Objectives: Living-related kidney donation is the main source of renal grafts in Jordan, since kidneys from deceased donors are scarce. Although the Jordanian community accepts the idea of kidney donation to family members, not all potential donors manage to complete the required psychologic and medical evaluations. We review the causes of kidney-donation cancellation and suggest options to increase the number of available organs.
Materials and Methods: We performed a retrospective chart review of all potential living-related kidney donors at King Hussein Medical Center between January 2008 and June 2016.
Results: Of 642 potential donors, 366 (57%) were male and 276 (43%) were female, ranging in age from 18 to 66 years with a mean age of 37 years. A total of 384 (59.8%) eventually donated a kidney. A donor issue was the cause of cancellation in 143 (22.3%), whereas 47 (32.9%) had a risk for renal impairment after donation (eg, hematuria, proteinuria, stones, multiple renal cysts, scarred kidney, congenital malformation, recurrent urinary tract infection), and 30 (21%) had blood group or immunologic incompatibilities. Fifteen (10.5%) withdrew during the evaluation process, 13 (9%) had hypertension, 10 (7%) had a high body mass index, 8 (5.6%) were diabetic or prediabetic, 7 (4.9%) were surgically unsuitable, 4 (2.8%) had hepatitis B virus infection, 4 (2.8%) were pregnant, 3 (2.1%) had significant cardiovascular disease, 1 (0.7%) had splenomegaly with lymph node enlargement, and 1 (0.7%) had thyroiditis.
Conclusions: Cancellation of kidney donation in Jordan is mainly for medical reasons, the most common being renal issues. Paired donation between blood group and immunologically incompatible duos may increase the number of organs available, as may good psychologic assessment and counseling of those likely to change their mind. Support should be provided for donors who drop out of donation for any cause, especially for renal and vascular issues.
Key words : Kidney transplant, Living donor assessment, Living donor contraindications
Living kidney transplant is the best option for renal replacement therapy and offers a longer half-life for the transplanted kidney than a graft from a deceased donor.1,2 Living related donors are the main source of transplanted kidneys in Jordan, accounting for more than 98% of grafts. The Jordanian Act of Organ Donation defines a donor who is genetically related to the index patient as a first-, second-, or third-degree relative or as emotionally related (ie, spouse).
Although the Jordanian community accepts the idea of kidney donations to family members, not all potential donors manage to complete the extensive workup involved. We review the reasons for failure to complete the living-donor assessment and suggest options to improve donation rates.
Materials and Methods
We conducted a retrospective chart review and data analyses of all potential living-related kidney donors attending the transplant clinic for adult and pediatric patients at King Hussein Medical Center over a period of 8 years (from January 2008 to June 2016).
Initially, the transplant coordinator met with potential donors to discuss the procedure in detail and perform blood-group testing. If the blood group matched between the donor and recipient, the donor then met the nephrologist who started the clinical assessment and investigation, designed to take a minimum of 2 months to give the donor enough time to fully contemplate the undertaking. The nephrologist stressed the point that the donor may withdraw at any time. The final step was a multidisciplinary team assessment that included nephrologists, urologists, vascular surgeons, and any other specialty according to the individual case. We applied the international guidelines for donor selection,3,4 with some exceptions for selected patients.
The initial clinical examination and investigation included measurement of blood pressure, body mass index (BMI), chest radiography, electrocardiography, complete blood count, renal function testing, liver function testing, urinalysis, renal ultrasonography, viral screening, tissue typing and crossmatching, and any additional investigations warranted by the donor-recipient pair (Figure 1). The final step was renal computed tomography to assess the anatomy and vascular supply.
Absolute contraindications to donation were an age less than 18 years, hypertension with end-organ damage, diabetes mellitus, pregnancy, BMI > 35 kg/m2, thrombophilic disorders, cardiovascular disease, psychiatric disorders, hepatitis B or hepatitis C infection, renal disorders (eg, polycystic kidney, significant proteinuria, hematuria, stones), and the presence of more than 2 renal arteries (Table 1).3,4
Donors with 2 or more properly measured, seated blood pressure readings ≥ 140/90 mm Hg at 2 or more visits, with or without end-organ damage (eg, left ventricular hypertrophy, retinopathy, proteinuria), were excluded. Hypertensive donors taking 2 or more antihypertensive medications and young donors with high blood pressure readings (properly measured) were also excluded.
Diabetes mellitus was defined as a fasting plasma glucose level of at least 126 mg/dL or a plasma glucose level of at least 200 mg/dL, 2 hours after a 75-g glucose challenge, confirmed by a repeat testing on a different day (Table 2).5 We excluded individuals at high risk for type 2 diabetes (eg, history of gestational diabetes, first-degree family history of diabetes, and obesity) with an abnormal oral glucose-tolerance test. Prediabetic individuals with any other risk factor for diabetic nephropathy, including obesity, hypertension, or proteinuria, were also excluded from donation. Split renal function was measured using technetium-99 m-dimercaptosuccinic acid (DMSA) scintigraphy for potential donors who were found to have a considerable disparity in the size of the kidneys or an anatomic abnormality. A difference in function of more than 10% between the kidneys was considered significant.6 Proteinuria was defined as a spot urine albumin-to-creatinine ratio > 30 mg/mmol, a protein-to-creatinine ratio > 50 mg/mmol, or a 24-hour urine total protein > 300 mg/day on 2 separate occasions and was a contraindication for donation.3,4 All potential living donors underwent dipstick urinalysis on at least 2 separate occasions. Those with 2 or more positive tests (3 to 5 red blood cells per high-power field) underwent further evaluation, including urine culture and renal imaging, to exclude common urologic causes of hematuria, such as infection, nephrolithiasis, and urothelial carcinoma. If no cause was found, cystoscopy was performed in patients aged > 40 years to exclude bladder pathology. If nothing was found at cystoscopy and the donor still wished to donate, a kidney biopsy was considered. Glomerular pathology precluded donation, with the possible exception of thin basement membrane disease. Potential donors with a history of recurrent kidney stones, multiple stones, struvite stones, or metabolic risk factors for recurrent stones (eg, cystinuria, primary hyperoxaluria, hypercalcuria, hyperuricemia, metabolic acidosis) were excluded from donation.
Figure 2 shows the transplant activity for adult and pediatric patients at King Hussein Medical Center during our study period. Living-related kidney transplant accounted for 98% of procedures (Figure 3).
A total of 642 potential donors were identified: 366 (57%) were male and 276 (43%) were female, with an age range of 18 to 66 years (mean, 37 y). The relations between donors and recipients are shown in Table 3. Around half of the donors were siblings. Of the 642 potential donors, 384 (59.8%) actually donated, with a male-to-female ratio of 1.3:1. Younger donors, aged 18 to 39 years, accounted for 74% of donated kidneys (Table 4). A total of 143 potential donors (22.3%) cancelled because of their own medical, immunologic, or surgical reasons or because they withdrew during the assessment process. A total of 42 donors (6.5%) cancelled because of recipient issues, including death or other morbidity that contraindicated the transplant. Finally, 73 (11.4%) of the potential donor-recipient pairs were lost to follow-up.
Most donors (121 potential donors) cancelled for medical and immunologic reasons (Figure 4). The immunologic causes were ABO incompatibility in 16 donors, positive cytotoxic antibodies in 10, a 0% human leukocyte antigen match in 3, and a 0% match with positive cytotoxic antibodies in 1 patient. The most common medical cause for donor rejection was renal disease, found in 47 patients. The issues included hematuria, stones, congenital malformations, polycystic kidneys, proteinuria, and recurrent urinary tract infection (Table 5). A total of 13 candidates were found to be hypertensive, 10 had a BMI greater than 35 kg/m2, and 8 were diagnosed as diabetic or prediabetic with risk factors for diabetes mellitus. Screening for hepatitis B virus was positive in 4 patients, and 4 were pregnant. Significant coronary artery disease was diagnosed in 3 potential donors by coronary angiography after a normal initial cardiac workup. One potential donor was found to have generalized lymph node enlargement, and 1 had thyroiditis.
Seven donors (4.9%) were rejected for surgical reasons: 5 were found to have 2 or more renal arteries bilaterally, 1 potential donor had significant bilateral renal atherosclerosis, and 1 had an abdominal aortic aneurysm. Fifteen (10.5%) donors withdrew for personal reasons: a work commitment in 2 patients, a change of mind in 5, fear of surgery in 3, and planning for pregnancy in 1 woman; 4 donors declined to give a reason.
Living-donor transplant offers a better outcome in terms of graft survival and function compared with deceased-donor transplant, regardless of human leukocyte antigen matching.6 It also allows for preemptive transplant, which further enhances patient and graft survival.7 We report a high donation rate (59.8%), compared with other studies that have shown rates of 13% to 34%.8-10 Most transplant programs in the United States do not currently have an upper age limit for donors but consider an age of less than 18 years to be a contraindication for donation.11 The majority (67.5%) of our potential donors were young (18-39 years). Because younger donors are more likely to have time to develop diabetes, hypertension, obesity, or other factors that may progress to chronic kidney disease and, ultimately, end-stage renal disease,12 we were more stringent in our selection of young donors. Typically, women are more likely to donate,10,13 but we found that more men came forward as potential and actual donors, although the sex difference was not significant. Chera and associates demonstrated that there is significant variability in accepting living kidney donors at 44 centers in the United Kingdom, particularly regarding age, BMI, and hypertension.14
Hypertension is present in 30% of the general population, and the prevalence increases with age; some studies report that it is present in 2% of living donors at the time of donation (we observed a rate of 5%) and develops in up to 40% of donors over time.15,16 Garg and associates reported a 10-year hypertension rate of 16% postdonation, about 5% higher than in the control population.16 The literature suggests that transplant programs generally exclude donors with a BMI > 35 kg/m², and 10% of programs exclude donors with a BMI > 30 kg/m².17 Hassan and associates found that a higher BMI is the single predonation variable associated with every adverse postdonation outcome except for death, and each increase of 1 kg/m² is associated with a 3% to 10% higher risk of proteinuria and a reduced glomerular filtration rate.18 Patients with a BMI > 30 kg/m² almost universally develop proteinuria after nephrectomy and have a much higher rate of chronic kidney disease than those with a BMI below this level.17
Potential donors with a family history of type 2 diabetes (sibling or parental) have a 30% risk of developing diabetes over 5 years, and donation is usually contraindicated.5 It is not known whether patients prone to nephrolithiasis who donate a kidney have worse renal function outcomes than those who retain 2 kidneys. However, a recurrent stone may not affect the function of a remaining kidney if it is carefully monitored. The risk of recurrence after any single stone is difficult to predict in any individual. The younger the donor (ie, age 25-35 y), the longer the exposure to the possibility of recurrence.3,4
The evaluation of potential living donors is an expensive and labor-intensive process, and a large proportion of individuals who volunteer as donors will be found unsuitable for a variety of clinical and nonclinical reasons during the evaluation process. With the limited data available, it is impossible to create exclusion criteria that apply to all donors. Hence, it is important to evaluate donors in their totality and use the exclusion criteria in the context of other findings. Because younger donors are more likely to have time for any renal risk factors to lead to end-stage renal disease, we are more stringent in their selection. The main causes of cancellation in our series were medical and immunologic. The most significant medical causes were renal and cardiovascular; we recommend medical support and long-term follow-up for those who drop out of donation for any cause. Blood-group incompatibility and a positive crossmatch are major causes of cancelled donation. A paired donor-exchange program would help address immunologic incompatibility: 2 willing but incompatible live donor-recipient pairs are brought together for a swap. Some potential donors change their mind during the assessment period. This is unpredictable, so we recommend routine psychosocial assessment of potential donors and evaluation of the reasons for nondonation to help target those most likely to complete the donation process and also to better identify the issues that lead to withdrawal. Currently, not all of these issues are known and thus cannot be addressed.
Volume : 15
Issue : 1
Pages : 116 - 120
DOI : 10.6002/ect.mesot2016.O114
From the 1Royal Medical Services and the 2King Hussein Cancer Center, Amman,
Acknowledgements: The authors declare that they have no sources of funding for this study, and they have no conflicts of interest to declare.
Corresponding author: Katibh Al-Rabadi, Internal Medicine Department, Renal Division, King Hussein Medical Center, PO Box: 541802, Abo-nusair 11937, Amman, Jordan
Phone: +962 77 778 7511
Table 1. Contraindications to Donation12
Table 2. Diagnosis of Diabetes and Prediabetes5
Table 3. The Relations Between Donors and Recipients
Table 4. Age Groups
Table 5. Renal Disease Preventing Donation
Figure 1. Donor Evaluation
Figure 2. Adult and Pediatric Transplants at King Hussein Medical Center, 2008-2016
Figure 3. Living Versus Deceased Donations at King Hussein Medical Center, 2008-2016
Figure 4. Medical and Immunologic Causes of Cancellation