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

Division of Nephrology and Genomic Medicine, Department of Medicine, University of Toronto and University Health Network, Toronto, Ontario, Canada.
Journal of the American Society of Nephrology (Impact Factor: 9.34). 06/2009; 20(8):1833-8. DOI: 10.1681/ASN.2009020162
Source: PubMed


Mutations of PKD1 and PKD2 account for 85 and 15% of cases of autosomal dominant polycystic kidney disease (ADPKD), respectively. Clinically, PKD1 is more severe than PKD2, with a median age at ESRD of 53.4 versus 72.7 yr. In this study, we explored whether a family history of renal disease severity predicts the mutated gene in ADPKD. We examined the renal function (estimated GFR and age at ESRD) of 484 affected members from 90 families who had ADPKD and whose underlying genotype was known. We found that the presence of at least one affected family member who developed ESRD at age < or =55 was highly predictive of a PKD1 mutation (positive predictive value 100%; sensitivity 72%). In contrast, the presence of at least one affected family member who continued to have sufficient renal function or developed ESRD at age >70 was highly predictive of a PKD2 mutation (positive predictive value 100%; sensitivity 74%). These data suggest that close attention to the family history of renal disease severity in ADPKD may provide a simple means of predicting the mutated gene, which has prognostic implications.

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    • "Autosomal dominant polycystic kidney disease (ADPKD) is the more common variant (80%) of polycystic kidney disease with a prevalence of 1 to 2 cases per 400 to 1000 live births [1]. It is the most common genetic cause of chronic kidney disease and accounts for five percent of patients who initiate dialysis in the US each year [2] [3]. However more than 50% of those carrying inherited mutations in the genes responsible for ADPKD will go undetected throughout a patient's lifetime. "
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    ABSTRACT: The average weight of a kidney is approximately 135 gm, measuring on average 10 × 6 × 4 cm. In hereditary conditions, autosomal dominant and autosomal recessive polycystic kidney disease, the shape, size, and the weight can be significantly abnormal, causing progressive renal failure, often necessitating dialysis or renal transplant for survival. We report a case of adult polycystic kidney disease in a 50-year-old female without a family history, who died of complications of the disease which included accelerated hypertension, and renal and cardiac failure.
    09/2014; 2014:727580. DOI:10.1155/2014/727580
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    • "PKD may have a autosomal dominant or recessive trait. The autosomal dominant PKD (ADPKD) is the most common genetic variant of CKD [8,9], at its final stage, requiring renal replacement commonly [8]. "
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    ABSTRACT: Background We investigated the changes in the values of carotid intima-media thickness (IMT) and Doppler index measurements in the autosomal dominant polycystic kidney disease (ADPKD), peritoneal dialysis (PD), and hemodialysis (HD) patients. Material/Methods Twenty outpatients on HD (mean age 46.1±16.4), 27 outpatients on PD (mean age 45±12.4), and 26 normotensive outpatients with ADPKD (mean age 52.4±16.7) as the case groups and 21 healthy subjects (mean age 48.4±7.2), as the control group, were included. The participants underwent ultrasonography of the common, right, and left carotid arteries for the IMT and Doppler flow measurements. Results Overall, compared to the normal group, in the study groups, the IMT and peak systolic velocity (PSV), end-diastolic velocity (EDV), resistive index (RI), and pulsatility index (PI) were significantly higher in common carotid arteries; however, their differences were not meaningful in internal carotid arteries (p<0.05). Conclusions Overall, ADPKD, PD, and HD increase the IMT, PSV, EDV, RI, and PI values of CCA; however, their effect considerable less on the study parameters of ICA. There is no considerable difference among the effects of ADPKD, HD, and PD on the study parameters. Of CKD patients during the first diagnostic and follow-up workups, the measurements of carotid IMT and Doppler indices may provide valuable data for improving success of the clinical management.
    Medical science monitor: international medical journal of experimental and clinical research 01/2014; 20:11-7. DOI:10.12659/MSM.889857 · 1.43 Impact Factor
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    • "At least one family member with ESRD at or after 70 years of age is highly predictive of PKD2 mutations [12]. Because of mild clinical course of ADPKD in grandmother (ESRD at the of 77) the mutational analysis of the PKD2 gene was first done. "
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    ABSTRACT: Background Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of inherited kidney disease that results in renal failure. ADPKD is a systemic disorder with cysts and connective tissue abnormalities involving many organs. ADPKD caused by mutations in PKD1 gene is significantly more severe than the cases caused by PKD2 gene mutations. The large intra-familial variability of ADPKD highlights a role for genetic background. Case presentation Here we report a case of ADPKD family initially appearing unlinked to the PKD1 or PKD2 loci and the influence of mosaicism and hypomorphic allele on the variability of the clinical course of the disease. A grandmother with the PKD1 gene mutation in mosaicism (p.Val1105ArgfsX4) and with mild clinical course of ADPKD (end stage renal failure at the age of 77) seemed to have ADPKD because of PKD2 gene mutation. On the other hand, her grandson had a severe clinical course (end stage renal disease at the age of 45) in spite of the early treatment of mild hypertension. There was found by mutational analysis of PKD genes that the severe clinical course was caused by PKD1 gene frameshifting mutation inherited from his father and mildly affected grandmother in combination with inherited hypomorphic PKD1 allele with described missense mutation (p.Thr2250Met) from his clinically healthy mother. The sister with two cysts and with PKD1 hypomorphic allele became the kidney donor to her severely affected brother. Conclusion We present the first case of ADPKD with the influence of mosaicism and hypomorphic allele of the PKD1 gene on clinical course of ADPKD in one family. Moreover, this report illustrates the role of molecular genetic testing in assessing young related kidney donors for patients with ADPKD.
    BMC Nephrology 03/2013; 14(1):59. DOI:10.1186/1471-2369-14-59 · 1.69 Impact Factor
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