scholarly journals The Kidney Genetics Clinic: delivering precision medicine for kidney patients

2021 ◽  
Vol 35 (3) ◽  
Author(s):  
Joaquim Calado ◽  
◽  
Rui Barata ◽  
Rita Lucas ◽  
Telma Francisco ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Kidney Disease ◽  
Tuberous Sclerosis ◽  
Polycystic Kidney Disease ◽  
Tuberous Sclerosis Complex ◽  
Autosomal Dominant ◽  
Molecular Testing ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney ◽  
The Impact

Molecular genetic testing in human traits has traditionally relied on affiliated academic facilities, been focused on specific phenotypes and supported by research funding. We report the experience of the Kidney Genetics Clinic (“consulta de Doenças Renais Hereditárias”) for the past 5 years, a period during which we have outsourced genetic testing. We evaluated the impact of molecular testing in patients’ care, but we also assessed disease‑specific imaging procedures and medicines provided. During the study period, 293 individuals were evaluated. Autosomal Dominant Polycystic Kidney Disease was the most frequent diagnosis (61.8%). In 125 patients, a genetic test was available, and for 76 of these (60.8%) a pathogenic/likely pathogenic variant was identified. Depend‑ ing on the phenotype, the mutation detection rate ranged from 100% (Tuberous Sclerosis Complex) to 15.4% (Autosomal Dominant Tubuloint‑ erstitial Kidney Disease). The impact of genetic testing on patients’ diagnosis and treatments is discussed. Total kidney volume was calculated in 6 patients with Autosomal Dominant Polycystic Kidney Disease and the combined volume for selected angiomyolipoma monitored in 3 individuals with the Tuberous Sclerosis Complex. Currently, 4 patients are being treated with Everolimus/Votubia™, 3 with Eculizumab/Soliris™ and 2 with Tolvaptan/Jinarc™. Our results demonstrate the feasibility of genetic molecular testing in a clinical setting while relying on outsourced sites for gene testing. We emphasize that it was only because the Kidney Genetics Clinic was given the opportunity to look after several patients affected by the same specific orphan or rare diseases (cohort enrichment) that we were able to improve diagnostic skills and deliver personalized medicines.

scholarly journals Cluster of differentiation 8 and programmed cell death ligand 1 expression in triple-negative breast cancer combined with autosomal dominant polycystic kidney disease and tuberous sclerosis complex: a case report

2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Kenji Gonda ◽  
Takanori Akama ◽  
Takayuki Nakamura ◽  
Eiko Hashimoto ◽  
Naomi Kyoya ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Kidney Disease ◽  
Tuberous Sclerosis ◽  
Polycystic Kidney Disease ◽  
Tuberous Sclerosis Complex ◽  
Triple Negative ◽  
Autosomal Dominant ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney ◽  
Cluster Of Differentiation

Abstract Background Autosomal dominant polycystic kidney disease is defined as an inherited disorder characterized by renal cyst formation due to mutations in the PKD1 or PKD2 gene, whereas tuberous sclerosis complex is an autosomal dominant neurocutaneous syndrome caused by mutation or deletion of the TSC2 gene. A TSC2/PKD1 contiguous gene syndrome, which is caused by a chromosomal mutation that disrupts both the TSC2 and PKD1 genes, has been identified in patients with tuberous sclerosis complex and severe early-onset autosomal dominant polycystic kidney disease. The tumor tissue of patients with breast cancer with contiguous gene syndrome has a high mutation burden and produces several neoantigens. A diffuse positive immunohistochemistry staining for cluster of differentiation 8+ in the T cells of breast cancer tissue is consistent with neoantigen production due to high mutation burden. Case presentation A 61-year-old Japanese woman who had been undergoing dialysis for 23 years because of end-stage renal failure secondary to autosomal dominant polycystic kidney disease was diagnosed as having triple-negative breast cancer and underwent mastectomy in 2015. She had a history of epilepsy and skin hamartoma. Her grandmother, mother, two aunts, four cousins, and one brother were also on dialysis for autosomal dominant polycystic kidney disease. Her brother had epilepsy and a brain nodule. Another brother had a syndrome of kidney failure, intellectual disability, and diabetes mellitus, which seemed to be caused by mutation in the CREBBP gene. Immunohistochemistry of our patient’s breast tissue showed cluster of differentiation 8 and programmed cell death ligand 1 positivity. Conclusions Programmed cell death ligand 1 checkpoint therapy may be effective for recurrence of triple-negative breast cancer in a patient with autosomal dominant polycystic kidney disease and tuberous sclerosis complex.

Autosomal Dominant Polycystic Kidney Disease: Clinical Assessment of Rapid Progression

2018 ◽  
Vol 48 (4) ◽  
pp. 308-317 ◽  
Author(s):  
Mónica Furlano ◽  
Irene Loscos ◽  
Teresa Martí ◽  
Gemma Bullich ◽  
Nadia Ayasreh ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Rapid Progression ◽  
Kidney Volume ◽  
Polycystic Kidney ◽  
Decision Algorithm ◽  
Autosomal Dominant Polycystic Kidney ◽  
The Impact

Background: Autosomal dominant polycystic kidney disease (ADPKD) causes the development of renal cysts and leads to a decline in renal function. Limited guidance exists in clinical practice on the use of tolvaptan. A decision algorithm from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Working Groups of Inherited Kidney Disorders and European Renal Best Practice (WGIKD/ERBP) has been proposed to identify candidates for tolvaptan treatment; however, this algorithm has not been assessed in clinical practice. Methods: Eighteen-month cross-sectional, unicenter, observational study assessing 305 consecutive ADPKD patients. The ERA-EDTA WGIKD/ERBP algorithm with a stepwise approach was used to assess rapid progression (RP). Subsequently, expanded criteria based on the REPRISE trial were applied to evaluate the ­impact of extended age (≤55 years) and estimated glomerular filtration rate (eGFR; ≥25 mL/min/1.73 m2). Results: Historical eGFR decline, indicative of RP, was fulfilled in 26% of 73 patients who were candidates for RP assessment, mostly aged 31–55 years. Further tests including ultrasound and MRI measurements of kidney volume plus genetic testing enabled the evaluation of the remaining patients. Overall, 15.7% of patients met the criteria for rapid or likely RP using the algorithm, and the percentage increased to 27% when extending age and eGFR. Conclusions: The ERA-EDTA WGIKD/ERBP algorithm provides a valuable means of identifying in routine clinical practice patients who may be eligible for treatment with tolvaptan. The impact of a new threshold for age and eGFR may increase the percentage of patients to be treated.

Evolving role of genetic testing for the clinical management of autosomal dominant polycystic kidney disease

2018 ◽  
Vol 34 (9) ◽  
pp. 1453-1460 ◽  
Author(s):  
Matthew B Lanktree ◽  
Ioan-Andrei Iliuta ◽  
Amirreza Haghighi ◽  
Xuewen Song ◽  
York Pei
Keyword(s):  
Genetic Testing ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Mutation Screening ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney

Abstract Autosomal dominant polycystic kidney disease (ADPKD) is caused primarily by mutations of two genes, PKD1 and PKD2. In the presence of a positive family history of ADPKD, genetic testing is currently seldom indicated as the diagnosis is mostly based on imaging studies using well-established criteria. Moreover, PKD1 mutation screening is technically challenging due to its large size, complexity (i.e. presence of six pseudogenes with high levels of DNA sequence similarity) and extensive allelic heterogeneity. Despite these limitations, recent studies have delineated a strong genotype–phenotype correlation in ADPKD and begun to unravel the role of genetics underlying cases with atypical phenotypes. Furthermore, adaptation of next-generation sequencing (NGS) to clinical PKD genetic testing will provide a high-throughput, accurate and comprehensive screen of multiple cystic disease and modifier genes at a reduced cost. In this review, we discuss the evolving indications of genetic testing in ADPKD and how NGS-based screening promises to yield clinically important prognostic information for both typical as well as unusual genetic (e.g. allelic or genic interactions, somatic mosaicism, cystic kidney disease modifiers) cases to advance personalized medicine in the era of novel therapeutics for ADPKD.

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