The genetic basis of endstage renal disease in the Newfoundland population

• Main Author: O'Dea, Daneile Flynn, 1971-
• Other Authors: Memorial University of Newfoundland. Faculty of Medicine
• Format: Thesis
• Language: English
• Published: 1997
• Subjects: Chronic renal failure > Newfoundland and Labrador > Genetic aspects; Kidney Failure; Chronic > Genetics > Newfoundland and Labrador; Newfoundland; Canada; Newfoundland studies; University of Newfoundland
• Online Access: http://collections.mun.ca/cdm/ref/collection/theses3/id/170738

Thesis (M. Sc.)--Memorial University of Newfoundland, 1998. Medicine Bibliography: leaves 98-135 .next of kin could be identified for 65 (11%) of the probands and 20 (3.4%) of potential controls refused to participate. -- To determine the original cause of renal disease in the probands the medical records were reviewed. The information gathered was reviewed by a single clinical nephrologist who was blinded to the identity of the patient Diseases with a Mendelian pattern of inheritance accounted for ESRD in 8.4% of the cases, 4.5% being autosomal dominant polycystic kidney disease, 2.5% Alport's syndrome and the remaining 1.4% to other genetic diseases. This group of cases was excluded from the subsequent familial risk analysis. Glomerulonephritis was the renal diagnosis in 25% of the probands, diabetes mellitus in 20%, unknown in 14%, other in 12%, interstitial in 11%, hypertensive sclerosis in 5% and multiple causes in 4%. -- Primary outcomes were defined as a positive family history of renal failure associated with renal replacement therapy in a first, second or third degree relative of a proband or control. In the group without a Mendelian pattern of inheritance, 28% had a first, second or third degree relative with renal failure associated with death or requiring dialysis versus 15% of controls. 1.2% of first degree relatives of probands developed renal failure compared to 0.4% of first degree relatives of controls (OR=3.0,95% CI: 1.7-5.2). No difference was observed in risk for second degree relatives, but a highly significant increased risk was observed for third degree relatives of probands (OR=2.1,95% CI: 1.2-3.4). The highest rate of affected first degree relatives occurred in relatives of probands with hypertensive nephrosclerosis (2.3%), diabetes mellitus (1.6%) and interstitial disease (1.6%). -- The second control group utilized was the provincial population. The proportion of relatives of probands registered with the Canadian Organ Replacement Registry (CORR) was compared to the rate of the general population. The provincial incidence of ESRD, registered with CORR, from 1981-1993 was 79/million, excluding 8% of patients with Mendelian inherited disease. The comparable rate of ESRD in first degree relatives of probands without Mendelian inherited renal disease was 297/million almost four times the provincial rate. The comparable rate for first degree relatives of controls was 135/million. -- Conclusions: We conclude that not only is the contribution of Mendelian inherited disease to ESRD high, but there is also an increased risk of renal failure in first degree relatives of probands without Mendelian inherited renal disease in a Caucasian population.