Blood Pressure Changes in Young Adulthood Associated with Subsequent Decline in Kidney Function

Studies of hypertension and related complications are conducted most often in populations >40 years of age; studies of outcomes associated with elevated blood pressure in young adulthood have been focused on associations between elevated blood pressure and cardiovascular risks. There are few available data on whether there is an association between exposure to elevated blood pressure early in life and adverse renal outcomes.

Elaine Ku, MD, MAS, and colleagues recently conducted an observational cohort study designed to assess the association between changes in blood pressure between ages 18 and 40 years and subsequent decline in kidney function in later life. The researchers sought to test the hypothesis that there would be an association between higher blood pressure during young adulthood and faster kidney decline. They also hypothesized that the association between changes in blood pressure during young adulthood, even at blood pressures currently not considered to meet the definition for hypertension, and future reduction in kidney function would remain strong. Results were reported in the American Journal of Kidney Diseases [2018;72(2):243-250]

The researchers utilized data from the CARDIA (Coronary Artery Risk Development in Young Adulthood) study, a prospective cohort study designed to examine the development of cardiovascular risk factors in young adults. The current analysis included data from participant examinations conducted at years 0, 2, 5, 7, 10, 15, and 20. At each visit, participants had blood pressure assessments. Starting at year 10 (1995-1996), the examinations included measurement of kidney function (urinary albumin, serum creatinine, and cystatin C).

The analysis included data on 3429 participants. At the time of enrollment in CARDIA, mean age was 25 years, approximately half were white and women, and very few had comorbid conditions such as diabetes or use of antihypertensive medications. At year 10, approximately 6% had diabetes and 3% were being treated with antihypertensive medications. Mean follow-up in the CARDIA study was 19.4 years.

An analysis of the distribution of change in blood pressure (determined from best linear unbiased predictions in linear mixed models) between year 0 and year 10 found clinically significant declines in systolic blood pressure (defined as >5-mm Hg decline over 5 years) in very few participants.

To examine model assumptions and understand the relative contribution of one-time blood pressures versus change in blood pressure to subsequent changes in estimated glomerular filtration rate based on serum cystatin C (eGFRcys), the researchers cross-tabulated changes in eGFRs across nine categories, defined by tertiles of change in blood pressure and tertiles of year-10 blood pressure. Following stratification by year-10 blood pressure, there was as association between qualitatively higher systolic blood pressure and diastolic blood pressure slope tertiles and a more rapid decline in eGFRcys (there was some overlap in confidence intervals [CIs], however).

To evaluate the association between blood pressure slope and change in eGFRcys, the cohort was divided into two time periods: years 0 to 10 were used for blood pressure determination and years 10 to 20 were used for determination of kidney function. The analysis found that every 10-mm Hg increase in systolic blood pressure per 5-year period was associated with a faster annual decline in eGFRcys (–0.72 [95% CI, –0.98 to –0.46], mL/min/1.73 m2 per year). Every 10-mm Hg increase in diastolic blood pressure per 5-year period was associated with a statistically significant annual decline in eGFRcys (­–0.80 [95% CI, ­–1.21 to ­–0.40] mL/min/1.73 m2 per year). The association between change in systolic blood pressure between years 0 and 10 and subsequent decline in kidney function remained statistically significant in this model, even following adjustment for year-10 systolic blood pressure. The effect size was not substantially altered after further adjustment for albuminuria at year 10.

Every 10-mm Hg increase in diastolic blood pressure per 5-year period was associated with a statistically significant annual decline in eGFRcys (­–0.80 [95% CI, ­–1.21 to ­–0.40] mL/min/1.73 m2 per year) in a second model. Diastolic blood pressure slope remained statistically significantly associated with subsequent decline in kidney function, even after accounting for 10-year diastolic blood pressure.

When the analyses allowed blood pressure slopes to vary over time in a time-dependent manner, findings regarding the associations between blood pressure slope and subsequent kidney function were similar to those of the primary analysis for systolic blood pressure. The association between diastolic blood pressure slope and decline in subsequent kidney function was no longer significant after accounting for 10-year diastolic blood pressure.

When one-time measurement of observed blood pressure was used as an independent predictor (year-10 systolic blood pressure and diastolic blood pressure), there was a statistically significant association between the blood pressures and decline in kidney function. Each 10-mm Hg higher baseline systolic blood pressure was associated with a faster annual decline in eGFR (­–0.09 [95% CI, –0.13 to –0.06] mL/min/1.73 m2 per year). There was also an association between each 10-mm Hg higher level of diastolic blood pressure at baseline and a faster annual decline in eGFR (–0.07 [95% CI, 0.12 to –0.03] mL/min/1.73 m2 per year). However, adding blood pressure slope to the models attenuated the association between one-time measures of systolic blood pressure and subsequent decline in kidney function.

Study limitations included the observational design of the study, and lack of data on measured GFR to confirm changes in kidney function estimated using cystatin C concentration.

“In conclusion, our results suggest that increasing blood pressures over a 10-year time span in young adulthood are significantly associated with early kidney function decline in individuals without decreased kidney function or clinical hypertension at baseline. Close monitoring of changes in blood pressure over time during early adulthood may help identify individuals at higher risk for subsequent renal complications. Young adults who have continued increases in their blood pressures over time, even in the absence of clinical hypertension, may warrant screening for kidney disease,” the researchers said.

Takeaway Points

  1. Researchers utilized data from the Coronary Artery Risk Development in Young Adulthood study to examine the association between changes in blood pressure between the ages of 18 and 40 years and subsequent decline in kidney function.
  2. There was an association between every 10-mm Hg higher level of systolic blood pressure and diastolic blood pressure in year 10 and a change in estimated glomerular filtration rate of –0.09 and –0.07 mL/min/1.73 m2, respectively.
  3. Following adjustment for comorbid conditions and systolic blood pressure at year 10, there was an association between every 10-mm Hg increase in systolic blood pressure slope between years 0 and 10 and a subsequent –0.52 mL/min/1.73 m2 change in kidney function.