CKD and hypertension during long-term follow-up in children and adolescents previously treated with extracorporeal membrane oxygenation

Abstract

Background and objectives: Many children receiving extracorporeal membrane oxygenation develop AKI. If AKI leads to permanent nephron loss, it may increase the risk of developing CKD. The prevalence of CKD and hypertension and its predictive factors during long-term follow-up of children and adolescents previously treated with neonatal extracorporeal membrane oxygenation were determined.

Design, setting, participants, & measurements: Between November of 2010 and February of 2014, neonatal survivors of extracorporeal membrane oxygenation who visited the prospective follow-up program at 1, 2, 5, 8, 12, and 18 years of age were screened for CKD and hypertension (BP≥95th percentile of reference values). CKD was suspected in children with either an eGFR<90 ml/min per 1.73 m(2) or proteinuria (urinary protein-to-creatinine ratio >0.50 for children ages ≤24 months and >0.20 at >24 months). The RIFLE classification (risk, injury, or failure as 150%, 200%, or 300% of serum creatinine reference values) was used to define AKI during extracorporeal membrane oxygenation without preemptive hemofiltration.

Results: Median follow-up of 169 screened participants was 8.2 years (interquartile range=5.2-12.1 years). Nine children had a lower eGFR, but all rates were >60 ml/min per 1.73 m(2). Proteinuria was observed in 20 children (median=0.26 mg protein/mg creatinine; interquartile range=0.23-0.32 mg protein/mg creatinine), and 32 children had hypertension. Only history of AKI was associated with CKD (P=0.004). Children with RIFLE scores injury and failure had 4.3 times higher odds of CKD signs or hypertension than those without AKI (95% confidence interval, 1.6 to 12.1; P=0.004).

Conclusions: Altogether, 54 participants (32%) had at least one sign of CKD and/or hypertension. However, most values were marginally abnormal, with no immediate consequences for clinical care. Nevertheless, a prevalence of 32% clearly indicates that survivors of neonatal extracorporeal membrane oxygenation, especially those with AKI, are at risk of a more rapid decline of kidney function with increasing age. Therefore, screening for CKD development in adulthood is recommended.

Keywords: CKD; acute renal; children; clinical nephrology; epidemiology and outcomes; failure.

Figure 1.

Flowchart of patient recruitment. Flowchart detailing inclusion and exclusion criteria for children who survived neonatal ECMO support, which resulted in the final study cohort. CAKUT, congenital abnormality of the kidneys and urinary tract; ECMO, extracorporeal membrane oxygenation.

Figure 2.

GFR screening results for all patients stratified by age group. GFR was estimated using the revised Schwartz Equation (0.413×height [centimeters]/serum creatinine). An eGFR<90 ml/min per 1.73 m² was considered abnormal. Glomerular hyperfiltration was defined as an eGFR≥150 ml/min per 1.73 m². SCr, serum creatinine.

Figure 3.

Urinary protein-to-creatinine screening results for all patients stratified by age group. Significant proteinuria was quantified as urinary protein-to-creatinine ratio >0.50 mg protein/mg creatinine for children ages ≤24 months and >0.20 mg protein/mg creatinine for children ages >24 months. If proteinuria was identified, urinalysis was repeated three times in a first morning sample to rule out an orthostatic effect. In case of orthostatic proteinuria, the participant was scored negative for proteinuria. uP/C ratio, urinary protein-creatinine ratio.

Figure 4.

BP screening results for all patients stratified by age group. Prehypertension and stages 1 and 2 hypertension were defined as a mean systolic and/or diastolic BP between 90th and 95th percentiles, BP≥95th and ≤99th percentiles, or BP>99th percentiles of reference values for sex, height SD score, and age, respectively.

Figure 5.

The primary outcome of all participants screened. GFR was estimated using the revised Schwartz Equation (0.413×height [centimeters]/serum creatinine). An eGFR<90 ml/min per 1.73 m² was considered abnormal. Significant proteinuria was quantified as a urinary protein-to-creatinine ratio >0.50 mg protein/mg creatinine for children ages ≤24 months and >0.20 mg protein/mg creatinine for children ages >24 months. Prehypertension and stages 1 and 2 hypertension were defined as a mean systolic and/or diastolic BP between 90th and 95th percentiles, BP≥95th and ≤99th percentiles, or BP>99th percentiles of reference values for sex, height SD score, and age, respectively.