019 May 28.

Department of Pediatrics, University Hospital of Cologne, Cologne, Germany.

Autosomal recessive polycystic kidney disease (ARPKD) is a severe pediatric hepatorenal disorder with pronounced phenotypic variability. A substantial number of patients with early diagnosis reaches adulthood and some patients are not diagnosed until adulthood. Yet, clinical knowledge about adult ARPKD patients is scarce. Here, we describe forty-nine patients with longitudinal follow-up into young adulthood that were identified in the international ARPKD cohort study ARegPKD. Forty-five patients were evaluated in a cross-sectional analysis at a mean age of 21.4 (±3.3) years describing hepatorenal findings. Renal function of native kidneys was within CKD stages 1 to 3 in more than 50% of the patients. Symptoms of hepatic involvement were frequently detected. Fourteen (31%) patients had undergone kidney transplantation and six patients (13%) had undergone liver transplantation or combined liver and kidney transplantation prior to the visit revealing a wide variability of clinical courses. Hepatorenal involvement and preceding complications in other organs were also evaluated in a time-to-event analysis. In summary, we characterize the broad clinical spectrum of young adult ARPKD patients. Importantly, many patients have a stable renal and hepatic situation in young adulthood. ARPKD should also be considered as a differential diagnosis in young adults with fibrocystic hepatorenal disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-43488-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538621PMC
May 2019

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Neuromyelitis Optica Spectrum Disorder in a 6-Year-Old Boy.

Klin Padiatr 2019 07 7;231(4):220-223. Epub 2019 May 7.

Department of Pediatrics, University of Erlangen, Erlangen.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-0860-5590DOI Listing
July 2019

Risk Factors for Early Dialysis Dependency in Autosomal Recessive Polycystic Kidney Disease.

J Pediatr 2018 08 9;199:22-28.e6. Epub 2018 May 9.

University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany.

Objective: To identify prenatal, perinatal, and postnatal risk factors for dialysis within the first year of life in children with autosomal recessive polycystic kidney disease (ARPKD) as a basis for parental counseling after prenatal and perinatal diagnosis.

Study Design: A dataset comprising 385 patients from the ARegPKD international registry study was analyzed for potential risk markers for dialysis during the first year of life.

Results: Thirty-six out of 385 children (9.4%) commenced dialysis in the first year of life. According to multivariable Cox regression analysis, the presence of oligohydramnios or anhydramnios, prenatal kidney enlargement, a low Apgar score, and the need for postnatal breathing support were independently associated with an increased hazard ratio for requiring dialysis within the first year of life. The increased risk associated with Apgar score and perinatal assisted breathing was time-dependent and vanished after 5 and 8 months of life, respectively. The predicted probabilities for early dialysis varied from 1.5% (95% CI, 0.5%-4.1%) for patients with ARPKD with no prenatal sonographic abnormalities to 32.3% (95% CI, 22.2%-44.5%) in cases of documented oligohydramnios or anhydramnios, renal cysts, and enlarged kidneys.

Conclusions: This study, which identified risk factors associated with onset of dialysis in ARPKD in the first year of life, may be helpful in prenatal parental counseling in cases of suspected ARPKD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2018.03.052DOI Listing
August 2018

[Flight Routes to Germany of Seriously Ill Children and Adolescents From Former Eastern Bloc Countries for Treatment of Renal Failure].

Klin Padiatr 2018 Jul 12;230(4):188-193. Epub 2018 Apr 12.

Department of Pediatrics and Adolescent Medicine, FAU Erlangen-Nurnberg.

Background: Increased patient mobility and restricted treatment of children with end-stage renal disease forced families from the former Eastern Bloc countries to flee with their children to Germany for adequate medical treatment.

Methods: In a case study, the patients' charts were analysed retrospectively. In structured interviews, parents and patients were asked about their flight routes to Germany, their medical treatment and their integration.

Results: From 2003 to 2013, eight children and adolescents with renal failure were treated with dialysis or renal transplantation in Erlangen. Most patients came with the help of human traffickers and a tourist visa. They often told that they had lost their papers in the excitement. One family received new passports from the trafficker with fake names and birth dates. The families had to pay high amounts of money in order to save their child's life. Although dialysis therapy was often difficult because of lower adherence, the overall course was satisfactory. Four patients have been transplanted successfully so far.

Conclusion: This case study reveals new facets of patient mobility, since leaving home was the only way for the family to ensure their child´s survival. An ethical problems arose, as a chronic dialysis treatment in children seems ethically only justifiable if a kidney transplant is the therapeutic goal. .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0044-101547DOI Listing
July 2018

Multimodal lipid-lowering treatment in pediatric patients with homozygous familial hypercholesterolemia-target attainment requires further increase of intensity.

Pediatr Nephrol 2018 07 3;33(7):1199-1208. Epub 2018 Mar 3.

Apheresis Research Institute, Stadtwaldguertel 77, 50935, Cologne, Germany.

Background: Familial hypercholesterolemia (FH) causes premature cardiovascular disease (CVD). Lipoprotein apheresis (LA) is recommended as first-line lipid-lowering treatment (LLT) for homozygous (ho) FH.

Methods: Efficacy of multimodal LLT including lifestyle counseling, drug treatment, and LA was analyzed in 17 pediatric hoFH or compound heterozygous (c-het) FH patients, who commenced chronic LA in Germany before the age of 18.

Results: At time of diagnosis, mean low-density lipoprotein cholesterol (LDL-C) concentration was 19.6 mmol/l (756 mg/dl). Multimodal LLT resulted in 73% reduction of mean LDL-C concentration including a 62% contribution of LA. Only three children (18%) achieved mean LDL-C concentrations below the recommended pediatric target of 3.5 mmol/l (135 mg/dl). In 13 patients (76%) during chronic LA, neither cardiovascular events occurred nor was CVD progression detected clinically or by routine imaging techniques. In four patients (24%), cardiovascular events documented progression of CVD despite weekly LA, including one death due to coronary and cerebrovascular CVD which was not stabilized after commencing LA. Based on the mutational status, only 6 out of the 17 children were candidates for proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibition. Two already responded with further LDL-C decrease by 40%.

Conclusions: Next to drug therapy, regular LA is an essential component of LLT for approaching LDL-C targets in children with hoFH or c-hetFH, which was successful only in a minority of children. Progression of CVD morbidity and resulting mortality remain unresolved issues. Early and intensified multimodal LLT guided by risk factors beyond LDL-C concentration is needed to improve outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-018-3906-6DOI Listing
July 2018

The Phenotypic Spectrum of Nephropathies Associated with Mutations in Diacylglycerol Kinase .

J Am Soc Nephrol 2017 10 19;28(10):3066-3075. Epub 2017 May 19.

Division of Pediatric Nephrology, Center for Pediatric and Adolescent Medicine, Heidelberg University, Heidelberg, Germany.

The recent discovery of mutations in the gene encoding diacylglycerol kinase (DGKE) identified a novel pathophysiologic mechanism leading to HUS and/or MPGN. We report ten new patients from eight unrelated kindreds with DGKE nephropathy. We combined these cases with all previously published cases to characterize the phenotypic spectrum and outcomes of this new disease entity. Most patients presented with HUS accompanied by proteinuria, whereas a subset of patients exhibited clinical and histologic patterns of MPGN without TMA. We also report the first two patients with clinical and histologic HUS/MPGN overlap. DGKE-HUS typically manifested in the first year of life but was not exclusively limited to infancy, and viral triggers frequently preceded HUS episodes. We observed signs of complement activation in some patients with DGKE-HUS, but the role of complement activation remains unclear. Most patients developed a slowly progressive proteinuric nephropathy: 80% of patients did not have ESRD within 10 years of diagnosis. Many patients experienced HUS remission without specific treatment, and a few patients experienced HUS recurrence despite complete suppression of the complement pathway. Five patients received renal allografts, with no post-transplant recurrence reported. In conclusion, we did not observe a clear genotype-phenotype correlation in patients with DGKE nephropathy, suggesting additional factors mediating phenotypic heterogeneity. Furthermore, the benefits of anti-complement therapy are questionable but renal transplant may be a feasible option in the treatment of patients with this condition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1681/ASN.2017010031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5619969PMC
October 2017

Clinical Characterization of the Pheochromocytoma and Paraganglioma Susceptibility Genes SDHA, TMEM127, MAX, and SDHAF2 for Gene-Informed Prevention.

JAMA Oncol 2017 Sep;3(9):1204-1212

Department of Pediatrics and Adolescent Medicine, University Hospital of Erlangen, Erlangen, Germany.

Importance: Effective cancer prevention is based on accurate molecular diagnosis and results of genetic family screening, genotype-informed risk assessment, and tailored strategies for early diagnosis. The expanding etiology for hereditary pheochromocytomas and paragangliomas has recently included SDHA, TMEM127, MAX, and SDHAF2 as susceptibility genes. Clinical management guidelines for patients with germline mutations in these 4 newly included genes are lacking.

Objective: To study the clinical spectra and age-related penetrance of individuals with mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes.

Design, Setting, And Patients: This study analyzed the prospective, longitudinally followed up European-American-Asian Pheochromocytoma-Paraganglioma Registry for prevalence of SDHA, TMEM127, MAX, and SDHAF2 germline mutation carriers from 1993 to 2016. Genetic predictive testing and clinical investigation by imaging from neck to pelvis was offered to mutation-positive registrants and their relatives to clinically characterize the pheochromocytoma/paraganglioma diseases associated with mutations of the 4 new genes.

Main Outcomes And Measures: Prevalence and spectra of germline mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes were assessed. The clinical features of SDHA, TMEM127, MAX, and SDHAF2 disease were characterized.

Results: Of 972 unrelated registrants without mutations in the classic pheochromocytoma- and paraganglioma-associated genes (632 female [65.0%] and 340 male [35.0%]; age range, 8-80; mean [SD] age, 41.0 [13.3] years), 58 (6.0%) carried germline mutations of interest, including 29 SDHA, 20 TMEM127, 8 MAX, and 1 SDHAF2. Fifty-three of 58 patients (91%) had familial, multiple, extra-adrenal, and/or malignant tumors and/or were younger than 40 years. Newly uncovered are 7 of 63 (11%) malignant pheochromocytomas and paragangliomas in SDHA and TMEM127 disease. SDHA disease occurred as early as 8 years of age. Extra-adrenal tumors occurred in 28 mutation carriers (48%) and in 23 of 29 SDHA mutation carriers (79%), particularly with head and neck paraganglioma. MAX disease occurred almost exclusively in the adrenal glands with frequently bilateral tumors. Penetrance in the largest subset, SDHA carriers, was 39% at 40 years of age and is statistically different in index patients (45%) vs mutation-carrying relatives (13%; P < .001).

Conclusions And Relevance: The SDHA, TMEM127, MAX, and SDHAF2 genes may contribute to hereditary pheochromocytoma and paraganglioma. Genetic testing is recommended in patients at clinically high risk if the classic genes are mutation negative. Gene-specific prevention and/or early detection requires regular, systematic whole-body investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaoncol.2017.0223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824290PMC
September 2017

Sustained Need for High-Dose Zinc Supplementation in Children With Acrodermatitis Enteropathica.

Clin Pediatr (Phila) 2018 01 5;57(1):99-102. Epub 2017 Jan 5.

1 University Hospital Erlangen, Erlangen, Germany.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0009922816685820DOI Listing
January 2018

Timing of first arteriovenous fistula cannulation in children on hemodialysis.

Pediatr Nephrol 2016 10 25;31(10):1647-57. Epub 2016 Apr 25.

Department of Vascular Surgery, Hospital of the Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Krankenhausstrasse 12, 91054, Erlangen, Germany.

Background: Due to lower complication rates in comparison to central venous catheter (CVC) arteriovenous fistulas (AVFs) are now the preferred hemodialysis access. Recommendations for the first access cannulation range from 6 to 12 weeks, which could lead to temporary or even permanent preference for CVC while awaiting the maturation of the newly created AVF. The aim of this study was to evaluate the influence of first cannulation of AVFs on primary (PP) and secondary (SP) patency rates in children on hemodialysis (HD).

Methods: This was a retrospective cohort study of 42 pediatric patients with a median age of 14 (range 7-17) years. At the time of surgical AVF creation 21 patients (end-stage renal disease) were still on HD via CVC or peritoneal catheter, while 21 were pre-emptive with initiation of HD expected within a few weeks. All patients received an AVF by the same experienced surgeon between February 1993 and May 2014. Primary failure (PF) was defined as the inability to use the AVF even once due to absent maturation or occlusion within 4 weeks after creation. PP was defined as the interval from time of access placement to any intervention designed to maintain or reestablish patency, to access thrombosis or the time of measurement of patency, while SP was defined as the total lifespan from creation to access abandonment, end of follow-up or loss.

Results: Primary failure was observed in six (14.3 %) of 42 AVFs (all radiocephalic fistulas) within the first 10 days after cannulation. Excluding PF, the PP/SP rates at 1, 3, 6, 12, 18 and 24 months were 100/100, 91/99, 86/98, 76/95, 55/85 and 44/77 %, respectively. There was a significant decrease in PP when first cannulation was performed within the first 30 days after creation compared to first cannulation performed after 30 days (p = 0.004). In terms of PP/SP outcome and timing of the first cannulation, there was no significant difference in thee outcome of PP/SP between first cannulation within the first 45 days after creation and that after 45 days (p = 0.091/0.883).

Conclusions: The findings suggest that cannulation of AVF within 30 days after surgical creation reduces PP, while SP may be influenced less by time until cannulation. We also found no significant differences in PP after maturing periods of >45 days.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-016-3382-9DOI Listing
October 2016

Autosomal-Recessive Mutations in SLC34A1 Encoding Sodium-Phosphate Cotransporter 2A Cause Idiopathic Infantile Hypercalcemia.

J Am Soc Nephrol 2016 Feb 5;27(2):604-14. Epub 2015 Jun 5.

Department of General Pediatrics, University Children's Hospital, Münster, Germany;

Idiopathic infantile hypercalcemia (IIH) is characterized by severe hypercalcemia with failure to thrive, vomiting, dehydration, and nephrocalcinosis. Recently, mutations in the vitamin D catabolizing enzyme 25-hydroxyvitamin D3-24-hydroxylase (CYP24A1) were described that lead to increased sensitivity to vitamin D due to accumulation of the active metabolite 1,25-(OH)2D3. In a subgroup of patients who presented in early infancy with renal phosphate wasting and symptomatic hypercalcemia, mutations in CYP24A1 were excluded. Four patients from families with parental consanguinity were subjected to homozygosity mapping that identified a second IIH gene locus on chromosome 5q35 with a maximum logarithm of odds (LOD) score of 6.79. The sequence analysis of the most promising candidate gene, SLC34A1 encoding renal sodium-phosphate cotransporter 2A (NaPi-IIa), revealed autosomal-recessive mutations in the four index cases and in 12 patients with sporadic IIH. Functional studies of mutant NaPi-IIa in Xenopus oocytes and opossum kidney (OK) cells demonstrated disturbed trafficking to the plasma membrane and loss of phosphate transport activity. Analysis of calcium and phosphate metabolism in Slc34a1-knockout mice highlighted the effect of phosphate depletion and fibroblast growth factor-23 suppression on the development of the IIH phenotype. The human and mice data together demonstrate that primary renal phosphate wasting caused by defective NaPi-IIa function induces inappropriate production of 1,25-(OH)2D3 with subsequent symptomatic hypercalcemia. Clinical and laboratory findings persist despite cessation of vitamin D prophylaxis but rapidly respond to phosphate supplementation. Therefore, early differentiation between SLC34A1 (NaPi-IIa) and CYP24A1 (24-hydroxylase) defects appears critical for targeted therapy in patients with IIH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1681/ASN.2014101025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4731111PMC
February 2016

Neuronal c-Jun is required for successful axonal regeneration, but the effects of phosphorylation of its N-terminus are moderate.

J Neurochem 2012 May 21;121(4):607-18. Epub 2012 Mar 21.

Perinatal Brain Repair Group, Inst Women's Health, University College London, London, UK.

Although neural c-Jun is essential for successful peripheral nerve regeneration, the cellular basis of this effect and the impact of c-Jun activation are incompletely understood. In the current study, we explored the effects of neuron-selective c-Jun deletion, substitution of serine 63 and 73 phosphoacceptor sites with non-phosphorylatable alanine, and deletion of Jun N-terminal kinases 1, 2 and 3 in mouse facial nerve regeneration. Removal of the floxed c-jun gene in facial motoneurons using cre recombinase under control of a neuron-specific synapsin promoter (junΔS) abolished basal and injury-induced neuronal c-Jun immunoreactivity, as well as most of the molecular responses following facial axotomy. Absence of neuronal Jun reduced the speed of axonal regeneration following crush, and prevented most cut axons from reconnecting to their target, significantly reducing functional recovery. Despite blocking cell death, this was associated with a large number of shrunken neurons. Finally, junΔS mutants also had diminished astrocyte and microglial activation and T-cell influx, suggesting that these non-neuronal responses depend on the release of Jun-dependent signals from neighboring injured motoneurons. The effects of substituting serine 63 and 73 phosphoacceptor sites (junAA), or of global deletion of individual kinases responsible for N-terminal c-Jun phosphorylation were mild. junAA mutants showed decrease in neuronal cell size, a moderate reduction in post-axotomy CD44 levels and slightly increased astrogliosis. Deletion of Jun N-terminal kinase (JNK)1 or JNK3 showed delayed functional recovery; deletion of JNK3 also interfered with T-cell influx, and reduced CD44 levels. Deletion of JNK2 had no effect. Thus, neuronal c-Jun is needed in regeneration, but JNK phosphorylation of the N-terminus mostly appears to not be required for its function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1471-4159.2012.07706.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4491308PMC
May 2012

The AP-1 transcription factor c-Jun is required for efficient axonal regeneration.

Neuron 2004 Jul;43(1):57-67

Perinatal Brain Repair Group, Department of Obstetrics and Gynaecology, University College London, 86-96 Chenies Mews, London WC1E 6HX, United Kingdom.

Nerve injury triggers numerous changes in the injured neurons and surrounding nonneuronal cells that ultimately result in successful target reinnervation or cell death. c-Jun is a component of the heterodimeric AP-1 transcription factor, and c-Jun is highly expressed in response to neuronal trauma. Here we have investigated the role of c-jun during axonal regeneration using mice lacking c-jun in the central nervous system. After transection of the facial nerve, the absence of c-Jun caused severe defects in several aspects of the axonal response, including perineuronal sprouting, lymphocyte recruitment, and microglial activation. c-Jun-deficient motorneurons were atrophic, resistant to axotomy-induced cell death, and showed reduced target muscle reinnervation. Expression of CD44, galanin, and alpha7beta1 integrin, molecules known to be involved in regeneration, was greatly impaired, suggesting a mechanism for c-Jun-mediated axonal growth. Taken together, our results identify c-Jun as an important regulator of axonal regeneration in the injured central nervous system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuron.2004.06.005DOI Listing
July 2004

Lymphocyte infiltration in the injured brain: role of proinflammatory cytokines.

J Neurosci Res 2003 Jun;72(6):726-33

Department of Neuromorphology, Max-Planck Institute for Neurobiology, Martinsried, Germany.

Studies using mouse axotomised facial motoneuron model show a strong and highly selective entry of CD3+ lymphocytes into the affected nucleus, with a maximum at Day 14, which coincides with the peak of neuronal cell death, microglial phagocytosis, and increased synthesis of interleukin-1 beta (IL1beta), tumour necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma). We explored the possible involvement of these cytokines during the main phase of lymphocyte recruitment into the axotomised facial motor nucleus 7-21 days after nerve cut using mice homozygously deficient for IL1 receptor type 1 (IL1R1-/-), TNF receptor type 1 (TNFR1-/-), type 2 (TNFR2-/-) and type 1 and 2 (TNFR1&2-/-), IFNgamma receptor type 1 (IFNgammaR1-/-), and the appropriate controls for the genetic background. Transgenic deletion of IL1R1 led to a 54% decrease and that of TNFR2 to a 44% reduction in the number of CD3+ T-cells in the axotomised facial motor nucleus, with a similar relative decrease at Day 7, 14, and 21. Deletion of TNFR1 or IFNgammaR1 had no significant effect. Deletion of both TNFR1 and 2 (TNFR1&2-/-) caused a somewhat stronger, 63% decrease than did TNFR2 deletion alone, but this could be due to an almost complete inhibition of neuronal cell death. No mutations seemed to inhibit aggregation of CD3+ T-cells around glial nodules consisting of Ca-ion binding adaptor protein-1 (IBA1)+ phagocytotic microglia and neuronal debris. Altogether, the current data show the importance of IL1R1 and TNFR2 as the key players during the main phase of lymphocyte recruitment to the damaged part of the central nervous system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jnr.10621DOI Listing
June 2003
-->