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Volume: 17 Issue: 1 January 2019 - Supplement - 1

FULL TEXT

Posttransplant Care of Kidney Transplant Recipients and Their Donors in Nigeria

Objectives: Kidney transplantation is not readily available in low-resource settings because of poor health structure, dearth of experts, and pervading poverty. Although many centers now offer kidney transplant, patients still travel outside Nigeria for this service for many reasons and many return home without a detailed medical report.

Materials and Methods: Medical records of individuals who underwent kidney transplant in Nigeria and elsewhere and who were presently receiving post-transplant care or had received such care from 2002 to 2018 at 4 Nigerian hospitals were retrospectively reviewed and analyzed.

Results: Of 35 patients (30 males; 85.7%) analyzed (mean ages of 42 ± 16 and 47 ± 8 years for men and women, respectively; P = .54), common primary kidney diseases included hypertension (27.2%), glomerulo-nephritis (24.2%), and diabetes mellitus/hypertension (18.3%). Most patients received transplants in India (48.6%), with others in Nigeria (23.0%) and Pakistan (8.6%). Relationships to recipient were unrelated (28.5%), living related (22.9%), and unknown (48.6%). Less than 30% of recipients had care details in their hospital records. Almost all transplant patients were treated with prednisolone (81.8%); cyclosporine (40.0%), mycophenolate mofetil (31.4%), tacrolimus (20.0%), and azathioprine (9.1%) were also used. Complications were documented in 88.9%, with57.0% due to bacterial infections/sepsis. Many (88.9%) had more than 2 complications. In follow-up, median first transplant duration was 24 months (interquartile range, 6-44). Of total patients, 25.7% were still alive, 17.1% had died, and 54.2% were lost to follow-up. Follow-up data for only 2 donors were available.

Conclusions: Lapses in follow-up care of kidney transplant recipients and donors continue in low-resource settings where transplant tourism is still rife, resulting in poor graft/patient survival. Adherence to transplant guidelines is advocated. We propose a transplant stratification model according to level of development and resources of countries or regions. This model will encourage customizing strategies for improving patient outcomes.


Key words : Posttransplant complications, Poverty, Transplant development stratification, Transplant tourism

Introduction

Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are increasing, and various meta-analysis have highlighted high prevalence globally,1 in Africa,2 and in Nigeria.3 Kidney transplantation is the preferred treatment for most patients with ESRD.4 However, this procedure is not readily available in low-resource settings because of poor health structure, dearth of experts, and pervading poverty that precludes many from accessing the criterion standard of care treatment.5,6 Potential kidney recipients and donors are routinely evaluated according to the guidelines.7-16 After successful transplant, recipients are followed up in accordance with guidelines adopted by the transplant program. Previously, kidney donors were thought to be largely free of long-term complications, especially if well matched.17 However, recent evidence shows that it may not be so. Studies from the United States18 and Norway19 have demonstrated some significant complications. These underscore the need for adequate and proper follow-up of both recipients and their donors. Newer guidelines have em-phasized the need for proper donor and recipient evaluations before and after transplant.7,13,16,20

Before 2000, kidney transplant procedures were not possible in Nigeria. Most patients who had ESRD received only dialysis (hemodialysis and peritoneal dialysis), and those who could afford it accessed kidney transplant abroad. However, the first kidney transplant procedure in Nigeria was performed in 2000, pioneered by a private hospital in Lagos.5,21 Since then, many other hospitals have introduced kidney transplant services. As of February 2018, there are 12 such centers with different levels of function and expertise.22 Despite this growth, many patients still travel outside the country to access transplant services for a variety of reasons, including cheaper cost of service and ease of accessing relevant medications.5 Many such patients who access kidney transplant abroad come back without proper medical reports,6,23 in particular essential information like HLA typing and tissue crossmatching and rela-tionship to donor. Donor evaluations and immediate care posttransplant are not included in reports. As a result, adequate and appropriate follow-up of recipients and donors have become a problem as they are transplanted in a different facility in the same or a different country from where they are followed-up.

The objective of this study was to evaluate kidney transplant recipients (and their donors) who were followed at 4 main facilities in 2 of 5 southeast states in Nigeria from 2002 to 2018.

Materials and Methods

Our retrospective study included individuals who underwent kidney transplant in Nigeria and else-where and who received posttransplant care in 4 hospitals in Southeast of Nigeria (Figure 1). The study was approved by the institutional ethics committee of the University of Nigeria Teaching Hospital (Ituku-Ozalla, Enugu, Nigeria).

The medical records of patients who were currently receiving posttransplant care or had received such care at 2 privately owned and 2 government-owned tertiary institutions in Ebonyi and Enugu States were reviewed. Data were extracted from hospital medical records, medical reports, referral letters, and investigation reports. Data included demographics (age, sex, occupation, place of domicile), medical history (primary cause of ESRD), and transplant-related information (kidney donor, relationship of donor to recipient, HLA typing, tissue crossmatching, date of transplant, place of transplant, immunosup-pression regimen, outcome of transplant, drug levels, posttransplant complications, and patient and graft survival).

Statistical analyses were performed with SPSS software (SPSS: An IBM Company, version 21.0, IBM Corporation, Armonk, NY, USA). Sociodemographic variables were collated and summarized. Inde-pendent variables were compared with t tests for continuous variables and chi-square tests for categorical variables. Statistical significance was set at P < .05.

Results

Demographic and other characteristics
Thirty-five kidney transplant recipients were followed-up from January 2002 to July 2018. The demographic attributes of kidney transplant recipients are shown in Table 1. Most patients were male (n = 30; 85.7%). The mean ages were similar in men and women: 46.9 ± 11.5 years for men versus 47 ± 8.5 years for women (P = .54). Most transplant recipients were fairly affluent, being mainly professionals and business owners, as payment was out-of-pocket. Two study patients (1 man and 1 woman) were sponsored by their employers.

The common primary kidney diseases included hypertension (27.2%), glomerulonephritis (24.2%), and diabetes mellitus with hypertension (18.3%) (Table 1).

Kidney transplant and follow-up of recipients
Most transplant procedures (48.6%) were performed in India, followed by 23% in Nigeria and 8.6% in Pakistan (Figure 2). A number of patients were not properly referred to the transplant centers. Further analysis showed that about one-quarter of patients transplanted in India were not referred, whereas about two-thirds of those who went to Pakistan were not referred (Table 2). Consequently, less than 30% of recipients had medical reports from the transplant centers detailing their posttransplant care. Many donors were unrelated (28.5%), with 22.9% being living related donors. The relationship of recipient to donor was not recorded in a significant number (48.6%).

Only 1 recipient had induction therapy with daclizumab. Every recipient who had records of treatment documented had prednisolone (81.8%), with use of cyclosporine (40.0%), mycophenolate mofetil (31.4%), tacrolimus (20.0%), and azathioprine (9.1%) also noted. Almost all patients who had full documentation had at least 1 complication during the course of their follow-up. Most recipients (88.9%) had more than 2 complications. Median first transplant duration was 24 months (interquartile range, 6-44 mo). However, many patients were lost to follow-up (54.2%), with 25.7% still alive and 17.1% known to be dead (Table 2). Of the 35 recipients, 2 had second transplant procedures. One had a first transplant from a cytomegalovirus-infected living relative and subsequently suffered graft loss. The second had the first kidney transplant from an unrelated Pakistani donor and had early graft loss.

Donor characteristics and follow-up
There was sparse information about donors; only 19 participants had donor type documented. Of these, only 2 donors were followed-up after the procedure, and both were donors seen at one of the government tertiary hospitals. Donor sex was documented in 9 donors (8 male and 1 female), and age was docu-men-ted in only 4 donors (range, 22-44 y); these donors were biologically or emotionally related to the recipients.

Of note was the poor documentation in many of the medical records of the kidney transplant reci-pients, with most recipients having scant information about their donors.

Discussion

Kidney transplant is the preferred and best form of treatment for most cases of ESRD because of its better outcome compared with other forms of renal replacement therapy.4 However, its outcome depends on many factors, including type of transplant, type of donation, and pretransplant evaluations and posttransplant care. In Nigeria, as in many deve-loping countries, living donations continue to be the prevalent type of donor source for transplant.

After transplant, there should be proper and ade-quate follow-up of recipients and donors. Several guidelines have stipulated immediate and long-term follow-up protocols for kidney transplant reci-pients.12,13,16,20 These guidelines are to ensure patient and graft survival. Previously, postoperative care of donors was less stringently monitored. Reports from the United States18 and Norway19 have since empha-sized the need for more structured follow-up of donors.

Our study documented the posttransplant care of kidney transplant recipients seen in southeast Nigeria. This subregion of the country until about 1 year ago did not have any centers with transplant services. Kidney transplant recipients received their procedures mostly outside the country for many reasons, ranging from transplant candidate preference, dearth of services, and cost of services.

Characteristics of the study population
The mean age of the study recipients was 47.0 ± 11.11 years, which is similar to other studies in Nigeria6 and other sub-Saharan African countries.2,24 These patients are in their prime productive age; hence, the implication on the family’s and nation’s economy is dire. This is in contrast to the experience of developed countries where most ESRD patients are in the 7th and 8th decades of life. Our kidney transplant recipients were predominantly males and mostly high-earning professionals and business owners. Previous studies have documented gender bias in favor of males.25,26 The most common primary cause of ESRD in our study population was hyper-tension followed by glomerulonephritis and diabetes mellitus. This agrees with previous data.27

Kidney transplant recipient follow-up and transplant destination
Our study shows that more kidney transplants took place outside the country than within, which is similar to what occurs in many sub-Saharan African countries where transplant programs are new.28,29 Reasons for sourcing kidney transplants abroad (transplant tourism) include scarcity of transplant centers, nonavailability of donors, and high cost of services in the native country.5,6,23 Many of these patients who receive transplant procedures outside the country come back without a detailed medical report, making subsequent follow-up problematic. In addition, some local transplant facilities have limited experience with aftercare of transplant recipients. In this study, more than half of the recipients were lost to follow-up.

For those who were followed up, many missed scheduled appointments, including the mandatory 1-year posttransplant evaluation at the center where the transplant had been performed. Many patients would present to the clinic when there was a problem or at their convenience or when they had funds for such appointments. Distance from service centers also militated against regular check-up.

Of the 35 patients analyzed in this study, only 8 procedures (23%) were performed in Nigeria. Most were done abroad in India, with 10 of the 19 documented cases (52%) being transplants from unrelated donors. Similarly, a previous study by Amira and associates6 showed that 77% (20/26) of the patients had transplant procedures in India. In that study, 14 of 26 (54%) were from unrelated donors and 18 of 26 (69%) were self-referred to the transplant center. This is in contrast to the findings in our study, in which 78% (22/28) were properly referred by a medical doctor. This may be explained in part on the basis of Lagos (the location in the study by Amira and colleagues6) being a more cosmopolitan and affluent economy and patients having preference for treatment abroad.

From our data, most patients did not have induction treatment for transplant; only 1 patient was documented to have daclizumab. All docu-mented patients in our study had prednisolone followed by mycophenolate mofetil, cyclosporine, and tacrolimus. Few patients received azathioprine. These regimens depended on the protocol of the transplant center.

Almost all patients who had full documentation had at least 1 complication during the course of follow-up. Most recipients (88.9%) had more than 2 complications. For example, 1 of the recipients who was not referred and had unrelated donation had several complications ranging from viral infections (herpes simplex virus and BK virus), sepsis, fungemia, Kaposi sarcoma, and bipolar affective disorder.

Donor follow-up
Of the 35 kidney transplants analyzed in our study, only 2 donors were followed-up after the procedure, with both seen at one of the government tertiary hospitals. This practice appears to be widespread.6,23 Follow-up of kidney donors was not structured previously because kidney donation was thought to be free of significant long-term consequences. Recent studies have associated kidney donation with some long-term risks.18,19 As a result, current guidelines recommend regular follow-up of kidney donors.16,20 Indeed, in the United States, centers must register new transplant donors and follow-up previous donors over a specified time frame.20,30

Transplant outcomes
Poor documentation and follow-up were prevalent; hence, graft and patient survival were not adequately established. In our study, 54.2% of patients were lost to follow-up.

In a review article, Akoh23 noted that outcomes of commercial kidney transplant procedures are unreliable for several reasons, including early return to home country soon after transplant without adequate postoperative follow-up and the transplant centers not interested in publishing poor outcome results.

Transplant tourism
The World Health Organization defines transplant tourism as “patients travelling across the borders to be transplanted elsewhere.”31 Transplant tourism is a global phenomenon, and it is estimated to account for about 10% of kidney transplants performed annually.32 Several studies have documented unfavorable safety and outcomes after such renal transplant procedures.6,23,33 However, the practice continues unmitigated due to a number of reasons, including (1) financial (transplant services are cheaper in Asia than in Nigeria); (2) dearth of active transplant centers and facilities (poorly developed tissue typing, drug level monitoring, and histo-pathology support services); (3) exorbitant drug prices for aftercare (because medications are imported from America and Europe but are considerably cheaper in India, where they are produced locally); (4) social reasons (sourcing of donors); and (5) loss of confidence in the local health care system.

India is a destination of choice for many Nigerians who need kidney transplant. This was observed in our study, which showed that 48.6% of kidney transplants took place in India. The next favored place was Pakistan. This experience has also been documented by Amira and associates6 who reviewed cases of kidney transplants procured outside Nigeria and followed-up in Nigeria. Many transplant candidates resort to transplant tourism because local transplant centers insist on living related donations and the prospective recipients may not have such donors. They travel abroad hoping to “purchase” or secure an organ from commercial donors. The Istanbul declaration on transplant tourism34 has clearly described reasons against this practice.

Stratification of transplant programs
Countries are at different stages of development of transplant services and programs, with those that have higher income economies having better developed transplant programs versus countries with lower income economies. Higher income countries have well-developed deceased donor programs, have advanced organ sharing guidelines and better kidney pair exchanges, are less dependent on living donations, and are better equipped and have better run transplant facilities. In contrast, countries with lower income economies may have a nonexistent transplant program or at best rudi-mentary facilities. In addition, lower income countries are more likely to have higher rates of transplant tourism. Similar transition patterns have been proposed in other spheres, such as demographic transition,35 epidemiological transition,36 nutritional transition,37 and obstetric transition.38

A transplant stratification model is hereby proposed according to level of development and resources. This model will encourage customizing strategies for improving transplant outcomes. The proposed stratification is stated in Table 3. A similar stratification has been proposed in the past by White and associates,39 titled “Definitions of hierarchical levels of capacity with respect to provision of organ donation and transplantation services in a given country”.

Conclusions

This study highlighted the lapses in follow-up of kidney transplant recipients and donors in a low-resource setting. In particular, many patients are not properly referred for transplant, most transplants are procured abroad, and many patients do not present detailed medical reports on return, resulting in less than optimal posttransplant care. The consequence of all of these factors is poor graft and patient survival.

It is recommended that transplant guidelines be adopted for better patient and graft outcomes. With regard to transplant tourism, the recently inaugurated World Health Organization Task Force (June 2018) is a solid move in the right direction. The Task Force should articulate credible and sustainable ways to stamp out transplant tourism.

We have proposed a transplant stratification model according to level of development and resources. This model will encourage customizing strategies for improving patient outcomes.


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Volume : 17
Issue : 1
Pages : 50 - 56
DOI : 10.6002/ect.MESOT2018.L44


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From the 1Department of Medicine, College of Medicine, University of Nigeria, Ituku-Ozalla, Enugu, Nigeria; and the 2Department of Medicine, Federal Teaching Hospital, Abakaliki,
Nigeria
Acknowledgements: The authors have no sources of funding for this study and have no conflicts of interest to declare.
Corresponding author: Ifeoma I. Ulasi, Department of Medicine, College of Medicine, University of Nigeria, Ituku/Ozalla Campus, Enugu, Nigeria
Phone: +234 8033262503
E-mail: ifeoma.ulasi@unn.edu.ng