Abstract
Optimal blood pressure (BP) management in children with chronic kidney disease (CKD) slows progression to end-stage renal disease. Studies often base progression risk on a single baseline BP measurement, which may underestimate risk. To determine whether time-varying BP measurements are associated with a higher risk of progression of CKD than baseline BP measurements. The ongoing longitudinal, prospective cohort study Chronic Kidney Disease in Children (CKID) recruited children from January 19, 2005, through March 19, 2014, from pediatric nephrology centers across North America, with data collected at annual study visits. Participants included children aged 1 to 16 years with a diagnosis of CKD and a glomerular filtration rate (GFR) of 30 to 90 mL/min/1.73 m2. Data were analyzed from February 11, 2005, through February 13, 2018. Office BP measurement classified as less than 50th percentile, 50th to less than 90th percentile, or at least 90th percentile. Blood pressure categories were treated as time fixed (baseline) or time varying (updated at each visit) in models. A composite renal outcome (50% GFR reduction from baseline, estimated GFR less than 15 mL/min/1.73 m2, or dialysis or transplant). Pooled logistic models using inverse probability weighting estimated the hazard odds ratio (HOR) of the composite outcome associated with each BP category stratified by CKD diagnosis. A total of 844 children (524 [62.1%] male; median age, 11 [interquartile range, 8-15] years; 151 [17.9%] black; 580 [68.7%] with nonglomerular CKD; and 264 [31.3%] with glomerular CKD) with complete baseline data and median follow-up of 4 (interquartile range, 2-6) years were included. One hundred ninety-six participants with nonglomerular diagnoses (33.8%) and 99 with glomerular diagnoses (37.5%) reached the composite outcome. Baseline systolic BP in at least the 90th percentile was associated with a higher risk of the composite outcome (HOR for nonglomerular disease, 1.58 [95% CI, 1.07-2.32]; HOR for glomerular disease, 2.85 [95% CI, 1.64-4.94]) compared with baseline systolic BP in less than the 50th percentile. Time-fixed estimates were substantially lower compared with time-varying systolic BP percentile categories (HOR among those with nonglomerular CKD, 3.75 [95% CI, 2.53-5.57]; HOR among those with glomerular diagnoses, 5.96 [95% CI, 3.37-10.54]) comparing those at or above the 90th percentile vs below the 50th percentile. Adjusted models (adjusted for proteinuria and use of antihypertensives) attenuated the risk in nonglomerular CKD (adjusted HOR for baseline measurement, 1.52 [95% CI, 0.98-2.36]; adjusted HOR for time-varying measurement, 2.25 [95% CI, 1.36-3.72]) and in glomerular CKD (adjusted HOR for baseline, 0.97 [95% CI, 0.39-2.36]; adjusted HOR for time-varying measurement, 1.41 [95% CI, 0.65-3.03]). Similar results were observed for diastolic BP. Among children with nonglomerular CKD included in this study, elevated time-varying BP measurements were associated with a greater risk of CKD progression compared with baseline BP measurement. This finding suggests that previous studies using only baseline BP likely underestimated the association between BP and CKD progression.
Highlights
Hypertension is a common comorbidity in children with CKD1,2 and is associated with progression of chronic kidney disease (CKD) in cohort studies and trials.[3,4,5] Effective treatment of hypertension is known to slow the rate of progression to end-stage renal disease, as highlighted by the Effect of Strict Blood Pressure Control and Angiotensin-Converting Enzyme Inhibition on the Progression of Chronic Renal Failure in Pediatric Patients (ESCAPE) trial,[4] which demonstrated that improved blood pressure (BP) management delayed the progression of CKD, especially among those with proteinuria
Baseline systolic BP in at least the 90th percentile was associated with a higher risk of the composite outcome (HOR for nonglomerular disease, 1.58 [95% CI, 1.07-2.32]; hazard odds ratio (HOR) for glomerular disease, 2.85 [95% CI, 1.64-4.94]) compared with baseline systolic BP in less than the 50th percentile
Time-fixed estimates were substantially lower compared with time-varying systolic BP percentile categories (HOR among those with nonglomerular CKD, 3.75 [95% CI, 2.53-5.57]; HOR among those with glomerular diagnoses, 5.96 [95% CI, 3.37-10.54]) comparing those at or above the 90th percentile vs below the 50th percentile
Summary
Hypertension is a common comorbidity in children with CKD1,2 and is associated with progression of CKD in cohort studies and trials.[3,4,5] Effective treatment of hypertension is known to slow the rate of progression to end-stage renal disease, as highlighted by the Effect of Strict Blood Pressure Control and Angiotensin-Converting Enzyme Inhibition on the Progression of Chronic Renal Failure in Pediatric Patients (ESCAPE) trial,[4] which demonstrated that improved blood pressure (BP) management delayed the progression of CKD, especially among those with proteinuria. Office BP measurements are commonly used in clinical practice, providing an immediate, noninvasive assessment during clinical review, and clinicians often consider a patient’s BP history, whether home monitoring or during clinic visits, when making treatment decisions. These timevarying BP measurements may reflect a change in a patient’s clinical status (ie, a child with previous normotension may develop hypertension and vice versa). The Chronic Kidney Disease in Children (CKID) and ESCAPE studies both demonstrated a similar association of elevated baseline systolic BP and progression in children.[6,7,8] Incorporating time-varying BP would reflect clinical practice and ongoing antihypertensive management better than using a single measurement, but analysis should account for other time-varying potential confounders. Several studies have demonstrated that longitudinal measurements of BP in adults were more strongly associated with progression of CKD than baseline BP measurements.[9,10,11,12] These results may reflect ongoing BP management and whether treated BP is well controlled, which are important factors in CKD management
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