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.

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.

Assessment of the older patient with chronic kidney disease and polypharmacy − the perspective of the family doctor

Medic ro ◽  
2018 ◽  
Vol 5 (125) ◽  
pp. 33
Author(s):  
Liliana-Ana Tuţă ◽  
Laura Condur ◽  
Alina Mihaela Stăniguţ ◽  
Camelia Pană
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Family Doctor ◽  
Older Patient ◽  
The Family

scholarly journals Drug Induced Encephalopathy in Patients with Chronic Kidney Disease: A Case Series

2018 ◽  
Vol 8 (2) ◽  
pp. 172-176
Author(s):  
Wasim Md Mohosin Ul Haque ◽  
Tabassum Samad ◽  
Muhammad Abdur Rahim ◽  
Shudhanshu Kumar Saha ◽  
Sarwar Iqbal
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Impairment ◽  
Side Effect ◽  
Case Series ◽  
Special Group ◽  
Drug Induced ◽  
Reduced Dose

Drug induced encephalopathy is an established side effect of many drugs when used in a higher dose. Though we do not encounter this side effect frequently in our day to day practice, yet with renal impairment this is not uncommon. Even with a reduced dose many of these can precipitate encephalopathy in this special group of patients. We are presenting here a series of seven such cases of drug induced encephalopathy in patients with renal impairment.Birdem Med J 2018; 8(2): 172-176

scholarly journals Novel SCN5A p.Val1667Asp Missense Variant Segregation and Characterization in a Family with Severe Brugada Syndrome and Multiple Sudden Deaths

2021 ◽  
Vol 22 (9) ◽  
pp. 4700
Author(s):  
Michelle M. Monasky ◽  
Emanuele Micaglio ◽  
Giuseppe Ciconte ◽  
Ilaria Rivolta ◽  
Valeria Borrelli ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Family History ◽  
Risk Stratification ◽  
Brugada Syndrome ◽  
Electrophysiological Study ◽  
Functional Characterization ◽  
The Family ◽  
Novel Variant ◽  
History Of ◽  
Scn5a Gene

Genetic testing in Brugada syndrome (BrS) is still not considered to be useful for clinical management of patients in the majority of cases, due to the current lack of understanding about the effect of specific variants. Additionally, family history of sudden death is generally not considered useful for arrhythmic risk stratification. We sought to demonstrate the usefulness of genetic testing and family history in diagnosis and risk stratification. The family history was collected for a proband who presented with a personal history of aborted cardiac arrest and in whom a novel variant in the SCN5A gene was found. Living family members underwent ajmaline testing, electrophysiological study, and genetic testing to determine genotype-phenotype segregation, if any. Patch-clamp experiments on transfected human embryonic kidney 293 cells enabled the functional characterization of the SCN5A novel variant in vitro. In this study, we provide crucial human data on the novel heterozygous variant NM_198056.2:c.5000T>A (p.Val1667Asp) in the SCN5A gene, and demonstrate its segregation with a severe form of BrS and multiple sudden deaths. Functional data revealed a loss of function of the protein affected by the variant. These results provide the first disease association with this variant and demonstrate the usefulness of genetic testing for diagnosis and risk stratification in certain patients. This study also demonstrates the usefulness of collecting the family history, which can assist in understanding the severity of the disease in certain situations and confirm the importance of the functional studies to distinguish between pathogenic mutations and harmless genetic variants.

scholarly journals EFFECT OF SUBCUTANEOUS RECOMBINANT HUMAN ERYTHROPOIETIN ON BLOOD PRESSURE IN PRE-DIALYSIS CHRONIC KIDNEY DISEASE (CKD) PATIENTS

2021 ◽  
Vol 71 (1) ◽  
pp. 261-65
Author(s):  
Muhammad Sajid Hussain ◽  
Qasim Raza ◽  
Muhammad Omer Aamir ◽  
Nadia Murtaza ◽  
Sadia Naureen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Body Weight ◽  
Kidney Disease ◽  
Recombinant Human Erythropoietin ◽  
Case Series ◽  
Military Hospital ◽  
P Value ◽  
Human Erythropoietin ◽  
Age Range

Objective: To determine the effect of subcutaneous recombinant human erythropoietin on blood pressure in predialysis chronic kidney disease (CKD) patients. Study Design: Case-series descriptive study. Place and Duration of Study: Combined Military Hospital Peshawar, from Mar 2016 to Sep 2016. Methodology: A total of 100 cases were enrolled. Inclusion criteria was patients of 18 to 60 years of both gender & estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m2 having Hb <10g/dL and pre-dialysis while Exclusion Criteria was pregnancy or lactation, BP more than 140/90 mmHg, patients on Haemodialysis and worsening renal function. Baseline BP, body weight and eGFR of anaemic chronic kidney disease patients were recorded prior to EPO Alpha therapy. Erythropoiesis-stimulating agents (ESAs) i.e. EPO Alpha (50-100 Units/kg thrice or once weekly) was administered subcutaneously. Subsequent blood pressure, body weight and eGFR monitoring was done after 2 and 4 weeks post EPO Alpha injection. Results: Mean age range was 46.71 years with range of 20-60 years, 73 (73%) were male while 27 (27%) werefemales. Mean ± SD for other quantitative variables like eGFR was 23.12 ± 5.28, Hb levels (g/dL) was 8.62 ± 0.85,Weight (kg) was 56.66 ± 6.62 and duration of CKD was 9.87 ± 4.02. Frequency of Hypertension (post EPO) was 2(2%) and p-value was 0.453. Conclusion: We concluded that the frequency of hypertension in pre-dialysis patients with chronic kidney disease (CKD) receiving recombinant human erythropoietin (rhEPo) subcutaneously (SC) in low doses, is very low, so rhEPo can be used subcutaneously......................

scholarly journals CONDITION AFTER HEMOLYTIC-UREMIC SYNDROME IN A CHILD WITH 3RD STAGE CHRONIC KIDNEY DISEASE (case report)

2017 ◽  
Vol 4 (3) ◽  
pp. 136-138
Author(s):  
M.O. Gonchar ◽  
T.B. Ishenko ◽  
N.V. Orlova ◽  
G.R. Muratov ◽  
T.F. Kolibaeva ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Failure ◽  
Case Report ◽  
Chronic Renal Failure ◽  
Kidney Disease ◽  
Hemolytic Uremic Syndrome ◽  
Clinical Case ◽  
Disease Case ◽  
Uremic Syndrome ◽  
The Given

Gonchar M.O., Ishchenko T.B., Orlova N.V., Muratov G., Kolibaeva T., Khmara N., Podvalnaya N.Currently, hemolytic-uremic syndrome is one of the frequent causes of acute kidney failure in children, so the timeliness of diagnosis and treatment determines the outcome of the disease. In the given clinical case, a set of certain factors that lead to an unfavorable outcome of the disease and the progression of chronic renal failure are presented. Clinical case of a 14-year-old child K., who was admitted to the nephrology department of the Regional Children's Clinical Hospital with the diagnosis: 3rd stage CKD, subcompensated stage of chronic renal failure and condition after hemolytic-uremic syndrome.KeyWords: hemolytic-uremic syndrome in children, chronic kidney disease. СТАН ПЫСЛЯ ПЕРЕНЕСЕНОГО ГЕМОЛІТИКО-УРЕМІЧНОГО СИНДРОМУ У ДИТИНИ З III СТАДІЄЮ ХРОНІЧНОГО ЗАХВОРЮВАННЯ НИРОК (КЛІНІЧНЕ СПОСТЕРЕЖЕННЯ)Гончарь М.О., Іщенко Т.Б., Орлова Н.В., Муратов Г.Р., Колібаєва Т.Ф., Хмара Н.В., Підвальна Н.А. В даний час гемолітико-уремічний синдром є однією з найчастіших причин гострої ниркової недостатності у дітей, тому своєчасність постановки діагнозу і лікування визначає результат захворювання. На наведеному клінічному випадку, представлено сукупність певних факторів, які привели до несприятливого результату захворювання і прогресування хронічної ниркової недостатності. Клінічний випадок дитини К. 14 років, який знаходився в нефрологічному відділенні Обласної дитячої клінічної лікарні з діагноз: ХХН III ст. Хронічна ниркова недостатність субкомпенсированная стадія. Стан після перенесеного гемолітико-уремічного синдрому.Ключові слова: гемолітико-уремічний синдром, діти, клінічний випадок, хронічне захворювання нирок. СОСТОЯНИЕ ПОСЛЕ ПЕРЕНЕСЕННОГО ГЕМОЛИТИКО-УРЕМИЧЕСКОГО СИНДРОМА У РЕБЕНКА С III СТАДИЕЙ ХРОНИЧЕСКОГО ЗАБОЛЕВАНИЯ ПОЧЕК (КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ)Гончарь М.А., Ищенко Т.Б., Орлова Н.В., Муратов Г.Р., Колибаева Т.Ф., Хмара Н.В., Подвальная Н.А. В настоящее время гемолитико-уремический синдром является одной из частых причин острой почечной недостаточности у детей, поэтому своевременность постановки диагноза и лечения определяет исход заболевания. На приведенном клиническом случае, представлено совокупность определенных факторов, которые привели к неблагоприятному исходу заболевания и прогрессированию хронической почечной недостаточности. Клинический случай ребенка К. 14 лет, который находился в нефрологическом отделении Областной детской клинической больнице с диагноз: ХБП III ст. Хроническая почечная недостаточность субкомпенсированная стадия. Состояние после перенесенного гемолитико-уремического синдрома.Ключевые слова: гемолитико-уремический синдром, дети, клинический случай, хроническое заболевание почек.

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