Myriad policy, ethical and legal considerations underpin the sharing of biological resources, implying the need for standardised and yet flexible ways to digitally represent diverse 'use conditions'. ...We report a core lexicon of terms that are atomic, non-directional 'concepts of use', called Common Conditions of use Elements. This work engaged biobanks and registries relevant to the European Joint Programme for Rare Diseases and aimed to produce a lexicon that would have generalised utility. Seventy-six concepts were initially identified from diverse real-world settings, and via iterative rounds of deliberation and user-testing these were optimised and condensed down to 20 items. To validate utility, support software and training information was provided to biobanks and registries who were asked to create Sharing Policy Profiles. This succeeded and involved adding standardised directionality and scope annotations to the employed terms. The addition of free-text parameters was also explored. The approach is now being adopted by several real-world projects, enabling this standard to evolve progressively into a universal basis for representing and managing conditions of use.
Unilateral nephrectomy is a relatively common procedure in children which results in a solitary functioning kidney (SFK). Living with an SFK predisposes to kidney injury, but it remains unknown which ...children are most at risk. We aimed to investigate kidney injury rates in patients who underwent unilateral nephrectomy in childhood and to investigate differences among nephrectomies performed for a congenital anomaly, malignancy or other condition.
MEDLINE and EMBASE were searched for studies reporting kidney injury rates i.e. proteinuria, hypertension and/or a decreased glomerular filtration rate (GFR) of patients who underwent unilateral nephrectomy during childhood. Studies including five or more patients with at least 12 months of follow-up were eligible. Analyses were performed using random effects models and stratified by indication for nephrectomy. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines were used for reporting.
Over 5000 unique articles were screened, of which 53 studies reporting on >4000 patients were included in the analyses. Proteinuria, hypertension and a decreased GFR were present in 15.3, 14.5 and 11.9% of patients, respectively. Heterogeneity among the studies was large in several subgroups, impairing quantitative meta-analyses. However, none of our analyses indicated differences in injury rates between a congenital anomaly or malignancy as an indication for nephrectomy.
Unilateral nephrectomy during childhood results in signs of kidney injury in >10% of patients, with no clear difference between the indications for nephrectomy. Therefore, structured follow-up is necessary in all children who underwent nephrectomy, regardless of the indication.
Hypospadias: risk factor patterns and different phenotypes Brouwers, Marijn M.; Van Der Zanden, Loes F.M.; De Gier, Robert P.E. ...
BJU international,
January 2010, 2010, 2010-Jan, 2010-01-00, 20100101, Volume:
105, Issue:
2
Journal Article
Peer reviewed
Open access
Study Type – Aetiologic (case‐referent) Level of Evidence 2a
OBJECTIVE
To obtain more insight into the origin of hypospadias by exploring a wide range of potential risk factors in a case‐referent ...study in which a distinction was made between different phenotypes.
PATIENTS AND METHODS
Cases and referents were 305 boys with hypospadias and 629 boys with middle ear effusion whose parents completed postal questionnaires. Hypospadias phenotype was classified as distal (195 boys), middle (67), and proximal (43). Adjusted odds ratios (OR) with 95% confidence intervals (CI) were estimated using logistic regression.
RESULTS
Low birth weight, being a twin or triplet, mother being a diethylstilbestrol‐daughter, fertility treatments, paternal subfertility, obesity, prescriptive drug use, and familial occurrence of hypospadias or testicular cancer were associated with hypospadias in general. For familial occurrence of hypospadias, there were high risk estimates for the distal and middle phenotypes with an OR (95%CI) of 10.4 (4.5–24.1) and 9.0 (3.1–26.0), but not for the proximal type at 1.8 (0.2–14.9). By contrast, the association with low birth weight (a proxy for placental dysfunction) seemed much stronger for proximal hypospadias with an OR (95%CI) of 9.1 (3.4–24.2) compared with distal and middle hypospadias at 2.6 (1.4–5.0) and 2.3 (0.8–6.5). There were similar estimates for pre‐eclampsia.
CONCLUSION
These findings indicate aetiological heterogeneity of hypospadias and provide indications for the possible mechanisms through which specific risk factors may interfere with penile development.
Individual response to sunitinib in metastatic renal cell carcinoma (mRCC) patients is highly variable. Earlier, sunitinib outcome was related to single nucleotide polymorphisms (SNPs) in CYP3A5 and ...ABCB1. Our aim is to provide novel insights into biological mechanisms underlying sunitinib action. We included mRCC patients from the European EuroTARGET consortium (n = 550) and the RIKEN cohort in Japan (n = 204) which were analysed separately and in a meta-analysis of genome-wide association studies (GWAS). SNPs were tested for association with progression-free survival (PFS) and overall survival (OS) using Cox regression. Summary statistics were combined using a fixed effect meta-analysis. SNP rs28520013 in PDLIM3 and the correlated SNPs rs2205096 and rs111356738 both in DSCAM, showed genome-wide significance (p < 5 × 10−8) with PFS and OS in the meta-analysis. The variant T-allele of rs28520013 associated with an inferior PFS of 5.1 months compared to 12.5 months in non-carriers (p = 4.02 × 10−10, HR = 7.26). T-allele carriers of rs28520013 showed an inferior OS of 6.9 months versus 30.2 months in non-carriers (p = 1.62 × 10−8, HR = 5.96). In this GWAS we identified novel genetic variants in PDLIM3 and DSCAM that impact PFS and OS in mRCC patients receiving sunitinib. The underlying link between the identified genes and the molecular mechanisms of sunitinib action needs to be elucidated.
Congenital lower urinary-tract obstruction (LUTO) is caused by anatomical blockage of the bladder outflow tract or by functional impairment of urinary voiding. About three out of 10,000 pregnancies ...are affected. Although several monogenic causes of functional obstruction have been defined, it is unknown whether congenital LUTO caused by anatomical blockage has a monogenic cause. Exome sequencing in a family with four affected individuals with anatomical blockage of the urethra identified a rare nonsense variant (c.2557C>T p.Arg853∗) in BNC2, encoding basonuclin 2, tracking with LUTO over three generations. Re-sequencing BNC2 in 697 individuals with LUTO revealed three further independent missense variants in three unrelated families. In human and mouse embryogenesis, basonuclin 2 was detected in lower urinary-tract rudiments. In zebrafish embryos, bnc2 was expressed in the pronephric duct and cloaca, analogs of the mammalian lower urinary tract. Experimental knockdown of Bnc2 in zebrafish caused pronephric-outlet obstruction and cloacal dilatation, phenocopying human congenital LUTO. Collectively, these results support the conclusion that variants in BNC2 are strongly implicated in LUTO etiology as a result of anatomical blockage.
Children with a solitary functioning kidney (SFK) have an increased risk of kidney injury. The exact risk of and risk factors for kidney injury remain unknown, which impedes personalized care. Here, ...we recruited a nationwide multicenter cohort of 944 patients with SFK to get more insight into this by consenting patients born in 1993-2020 and diagnosed with congenital or acquired SFK before adulthood. The median follow-up was 12.8 years and four indications of kidney injury were studied: urine protein-creatinine ratios, blood pressure, estimated glomerular filtration rate and use of anti-hypertensive/proteinuric medication. For each indicator except medication use, separate cut-off values for any injury and severe injury were used. Survival analyses indicated that at 18 years of age, any or severe kidney injury were present in 75% and 39% of patients with congenital SFK, respectively. Risk factors for kidney injury included kidney agenesis as cause of the SFK, anomalies in the SFK, and high body mass index at last follow-up. Kidney agenesis and being overweight were specifically associated with proteinuria and high blood pressure, whereas anomalies in the SFK were associated with reduced estimated glomerular filtration rates. The high prevalence of kidney injury in patients with SFK emphasizes the need for long-term follow-up, in which lifestyle is an important topic to address. More research into the etiological role of risk factors will help to translate our findings into individualized care strategies. Thus, our study shows that a significant proportion of children with SFK will develop kidney injury over time.
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A congenital solitary functioning kidney (cSFK) is a common developmental defect that predisposes to hypertension and chronic kidney disease (CKD) as a consequence of hyperfiltration. Every urologist ...takes care of patients with a cSFK, since some will need lifelong urological care or will come with clinical problems or questions to an adult urologist later in life.
We aim to provide clear recommendations for the initial clinical management and follow-up of children with a cSFK.
PubMed and EMBASE were searched to identify relevant publications, which were combined with guidelines on related topics and expert opinion.
Initially, cSFK diagnosis should be confirmed and risk factors for kidney injury should be identified using ultrasound. Although more research into early predictors of kidney injury is needed, additional congenital anomalies of the kidney or urinary tract and absence of compensatory kidney hypertrophy have repeatedly been associated with a worse prognosis. The role of voiding cystourethrography and antibiotic prophylaxis remains controversial, and is complicated by the exclusion of children with a cSFK from studies. A yearly follow-up for signs of kidney injury is recommended for children with a cSFK. As masked hypertension is prevalent, annual ambulatory blood pressure measurement should be considered. During puberty, an increasing incidence of kidney injury is seen, indicating that long-term follow-up is necessary. If signs of kidney injury are present, angiotensin converting enzyme inhibitors are the first-line drugs of choice.
This overview points to the urological and medical clinical aspects and long-term care guidance for children with a cSFK, who are at risk of hypertension and CKD. Monitoring for signs of kidney injury is therefore recommended throughout life. Large, prospective studies with long-term follow-up of clearly defined cohorts are still needed to facilitate more risk-based and individualized clinical management.
Many children are born with only one functioning kidney, which could lead to kidney injury later in life. Therefore, a kidney ultrasound is made soon after birth, and other investigations may be needed as well. Urologists taking care of patients with a solitary functioning kidney should realize the long-term clinical aspects, which might need medical management.
Urologists should be aware of the clinical aspects and long-term risks for their patients with a congenital solitary functioning kidney, which predisposes to kidney injury and warrants long-term follow-up. Kidney ultrasound is the preferred tool to confirm diagnosis and screen for additional urogenital anomalies. Thereafter, a yearly blood pressure and urine albumin-creatinine measurement is indicated, and additional treatments can be recommended depending on the long-term individual outcome of these patients.
Background
The etiology of congenital solitary functioning kidney (CSFK) is largely unknown but likely includes various risk factors. We performed a case–control study to compare exposure to ...environmental and parental risk factors during embryonic kidney development between children with CSFK and healthy controls.
Methods
We included 434 children with CSFK and 1302 healthy controls from the AGORA data- and biobank matched on year of birth. Exposure to potential risk factors was investigated using parental questionnaire data. Crude and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were estimated for each potential risk factor. Multiple imputation was used to deal with missing values. Confounders for each potential risk factor were selected using directed acyclic graphs.
Results
Maternal stress was newly identified as a risk factor for CSFK (aOR 2.1, 95% CI 1.2–3.5). Known associations with conception using in vitro fertilization/intracytoplasmic sperm injection (aOR 1.8, 95% CI 1.0–3.2), maternal infections during pregnancy (aOR 2.5, 95% CI 1.4–4.7), smoking during pregnancy (aOR 1.4, 95% CI 1.0–2.0), and parental CAKUT (aOR 6.6, 95% CI 2.9–15.1) were confirmed, but previous associations with diabetes and obesity could not be replicated. Folic acid supplement use and younger maternal age seemed to reduce the risk of CSFK (aORs 0.7, 95% CI 0.5–1.0, and 0.8, 95% CI 0.6–1.0, respectively).
Conclusions
Environmental and parental risk factors are likely to be involved in the development of CSFK and future studies should combine genetic, environmental, and gene-environment interaction analyses. Women wanting to become pregnant should consider optimizing their health and lifestyle.
Graphical abstract
A higher-resolution version of the Graphical abstract is available as
Supplementary information
Preoperative illnesses might induce immunosuppression and subsequently increase morbidity after surgery. Several studies have tried to identify risk factors for complications after hypospadias ...correction, but effects of illnesses in the weeks just before surgery are unknown. We aimed to determine the associations between preoperative illnesses not severe enough to postpone surgery and short-term complications after hypospadias repair in children.
In this retrospective cohort study, data were collected from 681 children with anterior or middle type hypospadias that had initial 1-stage repair in the period 1983-2012 in the Radboudumc, The Netherlands. The associations between common illnesses, such as common cold, fever and ear infection, within 2 weeks before repair, and postoperative complications, such as urethrocutaneous fistula, wound dehiscence and stenosis, within 2 months and 1 year after surgery, were analyzed using multivariable logistic regression analyses.
Of the 681 boys, 22% had preoperative illnesses, most often common cold, and 14% had postoperative complications. Children with preoperative illnesses had fewer postoperative complications within 2 months (n = 13, 9%) than children without preoperative illnesses (n = 79, 16%), resulting in a 50% risk reduction (odds ratio: 0.49; 95% confidence interval: 0.26-0.93). Preoperative infections (common cold, fever and ear infection), in particular, reduced the risk of postoperative infections (wound and urinary tract infections; odds ratio: 0.37; 95% confidence interval: 0.14-0.98). Results were similar for complications within 1 year.
Common preoperative illnesses not severe enough to postpone surgery did not increase the postoperative complication risk and even seemed to have a protective effect, especially for postoperative infections. Consequently, there is no reason to alter preoperative screening.
Patient data are increasingly available in (multi)national registries, especially for rare diseases. This study aims to provide an overview of current European registries of paediatric kidney ...transplantation (PKT) care, their coverage, and their focus. Based on these data, we assess whether the current status is optimal for achieving our common goal: the optimalisation of health care.
A list of all PKT centres within the European Union (EU) as well as active PKT registries was compiled using existing literature and the European Platform on Rare Disease Registration. Registry staff members were contacted to obtain information about the parameters collected and the registry design. These data were compared between registries.
In total, 109 PKT centres performing PKT surgery were identified in the 27 EU Member States. Currently, five European PKT registries are actively collecting data. In 39% of these centres, no data were registered within any of these five existing international registries. A large variety was observed in the number of patients, centres, and countries involved in the registries. Furthermore, variability existed regarding the inclusion criteria, definitions used, and parameters collected. Collection of perioperative urologic data are currently underrepresented in the registries.
Currently, multiple registries are collecting valuable information in the field of PKT, covering the majority of PKT centres in Europe. Due to a large variety in the parameters collected as well as different focuses, data collection is currently fragmented and suboptimal; therefore, the current existing data are incomplete. In addition, a considerable proportion of the transplantation centres do not enter data in any international registry. Combining available information and harmonising future data collection could empower the aim of these registries-namely increasing insights into the strengths and potential of current care and therefore improve healthcare.
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