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.

scholarly journals Diagnostic accuracy of administrative codes for autosomal dominant polycystic kidney disease in clinic patients with cystic kidney disease

2020 ◽  
Author(s):  
Vinusha Kalatharan ◽  
Eric McArthur ◽  
Danielle M Nash ◽  
Blayne Welk ◽  
Sisira Sarma ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
International Classification Of Diseases ◽  
Cystic Kidney Disease ◽  
Administrative Databases ◽  
Cystic Kidney ◽  
Polycystic Kidney ◽  
Icd 10 ◽  
Autosomal Dominant Polycystic Kidney

Abstract Background The ability to identify patients with autosomal dominant polycystic kidney disease (ADPKD) and distinguish them from patients with similar conditions in healthcare administrative databases is uncertain. We aimed to measure the sensitivity and specificity of different ADPKD administrative coding algorithms in a clinic population with non-ADPKD and ADPKD kidney cystic disease. Methods We used a dataset of all patients who attended a hereditary kidney disease clinic in Toronto, Ontario, Canada between 1 January 2010 and 23 December 2014. This dataset included patients who met our reference standard definition of ADPKD or other cystic kidney disease. We linked this dataset to healthcare databases in Ontario. We developed eight algorithms to identify ADPKD using the International Classification of Diseases, 10th Revision (ICD-10) codes and provincial diagnostic billing codes. A patient was considered algorithm positive if any one of the codes in the algorithm appeared at least once between 1 April 2002 and 31 March 2015. Results The ICD-10 coding algorithm had a sensitivity of 33.7% [95% confidence interval (CI) 30.0–37.7] and a specificity of 86.2% (95% CI 75.7–92.5) for the identification of ADPKD. The provincial diagnostic billing code had a sensitivity of 91.1% (95% CI 88.5–93.1) and a specificity of 10.8% (95% CI 5.3–20.6). Conclusions ICD-10 coding may be useful to identify patients with a high chance of having ADPKD but fail to identify many patients with ADPKD. Provincial diagnosis billing codes identified most patients with ADPKD and also with other types of cystic kidney disease.

Cystic Diseases of the Kidney

2017 ◽  
Author(s):  
Christian Riella ◽  
Peter G Czarnecki ◽  
Theodor I Steinman
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Disease Gene ◽  
Renal Cysts ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney ◽  
End Stage

The spectrum of cystic kidney diseases encompasses a wide range of genetic syndromes with different identified disease genes, modes of inheritance, extrarenal organ manifestations, and clinical progression. Depending on the given disease gene and type of mutation in a respective cystic kidney disease, the age of onset, pathologic characteristics, and rate of progression to end-stage kidney disease vary considerably. This review covers disease definitions, etiology and genetics, pathophysiology and pathogenesis, diagnosis, differential diagnosis, and treatment of cystic kidney disease. Additionally, simple and complex renal cysts in adults are discussed. Tables list the epidemiology of polycystic kidney disease, gene locus, and encoded protein, unified criteria for ultrasonographic diagnosis of autosomal dominant polycystic kidney disease (APDKD), risk factors for progressive kidney disease in APDKD, differential diagnosis of cystic diseases of the kidney, Halt Progression of Polycystic Kidney Disease trial summary, and other extrarenal manifestations of ADPDK. Key Words: Cystic kidney disease; Autosomal dominant polycystic kidney disease; APDKD; Polycystic kidney disease; PKD; End-stage renal disease; Renal cysts; Progressive kidney disease

scholarly journals Echocardiographic Findings and Genotypes in Autosomal Dominant Polycystic Kidney Disease

2021 ◽  
pp. 1-7
Author(s):  
Ryohei Miyamoto ◽  
Akinari Sekine ◽  
Takuya Fujimaru ◽  
Tatsuya Suwabe ◽  
Hiroki Mizuno ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Structural Data ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Polycystic Kidney ◽  
Cardiac Events ◽  
Significant Difference ◽  
Autosomal Dominant Polycystic Kidney

<b><i>Background:</i></b> Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cystic kidney disease and is well known to have extrarenal complications. Cardiovascular complications are of particular clinical relevance because of their morbidity and mortality; however, unclear is why they occur so frequently in patients with ADPKD and whether they are related to the genotypes. <b><i>Methods:</i></b> We extracted and retrospectively analyzed clinical data on patients with ADPKD who underwent echocardiography and whose genotype was confirmed by genetic testing between April 2016 and December 2020. We used next-generation sequencing to compare cardiac function, structural data, and the presence of cardiac valvular disease in patients with 1 of 3 genotypes: <i>PKD1</i>, <i>PKD2</i>, and non-<i>PKD1</i>, <i>2</i>. <b><i>Results:</i></b> This retrospective study included 65 patients with ADPKD. Patients were divided into 3 groups: <i>PKD1</i>, <i>n</i> = 32; <i>PKD2</i>, <i>n</i> = 12; and non-<i>PKD1</i>, <i>2</i>, <i>n</i> = 21. The prevalence of mitral regurgitation (MR) was significantly higher in the <i>PKD1</i> group than in the <i>PKD2</i> and non-<i>PKD1</i>, <i>2</i> group (46.9% vs. 8.3% vs. 19.0%, respectively; <i>p</i> = 0.02). In contrast, no significant difference was found for other cardiac valve complications. <b><i>Conclusion:</i></b> This study found a significantly higher prevalence of MR in patients with the <i>PKD1</i> genotype than in those with the <i>PKD2</i> or non-<i>PKD1</i>, <i>2</i> genotypes. Physicians may need to perform echocardiography earlier and more frequently in patients with ADPKD and the <i>PKD1</i> genotype and to control fluid volume and blood pressure more strictly in these patients to prevent future cardiac events.

scholarly journals Molecular Pathways and Therapies in Autosomal-Dominant Polycystic Kidney Disease

Physiology ◽  
2015 ◽  
Vol 30 (3) ◽  
pp. 195-207 ◽  
Author(s):  
Takamitsu Saigusa ◽  
P. Darwin Bell
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Primary Cilia ◽  
Autosomal Dominant ◽  
Molecular Pathways ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney ◽  
Multiple Cysts ◽  
Review Current

Autosomal-dominant polycystic kidney disease (ADPKD) is the most prevalent inherited renal disease, characterized by multiple cysts that can eventually lead to kidney failure. Studies investigating the role of primary cilia and polycystins have significantly advanced our understanding of the pathogenesis of PKD. This review will present clinical and basic aspects of ADPKD, review current concepts of PKD pathogenesis, evaluate potential therapeutic targets, and highlight challenges for future clinical studies.

scholarly journals Hypomagnesaemia is absent in children with autosomal dominant polycystic kidney disease

2018 ◽  
Vol 56 (1) ◽  
pp. 90-94 ◽  
Author(s):  
Tomáš Seeman ◽  
Magdaléna Fořtová ◽  
Bruno Sopko ◽  
Richard Průša ◽  
Michael Pohl ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Kidney Diseases ◽  
Differential Diagnostics ◽  
Cystic Kidney ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney ◽  
Cystic Kidney Diseases ◽  
Rule Out

Background Hypomagnesaemia is present in 40–50% of children with autosomal dominant renal cysts and diabetes syndrome (RCAD). On the contrary, the prevalence of hypomagnesaemia in children with autosomal dominant polycystic kidney disease (ADPKD) has never been examined. We aimed to investigate whether hypomagnesaemia is present in children with polycystic kidney diseases. Methods Children with cystic kidney diseases were investigated in a cross-sectional study. Serum concentrations of magnesium (S-Mg) and fractional excretion of magnesium (FE-Mg) were tested. Fifty-four children with ADPKD ( n = 26), autosomal recessive polycystic kidney disease (ARPKD) ( n = 16) and RCAD ( n = 12) with median age of 11.2 (0.6–18.6) years were investigated. Results Hypomagnesaemia (S-Mg < 0.7 mmol/L) was detected in none of the children with ADPKD/ARPKD and in eight children (67%) with RCAD. Median S-Mg in children with ADPKD/ARPKD was significantly higher than in children with RCAD (0.89 vs. 0.65 mmol/L, P < 0.01). The FE-Mg was increased in 23% of patients with ADPKD/ARPKD (all had chronic kidney disease stages 2–4) and in 63% of patients with RCAD, where it significantly correlated with estimated glomerular filtration rate (r = −0.87, P < 0.01). Conclusions Hypomagnesaemia is absent in children with ADPKD or ARPKD and could serve as a marker for differential diagnostics between ADPKD, ARPKD and RCAD in children with cystic kidney diseases of unknown origin where molecular genetic testing is lacking. However, while hypomagnesaemia, in the absence of diuretics, appears to rule out ADPKD and ARPKD, normomagnesaemia does not rule out RCAD at least in those aged <3 years.

Peritoneal Dialysis for Patients with Autosomal Dominant Polycystic Kidney Disease

2017 ◽  
Vol 37 (4) ◽  
pp. 384-388 ◽  
Author(s):  
Sana Khan ◽  
Anna Giuliani ◽  
Carlo Crepaldi ◽  
Claudio Ronco ◽  
Mitchell H. Rosner
Keyword(s):  
Peritoneal Dialysis ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Disease Patient ◽  
Cystic Kidney ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney ◽  
Stage Renal Disease ◽  
End Stage

End-stage renal disease secondary to autosomal dominant poly-cystic kidney (ADPKD) is a common issue worldwide. Peritoneal dialysis (PD) is a reasonable option for renal replacement therapy for these patients and should not be withheld due to concerns that the patient may not tolerate the fluid volumes in the peritoneal cavity. This review covers the existing data on the outcomes and complications associated with the use of PD in the polycystic kidney disease patient. In general, PD is well tolerated and outcomes in ADPKD patients are equivalent to or better than other patient groups.

scholarly journals Novel role of ouabain as a cystogenic factor in autosomal dominant polycystic kidney disease

2013 ◽  
Vol 305 (6) ◽  
pp. F797-F812 ◽  
Author(s):  
Gustavo Blanco ◽  
Darren P. Wallace
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Signal Transducer ◽  
Polycystic Kidney ◽  
Cell Functions ◽  
Cell Energy ◽  
High Concentrations ◽  
Autosomal Dominant Polycystic Kidney

The classic role of the Na-K-ATPase is that of a primary active transporter that utilizes cell energy to establish and maintain transmembrane Na+ and K+ gradients to preserve cell osmotic stability, support cell excitability, and drive secondary active transport. Recent studies have revealed that Na-K-ATPase located within cholesterol-containing lipid rafts serves as a receptor for cardiotonic steroids, including ouabain. Traditionally, ouabain was viewed as a toxin produced only in plants, and it was used in relatively high concentrations to experimentally block the pumping action of the Na-K-ATPase. However, the new and unexpected role of the Na-K-ATPase as a signal transducer revealed a novel facet for ouabain in the regulation of a myriad of cell functions, including cell proliferation, hypertrophy, apoptosis, mobility, and metabolism. The seminal discovery that ouabain is endogenously produced in mammals and circulates in plasma has fueled the interest in this endogenous molecule as a potentially important hormone in normal physiology and disease. In this article, we review the role of the Na-K-ATPase as an ion transporter in the kidney, the experimental evidence for ouabain as a circulating hormone, the function of the Na-K-ATPase as a signal transducer that mediates ouabain's effects, and novel results for ouabain-induced Na-K-ATPase signaling in cystogenesis of autosomal dominant polycystic kidney disease.

Sign in / Sign up

Export Citation Format

Share Document