The genetic basis of endstage renal disease in the Newfoundland population

O'Dea, Daneile Flynn (1997) The genetic basis of endstage renal disease in the Newfoundland population. Masters thesis, Memorial University of Newfoundland.

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The objectives of the current research were (1) to determine the contribution of Mendilian inherited disease to the burden of disease caused by Endstage renal disease; (2) to explore the possibility that polygenic disorders could contribute to the development of Endstage renal disease; and (3) to describe the natural history of single-gene disorders associated with Endstage renal disease identified in the Newfoundland population, with particular focus on new data associated with Bardet-Biedl Syndrome. – To determine the risk of renal failure in family members of probands with Endstage Renal Disease (ESRD), all patients who were receiving treatment for ESRD during 1987-1998 in the province of Newfoundland and Labrador, Canada were studied. Detailed family histories were taken from 584 (87%) of the 669 eligible probands. Of the 85 patients with incomplete family histories, 60 (9%) could not be located and 25 (3.6%) refused to participate. The rate of renal failure in relatives of probands was compared to the rate of renal failure in spousal control families. Spousal controls were chosen because they have been shown to be less subject to recall bias and generally are similar to their spouses for environmental influences. Family histories were collected on 499 (85.4%) of the eligible spouses of probands. No spouses or next of kin could be identified for 65 (I 1%) 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 or 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 1981-1993was 79/million, excluding 8% or 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 or renal Failure in first degree relatives of probands without Mendelian inherited renal disease in a Caucasian population.

Item Type: Thesis (Masters)
Item ID: 11160
Additional Information: Bibliography: leaves 98-135.
Department(s): Medicine, Faculty of
Date: 1997
Date Type: Submission
Library of Congress Subject Heading: Chronic renal failure--Newfoundland and Labrador--Genetic aspects.
Medical Subject Heading: Kidney Failure, Chronic--genetics--Newfoundland and Labrador.

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