Kidney transplantation in obese Black patients: Strategies to improve access and outcomes

Abstract

Kidney transplantation (KT) improves quality of life and confers a survival advantage compared to remaining on dialysis in suitable patients with end-stage renal disease. Black patients face challenges, as there are significant disparities in their access to KT and subsequent outcomes compared to other patient groups. This is further exacerbated by the rising prevalence of obesity and consequent health burdens. Controversies exist regarding the eligibility criteria for obese Black patients to undergo KT and factors influencing their long-term outcomes. There is limited evidence in the literature to allow the development of definitive criteria for KT in obese Black patients, given the challenges posed by differences in their genotypic and phenotypic characteristics compared to better-studied populations. There is sparse data on KT programmes for Black population groups in Africa. These patients face challenges such as low socioeconomic status, poor level of education, and awareness of health issues. Even if they do undergo KT, they tend to spend a longer period on dialysis beforehand, leading to poorer outcomes. Further evidence-based data on this patient group are therefore vital to improve their access to KT and subsequent outcomes. This review aims to evaluate the existing evidence, highlight challenges faced by obese Black patients with end-stage kidney disease, and discuss possible strategies to improve both their access to transplantation and subsequent outcomes.

Key Words: Kidney transplantation; Obesity; Black population; Access; Outcomes

Core Tip: Kidney transplantation (KT) is lifesaving as a treatment of kidney failure regardless of race and body habitus. However, long-term data on outcomes in people with obesity who are of Black ethnicity are limited, and this can be a significant deterrent to transplantation in this group. In addition, the available evidence supporting the benefits of KT in the Black population with obesity is controversial. We have reviewed the literature and discuss factors (both modifiable and non-modifiable) affecting access to and outcomes from KT. Issues such as suitable policy changes, better characterisation of Black patients (including genetic studies) and steps to ensure appropriate medication dosing are vital. Emerging medications and new surgical interventions also raise hope in improving access for Black patients.

INTRODUCTION

Kidney transplantation (KT) is the preferred modality of renal replacement therapy (RRT) for suitable patients with end-stage renal disease (ESRD). It confers a survival advantage, improves quality of life, and is cheaper than remaining on dialysis. The global increase in rates of obesity is having a significant effect not only on prevalence of ESRD, but also on access to KT and subsequent outcomes. It is estimated that 7% of mildly obese, 28% of moderately obese, and 46% of morbidly obese patients are precluded from KT based on their body weight[1].

Black patients (including Black Africans, Black British, African Americans and African Canadian), have higher rates of obesity together with an increased prevalence of chronic kidney disease (CKD) and accelerated progression to ESRD[2,3]. There is already a disparity in access to KT services among Black patients compared to their White counterparts, and obesity further increases their risk of being excluded from KT[4]. This group, therefore, merits specific attention, particularly since obesity is a modifiable risk factor and so should not automatically preclude Black patients from accessing this lifesaving intervention[5].

The prevalence of obesity is higher among patients with CKD and those starting any form of RRT compared to the general population[6]. Black patients face a double challenge. Compared to White Caucasians, they have significantly higher rates of obesity (and extreme obesity) both within the general population[7,8], and among potential KT recipients[2]. Many transplant centres are reluctant to accept obese Black patients for this important life-improving and cost-saving procedure despite the lack of definitive evidence to support this stance[9]. While there is an increased risk of surgical complications in obese patients, ongoing improvement in surgical techniques and perioperative management has led to better outcomes[10,11]. This review aims to evaluate the existing evidence and highlight challenges and potential interventions that may improve access to KT and subsequent outcomes for obese Black patients.

THE BURDEN OF OBESITY IN BLACK PATIENTS WITH CKD

Obesity is an independent risk factor for the development of CKD and progression to ESRD[12]. Studies from different continents have shown a significantly higher prevalence of obesity among Black patients than Caucasians (45.4% vs 37.4%)[13-15]. In the Coronary Artery Risk Development in Young Adults study, increasing class of obesity was associated with a higher risk of deterioration in kidney function among Black patients than Caucasians[16]. CKD is more prevalent (and, on average, diagnosed seven years earlier) in Black patients than in Caucasians, and albuminuria is 40% higher[17]. High-risk Black patients with hypertension or diabetes, the two main comorbidities associated with obesity, have a higher prevalence of CKD of 35.6% and 32.6% respectively, compared to 15.8% in the general population[18]. In a systematic review from Africa by Adeboye et al[19], obese Black Africans had a higher burden of inflammatory and cardiovascular risk markers and increased vascular resistance than Caucasians. In the United States, African Americans are 1.4 times more likely to be obese, and 40% and 60% more likely to be diagnosed with hypertension and diabetes respectively, than Caucasians[20]. As already mentioned, hypertension and diabetes are major risk factors for CKD, present in more than 70% of patients with ESRD[21]. Rates of hypertension in adults in Africa are amongst the highest globally, with almost half of adults over the age of 25 being affected[22,23]. The prevalence of obesity among urban dwellers in the region is 20%-50%, and individuals with obesity have double the risk of hypertension. In the Research on Obesity and Diabetes among African Migrants study, Agyemang et al[24], found a high prevalence of obesity (up to 21% and 54% in men and women, respectively) and diabetes (up to 15% and 10% in men and women, respectively) among African migrants living in Europe.

PREDISPOSITION TO CKD IN BLACK PATIENTS

In the United Kingdom, the median age for incident dialysis among Black patients is 56 years compared to 66 years in Caucasians. In addition, there is a higher prevalence of ESRD than in Caucasians: 12.3% vs 10.5% in 35-44-year-old. Among patients with ESRD, 43% of Black patients have functioning kidney transplants compared to 59% of Caucasians[25].

Data from the United States have shown that African Americans are four times more likely than Caucasians to be diagnosed with ESRD, and while constituting only 12% of the population, they represent 32% of dialysis patients[26]. The prevalence of ESRD is nearly three and a half times higher than in Caucasians (5854 vs 1703, per million people) and indeed any other ethnic group. Similarly, the incidence of ESRD is higher (834 vs 312, per million people). In terms of waiting time for KT, African Americans had a median of 60 months compared to 41 months in Caucasians. African Americans were also less likely than Caucasians to have received specialist pre-dialysis care for more than 12 months (27.1% vs 33.1%). Furthermore, 34.1% of Caucasians with ESRD underwent KT compared to only 19.5% of African Americans (a ratio of 1.7), and this gap has widened further with a ratio of Caucasians to Black patients of 2.5 in the 2020 report. Black patients are less likely to have pre-emptive KT, and the disparity continues up to 3 years on dialysis[17,26].

Obesity exerts multiple effects throughout the spectrum of kidney disease, from early CKD to ESRD (including dialysis and KT), and this influence is even more pronounced in Black patients. Compared to Caucasians, African Americans with CKD show an increase in mortality from all causes [relative risk (RR): 1.78, 95% confidence interval (CI): 1.14-2.78] and cardiovascular events (RR: 2.11, 95%CI: 1.00-4.47)[27,28]. Outcomes following KT are less clear-cut. While some authors have reported that obesity does not significantly impact results[29,30], others have suggested that it is associated with poorer outcomes, particularly among patients with extreme obesity[31]. Potential perceptions that obese Black patients have improved survival on dialysis and poorer outcomes following KT may lead to their further exclusion from or delay in undergoing transplantation, thus exacerbating the existing disparity. However, this misses the point that, even if there is some narrowing of the risk/benefit ratio, KT still confers better patient outcomes in Black patients than remaining on dialysis and is more cost-effective[32].

RACIAL DISPARITIES IN ACCESSING KT

Previous studies report that Black adults are less likely to receive both deceased and live donor KT. However, reassuringly, recent publications have reported improved deceased-donor KT rates among this group. The main current challenge is the delay in waitlisting[33-35]. Particularly prevalent among Black patients (compared to Caucasians) are low socioeconomic status, health illiteracy, mistrust of the healthcare system, perceived discrimination on referral, biases on the part of healthcare professionals, and increased burden of comorbidities. Black patients are still 13% less likely to be listed. In the last few decades, obesity has become a particular contributor to this disparity. Black adults are less often referred for transplantation and, even when referred, are more frequently not listed at all[36,37]. It is therefore imperative to institute targeted policy changes to address these modifiable factors and encourage early referral and evaluation to improve access to KT.

To date, most studies on this subject have been conducted in the United States and United Kingdom; however, this racial disparity is global; in Canada, patient race is a strong and independent predictor of access to KT[8], yet in terms of outcomes, graft and patient survival are comparable to Caucasians[38].

In insurance-based healthcare systems, the lower rate of coverage amongst these disadvantaged patients further impacts decisions by health care practitioners to list them for KT, leading to longer time on dialysis and poorer overall outcomes[39]. Even after successful KT, ongoing follow-up and provision and monitoring of immunosuppressive therapy can be a real challenge in this group, further compromising graft survival and other long-term outcomes. In the United Kingdom, up to 20% of Black patients are classified as socially deprived; despite the universal health care system, this group is less likely to be considered for pre-emptive or live donor transplantation [odds ratios (OR): 0.35 and 0.4, respectively], or to undergo KT (OR: 0.66)[40]. Improvement in socioeconomic status and other factors (Figure 1) will likely improve access to KT among this cohort.

Figure 1 Strategies that may improve access to kidney transplantation for obese Black patients. MDT: Multidisciplinary team.

An additional challenge is that Black patients still lag significantly behind in living kidney donation (LKD), which confers even better outcomes than cadaveric KT[41]. There is a clear need for a pragmatic solution to improve access to LKD. The National Black, Asian, Mixed Race and Minority Ethnic Transplant Alliance is heavily involved in raising awareness of organ and stem cell donation, with a view to increasing the number of Black, Asian, Mixed Race and Minority Ethnic donors. Health literacy, LKD transplant knowledge, and culturally sensitive community engagement peer support programmes are potential means of addressing barriers and inequity. Included in the National Black, Asian, Mixed Race and Minority Ethnic Transplant Alliance programme is the GOLD Phone Buddy Scheme, a good example of targeted, tailored peer support for Black patients at the start of their kidney journey to support living donation discussions[42].

In Africa, KT has lagged, with no robust data available. This is compounded by the non-availability of renal registries in most African countries, and the high cost of surgery and anti-rejection medication. The cost of KT for the first six months averages United States $17550[43]. This is out of the patient’s pocket and therefore prohibitive. Almost 60% of kidney grafts are from live donors, with 70% from family members. The bulk of KT in Africa occurs in South Africa, northern Africa, and Nigeria. The level of awareness, knowledge and perception of organ donation has been evaluated among health care workers in Nigeria. Despite good knowledge of organ donation among this group (> 90%), perception of health workers towards organ donation is poor. Only 1 in 10 would donate, while 1 in 3 would volunteer to counsel families of potential donors. Around 40% reported that their religion did not allow them to donate[44]. This implies that to move towards a successful deceased organ donation programme in this population, health care professionals and teams should be targeted for a change of public perception through education, trust building and communication. In Africa, there are legislative, socio-cultural, religious, and administrative challenges confronting cadaveric KT programmes, and there is no quick fix in sight. There is an urgent need for infrastructural development and support for the eager hands of trained transplant teams. Inclusion of transplant programmes in national health insurance schemes would massively improve access to this life-changing treatment. Despite the current limited practice, multinational cohort studies and clinical trials in African populations should be encouraged.

GEOGRAPHICAL AND RACIAL DIFFERENCES IN TRANSPLANT OUTCOMES

Analysis of outcomes following KT is complex, as many variables contribute. However, geographical and racial factors appear to play a significant part. In a report comparing United Kingdom and United States data at one year post KT, the incidence of graft failure in Black patients was twice as high in the United States than in the United Kingdom (hazard ratio: 2.15, 95%CI: 1.91-2.43). Recipient mortality was also 20% lower in the United Kingdom cohort than their United States counterparts[45]. A study examining a cohort of patients in France compared outcomes of Black adults and Caucasians. Encouragingly, there was no difference in patient or graft survival at 5 years[46]. Similarly, a Canadian registry analysis of over 20000 KT patients found that, although Black patients were less likely to be transplanted than Caucasians, there was no difference in graft survival even after correcting for co-morbidities and socioeconomic status. Furthermore, mortality was 50% lower among Black adults than Caucasians[47]. However, it is important to note that the proportions of Black patients in the French and Canadian studies, at 12.8% and 4% respectively, were lower than those reported in most United States studies (sometimes up to 50%)[48]. In contrast, an analysis by Chakkera et al[49] of data from the United States Department of Veterans Affairs revealed that, even in the presence of free access to healthcare, KT graft survival was inferior among Black patients compared to Caucasians (RR: 1.31; 95%CI: 1.26-1.36). The authors could not account for this difference through analysis of comorbidities or socioeconomic factors. However, it should be noted that patients in this study were transplanted before 2000, and clinical practice, particularly regarding the use of immunosuppression, has evolved significantly[50,51].

CLINICAL CHALLENGES OF TRANSPLANTING BLACK PATIENTS WHO ARE OBESE

Obese Black patients face significant challenges in undergoing KT. For surgical procedures generally, Black patients have been demonstrated to have an increased risk of perioperative complications[52]. In KT recipients, obesity is associated with an increase in duration of operation and intensive care unit admission, delayed wound healing and risk of wound infection, delayed graft function, and premature death[31]. However, in a study by Gore et al[53], outcomes of KT in morbidly obese patients were like those in recipients with diabetes. Compared to normal weight Black recipients, in univariate analysis, overall graft and patient survival rates are lower by 38% and 30%, respectively among obese Black patients; however, there is no significant difference in graft failure and patient survival between Black patients and Caucasians in multivariate analysis[54].

Currently, there remains a lack of consensus around the criteria for KT in obese patients in general. This is compounded further by the methods used to define obesity. Although body mass index (BMI) is easy to calculate, its use is not straightforward. The body composition of Black and White adults is different. The distribution of subcutaneous fat and length of bones compared to the trunk are different in the two groups. Black females have higher musculoskeletal mass than White females. Consequently, a methodological error can occur when estimating relative body fat in Black adults if these differences are not taken into account and leading to misclassification of obesity[55].

BMI cannot differentiate between peripheral and visceral adiposity, and it does not account for body composition, thereby overestimating obesity in patients with large muscle mass. As BMI has low sensitivity, the United Kingdom National Institute for Health and Care Excellence (NICE) recommends waist circumference when BMI is less than 35 kg/m²[56]. Interestingly, Kovesdy et al[57] reported lower mortality following KT in people with higher BMI, whereas, after adjusting for BMI, higher waist circumference was associated with a significant increase in mortality. The experience and expertise of the transplanting centre also play an important role in the outcome of KT in obese patients.

PATHOPHYSIOLOGY OF GRAFT DYSFUNCTION IN OBESE KT RECIPIENTS: IS THERE A RACIAL LINK?

Delayed graft function and acute rejection episodes are more common in obese recipients, who also have a higher prevalence of cardiovascular disease, tend to be older, and are on dialysis for longer before KT than non-obese patients. These differences are often even more marked among Black patients (Table 1)[58].

Table 1 Potential factors contributing to kidney graft dysfunction in obese Black patients.

Modifiable factors	Effect on kidney graft dysfunction	Non-modifiable factors	Effect on kidney graft dysfunction
Increasing waiting time	Enhance	APOL1	Enhance
Hypertension	Enhance	MYH9 gene	Enhance
Cardiovascular risk factors	Enhance	CYP3A5	Enhance
Induction protocol; alemtuzumab; OKT3; ATG vs IL-2 Ab	Reduce	MDR1 polymorphism	Enhance
Poor medication compliance	Enhance
Persistent proteinuria	Enhance
New onset diabetes after transplant	Enhance
Increased leptin: Adiponectin ration	Enhance
Obesity	Enhance

OKT3: Muromonab (anti-CD3); ATG: Anti-thymocyte globulin; IL-2 Ab: Anti-interleukin-2 receptor antibody; APOL1: Apolipoprotein L1; MYH9: Myosin heavy chain 9; CYP3A5: Cytochrome P450 family 3 subfamily A member 5; MDR1: Multidrug resistance mutation 1.

Factors related to immunosuppressive regimens also play an important role in graft outcomes, as both obese individuals and Black patients exhibit significant differences in pharmacokinetic and pharmacodynamic characteristics. Drug absorption, distribution, metabolism and excretion can be affected in obese patients, with a significant contribution from racial pharmacogenetic differences. For example, compared to Caucasians, a greater proportion of Black patients (50% vs 10%-30%) express polymorphisms of the cytochrome P450 family 3 subfamily A member 5 enzyme, affecting the metabolism of drugs such as tacrolimus and potentially resulting in increased rates of acute rejection, drug toxicity, or chronic allograft dysfunction[59,60]. Similarly, polymorphism of the multi-drug resistance gene 1 that affects drug absorption, distribution, and metabolism is more common among Black patients than Caucasians (84% vs 22%); this can lead to “steroid-resistant” rejection, in turn resulting in higher intensity immunosuppressive regimens[61]. In Black patients, induction protocols using agents such as alemtuzumab, muromonab (anti-CD3), or anti-thymocyte globulin, when compared to more common regimens using anti-interleukin 2 receptor antibodies (such as basiliximab), are associated with a 32% reduction in the incidence of acute rejection and 9% increase in graft survival, an effect more marked than in Caucasians[62]. In addition to these biological factors, poor concordance with medication regimens is commoner among Black recipients, with one United States study showing rates of 50% compared to 28% in Caucasians[63]. Proteinuria, an independent risk factor for cardiovascular disease and progression of kidney disease, is more common in both obese patients and Black patients. In a cohort of KT recipients with a predominantly obese Black group, Kwan et al[48] showed that proteinuria increased with adiposity, and severity of obesity was associated with an increasing level of proteinuria (OR: 1.48-2.43) and increased risk of graft failure (OR: 1.02-1.25) at 4 years. Obesity likely contributes to this risk by promoting a chronic inflammatory state with resultant metabolic stress that may also reduce graft longevity and increase cardiovascular risk[64].

Other racial and genetic differences may also affect the development and progression of CKD and outcomes following KT. Black patients more commonly express isoforms of the apolipoprotein L1 (APOL1) and myosin heavy chain 9 genes in podocytes, and these are associated with higher rates of hypertensive nephrosclerosis, focal segmental glomerulosclerosis, proteinuria, interstitial fibrosis, human immunodeficiency virus-associated nephropathy, and other renal diseases[65-68]. Such APOL1 variants are present in only around 13% of all United States patients with African ancestry, but in almost 70% of those who develop focal segmental glomerulosclerosis and human immunodeficiency virus-associated nephropathy[69]. There also appear to be racial differences in the pathophysiology of renal disease. For example, while the histopathological features of hypertensive nephropathy in Black patients are mainly glomerulosclerosis and interstitial fibrosis, Caucasians more commonly exhibit intimal and medial thickening[70]. In a United States prospective cohort study by Grams et al[71], the rate of decline in kidney function was 1.5 mL/minute/1.73 m²/year among Caucasians with CKD compared to 2.1 mL/minute/1.73 m²/year and 2.3 mL/minute/1.73 m²/year for African Americans with low and high-risk variants of APOL1, respectively. It is therefore possible that addressing risk factors such as dyslipidaemia, hypertension, and cigarette smoking may confer less benefit on the progression of CKD among Black patients than Caucasians[72]. Post transplant diabetes mellitus (PTDM) is common after KT, with an overall prevalence of around 10%, and the incidence is highest in the first six months (4%-25%)[73,74]. The precise role of PTDM in outcomes following KT is, however, not entirely clear. It is more prevalent among Black recipients than their Caucasian counterparts (OR: 2) and shows a linear increase in prevalence for every 1 kg increase in body weight above 45 kg[75]. Kasiske et al[76] reported a 60% increase in the risk of graft failure in affected patients. Conversely, data from the United States Organ Procurement and Transplantation Network suggest that PTDM alone does not adversely affect graft survival[61]. Regardless, Black recipients have a 1.5-2-fold increased incidence of PTDM compared to Caucasians over and above the effect of obesity[77,78]. Hepatitis C infection, which tends to be more prevalent among Black recipients, has also been suggested to predispose to PTDM[79]. Hypomagnesaemia is common among Black recipients than Caucasians and may promote insulin resistance[80]. Use of steroid-free or steroid-sparing immunosuppressive regimens has been reported to reduce the incidence of PTDM, as have calcineurin inhibitors: For example, prescribing ciclosporin in place of tacrolimus if the immunological risk is low, and avoiding combined use of sirolimus and tacrolimus[51]. Bariatric surgery has been reported to reduce the incidence of PTDM among KT recipients with severe obesity[81].

Application of precision medicine is a viable option to improve transplant outcomes in Black recipients. This combines clinical phenotypes and biological information to formulate suitably refined treatment strategies, rather than a one-size-fits-all approach. For example, a single-centre study in the United Kingdom, where all patients received tacrolimus according to their weights, reported lower median tacrolimus levels among Black patients in the first 4 weeks post KT, leading to a higher incidence of acute rejection compared to other ethnicities[82]. Personalised plans using pharmacogenomic information, monitoring biomarkers, artificial intelligence, and strategies to improve patient concordance may further bolster outcomes. Pre-transplant genotyping of Black patients should be encouraged as it may improve graft and recipients’ survival.

WEIGHT LOSS AND KT

Generally, there is no standardized approach to management strategies and treatment goals in potential KT recipients who are obese. Despite the disproportionately high prevalence of obesity among Black patients, participation in weight loss intervention programmes are lower than that of Caucasians. There is a disparity in the outcomes of behavioural weight intervention programmes, and it is important to review what approaches are most appropriate and effective for Black patients[83]. In managing weight among people with obesity, different approaches, including lifestyle changes, pharmacological and surgical interventions, have been employed.

NON-PHARMACOLOGIC APPROACHES

Structured weight loss programmes for obese potential KT candidates require a multifaceted approach, including dietary and lifestyle changes, psychological interventions, use of pharmacological therapy, and surgery. A personalized, patient-centred programme and a multidisciplinary team (including an experienced renal dietician) are crucial[84]. In one United States study, Black candidates on the KT waiting list were 24% more likely to have lost weight than Caucasians, but improved access to KT following weight loss was only achieved in the latter group[85].

Generally, lifestyle interventions to aid weight loss are extremely challenging, and even more so in Black patients. In a population-based study of about 33000 participants in the United States, middle-aged Black adults were 43% less likely than Caucasians to engage in moderate physical activity. It has been suggested that reduced levels of physical activity and fitness confer as much as a 20% excess risk of CKD in Black patients than Caucasians[86]. Sadly, attempts to modify diet and exercise habits often yield disappointing results, and any weight loss achieved is rarely sustained[87]. Dialysis is associated with fatigue and reduced exercise tolerance, further challenging weight loss. Nevertheless, moderate to vigorous physical activity is recommended to improve health-associated quality of life and exercise tolerance, and to reduce cardiovascular risk in patients with CKD. Regarding dietary interventions, caution is warranted in their use to reduce weight loss in dialysis patients as this group is already subject to significant restrictions (such as potassium and phosphate intake), and further restrictions can increase the risk of malnutrition.

PHARMACOLOGIC MANAGEMENT OF OBESITY

Pharmacological therapy with drugs such as glucagon-like peptide-1 receptor agonists (GLP-RAs) gives a glimmer of hope with obesity management beyond lifestyle modifications (Figure 2)[88]. In a United States-based retrospective study that included KT recipients with type 2 diabetes mellitus and a considerable proportion of Black patients, use of GLP-RAs among dialysis patients was associated with significant weight loss, 23% lower mortality risk, and 66% better chance of being listed for KT[89]. However, in that study, there was a concern about a possible 32% increase in the risk of diabetic retinopathy. In another study, use of GLP-RAs in KT recipients led to a 49% reduction in death-censored graft loss and a 31% reduction in mortality[90]. In the United Kingdom, in addition to reduced calorie intake and regular physical exercise, NICE has now approved both semaglutide and tirzepatide for use in adults with a BMI of at least 35 kg/m² (reduced by 2.5 kg/m²) in groups with increased risk (including Black Africans) and at least one weight-related health condition. At 6 months, the dose and decision to continue with the medication are to be reviewed if weight reduction is less than 5%. Currently, GLP-RAs are available only as injections, but upcoming oral agents would reduce the burden of repeated injections. In the phase 3 ATTAIN-1 and OASIS-1 trials of oral GLP-RAs, orforglipron and semaglutide reduced average body weight by 12.4% and 15.1% over 72 weeks and 68 weeks, respectively[91,92].

Figure 2 Steps in weight management. Percentage weight reduction: ¹5%-10%, ²1%-3%, ³4.1%, ⁴4.8%, ⁵5.4%, ⁶12.5%, ⁷17.8%, ⁸30%. BMI: Body mass index.

In a United States Renal Data System (USRDS) analysis of 127327 participants, there was 85% higher chance of kidney transplant waitlisting and 21% lower risk of mortality with GLP-RA use[93]. When GLP-RA was compared with bariatric surgery, GLP-RA demonstrated consistently reduced risk of mortality. Those who had surgery were more likely to be Black than were glucagon-like peptide-1 users. There was an initial higher mortality among those who had bariatric surgery, but there was a long-term survival advantage and improved transplant access[94].

SURGICAL MANAGEMENT OF OBESITY

In recent years, bariatric surgery has gained an increasingly important role in the management of obesity, with such procedures recommended in patients with a BMI over 40 kg/m² or who have one or more obesity-related comorbidities (which may improve with weight loss) and a BMI above 35 kg/m². To expand the uptake and reduce inequalities in access to surgery, NICE in the United Kingdom recommends a 2.5 kg/m² lower BMI threshold for at-risk ethnic populations, including Black patients. Interestingly, and of benefit to potential KT recipients with obesity, the previous recommendation requiring all non-surgical approaches to have been implemented before considering bariatric surgery has been removed[95].

There are varying opinions on the use of BMI cut-offs for eligibility for KT and indication for bariatric surgery. This may contribute to reduced access to KT by Black patients. While the limits for KT are most commonly around 35 kg/m² in the United Kingdom, higher levels of 35-45 kg/m² are often used in the United States and in Canada[96-98]. There is now a more liberal approach, as evidenced by a recent survey of United States transplant programmes where a BMI cutoff of 40 kg/m² was commonly used for evaluation and listing at more than two-thirds of centres, and over 70% of programmes had weight management units within their centre, with specific integration into transplant program in 1 out of 5 institutions[99].

Bariatric surgical techniques lead to weight reduction by physically restricting the ability to take in food [such as laparoscopic sleeve gastrectomy (LSG), or laparoscopic adjustable gastric bands (LAGB)], by impairing nutrient absorption [for example, by Roux-en-Y gastric bypass (RYGB)], or through a combination of both. Impressive weight loss of up to 70% can be seen in patients undergoing such procedures, but with a reported mortality rate of around 2%[100]. RYGB carries significant risks, including postoperative acute kidney injury, long-term oxalate nephropathy, and nephrolithiasis. In addition, the effects on gut absorption can lead to difficulties in achieving stable levels of immunosuppressant drugs, potentially affecting outcomes following KT[101,102]. A more recent development in bariatric surgery is the use of laparoscopic techniques. These are associated with shorter operating times and lower rates of complications such as post-operative leaks, and their use has further widened the eligibility criteria for bariatric surgery, in turn leading to KT being undertaken in patients who would previously have been excluded[103-105].

In a study by Thomas et al[106] of 31 patients undergoing RYGB before KT (including over 50% Black patients), there were significant improvements in blood pressure and glycaemic control; 90% of patients attained a BMI of < 35 kg/m² following surgery. There was no reported difference in subsequent overall graft outcome compared with normal-weight recipients. However, surgical complications did occur in 25.8% of patients, and the acute rejection rate was higher than in control KT patients who had not undergone bariatric surgery (42.8% vs 15.7%). In another study of 41 patients (35% Black patients) with morbid obesity undergoing LSG before KT, mean BMI reduction over 16 months after LSG and before KT was 9 kg/m², with a significant reduction in blood pressure, need for antihypertensive therapy, and insulin requirements. There was a 97% graft survival among the LSG group at 12 months[107]. Lee et al[108] conducted a meta-analysis that included 453 patients undergoing bariatric surgery prior to KT and 201 patients undergoing bariatric surgery after KT (4.6-15 years), respectively. The 1-year graft survival among those who had bariatric surgery ranged from 70% (in the early studies) to 100% most recently. A limitation of this analysis was that the studies included were not randomised controlled trials. A United USRDS registry report of 188 patients (> 40% Black) who underwent bariatric surgery and were then placed on the KT waiting list showed an average reduction in BMI from 40.1 kg/m² to 35.1 kg/m² over 16 months following bariatric surgery. Almost 70% of those on the waiting list subsequently underwent KT[109]. There was no mortality up to 3 months post-operatively. Fifteen years on, Sheetz et al[110] analysed updated USRDS data (2006-2015) and reported that, at 5 years, bariatric surgery was associated not only with an increase in the chance of KT by 82%, but also a reduction in all-cause mortality by 49% at 1 year post KT when compared with standard care.

To further reduce waiting times for KT, LSG has been performed concurrently with robot-assisted KT. In one such series of 18 patients, the LSG group had a mean BMI of 46 kg/m² at the time of transplantation, 36.6 kg/m² at 3 months and 32 kg/m² at 12 months. The simultaneous LSG and KT procedure was associated with a longer operative time, but warm ischaemic time and hospital stay were comparable to those in the KT group. Graft function at 12 months showed no statistical difference[111]. However, this data should be interpreted with caution due to the small sample size and the relatively short period of follow-up. Nevertheless, this strategy merits further evaluation.

Despite these potentially positive reports, some cautions have been raised around the role of bariatric surgery in KT. In an analysis of over 430000 patients (including 17.6% Black patients), thirty days after bariatric surgery the Black patient cohort had significantly higher rates of mortality (0.13% vs 0.09%), operative complications (4.14% vs 3.41%), need for further intervention (1.34% vs 1.24%), and hospital readmission (5.03% vs 3.56%) than the overall group[112]. Surgical problems included band displacement and erosion, visceral obstruction, dysfunction of LAGB ports, and infection related to the foreign bodies. LSG has a shorter operative time than RYGB and may be more suitable for patients with significant comorbidities, in whom prolonged anaesthesia and surgery are not ideal[113].

As alluded to above, the effect of bariatric surgery on the absorption of immunosuppressive drugs needs to be considered. Unlike LSG and LAGB, RYGB interferes with gut absorption. It has been shown to affect the pharmacokinetics of tacrolimus, sirolimus, and mycophenolate mofetil, both in terms of the maximum plasma concentration achieved and the time to reach that level[108]. However, if these issues are considered, RYGB can still yield positive outcomes: Choudhury et al[114] found that obese patients with ESRD who had RYGB showed improved survival, gaining 1.3 years of life compared to those undergoing LSG before KT. In a cohort studied by Cohen et al[115], 64 patients (from 1994 to 2017) underwent bariatric surgery before or after KT. Both groups had a reduced risk of graft failure at 5 years compared with obese patients undergoing KT without bariatric surgery, with hazard ratios of 0.31 and 0.85 respectively. BMI reduction was also maintained for at least 5 years after bariatric surgery.

There are other potential risks from bariatric surgery that can particularly affect patients with renal disease. Post-operative acute kidney injury has been described in 2.9% to 10% of cases, so careful attention should be paid to perioperative fluid management as fluid balance and haemodynamic factors may play a role[116,117]. Short bowel syndrome (resulting from issues such as bowel adhesions and mesenteric ischaemia, leading to the need for small bowel resection) can occur in around 4% of patients and may also affect the absorption and monitoring of immunosuppressive drugs[118]. In severe cases, short bowel syndrome, common in RYGB, may necessitate the use of parenteral nutrition or even small bowel transplantation[119]. Finally, bariatric surgical techniques (such as RYGB) that lead to malabsorption can result in the development of hyperoxaluria and consequent oxalate nephropathy, although this does appear to be rare among Black patients[120-122].

MAINTAINING WEIGHT LOSS POST TRANSPLANTATION

Post KT, there is an average weight gain of about 10 kg, exacerbated when steroids are used, and this is worse in recipients with pre-existing obesity. Indiscriminate eating habits and poor physical exercise contribute to this. While it is important to avoid malnutrition and metabolic disorders, it is essential to promote a healthy lifestyle[122].

CONCLUSION

The global burden of obesity is increasing, contributing to the burden of CKD. Black patients face challenges: Their underlying rates of CKD are higher, they show a faster progression to ESRD, and they tend to have more comorbidities. They suffer longer delays in being listed for KT, and the resultant increased time spent on dialysis further worsens long-term outcomes. The current consensus is that, despite the increased perioperative risks, KT results in better long-term survival than other forms of RRT. Data regarding KT in obese sub-Saharan African patients are particularly limited. There is a need for renal registries, multinational cohort studies, and clinical trials in this population. It is imperative to conduct longitudinal studies on BMI and other relevant anthropometric measurements, adjusted for ethnicity. There is a need for research to establish the mechanistic relationship between obesity and poor outcomes post-KT. Proactive drug prescription, including the use of pharmacogenetics, should help to reduce the risk of under- or over-dosing immunosuppressive medication. The utility of integrated weight management strategies and teams within transplant programmes cannot be over-emphasized. Ethical, cultural, and logistical factors pose major challenges and are daunting the design of randomized controlled trials and establishment of registries. However, it is vital to overcome these obstacles to improve access to optimal treatments and outcomes in these disadvantaged populations.

ACKNOWLEDGEMENTS

The authors acknowledge John Losasso of Sir Thomas Browne Library, Norfolk and Norwich University Hospital, Norwich for his tireless assistance in helping with literature search.