|Year : 2021 | Volume
| Issue : 3 | Page : 215-222
Value of ambulatory blood pressure monitoring in potential renal donors - A prospective observational study
Mital Dipakkumar Parikh, Umapati Hegde, Mohan Rajapurkar, Sishir Gang, Abhijit Konnur, Hardik Patel
Department of Nephrology, Muljibhai Patel Urological Hospital, Nadiad, Gujarat, India
|Date of Submission||28-Jun-2020|
|Date of Decision||30-Sep-2020|
|Date of Acceptance||28-Apr-2021|
|Date of Web Publication||30-Sep-2021|
Dr. Mital Dipakkumar Parikh
A/5 Vrundavan Park Society, VIP Road, Karelibaug, Vadodara - 390 018, Gujarat
Source of Support: None, Conflict of Interest: None
Introduction: Hypertension is very common among urban as well as rural population. In our donor selection policy, uncontrolled hypertension or target organ damage is a contraindication to kidney donation. Studies of blood pressure (BP) response to unilateral nephrectomy in kidney donors in short- and long-term are needed. We studied BP in kidney donors by ambulatory BP monitoring (ABPM) and the effect of unilateral nephrectomy on BP in them for 1 year following kidney donation. Methodology: We enrolled 80 consenting kidney donors aged between 20 and 65 years and followed them serially at pre, 6, and 12 months postkidney donation. Estimated glomerular filtration rate (eGFR) was measured using chronic kidney disease exocrine pancreatic insufficiency (CKD EPI) formula. BP was measured in the clinic (sphygmomanometer) and by ABPM (MeditechABPM05). eGFR, two-dimensional echocardiography, ophthalmological fundus examination, and 24 h proteinuria measurement were done at each visit. Results: There was a significant difference in predonation systolic BP by clinic and ABPM (138.07 + 5.5 vs. 117.17 + 10.2; P < 0.001) suggestive of white coat hypertension (WC) effect in 32 donors (40%) which decreased to only 21 (26.25%) donors having WC effect at 12 months of follow-up. There was masked hypertension (MH) in total 3 (3.75%) donors with sustained hypertension (SH) in 10 (12.5%) donors. BP was stable by ABPM till 1-year postdonation. Mean systolic and diastolic BP by ABPM was significantly higher in SH and MH groups as compared to WC and sustained normotensives. Baseline predonation eGFR measured by CKD-EPI was 106.0 + 12.35. eGFR decreased to 80.15 ± 15.76, i.e. 76% of the baseline eGFR. Hypertension by ABPM at baseline was associated with more decrease in the eGFR at 1 year of follow-up particularly in those with age > 50 years and higher body mass index. Proteinuria increased from the baseline value of 82.7 ± 29.94–104.07 ± 49.36 mg/day at 1 year of follow-up. Conclusions: ABPM provides a more accurate and reproducible estimate of BP compared to clinic BP to rule out WC hypertension and MH in kidney donors. Unilateral nephrectomy has no significant impact on kidney function or proteinuria over 1 year.
Keywords: Ambulatory blood pressure monitoring, hypertension, nephrectomy, proteinuria, renal donors
|How to cite this article:|
Parikh MD, Hegde U, Rajapurkar M, Gang S, Konnur A, Patel H. Value of ambulatory blood pressure monitoring in potential renal donors - A prospective observational study. Indian J Transplant 2021;15:215-22
|How to cite this URL:|
Parikh MD, Hegde U, Rajapurkar M, Gang S, Konnur A, Patel H. Value of ambulatory blood pressure monitoring in potential renal donors - A prospective observational study. Indian J Transplant [serial online] 2021 [cited 2021 Dec 5];15:215-22. Available from: https://www.ijtonline.in/text.asp?2021/15/3/215/327394
| Introduction|| |
Renal transplant is the best renal replacement therapy for end-stage renal failure. Live donor kidney transplant has better outcome than deceased donor transplant but is limited by the availability of a suitable donor. Hypertension is a common disorder, majority are asymptomatic, often found incidentally. Donor selection policy at our institute allows taking donor with hypertension easily controlled by one drug without any evidence of end-organ damage (proteinuria <150 mg/24 h, no evidence of hypertensive retinopathy) with age >50 years with estimated glomerular filtration rate (eGFR) >80 ml/m2 particularly if no other living related donor or adequate dialysis facilities are unavailable. Roy et al. showed that there is increase in hypertension prevalence from 23% to 43% in urban and 11.2% to 52.9% in rural NCR over 20 years (1991–1994 survey to 2010–2012). An increase in BP is commonly observed following nephrectomy, however, an increase in BP into the hypertensive range in previously normotensive individuals remains to be determined.
Manual BP monitoring/Office BP measurement (OBPM) may show increased levels of blood pressure (BP), due to the white coat (WC) effect or stress of kidney donation/investigations. Many patients with WC hypertension are regarded to be at increased risk simply if BP is measured only by OBPM. Ambulatory BP monitoring (ABPM) helps to identify truly hypertensive, by ruling out WC hypertension and also to confirm masked hypertension (MH). Tom Pickering used the figure of 10% in the general population, which clarifies that MH is not an uncommon finding. In contrast to WC hypertension, MH is seen much more frequently in younger patients, and more so in males than in females. Bobrie et al. showed that the relative risk for cardiovascular disease (CVD) in MH is 2.06. ABPM is the best measurement methodology for assessing BP during sleep. Nocturnal nondipping increases the risk of target organ damage. ABPM predicts significantly better of cardiovascular (CV) and cerebrovascular events than OBPM and correlates with end-organ damage including left ventricular hypertrophy, proteinuria. 10-year follow-up from the OHASAMA study showed RH (95% confidence interval) of 2.13 for CVD mortality/stroke. Ohkubo et al. showed 2.56 times the risk of CV mortality among nondippers.
We undertook this study to correctly identify various forms of hypertension among potential kidney donors using the ABPM technique.
| Methodology|| |
This is a prospective observational study conducted in the Department of Nephrology of Muljibhai Patel Urological Hospital, Nadiad, Gujarat after prior approval of the scientific and ethics committee.
Aims and objectives
(1) To establish the diagnosis of hypertension in voluntary kidney donors by ABPM (2). To study the effect of unilateral nephrectomy on BP in kidney donors up to 1 year after donation.
All voluntary kidney donors evaluated at our institute between May 2016 and April 2017 were enrolled.
All kidney donors willing to give written informed consent.
Donors rejected for medical reasons.
All donors were evaluated in standard clinical examination including detailed history and examination. All donors were followed for 1 year after donation as per the study protocol.
Three readings of OBPM were done during clinic visits under identical conditions, in supine and standing positions by the physician according to the WHO/ISH guidelines and the mean of 3 was taken. ABPM was recorded using Meditech ABPM 05. Normal ABPM was defined as global arithmetic mean of ABPM <130/85 mmHg in a patient not on antihypertensive drugs with a “dipper circadian profile pressure.” Donor was said to have well-controlled hypertension if global mean ABPM of <130/85 mmHg on drug therapy. Evidence of end-organ damage (cardiac/renal/ophthalmology) was measured by two-dimensional echocardiography (2DEcho) to look for hypertrophy, ophthalmological examination for evidence of hypertensive retinopathy and 24 h urine for protein measurement and by calculating eGFR (using chronic kidney disease-exocrine pancreatic insufficiency [CKD-EPI]). Similar protocol (OBPM, ABPM, 2DEcho, Ophthalmology, renal evaluation-creatinine, and proteinuria) was carried out postkidney donation at 6 months and 1 year of follow-up to look for the effect of unilateral nephrectomy on BP and target organs.
The number of renal transplants in 1 year is approximately 120 at our center. Student's t-test and Chi-square test were used for testing the effect of donor nephrectomy on Hypertension occurrence with Power of test (1‒β) = 0.84 odds ratio 84% and Level of significance (α) = 0.05 or 5%. The sample size was calculated with the reference from the study “ABPM in potential renal transplant” Nephrol Dial transplant (2000) by Ozdemir et al. We could recruit 102 donors in our study with the power of study being 82%.
Declaration of patient consent
Patient consent has been taken for participation in the study and for publication of clinical details and images. Patients understand that the names, initials would not be published, and all standard protocols will be followed to conceal their identity.
Muljibhai Patel Society for Research in Nephro-Urology Ethics Committee (MPSRNUEC). Registration no.- ECR/276/Muljibhai/Inst/GJ/2013/RR-19. All protocols were followed as per Declaration of Helsinki. The procedure was carried out in accordance with the Declaration of Helsinki and International Council for Harmonization-Good Clinical Practice (ICH-GCP).
| Results|| |
Total 108/110 patients underwent live renal transplants during May 2016 to April 2017. Total 80 donors were included in the final analysis- as shown in [Figure 1].
Total 80 donors were included in the final analysis. 74% of donors were females with a mean age of 47.16 ± 9.9 years. By Indian standards, 13 (16.25%) donors were overweight and 45 (56.25%) were obese. There were 7 donors who were hypertensive before enrolment for kidney donation, their BP was well controlled on medications and no evidence of end-organ damage and hence they were selected for kidney donation. The mean age of the donors was 47.16 ± 9.92 years with a mean body mass index (BMI) of 25.85 ± 3.86 kg/m2.
Prevalence of white coat hypertension and sustained hypertension at baseline, 6 months and 12 months
Donors were divided into following four category as per their ABPM results (1) sustained normotension (n = 35), (2) MH (n = 3), (3) WC hypertension (n = 32) and (4) sustained hypertension (SH) (n = 10). WC hypertension which was 40% at baseline, remained at 26.25% at 12 months.
SH reduced to 7.54% at 12 months from 15.5% at baseline. MH reduced to 1.25% at 12 months from 3.75%. Sustained normotensives (SN) were 65% at 6 months as compared to 43.75% at baseline [details shown in [Figure 2] below]. WC hypertension and SH reduced as compared to baseline clinic BP and ABPM.
Amongst all groups, the sustained HTN group had high mean BMI, S. creatinine and 24 h urinary protein with lower eGFR at baseline, however, it did not reach a significant level. Masked hypertensive donors had higher mean age and lower eGFR at baseline as compared to the other 3 groups [Table 1].
|Table 1: Demographic characteristics and laboratory parameters of all donors over 12 months|
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Such high prevalence of WC HTN at baseline may be related to anxiety and stress of kidney donation and related investigations. Subsidence to normotension with time in majority suggests its benign nature and requiring only close follow-up.
Mean systolic BP by clinic method as well as by ABPM were higher in MH group as compared to SN (P < 0.0001 and P = 0.03 respectively). There was a statistically significant difference between SN and WC with respect to mean systolic BP by clinic and ABPM (P < 0.0001 and P = 0.004 resp.) Mean systolic-diastolic BP by clinic method was significantly higher in MH group as compared to the WC group (P < 0.0001) [Table 2].
Hypertenive kidney donors
When all 10 sustained hypertensive donors were followed as a group, there was 33.15 ml/min/m2 reduction in eGFR at 6 months (P < 0.0001) and 31.73 ml/min/m2 at 12 months as compared to baseline (P < 0.0001). Furthermore, the reduction in eGFR was statistically significant when compared to all other three groups together at 6 and 12 months (P < 0.05). As all of these were given treatment, only 5 remained HTN. MH had more percentage decrease in eGFR as compared to sustained normotension and WC hypertensives, though not statistically significant.
There was 43 mg/day increase in proteinuria at 6 months (P = 0.03) and 23.10 mg/day increase at 12 months (P = 0.06) when compared to baseline, however it was not found to be statistically significant when compared to all other groups.
The change in systolic BP by ABPM at 6 and 12 months was statistically significant when compared to their baseline (a decrease of 4.9 mmHg at 6 months, P < 0.05 and a decrease of 8.6 mmHg at 12 months, P < 0.05) as well as compared to other 3 groups (P < 0.05). The diastolic BP didn't differ much between the groups at 6 and 12 months.
Relationship between estimated glomerular filtration rate and ambulatory blood pressure monitoring
Percentage decrease in eGFR was statistically higher in hypertensives at 6 months (34%, P = 0.01) and at 12 months (30%, P = 0.008) as compared to normotensives (26% and 24%, respectively showing that those who had hypertension by ABPM were more likely to show less increase in eGFR by hyperfiltration/adaptation or have less renal reserve by 1 year of follow-up. But similar fining was not found when decrease in eGFR and hypertensives by OBPM was considered. This may be related to the difference in the method of measuring BP suggesting ABPM to be better method for identifying true hypertensives. There was no statistically significant difference in 24 h urinary protein increase amongst the hypertensives and normotensives at 6 and 12 months follow-up by both OBPM and ABPM [Table 3].
|Table 3: Relationship between estimated glomerular filtration rate and ambulatory blood pressure monitoring/office blood pressure measurement|
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Change in renal parameters after nephrectomy
When we compared the mean hemoglobin of the donors at baseline and at 6 and 12 months, there was no statistically significant difference with mean hemoglobin. There was statistically significant increase in serum creatinine at 6 and 12 months as compared to baseline (0.67 mg%, 0.97 mg% and 0.94 mg% P < 0.001. Similar reductions in estimated GFR was noted at 6 and 12 months with respect to baseline (106, 77.9 and 80.15 ml/min/m2 - P < 0.001). The average decrease in eGFR was 28.5% after kidney donation. Furthermore, there was statistically significant increase in mean 24 h urinary protein excretion at 6 and 12 months compared to baseline (82.7 mg/day, 103.3 mg/day and 104 mg/day P < 0.001) [Table 4].
|Table 4: Effect of nephrectomy on hemoglobin, creatinine, estimated glomerular filtration rate and proteinuria|
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The overall eGFR reduction after kidney donation was 28.5% at 6 months and 24.5% at 12 months compared to baseline. The reduction in eGFR was significantly higher in the sustained HTN group when compared to those who had WC HTN or sustained normotension both at 6 and 12 months [Table 5]. Even though the proteinuria increased post kidney donation, it was within the normal limits. Type of hypertension did not make any difference on proteinuria over 12 months period.
|Table 5: Effect of pattern of hypertension on estimated glomerular filtration rate and proteinuria post kidney donation|
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Kidney donation and changes in blood presure, estimated glomerular filtration rate and proteinuria as per age groups
We arbitrarily divided donors into three age groups as shown in [Table 6] and studied their effects on kidney donation. As the age advances, there was steady increase in serum creatinine and reduction in estimated GFR which was statistically significant between the three groups (P < 0.05). The percentage change in eGFR at 6 months between Group 2 and 3 was statistically significant (P = 0.03). Observed 24 h urine protein excretion showed increase in the levels as age advances and also as the time post kidney donation, although nonsignificant statistically between Groups 1 and 2 and Groups 2 and 3 except when compared between Groups 1 and 3 at baseline (P = 0.03).
|Table 6: Effect of kidney donation on blood pressure, estimated glomerular filtration rate and proteinuria as per age groups|
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BP by clinic method showed an increase as the age advances which was statistically significant (P < 0.05). However, as time passed, the BP showed a downward trend implying WC effect at baseline. BP by ABPM also showed a similar increase in trend with age (P < 0.05), this difference was maintained till 6 months of age.
Proteinuria more than 150 mg post kidney donation
At the end of follow-up of 1 year, 8 donors had their 24 h urine protein excretion >150 mg/day-1 of whom had MH and 4 had WC hypertension. Mean 24 h urine protein increased to 210 mg/day at 12 months from mean value of 104 mg/day at baseline in this group. The mean age of this group was 48.87 years with a mean BMI of 25.58. However, none had SH.
Estimated glomerular filtration rate <60 ml post kidney donation
At the end of 1 year, total 8 donors had eGFR of <60 ml/min/m2 - of whom 1 had SH and 2 showed WC hypertension. Mean eGFR decreased from 88.33 ml/min/m2 at baseline to 54.71 ml/min/m2 at 12 months. The mean age of this group was higher (52.37 years) with a mean BMI of 25.07.
| Discussion|| |
Our study showed a significant difference in predonation systolic BP by clinic method and ABPM suggestive of WC effect which was 40% in our case. About 12.5% of patients were SH which reduced to 7.5% at the end of 1 year. BP increased with age. Proteinuria mildly increased after kidney donation. Kidney function measured by eGFR (CKDEPI) reduced significantly by 24.5% of the baseline by 1 year.
A number of studies have noted that among those who have elevated BP by clinic method, 30%–60% have BP in normotensive range by ABPM. Our study adds to this literature.
Grossman et al. in his cohort of 152 donors with a mean follow up time after uninephrectomy of 11 ± 7 (range: 1–28) years found increase of BP from 125 ± 15/79 ± 11–134 ± 19/81 ± 9 mmHg (P < 0.01) (still in the normotensive range). Thiel et al. found that the risk of developing hypertension, defined as >140/90 mm Hg, increased 3.64-fold 1-year post kidney donation. Those who developed hypertension at 1 year may have been prehypertensive or more susceptible to developing hypertension.
Hypertension (defined as >140/90 mm Hg) was identified in 41% of African-American donors in a study with an average follow-up length of 7 years, compared with 30% of Caucasians. African-American and Hispanic donors are also at about a 50% increased relative risk of developing hypertension postdonation., Higher incidence of hypertension and kidney disease in African American's might be due to APOL1 and MYH 9 mutations. A prospective study by Kasiske et al. followed living kidney donors over a 3-year period, observed systolic and diastolic BP increased slightly and significantly over time in both donors and controls, but there were no significant differences between the two groups; in addition, the 24-h ABPM of both groups was not statistically significant after 3 years. In our prospective analysis, we demonstrate similarly that early after-donor nephrectomy BP is stable by ABPM. The short-term effects of donor nephrectomy upon ambulatory BP support the assumption of low CV risk of the procedure for well-selected donors. ABPM showed less change after 6 months, unlike clinic SBP.
In addition, we observed that the WC effect started waning as time passes after donation providing assurance about the CV safety of kidney donation in this group.
Recently published cross-sectional retrospective study on a population of 573 kidney donors (mean age at donation 47 years) with a follow-up of 14 years, GFR increased during the 1st years after donation and decreased thereafter. The most cited factor associated with the risk of decreased GFR is age,,,,,, and high BMI has also been associated with the risk of a lower postdonation GFR in the study of Ibrahim et al. Similar to this we also found significant decrease in eGFR at 6 months (drop of approximately 24%), by 12 months, it showed an increase of 2% reaching to 76% of the baseline value.
The sustained hypertensives and masked hypertensives had more decrease in eGFR at 6 and 12 months post kidney donation as compared to WC hypertensives and SN with no significant change in 24 h urine protein excretion. Thus the two groups at significant higher risk for progression and CV risk were sustained hypertensives and masked hypertensives which could be picked up only by the ABPM method.
There were total of 42 normal dippers (52.5%). Around 78.5% of normal dippers were normotensive by ABPM while 21.5% had hypertension by ABPPM. This dipping characteristic could be picked up only ABPM method. Also, it suggests a higher percentage of nondippers (including reverse dipper and extreme dippers) in the hypertensive group. Nondippers have increased CV risk and identifying this nondipper group by ABPM helps to risk stratify those donors. It is clear that ABPM in patients deemed to have hypertension by clinic BP will identify a large number of individuals with WC hypertension and therefore enable otherwise ineligible patients to proceed with donation. This significantly benefits potential donors who are eager to donate and also recipients who are otherwise faced with an extended waiting before receiving a transplant.
Proteinuria postnephrectomy is due to hyperfiltration, effect of the aging process or due to the coexisting co-morbidities in the kidney donor. In the study involving 70 living kidney donors from Cleveland clinic, there were 13 (19%) patient who had a 24 h urinary protein excretion >0.15 g/day. Garg et al. in his meta-analysis of 42 trials (n = 4793) with a mean follow up of 7 years showed a prevalence of 12% in proteinuria (>150 mg/day) which is comparable to the prevalence of proteinuria of 10% at 1 year in our study, however the mean 24 h urine protein excretion at 12 months was (104.07 ± 49.36).
Elderly donors >50 years had significantly low eGFR at baseline along with increase in 24 h urine protein excretion, their BP by OBPM and ABPM and mean interventricular septum thickness was higher compared to those <35 years and 36–49 years. Also, they showed more decrease in their eGFR as time passed postdonation with similar increasing trend in 24 h urine protein excretion similar to the results by Miller et al.
Limitations of the study
Duration of follow-up of 1 year is short, further follow-up may detect more increase in BP and decline in eGFR with increasing proteinuria among kidney donors and high-risk groups (elderly obese hypertensives) in particular. We didn't measure creatinine clearance either 24 h urine collection or isotope scan, but only estimated GFR was measured by CKD-EPI equation. Single-center study and sample size was smaller to draw any conclusion.
It has been planned to continue this study further by following these kidney donors over 5 and 10 years to fulfill the stated objectives over long term.
| Conclusions|| |
ABPM is a better method of assessing BP in potential kidney donation. It increases the donor's pool by identifying WC effect (40%). SH was 12.5% and MH was seen in 3.75% of kidney donors. With increasing age, BP by OBPM and ABPM showed significant increase in systolic BP. eGFR also reduced as the age advanced. Unilateral nephrectomy is associated with no short-term (1 year) increased risk of hypertension, proteinuria and decline in eGFR among carefully selected donors by ABPM. Mean eGFR at 1 year after kidney donation was 75.45% of the baseline eGFR. In our experience, evaluation of prospective donors by ABPM provides, a more accurate and reproducible estimate of BP when compared with the OBPM.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]