Family History of Renal Disease Severity Predicts the Mutated Gene in ADPKD

Barua, Moumita; Çil, Onur; Paterson, Andrew D.; Wang, Kairon; He, Ning; Dicks, Elizabeth; Parfrey, Patrick S.; Pei, York

doi:10.1681/asn.2009020162

Cited by 112 publications

(89 citation statements)

References 19 publications

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“…Our data also indicate that 58 renal transplants were performed on CKD patients between 2000 and 2006, which is 13% of the total number (416) performed in WA (McDonald et al 2007). This is consistent with previously published data which indicated that CKD accounted for 5% of patients newly diagnosed with primary renal disease in WA (McDonald et al 2007) and Barua et al (2009), who reported that CKD accounted for 5% of individuals with ESRF in the USA.…”

Section: Discussionsupporting

confidence: 93%

“…For example, we found that there was a high demand placed on hospital services by CKD (Q61) in middle to late adulthood, consistent with the disease phenotype of polycystic kidney disease 1 (PKD1), which accounts for approximately 85% of people with CKD (Barua et al 2009). The median age of onset of end stage renal failure (ESRF) of patients with PKD1 is estimated at 53 years (Barua et al 2009;Hateboer et al 1999), and we found that 80% of the admissions and costs due to CKD were in adults >50 years and that 90% of admissions for CKD patients were for hemodialysis. Our data also indicate that 58 renal transplants were performed on CKD patients between 2000 and 2006, which is 13% of the total number (416) performed in WA (McDonald et al 2007).…”

Section: Discussionmentioning

confidence: 61%

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The impact of single gene and chromosomal disorders on hospital admissions in an adult population

Dye¹,

Brameld

Maxwell

et al. 2011

J Community Genet

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Although the role of single gene and chromosomal disorders in pediatric illness has been recognized since the 1970s, there are few data describing the impact of these often severe disorders on the health of the adult population. In this study, we present population data describing the impact of single gene and chromosomal disorders on hospital admissions of patients aged 20 years and over in Western Australia between 2000 and 2006. The number, length, and cost of admissions were investigated and compared between disease categories and age groups and to hospital admissions for any reason. In total, 73,211 admissions and 8,032 patients were included in the study. The most costly disorders were cystic kidney disease, α-1 anti-trypsin deficiency, hemochromatosis, von Willebrand disease, and cystic fibrosis. Overall, patients with single gene and chromosomal disorders represented 0.5% of the patient population and were responsible for 1.9% of admissions and 1.5% of hospital costs. These data will enable informed provision of health care services for adults with single gene and chromosomal disorders in Australia.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 61%

The impact of single gene and chromosomal disorders on hospital admissions in an adult population

Dye¹,

Brameld

Maxwell

et al. 2011

J Community Genet

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“…3 However, a higher prevalence of PKD2 of 26% has been recently reported in a population-based study. 4 Disease progression of ADPKD is highly variable, in part because of a strong gene locus effect. [5][6][7][8] Adjusted for age, patients with PKD1 have larger kidneys and earlier onset of ESRD than patients with PKD2 (mean age at ESRD, 53.4 versus 72.7 years old, respectively).…”

Section: Introductionmentioning

confidence: 99%

Refining Genotype-Phenotype Correlation in Autosomal Dominant Polycystic Kidney Disease

Hwang

Conklin

Chan

et al. 2015

JASN

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133

143

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Renal disease variability in autosomal dominant polycystic kidney disease (ADPKD) is strongly influenced by the gene locus (PKD1 versus PKD2). Recent studies identified nontruncating PKD1 mutations in approximately 30% of patients who underwent comprehensive mutation screening, but the clinical significance of these mutations is not well defined. We examined the genotype-renal function correlation in a prospective cohort of 220 unrelated ADPKD families ascertained through probands with serum creatinine #1.4 mg/dl at recruitment. We screened these families for PKD1 and PKD2 mutations and reviewed the clinical outcomes of the probands and affected family members. Height-adjusted total kidney volume (htTKV) was obtained in 161 affected subjects. Multivariate Cox proportional hazard modeling for renal and patient survival was performed in 707 affected probands and family members. Overall, we identified pathogenic mutations in 84.5% of our families, in which the prevalence of PKD1 truncating, PKD1 in-frame insertion/deletion, PKD1 nontruncating, and PKD2 mutations was 38.3%, 4.3%, 27.1%, and 30.3%, respectively. Compared with patients with PKD1 truncating mutations, patients with PKD1 in-frame insertion/deletion, PKD1 nontruncating, or PKD2 mutations have smaller htTKV and reduced risks (hazard ratio Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease worldwide, responsible for 5%-10% of ESRD. 1,2 Mutations in two genes (PKD1 and PKD2) account for most patients with ADPKD. 2,3 Previous studies of European families ascertained through probands enriched with renal failure reported that approximately 85% and approximately 15% of ADPKD families were linked to the PKD1 and PKD2 loci, respectively. 3 However, a higher prevalence of PKD2 of 26% has been recently reported in a population-based study. 4 Disease progression of ADPKD is highly variable, in part because of a strong gene locus effect. [5][6][7][8] Adjusted for age, patients with PKD1 have larger kidneys and earlier onset of ESRD than patients with PKD2 (mean age at ESRD, 53.4 versus 72.7 years old, respectively). 5,6,8 Additionally, significant intrafamilial renal disease variability in ADPKD suggests a modifier effect. [9][10][11] [

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“…More recently, a higher incidence of PKD2 mutations has been reported in the Canadian and US populations (26% and 36%, respectively). 39,40 There is significant heterogeneity in disease phenotype between affected individuals. PKD1 mutation is associated with more severe and rapidly progressive disease, with onset of end-stage renal disease occurring by the mid to late 50s.…”

Section: Genetics Of Adpkd Genesmentioning

confidence: 99%

Autosomal dominant polycystic kidney disease: genetics, epidemiology, and treatment

Reed-Gitomer¹

2014

AGG

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Abstract:Autosomal dominant polycystic kidney disease (ADPKD) is the most common potentially lethal genetic disorder, accounting for 2%-8% of end-stage renal disease worldwide. While development of renal cysts is the major characteristic of ADPKD, several disease-related complications contribute significantly to morbidity and mortality. Since introduction of renal replacement therapies, cardiovascular disease is the leading cause of death among ADPKD patients. Loss of renal function requiring renal replacement therapy occurs in 50% of patients by the age of 60 years. The results of recent large epidemiological studies in ADPKD have shown little progress in delaying onset of renal failure despite an improvement in patient mortality. Significant progress has been made over the past decade in elucidating the genetics of the disorder. Genetic testing is now available in most countries, and development of more reliable methods for prenatal diagnosis of ADPKD has increased the sensitivity of testing. While there are no approved drugs for treatment of ADPKD within the USA, the first agent targeting renal disease progression in this disorder was recently approved for clinical use in Japan. Furthermore, several additional drugs for treatment of ADPKD are currently under clinical investigation. Overall, this presents an optimistic future for new therapeutic interventions in this disease. This paper reviews the current knowledge related to the epidemiology, genetics, and treatment of ADPKD.

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Family History of Renal Disease Severity Predicts the Mutated Gene in ADPKD

Cited by 112 publications

References 19 publications

The impact of single gene and chromosomal disorders on hospital admissions in an adult population

The impact of single gene and chromosomal disorders on hospital admissions in an adult population

Refining Genotype-Phenotype Correlation in Autosomal Dominant Polycystic Kidney Disease

Autosomal dominant polycystic kidney disease: genetics, epidemiology, and treatment

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