Autosomal dominant polycystic kidney disease.

The lack of reliable data on frequency, age of onset, survival, spontaneous mutation rate and prognosis in autosomal dominant polycystic kidney disease is a continual source of frustration to physicians involved in counselling patients and their relatives. The only major study to address all of these issues in a defined population was presented by Dalgaard as a 251-page doctoral thesis in 1957 [1]. Although Dalgaard's work is a perfect example of careful characterization of a genetic disease, the development of more sensitive, non-invasive cyst imaging methods and the advent of chronic dialysis and transplantation have weakened many of his conclusions. Fortunately, Davies et al. [2] have begun to obtain the data required to satisfy the urgent need for answers to the above questions by studying the families of all affected individuals in a Welsh population of 2.1 million. The first report of this study deals with prevalence, de novo mutation rate and trends in dialysis acceptance and survival [2]. Davies et al. estimate the prevalence of autosomal dominant polycystic kidney disease in Wales to be 1:2459, a figure which is substantially lower than the previous estimates of between 1:400 and 1:1000 in other Caucasian populations [1,3]. There are several possible explanations for this discrepancy. First, all the probands in the Welsh study had symptomatic renal disease or hypertension. If a substantial number of all patients are asymptomatic, and if asymptomatic disease runs true in families, the selection of symptomatic probands would be expected to lead to low estimates of frequency. The fact that higher frequencies of polycystic kidney disease have been observed at autopsy than have been estimated clinically lend credence to this possibility. Hatfield and Pfister [4], for example, found that less than half of patients with polycystic kidney disease diagnosed at autopsy had symptoms, and only one of 32 asymptomatic cases had a family history. The increasing use of ultrasonography in the screening of undiagnosed abdominal illness is also bringing many additional cases of asymptomatic polycystic kidney disease to light. Therefore, whereas symptomatic disease was previously considered to be the predominant form, it now appears that it may be just the tip of the iceberg. The difference between symptomatic and asymptomatic disease has not been explained at the molecular level but Parfrey et al. [5] have recently shown that a form of autosomal dominant polycystic kidney diseases that is not linked to chromosome 16 markers has a significantly better prognosis than the linked form. Once the genes coding for autosomal dominant polycystic kidney disease have been cloned, direct analysis of their mutations may allow a better understanding of the genetic influences on prognosis.