EXPERIMENTAL AND CLINICAL TRANSPLANTATION

We conducted a literature search on the status of living donors, donor health, and risks of donations in living liver, kidney, pancreas, lung, and small intestine donors. The literature search was made using the PubMed database and the following key words: living donor, transplantation, liver, kidney, lung, pancreas, and small intestine. We found that living donors have a generally favorable outcome; however, follow-up should not be limited to 2 years since some complications may be seen in later years. Systems should be developed for early detection of problems, and future research should be directed to nonhuman sources for the treatment of end-stage solid-organ diseases.

Key words : Intestine, Kidney, Liver, Living donor, Lung, Pancreas, Transplantation

Because living donors are healthy individuals with normal functioning organs and are performing an altruistic act, extreme care must be given at every phase of the donation process. The initial step includes informing the candidate about every aspect of donation, especially about the risks of surgery and the postoperative period. The second step is a thorough medical evaluation to decide whether the candidate is eligible as a donor, and the third step is the surgery. The postoperative period can be divided into the early phase and the long-term follow-up. The possible expected complications and consequences encountered later are especially important both for the actual donors and for future potential donors. Data about such problems should be recorded in registries and stored to better inform future living donors and to maximize their safety. Such data are particularly useful for meta-analysis studies.

The risks to living donors may be divided into 3 basic categories. The first one is the psychologic status during the process of contemplation over the decision to be a donor. A potential donor generally experiences stress, anxiety, hesitation, and fear during this period. Living donors may be frustrated if they are rejected because of medical reasons. The postoperative emotions are generally positive, which include pride, feeling of doing something good, and more conviction about the benefits of organ transplant. If the recipient faces serious complications and possible graft rejection, then the donor can easily develop a negative mood. If the individual is psychologically ready to be a donor, then thorough information and literature data should be conveyed to help with the final decision. The person should give consent without any interference and pressure of any kind and only under their own will. The second phase is the detailed medical investigation and examination to confirm that the candidate has no contraindications to be a donor. The surgical complications can be categorized as general complications that may be faced during any kind of surgery and specific complications associated with organ retrieval. Morbidity and mortality seen in the first 30 days of surgery are considered to be related to surgery. Donors are generally followed for 2 years. Experience has shown the need for long-term follow-up because it allows a more accurate documentation of the consequences of being a living donor.

Liver, kidney, lung, pancreas, and small intestine can be transplanted from living individuals to recipients. Although the aim remains to increase the rate of deceased organ donations, it is apparent that the present demand exceeds the available organs from deceased donors, which in turn creates the need to obtain organs from living donors. There are guidelines for evaluation and preparation of living donors. The quotation from the World Health Organization, “Live donations are acceptable when the donor is informed and voluntary consent is obtained, when professional care of donors is ensured and follow-up is well organized, and when selection criteria for donors are scrupulously applied and monitored,” summarizes the basic principles to be followed for living donors.¹ The Istanbul Declaration,² the Vancouver Forum,³ and the Amsterdam Forum4 are other important sources of reference.

Advantages of using organs from living donors for transplant are optimal timing of surgery, better organ quality, and decreased recipient mortality. Globally, 42% of kidney and 18% of liver transplants are from living donors; when all transplant activities are taken into consideration, 35% of transplants are from living organ donors. In Turkey, 78% of kidney transplants were from living donors in 2016, whereas, in 2017, this rate was 76% (3736/4908).

The first successful transplant in Turkey was a kidney transplant from a related living donor. The surgery was performed by Prof. Mehmet Haberal and his team at Hacettepe University Medical Center (Ankara, Turkey) in November 1975. The first successful living-donor liver transplant in a child was also performed by Prof. Haberal and his coworkers at the Turkish Transplantation and Burn Treatment Foundation Hospital (Ankara, Turkey) in March 1990. The same team also conducted the first adult living related liver transplant at the same medical center in Turkey in April 1990. From December 1988 to May 2018, 69% of the 598 liver transplants were performed with organs obtained from living donors. In the same period, 77% of 2868 renal transplants were done with kidneys from living individuals.⁵

The present Turkish law permits living organ donation under certain circumstances. The related donation includes up to fourth-degree kinship and also relatives-in-law of the same closeness. In marriages of at least 2 years, the husband and wife can donate to each other. Cases of unrelated donations are brought to the city ethical council for decision. The council is composed of a lawyer, a social worker, a physician, and a psychiatry specialist from both a nontransplant medical center and a government representative. The council has the right to ask for any information aside from the medical data of the potential donor and the recipient that have been registered to the national data center.

Although the goal remains to increase deceased organ donations, the combination of deceased and living organ donors has not satisfactorily supplied the growing demand, which has grown over the past 6 decades despite efforts in educating the general public and medical staff and other activities aimed to increase organ donation. Therefore, the hope is for future research and treatment options for end-stage organ diseases to include cell transplant, artificial liver support systems, bioartificial livers, bioreactors filled with functioning liver cells, and extracorporeal devices.

Liver
In a Medline data search from 2000 to 2017 of morbidity and mortality in adult-to-adult living-donor liver transplant, the investigators reviewed 382 articles and 23 papers that mentioned donor deaths. This review showed that the major cause of death was sepsis and that morbidity ranged from 10% to 78.3% depending on the study. Risk factors for donors were right liver donation, being overweight, amount of liver removed, and biliary complications. Donor preconditioning and donor portal vein flow modulation were suggested as techniques to reduce donor complications.⁶

Abecassis and colleagues⁷ reported a 40% overall incidence of complications; 1% incidence of residual disability, liver failure, or death; and 2% to 5% risk of aborted donations in living-donor hepatic lobectomy. Complications were classified as Clavien-Dindo grade I (minor), grade II, and grade III (residual disability) at 1.1% and grade IV (death) at 0.4%. The authors noted transfusion requirement, intraoperative hypotension, and predonation serum bilirubin value as risk factors. Resolution rate of overall complications at 1 year was 95%; however, hernias and psychologic complications resolved at 75% and 42%, respectively, at the end of the first year.⁷

In a study of biliary complications in living liver donors, Shaji Mathew8 and associates found no correlation between postoperative biliary complications and type of graft, portal vein anatomy, or biliary anatomy. One case of mortality was noted in 452 hepatectomies. Biliary complications that caused important perioperative morbidity to donors were seen in 3% of patients.⁸

Woo and associates⁹ also reviewed biliary complications after living liver donation. Biliary complications occurred in 49 of 337 right lobe donors, with biliary leakage observed in 36 patients and biliary stricture in 13 patients. In 35 patients, complications were successfully managed by endoscopic retrograde cholangiography, balloon dilatation, or endobiliary stenting.⁹

Hsu and colleagues¹⁰ reported that small remnant liver volume, defined as less than 35% remnant liver, can harbor a higher risk of developing minor complications. The authors noted that left lobe liver donations in middle hepatic vein-dominant donor candidates present potential risks.¹⁰

In a series of 587 patients who underwent right lobe hepatectomy over a 17-year period, 187 postoperative complications were observed in 141 patients (24%). There were no donor deaths. The authors concluded that only the center volume of right hepatectomy was associated with postoperative complications.¹¹

In a review of 473 consecutive living liver donors over a 19-year period, Ho and associates¹² found a 20.9% overall complication rate and 3.2% biliary morbidity rate. Morbidity rates were 27.2% and 9.5% for right and left hepatectomies, respectively. Right liver donation was regarded as a risk factor. Being overweight was thought of as having a possible protection against right hepatectomy morbidity.¹²

Contradictory reports have been published about liver donations from living elderly individuals, and biliary complications seemed to be increased with use of livers from older donors. Lue and associates¹³ reported that morphologic and structural changes in the liver occur over time and that biological changes in the aging liver can lead to loss of proliferative response and regeneration. However, in contrast to these findings, the investigators reported that liver function seemed to be nearly normal.¹³

Kidney
Na and colleagues¹⁴ reported on creatinine levels at 1 year and at greater than 3 years posttransplant in living kidney donors. Of 362 patients included in the study, 15.7% had chronic kidney disease after 3-year follow-up. The authors reported that 43.2% of those patients had failed to recover renal function. Older age, history of hypertension, and low glomerular filtration rate at 1 year posttransplant were risk factors.¹⁴

In a meta-analysis of 52 studies on long-term health risks that included 118 426 adult living kidney donors and 117 656 nondonors, living kidney donors had no increased risk for development of major chronic diseases, including type 2 diabetes mellitus and adverse psychosocial outcomes compared with that shown in the nondonor population.¹⁵

Keys and associates¹⁶ reported their experience with living kidney donor outcomes after 50 or more years of follow-up. Of 66 donors, only one-third were alive after this long follow-up time. Hypertension was observed in 74% of the living donors at a mean age of 59.9 ± 14.0 years. Diabetes mellitus was seen in 18% at a mean age of 62 ± 19.4 years. Proteinuria developed in 16.7% at a mean age of 60.6 ± 18.2 years. For all of these findings, the incidence was similar to an age-matched general population.¹⁶

Hong and coworkers¹⁷ reported on the benefits of a laparoscopic approach in obtaining kidneys from living donors. The authors reported that laparoscopy decreased perioperative blood loss and shortened hospital stay and found neither mortality nor renal failure with this approach. Of the 83 patients included in the study, hypertension developed in 18.2%, diabetes mellitus was shown in 2 patients (2.6 %), and proteinuria was seen in 4%.¹⁷

Complications in complex living renal donations were studied by Thukral and associates.¹⁸Donors were 60 years or older or younger than 60 years. The latter group had hypertension and obesity. Results at 5 years posttransplant revealed significant deterioration in renal function, blood pressure, and body mass index.¹⁸

In a report on 3 prospective studies on quality of life in living renal donors from 2001 to 2010, Klop and associates¹⁹ found overall quality of life to be excellent. A lowered physical component scale was found to be related to age and body weight. The authors drew attention to older and obese donors, stating that these donors may have reduced physical quality of life after donation. The authors concluded that, if a choice between available donors could have been made, younger donors and donors with lower body mass index would be preferred.¹⁹

The impact of smoking on living kidney donors was assessed in 612 individuals in which 68.1% never smoked, 8% were former smokers, and 23.9% were current smokers. Donors with smoking history, even if they did not smoke during the transplant process, carry increased risk of developing chronic kidney disease after kidney donation.²⁰

Age alone has not been considered as an absolute contraindication to kidney donation provided that careful selection is made for candidates over 60 years of age.²¹ On the other hand, obese donors were found to develop diabetes mellitus and hypertension more frequently and earlier than nonobese donors after donation.²²

Perioperative mortality is generally below 1% in living kidney donors. Early perioperative risks include bleeding, deep vein thrombosis, pulmonary embolism, wound complications, urinary tract infection, atelectasis, and pneumothorax. Significant chronic disease, obesity, hypertension, intolerance to oral glucose test, anticoagulation, chronic viral infection, active cancer or history of cancer, high body mass index, low glomerular filtration rate in relation to age, proteinuria, hematuria, anatomic anomalies, nephrocalcinosis, and bilateral kidney stones have all been considered as contraindications for being a living renal donor.

Lung
In a review of 369 living lung donors (72% having biologic relationship with the recipients and 30% being parents of recipients), Yusen and colleagues²³ found no related mortality but reported that 18% had serious complications. The most common complications were postoperative cardiac arrhythmia, pericarditis in 3% of the patients, pneumothorax, pleural effusion, and bleeding that required chest tube drainage. In addition, the authors noted that 2.2% of the patients had reoperation and 6.5% had early rehospitalization. However, no donors required lung transplant.²³

Pancreas
Boggi and associates²⁴ reported that segmental (spleen-preserving) living pancreas donation carries a low rate of complications. The authors claimed that the risk of mortality was not lower than that shown with living kidney donation; however, because of lack of available data, the authors stated that estimating risk of death for living pancreas donors is not accurately possible. The group reported that prevalence of type 2 diabetes mellitus in nonobese donors did not exceed 3% and the risk of type 1 diabetes mellitus did not seem to increase. Splenectomy was expected to be performed in up to 15% of living donors due to ischemia or bleeding. Specific surgical complications were found to be related to management of pancreatic stump, and general complications were expected to be around 5% for living pancreas donors. A rare late bleeding from esophogastric varices was also observed.²⁴

Margreiter and associates25 reported no deaths in living pancreas donors, but 3 of 78 patients required splenectomy. Drainage of abscesses or fluid collections was done percutaneously in some patients. The group noted that serious complications may include impaired glucose tolerance after pancreas donation, with 3 donors found to be nonnormoglycemic during follow-up.²⁵

Small intestine
Pain and changes in defecation and frequent diarrhea have been reported in living small bowel donors posttransplant. However, complications had recovered fully within 2 to 6 months, and education on diet was suggested.²⁶

Tzvetanov and colleagues²⁷ stated that intestinal grafts may be susceptible to rejection because of high concentrations of lymphoid tissue and the consequent need of high levels of immune suppression to prevent rejection. The authors reported no deaths and no life-threatening complications. Close monitoring on a monthly basis and then annually to review nutritional habits and bowel habits was suggested.²⁷

The demand for small bowel transplant has been calculated to be 1 to 2 per million; therefore, it has been suggested that there should be enough deceased donors.²⁵ Potential living organ donors can be actual donors only after they are fully informed on every step of the transplant process, including unexpected consequences related to the recipient. All possible medical and surgical risks, work and financial losses, and alternative treatment options for the recipient must be explained in detail. The potential donor can then consider these factors and make an informed decision. There should be no pressure on the individual, and the final decision to donate must be taken with free will, free from coercion and under the most favorable conditions.

Living-donor eligibility criteria and contraindications to donate should be homogenized, and common guidelines and algorithms should be developed for use among all societies to minimize donor risks and morbidity and mortality rates. An example is a clinical decision support system developed by Knight and colleagues based on national living-donor guidelines covering different aspects of nephrectomy in potential living donors.²⁸

With the global demand exceeding the availability of organs from deceased donors, organs from living individuals are necessary. Although literature reports have revealed that organ retrieval from living donors is safe, living donations are not part of the solution for organ shortages. Furthermore, even when deceased and living donations are combined, supply is still short versus the growing demand. Therefore, new research areas, including cell transplant, bioartificial livers, artificial liver support systems, bioreactors filled with functioning liver cells, and extracorporeal devices, may bring hope and new alternatives for treatment of end-stage organ failure.

Volume: 18 Issue: 1 January 2020 - Supplement - 1

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