Most of these are retrospective or prospective observational studies that describe a heterogeneous group of donors that are considered medically complex. All have different definitions of hypertension (either because of the retrospective nature of the studies or because of the evolving definition of hypertension). All excluded donors on three or more antihypertensive medications, and all included donors with well controlled BP on one or more antihypertensive medication. Of these studies, only one  specifically mentioned looking for end-organ damage (with direct fundoscopy and transthoracic echocardiogram) and excluding patients with any evidence of end-organ damage. None of the studies included black donors. Donors’ median age ranged between the mid-40s to the mid-50s and median BMI was in the 26–30 kg/m2 range. About half of the donors were men, and all were described as having a ‘normal creatinine’ or ‘normal glomerular filtration rate (GFR)’ with no detectable proteinuria.
Of the more recent studies, a prospective study by Gracida et al. described a higher creatinine rise compared with controls among Mexican donors with preexisting hypertension and unmatched normal donors, whereas prospective studies by Textor et al. and Tent et al. both showed no significant change in BP, creatinine, and GFR among white donors with preexisting hypertension compared with matched controls. All three studies were limited by small number of patients and short follow-up period. A meta-analysis of long-term outcomes of hypertensive donors that included six small studies (five of which are in the table above) showed inconclusive results .
Looking more closely at the kidney and its adaptive physiology, Lenihan et al.[5▪] assessed the effect of predonation hypertension on 6-month postdonation BP, glomerular filtration rate, and glomerular volumes, estimated from renal cortical volumes measured radiologically, among 51 living donors that were categorized as normotensive young donors, normotensive older donors, and hypertensive older donors [5▪]. Despite the greater magnitude of glomerulopenia noted in hypertensive donors, no difference was noted in their postdonation BP, adaptive hyperfiltration (by iothalamate and hippurate clearances), and compensatory glomerular hypertrophy at 6 months.
In summary, these studies suggest that in the short term, white living donors with preexisting hypertension who have well controlled BP (<140/90) on less than two antihypertensive medications, seem to fare as well as control donors as long they are older (age >50), nonobese (BMI 26–30 range), and have no evidence of end-organ damage. In our experience with hypertensive kidney donors at the University of Pennsylvania, their perioperative BP management can be complicated. If they are on angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, or diuretics before donation, we usually need to alter this perioperatively because of expected volume shifts and adaptive hyperfiltration. This requires some time to allow adjustment to a new regimen and flexibility with dosing and agent choice because of side-effects. After donation, now with a single kidney and pain in the clinical scenario, these patients frequently experience a period wherein BP is more difficult to manage, potentially requiring more intense antihypertensive treatment post donation.
Compared with recipients of kidneys from normotensive donors, allograft outcomes from hypertensive donors are conflicting based on results from small studies with short-term follow-up. Although donor BP has been reported to be an independent predictor of 2-year allograft function in a retrospective study by Issa et al., Textor et al. showed no difference in mean serum creatinine, GFR, and urinary protein excretion at 1 year posttransplant. A study in Japan showed that although preexisting arteriosclerotic vasculopathy had lower allograft function at 1 and 3 years after transplantation as compared with arteriosclerosis-free kidneys, donor hypertension did not seem to play a role . This suggests that it is the extent of end-organ damage (i.e. arteriosclerotic vasculopathy) that may contribute to lower allograft function and not the diagnosis of hypertension per se; even then, Sofue et al. showed that 3-year patient and allograft outcomes are similar in those with and without preexisting arteriosclerotic vasculopathy. Whether longer-term follow-up will show any difference remains unclear.
At worst, these studies suggest lower allograft function from living donors with preexisting hypertension with end-organ damage when compared with normotensive donors. At best, they suggest similar allograft survival on short-term follow-up compared with living normotensive donors. To our knowledge, there have been no studies comparing hypertensive living donors with normotensive deceased donors or hypertensive deceased donors.
The clear benefit of transplantation with living donors vs. deceased donors , preemptive transplantation vs. not, less dialysis vintage, and marginal deceased donors (for certain groups of patients), compared with staying on the wait-list while receiving dialysis, has been well established [30,31]. Thus, although no data exist on this, we believe that living donor transplantation from hypertensive donors without end-organ damage will offer substantial benefits to patients compared with staying on dialysis.
CURRENT AVAILABLE GUIDELINES IN THE SELECTION OF HYPERTENSIVE LIVING DONORS
Several renal and transplantation societies have offered guidelines with regards to screening for and allowing hypertensive living donors; however, the various guidelines differ in the amount of detail provided.
The European Renal Association-European Dialysis and Transplant Association lists hypertension ‘without good control’ as an exclusion criteria from living donation . The Amsterdam Forum  recommends that patients with a BP of higher than 140/90 should not generally be accepted as donors. In addition, it recommends that BP be measured by ABPM, particularly for older donors (age >50) and those with high clinic BP readings. It also considers ‘easily controlled hypertension’ in donors who meet other defined criteria (e.g., age >50 years, estimated GFR >80 ml/min, and urinary albumin excretion <30 mg/day) as representing a low-risk group for the development of kidney disease after donation and suggests accepting these kidney donors.
The British Transplant Society  considers office BP measurements as being sufficient for most donors, and recommends only considering ABPM for hypertensive donors (defined as BP >140/90 or on antihypertensive medications). It further recommends that donors should be encouraged to minimize the risk of hypertension and its consequences (i.e. smoking cessation, frequent exercise, and weight loss when needed), and annual donor monitoring that includes BP measurement. It provided a more liberal approach to living donation stating that:
- BP that is controlled with one to two medications is not considered a contraindication to kidney donation provided significant organ damage has been excluded.
- Relative contraindications to donation include: end-organ damage, poorly controlled hypertension, and three or more antihypertensive medications.
More recently, the American Society of Transplant, American Society of Transplant Surgeons, Organization of Transplant Professionals, and United Network of Organ Sharing came together and released a Joint Societies Work Group Consensus Statement that detailed certain guidelines for transplant centers in the United States :
- BP should be measured in the office after a period of rest with an appropriate sized cuff on at least two occasions or by ABPM.
- Hypertension should be defined as a BP above 140/90 or an average day time BP above 135/85 on ABPM.
- ABPM should be considered in patients who appear to have white coat hypertension.
- Absolute contraindications for living donation included:
- Candidates with uncontrollable hypertension.
- Evidence of end-organ damage (proteinuria, left ventricular hypertrophy, retinopathy).
- Relative contraindications for living donation included:
- Hypertension in white donors older than 50 years.
- Hypertension in non-white donors at any age.
- Hypertension in white donors older than 50 years on more than one antihypertensive medication.
- White donors older than 50 years with hypertension that is easily controlled on a single medication with careful evaluation of other risk factors of metabolic syndrome and with adequate counseling of risks may be permitted.
Our center's general approach to hypertensive living donors contains elements of all of the above guidelines. We consider office BP measurements obtained while the patient is seated using an appropriate-sized cuff as sufficient for most donors. ABPM is used for donors suspected of having white coat hypertension and, occasionally, to assess BP control in hypertensive individuals. We use the JNC 8 guidelines with hypertension defined as BP above 140/90 . We screen all hypertensive donors for end-organ damage using urinalysis and transthoracic echocardiogram. In general, we will accept white hypertensive donors with BP that is well controlled on a single antihypertensive medication if the donor is older than 50 years and has no end-organ damage. For non-white donors, they may be considered on a case-to-case basis if they are otherwise in excellent health and are older than 55 years of age. A family history of hypertension, diabetes, and renal disease in first and second-degree relatives are the conditions which modifies the decision to proceed with donation.
We advise all donors on cardiovascular risk modification using lifestyle changes (i.e. weight loss, smoking cessation, among others) and medications. Consistent with the United Network for Organ Sharing (UNOS) guidelines, we collect outcomes data in all donors for more than 2 years.
In the past 5 years, the University of Pennsylvania has performed 300 living donor kidney transplants. Sixteen of these donors required single drug therapy for control of hypertension prior to donation. The average donor age was 56.1 years (range 48–66). Predonation, we make sure that the donor's BP is well controlled on a regimen that excludes renin–angiotensin–aldosterone system blockade and diuretics. Postdonation, donors with preexisting hypertension are followed more frequently than the average donor.
Considering the current shortage of organ donors and the evidence of clearly improved morbidity, mortality, and quality of life that transplants confer, transplant centers should make a concerted effort to expand the pool of potential living donors while protecting donor health. Although the data behind the absolute long-term safety of nephrectomy in hypertensive donors are lacking, small studies with short-term follow-up suggest no increase in incidence kidney disease or worsening of hypertension. Centers may consider following these donors more closely after donation, anticipating that changes in BP regimen after donation may be needed. To ensure the long-term safety of these hypertensive living donors, transplant centers should thoroughly screen hypertensive donors for other potential renal and cardiovascular risk factors, and have a collaborative effort (perhaps in the form of a donor registry) for the meticulous and long-term follow-up of these patients (not only for the current donors sake’ – but also to clearly establish the risks and help guide future donors).
The authors acknowledge the help of Dr Peter Abt from the Department of Surgery at the University of Pennsylvania who provided several suggestions for this manuscript based on his surgical experience with living kidney donors.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
- ▪ of special interest
- ▪▪ of outstanding interest
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Keywords:Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
cardiovascular risk; chronic kidney disease; hypertension; living kidney donation