Objectives: The development of hypertension can negatively affect cardiovascular and renal outcomes in renal kidney donors. Here, we retrospectively investigated the frequency and risk factors of hypertension development in healthy renal donors at our center.
Materials and Methods: Living donors of kidney transplants performed between January 1998 and December 2016 were evaluated. Those > 18 years old, having glomerular filtration rate > 70 mL/min/1.72 m2, body mass index ≤ 35 kg/m2, and proteinuria < 300 mg/day were eligible. Those with a history of diabetes and hypertension and < 1 year of follow-up were excluded.
Results: In the 190 included donors, mean follow-up was 56 ± 45 months, mean age was 47 ± 10 years, and 48% were women. Baseline systolic and diastolic blood pressures were 118 ± 13 and 76 ± 8.8 mm Hg. Follow-up showed that 19 donors (10%) developed hypertension. These donors were older and had higher baseline systolic blood pressure (126 ± 13 vs 117 ± 12 mm Hg; P = .003), proteinuria (162 ± 89 vs 117 ± 63 mg/day; P = .05), fasting blood glucose (99 ± 10 vs 94 ± 9.6 mg/dL; P = .03), and uric acid levels (5.4 ± 1.7 vs 4.5 ± 1.2 mg/dL; P = .04). Although these donors had baseline glomerular filtration rates (97 ± 22 vs 104 ± 22 mL/min/1.72 m2; P = .19) similar to other donors, levels were lower at last follow-up (62 ± 14 vs 71 ± 19 mL/min/1.72 m2; P = .03). In multiple regression analysis, preoperative fasting blood glucose, systolic blood pressure, and serum uric acid levels independently predicted hypertension development.
Conclusions: In healthy renal donors, preoperative detailed evaluations can provide important information foreseeing the development of hypertension after nephrectomy.
Key words : Aneurysm, Brain death, Renal transplant
Because of a shortage of deceased donations, the rate of living-donor kidney transplant has gradually increased in Turkey and in the world. Hemodynamic and metabolic changes are commonly observed in healthy donors after nephrectomy.1-3 Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) have been shown to increase after donation, with relative risk for hypertension shown to be about 1.9.1,2 Although ethnicity and genetic differences can affect hypertension development, hypertension can occur in all donors, negatively affecting cardiovascular and renal outcomes. In this study, our aim was to evaluate the frequency of hypertension development after kidney donation in a healthy Turkish population and to identify the risk factors.
Materials and Methods
Living donors of kidney transplant procedures performed in our center between January 1998 and December 2016 were evaluated. Eligible living donors were those > 18 years old, having glomerular filtration rate (GFR) > 70 mL/min/1.73 m2, having body mass index (BMI) ≤ 35 kg/m2, and having proteinuria level of < 300 mg/day. Donors with a history of diabetes and hypertension and less than 1 year of follow-up were excluded from the study. Baseline and follow-up data of donors were extracted from medical records and reviewed retrospectively. Donors were divided into 2 groups according to median serum uric acid level.
Our study included 190 donors. The mean follow-up was 56 ± 45 months (range, 12-215 mo). The mean age was 47 ± 10 years (range, 19-72 y), and 48% of donors were women. Baseline and last follow-up GFR, serum urea, and uric acid results in donors were 103 ± 22 mL/min/1.73 m2 (range, 70-177) versus 70 ± 18 mL/min/1.73 m2 (range, 19-145), 29.2 ± 8.7 mg/dL (range, 14-50) versus 29.2 ± 8.7 mg/dL, and 4.6 ± 1.3 mg/dL (range, 1.0-9.2) versus 5.6 ± 1.4 mg/dL (range, 2.6-9.5), respectively (P < .001).
Mean baseline SBP was 118 ± 13 mm Hg (range, 160-80 mm Hg), and mean baseline DBP was 76 ± 8.8 mm Hg (range, 90-50 mm Hg), whereas results at last follow-up showed that mean SBP (125 ± 15 mm Hg) and DBP (79 ± 9.6 mm Hg) had increased (P < .001). During follow-up evaluations, 19 donors (10%) had developed hypertension. Donors with hypertension were older (52 ± 6.9 vs 47 ± 11 y; P = .03) and had higher baseline SBP (126 ± 13 vs 117 ± 12 mm Hg; P = .003), proteinuria levels (162 ± 89 vs 117 ± 63 mg/day; P = .05), fasting blood glucose levels (99 ± 10 vs 94 ± 9.6 mg/dL; P = .03), and uric acid levels (5.4 ± 1.7 vs 4.5 ± 1.2 mg/dL; P = .04). The donors with new-onset hypertension had baseline GFR results (97 ± 22 vs 104 ± 22 mL/min/1.73 m2; P = .19) similar to other donors but had lower GFR results at the last follow-up (62 ± 14 vs 71 ± 19 mL/min/1.73 m2; P = .03). These results are shown Table 1.
When the donors were divided into 2 groups according to baseline uric acid level, those with uric acid > 4.5 mg/dL had higher BMI (27.7 ± 3.6 vs 25.8 ± 3.6 kg/m2; P < .01) but similar baseline GFR (101 ± 22 vs 105 ± 22 mL/min/1.73 m2; P = .32) and serum urea values (30 ± 8.7 vs 28 ± 8.7 mg/dL; P = .14). However, GFR was lower in the hyperu-ricemic group at last follow-up (67 ± 17 vs 72 ± 18 mL/min/1.73 m2; P = .05).
Our Kaplan-Meier analysis showed that rate of hypertension development was higher in the group with high baseline uric acid level (P < .05) (Figure 1). In multiple regression analysis, which included age, sex, SBP, preoperative fasting blood glucose, GFR, uric acid, and proteinuria as variables, we found that preoperative fasting blood glucose, SBP, and serum uric acid levels independently predicted hyper-tension development.
We observed a mean increase of 7 mm Hg in SBP and 3 mm Hg in DBP after 5 years of follow-up in our donors. Hypertension developed in 10% of our patients. In various studies and meta-analyses, in-creases in both SBP and DBP after donor nephrectomy or occurrence of non-dipper-type blood pressure (which indicates a nocturnal reduction in average daytime blood pressure of less than 10%) have been reported.1,2,4-6 A high incidence of hypertension (up to ~30%) has been shown in both predominantly White and Japanese cohorts after a mean of at least 15 years of follow-up.6,7 However, these studies had a retrospective case cohort design and lacked a comparable control group. In the meta-analysis of Boudville and associates, which included 5145 donors, a 5-mm Hg increase in SBP and a 1.9-fold increase in the risk of developing hypertension were observed at 5 to 10 years after donation.1 In a recent meta-analysis that evaluated the results of 52 studies involving 118 626 living donors and 117 656 healthy controls (nondonors), O’Keeffe and associates found a higher DBP and 5-fold worse renal outcome in living donors than in the nondonors. However, there was no difference in SBP and hypertension frequency.2 In contrast, in a recent prospective randomized study of living kidney donors, Kasiske and colleagues did not find any statistically significant differences between donors and controls in 24-hour ambulatory blood pressure measurements at year 3 after donation.8 The only limitation of the study was the relatively short follow-up, which hindered observation of donor changes that may occur in later periods.
Many risk factors leading to the development of hypertension, including advanced age, male sex, baseline blood pressure, and high BMI, have been identified.1-3,6,7 Similarly, in our study, those who developed hypertension were older and had higher BMI and fasting blood glucose values. Donors with these risk factors should be assessed before donation with ambulatory blood pressure and microalbuminuria measurements in terms of predicting hypertension development.
Hyperuricemia is associated with hypertension, cardiovascular disease, and chronic kidney disease.5 Kulah identified an association between worsening kidney function and predonation elevated serum uric acid levels and suggested that pretransplant uric acid levels > 6 mg/dL in men and > 5 mg/dL in women could predict posttransplant creatinine levels for the remaining kidney with almost 80% accuracy.9 Undurraga and associates reported a gradual increase of uric acid up to > 7.5 mg/dL in nearly one-third of donors 5 to 10 years after donation.10
In an interesting work that offers reliable evidence, Matsukuma and colleagues demonstrated arteriolar hyalinization in “time 0” biopsies of 393 living kidney donors and found a significant association between arteriolar hyalinization and serum uric acid levels in multivariable logistic analysis. In their study, the severity of hyalinosis was directly proportional to the level of serum uric acid.11 In our study, a high uric acid level before donation was a sign of hypertension development. This elevation may be an early indicator of endothelial damage in the kidney or in macrovascular structures, even in healthy donors.
Our study had some limitations. It was relatively small, lacked an adequate control group, and had a short follow-up period. In addition, microalbu-minuria, an important parameter in predicting endothelial injury and renal survival, was not analyzed.
In conclusion, preoperative detailed evaluations in healthy renal donors can provide important information that could foresee the development of hypertension after nephrectomy. We found that preoperative SBP, fasting blood glucose, and serum uric acid levels were associated with the development of hypertension.
Volume : 17
Issue : 1
Pages : 156 - 158
DOI : 10.6002/ect.MESOT2018.P32
From the 1Department of Nephrology and the 2Department of General Surgery and
Transplantation, University of Health Sciences, Izmir Bozyaka Education and
Research Hospital, Izmir, Turkey
Acknowledgements: The authors have no sources of funding for this study and have no conflicts of interest to declare.
Corresponding author: Adam Uslu, University of Health Sciences, Izmir Bozyaka Education and Research Hospital, Bahar Mahallesi, Saim Çıkrıkçı Cd. No:59, 35170 Karabağlar/İzmir, Turkey
Phone: +90 542 656 10 10
Table 1. Comparison of Donors With and Without Hypertension
Figure 1. Kaplan-Meier Analyses Comparing Hypertension Development Rates in Groups With High and Low Uric Acid Levels