Các tác động nguyên nhân phi tuyến của tỷ lệ lọc cầu thận ước lượng đến nguy cơ nhồi máu cơ tim: Nghiên cứu ngẫu nhiên Mendelian

BMC Medicine - Tập 20 - Trang 1-12 - 2022
Sehoon Park1,2, Soojin Lee3,4, Yaerim Kim5, Semin Cho4,6, Hyeok Huh6, Kwangsoo Kim7, Yong Chul Kim6, Seung Seok Han6,8, Hajeong Lee6, Jung Pyo Lee4,8,9, Kwon Wook Joo4,6,8, Chun Soo Lim4,8,9, Yon Su Kim1,4,6,8, Dong Ki Kim4,6,8
1Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea
2Department of Internal Medicine, Armed Forces Capital Hospital, Gyeonggi-do, South Korea
3Department of Internal Medicine, Uijeongbu Eulji University Medical Center, Seoul, South Korea
4Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
5Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea
6Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
7Transdisciplinary Department of Medicine & Advanced Technology, Seoul National University Hospital, Seoul, South Korea
8Kidney Research Institute, Seoul National University, Seoul, South Korea
9Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, South Korea

Tóm tắt

Các nghiên cứu quan sát trước đây đã gợi ý rằng sự giảm tỷ lệ lọc cầu thận ước lượng (eGFR) hoặc một giá trị eGFR vượt mức bình thường có liên quan đến các nguy cơ tim mạch xấu. Tuy nhiên, một nghiên cứu ngẫu nhiên Mendelian (MR) trước đó dưới giả định tuyến tính đã báo cáo không có tác động nguyên nhân từ eGFR đến nguy cơ nhồi máu cơ tim (MI). Việc điều tra thêm về tác động nguyên nhân phi tuyến của chức năng thận được đánh giá bởi eGFR đối với nguy cơ MI qua phân tích MR phi tuyến là điều cần thiết. Trong nghiên cứu MR này, các công cụ di truyền cho log-eGFR dựa trên creatinine huyết thanh đã được phát triển từ các mẫu của người châu Âu có trong phân tích tổng hợp nghiên cứu liên kết toàn bộ bộ gen CKDGen (N=567,460). Các công cụ thay thế cho log-eGFR dựa trên cystatin C đã được phát triển từ một nghiên cứu GWAS của những cá nhân châu Âu đã bao gồm dữ liệu CKDGen và UK Biobank (N=460,826). Phân tích MR phi tuyến cho nguy cơ MI đã được thực hiện sử dụng phương pháp đa thức phân đoạn và phương pháp tuyến tính đoạn trên dữ liệu từ những cá nhân có nguồn gốc Anh trắng trong UK Biobank (N=321,024, với 12,205 trường hợp MI). Phân tích MR phi tuyến đã chứng minh một mối liên hệ hình chữ U (giá trị P bậc hai < 0.001) giữa nguy cơ MI và các giá trị eGFR (creatinine) được dự đoán theo di truyền, khi nguy cơ MI tăng lên khi eGFR giảm trong khoảng eGFR thấp và nguy cơ tăng lên khi eGFR tăng trong khoảng eGFR cao. Kết quả tương tự vẫn được ghi nhận ngay cả sau khi điều chỉnh cho các biến lâm sàng, chẳng hạn như huyết áp, bệnh tiểu đường, rối loạn lipid máu, hoặc mức vi albumin niệu, hoặc khi eGFR (cystatin C) dự đoán theo di truyền được đưa vào như một yếu tố phơi nhiễm. eGFR được dự đoán theo di truyền có liên quan đáng kể đến nguy cơ MI với hình dạng parabol, điều này cho thấy rằng sự suy giảm chức năng thận, bất kể bởi eGFR giảm hay vượt mức bình thường, có thể liên quan nguyên nhân đến nguy cơ MI cao hơn.

Từ khóa


Tài liệu tham khảo

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