Medical Research Council Population Health Research Unit at the University of Oxford, Nuffield Department of Population Health (NDPH), United Kingdom (N.S., W.G.H., S.Y.A.N., M.T., D.Z., J.E., M.J.L., C.B., R.H., J.C.H.).
Clinical Trial Service Unit and Epidemiological Studies Unit, NDPH (N.S., W.G.H., F.M., M.I., P.J., S.Y.A.N., M.T., D.Z., J.E., M.J.L., C.B., R.H., J.C.H.), University of Oxford, Oxford, United Kingdom.
Hypertension. 2022 Dec;79(12):2671-2681. doi: 10.1161/HYPERTENSIONAHA.122.19354. Epub 2022 Sep 9.
It is well established that decreased kidney function can increase blood pressure (BP), but it is unproven whether moderately elevated BP causes chronic kidney disease (CKD) or glomerular hyperfiltration.
311 119 White British UK Biobank participants were included in logistic regression analyses to estimate the odds of CKD (defined as long-term kidney replacement therapy, estimated glomerular filtration rate [eGFR]< 60mL/min/1.73m, or urinary albumin:creatinine ratio ≥3 mg/mmol) associated with higher genetically predicted BP using genetic risk scores comprising 219 systolic and 223 diastolic BP loci. Analyses estimating associations with clinical categories of eGFR and urinary albumin:creatinine ratio were also conducted, with an eGFR ≥120 mL (min·1.73m) considered evidence of glomerular hyperfiltration.
21 623 participants had CKD: 7781 with reduced eGFR and 15 500 with albuminuria. 1828 participants had an eGFR ≥120 mL/min/1.73m. Each genetically predicted 10 mmHg higher systolic BP and 5 mmHg higher diastolic BP were associated with a 37% (95% CI, 1.29-1.45) and 19% (1.14-1.25) higher odds of CKD, respectively. Associations were evident for both the reduced eGFR and albuminuria components of the CKD outcome. The odds of hyperfiltration (versus an eGFR ≥60 and <90 mL/min/1.73m were 49% higher (95% CI, 1.21-1.84) for each genetically predicted 10 mmHg higher systolic BP. Associations with CKD and hyperfiltration were similar irrespective of preexisting diabetes, vascular disease, or different levels of adiposity.
In this general population, genetic epidemiological evidence supports a causal role of life-long differences in BP for decreased kidney function, glomerular hyperfiltration, and albuminuria. Physiological autoregulation may not afford complete renal protection against the moderate BP elevations.
已有研究证实，肾功能下降可导致血压升高（BP），但尚未明确血压轻度升高是否会导致慢性肾脏病（CKD）或肾小球高滤过。
共纳入 311119 名白种人英国生物银行参与者，采用逻辑回归分析估计遗传风险评分与 CKD（定义为长期肾脏替代治疗、估算肾小球滤过率[eGFR]＜60ml/min/1.73m2 或尿白蛋白/肌酐比值≥3mg/mmol）之间的关联，遗传风险评分包含 219 个收缩压和 223 个舒张压相关位点。还进行了与 eGFR 和尿白蛋白/肌酐比值临床分类相关的分析，eGFR≥120ml/min（min·1.73m）被认为是肾小球高滤过的证据。
共有 21623 名参与者患有 CKD：7781 名参与者 eGFR 降低，15500 名参与者存在白蛋白尿。1828 名参与者 eGFR≥120ml/min/1.73m。遗传预测的收缩压每升高 10mmHg 和舒张压每升高 5mmHg，分别与 CKD 的风险增加 37%（95%CI，1.29-1.45）和 19%（1.14-1.25）相关。在 CKD 的降低 eGFR 和白蛋白尿两方面均存在这种关联。与 eGFR≥60 且＜90ml/min/1.73m 相比，遗传预测的收缩压每升高 10mmHg，发生高滤过（肾小球高滤过）的几率增加 49%（95%CI，1.21-1.84）。无论是否存在糖尿病、血管疾病或不同程度的肥胖，与 CKD 和高滤过的关联均相似。
在本普通人群中，遗传流行病学证据支持终生血压差异导致肾功能下降、肾小球高滤过和白蛋白尿的因果关系。生理自动调节可能无法完全防止中度血压升高对肾脏的损害。
