Causes of death in autosomal dominant polycystic kidney disease.

To determine the causes of death in autosomal dominant polycystic kidney disease (ADPKD) patients and to examine whether the extrarenal manifestations of ADPKD influence the causes of death, the medical records of 129 patients who died between 1956 and 1993 were reviewed; 58% of the 129 patients had an autopsy performed. Seventy-seven percent died after reaching ESRD. The mean age at death increased from 51 yr for those who died before 1975 to 59 yr for those who died after 1975, reflecting the introduction of renal replacement therapies. The most common cause of death before 1975 was infection (30%), followed by uremia (28%) and cardiac disease (21%); after 1975, these were cardiac disease (36%) and infection (24%). Infection was equally prevalent before and after 1975, presenting as sepsis in 94% and directly relating to ADPKD in 47% of these patients. Underlying factors for cardiac death were cardiac hypertrophy, seen in 89% of all autopsied patients, and coronary artery disease, seen in 81%. A neurologic event was the cause of death in 12% of patients; these were ruptured intracranial aneurysm in 6%, hypertensive intracranial hemorrhage in 5%, and ischemic stroke in 1%. The mean age of those who died of ruptured intracranial aneurysm was 37 yr. No patient died of renal cancer. Liver cysts were the most common extrarenal manifestation, seen in 70% of the autopsied cases; cysts in other organs were very rare. Colonic diverticula were found in 21%. Thus, the renal and extrarenal manifestations of ADPKD are important contributors to morbidity and mortality.

Is there evidence for anticipation in autosomal-dominant polycystic kidney disease?

The heritability of autosomal-dominant polycystic kidney disease (ADPKD) is marked by an apparent high mutation rate, neonatal onset of disease in some patients and intrafamily variability. These findings raise the possibility of genetic anticipation in ADPKD as has been observed in fragile-X syndrome, myotonic dystrophy and Huntington's disease. We reviewed 242 pedigrees obtained during our prospective studies on the natural history of ADPKD. Anticipation was defined as a 10 year earlier onset of ESRD in offspring as compared to their affected parent or a child diagnosed in the first year of life. Due to the slowly progressive nature of ADPKD, 148 pedigrees were uninformative. Anticipation of ESRD was found in 49% of informative families in at least one parent-offspring pair, and when early onset children were included, 53% of informative families had at least one parent-offspring pair with anticipation. Moreover, the transmitting parent in the pairs with anticipation was more often the mother than the father, similar to myotonic dystrophy, where the most dramatic form of anticipation, congenital disease, occurs almost exclusively with maternal transmission. These observations suggest that ADPKD may be another genetic disorder characterized by heritable unstable DNA.

The spectrum of autosomal dominant polycystic kidney disease in children.

The natural history of autosomal dominant polycystic kidney disease (ADPKD) has not been well described in children, and it is not known whether a relationship exists between renal structural abnormalities and function in children as has been seen in adults. Therefore, 140 children from 67 ADPKD families were studied in a prospective study. Only 22 children came with a previous diagnosis of ADPKD. In 44% of all children, at least one cyst was found on ultrasound at a mean age of 8.7 yr. Of these, 60% were classified as having moderate disease on the basis of a total cyst number of 1 to 10 cysts, whereas 40% were considered to have severe disease with a total of more than 10 cysts. There was a significant relationship between the severity of the renal structural involvement and the frequency of flank and back pain, hypertension, and impaired renal concentrating capacity. However, GFR were not reduced in children with ADPKD and did not relate to structural severity. Thirty-nine children were seen for a follow-up visit 2 to 5 yr after the initial visit. No child had progressed from nonaffected to affected with ADPKD, but three of four children with only one cyst at the time of the initial study had progressed to bilateral cysts. Among the 22 ADPKD children who had a follow-up study, there was progression of the disease, reflected by an increase in cyst number and an increase in the frequency of pain and hypertension. However, GFR remained stable in all children.(ABSTRACT TRUNCATED AT 250 WORDS)

Natural history of autosomal dominant polycystic kidney disease.

At least two different genes, which have been mapped to chromosomes 4 and 16, cause autosomal dominant polycystic kidney disease, a disorder with renal and extrarenal manifestations. Although gene-linkage testing is possible, the disease is diagnosed mainly through ultrasonography. Renal disease is characterized clinically by hypertension, acute and chronic pain, and variable progression to end-stage renal disease. Extrarenal manifestations include liver cysts, which may lead to complications; ruptured intracranial aneurysms; cardiac valvular disease; colonic diverticula; and inguinal hernias. Disease management is directed at minimizing and treating the complications of this illness.

Characteristics of very early onset autosomal dominant polycystic kidney disease.

Eleven children from eight families with autosomal dominant polycystic kidney disease who were diagnosed in utero (6 children) or in the first year of life (5 children) are reported here. Four children were evaluated for symptoms and three because of a sibling with very early onset disease. In three children, abnormal kidneys were found incidentally on a pregnancy screening ultrasound, and in only one child, the diagnosis was made by an ultrasound specifically directed at detecting polycystic kidney disease. Females were disproportionately represented among both the affected parents and offspring. Eight of the children were girls, and all affected parents were mothers. In three families, the parent's diagnosis was established only after the birth of the affected child. In two of these and in one other family, the mother's disease appeared to be the result of a new mutation. The most consistent renal ultrasonographic findings in the children were enlargement and increased echogenicity. On follow-up over 3 to 15 yr (mean, 6.8 yr) two children had ESRD and eight children had normal or nearly normal renal function as assessed by creatinine clearance. Renal concentrating ability was reduced in four children in whom it was measured. All children had bilateral renal cysts on follow-up, and nine children were hypertensive. Possible risk factors for early-onset disease identified in this study were an affected mother, an affected sibling, and an apparent parental new mutation. Symptoms and complications occurred frequently, but outcome was better than reported previously.