scholarly journals P0050PRE-IMPLANTATION GENETIC TESTING FOR MONOGENIC KIDNEY DISEASE: TWENTY-FIVE YEAR EXPERIENCE IN THE NETHERLANDS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
R Snoek ◽  
Marijn F Stokman ◽  
Klaske D Lichtenbelt ◽  
Cindy E Simcox ◽  
Theodora C Van Tilborg ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Kidney Disease ◽  
The Netherlands ◽  
Live Birth ◽  
Kidney Diseases ◽  
Small Sample ◽  
Early Years ◽  
Adult Onset ◽  
Total N ◽  
Prospective Parents

Abstract Background and Aims Due to the fast-paced developments in human genetics, a genetic cause can now be identified for an increasing number of pediatric and adult-onset kidney diseases. A monogenic kidney disease (MKD) can impact prognostication and therapy decisions. It also provides patients with options regarding family planning such as preimplantation genetic testing (PGT), a reproductive technology that helps prospective parents prevent passing on a disease-causing mutation to their offspring. There are limited reports on PGT for MKD and most are focused on severe pediatric-onset diseases. The Dutch system of insurance reimbursement and nationwide regulation is unique, and it has allowed the Netherlands to be one of a handful of countries where couples have the option to choose PGT for MKD, including adult-onset forms of kidney disease. Here we provide the 25-year Dutch experience with PGT for MKD. Method We performed a retrospective cohort study of all couples counselled on PGT for MKD in the Maastricht University Medical Center+, the expert centre where all Dutch single cell genetic testing on embryos is performed, from January 1995 until June 2019. Results 99 couples were counseled for PGT, of which currently 15% is waiting for the genetic test to be validated. In the early years of PGT for MKD, referrals were incidental and only for couples at risk for offspring with paediatric-onset disease. From 2009 onwards, the number of referrals has steadily increased as has the number of couples referred for adult-onset MKD. Overall, the most frequent indications for referral for PGT were ADPKD (37%), X-linked Alport syndrome (25%) and ARPKD (9%). After counselling, 36% of n=99 couples started PGT treatment. In total n=80 cycles with oocyte retrieval were performed (median 2 cycles [range 1-4]). These cycles led to a median of n=10 embryos (range 2-31) suitable for biopsy and a median of n=3 embryos (range 1-14) being genetically unaffected. Seventy-five percent (n=) of couples achieved at least one live birth. Of n=99, 48% did not proceed with PGT, for various personal and technical reasons. Major reasons for opting out of PGT were that prospective parents did not want to wait for the lengthy PGT procedure (9%) or had a wish for natural conception with prenatal genetic testing (11%). Live birth rate was 40% (n=19) in the non-PGT group, with notably a similar duration to a live birth as the PGT group (2 years, range 0-5 years). Conclusion We provide the largest overview to date of the indications, uptake and results of PGT for MKD. Referrals for PGT, including adult-onset disease, have increased steadily over the past decade. PGT has favorable outcomes, with 75% of couples having at least one live birth, though this is likely due to our small sample size. Genetic and reproductive counseling, including information on PGT, should be provided to all patients and prospective parents from families with MKD to enable informed decision making.

scholarly journals Preimplantation Genetic Testing for Monogenic Kidney Disease

2020 ◽  
Vol 15 (9) ◽  
pp. 1279-1286 ◽  
Author(s):  
Rozemarijn Snoek ◽  
Marijn F. Stokman ◽  
Klaske D. Lichtenbelt ◽  
Theodora C. van Tilborg ◽  
Cindy E. Simcox ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Kidney Diseases ◽  
Medical Center ◽  
Live Birth Rate ◽  
Genetic Diagnostics ◽  
Adult Onset ◽  
Polycystic Kidney ◽  
Preimplantation Genetic Testing

Background and objectivesA genetic cause can be identified for an increasing number of pediatric and adult-onset kidney diseases. Preimplantation genetic testing (formerly known as preimplantation genetic diagnostics) is a reproductive technology that helps prospective parents to prevent passing on (a) disease-causing mutation(s) to their offspring. Here, we provide a clinical overview of 25 years of preimplantation genetic testing for monogenic kidney disease in The Netherlands.Design, setting, participants, & measurements This is a retrospective cohort study of couples counseled on preimplantation genetic testing for monogenic kidney disease in the national preimplantation genetic testing expert center (Maastricht University Medical Center+) from January 1995 to June 2019. Statistical analysis was performed through chi-squared tests.ResultsIn total, 98 couples were counseled regarding preimplantation genetic testing, of whom 53% opted for preimplantation genetic testing. The most frequent indications for referral were autosomal dominant polycystic kidney disease (38%), Alport syndrome (26%), and autosomal recessive polycystic kidney disease (9%). Of couples with at least one preimplantation genetic testing cycle with oocyte retrieval, 65% experienced one or more live births of an unaffected child. Of couples counseled, 38% declined preimplantation genetic testing for various personal and technical reasons.ConclusionsReferrals, including for adult-onset disease, have increased steadily over the past decade. Though some couples decline preimplantation genetic testing, in the couples who proceed with at least one preimplantation genetic testing cycle, almost two thirds experienced at least one live birth rate.

scholarly journals Clinical Genetic Screening in Adult Patients with Kidney Disease

2020 ◽  
Vol 15 (10) ◽  
pp. 1497-1510 ◽  
Author(s):  
Enrico Cocchi ◽  
Jordan Gabriela Nestor ◽  
Ali G. Gharavi
Keyword(s):  
Genetic Testing ◽  
Kidney Disease ◽  
Massively Parallel Sequencing ◽  
Kidney Diseases ◽  
Chromosomal Microarray ◽  
Ethical Considerations ◽  
Clinical Genetic ◽  
Genetic Sequencing ◽  
Sequencing Technologies ◽  
Potential Benefits

Expanded accessibility of genetic sequencing technologies, such as chromosomal microarray and massively parallel sequencing approaches, is changing the management of hereditary kidney diseases. Genetic causes account for a substantial proportion of pediatric kidney disease cases, and with increased utilization of diagnostic genetic testing in nephrology, they are now also detected at appreciable frequencies in adult populations. Establishing a molecular diagnosis can have many potential benefits for patient care, such as guiding treatment, familial testing, and providing deeper insights on the molecular pathogenesis of kidney diseases. Today, with wider clinical use of genetic testing as part of the diagnostic evaluation, nephrologists have the challenging task of selecting the most suitable genetic test for each patient, and then applying the results into the appropriate clinical contexts. This review is intended to familiarize nephrologists with the various technical, logistical, and ethical considerations accompanying the increasing utilization of genetic testing in nephrology care.

scholarly journals Case Report: Preimplantation Genetic Testing and Pregnancy Outcomes in Women With Alport Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Wei-Hui Shi ◽  
Mu-Jin Ye ◽  
Song-Chang Chen ◽  
Jun-Yu Zhang ◽  
Yi-Yao Chen ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Kidney Disease ◽  
Pregnancy Outcomes ◽  
Alport Syndrome ◽  
Kidney Diseases ◽  
High Rate ◽  
Singleton Pregnancy ◽  
Fetal Outcomes ◽  
Preimplantation Genetic Testing ◽  
Monogenic Diseases

BackgroundAlport syndrome, a monogenic kidney disease, is characterized by progressive hemorrhagic nephritis, sensorineural hearing loss, and ocular abnormalities. Mutations in COL4A5 at Xq22 accounts for 80–85% of X-linked Alport syndrome patients. Three couples were referred to our reproductive genetics clinic for prenatal or preconception counseling.MethodsPrenatal diagnoses were performed by amplifying targeted regions of COL4A5. Targeted next-generation sequencing (NGS)-based haplotype analysis or karyomapping was performed in two patients. Pregnancy outcomes in the three patients were collected and analyzed. Published Alport syndrome cases were searched in Pubmed and Embase.ResultsPrenatal diagnoses in two cases showed one fetus harbored the same pathogenic mutation as the proband and the other was healthy. The couple with an affected fetus and the patient with a family history of Alport syndrome chose to take the preimplantation genetic testing (PGT) procedure. One unaffected embryo was transferred to the uterus, and a singleton pregnancy was achieved, respectively. Two patients presented non-nephrotic range proteinuria (<3 g/24 h) during pregnancy and the three cases all delivered at full-term. However, published Alport cases with chronic kidney disease or proteinuria during pregnancy were came with a high rate (75%) of adverse maternal and fetal outcomes.ConclusionThe PGT procedure performed in this study was proven to be practicable and might be expanded to be applied in other monogenic diseases. Moderate or severe renal impairments in Alport syndrome were strongly associated with adverse maternal and fetal outcomes, and baseline proteinuria was a potential predictor for pregnancy outcomes of Alport syndrome as other kidney diseases.

Inherited renal disease

2021 ◽  
pp. 339-401
Keyword(s):  
Genetic Testing ◽  
Kidney Disease ◽  
Kidney Diseases ◽  
Therapeutic Option ◽  
Genetic Diagnosis ◽  
Cystic Kidney ◽  
Disease Pathogenesis ◽  
Rna Molecules ◽  
Molecular Therapies ◽  
Cystic Kidney Diseases

With the advancement in, and increased availability of, genetic testing and a rapidly growing understanding of the genetic basis of many kidney diseases, it is important that nephrologists understand the rationale, limitations, and implications of making a genetic diagnosis in patients with kidney disease. While most inherited kidney diseases are rare, all nephrologists will encounter patients with genetic forms of kidney disease, particularly the cystic kidney diseases. An understanding of the genotype–phenotype relationships across the different inherited kidney diseases provides the nephrologist with an unprecedented understanding of disease pathogenesis. The evolving use of gene-based and molecular therapies utilizing silencing RNA molecules in kidney diseases are likely to become a growing therapeutic option in the future. Nephrologists will need to understand and embrace these new therapies, particularly for this group of kidney diseases.

Clinical utility of genetic testing in early-onset kidney disease: seven genes are the main players

2021 ◽  
Author(s):  
Andrea Domingo-Gallego ◽  
Marc Pybus ◽  
Gemma Bullich ◽  
Mónica Furlano ◽  
Laia Ejarque-Vila ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Kidney Disease ◽  
Clinical Diagnosis ◽  
Early Onset ◽  
Kidney Diseases ◽  
Diagnostic Yield ◽  
Genetic Diagnosis ◽  
Diagnostic Group ◽  
Cystic Kidney ◽  
Clinical Diagnostic

Abstract Background Inherited kidney diseases are one of the leading causes of chronic kidney disease (CKD) that manifests before the age of 30 years. Precise clinical diagnosis of early-onset CKD is complicated due to the high phenotypic overlap, but genetic testing is a powerful diagnostic tool. We aimed to develop a genetic testing strategy to maximize the diagnostic yield for patients presenting with early-onset CKD and to determine the prevalence of the main causative genes. Methods We performed genetic testing of 460 patients with early-onset CKD of suspected monogenic cause using next-generation sequencing of a custom-designed kidney disease gene panel in addition to targeted screening for c.428dupC MUC1. Results We achieved a global diagnostic yield of 65% (300/460), which varied depending on the clinical diagnostic group: 77% in cystic kidney diseases, 76% in tubulopathies, 67% in autosomal dominant tubulointerstitial kidney disease, 61% in glomerulopathies, and 38% in congenital anomalies of the kidney and urinary tract. Among the 300 genetically diagnosed patients, the clinical diagnosis was confirmed in 77%, a specific diagnosis within a clinical diagnostic group was identified in 15%, and 7% of cases were reclassified. Of the 64 causative genes identified in our cohort, seven (COL4A3, COL4A4, COL4A5, HNF1B, PKD1, PKD2, and PKHD1) accounted for 66% (198/300) of the genetically diagnosed patients. Conclusions Two-thirds of patients with early-onset CKD in this cohort had a genetic cause. Just seven genes were responsible for the majority of diagnoses. Establishing a genetic diagnosis is crucial to define the precise etiology of CKD, which allows accurate genetic counseling and improved patient management.

Family History is Important to Identify Patients with Monogenic Causes of Adult-Onset Chronic Kidney Disease

Nephron ◽  
2021 ◽  
pp. 1-9
Author(s):  
Jeff Granhøj ◽  
Birgitte Tougaard ◽  
Dorte L. Lildballe ◽  
Maria Rasmussen
Keyword(s):  
Chronic Kidney Disease ◽  
Genetic Testing ◽  
Family History ◽  
Kidney Disease ◽  
Case Series ◽  
Genetic Diagnostics ◽  
Compound Heterozygous ◽  
Adult Onset ◽  
Disease Case ◽  
The Family

Monogenic causes of chronic kidney disease (CKD) are more prevalent in adults than previously thought, as causative gene variants are found in almost 10% of unselected patients with CKD. Even so, genetic testing in patients with adult-onset CKD is uncommon in clinical practice and the optimal criteria for patient selection remain unclear. A family history of kidney disease emerges as one marker associated with a high diagnostic yield of genetic testing. We present 3 cases of adult-onset CKD with underlying monogenic causes exemplifying different modes of inheritance. Case 1 is a 60-year-old male with slowly progressive CKD initially ascribed to hypertension and diabetes despite a family history with several affected first-degree relatives. A pathogenic <i>MUC1</i> variant was found, and thus we identified the first Danish family of <i>MUC1</i>-associated autosomal dominant tubulointerstitial kidney disease. Case 2 is a 40-year-old female with nephrocalcinosis, nephrolithiasis, and unexplainable hypercalcemia consistent with vitamin D intoxication. The family history indicated autosomal recessive inheritance, and genetic testing revealed 2 pathogenic <i>CYP24A1</i> variants in compound heterozygous form associated with idiopathic infantile hypercalcemia. Case 3 is a 50-year-old male with microscopic hematuria, proteinuria, and hearing loss. Electron microscopy of renal biopsy showed thin basal membrane syndrome, and the family history indicated X-linked inheritance. A novel missense variant in <i>COL4A5</i> was identified, suggesting an atypical late-onset form of X-linked Alport syndrome. This case series illustrates the heterogeneous presentations of monogenic kidney disease in adults and emphasizes the importance of family history for initiating genetic testing to identify underlying monogenic causation. Moreover, we discuss the potential impact of genetic diagnostics on patient management and genetic family counseling.

Stroke in chronic renal failure

2008 ◽  
Vol 149 (15) ◽  
pp. 691-696
Author(s):  
Dániel Bereczki
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Disease ◽  
Chronic Renal Disease ◽  
Kidney Diseases ◽  
Cerebrovascular Diseases ◽  
Lipid Lowering ◽  
Increased Risk ◽  
Intracerebral Hemorrhages

Chronic kidney diseases and cardiovascular diseases have several common risk factors like hypertension and diabetes. In chronic renal disease stroke risk is several times higher than in the average population. The combination of classical risk factors and those characteristic of chronic kidney disease might explain this increased risk. Among acute cerebrovascular diseases intracerebral hemorrhages are more frequent than in those with normal kidney function. The outcome of stroke is worse in chronic kidney disease. The treatment of stroke (thrombolysis, antiplatelet and anticoagulant treatment, statins, etc.) is an area of clinical research in this patient group. There are no reliable data on the application of thrombolysis in acute stroke in patients with chronic renal disease. Aspirin might be administered. Carefulness, individual considerations and lower doses might be appropriate when using other treatments. The condition of the kidney as well as other associated diseases should be considered during administration of antihypertensive and lipid lowering medications.

Political bullshit receptivity and its correlates: a cross-cultural validation of the concept

2020 ◽  
Author(s):  
Vukašin Gligorić ◽  
Allard Feddes ◽  
Bertjan Doosje
Keyword(s):  
The Netherlands ◽  
Political Ideology ◽  
Voting Behavior ◽  
Free Market ◽  
Meta Analysis ◽  
The United States ◽  
Persuasive Communication ◽  
Lower Probability ◽  
Left Wing ◽  
Total N

Frankfurt defined persuasive communication that has no regard for truth, knowledge, or evidence as bullshit. Although there has been a lot of psychological research on pseudo-profound bullshit, no study examined this type of communication in politics. In the present research, we operationalize political bullshit receptivity as endorsing vague political statements, slogans, and political bullshit programs. We investigated the relationship of these three measures with pseudo-profound bullshit, ideology (political ideology, support for neoliberalism), populism, and voting behavior. Three pre-registered studies in different cultural settings (the United States, Serbia, The Netherlands; total N = 534) yielded medium to high intercorrelations between political bullshit measures and pseudo-profound bullshit, and good construct validity (hypothesized one-factor solution). A Bayesian meta-analysis showed that all political bullshit measures positively correlated with support for the free market, while only some positively correlated with social (political statements and programs) and economic conservatism (programs), and populism (programs). In the U.S., higher receptivity to political bullshit was associated with a higher probability that one voted for Trump (vs Clinton) in the past and higher intentions to vote for Trump (vs Biden and Sanders). In the Netherlands, higher receptivity to political bullshit predicted the intention to vote for the conservative-liberal People's Party for Freedom and Democracy. Exploratory analyses on merged datasets showed that higher receptivity to political bullshit was associated with a higher probability to vote for right-wing candidates/parties and lower probability for the left-wing ones. Overall, political bullshit endorsement showed good validity, opening avenues for research in political communication, especially when this communication is broad and meaningless.

Ethnopharmacological Survey of Medicinal Plants Used in Traditional Treatment of Kidney Diseases in Fez–Meknes Region, Morocco

2019 ◽  
Vol 18 (2) ◽  
pp. 99-114
Author(s):  
M. Chebaibi ◽  
D. Bousta ◽  
I. Iken ◽  
H. Hoummani ◽  
A. Ech-Choayeby ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Medicinal Plants ◽  
Kidney Diseases ◽  
Rank Order ◽  
Pearson Correlation ◽  
Use Value ◽  
Traditional Treatment ◽  
Toxic Plants ◽  
A Value ◽  
Chi Squared

The purpose of this study was to inventory and collect information on plants and mixtures commonly used by herbalists to treat kidney disease in the Fez–Meknes region. We also aimed to compare the results obtained with the results of the other studies and exploit the correlations between different factors. An ethnopharmacological survey was conducted from 289 local herbalists in eight different areas of Fez–Meknes region. Ethnomedicinal uses and ethnobotanical indices were analyzed using quantitative tools, i.e., the total number of citation (TNC), use value (UV), family use value (FUV), fidelity level (FL), and rank order priority (ROP). Statistical analyses such as Pearson correlation and chi-squared test were performed to delineate any correlation. Two hundred and eighty-nine herbalists were questioned. Sixty-nine plant species belonging to 38 families were cited by herbalists for traditional treatment of kidney disease. The highest value of UV was obtained for Herniaria glabra L. (UV = 0.79), and Caryophyllaceae was the family frequently cited (FUV = 0.795). Ammodaucus leucotrichus Coss. & Dur. had the highest value of FL with a value of 100%, and the highest value of ROP was recorded for Herniaria glabra L. (ROP = 91%). Sociodemographic characteristics had a significant impact on the knowledge of toxic plants. Our study has revealed a cultural heritage linked to herbalism and a great wealth of medicinal plants, whose valorization and protection are necessary. Several studies are needed to sensitize herbalists and population on the danger of toxic plants, to extract chemical compounds from the main plants used, and to evaluate their toxicity.

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