Navigating Risks: Insights on Unrelated Overseas Renal Transplantations from Two Saudi Centers

Navigating Risks: Insights on Unrelated Overseas Renal Transplantations from Two Saudi Centers | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Navigating Risks: Insights on Unrelated Overseas Renal Transplantations from Two Saudi Centers Hany M El Hennawy, Omar Safar, Abdullah S Al Faifi, Maryam H El Hennawy, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5418384/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 02 May, 2025 Read the published version in BMC Nephrology → Version 1 posted 4 You are reading this latest preprint version Abstract Background: Due to a shortage of cadaveric organs for transplantation, some Saudi patients seek to purchase kidneys in other countries. However, kidney transplantation (KT) abroad is often associated with negative outcomes. This study shared the experiences of two Saudi transplantation centers regarding unrelated KT overseas. Methods: This retrospective comparative cohort study included patients who underwent unrelated KT abroad (Group I) and local patients who received living unrelated KT from September 2017 to July 2024, with follow-up for at least one year at AFHSR and Tabouk. Results: we studied 204 patients, including 96 who underwent commercial KT (Group I) and 108 who received living unrelated KT(Group II), with an average follow-up of 42 months. Immediate graft function was lower in Group I (83.33%) than in Group II (93.51%; p=0.0104). One-year patient survival was significantly lower in Group I (94.8%) than in Group II (100% in Group II (p=0.0167), along with poorer long-term kidney function. Conclusion: commercial transplantation patient survival rates are lower, and overall outcomes are worse than those of traditional unrelated transplantation in the midterm. Educating patients about the risks associated with overseas KT and promoting public registration for deceased organ donation could help mitigate this practice. Figures Figure 1 Introduction The global burden of kidney failure is increasing. Kidney transplantation (KT) remains the preferred treatment for end-stage renal disease (ESRD) [1]. However, waiting times for KT continue to increase despite ongoing efforts to enhance the supply of deceased and living donor organs. Consequently, many patients, despite ethical concerns, are turning to commercial living without KT [2], [3], [4], [5]. Most countries currently allowing commercial KT are in the developing world, including Brazil, China, Egypt, India, Iraq, Pakistan, the Philippines, Romania, Russia, South Africa, Turkey, and Venezuela [6]. Concerns have been raised about the medical safety of KT abroad, highlighting issues such as lower graft survival rates, increased infection rates, and inadequate communication between transplant centers and follow-up facilities [3]. Conflicting data concerning the outcomes and complications associated with living-unrelated KT has been published. [3], [4], [5], [6], [7]. Data from the Far East showed no significant differences in graft survival and perioperative complications between commercial and non-commercial KT. Meanwhile, Western countries' data showed statistically significantly lower patient and graft survival rates and higher infection and complication rates among the commercial KT groups [3]. Recent data, including Saudi patients with overseas commercial KT, showed a significantly higher rejection rate in patients transplanted overseas (OR=5.4, p<0.001) [5]. This study aimed to share our experiences with transplantation tourism and to offer insights into the trends, outcomes, and challenges related to this practice. METHODS This retrospective cohort study was conducted at two Saudi transplantation centers (AFHSR and KSAFH). The study included all patients who underwent live unrelated KT abroad, attended follow-ups at both centers between September 2017 and July 2023 and were followed up for at least one year. Patients with no data regarding the transplantation process (countries, date of surgery, type of donor, immunosuppression medications) or one-year follow-up were excluded from the study. The study was approved by the local ethical committee of both centers (AFHSR: AFHSRMREC/SURGERY, SECTION OF TRANSPLANTATION/746; KSAFH: KSAFH-RET:2024 − 595) Intervention: Recipients in this cohort sought overseas transplants at their own risk without the consent or endorsement of their treating nephrologists. Although our centers do not support transplant tourism, we do not deny access to care for those in need. All transplanted patients in other countries attended either center according to geographical distribution. Most patients arrived within the first week after KT. All patients were evaluated by the attending transplant team regarding their general condition, kidney function, wound status, medications, and immediate renal graft. Patients were admitted on arrival, IS medications were started according to the local protocol, and patients were followed until stabilization of their condition and maintenance of IS was initiated. Data acquisition: We collected the baseline characteristics of the study group (Group I) , including age, sex, pre-KT comorbidities, causes of end-stage renal disease (ESRD), hemodialysis duration, and hepatitis status. Transplant data included the donor source, country visited, length of stay at the transplant center, date and location of the transplant, transplant-related variables (such as induction therapy and immunosuppressive agents used, delayed graft function, and kidney function at discharge), and post-KT complications (including post-KT diabetes, rejection episodes, and other medical and surgical complications related to the procedure). A control group (Group II) of local unrelated live donor KTs in the same period at the same centers was reviewed for similar data collection. Measured outcomes: The primary outcome was to compare perioperative outcomes, including primary graft function, length of hospital stay, and 90-day postoperative complications. The secondary outcome was to compare the 1-year patient and graft survival between both groups. Statistical analysis: Continuous data were expressed as mean ± SD and categorical variables were expressed as numbers and percentages. Comparisons between both groups were performed using Chi-square and independent sample T-tests. Life tables obtained the survival data, and comparison was done using a Cox regression analysis. Data were analyzed using the Statistical Package for the Social Sciences (SPSS) Version 29 (IBM, New York, USA). Categorical data are presented as frequencies and percentages, whereas continuous data are reported as medians, means, and standard deviations. Results The study group (Group I) comprised 96 patients (64 males and 32 females) who were significantly older, with a mean ±SD age of (54.3± 16.6 years), (p=0.001). Their first KT took place in Egypt (34), Pakistan (30), China (8), India (10), Jorden (8), and the Philippines (6). Group II included 108 patients (67 males and 41 females) with ±SD age of 48.7±16.2 years. Regarding immunosuppression induction, Group I primarily used basiliximab, with 62.5% of patients receiving this treatment and 95.3% receiving Group II. A notable proportion of Group I patients (26.0%) received ATG, whereas 11.5% received unknown induction therapy. The significant difference in the use of immunosuppressive agents highlights a divergence in treatment protocols between the two groups, which may have affected the overall outcomes and complications following KT. In both groups, the immunosuppressive regimen consisted of tacrolimus, mycophenolate mofetil (MMF), and prednisolone. In Group I, 100% of patients underwent their first KT; in Group II, this proportion was 96.3%. Group I had a significantly longer hospital stay (9±5.1 vs. 5±2.3 days) (P=0.0001). In Group I, 80(83.3%), 6 (6.3%), and 10 (10.4%) patients had primary functioning graft (PFG), slow graft function (SGF), and delayed graft function (DGF), respectively. In Group II, 101 (93.5%), six (5.5%), and one (1%) had PGF, SGF, and DGF, respectively (P=0.01). Table 1 illustrates the comparison of demographic criteria between the two groups. At 90 days postoperatively, seven patients (7.3%) in Group I and two patients (1.8%) in Group II experienced acute rejection episodes (P=0.5). All patients with acute cellular rejection (ACR) received pulse steroids and anti-thymocyte globulin (ATG) at doses of 4-7 mg/kg. Patients with combined ACR and acute antibody-mediated rejection (ABMR) in Group I received ATG at 6-7 mg/kg, pulse steroids, five sessions of plasma exchange, intravenous immunoglobulin at 100 mg/kg after each exchange, and rituximab at 375 mg/m² once weekly for four doses. Surgical complications were more frequent in Group I, with higher rates of surgical site infections (SSI) (8.33% vs. 1.85%, P=0.03) and lymphocele (18.75% vs. 6.48%, p=0.007). Urinary tract infections (UTIs) occurred more frequently in Group I (12.5% vs. 1.8%; p=0.002). (Table 2) Additionally, Group I had three cases of cytomegalovirus (CMV) infections (3.12%), whereas Group II had none, although this difference was not statistically significant (p=0.102). For BK virus (BKV) infections, Group I had two cases (2.0%) compared with one case (0.9%) in Group II, showing no significant difference (p=0.493). Both groups had no reported cases of Epstein–Barr virus (EBV) or HIV infection, and the rates of hepatitis B and C infections were similar, with no significant differences. In group I, the most frequently isolated bacterium in early recurrent UTIs was Escherichia coli, accounting for 80.9% of cases. Extended-spectrum beta-lactamases (ESBL) and multidrug-resistant organisms (resistant to three or more drugs) were present in 82.4% of the isolates. Additionally, meropenem was identified as the most effective antibiotic, with an effectiveness rate of 86.7%. Moreover, 65% of UTIs were managed with a single antibacterial course. The mean peak creatinine level at the time of rejection was 320 μmol/L, which decreased to 140 μmol/L at discharge and 125 μmol/L after one year. One-year patient survival was significantly lower in Group I (94.8%) than in Group II (100% in Group II (p=0.0167). Additionally, Group I had poorer long-term kidney function, as indicated by higher serum creatinine levels at one year (112.6 vs. 91.7; p=0.008) and five years (142.2 vs. 111.0; p=0.00001). Overall, the outcomes for Group I were notably worse than those for Group II, highlighting the risks associated with commercial KT. The detailed results are summarized in Tables 1 and 2. In group I, the overall graft survival was 68 (71%), and the 1-, 2-, 3-, and 5-year cumulative graft survivals were 80%, 79%, 74%, and 54%, respectively. In Group II, the overall graft survival was 92(85%), and the 1-, 2-, 3-, and 5-year cumulative graft survival rates were 98%, 97%, 90%, and 60%, respectively. [HR= 2, 95% CI= 1.1-3.8, P=0.02] (Figure 1). Discussion The overseas KT is a significant international concern [8]. This study's primary reason for these patients seeking KT abroad was the lack of available donors. In our study, we observed unfavorable outcomes in the cohort that received KT abroad, which included higher rates of SSI (8.33% vs. 1.85%, p = 0.032) and lymphocele (18.75% vs. 6.48%, p = 0.0076), as well as significantly more UTI (12.5% vs. 1.8%, p = 0.0026). This Group also had a higher rate of acute rejection (7.29% compared to 1.85% in Group II). Furthermore, 1-year patient survival was significantly lower in Group I (94.8% alive vs. 100% in Group II (p = 0.0167). We also observed significant differences in induction therapy between the local and overseas groups. Using basiliximab in high-risk patients or patients without appropriate immunological risk assessment may partly account for the higher rejection rates observed in our overseas KT cohort [5]. The 1-year survival rate of living-related KT in Saudi Arabia is 98.4 [9]. In this study, the 1-year patient survival rate was 94.8% for those who underwent overseas KT and 100% for those who underwent local KT. There are conflicting reports regarding the outcomes of patients receiving commercial KT, with both unfavorable and favorable results documented [10]. Several international studies have reported favorable outcomes, including one of the most extensive analyses comparing graft and patient survival rates between transplanted domestically. In 2000, Morad et al. examined Malaysian patients (n = 515) who underwent KT in India and China, and > 90% of the grafts and patients survived. Among the 258 patients who received kidneys from living donors, the rates of infectious complications and patient and graft survival were similar between the groups [11]. This outcome contrasts recent studies reporting poor graft and patient survival rates. For instance, Sever et al. examined the mid-term outcomes of 115 patients who underwent commercial KT in multiple countries, primarily India, Iran, and Iraq [12]. Notably, 15 recipients experienced unconventional infections, including 10 with malaria, 3 with aspergillosis, and 2 with mucormycosis [12]. The graft and patient survival rates at seven years for those who underwent commercial KT were 53% and 74%, respectively, whereas the rates for living-related KT performed at their center were 73% and 80% [12]. Moreover, Sever et al. reported that although mid-term graft survival was worse, patient survival was comparable to that following commercial living KT [12]. In another study by Salahudeen et al., a high early postoperative mortality rate was reported in a case series of 16 patients. The 1-year patient survival rate for overseas commercial KT ranged from 80–96%, whereas the rate for living-related KT in Australia exceeded 95%. Additionally, the 5-year patient survival rate was 60%. The study also reported high rates of infectious complications, including hepatitis B, cytomegalovirus, aspergillus, and multidrug-resistant Pseudomonas aeruginosa infections [13]. Additionally, Sajjad et al. emphasized that recipients face surgical risks in poorly equipped and unsanitary clinics, which increases the likelihood of infection. Meanwhile, donors are mainly from lower socioeconomic groups in developing countries who often need more access to follow-up care. In some instances, these donors may even carry infectious diseases such as tuberculosis, AIDS, and hepatitis [3]. De Souza et al. reported a 1-year infection rate of 42.2%, with UTIs being the most common. This finding is consistent with the established view that UTIs are the most prevalent infections among patients undergoing KT [14]. Similarly, in our cohort, patients who underwent overseas KT had higher rates of SSIs and UTIs, with rates of 12.5% compared with 1.8% (p = 0.0026). The onset of acute rejection of KT significantly reduces long-term graft survival, especially if rejection is not completely reversed [15]. In our study, seven patients who underwent overseas KT experienced graft rejection, whereas only two patients from the local cohort experienced similar issues. Because overseas KT is often commercially motivated, patients at these centers typically experience the shortest postoperative hospital stay and are encouraged to return to their home countries upon discharge [5]. In our study, the average length of stay of the overseas KT group was 9 ± 5.1 days. STUDY LIMITATIONS The primary limitations of our study include the small sample size and the fact that it was conducted at two centers. Furthermore, observational and retrospective designs may introduce various biases. Conclusions Commercial KT is associated with a higher incidence of infections and rejection episodes than locally performed unrelated KT. Further studies are critical for investigating commercial KT’s long-term outcomes and identifying the factors that drive this practice. Declarations Consent for publications Not applicable Data Availability The data supporting this study's findings are available from the corresponding author upon reasonable request. Competing Interests The authors declare no competing interest. Funding None Clinical trial number: Not Applicable Authors contributions: H M El Hennawy: protocol development, manuscript writing, manuscript review, and senior author., O Safar: protocol development, manuscript writing, manuscript review., A S Al Faifi: data analysis, manuscript writing., M H El Hennawy: manuscript Review and editing., B Alghamdi: protocol development and data collection., A Ali: protocol development., M Alqahtani: protocol development and manuscript Review., M F Zaitoun: data collection., S A. Alasmari: protocol development and data collection., A Serageldeen: data collection and manuscript review., T A. Abouelgreed: data collection and manuscript review. K Fourtounas: data collection and manuscript review. M Ayyad: data collection and manuscript review., A Ali: data collection and manuscript review., M H Zahran: manuscript review, editing, and senior author. Acknowledgments Not applicable References H. Liman, M. Makusidi, and A. Sakajiki, “Kidney transplant-related medical tourism in patients with end-stage renal disease: A report from a renal center in a developing nation,” Sahel Medical Journal , vol. 23, no. 1, p. 7, 2020, doi: 10.4103/smj.smj_17_19. Jafar, T. H. “Organ trafficking: global solutions for a global problem.,” Am. J. Kidney Disease , vol. 54, no. 6, pp. 1145–57, Dec. 2009, doi: 10.1053/j.ajkd.2009.08.014. I. Sajjad, L. S. Baines, P. Patel, M. O. Salifu, and R. M. Jindal, “Commercialization of kidney transplants: a systematic review of outcomes in recipients and donors.,” Am J Nephrol , vol. 28, no. 5, pp. 744–54, 2008, doi: 10.1159/000128606. B. Adamu, M. Ahmed, R. F. Mushtaq, and F. Alshaebi, “Commercial kidney transplantation: trends, outcomes and challenges-a single-center experience.,” Ann Afr Med , vol. 11, no. 2, pp. 70–4, 2012, doi: 10.4103/1596-3519.93527. M. Tawhari and M. Radwi, “A Three-Year Experience With Overseas Kidney Transplantation in a Tertiary Transplant Center in Saudi Arabia,” Cureus , Apr. 2022, doi: 10.7759/cureus.23988. M. M. Friedlaender, “The role of commercial non-related living kidney transplants.,” J Nephrol , vol. 16 Suppl 7, pp. S10-5, 2003. J. Augustine, “Kidney transplant: New opportunities and challenges,” Cleve Clin J Med , vol. 85, no. 2, pp. 138–144, Feb. 2018, doi: 10.3949/ccjm.85gr.18001. AlBugami M, Hussein M, Alsaeed S, Almubarak A, Bel ’eed-Akkari, “Outcome of Saudi Patients Returning after Commercial Kidney Transplantation Abroad,” in ERA-EDTA Annual Meeting , Amsterdam, Netherland, Mar. 2014, p. 548. F. A. M. Shaheen, H. and M. Z. Souqiyyeh, “Current status of renal transplantation in the Kingdom of Saudi Arabia.,” Transplant Proc , vol. 36, no. 1, pp. 125–7, 2004, doi: 10.1016/j.transproceed.2003.11.037. M. Suthanthiran and T. B. Strom, “Renal transplantation.,” N Engl J Med , vol. 331, no. 6, pp. 365–76, Aug. 1994, doi: 10.1056/NEJM199408113310606. Z. Morad, and T. O. Lim, “Outcome of overseas kidney transplantation in Malaysia.,” Transplant Proc , vol. 32, no. 7, pp. 1485–6, Nov. 2000, doi: 10.1016/s0041-1345(00)01300-2. M. S. Sever et al. , “Outcome of living unrelated (commercial) renal transplantation.,” Kidney Int , vol. 60, no. 4, pp. 1477–83, Oct. 2001, doi: 10.1046/j.1523-1755.2001.00951.x. A. K. Salahudeen et al. , “High mortality among recipients of bought living-unrelated donor kidneys.,” Lancet , vol. 336, no. 8717, pp. 725–8, Sep. 1990, doi: 10.1016/0140-6736(90)92214-3. R. M. de Souza and J. Olsburgh, “Urinary tract infection in the renal transplant patient.,” Nat Clin Pract Nephrol , vol. 4, no. 5, pp. 252–64, May 2008, doi: 10.1038/ncpneph0781. G. Opelz and B. Döhler, “Influence of Time of Rejection on Long-Term Graft Survival in Renal Transplantation,” Transplantation , vol. 85, no. 5, pp. 661–666, Mar. 2008, doi: 10.1097/TP.0b013e3181661695. Tables Tables 1 to 2 are available in the Supplementary Files section Additional Declarations No competing interests reported. Supplementary Files tables.docx Cite Share Download PDF Status: Published Journal Publication published 02 May, 2025 Read the published version in BMC Nephrology → Version 1 posted Editorial decision: Revision requested 19 Nov, 2024 Editor assigned by journal 15 Nov, 2024 Submission checks completed at journal 15 Nov, 2024 First submitted to journal 08 Nov, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Kidney transplantation (KT) remains the preferred treatment for end-stage renal disease (ESRD) [1]. However, waiting times for KT continue to increase despite ongoing efforts to enhance the supply of deceased and living donor organs. Consequently, many patients, despite ethical concerns, are turning to commercial living without KT [2], [3], [4], [5]. Most countries currently allowing commercial KT are in the developing world, including Brazil, China, Egypt, India, Iraq, Pakistan, the Philippines, Romania, Russia, South Africa, Turkey, and Venezuela [6]. Concerns have been raised about the medical safety of KT abroad, highlighting issues such as lower graft survival rates, increased infection rates, and inadequate communication between transplant centers and follow-up facilities [3].\u003c/p\u003e\n\u003cp\u003eConflicting data concerning the outcomes and complications associated with living-unrelated KT has been published. [3], [4], [5], [6], [7]. Data from the Far East showed no significant differences in graft survival and perioperative complications between commercial and non-commercial KT. Meanwhile, Western countries' data showed statistically significantly lower patient and graft survival rates and higher infection and complication rates among the commercial KT groups [3]. Recent data, including Saudi patients with overseas commercial KT, showed a significantly higher rejection rate in patients transplanted overseas (OR=5.4, p\u0026lt;0.001) [5].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study aimed to share our experiences with transplantation tourism and to offer insights into the trends, outcomes, and challenges related to this practice.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eThis retrospective cohort study was conducted at two Saudi transplantation centers (AFHSR and KSAFH). The study included all patients who underwent live unrelated KT abroad, attended follow-ups at both centers between September 2017 and July 2023 and were followed up for at least one year. Patients with no data regarding the transplantation process (countries, date of surgery, type of donor, immunosuppression medications) or one-year follow-up were excluded from the study. The study was approved by the local ethical committee of both centers (AFHSR: AFHSRMREC/SURGERY, SECTION OF TRANSPLANTATION/746; KSAFH: KSAFH-RET:2024\u0026thinsp;\u0026minus;\u0026thinsp;595)\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eIntervention:\u003c/h2\u003e \u003cp\u003eRecipients in this cohort sought overseas transplants at their own risk without the consent or endorsement of their treating nephrologists. Although our centers do not support transplant tourism, we do not deny access to care for those in need. All transplanted patients in other countries attended either center according to geographical distribution. Most patients arrived within the first week after KT. All patients were evaluated by the attending transplant team regarding their general condition, kidney function, wound status, medications, and immediate renal graft. Patients were admitted on arrival, IS medications were started according to the local protocol, and patients were followed until stabilization of their condition and maintenance of IS was initiated.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData acquisition:\u003c/h3\u003e\n\u003cp\u003eWe collected the baseline characteristics of the study group \u003cb\u003e(Group I)\u003c/b\u003e, including age, sex, pre-KT comorbidities, causes of end-stage renal disease (ESRD), hemodialysis duration, and hepatitis status. Transplant data included the donor source, country visited, length of stay at the transplant center, date and location of the transplant, transplant-related variables (such as induction therapy and immunosuppressive agents used, delayed graft function, and kidney function at discharge), and post-KT complications (including post-KT diabetes, rejection episodes, and other medical and surgical complications related to the procedure). A control group \u003cb\u003e(Group II)\u003c/b\u003e of local unrelated live donor KTs in the same period at the same centers was reviewed for similar data collection.\u003c/p\u003e\n\u003ch3\u003eMeasured outcomes:\u003c/h3\u003e\n\u003cp\u003eThe primary outcome was to compare perioperative outcomes, including primary graft function, length of hospital stay, and 90-day postoperative complications. The secondary outcome was to compare the 1-year patient and graft survival between both groups.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis:\u003c/h2\u003e \u003cp\u003eContinuous data were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD and categorical variables were expressed as numbers and percentages. Comparisons between both groups were performed using Chi-square and independent sample T-tests. Life tables obtained the survival data, and comparison was done using a Cox regression analysis. Data were analyzed using the Statistical Package for the Social Sciences (SPSS) Version 29 (IBM, New York, USA). Categorical data are presented as frequencies and percentages, whereas continuous data are reported as medians, means, and standard deviations.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe study group (Group I) comprised 96 patients (64 males and 32 females) who were significantly older, with a mean \u0026plusmn;SD age of (54.3\u0026plusmn; 16.6 years), (p=0.001). Their first KT took place in Egypt (34), Pakistan (30), China (8), India (10), Jorden (8), and the Philippines (6). Group II included 108 patients (67 males and 41 females) with \u0026plusmn;SD age of 48.7\u0026plusmn;16.2 years.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRegarding immunosuppression induction, Group I primarily used basiliximab, with 62.5% of patients receiving this treatment and 95.3% receiving Group II. A notable proportion of Group I patients (26.0%) received ATG, whereas 11.5% received unknown induction therapy. The significant difference in the use of immunosuppressive agents highlights a divergence in treatment protocols between the two groups, which may have affected the overall outcomes and complications following KT. In both groups, the immunosuppressive regimen consisted of tacrolimus, mycophenolate mofetil (MMF), and prednisolone. In Group I, 100% of patients underwent their first KT; in Group II, this proportion was 96.3%.\u003cs\u003e\u0026nbsp;\u003c/s\u003e\u003c/p\u003e\n\u003cp\u003eGroup I had a significantly longer hospital stay (9\u0026plusmn;5.1 vs. 5\u0026plusmn;2.3 days) (P=0.0001). In Group I,\u0026nbsp;80(83.3%), 6 (6.3%), and 10 (10.4%) patients had primary functioning graft (PFG), slow graft function (SGF), and delayed graft function (DGF), respectively. In Group II, 101 (93.5%), six (5.5%), and one (1%) had PGF, SGF, and DGF, respectively (P=0.01).\u0026nbsp;\u003cstrong\u003eTable 1\u003c/strong\u003e illustrates the comparison of demographic criteria between the two groups.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAt 90 days postoperatively,\u0026nbsp;seven patients (7.3%) in Group I and two patients (1.8%) in Group II experienced acute rejection episodes (P=0.5). All patients with acute cellular rejection (ACR) received pulse steroids and anti-thymocyte globulin (ATG) at doses of 4-7 mg/kg. Patients with combined ACR and acute antibody-mediated rejection (ABMR) in Group I received ATG at 6-7 mg/kg, pulse steroids, five sessions of plasma exchange, intravenous immunoglobulin at 100 mg/kg after each exchange, and rituximab at 375 mg/m\u0026sup2; once weekly for four doses. Surgical complications were more frequent in Group I, with higher rates of surgical site infections (SSI) (8.33% vs. 1.85%, P=0.03) and lymphocele (18.75% vs. 6.48%, p=0.007). Urinary tract infections (UTIs) occurred more frequently in Group I (12.5% vs. 1.8%; p=0.002). \u003cstrong\u003e(Table 2)\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAdditionally, Group I had three cases of cytomegalovirus (CMV) infections (3.12%), whereas Group II had none, although this difference was not statistically significant (p=0.102). For BK virus (BKV) infections, Group I had two cases (2.0%) compared with one case (0.9%) in Group II, showing no significant difference (p=0.493). Both groups had no reported cases of Epstein\u0026ndash;Barr virus (EBV) or HIV infection, and the rates of hepatitis B and C infections were similar, with no significant differences. In group I, the most frequently isolated bacterium in early recurrent UTIs was Escherichia coli, accounting for 80.9% of cases. Extended-spectrum beta-lactamases (ESBL) and multidrug-resistant organisms (resistant to three or more drugs) were present in 82.4% of the isolates. Additionally, meropenem was identified as the most effective antibiotic, with an effectiveness rate of 86.7%. Moreover, 65% of UTIs were managed with a single antibacterial course.\u003c/p\u003e\n\u003cp\u003eThe mean peak creatinine level at the time of rejection was 320 \u0026mu;mol/L, which decreased to 140 \u0026mu;mol/L at discharge and 125 \u0026mu;mol/L after one year. One-year patient survival was significantly lower in Group I (94.8%) than in Group II (100% in Group II (p=0.0167). Additionally, Group I had poorer long-term kidney function, as indicated by higher serum creatinine levels at one year (112.6 vs. 91.7; p=0.008) and five years (142.2 vs. 111.0; p=0.00001). Overall, the outcomes for Group I were notably worse than those for Group II, highlighting the risks associated with commercial KT. The detailed results are summarized in Tables 1 and 2.\u003c/p\u003e\n\u003cp\u003eIn group I, the overall graft survival was 68 (71%), and the 1-, 2-, 3-, and 5-year cumulative graft survivals were 80%, 79%, 74%, and 54%, respectively. In Group II, the overall graft survival was 92(85%), and the 1-, 2-, 3-, and 5-year cumulative graft survival rates were 98%, 97%, 90%, and 60%, respectively. [HR= 2, 95% CI= 1.1-3.8, P=0.02] \u003cstrong\u003e(Figure 1).\u003c/strong\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe overseas KT is a significant international concern [8]. This study's primary reason for these patients seeking KT abroad was the lack of available donors.\u003c/p\u003e \u003cp\u003eIn our study, we observed unfavorable outcomes in the cohort that received KT abroad, which included higher rates of SSI (8.33% vs. 1.85%, p\u0026thinsp;=\u0026thinsp;0.032) and lymphocele (18.75% vs. 6.48%, p\u0026thinsp;=\u0026thinsp;0.0076), as well as significantly more UTI (12.5% vs. 1.8%, p\u0026thinsp;=\u0026thinsp;0.0026). This Group also had a higher rate of acute rejection (7.29% compared to 1.85% in Group II). Furthermore, 1-year patient survival was significantly lower in Group I (94.8% alive vs. 100% in Group II (p\u0026thinsp;=\u0026thinsp;0.0167). We also observed significant differences in induction therapy between the local and overseas groups. Using basiliximab in high-risk patients or patients without appropriate immunological risk assessment may partly account for the higher rejection rates observed in our overseas KT cohort [5].\u003c/p\u003e \u003cp\u003eThe 1-year survival rate of living-related KT in Saudi Arabia is 98.4 [9]. In this study, the 1-year patient survival rate was 94.8% for those who underwent overseas KT and 100% for those who underwent local KT.\u003c/p\u003e \u003cp\u003eThere are conflicting reports regarding the outcomes of patients receiving commercial KT, with both unfavorable and favorable results documented [10]. Several international studies have reported favorable outcomes, including one of the most extensive analyses comparing graft and patient survival rates between transplanted domestically. In 2000, Morad et al. examined Malaysian patients (n\u0026thinsp;=\u0026thinsp;515) who underwent KT in India and China, and \u0026gt;\u0026thinsp;90% of the grafts and patients survived. Among the 258 patients who received kidneys from living donors, the rates of infectious complications and patient and graft survival were similar between the groups [11].\u003c/p\u003e \u003cp\u003eThis outcome contrasts recent studies reporting poor graft and patient survival rates. For instance, Sever et al. examined the mid-term outcomes of 115 patients who underwent commercial KT in multiple countries, primarily India, Iran, and Iraq [12]. Notably, 15 recipients experienced unconventional infections, including 10 with malaria, 3 with aspergillosis, and 2 with mucormycosis [12]. The graft and patient survival rates at seven years for those who underwent commercial KT were 53% and 74%, respectively, whereas the rates for living-related KT performed at their center were 73% and 80% [12]. Moreover, Sever et al. reported that although mid-term graft survival was worse, patient survival was comparable to that following commercial living KT [12].\u003c/p\u003e \u003cp\u003eIn another study by Salahudeen et al., a high early postoperative mortality rate was reported in a case series of 16 patients. The 1-year patient survival rate for overseas commercial KT ranged from 80\u0026ndash;96%, whereas the rate for living-related KT in Australia exceeded 95%. Additionally, the 5-year patient survival rate was 60%. The study also reported high rates of infectious complications, including hepatitis B, cytomegalovirus, aspergillus, and multidrug-resistant Pseudomonas aeruginosa infections [13].\u003c/p\u003e \u003cp\u003eAdditionally, Sajjad et al. emphasized that recipients face surgical risks in poorly equipped and unsanitary clinics, which increases the likelihood of infection. Meanwhile, donors are mainly from lower socioeconomic groups in developing countries who often need more access to follow-up care. In some instances, these donors may even carry infectious diseases such as tuberculosis, AIDS, and hepatitis [3].\u003c/p\u003e \u003cp\u003eDe Souza et al. reported a 1-year infection rate of 42.2%, with UTIs being the most common. This finding is consistent with the established view that UTIs are the most prevalent infections among patients undergoing KT [14]. Similarly, in our cohort, patients who underwent overseas KT had higher rates of SSIs and UTIs, with rates of 12.5% compared with 1.8% (p\u0026thinsp;=\u0026thinsp;0.0026).\u003c/p\u003e \u003cp\u003eThe onset of acute rejection of KT significantly reduces long-term graft survival, especially if rejection is not completely reversed [15]. In our study, seven patients who underwent overseas KT experienced graft rejection, whereas only two patients from the local cohort experienced similar issues.\u003c/p\u003e \u003cp\u003eBecause overseas KT is often commercially motivated, patients at these centers typically experience the shortest postoperative hospital stay and are encouraged to return to their home countries upon discharge [5]. In our study, the average length of stay of the overseas KT group was 9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.1 days.\u003c/p\u003e\n\u003ch3\u003eSTUDY LIMITATIONS\u003c/h3\u003e\n\u003cp\u003eThe primary limitations of our study include the small sample size and the fact that it was conducted at two centers. Furthermore, observational and retrospective designs may introduce various biases.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eCommercial KT is associated with a higher incidence of infections and rejection episodes than locally performed unrelated KT. Further studies are critical for investigating commercial KT\u0026rsquo;s long-term outcomes and identifying the factors that drive this practice.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eConsent for publications\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eData Availability\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data supporting this study's findings are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCompeting Interests\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eClinical trial number:\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors contributions:\u0026nbsp;\u003c/strong\u003eH M El Hennawy: protocol development, manuscript writing, manuscript review, and senior author., O Safar: protocol development, manuscript writing, manuscript review., A S Al Faifi: data analysis, manuscript writing., M H El Hennawy: manuscript Review and editing., B Alghamdi: protocol development and data collection., A Ali: protocol development., M Alqahtani: protocol development and manuscript Review., M F Zaitoun: data collection., S A. Alasmari: protocol development and data collection., A Serageldeen: data collection and manuscript review., T A. Abouelgreed: data collection and manuscript review. K Fourtounas: data collection and manuscript review. M Ayyad: data collection and manuscript review., A Ali: data collection and manuscript review., M H Zahran: manuscript review, editing, and senior author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAcknowledgments\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eH. Liman, M. Makusidi, and A. Sakajiki, \u0026ldquo;Kidney transplant-related medical tourism in patients with end-stage renal disease: A report from a renal center in a developing nation,\u0026rdquo; \u003cem\u003eSahel Medical Journal\u003c/em\u003e, vol. 23, no. 1, p. 7, 2020, doi: 10.4103/smj.smj_17_19.\u003c/li\u003e\n \u003cli\u003eJafar, T. H. \u0026ldquo;Organ trafficking: global solutions for a global problem.,\u0026rdquo; \u003cem\u003eAm. J. Kidney Disease\u003c/em\u003e, vol. 54, no. 6, pp. 1145\u0026ndash;57, Dec. 2009, doi: 10.1053/j.ajkd.2009.08.014.\u003c/li\u003e\n \u003cli\u003eI. Sajjad, L. S. Baines, P. Patel, M. O. Salifu, and R. M. Jindal, \u0026ldquo;Commercialization of kidney transplants: a systematic review of outcomes in recipients and donors.,\u0026rdquo; \u003cem\u003eAm J Nephrol\u003c/em\u003e, vol. 28, no. 5, pp. 744\u0026ndash;54, 2008, doi: 10.1159/000128606.\u003c/li\u003e\n \u003cli\u003eB. Adamu, M. Ahmed, R. F. Mushtaq, and F. Alshaebi, \u0026ldquo;Commercial kidney transplantation: trends, outcomes and challenges-a single-center experience.,\u0026rdquo; \u003cem\u003eAnn Afr Med\u003c/em\u003e, vol. 11, no. 2, pp. 70\u0026ndash;4, 2012, doi: 10.4103/1596-3519.93527.\u003c/li\u003e\n \u003cli\u003eM. Tawhari and M. Radwi, \u0026ldquo;A Three-Year Experience With Overseas Kidney Transplantation in a Tertiary Transplant Center in Saudi Arabia,\u0026rdquo; \u003cem\u003eCureus\u003c/em\u003e, Apr. 2022, doi: 10.7759/cureus.23988.\u003c/li\u003e\n \u003cli\u003eM. M. Friedlaender, \u0026ldquo;The role of commercial non-related living kidney transplants.,\u0026rdquo; \u003cem\u003eJ Nephrol\u003c/em\u003e, vol. 16 Suppl 7, pp. S10-5, 2003.\u003c/li\u003e\n \u003cli\u003eJ. Augustine, \u0026ldquo;Kidney transplant: New opportunities and challenges,\u0026rdquo; \u003cem\u003eCleve Clin J Med\u003c/em\u003e, vol. 85, no. 2, pp. 138\u0026ndash;144, Feb. 2018, doi: 10.3949/ccjm.85gr.18001.\u003c/li\u003e\n \u003cli\u003eAlBugami M, Hussein M, Alsaeed S, Almubarak A, Bel \u0026rsquo;eed-Akkari, \u0026ldquo;Outcome of Saudi Patients Returning after Commercial Kidney Transplantation Abroad,\u0026rdquo; in \u003cem\u003eERA-EDTA Annual Meeting\u003c/em\u003e, Amsterdam, Netherland, Mar. 2014, p. 548.\u003c/li\u003e\n \u003cli\u003eF. A. M. Shaheen, H. and M. Z. Souqiyyeh, \u0026ldquo;Current status of renal transplantation in the Kingdom of Saudi Arabia.,\u0026rdquo; \u003cem\u003eTransplant Proc\u003c/em\u003e, vol. 36, no. 1, pp. 125\u0026ndash;7, 2004, doi: 10.1016/j.transproceed.2003.11.037.\u003c/li\u003e\n \u003cli\u003eM. Suthanthiran and T. B. Strom, \u0026ldquo;Renal transplantation.,\u0026rdquo; \u003cem\u003eN Engl J Med\u003c/em\u003e, vol. 331, no. 6, pp. 365\u0026ndash;76, Aug. 1994, doi: 10.1056/NEJM199408113310606.\u003c/li\u003e\n \u003cli\u003eZ. Morad, and T. O. Lim, \u0026ldquo;Outcome of overseas kidney transplantation in Malaysia.,\u0026rdquo; \u003cem\u003eTransplant Proc\u003c/em\u003e, vol. 32, no. 7, pp. 1485\u0026ndash;6, Nov. 2000, doi: 10.1016/s0041-1345(00)01300-2.\u003c/li\u003e\n \u003cli\u003eM. S. Sever \u003cem\u003eet al.\u003c/em\u003e, \u0026ldquo;Outcome of living unrelated (commercial) renal transplantation.,\u0026rdquo; \u003cem\u003eKidney Int\u003c/em\u003e, vol. 60, no. 4, pp. 1477\u0026ndash;83, Oct. 2001, doi: 10.1046/j.1523-1755.2001.00951.x.\u003c/li\u003e\n \u003cli\u003eA. K. Salahudeen \u003cem\u003eet al.\u003c/em\u003e, \u0026ldquo;High mortality among recipients of bought living-unrelated donor kidneys.,\u0026rdquo; \u003cem\u003eLancet\u003c/em\u003e, vol. 336, no. 8717, pp. 725\u0026ndash;8, Sep. 1990, doi: 10.1016/0140-6736(90)92214-3.\u003c/li\u003e\n \u003cli\u003eR. M. de Souza and J. Olsburgh, \u0026ldquo;Urinary tract infection in the renal transplant patient.,\u0026rdquo; \u003cem\u003eNat Clin Pract Nephrol\u003c/em\u003e, vol. 4, no. 5, pp. 252\u0026ndash;64, May 2008, doi: 10.1038/ncpneph0781.\u003c/li\u003e\n \u003cli\u003eG. Opelz and B. D\u0026ouml;hler, \u0026ldquo;Influence of Time of Rejection on Long-Term Graft Survival in Renal Transplantation,\u0026rdquo; \u003cem\u003eTransplantation\u003c/em\u003e, vol. 85, no. 5, pp. 661\u0026ndash;666, Mar. 2008, doi: 10.1097/TP.0b013e3181661695.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 2 are available in the Supplementary Files section\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnep","sideBox":"Learn more about [BMC Nephrology](http://bmcnephrol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bnep/default.aspx","title":"BMC Nephrology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-5418384/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5418384/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Due to a shortage of cadaveric organs for transplantation, some Saudi patients seek to purchase kidneys in other countries. However, kidney transplantation (KT) abroad is often associated with negative outcomes. This study shared the experiences of two Saudi transplantation centers regarding unrelated KT overseas.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e This retrospective comparative cohort study included patients who underwent unrelated KT abroad (Group I) and local patients who received living unrelated KT from September 2017 to July 2024, with follow-up for at least one year at AFHSR and Tabouk.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003ewe studied 204 patients, including 96 who underwent commercial KT (Group I) and 108 who received living unrelated KT(Group II), with an average follow-up of 42 months. Immediate graft function was lower in Group I (83.33%) than in Group II (93.51%; p=0.0104). One-year patient survival was significantly lower in Group I (94.8%) than in Group II (100% in Group II (p=0.0167), along with poorer long-term kidney function.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e commercial transplantation patient survival rates are lower, and overall outcomes are worse than those of traditional unrelated transplantation in the midterm. Educating patients about the risks associated with overseas KT and promoting public registration for deceased organ donation could help mitigate this practice.\u003c/p\u003e","manuscriptTitle":"Navigating Risks: Insights on Unrelated Overseas Renal Transplantations from Two Saudi Centers","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-18 09:43:01","doi":"10.21203/rs.3.rs-5418384/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-11-19T05:43:24+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-11-15T06:05:11+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-11-15T06:03:50+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Nephrology","date":"2024-11-08T18:24:47+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnep","sideBox":"Learn more about [BMC Nephrology](http://bmcnephrol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bnep/default.aspx","title":"BMC Nephrology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d5539462-d6d6-4d9f-97da-ca309b0e5f36","owner":[],"postedDate":"December 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-05-05T16:05:58+00:00","versionOfRecord":{"articleIdentity":"rs-5418384","link":"https://doi.org/10.1186/s12882-025-04143-x","journal":{"identity":"bmc-nephrology","isVorOnly":false,"title":"BMC Nephrology"},"publishedOn":"2025-05-02 15:57:37","publishedOnDateReadable":"May 2nd, 2025"},"versionCreatedAt":"2024-12-18 09:43:01","video":"","vorDoi":"10.1186/s12882-025-04143-x","vorDoiUrl":"https://doi.org/10.1186/s12882-025-04143-x","workflowStages":[]},"version":"v1","identity":"rs-5418384","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5418384","identity":"rs-5418384","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}