O'Dea D F, Murphy S W, Hefferton D, Parfrey P S
Division of Nephrology, The Health Sciences Center, Memorial University of Newfoundland, St John's, Canada.
Am J Kidney Dis. 1998 Nov;32(5):794-801. doi: 10.1016/s0272-6386(98)70135-0.
To explore the possibility that hereditary factors increase the risk for end-stage renal disease (ESRD), 669 patients with ESRD in the province of Newfoundland, Canada from 1987 to 1993 were studied. Detailed family histories were obtained from 584 (87%) consecutive probands and 499 spousal control subjects. Diseases with a Mendelian pattern of inheritance accounted for 8.4% of the cases; 4.5% of the cases were caused by autosomal dominant polycystic kidney disease (ADPKD). Glomerulonephritis was the original cause of renal failure in 25% of the probands, diabetes mellitus (DM) in 20%, unknown in 14%, interstitial kidney disease in 11%, other disease in 12%, multifactorial in 4%, and hypertension in 5%. In the group without a Mendelian pattern of inheritance, 28% of the probands had a first-, second-, or third-degree relative with renal failure associated with death or dialysis versus 15% of the controls. Compared with 0.4% of the control group, 1.2% of the first-degree relatives of probands developed renal failure (odds ratio [OR]=3.0; 95% confidence interval [CI], 1.7 to 5.2). No difference was observed when risks were compared for second-degree relatives, but a highly significant increased risk was observed for third-degree relatives (OR=2.1; 95% CI, 1.2 to 3.4). The highest rates of affected first-degree relatives occurred in probands with hypertensive renal failure (2.3%), DM (1.6%), and interstitial kidney disease (1.6%). The annual provincial incidence of ESRD, registered with the Canadian Organ Replacement Registry (CORR) from 1981 to 1993 was 79 per million, excluding the 8% of patients with Mendelian inherited disease. The similar rate of ESRD in first-degree relatives of probands without Mendelian inherited disease was 297 per million. We conclude that not only is the contribution of Mendelian inherited diseases to ESRD high, but there is also an increased risk for renal failure in first-degree relatives of probands without a Mendelian inherited renal disease in a white population.
为探究遗传因素是否会增加终末期肾病（ESRD）的发病风险，对1987年至1993年加拿大纽芬兰省的669例ESRD患者进行了研究。从584例（87%）连续的先证者及499例配偶对照者处获取了详细的家族病史。符合孟德尔遗传模式的疾病占病例总数的8.4%；4.5%的病例由常染色体显性多囊肾病（ADPKD）引起。25%的先证者肾衰竭的原因为肾小球肾炎，20%为糖尿病（DM），14%病因不明，11%为间质性肾病，12%为其他疾病，4%为多因素致病，5%为高血压。在不符合孟德尔遗传模式的组中，28%的先证者有与肾衰竭相关的死亡或透析的一级、二级或三级亲属，而对照组这一比例为15%。与对照组的0.4%相比，先证者的一级亲属中有1.2%发生肾衰竭（优势比[OR]=3.0；95%置信区间[CI]，1.7至5.2）。二级亲属的风险比较时未观察到差异，但三级亲属的风险显著增加（OR=2.1；95%CI，1.2至3.4）。受影响的一级亲属比例最高的是患有高血压性肾衰竭（2.3%）、DM（1.6%）和间质性肾病（1.6%）的先证者。1981年至1993年在加拿大器官替代登记处（CORR）登记的该省ESRD年发病率为每百万人口79例，不包括8%患有孟德尔遗传病的患者。无孟德尔遗传病的先证者的一级亲属中ESRD的相似发病率为每百万人口297例。我们得出结论，孟德尔遗传病不仅对ESRD的影响很大，而且在白种人群中，无孟德尔遗传性肾病的先证者的一级亲属发生肾衰竭的风险也会增加。
