Clinical profile and outcome of kidney transplantation at Muhimbili National Hospital, Tanzania

doi:10.21203/rs.3.rs-4813058/v1

Background: Kidney transplantation is the definitive treatment option for end-stage renal disease (ESRD), offering improved quality of life and extended survival. Access to kidney transplantation is limited in the Sub-Saharan Africa (SSA) region, with only a few countries with established services. Tanzania started its program five years ago, for the sustainability of the program it is important to understand the outcome. Therefore, this study was conducted to document the outcome of transplantation at MNH in Tanzania.

Methods: This was a retrospective study conducted among patients who were transplanted at MNH between November 2017 and February 2022. Analyses were performed to assess baseline characteristics, post-transplant complications, and patient and graft survival.

Results: In our study of 68 kidney transplant recipients, the majority of recipients were male (63.2%) with a mean age of 45.8 years and under medical insurance (88.2%). The predominant cause of CKD was hypertension (58.2%) with recipients undergoing dialysis for a mean duration of 14.4 months, and basiliximab being the most commonly used induction medication (57.3%). The majority of donors were males (64.7%) and had first-degree relationships with recipients (76.5%). Haploid HLA mismatch was observed in 36.8% of cases. One-year patient and graft survival rates were 91.2% and 96.7%, respectively, with infection being the primary cause of death (n=5), and more than half of deceased patients died with a functioning graft (n=4).

Conclusion: Our study underscores favorable one-year patient and graft outcomes among kidney transplant recipients at Muhimbili National Hospital, Tanzania. However, challenges persist, notably with infections posing ongoing difficulties for this cohort

Chronic kidney disease

kidney transplantation

Muhimbili National Hospital

Chronic kidney disease (CKD) presents a significant health challenge globally, and the burden is disproportionately affecting SSA regions which have the least resources. Tanzania has a CKD prevalence of about 14%.(1). The high burden of CKD in Tanzania is attributed to the increasing prevalence of risk factors such as diabetes mellitus (DM), hypertension (HTN), and infectious conditions such as Human Immunodeficiency Virus (HIV) (2, 3). There are limited care options for patients with kidney failure in SSA with the majority of patients relying on hemodialysis therapy as the main form of renal replacement therapy (RRT). Kidney transplantation is accessible in a few countries in the region including South Africa, Kenya, Sudan, and Nigeria(4, 5).

Few countries in SSA with established programs are offering predominantly living donor transplantation which is in contrast to high-income countries with both deceased and living donation (4)(6, 7). Good graft (80%) and patient (90%) survival rates have been achieved in high-income countries, this is attributed to availability and access to immunosuppression and prophylaxis medications, this is not the case in low-income countries as patients are paying out of pocket and have limited access to the modern immunosuppressive agents(7)

Tanzania has joined other countries in setting up kidney transplantation services with two transplant centers, this reflects the increasing recognition of this option as a feasible treatment of chronic kidney failure in SSA(8). The Tanzania program which is five years old is still faced with many challenges as has been the case for other countries including a lack of supplies and difficulties in getting donors(4, 9). Registries are useful for providing Information about outcomes which is essential in assessing the progress of the program, this information may provide confidence in society and motivate kidney donation (10, 11). In Tanzania, there is no registry and there has been no documentation of the outcome of the transplant program, therefore this study was conducted to determine the outcome of kidney transplantation at Muhimbili National Hospital.

This was a retrospective cohort study aimed to describe the clinical profile and determine the one-year outcome of kidney transplant recipients at Muhimbili National Hospital (MNH) between November 2017 and February 2022. MNH is the first medical facility in Tanzania to start kidney transplantation services. Kidney transplantation at MNH utilizes organs from living donors, and the immunosuppression used include basiliximab and Anti-thyroglobulin (rATG) for induction, while mycophenolate/azathioprine, tacrolimus/cyclosporine, and prednisolone are used for maintenance immunosuppression (9). Few patients are using sirolimus or everolimus as a substitution for calcineurin inhibitors.

Data was collected using a standardized tool which was prepared in English language, these were obtained from patients’ charts and the electronic patient information system. Collected information included donors' and recipients' clinical profiles, human leucocyte antigen (HLA) matching, laboratory results before and after kidney transplantation, immunosuppression, and complications. Other information collected included socio-demographic details and the relationship between donors and recipients. One-year outcome was determined based on the survival and graft function of recipients.

Collected data was entered into Statistical Package for Social Sciences (SPSS) version 25 and checked for consistency. Analysis was performed using the same software and frequency distribution and two-way tables were prepared. Descriptive data of the subject’s characteristics and survival rate were described by medians or means for continuous variables and by number and percentage for categorical variables

Clinical profile of recipients

A total of 68 kidney transplantations were performed between November 2017 and February 2022 and were included in our analysis. The majority were male (63.2%), and mean age of participants was 45.8 years (Range 13–65). Most participants (63.2%) were married, more than half (51.5%) were employed, and 45.6% had a college or university education. The majority of participants (88.2%) were insured under the National Health Insurance Fund. More than half of the participants had hypertension (58.2%), and 36% had diabetes mellitus. Renal biopsy was performed for only 3 patients. The mean duration of hemodialysis before transplantation was 14.4 months. Basiliximab was more frequently used as an induction immunosuppressant (57.3%) (Table 1).

Clinical profile of donors

The donors were predominantly males (64.7%) with a mean age of 42.2 years, and the majority (76.5%) had first-degree relationships with recipients. HLA matching between donors and recipients revealed total match, haploid match, and a total mismatch in 5.9% (4/66), 36.8%, and 1.5% (1/66) respectively, (Table 2).

Outcome of transplantation

The one-year patient and graft survival rate was 91.2% and 96.7% respectively. The average serum creatinine levels of post-kidney transplant patients were 121 µmol/L, 125 µmol/L, 119 µmol/L, and 129 µmol/L at 1,3,6 and 12 months respectively. The primary cause of death was infection (n = 5) and two-thirds of the deceased patients died with a functioning graft (n = 4). Throughout the 12 months, the highest number of deaths (2) occurred in the first and third quarters. (Fig. 1 and Table 3)

Transplant related complications

Transplant complications reported in graft recipients included delayed graft function (30.8%), perinephric collection (23%), intra-operative bleeding (15.4%), urine retention (15.4%), and perinephric hematoma (7.7%), Table 4.

Table 1

Sociodemographic and clinical characteristics of kidney transplant recipients (N = 68)
Factors	N (%)
Sex Male Female	43 (63.2) 25 (36.8)
Age < 35 36–60 > 60 Mean age (years)	26 (38.2) 34 (50) 8 (11.8) 45.8
Marital status Single Married Widowed	21 (30.9) 43 (63.2) 4 (5.8)
Education level Primary Secondary College or University	17 (25) 20 (29.4) 31 (45.6)
Occupation Unemployed Employed Retired Students	14 (20.5) 35 (51.5) 10 (14.7) 9 (13.3)
Mode of payment Paying from pocket Insured	8 (11.8) 60 (88.2)
Etiology of CKD Hypertension Diabetes mellitus Hepatitis B infection Polycystic kidney disease	40 (58.2) 24 (36) 2 (2.9) 2 (2.9)
Duration of RRT before transplantation (months) Pre-emptive transplant 1–6 7–12 13–24 25–59 Mean duration of RRT before transplant (months)	2 (3.0) 8 (11.7) 30 (44.1) 20 (29.4) 8 (11.8) 14.4
Induction medication Basiliximab Antithyroglobulin (rATG)	39 (57.3) 29 (42.6)

Hb-Hemoglobin, RRT-Renal replacement therapy

Table 2

Social demographic and clinical characteristics of kidney donors
Kidney donor characteristics	N (%)
Age (Mean/SD)	42.2 (11.5)
Sex Male Female	44 (64.7) 24 (35.3)
Donor relationship First degree Second degree	52 (76.5) 16 (23.5)
HLA matching 0/6 1/6 *2/6 3/6 4/6 5/6 6/6	1 (1.5) 2 (2.9) 15 (22.1) 25 (36.8) 14 (20.6) 7 (10.3) 4 (5.9)

* DNA fingerprinting was also done

Table 3

Timeline of deaths and return to hemodialysis over 12 months
Duration	First quarter (1-3months)	Second quarter (4–6 months)	Third quarter (7–9 months)	Fourth quarter (10–12 months)
Number of deaths	2	1	2	1
Number of patients returning to HD	0	1	0	2
HD-Hemodialysis

Table 4

**Post-transplant complications** (**N = 13)**
Complication	N (%)
Delayed graft function	4 (30.8)
Intraoperative bleeding	2 (15.4)
Perinephric collection	3 (23)
High drain output	2 (15.4)
Urine retention	2 (15.4)
Iatrogenic pleural effusion	1 (7.7)
Hematoma on the graft site	1 (7.7)
Graft ureteric fibrosis	2 (15.4)

This study was conducted to determine the outcome of kidney transplant recipients after establishing the program at Muhimbili National Hospital, Tanzanian in November 2017. Sixty-eight kidney graft recipients were included in this study and information regarding the clinical profile and one-year outcomes of recipients were evaluated. Notably, our findings reveal a good patient and graft survival comparable to outcomes reported in other settings globally. (12, 13).

Among patients who were alive by one year, the one-year graft survival in our study showed good outcome comparable with kidney transplant outcomes reported in various other settings globally. (6, 12–14). This outcome is attributable to several factors including the selection of relatively young recipients with low risk of comorbid conditions, and the high likelihood of good short-term surgical outcomes. (15). Additionally, all donors were related to the recipients and most had a good HLA matching as they are first-degree relatives. Good HLA matching is an indicator of genetic compatibility and has been reported to reduce reducing the incidence of graft rejection. (16, 17). The choice of recipients was deliberately made in this new program to promote kidney transplantation as a viable intervention for CKD in Tanzania community and to foster confidence among prospective donors for sustaining the program.

Complications are commonly reported following kidney transplantation, and in this study, several complications were noted including intraoperative bleeding, perinephric collection, hematoma, urine retention, and delayed graft dysfunction. Of note, one recipient had iatrogenic pleural effusion, that was caused by central line insertion problems. These complications indicate the importance of monitoring closely patients after transplantation to identify these complications and manage them timely.

Infections emerged as the primary cause of mortality in transplant recipients, attributable mainly to viral pneumonia and pulmonary tuberculosis, which together accounted for over two-thirds of observed deaths in this study, remarkably most of the recipients who died had functioning grafts. Infections are attributed to high immunosuppression induced in the recipients by the potent medicines, and globally infections are the leading causes of mortality among transplant recipients especially in the first year following transplantation (18–20).

Muhimbili National Hospital was the first center to establish kidney transplantation in Tanzania, and now Tanzania has two centres offering kidney transplantation services. The outcome of this study indicates the viability of establishing these services in low-income settings with the potential for good outcomes as was advocated in the Bamako resolutions of 2008(21)

Our study has provided valuable insights into the operationalization of kidney transplantation in Tanzania and the remarkable one-year outcome. However, it is limited by sample size, potentially compromising the generalizability of findings and impeding predictive analyses for identifying factors influencing transplant success. Furthermore, as a single-center study, our results may not fully capture the diversity of transplant recipients nationwide.

In conclusion, our study provides valuable results showing kidney transplant recipients' clinical characteristics and one-year outcomes at Muhimbili National Hospital in Tanzania. We observed a significant proportion of patients achieving a good one-year survival, with a favorable graft survival rate mirroring global kidney transplantation trends. Infections emerged as the leading cause of mortality, emphasizing the need for close monitoring of recipients for potential infections.

Conflicts of interest

We declare no conflicts of interest.

Acknowledgements

We thank the Muhimbili National Hospital for approving the research and providing access to patient’s information

Funding

The author(s) received no financial support for the research, authorship, or publication of this article.

Ethical approval: The study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. The research protocol was reviewed and approved by the Institutional Review Board (IRB) of Muhimbili National Hospital, Clinical Research, Training and Consultancy Unit with reference number MNH/IRB/I/2022/061. For this retrospective cohort study, the requirement for informed consent was waived by the IRB of the MNH as the research involved the use of existing data and posed no more than minimal risk to the participants.

Author Contribution

J.S. conceptualized the study designed the methods and wrote the first draft of the manuscriptJ.M., D.M., and G.V. participated in designing the methods and analyzing the dataP.K. M.N. and D.B. participated in data collection, entry, and results writingF.F reviewed the final draft

Stanifer JW, Maro V, Egger J, Karia F, Thielman N, Turner EL, et al. The epidemiology of chronic kidney disease in Northern Tanzania: A population-based survey. PLoS One. 2015;10(4):1–12.
Ploth DW, Mbwambo JK, Fonner VA, Horowitz B, Zager P, Schrader R, et al. Prevalence of CKD, Diabetes, and Hypertension in Rural Tanzania. Kidney Int Rep [Internet]. 2018;3(4):905–15. Available from: https://doi.org/10.1016/j.ekir.2018.04.006
Mwemezi O, Ruggajo P, Mngumi J, Furia FF. Renal Dysfunction among HIV-Infected Patients on Antiretroviral Therapy in Dar es Salaam, Tanzania: A Cross-Sectional Study. Int J Nephrol. 2020;2020.
Bamgboye EL. Kidney Transplantation in Sub-Saharan Africa: History and Current Status. Kidney360. 2023 Dec 1;4(12):1772–5.
Furia FF, Shoo J, Ruggajo PJ, Kilonzo K, Basu G, Yeates K, et al. Developing nephrology services in low income countries: A case of Tanzania. BMC Nephrol. 2019 Oct 17;20(1).
Boenink R, Kramer A, Tuinhout RE, Savoye E, Åsberg A, Idrizi A, et al. Trends in kidney transplantation rate across Europe: a study from the ERA Registry. Nephrology Dialysis Transplantation. 2023 Jun 1;38(6):1528–39.
Garcia-Garcia G, Harden P, Chapman J. The global role of kidney transplantation. Indian J Nephrol. 2012;22(2):77–82.
Matsha TE, Erasmus RT. Chronic kidney disease in sub-Saharan Africa. Lancet Glob Health [Internet]. 2019;7(12):e1587–8. Available from: http://dx.doi.org/10.1016/S2214-109X(19)30467-X
Furia FF, Shoo JG, Ruggajo PJ, Mngumi JW, Valentine G, Muhiddin MA, et al. Establishing kidney transplantation in a low-income country: a case in Tanzania. Ren Replace Ther. 2024 Dec 1;10(1).
Rosa-Diez G, González-Bedat MC, Luxardo R, Ceretta ML, Ferreiro-Fuentes A. Step-by-step guide to setting up a kidney replacement therapy registry: the challenge of a national kidney replacement therapy registry. Clin Kidney J. 2021;14(7):1731–7.
Davids MR, Caskey FJ, Young T, Balbir Singh GK. Strengthening Renal Registries and ESRD Research in Africa. Semin Nephrol [Internet]. 2017;37(3):211–23. Available from: http://dx.doi.org/10.1016/j.semnephrol.2017.02.002
Ghelichi-Ghojogh M, Ghaem H, Mohammadizadeh F, Vali M, Ahmed F, Hassanipour S, et al. Graft and Patient Survival Rates in Kidney Transplantation, and Their Associated Factors: A Systematic Review and Meta-Analysis [Internet]. Vol. 50, Iran J Public Health. 2021. Available from: https://creativecommons.org/licenses/by-nc/4.0/
Ghelichi-Ghojogh M, Mohammadizadeh F, Jafari F, Vali M, Jahanian S, Mohammadi M, et al. The global survival rate of graft and patient in kidney transplantation of children: a systematic review and meta-analysis. BMC Pediatr. 2022 Dec 1;22(1).
Arogundade FA. Kidney transplantation in a low-resource setting: Nigeria experience. Kidney Int Suppl (2011). 2013 May 1;3(2):241–5.
Beerli N, Denhaerynck K, Binet I, Dahdal S, Dickenmann M, Golshayan D, et al. Age at Time of Kidney Transplantation as a Predictor for Mortality, Graft Loss and Self-Rated Health Status: Results From the Swiss Transplant Cohort Study. Transplant International. 2022 Jan 27;35.
Shi X, Lv J, Han W, Zhong X, Xie X, Su B, et al. What is the impact of human leukocyte antigen mismatching on graft survival and mortality in renal transplantation? A meta-analysis of 23 cohort studies involving 486,608 recipients. BMC Nephrol. 2018 May 18;19(1).
Manski CF, Tambur AR, Gmeiner M. Predicting kidney transplant outcomes with partial knowledge of HLA mismatch. Proc Natl Acad Sci U S A. 2019 Oct 8;116(41):20339–45.
Khedr L, Teama N, El Sharkawy M. Infections in the first year of living related kidney transplantation in a young transplant cohort. BMC Nephrol. 2023 Dec 1;24(1).
De Keyzer K, Van Laecke S, Peeters P, Vanholder R. Human cytomegalovirus and kidney transplantation: A clinician’s update. Vol. 58, American Journal of Kidney Diseases. 2011. p. 118–26.
Goldberg RJ, Weng FL, Kandula P. Acute and Chronic Allograft Dysfunction in Kidney Transplant Recipients. Medical Clinics of North America [Internet]. 2016;100(3):487–503. Available from: http://dx.doi.org/10.1016/j.mcna.2016.01.002
Persy VP RGPNBGMADJVRAAMFSDBM. Prevention and Transplantation in Chronic Kidney Disease: What Is Achievable in Emerging Countries? Nephron Clin Pract. 2010;155(2):122–32.

No competing interests reported.

Clinical profile and outcome of kidney transplantation at Muhimbili National Hospital, Tanzania

Status:

Journal Publication

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Abstract

Figures

Introduction

Methodology

Results

Clinical profile of recipients

Clinical profile of donors

Outcome of transplantation

Transplant related complications

Discussion

Declarations

Author Contribution

References

Additional Declarations

Status:

Journal Publication

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