Risk of post-transplant cardiovascular events in kidney transplant recipients with preexisting aortoiliac stenosis

Prediction of the risk of cardiovascular events (CVE's) is important to optimize outcomes after kidney transplantation. Aortoiliac stenosis is frequently observed during pre‐transplant screening. We hypothesized that these patients are at higher risk of post‐transplant CVE's due to the joint underlying atherosclerotic disease. Therefore, we aimed to assess whether aortoiliac stenosis was associated with post‐transplant CVE's. This retrospective, single‐center cohort study included adult kidney transplant recipients, transplanted between 2000 and 2016, with contrast‐enhanced imaging available. Aortoiliac stenosis was classified according to the Trans‐Atlantic Inter‐Society Consensus (TASC) II classification and was defined as significant in case of ≥50% lumen narrowing. The primary outcome was CVE‐free survival. Eighty‐nine of 367 patients had significant aortoiliac stenosis and were found to have worse CVE‐free survival (median CVE‐free survival: stenosis 4.5 years (95% confidence interval (CI) 2.8–6.2), controls 8.9 years (95% CI 6.8–11.0); log‐rank test P < .001). TASC II C and D lesions were independent risk factors for a post‐transplant CVE with a hazard ratio of 2.15 (95% CI 1.05–4.38) and 6.56 (95% CI 2.74–15.70), respectively. Thus, kidney transplant recipients with TASC II C and D aortoiliac stenosis require extensive cardiovascular risk management pre‐, peri,‐ and post‐transplantation

The prognosis of kidney transplant recipients with aorto-iliac calcification: a systematic review and meta-analysis

The prognosis of kidney transplant recipients (KTR) with vascular calcification (VC) in the aorto-iliac arteries is unclear. We performed a systematic review and meta-analysis to investigate their survival outcomes. Studies from January 1st, 2000 until March 5th, 2019 were included. Outcomes for meta-analysis were patient survival, (death-censored) graft survival and delayed graft function (DGF). Twenty-one studies were identified, eight provided data for meta-analysis. KTR with VC had a significantly increased mortality risk [1-year: risk ratio (RR) 2.19 (1.39–3.44), 5-year: RR 2.28 (1.86–2.79)]. The risk of 1-year graft loss was three times higher in recipients with VC [RR 3.15 (1.30–7.64)]. The risk of graft loss censored for death [1-year: RR 2.26 (0.58–2.73), 3-year: RR 2.19 (0.49–9.82)] and the risk of DGF (RR 1.24, 95% CI 0.98–1.58) were not statistically different. The quality of the evidence was rated as very low. To conclude, the presence of VC was associated with an increased mortality risk and risk of graft loss. In this small sample size, no statistical significant association between VC and DGF or risk of death-censored graft loss could be demonstrated. For interpretation of the outcomes, the quality and sample size of the evidence should be taken into consideration

Impact of Extraction Time during Donation after Circulatory Death Organ Procurement on Kidney Function after Transplantation in the Netherlands

Background:In The Netherlands, 60% of deceased-donor kidney offers are after donation after circulatory death. Cold and warm ischemia times are known risk factors for delayed graft function (DGF) and inferior allograft survival. Extraction time is a relatively new ischemia time. During procurement, cooling of the kidneys is suboptimal with ongoing ischemia. However, evidence is lacking on whether extraction time has an impact on DGF if all ischemic periods are included.Methods:Between 2012 and 2018, 1524 donation after circulatory death kidneys were procured and transplanted in The Netherlands. Donation and transplantation-related data were obtained from the database of the Dutch Transplant Foundation. The primary outcome parameter was the incidence of DGF. Results:In our cohort, extraction time ranged from 14 to 237 min, with a mean of 62 min (SD 32). In multivariate logistic regression analysis, extraction time was an independent risk factor for incidence of DGF (odds ratio per minute increase 1.008; 95% confidence interval, 1.003-1.013; P = 0.001). The agonal phase, hypoperfusion time, and anastomosis time were not independent risk factors for incidence of DGF. Conclusions:Considering all known ischemic periods during the donation after the circulatory death process, prolonged kidney extraction time increased the risk of DGF after kidney transplantation.</p

Human Transplant Kidneys on Normothermic Machine Perfusion Display Endocrine Activity

Background. Normothermic machine perfusion (NMP) is an alternative to hypothermic machine perfusion (HMP) for donor kidney preservation before transplantation. Contrary to HMP, NMP allows for functional assessment of donor kidneys because normothermic conditions allow for metabolic activity. The kidneys are key producers of hormones. Yet, it remains unknown whether donor kidneys during NMP display endocrine functions. Methods. Fifteen donor kidneys were subjected to HMP followed by 2 h of NMP before transplantation. NMP perfusate was collected at 3 time points (0, 1, 2 h) for the measurements of prorenin/renin, erythropoietin (EPO), and vitamin D, and urine samples were collected at 1 h and 2 h for urodilatin measurement. Fifteen HMP perfusate samples were collected for the same measurements. Results. Kidneys on NMP secreted significantly more prorenin, renin, EPO, and active vitamin D than during HMP. EPO and vitamin D secretion remained stable during 2 h of NMP, whereas the prorenin release rate increased and renin release rate decreased after 1 h. Donation after brain death kidneys secreted more vitamin D and less EPO during NMP than donation after circulatory death kidneys. Twelve donor kidneys produced urine during NMP and released detectable levels of urodilatin. Kidneys exhibited a large variation in hormone release rates. No significant differences were found in hormone release capacity between delayed graft function (DGF) and non-DGF kidneys, and no significant correlations were found between hormone release rates and the duration of DGF or 1-mo posttransplant serum creatinine levels. Conclusions. Human transplant kidneys display endocrine activity during NMP. To explore whether correlations exist between hormone release rates and posttransplant kidney function, large numbers of kidneys are required.</p

Aorto-Iliac Artery Calcification Prior to Kidney Transplantation

As vascular calcification is common in kidney transplant candidates, aorto-iliac vessel imaging is performed for surgical planning. The aim of the present study was to investigate whether a novel non-contrast enhanced computed tomography-based quantification technique for aorto-iliac calcification can be used for cardiovascular risk stratification prior to kidney transplantation. In this dual-center cohort study, we measured the aorto-iliac calcium score (CaScore) of 547 patients within three years prior to transplantation (2005-2018). During a median (interquartile range) follow-up of 3.1 (1.4, 5.2) years after transplantation, 80 (14.7%) patients died, of which 32 (40.0%) died due to cardiovascular causes, and 84 (15.5%) patients had a cardiovascular event. Kaplan-Meier survival curves showed significant differences between the CaScore tertiles for cumulative overall-survival (Log-rank testp<0.0001), cardiovascular survival (p<0.0001), and cardiovascular event-free survival (p<0.001). In multivariable Cox regression, the aorto-iliac CaScore was associated with all-cause mortality (hazard ratio 1.53, 95%CI 1.14-2.06,p= 0.005), cardiovascular mortality (2.04, 1.20-3.45,p= 0.008), and cardiovascular events (1.35, 1.01-1.80,p= 0.042). These independent associations of the aorto-iliac CaScore with the outcome measures can improve the identification of patients at risk for (cardiovascular) death and those who could potentially benefit from stringent cardiovascular monitoring to improve their prognosis after transplantation

Aorto-Iliac Artery Calcification and Graft Outcomes in Kidney Transplant Recipients

While the association of vascular calcification with inferior patient outcomes in kidney transplant recipients is well-established, the association with graft outcomes has received less attention. With this dual-centre cohort study, we aimed to determine the clinical impact of recipient pre-transplant aorto-iliac calcification, measured on non-contrast enhanced computed tomography (CT)-imaging within three years prior to transplantation (2005&ndash;2018). We included 547 patients (61.4% male, age 60 (interquartile range 51&ndash;68) years), with a median follow-up of 3.1 (1.4&ndash;5.2) years after transplantation. The aorto-iliac calcification score (CaScore) was inversely associated with one-year estimated-glomerular filtration rate (eGFR) in univariate linear regression analysis (standard &beta; &minus;3.3 (95% CI &minus;5.1 to &minus;1.5, p &lt; 0.0001), but not after adjustment for potential confounders, including donor and recipient age (p = 0.077). In multivariable Cox regression analyses, a high CaScore was associated with overall graft failure (p = 0.004) and death with a functioning graft (p = 0.002), but not with death-censored graft failure and graft function decline. This study demonstrated that pre-transplant aorto-iliac calcification is associated with one-year eGFR in univariate, but not in multivariable linear regression analyses. Moreover, this study underlines that transplantation in patients with a high CaScore does not result in earlier transplant function decline or worse death censored graft survival, although ongoing efforts for the prevention of death with a functioning graft remain essential