CTS Collaborative Transplant Study

Newsletter 2:2023

May 1, 2023

Dear Colleague


Information on post-transplant blood pressure has been recorded in the CTS at annual intervals since 1990. Based on these data, the seminal paper "Association of chronic kidney graft failure with recipient blood pressure" by G. Opelz et al. was published 25 years ago in "Kidney International" (doi: 10.1046/j.1523-1755.1998.00744.x). In addition, CTS Newsletter 3:2004 showed that there is a strong association between arterial hypertension and the graft outcome in pediatric patients. In this Newsletter, we explore this topic further for different age groups of children.

We analyzed 6,449 pediatric patients aged 1 to 17 years who received a kidney-only transplant between 1990 and 2020. All recipients considered had a functioning graft 1 year after transplantation and their 1-year blood pressure values were available. 7.3% of the transplants were retransplants and 38.8% were from living donors. It is well known that blood pressure level strongly correlates with age in pediatric patients. To identify an influence of blood pressure on transplant outcomes in meaningful Kaplan-Meier curves with sufficient cases, we divided the age of the pediatric recipients at the time of transplantation into the age categories: 1–5 years, 6–9 years, 10–13 years, and 14–17 years. Figure 1 illustrates the median and interquartile range of 1-year systolic blood pressure (SBP) and number of cases for these four age categories.




Figure 1. Median and percentiles of post-transplant 1-year systolic blood pressure (SBP) by recipient age at time of kidney transplantation.

A recommendation for defining hypertension in children is the "Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents", published by J.T. Flynn et al. in "Pediatrics" in 2017 (doi: 10.1542/peds.2017-1904). In this publication, SBP ≥ 95% percentile is defined as hypertension stage 1 and ≥ 95% percentile + 12 mm Hg as hypertension stage 2, given in detailed tables depending on age, sex and height. However, Flynn et al. also present a simplified table for screening blood pressure by age that starts with a SBP cut-off of 98 mm Hg for 1-year-old children and ends with 120 mm Hg for 13-year-old children. For the four age groups indicated in Figure 1, we used the following simplified classification to define pediatric hypertension, considering only 1-year systolic blood pressure for simplicity.



Table 1. Age-specific definition of hypertension based on 1-year systolic blood pressure in mm Hg of pediatric renal transplanted patients reported to CTS.

Applying these definitions of hypertension for pediatric renal transplant recipients to the CTS study cohort, we found a significant decrease in the proportion of hypertensive renal transplant children with increasing age and transplant period (Figure 2).



Figure 2. Distribution of children with normal reference 1-year systolic blood pressure (Ref.), hypertension grade 1 (HT 1), and grade 2 (HT 2), depending on (A) age at the time of transplantation and (B) transplant period.

For the following survival analyses, a period of three years after the measured one-year blood pressure was considered. One should keep in mind that stratification is based on age at the time of transplantation and blood pressure increases with increasing age during follow-up.




Figure 3. Influence of hypertension grade 1 (HT 1) and grade 2 (HT 2) in comparison to reference (non-hypertensive) 1-year systolic blood pressure on graft survival of (A) 1–5 years, (B) 6–9 years, (C) 10–13 years, and (D) 14–17 years old recipients at time of transplant (log rank P values with trend of Kaplan-Meier analyses are shown).

Figure 3 shows similar pictures for all four age groups and thereby supports the appropriateness of the chosen SBP cut-offs. The results impressively document the strong correlation between 1-year systolic blood pressure and graft failure rate during the following three years. Therefore, based on the age-specific definition of hypertension indicated in Table 1, it is possible to pool the age groups for more in-depth analyses.

Multivariable Cox regression with other important confounders for graft survival, such as transplant number, transplant year, recipient sex, race and age, end-stage renal disease, time on dialysis, pre-transplant antibodies, donor age and relationship, revealed a hazard ratio (HR) of 1.60 (95% confidence interval (CI) 1.30–1.98, P<0.001) for hypertension grade 1 and a HR of 2.48 (95% CI 2.02–3.03, P<0.001) for hypertension grade 2. In these analyses, we focused on overall (rather than death-censored) graft survival because mortality plays only a minor role in the analysis of transplanted children and no significant effect of systolic blood pressure on mortality in children was observed (Figure 4).




Figure 4. Influence of 1-year post-transplant hypertension on (A) death-censored graft survival and (B) patient survival during post-transplant years 2–4 of pediatric renal transplantations (log rank P values with trend of Kaplan-Meier analyses are shown).

Analysis of interactions with hypertension in the Cox regression as well as stratification according to recipient sex showed no significant differences, as female and male patients both suffered similarly from the negative impact of hypertension on graft survival (Figure 5). There were also no significant differences in the analyses of antihypertensive medication (with vs. without any antihypertensives) and the transplantation period 1990–2004 vs. 2005–2020 (not shown).




Figure 5. Influence of 1-year post-transplant hypertension on graft failure during years 2–4 in (A) female and (B) male pediatric patients (log rank P values with trend of Kaplan-Meier analyses are shown).

In summary, the graft outcome results show that the hypertension grades are associated with inferior graft survival. Therefore, it would seem important to continue efforts in the treatment of post-transplant high blood pressure in pediatric transplant patients, although it is gratifying to note that the proportion of hypertensive patients one year after transplantation has decreased significantly over time.




The next shipping date of Serum and DNA

for the Biomarker Studies is

July 14, 2023.






Thank you for your continued support and best wishes,


Hien Tran


for your CTS Team in Heidelberg:
Christian Unterrainer Andrea Ruhenstroth Sofia Cinca Bernd Döhler
Gesine Mehlich Michael Döntgen Kezban Ozansoy Cornelia Mohr