2 mm) was significantly higher in non-responder group (p = 0.038). Among 70 patients in 2nd study population, 45 patients were responder (64.2%), and the proportion of patients who had larger parathyroid glands than cutoff value was significantly higher in nonresponder group (responsder vs nonresponder 60.5 vs 87.0%, p = 0.028). Conclusions: Measurement of parathyroid gland diameters with CT scan was useful to predict the response of cinacalcet therapy. KURASHIGE MAHIRO1,2, HANAOKA KAZUSHIGE1, IMAMURA MINAKO2, UDAGAWA TAKASHI1, KAWAGUCHI YOSHINDO1,3, HASEGAWA TOSHIO1,3, HOSOYA TATSUO1, YOKOO TAKASHI1, MAEDA
SHIRO2 1Division of Kidney and Hypertension, Department of Internal Medicine, The Jikei University, School of Medicine, Minato, Tokyo, Japan; 2Laboratory for Endocrinology, Metabolism and Protein Tyrosine Kinase inhibitor Kidney Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan; 3Department of Medicine, FK228 cell line Kanagawa Prefectural Shiomidai Hospital, Yokohama, Kanagawa, Japan Introduction: Autosomal
Dominant Polycystic Kidney Disease (ADPKD) is a common hereditary kidney disorder, and most of its heritability could be explained by mutations in two genes, PKD1 and PKD2 in populations of European descent. However little is known about Asian ADPKD including Japanese. To elucidate the genotypic and phenotypic characteristics of ADPKD in Japanese populations, we performed a comprehensive search for mutations in PKD1 and PKD2 in 180 Japanese ADPKD patients from 161 unrelated Anacetrapib families. Methods: We screened the entire coding regions and their flanking regions of the PKD1/PKD2 by direct sequencing, and evaluated candidates for causal variants by subsequent in-silico and/or bio-analyses. We also searched for large genomic rearrangements within PKD1/PKD2 loci by using quantitative PCR. Results: We identified 111 mutations within 134 families (detection rate = 83.2%), including 88 PKD1 mutations (48 truncating, 6 atypical splice, 29 missense and 5 in-frame mutations) in 96 families, and 23 PKD2 mutations (18 truncating, 1
atypical splice and 3 missense mutations and 1 large deletion) in 38 families. Patients with PKD2 mutations account for 23.6% of all Japanese ADPKD families in this study. Seventy-four out of the 111 mutations have not been reported previously. The estimated glomerular filtration rate (eGFR) decline was significantly faster in patients with PKD1 mutations than in those with PKD2 mutations (−3.25 and −2.08 ml·min−1·year−1 for PKD1 and PKD2, respectively, p < 0.01). Conclusion: Mutations within PKD1 and PKD2 can be linked to most of the cases of Japanese ADPKD, and the renal function decline was faster in patients with PKD1 mutations than in those with PKD2 mutations also in the Japanese ADPKD. We also found that PKD2 mutations were more frequent in Japanese ADPKD than that in European or American ADPKD.