A CENTURY OF MORTALITY IN 5 LARGE FAMILIES WITH POLYCYSTIC KIDNEY-DISEASE

Autosomal dominant polycystic kidney disease (ADPKD) characteristicall y leads to end-stage renal failure in the fifth or sixth decade of lif e, which in the absence of therapeutic measures will lead to premature death, To determine excess mortality relative to the general populati on and chromosome 16-linked ADPKD patients, we studied 348 individuals who belonged to five large ADPKD families and who had at least a 50% probability of carrying the gene; the study data derive from a time sp an of approximately one century, Assessment of the diagnosis of ADPKD in the present generation was based on the characteristic roentgenogra phic appearance of polycystic kidneys and was confirmed by DNA analysi s with flanking polymorphic markers around the polycystic gene, In the previous generation, we used Mendelian reasoning after pedigree analy sis to identify persons with a 50% or 100% probability of carrying the polycystic gene, During the study period (1889 to 1992), 83 deaths oc curred in 10,279 person-years, Mortality was increased 1.6-fold (95% c onfidence interval, 1.3 to 2.0) relative to the general population and was independent of the gender of the affected family member as well a s the gender of the transmitting parent, The increased mortality was s trongest in the 50 to 59 year age group (relative mortality, 3.2; 95% confidence interval, 2.0 to 4.8), but decreased after the 1970s, proba bly as a result of improvements in supportive care and, eventually, re nal replacement therapy, In conclusion, the total life-span in ADPKD p atients is improving, but remains low in comparison to the general pop ulation, and the gender of the transmitting parent or of the affected individual does not influence relative mortality. (C) 1995 by the Nati onal Kidney Foundation, Inc.