Summary: | <p><strong>Background:</strong></p>
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.
<p><strong>Methods:</strong></p>
Three hundred eleven thousand one hundred nineteen 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]<60 mL (min·1.73m2), 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·1.73m2) considered evidence of glomerular hyperfiltration.
<p><strong>Results:</strong></p>
Twenty-one thousand six hundred twenty-three participants had CKD: 7781 with reduced eGFR and 15 500 with albuminuria. One thousand eight hundred twenty-eight participants had an eGFR ≥120 mL (min·1.73m2). Each genetically predicted 10 mm Hg higher systolic BP and 5 mm Hg 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·1.73m2]) were 49% higher (95% CI, 1.21–1.84) for each genetically predicted 10 mm Hg higher systolic BP. Associations with CKD and hyperfiltration were similar irrespective of preexisting diabetes, vascular disease, or different levels of adiposity.
<p><strong>Conclusions:</strong></p>
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.
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