Disparities in Access to Kidney Transplantation in Developing Countries : Transplantation

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Disparities in Access to Kidney Transplantation in Developing Countries

Elrggal, Mohamed Essam MD1; Gokcay Bek, Sibel MD2; Shendi, Ali M MD3; Tannor, Elliot Koranteng MD4; Nlandu, Yannick Mayamba MD5; Gaipov, Abduzhappar MD6

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Transplantation 105(11):p 2325-2329, November 2021. | DOI: 10.1097/TP.0000000000003585
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Abstract

BACKGROUND

Chronic kidney disease (CKD) is a global health problem with nearly 0.1% of the world’s population suffering from end-stage kidney disease (ESKD).1 The availability and accessibility to treatments for ESKD differ around the globe because of variations in healthcare budgets and availability of treatments. Although the prevalence of ESKD in low-income countries (LICs, 0.05%) and lower middle–income countries (L-MICs, 0.07%) is estimated to be lower than in high-income countries (HICs, 0.2%), or potentially underdiagnosed, the proportion of patients who are not receiving effective treatment is much higher in LICs (96%) and L-MICs (90%) compared with upper middle–income countries (U-MICs, 70%) and HICs (40%).2 In some L-MICs, it is impossible to support hemodialysis treatment for every ESKD patient, and most patients are unable to pay for dialysis out of pocket.2

Access to kidney replacement therapy (KRT) and distribution of KRT is thus highly inequitable. In a recent report investigating international disparities for ESKD treatment, >90% of U-MICs and HICs reported having kidney transplant services, with >85% of these countries offering both living and deceased donor transplants; LICs had the lowest availability of kidney transplant services (12%), with living donor transplants as the only organ source.3 Moreover, the successful implementation of kidney transplant programs in LICs and L-MICs is hampered by many challenges. Thus, understanding the access to transplantation in these countries, in addition to specific challenges, appears paramount.

The aim of this work led by fellows of the International Society of Nephrology (ISN) and country representatives from 23 LICs, L-MICs, and U-MICs delineates international disparities in delivering proper kidney transplantation service for patients with ESKD and proposes a roadmap toward equitable access to kidney transplantation globally.

GENERAL INFORMATION OF LOW- AND MIDDLE-INCOME COUNTRIES

Demographic and economic country profiles were referenced from the World Bank4 and World Health Organization5 online data source, stratified by World Bank ranking of country’s economies, and presented in Table 1. Information on national transplant programs was collected from each ISN fellow or country representative and literature search (Table 2).

TABLE 1. - Country profiles
Country (by world bank rank) Population (2019), million Population density person/km2 (2018) Gross national income per capita (PPP Intl $, 2019) Atlas Method Current health expenditure per capita (PPP Intl $, 2017) Current health expenditure as % of GDP (2017) Life expectancy at birth total (y, 2018)
Low-income countries
 Afghanistan 38.04 56.9 540 174.7 11.8 64
 DRC 86.7 37.1 520 37.3 3.98 60
 Nepal 28.60 195.9 1090 150.1 5.55 70
 Tajikistan 9.32 65.6 1030 231.4 7.23 71
Lower-middle-income countries
 Bolivia 11.51 10.5 3530 491.6 6.44 71
 Cameroon 25.87 53.3 1500 173.8 4.67 59
 Egypt 100.388 98.9 2690 613.8 5.29 72
 Ghana 30.41 130.8 2220 146.8 3.26 64
 India 1.366 454.9 2130 253.3 3.53 69
 Kenya 52.57 90.3 1750 158.2 4.80 66
 Kyrgyzstan 6.4 32.9 1240 241.2 6.19 71
 Moldova 2.65 123.5 3930 476.7 7.01 72
 Morocco 36.47 80.7 3190 438.1 5.25 76
 Pakistan 216.5 275.3 1530 160.5 2.90 67
 Palestinea 4.68 759.0 3710 330.3 9.3 74
 Ukraine 44.38 77.0 3370 584.6 7.00 72
 Uzbekistan 33.5 77.5 1800 447.8 6.41 72
 Algeria 43 17.7 3970 974.8 6.37 77
Upper-middle-income countries
 Armenia 2.95 103.7 4680 1001 10.36 75
 Kazakhstan 18.5 6.8 8810 820.3 3.13 73
 Malaysia 31.9 96.0 11 200 1139 3.86 76
 Perú 32.5 25.0 6740 681.2 5.00 77
 Turkey 83.4 107.0 9610 1180 4.22 77
aData on health expenditure were obtained from Palestinian Central Bureau of Statistics website: http://www.pcbs.gov.ps/PCBS_2012/Publications.aspx?CatId=56.
DRC, Democratic Republic of Congo; GDP, gross domestic product; Intl $, international dollar; PPP, purchasing power parity.

TABLE 2. - Kidney transplant services and barriers in middle- and low-income countries
Country Transplant Registry Health coverage Transplant national coordination Regular transplant program started Donor type available Follow-up team Barriers category a Ethical laws Immigrant transplant policy Organ trafficking
Low-income countries
 Afghanistan No No coverage No 2015 LIV OTHER C, F, G, H No No Yes
 DRC No No coverage No Not started yet No NEPH/OTHER F, G No No Possible
 Nepal No Partial coverage No 2008 LIV and DEC NEPH A, C, D, G Yes Yes Yes
 Tajikistan Partially Partial coverage Yes 2010 LIV NEPH C, D Yes Yes No
Lower-middle–income countries
 Bolivia Partially Partial coverage Yes 2014 LIV and DEC NEPH A, C, D, E, G, H Yes Yes No
 Cameroon No No coverage No Not started yet No No F, G, H No No No
 Egypt No Partial coverage Yes 1976 LIV NEPH A, С, D, E Yes Yes Possible
 Ghana No No coverage No 2008 LIV NEPH C, F, G, H In process No Possible
 India Partially Partial coverage Yes 1971 LIV and DEC NEPH/SUR A, D, G Yes Yes Yes
 Kenya Yes Partial coverage No 2006 LIV and DEC NEPH A, C, G Yes No No
 Kyrgyzstan Partially Partial coverage No 2018 LIV NEPH A, C, D,F, H In process No No
Moldova Yes Full coverage Yes 2012 LIV and DEC NEPH/URO B, C, D Yes No No
 Morocco No Partial coverage Yes 1985 LIV and DEC NEPH A, B, C, D Yes No No
 Pakistan No Partial coverage No 1979 LIV NEPH C, F, G, Yes Yes Yes
 Palestine Partially Full coverage No 2010 LIV NEPH A Yes No No
 Ukraine Partially Partial coverage No 2006 LIV and DEC NEPH/OTH A, C, D In process No No
 Uzbekistan Partially Partial coverage Yes 2017 LIV NEPH A, C, D In process No No
 Algeria Yes Full coverage Yes 1986 LIV and DEC NEPH A, B, D Yes Yes No
Upper-middle–income countries
 Armenia Yes Partial coverage Yes 2002 LIV NEPH C Yes No No
 Kazakhstan Partially Full coverage Yes 2012 LIV and DEC NEPH A, C, D Yes No No
 Malaysia Yes Partial coverage Yes 1975 LIV and DEC NEPH A, B, C, G, H Yes No Possible
 Peru Partially Full coverage Yes 1969 LIV and DEC NEPH A, C, D, H Yes No No
 Turkey Yes Full coverage Yes 1968 LIV and DEC NEPH A, C, D Yes Yes No
aBarriers category: A, cultural/spiritual impediments; B, low number of referrals; C, donor shortage; D, long waiting time; E, organ trafficking; F, lack of legal framework; G, insufficient financial support; H, lack of tissue typing.
DEC, deceased; DRC, Democratic Republic of Congo; LIV, live; NEPH, nephrologists; OTH, other specialities; SUR, surgery; URO, urologists.

Among the surveyed 4 LICs, Nepal and Tajikistan have relatively higher gross national income per capita (compared with Afghanistan and the Democratic Republic of Congo, DRC), and their governments partially support the cost of kidney transplantation. There is no national transplant program in DRC; transplant costs are not covered in Afghanistan. Only Tajikistan reports on a partial transplant registry and national transplant coordination with some costs for transplantation covered.

Among the surveyed 14 L-MICs, only Cameroon has not started a regular kidney transplant program. Although Moldova, Algeria, and Palestine cover all costs for transplantation, Ghana and Cameroon provide no coverage, and the remaining 9 L-MICs provide only partial coverage. A nationwide allocation and procurement service has been launched in Bolivia, Egypt, India, Moldova, Morocco, and Uzbekistan; however, a transplant registry has not been implemented yet in Cameroon, Egypt, Ghana, Morocco, and Pakistan.

Transplant programs in LICs, L-MICs, and even U-MICs suffer a number of challenges that adversely impact effectiveness, solidarity, development, and the ability to control unethical practices (Table 2).

All 5 U-MICs, Armenia, Kazakhstan, Malaysia, Peru, and Turkey, have established kidney transplant programs with at least partial coverage of transplant expenses, national transplant coordination, and partial or full transplantation registries.

CULTURAL, RELIGIOUS, AND EDUCATIONAL BARRIERS

Country-specific cultural characteristics shape the acceptance of organ donation, the concept of brain death, and the overall perspective on treating patients with ESKD including transplantation. The majority of countries (15 of 23) reported on cultural and spiritual factors as barriers to organ transplantation. Some ethnic minorities have been identified as having misconceptions about organ transplantation due to lack of education, religious myths, medical distrust, or fear of premature death of donors; racism appears as a driving force by some, leading to reluctance in organ donation. Patients with ESKD do not feel comfortable in asking family members to donate, fearing complications, having concerns about burdening the family, and being concerned about the impact that donation may have on family relations.

Religious beliefs play a significant role in patients’ views and attitudes toward transplantation.6 Islam, for example, emphasizes the importance of saving the lives of others but forbids the violation of the human body, whether alive or dead. Different associations of Islamic law have put forward regulations for organ donation, either living or deceased, considering the fine balance between saving lives while avoiding potential harm to the donor. However, in LICs and L-MICs, regulations concerned with deceased donation have not convinced the entire Muslim population, mainly because of cultural, environmental, and misinterpreted religious reasons. Consequently, deceased donation is scarce in most low-income and lower middle–income Islamic countries that have therefore expanded living donation with risks for unethical practices.

In general, Christianity is supportive of organ transplantation and donation. The Catholic, Anglican, and Protestant churches agree that organ donation is an act of selflessness, exemplifying Christian love. The Church of Jesus Christ of the Latter-day Saints teaches that organ donation should be left to an individual decision. Jehovah’s Witnesses do not accept blood transfusion and will leave organ transplantation to the individual’s discretion. However, some still have concerns about living donations, questioning the passage of the donor’s blood through their organ.

Recognition and acceptance of “brain death” are a prerequisite to establishing deceased donor transplant programs. However, this is a quite challenging issue in most LICs and MICs. Thirteen of 23 countries reported misconceptions of brain death by patients’ relatives. This lack of understanding represents a major barrier to deceased transplantation.

Many patients present with advanced CKD leading to increased mortality even before considering kidney transplantation. In addition, poverty and the unequal distribution of hemodialysis machines in some countries add to high mortality rates.7 In our report, 4 countries (Algeria, Malaysia, Moldova, and Morocco) reported low referral rates as a barrier to transplantation.

Limited expertise with few nephrologists represents another challenge. The median number of nephrologists worldwide is 9.95 per million population (pmp); the “density” of nephrologists increases from 0.2 pmp in LICs to 1.6 pmp in L-MICs, 10.8 pmp in U-MICs, and 23.2 pmp in HICs.1 In 1 study, only 43% of nephrologists dedicated some time to educate patients about transplantation within the first 3 mo of dialysis treatment.8 Consequently, many patients are not well informed about transplantation as a modality for KRT, and there may even be a financial incentive to keep patients on dialysis in some countries.

ORGAN SHORTAGE AND PROLONGED WAITING TIME

The discrepancy between demand and supply is even more obvious in LICs and L-MICs. The lack of a deceased donor program in 11 of 23 countries we surveyed aggravates organ shortage furthermore. Although Nepal is the only LIC with both living and deceased donation programs, Armenia is the only U-MIC without a deceased donor program. Globally, transplant rates of living donor kidney average 5.3 pmp, ranging from 0.4 pmp in Myanmar to 33.2 pmp in Turkey. Among the 75 countries that offer deceased kidney transplants worldwide, the average volume is 15.1 pmp,8 and rates increase with income level. Overall, deceased donor kidney transplant rates are below the global average in Africa, Latin America, the Middle East, North and East Asia, Newly Independent States, and Russia.9

Organ shortage will result in an unduly long waiting list. At Mansoura Urology and Nephrology Center in Egypt, where only living-related transplants are performed, wait-times for a matched donor and recipient average approximately 1.5 y.

TRANSPLANT TOURISM, ORGAN TRAFFICKING, AND LEGAL CHALLENGERS

The Declaration of Istanbul (DoI) and the Declaration of Istanbul Custodian Group defined and continue to battle transplant tourism and organ trafficking (OT).10 According to the World Health Organization’s Second Consultation on Human Transplantation in 2007, OT accounts for 5%–10% of the kidney transplants annually.9

In our report, possible OT was present in 8 countries and more prominent in LICs (3 of 4) than in L-MICs (4 of 14) and U-MICs (1 of 5). This is because tourism trafficking and OT are linked to a lack of national transplant programs, organ shortage, absence of deceased donation, lack of specific regulations for immigrants in need of kidney transplantation, and religious and cultural beliefs that are not in support of donation. Unfortunately, it is particularly the vulnerable and poor population that is suffering and exploited by organ brokers to sell their organs.

A legal framework is mandatory and should comply with the principles of DoI,10 aiming to ensure donor and recipient safety and equity in access to transplantation. Moreover, brain death needs to be defined, and the rules governing deceased donation, allocation, and recipient listing need to be clear. Seven countries (2 LICs and 5 L-MICs) are still lacking legal frameworks for deceased donation and do not regulate transplant activities involving immigrants. Except for Afghanistan, all countries have ongoing attempts to implement legal frameworks, and all countries with transplant programs are expected to adopt the principles of DoI. We assume that professional societies base their work on the principles of DoI. Individuals violating those principles should therefore not be members of those societies. Moreover, pharmaceutical companies and public and private funding agencies must affirm that any clinical trial or support is not in violation of DoI.

FINANCIAL AND ORGANIZATIONAL BARRIERS

Globally, 64% of all countries provide full coverage for kidney transplantation, with 43% charging fees at the point of delivery.1 LICs have the highest private funding for kidney transplantation with the least governmental support. Those countries also suffer shortages especially in their workforce (90%), particularly for transplant coordinators.9 All LICs in our survey reported insufficient financial support with the exception of Tajikistan. Malaysia was the only U-MIC to report insufficient financial support. Three of 5 U-MICs provide full financial coverage for kidney transplantation, whereas Moldova, Palestine, and Algeria (3 of 14) were the only L-MICs to provide full coverage.

Seven countries reported having insufficient tissue typing services. In most LICs and L-MICs, tissue typing facilities are central, challenging the successful implementation of deceased-donation programs. Moreover, financial constraints also limit best practice guidelines. In some transplant facilities, for example, anti-HLA antibodies are not routinely screened pretransplant. In Malaysia, for example, HLA-typing can only be offered infrequently as reagents are often not available.

Renal registries are essential for monitoring trends and outcomes as a basis for policymaking. Globally, there are many renal registries (144 in 2014), yet only a small minority have comprehensive, readily accessible patient-level data, and these tend to be in HICs (17 in 2014). In much of the Asia-Pacific region, the Middle East, and Africa, registries were either absent or had limited data or poor accessibility. Six of 23 surveyed countries reported having transplant registries. Armenia, Moldova, and Algeria are the only LICs and L-MICs with established transplant registries; Palestine, Tajikistan, and Ukraine have ongoing efforts to establish transplant registries. Among the 6 African countries in our survey, only Algeria and Kenya have transplant registry. Only about half of the surveyed countries provide national transplant coordination (LICs: 1 of 4; L-MICs: 7 of 14; U-MICs: 5 of 5).

A ROADMAP FORWARD

Developing countries face multiple challenges to provide universal and equitable access to kidney transplantation. Although there are commonalities, each country needs to identify its own needs to set up a successful transplant program.

Overall, educational and governmental awareness programs should be encouraged to increase public acceptance of both live and deceased donation and to correct faulty beliefs preventing deceased donation. It is also necessary to convince both policymakers and the public to implement comprehensive kidney transplant programs. In many countries, the concept of brain death needs to be clarified and legislations for deceased donation need to be adopted to pave the way for a deceased transplant program.

Another effective way to expand the donor pool and thus to shorten waiting times is to encourage paired or pooled kidney donation programs in countries with regular transplant activities. Strict regulations stopping OT are also much needed. The fight against OT should have special governmental concerns with extensive inspection measures and tough penalties.

Improvement in healthcare funding to reimburse transplant cost is mandatory to establish national transplant programs. Deficient infrastructural domains in every country need to be identified and addressed in collaboration with transplant-oriented professional bodies and well-established transplant programs. Examples of such collaborations include the sister center projects between developing and developed transplant centers and the fellowship training opportunities for nephrologists from developing countries to lead their transplant programs.

CONCLUSION

LICs and L-MICs suffer major challenges to develop transplant programs and to provide equitable access to kidney transplantation. Large-scale, well-planned solutions to these obstacles include accessible public health and mandate international efforts to improve the care of patients with ESKD.

ACKNOWLEDGMENTS

The authors gratefully thank the following ISN Fellows and country representatives for their participation in data collection: Klara Poudel, Department of Nephrology, Charak Memorial Hospital, Pokhara, Nepal; Aiperi Asanbek Kyzy, Department of Clinical Disciplines, International Medical Faculty, Osh State University, Osh, Kyrgyzstan; Ismoil Rashidov, Department of Nephrology, National Medical Center of the Republic of Tajikistan, Dushanbe, Tajikistan; Sherzod Abdullaev, Department of Internal Medicine, Tashkent Pediatric Medical Institute, Tashkent, Uzbekistan; Olena Loboda, Department of Efferent Technologies, SI Institute of Nephrology of NAMS of Ukraine, Kiev, Ukraine; Elena Cuiban, Haemodialysis and Kidney Transplantation Unit, Republican Clinical Hospital, Chisinau, Moldova; Milena Voskanyan, Division of Hemodialysis & Kidney Transplantation, “ARABKIR” Medical Centre, Yerevan, Armenia; Nidhi Singh, Department of Nephrology, Rabindranath Tagore International Institute of Cardiac Sciences, Kolkata, West Bengal, India; AE Nono Tomta, Department of Internal Medicine/Nephrology, Yaounde General Hospital, Yaounde, Cameroon; Khalida B. Soki, Kenya Renal Association Nephrology Unit, Nairobi, Kenya; M Jalalonmuhali, Department of Nephrology, University Malaya Medical Center, Kuala, Lumpur, Malaysia; Khadidja Habchi, Nephrology & Transplantation Department, University Hospital of Beni Messous, Beni Messous, Algiers, Algeria; and Mustafa Habiballah, Targa Hemodialysis Center, Marrakech, Morocco.

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