| Abstract|| |
Living donor kidney transplantation is the treatment of choice for the patients with end-stage renal disease, especially where deceased donor programs are limited. There are limited data on the outcomes of living kidney donors (LKD) from developing countries, especially from North Africa. The aim of this study is to evaluate the prevalence of hypertension (HTN) in LKD and to analyze its risk factors. This is a longitudinal monocentric study, and the donors who underwent nephrectomy for donation between 2006 and 2015 were included. Ninety-two donors were assessed. The mean age at the time of nephrectomy was 42.8 ± 10 years (21–68 years). The sex ratio was 0.6. At the time of donation, the median systolic blood pressure was 120 mm Hg and the median diastolic blood pressure was 70 mm Hg. HTN was noted in 4% of donors. The median follow-up duration was 26 months. Two years after donation, the prevalence of HTN was 28% in the study group (8% male and 20% female). The mean time to development of HTN was 16 months. Associations between HTN after donation and the cardiovascular family history, age >40 years, HTN, obesity, android obesity, glomerular filtration rate GFR <90 mL/min/1.73 m2, perioperative HTN, and dyslipidemia were noted. The multivariate analysis showed that obesity at the time of donation was a risk factor for HTN (odds ratio = 4.8; P = 0.04). Obese donor [body mass index (BMI) ≥30)] has higher risk of HTN after nephrectomy than nonobese donor.
|How to cite this article:|
Abdellaoui I, Sahtout W, Awatef A, Zallama D, Achour A. Prevalence and risk factors of hypertension following nephrectomy in living kidney donors. Saudi J Kidney Dis Transpl 2019;30:873-82
|How to cite this URL:|
Abdellaoui I, Sahtout W, Awatef A, Zallama D, Achour A. Prevalence and risk factors of hypertension following nephrectomy in living kidney donors. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2020 Mar 30];30:873-82. Available from: http://www.sjkdt.org/text.asp?2019/30/4/873/265463
| Introduction|| |
Kidney transplantation is the treatment of choice for the ever-increasing number of patients with end-stage renal disease. Living kidney donors (LKD) transplantation offers longer survival and a better quality of life at a lower cost than dialysis., In one hand, a randomized controlled American study (3698 donors) showed no significant difference in mortality and in chronic kidney disease (CKD) occurrence in donors compared to general population over 30 years of follow-up. On the other hand, a Chinese meta-analysis published in 2016 (including 62 study and 19 country), concluded to a prevalence of CKD of 1.1% and a mortality rate of 3.8% (all causes included). Moreover, renal-related mortality occurred after 10 years of follow-up. Those contradictions in donors’ outcomes led to many interrogations about the future of donors. Particularly, hypertension (HTN) is a major health problem in the general population in Tunisia. A significantly increased risk of HTN in donors compared to the general population was found in few studies since 1987., In a meta-analysis, Boudville et al found a higher prevalence of HTN after donation. Therefore, the occurrence of HTN in kidney donors and its risk factors are questioned. It is important to prevent HTN, by selecting candidates with lower risk, especially in Arab Muslim developing country like Tunisia, where the lack of cadaveric donors is leading to an increase in LKD numbers.
The aim of this study is to evaluate the prevalence of HTN in LKD and to analyze the possible risk factors in order to improve donors’ selection by avoiding the preventable factors.
| Material and Methods|| |
This is a longitudinal monocentric study, involving a cohort of 106 LKD which nephrectomies were performed between November 2007 and April 2015 in the nephro-logy ward in Sahloul Hospital, Sousse, Tunisia. All the donors were chosen following the Amsterdam Consensus Recommendations and the nephrectomies were performed respecting the Istanbul consensus.
In April 2016, the data of followed up donors were collected. Criteria of exclusion were lost of sight or lack of data at the time of donation or during the follow-up. The 91 donors, who attended medical visits as recommended by the European Renal Best Practice group, were included. Due to the irregularity of visits, we defined visits as following: M1 = from hospital discharge to the 3rd month, M3 = 3rd to 6th month, M6 = 6th month to the 1st year, A1 = 1st to 2nd year, A2 = 2nd to 4th year, and A4 = after 4 years.
We noted at the time of evaluation and at the periodical checkups, the physical (mainly HTN) and the laboratory parameters (the details are provided in the previous study in press: surgical wound).
Weight, height, diuresis, body mass index (BMI), systolic and diastolic blood pressure (SBP and DBP), urine stick test, creatinine blood level, estimated glomerular filtration rate (GFR), glycemia, lipids levels, uric acid blood rate, urine cytology test, 24 h proteinuria and microalbuminuria. HTN was defined as SBP superior or equal to 140 mm Hg or DBP superior or equal to 90 mm Hg and the measurements were performed in two consecutive visits. The BP was measured after the patient has been seated for 5 min with back supported and legs resting on the ground (not crossed). Arm used for measurement was rested on a table, at heart level. A sphygmomanometer/ stethoscope method was used with the correct size arm cuff. Two readings, 1–2 min apart, and the average readings values were noted. The diagnosis of HTN was confirmed at the subsequent visit three months after the first, after establishing lifestyle and diet changes. Obesity was defined as a BMI ≥30 kg/m2 and android obesity as waist circumference in men >102 and in women ≥88, according to criteria of the World Health Organization (WHO). Creatinine blood level was measured in the laboratory by means of a kinetic Jaffé method (Hitachi 917, Roche Diagnostics). The GFR was estimated using Modification of the Diet in Renal Disease formula and expressed in mL/min/1.73 m2 corporal surface. Proteinuria is defined as urinary protein excretion of >150 mg/24 h and microalbuminuria as excretion of albumin between 30 and 300 mg. the measurements were quantitative based on urine specimen collection (always discard the first morning void then a specimen of all subsequent voidings were collected, including the first morning void on the 2nd day). Proteinuria is expressed in g/24 h and microalbuminuria in mg/24 h.
| Statistical Analysis|| |
Data were statistically analyzed by Statistical Package for the Social Sciences version 20.0 software (IBM Corp., Armonk, NY, USA). The analysis of quantitative variables distribution was executed using the Kolmogorov–Smirnov test. Categorical variables were presented as percentages. Continuous variables as mean if data are normally distributed (±ET) and median if not (quartiles Q1, Q4). Paired t-test sample was used to compare mean values between visits. The prevalence of HTN was calculated with the prevalence rate formula (all new and preexisting cases during a given time period/population during the same time period *10n) and was expressed in percentage. Pearson Chi-squared test was used to analyze associations between normally distributed independent variables and the binary logistic regression for the multivariate analysis.
For all analyses, P <0.05 was considered to indicate statistical significance.
| Results|| |
Data at the time of donation
In this study, 106 donors (66 females and 40 males) were assessed at M1, M3, M6, Y1, Y2, and Y4 after donation. The median follow-up was 4.8 years (range: 3.5–8.5 years). The mean age was 42.8 ± 10.6 years (ranges: 21–68 years). Donors who had a family history of HTN were 28%, who had family history of diabetes were 25%, who had family history of cardiovascular diseases were 6.6% and 8.4% had family history of kidney disease. Characteristics of donors were detailed in the manuscript that described the donors’ follow- up.
The median SBP was 120 mm Hg and the median DBP was 70 mm Hg. Only 4% had HTN at the time of donation [Table 1]. One female donor was already taking angiotensin receptor II blocker (Irbesartan 150 mg/day) two years preceding donation and three donors were diagnosed with HTN at the moment of donation and treated by angiotensin-converting-enzyme inhibitor (ACE) (Enalapril 10 mg/ day). Their 24 h BP ambulatory monitoring (BPAM) were satisfying under one anti-HTN drug at the moment of donation. The mean BMI was 26 ± 4 (ranges: 16.6–26.2): 25.8 ± 3.5 among men and 26.9 ± 4.4 among women. Thirty-seven percent had a normal BMI, 41% had overweight, 20% had obesity stage 1 (WHO classification) and two donors have BMI ≥35 kg/m2 [Table 1].
|Table 1: Comparative study of the clinical parameters preceding and following donation.|
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Laboratory data at the time of donation
The mean serum creatinine level at the time of donation was 65 ± 14 μmol/L: 78 ±11 μmol/L for men and 57 ± 10 for women. The median GFR estimation was 105 mL/min/1.73 m2.sc: 105 mL/min/1.73 m2.sc for men and 110 mL/min/1.73 m2.sc for women. The majority of donors (more than 95%) had e- GFR >80 mL/min/1.73 m2.sc at the time of donation.
Metabolic profile: The median glycemia was 5.1 mmol/L (4.7; 5.7). The mean total choles-terolemia was 4.36 ± 0.8 mmol/L, the mean low-density lipoproteins-cholesterol rate was 2.84 ± 0.7 mmol/L and the mean triglycerides level was 0.79 ± 0.5 mmol/L.
Data at two years following donation
An increase in the mean SBP was noted immediately after nephrectomy, then it remained stable all along the follow-up (inferior to 140 mm Hg). The mean value of DBP was increasing all along the follow-up remaining inferior to 90 mm Hg. Comparison of mean values was detailed in [Table 1].
The prevalence of HTN in male donors two years after donation was 8%, and it was 20% in female donors. The prevalence of HTN in this study was 28% (14 donors). The mean period between donation and HTN occurrence was 16 months [Table 2]. No cases of gesta-tional HTN or preeclampsia were noted in female donors during follow-up. Six donors had HTN diagnosed with 24 h BPAM then treated by ACE inhibitor (enalapril 10 mg) and diet/lifestyle change recommendations followed. Four donors had normal BPAM after diet/ lifestyle change recommendations followed and have more frequent visits (every 3 months). Four hypertensive donors before donation were equilibrated under same treatment doses with strict diet/lifestyle change recommendations followed.
|Table 2: Prevalence of hypertension and other diseases two years after donation.|
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The prevalence of obesity was 22% before donation and 26% at Y2. The prevalence of obesity was higher among women before and after donation [Table 2].
The prevalence of e-GFR’s decrease (50–59 mL/min) was 14% at Y2.
The prevalence of proteinuria was 24% and equivalent in both genders. The prevalence of microalbuminuria was greater in women (18%) and 24% in all donors [Table 2].
Factors related to donors that may be associated with HTN onset were statistically analyzed. Regarding factors preceding the donation, we noted that an age ≥40 years, family history of cardiovascular diseases, HTN, obesity Stage 1 (WHO), android obesity, and a baseline e-GFR between 60 and 89 mL/min/1.73 m2 were associated with HTN following donation [Table 3] and [Table 4] .
|Table 3: Univariate analysis of associations between clinical parameters preceding donation and HTN.|
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|Table 4: Univariate analysis of associations between laboratory data preceding donation and HTN.|
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The removal of the left kidney seems to be a selection bias [Table 5].
|Table 5: Univariate analysis of association between clinical parameters following donation and HTN.|
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Regarding factors following donation, it was noted that transient postoperative HTN and hyperlipidemia were statistically associated [Table 6].
|Table 6: Univariate analysis of associations between laboratory data following donation and HTN.|
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The risk for an obese donor to develop HTN after donation is multiplied by 4.8 with a confidence interval of [CI (1.23–17); P = 0.04]. The obesity Stage 1 of the WHO classification is an independent risk factor for HTN at two years following donation.
The other parameters: age ≥ 40 years, an e-GFR <90 mL/min/1.73 m2 preceding donation, postoperative transient HTN, and hyperlipi-demia following donation were associated with a higher risk of HTN following donation but were not associated significantly in the multivariate study [Table 7].
|Table 7: Multivariate analysis of risk factors related to hypertension following kidney donation.|
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The multivariate analysis of associations between HTN and obesity preceding donation with proteinuria following donation is detailed in [Table 8]. It showed a significant relationship between android obesity (WHO criteria) with occurrence of proteinuria. The odds ratio was 0.17, with a CI of 0.02–1.2 and P = 0.07. The association was not significant for both BMI and HTN.
|Table 8: Multivariate analysis of associations between hypertension and obesity preceding donation with proteinuria following donation.|
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| Discussion|| |
The proportion of donors who had HTN preceding donation in this study was 4%. It was lower than proportions noted in the North American studies (11%–15%) and worldwide. It reached 17% in an American cohort and 18% in a French study and 24% in a Tunisian study., Reese et al and Briangon et al attributed this variability to the differences in transplantation hospitals and teams habits depending on the geographic location, donors availability, predominant age of donors, and transplantation activity frequency. Moreover, Segev et al noted that 7% of his study population had HTN before nephrectomy (7%). After nephrectomy in LKD, many studies did not show elevation in SBP or DBP after donation.,, However, others found an increase in SBP and in DBP. Surprisingly, Yazawa et al noted a decrease in DBP after nephrectomy in LKD. The prevalence of HTN, according to this study, increased from 4% to 28% two years following the donation. The prevalence of HTN is lower than the general population (35.9% in men and 46.2% in women). A significantly increased risk of HTN in donors compared to the general population has been observed in few studies since 1987., Boudville et al who found a higher prevalence of HTN following donation, had the limit of a high proportion of loss of sight donors. However, in other studies with less loss of sight, they found a lower prevalence., According to another Tunisian cohort of Helal et al with a 21-years follow-up study, 24% of donors were diagnosed with HTN. But a rate closer to 30%, like ours, was noted in other studies.,, According to El-Agroudy et al and Haberal et al, HTN in kidney donors was also less common than in the respective Egyptian and Turkish general populations. Garg et al found that gestational HTN and preeclampsia were noted among female donors in 8%–11% in their Canadian study. The Norway study and Minnesota study showed a prevalence of gestational HTN, respectively, 8% and 11% among female donors. In our study, two female donors did have a history of preeclampsia, but gestational HTN was not reported after donation. Disturbances in fasting glycemia and postprandial glycemia (metabolic syndrome) were described to be associated with increased risk of HTN and cardiovascular complications. These consequences seem to be more pronounced after nephrec- tomy. In an American large cohort, demographic changes in the US donor population including the increasing of older donors and the high-risk ethnic backgrounds proportions, such as African American, Native American, and Hispanic, influenced the prevalence of HTN and glucose intolerance among donors during the last 20 years. However, the same study showed that nephrectomy does not expose the donor to an increased risk of HTN. In 2010, Okamoto et al found that donors with glucose intolerance and nondege-nerative diabetes mellitus have the same risk of developing HTN as the general Japanese population. In our study, only obesity at the time of donation was identified as an independent risk factor. In the contrary, Boudville et al and Torres et al described several factors such as age >40 years, cardiovascular family history, and hyperlipidemia following donation. But in our study, we found those associations only in univariate analysis. Many studies agreed about the influence of obesity preceding donation on the onset of HTN following nephrectomy., However, Gossmann et al did not conclude to that association.
According to several studies, HTN occurrence is positively correlated with the age of the donor at the moment of nephrectomy. As for our study, Boudville et al and Gossmann et al did not prove it., On the contrary, elderly donors lowered their BP one year of nephrec-tomy, according to Dols et al. Same as the general population, probability of developing HTN in donors increases with aging during follow-up. Donor’s gender is still controversial, some studies, found that HTN following donation was independent of sex. Other authors considered that male gender is a risk factor of HTN after nephrectomy. In our study, HTN was diagnosed three times more in women than men. This seems to be a selection bias (sex ratio of 0.6). High SBP or DBP at the time of donation was associated with HTN following donation in some studies, but not in ours. Textor et al found a larger decrease in BP after donation in initially hypertensive donors, compared to normotensive donors. Moreover, a low GFR at the time of donation would be, for some authors, an independent predictor of HTN but in a specific population (African American ethnic groups). The correlation between proteinuria and increased microalbuminuria preceding donation with HTN following donation was not noted in several studies as well as ours. El-Agroudy et al found that proteinuria during donors follow-up was correlated with the elevated BP rates noted at the time of donation.
The limits of this study are the design, which is longitudinal and retrospective, and a short follow-up mean time, that was restrained for the majority (2 years) and a minority (>4 years). Also, it is a monocentric study, including a bigger sample of different centers, would be interesting. Furthermore, psycho-social and occupational outcomes were not mentioned in this study. The female gender was studied as risk factor for HTN, but another study with equal gender groups randomly enrolled is needed to analyze it correctly.
| Conclusion|| |
An obese donor with a BMI ≥30 kg /m2 is at high risk to have HTN after donation compared to nonobese donor. Other risk factors such as age >40 years, e-GFR <90 mL/min/ 1.73 m2 preceding donation, postoperative transient HTN, and hyperlipidemia following donation were associated with a higher risk of HTN, but the association was not significant in the multivariate study.
Conflict of interest: None declared.
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Department of Nephrology, Dialysis and Transplantation, Sahloul Hospital, University of Medicine, Sousse
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]