Trajectories of eGFR after kidney transplantation according to trajectories of eGFR prior to kidney replacement therapies in children with chronic kidney disease

Abstract

Background: In children with chronic kidney disease (CKD), certain risk factors are associated with faster eGFR decline and earlier kidney failure. Whether these factors have lingering effects on post-transplant eGFR trajectory remains unclear. We characterized pre- and post-transplant eGFR trajectories in pediatric kidney transplant recipients by their pre-kidney replacement therapy (KRT) risk factors.

Methods: We studied eGFR trajectories before KRT initiation and after transplantation among Chronic Kidney Disease in Children (CKiD) Study participants. We used mixed-effects models to compare pre-KRT versus post-transplant eGFR trajectories within individual participants by 7 pre-KRT risk factors: glomerular/non-glomerular etiology, race, preemptive transplant, proteinuria, albuminuria, and systolic/diastolic blood pressure (SBP/DBP).

Results: We analyzed 1602 pre-KRT and 592 post-transplant eGFR measurements from 246 transplant recipients. Mean annual eGFR decline was decreased from 18.0% pre-KRT (95%CI, 16.1-19.8) to 5.0% post-transplant (95%CI, 3.3-6.7). All 7 pre-KRT risk factors showed strong associations with faster pre-KRT eGFR decline, but not with post-transplant eGFR decline; only albuminuria, high SBP, and high DBP reached statistical significance with notably attenuated associations. In our multivariable model of the pre-KRT risk factors, post-transplant eGFR decline was more rapid only when albuminuria and high SBP were both present.

Conclusions: eGFR decline substantially slows down after transplant even among children with rapidly progressing forms of CKD. Nonetheless, those who had albuminuria and high SBP before KRT might continue to show faster eGFR decline after transplant, specifically when both risk factors were present. This subgroup might benefit from intensive pre-transplant management for at least one of the two risk factors. A higher resolution version of the Graphical abstract is available as Supplementary information.

Keywords: Children; Estimated glomerular filtration rate; Risk factors; Transplantation.

Figure 1.. Estimated Glomerular Filtration Rate (GFR) before kidney replacement therapy (KRT) and after transplant in 246 pediatric kidney transplant recipients in the CKiD study, 2005–2021.

Our data included 1602 pre-KRT and 592 post-transplant measurements. We used the U25 equations to estimate GFR [12]. The eGFR trajectory was characterized using a longitudinal model with 4 regression terms after a log transformation. Acronyms: KRT, kidney replacement therapy.

Figure 2.. Annual Decline in Estimated Glomerular Filtration Rate (eGFR), Pre-Kidney Replacement Therapy versus Post-Transplant.

Solid curve line represents a loess model between pre-KRT and post-Tx eGFR annual decline. Grey band represents the 95% confidence band. There was little correlation between the pre-KRT and post-Tx eGFR annual decline (r= 0.14). Acronyms: Tx, transplant; and KRT, kidney replacement therapy.

Figure 3.. Comparison of Annual Decline in Estimated Glomerular Filtration Rate (eGFR) by Urine Albumin-Creatinine Ratio and Systolic Blood Pressure.

The low-uACR & low-SBP group (first row) was used as the reference group for each of the two phases. Urine albumin-creatinine ratio and blood pressure were taken from the last measurements prior to the initiation of kidney replacement therapy. Acronyms: KRT, kidney replacement therapy; Tx, transplant; uACR, urine albumin-creatinine ratio; SBP, systolic blood pressure; and pct, percentile (for age, gender, and height). ^a 21 measurements during pre-KRT and 7 during post-Tx excluded for missing data in uACR or SBP.