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Research Articles

Kidney transplantation and kidney donation do not affect short-term blood pressure variability

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Article: 2181640 | Received 03 Jan 2023, Accepted 11 Feb 2023, Published online: 22 Feb 2023

Abstract

Purpose

Blood pressure variability (BPV) is an independent cardiovascular risk factor in CKD. Kidney transplantation (KTx) is associated with improved BP levels for kidney transplant recipient (KTRs), without evoking significant changes in donors. The aim of this study was to assess the short- and mid-time effects of KTx and donation on short-term BPV in KTRs and their respective living kidney donors.

Materials and Methods

Forty KTRs and their respective donors were evaluated with 24-h ABPM (Mobil-O-Graph-NG) at baseline (1 month before), 3-months and 12-months after KTx. Standard-deviation (SD), weighted-SD (wSD), coefficient-of-variation (CV), average-real-variability (ARV) and variability independent of mean (VIM) for SBP/DBP were calculated with validated formulas

Results

All 24-h systolic and diastolic BPV indexes studied did not change significantly from baseline to 3-month (SBP-wSD: 12.8 ± 3.0 vs 13.2 ± 3.4 mmHg, p = 0.608; SBP-ARV: 10.3 ± 2.4 vs 10.8 ± 2.6 mmHg, p = 0.463) and 12-month evaluation (SBP-wSD 12.8 ± 3.0 vs 12.1 ± 2.8; p = 0.424 and SBP-ARV: 10.3 ± 2.4 vs 10.2 ± 2.5; p = 0.615) after kidney transplantation in the KTRs.In kidney donors, all 24-h systolic BPV indices displayed a trend towards higher values at 3 months compared to baseline, but without reaching statistical significance (SBP-wSD: 12.2 ± 2.8 vs 13.6 ± 4.2 mmHg, p = 0.107 and SBP-ARV: 10.1 ± 2.1 vs 11.2 ± 3.1 mmHg, p = 0.099), the levels of 24-h systolic SBP indices at 12-months were almost identical to baseline values. 24-h diastolic BPV indices at 3-month and 12-month evaluation were similar to baseline.

Conclusion

Short-term BPV did not change significantly 3 and 12 months after kidney transplantation/donation neither in KTRs nor in living kidney donors. Longitudinal studies examining associations of BPV with adverse outcomes in these individuals are needed.

PLAIN LANGUAGE SUMMARY

What is the context?

  • Previous studies have shown that both office and ambulatory BP levels are significantly reduced after kidney transplantation in KTRs.

  • On the other hand, existing evidence suggests that kidney donors’ BP levels do not change significantly after kidney donation.

  • Existing studies on BPV in KTRs are limited. The available data for living kidney donors are even fewer.

What is new?

  • This is the first study assessing short-term BPV levels in ΚTRs undergoing living donor kidney transplantation, and their respective donors in short-term and mid-term follow-up. The main findings were:

  • All 24-h, daytime and night-time BPV indexes did not change significantly from baseline to 3- and 12-month evaluation after kidney transplantation in the KTRs.

  • No significant changes for the 24-h, daytime and night-time BPV were observed in their respective kidney donors at the same follow-up periods.

What is the impact?

  • High BPV, which seems to remain unaltered after kidney transplantation, may be one of the many factors involved in the high cardiovascular risk observed in KTRs.

  • Unchanged BPV levels further supports the evidence suggesting no higher risks of arrhythmias, cardiovascular events or death after living kidney donation.

Introduction

Kidney transplantation is the best treatment option for patients with end-stage kidney disease (ESKD), as it is associated with highest survival rates and improved quality of life compared to dialysis [Citation1,Citation2]. Although survival of kidney transplant recipients (KTRs) further improved in the last decades, the risk of cardiovascular death remains higher than in general population [Citation3,Citation4]. Hypertension is a major cardiovascular risk factor in KTRs [Citation5] and it is also strongly associated with target-organ damage and poor graft survival [Citation6,Citation7]. Kidney transplantation from a living donor is considered superior compared to transplantation from a deceased donor for both short- and long term patient and graft survival [Citation8].

Previous studies have shown that both office and ambulatory BP levels are significantly reduced after kidney transplantation compared with the pre-transplant condition [Citation9–11]. In a recent study from our group, we showed that ambulatory BP levels and trajectories were decreased in 40 KTRs at 3 months and further so at 12 months post-transplantation [Citation11]. Other studies have also demonstrated that KTRs have lower ambulatory BP levels compared with age- and sex-matched haemodialysis patients [Citation12]. With regards to the living kidney donors, existing evidence suggest that ambulatory BP does not change after 1, 5 and 9 years of follow-up after kidney donation surgery [Citation11,Citation13–15].

The term ‘BP variability’ (BPV) is used to describe the BP fluctuations over time, and based on the time interval over which is measured, it can be categorised into 4 groups: very short-term (beat-to-beat), short-term (within 24 h), mid-term (day-to-day) and long-term (visit-to-visit) BPV [Citation16,Citation17]. All these types of BPV have been associated with cardiovascular and renal outcomes, and total mortality in various populations [Citation16–18]. In chronic kidney disease (CKD) patients, previous works showed that short-term BPV increases with CKD progression towards to end-stage [Citation19], while both short- and long-term BPV are strong and independent predictors of cardiovascular events and all-cause mortality in ESKD individuals [Citation20,Citation21].

Existing evidence on BPV in KTRs is limited. A recent study showed that short-term BPV indices are similar between 93 KTRs and 93 age-, sex- and eGFR-matched pre-dialysis CKD patients [Citation22]. In another study from our group we found that KTRs had significantly lower short-term BPV compared to haemodialysis patients [Citation12]. For living kidney donors, the available data are even fewer. In the only study in the field, Price et al. showed that short term BPV did not differ between kidney donors and healthy controls [Citation23]. Τo the best of our knowledge, this is the first study assessing short-term BPV levels in ΚTRs undergoing living donor kidney transplantation, and their respective donors during short-term and mid-term follow-up after kidney transplantation.

Materials and methods

Study population

This is a pre-specified secondary analysis of a prospective cohort study aiming to evaluate in parallel ambulatory BP levels in ΚTRs and their respective donors at the short-term and mid-term periods after kidney transplantation [Citation11]. We recruited ΚTRs undergoing living donor kidney transplantation at the Clinic of Nephrology and Renal Transplantation, Laiko General Hospital, Athens, Greece, and their respective donors. Approval of this study was obtained by the Institutional Review Board of Laiko General Hospital and School of Medicine, National & Kapodistrian University of Athens, Greece (1053/27-09-2018). All evaluations were performed according to the Declaration of Helsinki (2013 Amendment). Inclusion criteria consisted of: (a) patients assessed suitable for kidney transplantation and their respective donors assessed suitable for kidney donation; (b) age >18 years and (c) provision of informed written consent. Exclusion criteria were: (a) eGFR decline >30% during the last 3 months in living kidney donors; (b) change in antihypertensive treatment during the last 6 weeks in both KTRs and donors; (c) chronic atrial fibrillation or other arrhythmias that that could interfere with proper ABPM recording; (d) presence of bilateral arteriovenous fistulae that could interfere with proper ABPM recording (for KTRs only).

Study procedures and data collection

All study procedures were performed at the Nephrology and Renal Transplantation Centre, and the Cardiovascular Prevention & Research Unit of the Department of Pathophysiology, Laiko General Hospital, National & Kapodistrian University of Athens, Greece. Participants were evaluated at three different time-points, during a scheduled morning visit, as described previously: (i) Baseline (1 month ± 10 days before scheduled kidney transplantation/donation), (ii) 3 months (±10 days) after kidney transplantation/donation) and (iii) 12 months (±2 weeks) after kidney transplantation/donation. At baseline, demographic and anthropometric characteristics, medical history, medication, co-morbidities, as well as other transplantation/donation-related parameters were recorded for each participant. A physical examination was also performed, and blood samples were obtained for routine laboratory testing at each visit.

ABPM was performed with the Mobil-O-Graph device (IEM, Stolberg, Germany), a validated automated oscillometric device [Citation24,Citation25], that was shown to provide identical values with a widely used ABPM monitor [Citation26]. The device was set to measure BP for 24-h, every 15 min during daytime and every 30 min during night-time on the non-fistula arm of the participants using appropriate-size cuffs. All participants were instructed to continue their usual daily activities and receive their regular medication. Measurements were used for the analysis if >70% of recordings were valid with ≤2 non-consecutive day-hours with <2 valid measurements, and ≤1 night-hour without valid recording for each 24-hour period. In case of invalid recordings, ABPM was repeated within 1 week. Pairs that had at least one invalid ABPM recording at baseline for either the donor or the recipient were excluded from further evaluation. In addition, pairs who failed to obtain valid ABPM for either the donor or the recipient at both 3-month and 12-month evaluations were also excluded from the analysis. To minimise the possible effect of manual BP measurements, only measurements taken at the pre-specified time intervals at which the device was set to take measurements were used in this analysis.

Blood pressure variability indices

Based on data obtained from ABPM recordings, the following systolic and diastolic BPV parameters for the total 24-hour, daytime and night-time periods were calculated utilising appropriate formulae [Citation27–29]:

  1. Standard deviation (SD) calculated as:  SD=1N1k=1N(BPk+1 BP)¯2; N, the number of valid BP measurements, BP¯, average of ABPM readings.

  2. Coefficient of variation (CV), defined as the ratio of the SD to the mean BP and calculated as: CV=SDmean BP×100.

  3. Weighted SD (wSD), defined as the average of daytime and night-time SD of BP, each weighted for the duration of the day- and night-time periods, respectively and calculated as:

wSD={(daytime SD×daytime hrs)+(nighttime SD×nighttime hrs)}24hour period
  • Average real variability (ARV), defined as the average of the absolute differences between consecutive BP measurements and calculated as: ARV=1N1k=1N1|BPk+1 BPk|; N, the number of valid BP measurements, BPk, BP at measurement number k.

  • Variability independent of mean (VIM), calculated as: =k x SD BPmean BPx; x = regression coefficient obtained by fitting a curve through a plot of SD against mean using the model SD = a x meanx, k = population mean BP to the power x.

Statistical analysis

Continuous variables are presented as mean ± standard deviation (mean ± SD) or median [interquartile range, IQR], according to the normality of distribution. Categorical variables are presented as absolute frequencies and percentages (n, %). The Shapiro-Wilk test was applied to examine the normality of distribution for quantitative variables. Within-groups comparisons for continuous variables were performed with the paired t-test or Wilcoxon signed-rank test, according to normality of the distribution. A P-value of <0.05 (two-tailed) was considered statistically significant for all comparisons. Statistical analysis was performed with the Statistical Package for Social Sciences version 23.0 (SPSS Inc, Chicago, IL, USA).

Results

Baseline characteristics

From a 52 KTRs and their respective donors that fulfilled the inclusion and exclusion criteria, 9 kidney transplant donor-recipient pairs were excluded (5 KTRs and 7 donors had an invalid 24-h ABPM at baseline and 1 KTR had acute graft rejection). In addition, 2 kidney donors were lost to follow up, while 1 kidney donor had invalid ABPM recording at both 3-month and 12-month evaluations. Thus, a total of 40 pairs of KTRs and their respective donors were included in the final analysis. From these, 40 pairs had full ABPM sets at baseline evaluation, 36 pairs had also full ABPM sets at 3-month evaluation and 32 full ABPM sets at 12-month evaluation. Demographics, clinical and laboratory characteristics of the two study groups at baseline are presented in . A total of 40 KTRs (70.0% males) with mean age of 45.61 ± 13.93 years and 40 living kidney donors (27.5% males) with mean age of 53.91 ± 17.25 years were included. Hypertension was the most common among major comorbidities in both KTRs (97.5%) and donors (27.5%)

Table 1. Baseline demographic, anthropometric and clinical characteristics of study participants.

BPV indices in KTRs

presents the 24-h systolic and diastolic BPV indices at baseline, 3-month and 12-month evaluation in KTRs. As noted in the table, 24-h systolic BPV indices were not significantly different between baseline and 3-month evaluation (SBP-SD: baseline: 13.8 ± 3.4 vs 3-month evaluation: 13.7 ± 3.6 mmHg, p = 0.890; SBP-wSD: 12.8 ± 3.0 vs 13.2 ± 3.4 mmHg, p = 0.608; SBP-CV: 10.5 ± 2.3 vs 10.9 ± 2.7%, p = 0.450; SBP-ARV: 10.3 ± 2.4 vs 10.8 ± 2.6 mmHg, p = 0.463 and SBP-VIM: 13.2 ± 2.9 vs 13.4 ± 3.4, p = 0.818, respectively). At 12-month evaluation, no differences versus baseline was again noted for all systolic BPV indices studied. With regards to 24-h diastolic BPV (), all indices displayed minor drops at the 3-month and 12-month evaluation compared to baseline (with the exception of DBP-CV at 12-month), but again without reaching statistical significance.

Table 2. 24-h systolic and diastolic BPV at baseline, 3-months and 12-months after kidney transplantation surgery in KTRs.

The systolic and diastolic BPV indices during the day- and night-time periods at baseline, 3-month and 12-month evaluations in KTRs are shown in Supplementary Table 1S. Again, no significant differences in any of the studied indices between baseline and 3- or 12-month evaluation were detected.

We should notice that the mean number of antihypertensive drugs required was reduced from baseline to 3 months (1.65 ± 1.03 versus 1.27 ± 1.01; p = 0.042) and remained stable thereafter (1.25 ± 1.08; ANOVA p = 0.108). However, the changes in the mean number of antihypertensive drugs showed no associations with the changes in BPV parameters at 3 months (24-h SBP-ARV: r= −0.234, p = 0.163 and 24-h SBP-wSD: r= −0.100, p = 0.558) nor at 12 months (24-h SBP-ARV: r= −0.019, p = 0.916 and 24-h SBP-wSD: r= −0.108, p = 0.555). No significant differences in any of drug classes used were noted between baseline and both 3- and 12-month evaluations.

BPV indices in living kidney donors

presents the 24-h systolic and diastolic BPV at baseline, 3-month and 12-month evaluation in living kidney donors. At 3-month evaluation, all 24-h systolic BPV indices displayed a trend towards higher values compared to baseline, but without reaching statistical significance (SBP-SD: baseline: 13.7 ± 3.7 vs 3-month evaluation: 15.2 ± 5.7 mmHg, p = 0.170; SBP-wSD: 12.2 ± 2.8 vs 13.6 ± 4.2 mmHg, p = 0.107; SBP-CV: 11.6 ± 2.8 vs 12.8 ± 4.1%, p = 0.140; SBP-ARV: 10.1 ± 2.1 vs 11.2 ± 3.1 mmHg, p = 0.099 and SBP-VIM: 14.3 ± 3.5 vs 15.6 ± 5.1, p = 0.192, respectively). At 12-month evaluation, 24-h SBP-ARV was numerically but non-significantly higher than baseline (10.1 ± 2.1 vs 11.0 ± 2.5 mmHg, p = 0.086); the levels of all other 24-h systolic SBP indices at 12-months were almost identical to baseline values. 24-h diastolic BPV indices at the 3-month and 12-month evaluation were similar to baseline ().

Table 3. 24-h systolic and diastolic BPV at baseline, 3-months and 12-months after kidney donation surgery in kidney donors.

Systolic and diastolic BPV indices during the respective day- and night-time periods at baseline, 3-month and 12-month evaluation are shown in Supplementary Table 2S. No significant differences between any of the studied parameters were observed, although most indices were numerically higher at 3-month evaluation compared to baseline.

The mean number of antihypertensive drugs did not change from baseline to 3 months (0.38 ± 0.77 versus 0.25 ± 0.67; p = 0.096) and remained stable at 12 months (0.22 ± 0.61; ANOVA p = 0.146). The changes in the mean number of antihypertensive drugs showed no associations with the changes in BPV parameters at 3 months (24-h SBP-ARV: r= −0.045, p = 0.798 and 24-h SBP-wSD: r = 0.017, p = 0.924) nor at 12 months (24-h SBP-ARV: r= −0.185, p = 0.312 and 24-h SBP-wSD: r= −0.075, p = 0.684). No significant differences in any of drug classes used were noted between baseline and both 3- and 12-month evaluation.

Discussion

The present study is the first to investigate the short- and mid-time effects of kidney transplantation and donation on short-term BPV in KTRs and their respective living kidney donors. All 24-h BPV indexes studied (SD, wSD, CV, ARV and VIM) did not change significantly from baseline to 3- and 12-month evaluation after kidney transplantation in the KTRs; day- and night-time BPV indexes followed a similar pattern. No significant changes for the 24-h, daytime and night-time BPV were observed in the kidney donors at the same follow-up periods.

Previous studies suggested that BPV is increased in patients with CKD and associated with cardiovascular events and mortality [Citation19]. Among several mechanisms, SNS and renin-angiotensin system (RAS) hyperactivation, impaired baroreflex function, sodium and volume overload, arterial stiffness and sleeping disorders, have been proposed to contribute to the increased BPV in the CKD population [Citation16]. In KTRs, additional factors that are specific for these individuals, such as activation of immune system response against graft and the effects of various immunosuppressive drugs also play a role in the regulation of BP and may interact with the above mechanisms of BPV [Citation30,Citation31].

Studies evaluating BPV in KTRs are few and examined different questions. In a preliminary work in 73 KTRs, participants with endothelial dysfunction had significantly higher BPV levels than those without [Citation32]. A case-control study from our group with 306 participants (204 KTRs and 102 haemodialysis patients matched for age and sex) showed that short-term BPV levels are significantly lower in KTRs than in haemodialysis patients [Citation12]. Another study comparing short-term BPV between KTRs and individuals in pre-dialysis CKD (matched for age, sex and eGFR) found no significant differences between the two groups in all BPV indices studied except for DBP-SD [Citation22]. Finally, a work examining sex differences in short-term BPV in 136 male and 69 female KTRs showed that 24-h systolic and diastolic BPV parameters did not differ between groups; however short-term BPV over the night-time period showed different trends in men and women (increase versus drop) [Citation33]. With regards to living kidney donors, there is only one study in the field showing no significant differences in SBP-ARV and SBP-wSD between donors at five years after kidney donation and controls [Citation23].

Our previous work in the same population [Citation11], showed a reduction on BP levels and trajectories in KTRs after transplantation; however, in the present analysis, we found that BPV levels did not change over short- and mid-term follow-up. In general, simultaneous reductions of BP and BPV were observed with the use of some antihypertensive agents [Citation34,Citation35]; however, it has been previously shown that the reduction of BP is not always accompanied by short-term BPV changes (i.e. reduction of volume overload or use of agents with mild diuretic action [Citation27,Citation36]. As such, it has been assumed that changes in BPV may not be primarily attributed to change of BP per se but could depend on whether the studied intervention can also significantly modify the main pathogenetic mechanisms of BPV [Citation27]. Increased short-term BPV is a strong predictor of cardiovascular outcomes and death in CKD [Citation19]. Hence, one could assume that high BPV, which remained unaltered in the follow-up period after kidney transplantation, could be one of the many factors involved in the high cardiovascular risk observed in KTRs [Citation3,Citation4]. This hypothesis should be tested by studies specifically designed to examine the associations between BPV and adverse cardiovascular and renal outcomes in these individuals. Until then, physicians should keep in mind that part of the increased cardiovascular risk of KTRs may be due to high BPV, which remains unaltered after transplantation.

With regards to kidney donors, our analysis showed that BPV parameters remained almost unchanged at 3-month and 12-month after kidney donation, which came in agreement with previous studies showing no changes in BP levels over short and mid-term follow up [Citation11,Citation13–15,Citation37–40]. As far as long term changes concerned, although some studies suggest mild increase in BP [Citation41], most of the available evidence suggest that BP levels and hypertension incidence does not increase after kidney donation [Citation42–45]. These findings further support the evidence suggesting no higher risks of arrhythmias, cardiovascular events or death after living kidney donation when comparing with groups of the general population of the same age and characteristics [Citation42].

This study is the first to investigate the effect of kidney transplantation and kidney donation on short-term BPV parameters. It followed a prospective design and applied a strict methodology using valid 24-h ABPM readings at 3 different study time-points. In addition, we have measured all modern short-term BPV indices for different recording periods (24-h, daytime, night-time) to capture different components of it. As this is a secondary analysis of a prospective study aiming to ambulatory BP levels in ΚTRs and their respective donors at the short-term and mid-term periods after kidney transplantation, one could argue that the absence of significant differences with regards to BPV may be relevant to low study power for this secondary parameter [Citation11]; however, since statistically significant and clinically meaningful BP drops were found in KTRs and since the differences in BPV observed were small and without clinical importance, we have reasons to believe that our findings are true and not related to power issues. Finally, this is a single-centre study and participants were Caucasian, and thus, the conclusions cannot be directly generalised to other populations.

The present analysis showed that short-term systolic and diastolic BPV indices did not change significantly from baseline to 3- and 12-month evaluation after kidney transplantation/donation neither in the KTRs nor in living kidney donors. Future studies are warranted to shed more light in this field, by investigating the short- and long-term effects of kidney transplantation and donation on other types of BPV (i.e. long-term) and examine the associations between BPV with hard outcomes in these individuals.

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Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This article was not supported by any source and represents an original effort of the authors.

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