17
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: not found
      • Article: not found

      New treatment paradigms for ADPKD: moving towards precision medicine

      ,
      Nature Reviews Nephrology
      Springer Nature

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Related collections

          Most cited references152

          • Record: found
          • Abstract: found
          • Article: not found

          Unified criteria for ultrasonographic diagnosis of ADPKD.

          Individuals who are at risk for autosomal dominant polycystic kidney disease are often screened by ultrasound using diagnostic criteria derived from individuals with mutations in PKD1. Families with mutations in PKD2 typically have less severe disease, suggesting a potential need for different diagnostic criteria. In this study, 577 and 371 at-risk individuals from 58 PKD1 and 39 PKD2 families, respectively, were assessed by renal ultrasound and molecular genotyping. Using sensitivity data derived from genetically affected individuals and specificity data derived from genetically unaffected individuals, various diagnostic criteria were compared. In addition, data sets were created to simulate the PKD1 and PKD2 case mix expected in practice to evaluate the performance of diagnostic criteria for families of unknown genotype. The diagnostic criteria currently in use performed suboptimally for individuals with mutations in PKD2 as a result of reduced test sensitivity. In families of unknown genotype, the presence of three or more (unilateral or bilateral) renal cysts is sufficient for establishing the diagnosis in individuals aged 15 to 39 y, two or more cysts in each kidney is sufficient for individuals aged 40 to 59 y, and four or more cysts in each kidney is required for individuals > or = 60 yr. Conversely, fewer than two renal cysts in at-risk individuals aged > or = 40 yr is sufficient to exclude the disease. These unified diagnostic criteria will be useful for testing individuals who are at risk for autosomal dominant polycystic kidney disease in the usual clinical setting in which molecular genotyping is seldom performed.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Imaging classification of autosomal dominant polycystic kidney disease: a simple model for selecting patients for clinical trials.

            The rate of renal disease progression varies widely among patients with autosomal dominant polycystic kidney disease (ADPKD), necessitating optimal patient selection for enrollment into clinical trials. Patients from the Mayo Clinic Translational PKD Center with ADPKD (n=590) with computed tomography/magnetic resonance images and three or more eGFR measurements over ≥6 months were classified radiologically as typical (n=538) or atypical (n=52). Total kidney volume (TKV) was measured using stereology (TKVs) and ellipsoid equation (TKVe). Typical patients were randomly partitioned into development and internal validation sets and subclassified according to height-adjusted TKV (HtTKV) ranges for age (1A-1E, in increasing order). Consortium for Radiologic Imaging Study of PKD (CRISP) participants (n=173) were used for external validation. TKVe correlated strongly with TKVs, without systematic underestimation or overestimation. A longitudinal mixed regression model to predict eGFR decline showed that log2HtTKV and age significantly interacted with time in typical patients, but not in atypical patients. When 1A-1E classifications were used instead of log2HtTKV, eGFR slopes were significantly different among subclasses and, except for 1A, different from those in healthy kidney donors. The equation derived from the development set predicted eGFR in both validation sets. The frequency of ESRD at 10 years increased from subclass 1A (2.4%) to 1E (66.9%) in the Mayo cohort and from 1C (2.2%) to 1E (22.3%) in the younger CRISP cohort. Class and subclass designations were stable. An easily applied classification of ADPKD based on HtTKV and age should optimize patient selection for enrollment into clinical trials and for treatment when one becomes available.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Volume progression in polycystic kidney disease.

              Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive enlargement of cyst-filled kidneys. In a three-year study, we measured the rates of change in total kidney volume, total cyst volume, and iothalamate clearance in patients with ADPKD. Of a total of 241 patients, in 232 patients without azotemia who were 15 to 46 years old at baseline we used magnetic-resonance imaging to correlate the total kidney volume and total cyst volume with iothalamate clearance. Statistical methods included analysis of variance, Pearson correlation, and multivariate regression analysis. Total kidney volume and total cyst volume increased exponentially, a result consistent with an expansion process dependent on growth. The mean (+/-SD) total kidney volume was 1060+/-642 ml at baseline and increased by a mean of 204+/-246 ml (5.27+/-3.92 percent per year, P<0.001) over a three-year period among 214 patients. Total cyst volume increased by 218+/-263 ml (P<0.001) during the same period among 210 patients. The baseline total kidney volume predicted the subsequent rate of increase in volume, independently of age. A baseline total kidney volume above 1500 ml in 51 patients was associated with a declining glomerular filtration rate (by 4.33+/-8.07 ml per minute per year, P<0.001). Total kidney volume increased more in 135 patients with PKD1 mutations (by 245+/-268 ml) than in 28 patients with PKD2 mutations (by 136+/-100 ml, P=0.03). Kidney enlargement resulting from the expansion of cysts in patients with ADPKD is continuous and quantifiable and is associated with the decline of renal function. Higher rates of kidney enlargement are associated with a more rapid decrease in renal function. Copyright 2006 Massachusetts Medical Society.
                Bookmark

                Author and article information

                Journal
                Nature Reviews Nephrology
                Nat Rev Nephrol
                Springer Nature
                1759-5061
                1759-507X
                October 9 2017
                October 9 2017
                :
                :
                Article
                10.1038/nrneph.2017.127
                28989174
                ba00e281-82b7-418e-b576-7625713baace
                © 2017
                History

                Comments

                Comment on this article