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Should living kidney donors with hypertension be considered for organ donation?

Townsend, Raymond R.a; Reese, Peter P.a,b; Lim, Mary Anna

Current Opinion in Nephrology and Hypertension: November 2015 - Volume 24 - Issue 6 - p 594–601
doi: 10.1097/MNH.0000000000000169
DIALYSIS AND TRANSPLANTATION: Edited by J. Kevin Tucker and Mario F. Rubin
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Purpose of review The large number of end-stage kidney disease patients waiting for a kidney transplant often means years of delay before a suitable organ becomes available. Living kidney donors are one way to circumvent such long waiting times, and the desire to increase the pool of living kidney donors has allowed the selection of donors with hypertension.

Recent findings Hypertensive kidney donors, despite having larger glomeruli, and fewer glomeruli, particularly when over the age of 50 years, do well in follow-up. The data are mainly in white living kidney donors whose preexisting hypertension has been well controlled [blood pressure (BP) <140/90 mmHg] on one or two antihypertensive medications. Those selected for donation do as well as nonhypertensive donors as long they are older (age >50 years), nonobese (BMI 26–30 kg/m2), and have no evidence of end-organ damage prior to donation.

Summary Although the data supporting long-term safety of nephrectomy in hypertensive donors are modest, small studies with short-term follow-up suggest no increase in the incidence of kidney disease or worsening of the control of hypertension in donors with a history of high BP.

aDepartment of Medicine, Perelman School of Medicine

bDepartment of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania

Correspondence to Raymond R. Townsend, MD, Perelman School of Medicine at the University of Pennsylvania, Renal, Electrolyte and Hypertension Division, 122 Founders Building 3400 Spruce Street, Philadelphia, PA 19104, USA. Tel: +1 215 662 0430; fax: +1 215 662 3459; e-mail: townsend@exchange.upenn.edu

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INTRODUCTION

In 2014, there were more than 17 000 kidney transplants performed in the United States to benefit patients with poor or no kidney function. Breaking this down further, 11 570 kidneys were procured from deceased donors, and 5535 (∼32% of all transplanted kidneys in 2014) were removed from living donors (https://www.kidney.org/news/newsroom/factsheets/Organ-Donation-and-Transplantation-Stats, accessed 7 July 2015). Many more patients are on waiting lists at various transplant centers as the number of potential recipients greatly outstrips the number of available organs. Kidney transplants from living donors are often recovered from a family member, who graciously agrees to undergo unilateral nephrectomy for the sake of someone else. Kidney donation has traditionally been considered a procedure with reasonable risks, in part because the screening and selection process for donors is constructed in such a way as to minimize the lifetime risk of kidney disease or cardiovascular disease to the donor by selecting people at a low baseline risk level for these outcomes.

A common reason for discouraging a potential kidney donor from pursuing candidacy for kidney donation has been the presence of increased arterial blood pressure (BP) in the donor. These refusals to allow kidney donation are based on two rationales. First is the clear relationship between increased BP and the lifetime risk of end-stage kidney disease [1,2] as well as the higher likelihood of incident cardiovascular disease [3,4]. The second reason is that in the case of a living-related donation scenario, for example donation from a daughter to a mother, there is often a history of hypertension in the potential kidney recipient. Thus, a potential donor may have a family history of both kidney disease and hypertension, even though the donor is not hypertensive and has good kidney function at the time of evaluation.

The presence of established hypertension in a potential kidney donor, which may be well controlled either with lifestyle measures alone, or with one or two antihypertensive agents, is an increasingly common presentation for kidney donor selection committees. In general, the evaluation process for future cardiovascular and kidney function risk for a potential kidney donor will include the assessment of the duration of the potential donor's hypertension, how well controlled has it been, and whether there been a known target organ event such as heart attack, heart failure, stroke, or peripheral arterial disease. Hypertension tends to be more likely in an older potential donor. In limited studies of donors older than 50 years of age with hypertension on two or fewer antihypertensives, or hypertensive as determined by an ambulatory BP monitor study but not currently treated, Lenihan et al.[5▪] demonstrated that they have a reduced number of glomeruli, and larger glomeruli compared with age-matched normotensive donors in biopsies done at the time of donation. Nonetheless, these donors had similar increases in renal cortical hypertrophy at 6 months, and similar increased single kidney filtration with no obvious worsening of their BP at 6 months after donation compared with normotensive kidney donors [5▪].

To our knowledge, there is no standardized method to evaluate the degree of BP control at transplant centers that allow controlled hypertension patients to be kidney donors. At the University of Pennsylvania, we use 24-h ambulatory BP monitoring because of its established value as a cardiovascular and renal function loss risk predictor [6▪,7], although home BP monitoring likely provides a reasonable reflection of overall control when properly performed [8]. Ambulatory monitoring allows not only an assessment of daytime BP control, but also provides information on the BP level during the night, which provides additional insight into the future risk of target organ damage [9]. Both ambulatory BP monitoring and home BP monitoring allow the detection of masked hypertension wherein the out-of-clinic BPs are higher than those recorded in the clinic setting. It is important to detect masked hypertension as it carries a similar risk for target organ damage as sustained uncontrolled hypertension, and is present in up to 20% of office-controlled hypertensive patients [10].

We allow controlled hypertensives on one antihypertensive medication to donate when our living kidney donation transplant donor selection committee is convinced that the overall risks to the potential donor are acceptable given the potential for benefit to the recipient, and psychologic benefit to the donor. Specific criteria we use are presented in the final section of this review.

Box 1

Box 1

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HYPERTENSION IN LIVING KIDNEY DONORS

Kidney transplants from living donors with preexisting hypertension have been reported for over two decades. However, perhaps owing to the restricted use and inconsistent follow-up of these donor and recipient pairs, data on the outcomes of these donors and recipients remain sparse. The Organ Procurement and Transplant Network (OPTN) started collecting living organ donor data in 1987. This has been used to look at large-scale donor outcomes. However, the OPTN did not collect donor BPs until 1999, and even then, BP data were often missing, incomplete and lacked ambulatory BP recordings, thus preventing subgroup analysis of outcomes from hypertensive donors.

The unease for accepting living donors with preexisting hypertension stems from a concern for recipient safety and, to a limited extent, uncertainty regarding allograft outcome. Safety concerns for the donors arose from previous consideration of hypertension as a risk factor of end-stage kidney disease, and the concern that a reduction in renal mass from donation will result in an even higher risk for kidney disease. Apart from these, the conflicting results regarding any increased risk of hypertension on long-term follow-up of normal donors added to the apprehension in accepting hypertensive individuals as living donors [11–17]. It should be noted that among normal donors, a higher incidence of postdonation hypertension was observed on studies with longer periods of follow-up time, whereas studies with shorter follow-up periods showed no change to a lower incidence of postdonation hypertension. Some authors argue that although hypertension is present postdonation, this appears to be similar to the general population when corrected for age and sex, thus arguing against the increased risk conferred by nephrectomy [11,15,17]. Furthermore, in a Canadian study, although donors had a higher incidence of hypertension, they were also seen more frequently by their primary care providers, suggesting the higher incidence of hypertension in donors may be a result of surveillance bias [18].

What follows is a short review on the available data regarding donor and recipient outcomes in kidney transplants performed from living donors with preexisting hypertension. This will be followed by a brief review of available guidelines in the selection of living donors with preexisting hypertension, suggestions to improve the selection process, and an outline of our center's approach to donors with preexisting hypertension.

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DONOR OUTCOMES

Published data on recipient outcomes of living donors with preexisting hypertension are summarized in Table 1[5▪,19–25].

Table 1

Table 1

Table 1

Table 1

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 [22] 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.[21] 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.[22] and Tent et al.[24] 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 [26].

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.

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RECIPIENT OUTCOMES

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.[27], Textor et al.[22] 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 [28]. 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.[28] 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 [29], 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.

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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 [32]. The Amsterdam Forum [33] 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 [34] 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:

  1. BP that is controlled with one to two medications is not considered a contraindication to kidney donation provided significant organ damage has been excluded.
  2. 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 [35]:

  1. 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.
  2. Hypertension should be defined as a BP above 140/90 or an average day time BP above 135/85 on ABPM.
  3. ABPM should be considered in patients who appear to have white coat hypertension.
  4. Absolute contraindications for living donation included:
    1. Candidates with uncontrollable hypertension.
    2. Evidence of end-organ damage (proteinuria, left ventricular hypertrophy, retinopathy).
  5. Relative contraindications for living donation included:
    1. Hypertension in white donors older than 50 years.
    2. Hypertension in non-white donors at any age.
    3. Hypertension in white donors older than 50 years on more than one antihypertensive medication.
  6. 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 [36]. 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.

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CONCLUSION

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).

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Acknowledgements

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.

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Financial support and sponsorship

None.

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Conflicts of interest

There are no conflicts of interest.

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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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REFERENCES

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This is a nicely done study with careful renal function evaluation using clearances of iothalamate and hippuran so that filtration fraction, and degree of hyperfiltration, could be assessed in the postdonation period.

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Thorough overview of the literature attesting to the value of ABPM in the diagnosis of hypertension and in risk assessment.

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Keywords:

cardiovascular risk; chronic kidney disease; hypertension; living kidney donation

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