Membership of some ethnic groups has an effect on renal transplant outcome but little is known about the impact of Indo-Asian ethnicity, despite this group's high incidence of renal disease. We compared outcomes in Indo-Asians and Caucasians at the Hammersmith Hospital (Indo-Asians, N = 46; Caucasians, N = 90), in the Long-Term Efficacy and Safety Surveillance (LOTESS) database of cyclosporin-treated renal transplant recipients (Indo-Asians, N = 254; Caucasians, N = 4262) and the National Transplant Database held by UK Transplant (Indo-Asians, N = 459; Caucasians, N = 4831). The baseline demographic and co-morbid characteristics of the two ethnic groups were comparable, save for more diabetes in the Indo-Asian community. Following transplantation, the incidence of delayed graft function and steroid-resistant acute rejection were also comparable, as were graft and patient survival (out to 5 years) and graft function. In addition, post-transplant blood pressure, levels of cholesterol and triglycerides and exposure to corticosteroids and cyclosporin were comparable. However, when patients who were not diabetic before transplantation were studied separately, there was an increased incidence of diabetes in the Indo-Asian community (Hammersmith data: Indo-Asians 10.9% vs. Caucasians 3.3%, p = 0.02; LOTESS data Indo-Asians 5.5% vs. Caucasians 1.6%, p < 0.0001). Subsequent management of this group should pursue immunosuppressive regimens less likely to impair post-transplant glucose tolerance.
The role of ethnicity in the success of kidney transplantation has been the subject of considerable debate. This is particularly important in the Indo-Asian community because of its high prevalence of renal disease. (We define “UK Indo-Asians” as UK residents born in India, Pakistan, Bangladesh or Sri Lanka or whose parents had emigrated from that region. This group is sometimes known as “South Asians”). The incidence of non-insulin dependent diabetes in Indo-Asians in the middle years of life is up to five times greater than in Caucasians: up to 20% of Indo-Asians aged 40–69 have diabetes, compared with about 5% of Caucasians (1,2). To compound the problem, the incidence of diabetic nephropathy is higher in Indo-Asian diabetics than in Caucasian diabetics, with a relative risk of up to 14 (3). Other causes of renal disease also appear to be higher in this ethnic minority. The cause of this variation is probably multifactorial, including genetic, environmental and socioeconomic factors, and the propensities of Asian people to central obesity and a sedentary lifestyle also place them in a high-risk category. In total, the risk of end-stage renal disease is some three- to fivefold greater among Indo-Asians compared with Caucasians. One study reported a “take-on” rate for dialysis of 90 and 50 per million population (pmp) in European men and women over 16, respectively, compared with 281 and 196 pmp for Indo-Asians (4).
Very little has been reported about renal allograft survival in Asian recipients. The higher incidence of diabetes and a metabolic syndrome characterized by central obesity, insulin resistance and hypercholesterolemia and possibly hypertension might be expected adversely to affect patient and graft survival. US studies have suggested superior graft survival among Asian recipients (5). However, the US Asian population predominantly originates from the Pacific Rim rather than the Indian subcontinent and is thus ethnically very different. Three small UK studies appear to draw contradictory conclusions. Jeffrey et al., comparing the graft outcomes of 52 Indo-Asian transplant recipients with those of 556 non-Indo-Asians, reported a trend toward lower 5-year graft survival and a higher incidence of death with a functioning graft (6). However, Loucaidou et al., comparing 53 Indo-Asian transplant recipients with 192 non-Indo-Asians, (7) and Higgins et al., comparing 19 Indo-Asian transplant recipients with 157 non-Indo-Asians, (8) both found no differences in outcome, although even Loucaidou et al. noted a tendency to worse 3–5 year survival in Indo-Asians, (which was not statistically significant). The major problem with these studies was the relatively low numbers of patients involved. In an attempt to clarify this issue, in this study we report experience with two cohorts which include 46 and 254 recent Indo-Asian transplant recipients and consider co-morbid complications as well as graft and patient survival.
Hammersmith Hospital cohort
We initially conducted a retrospective review of a cohort of patients transplanted at Hammersmith Hospital, London, from January 1995 to December 2000 (N = 157). Of these, 46 were Indo-Asian and 90 Caucasian. (Indo-Asian ethnicity was self-reported on direct questioning by patients or their family and was defined on the basis of birth or parental birth in India, Pakistan, Bangladesh or Sri Lanka.). The rest were of other ethnic origins. Mean follow-up was 5.5 (±3.0) years.
Patients received two peri-operative doses of methylprednisolone (500 mg) intravenously (at induction and after the vascular anastomosis was fashioned). Thereafter, all patients were managed with prednisolone 20 mg/day, reducing to 7.5 mg/day over the first 3 months and remaining at that dose until 1 year post-transplantation. After 1 year, patients were selected on the basis of clinically assessed immunological risk to have their prednisolone withdrawn over the course of their second post-transplant year. Criteria used to define high immunological risk (and thus inappropriateness for steroid withdrawal) were three or more rejection episodes during the first year or a rejection episode within the preceding 6 months, retransplantation or plasma creatinine >200 μmol/L. Neither membership of any particular ethnic group nor development of post-transplantation diabetes mellitus (PTDM) was considered a reason for deviating from the protocol just outlined in the era covered by this study. No patient undergoing steroid withdrawal in this study suffered late rejection as a result. Patients were also given azathioprine 1 mg/kg/day and ciclosporin from their first post-operative day. Target ciclosporin (CsA) 12-hour trough levels were as follows: 0–3 months, 250–350 ng/mL; 3–6 months, 200–300 ng/mL; 6–12 months, 150–250 ng/mL; and after 12 months, 100–200 ng/mL. No patients were given tacrolimus.
The following clinical data were collected: age, gender, type of transplantation (live or deceased donor), pre-transplant dialysis modality, co-morbidity (which included hypertension, ischemic heart disease, peripheral vascular disease and diabetes mellitus) and HLA mismatch. We also identified the following post-transplantation parameters: delayed graft function, acute rejection (number of episodes, time to first rejection and steroid-resistance), hyperlipidemia and hypertension, as well as graft and patient survival and graft function.
In order to compare immunosuppression in the two groups, we generated an arbitrary measure of exposure to CsA and prednisolone. CsA levels were measured at each clinic visit (12-hour trough levels). To quantify CsA exposure, we charted all 12-hour trough levels of CsA measured over the first year and calculated the area under the curve (AUC) for this level–time graph. A similar measure for steroid exposure was produced by charting the prednisolone dose prescribed on each occasion on which the patient was seen over the first year and again calculating the AUC for this dose–time graph.
Diabetes mellitus was defined as the need for insulin or oral hypoglycemic therapy. The definition of a normal random glucose pre-transplant was less than 5.5 mmol/L, as indicated by the WHO (9). Only one patient who subsequently developed post-transplant diabetes mellitus had a pre-transplant random blood glucose >5.5 mmol/L. (The single exception had a pre-transplant random blood glucose of 5.7 mmol/L.) No patient was allowed to remain hyperglycemic in the absence of treatment for more than a month, and usually much less. Five patients were hepatitis C-positive, two of whom developed post-transplant diabetes mellitus.
Follow-up policy was the same for all patients. In the first year, no patient was seen less frequently than once every 4 weeks, and usually much more frequently, particularly early in the post-transplant period. On each occasion, glucose, lipids and renal function, as well as standard clinical and other laboratory parameters, were measured.
The diagnosis of acute rejection was based on renal transplant biopsy undertaken on account of an otherwise unexplained rise in serum creatinine. Rejection was treated in the first instance by four consecutive daily doses of methylprednisolone 500 mg intravenously.
Long-Term Efficacy and Safety Surveillance (LOTESS): In order to confirm the findings of our local study in the wider UK transplant population, we addressed the same question in a larger registry, from which we were able to gather data on a much larger number of patients, but in less detail. The Long-Term Efficacy and Safety Surveillance (LOTESS) database is a Novartis-funded project collecting data on renal allograft recipients being treated with ciclosporin microemulsion (CsA-ME). 6574 patients were recruited from 64 hospitals throughout the UK over the period January 1995 to December 1998 and followed prospectively. Data were collected by trained professional study monitors operating under good clinical practice (GCP)-compliant procedures and were comprehensively checked against the patients' original medical notes. While it is not possible to quantitate it precisely, given UK practice in the late 1990s, this undoubtedly is representative of the immunosuppressive management of the majority of UK patients, since the use of either tacrolimus or calcineurin-inhibitor-free immunosuppression was still uncommon in the UK in that era. Participating centers submitted trimonthly reports detailing adverse events, including episodes of graft dysfunction. All data were collated centrally by the Medical Information Processing & Statistics Department at Novartis UK. From this dataset, we identified adult Caucasian (N = 4262) and Indo-Asian (N = 254) allograft recipients. Ethnicity was self-reported and documented by questionnaire.
The following data were collected: age, gender, pre-operative co-morbidity (including myocardial infarction, ischemic heart disease, arterial disease, body mass index and diabetes mellitus) as well as HLA mismatch. Post-transplant outcomes included graft and patient survival, incidence of diabetes mellitus and time to onset of treatment.
The Hammersmith Hospital was a contributing center to the LOTESS study, so approximately half of the Hammersmith patients (N = 74) appeared in the LOTESS cohort. This represents less than 4% of the LOTESS population.
During the period covered by this project, the WHO definition of diabetes changed and the implementation of the new criteria will have differed among LOTESS centers. The definition of diabetes used in this dataset is according to the then current local practice. On retrospective review of that practice, the following criteria define all those who were categorized as having pre-transplant diabetes mellitus: a record in the medical notes of a personal history of diabetes mellitus, the use of oral hypoglycemic agents or insulin or an elevated random blood glucose on two occasions. The definition of the last criterion was >5.5 mmol/L in 97% of recruiting centers, and >6.0 mmol/L in the other 3%.
Eighteen patients of the 4516 patients in the LOTESS cohort were hepatitis C-positive pre-transplantation. Of them, only one developed post-transplant diabetes mellitus.
UK Transplant: The governmental body, UK Transplant (UKT), maintains a database of transplant activity in the UK, the National Transplant Database. Since January 2000, it has 96.9% complete data on the ethnic origin of organ recipients, as self-reported to referring hospitals and returned to UKT. The comparable figure for the period 1995–1999 was 95.7%. Insufficient data have been recorded to comment on pre- or post-transplantation co-morbid factors. Patient and graft survival was recorded for 4831 Caucasian and 459 Indo-Asian transplant recipients in the calendar years 1998–2003.
Skewed datasets were expressed as the median and interquartile range and analyzed using non-parametric tests. Normally distributed datasets were expressed as mean and standard deviation. Univariate analysis of the influence of ethnicity on patient co-morbidity and transplant outcomes was performed using the Chi-square test or Student's t-test, as appropriate. Multivariate analysis was performed, beginning with an exploratory phase, using a forward conditional sequential stepwise method of binary logistic regression analysis for new PTDM by entering variables that we considered clinically relevant into a computerized model (SAS software package for Windows version 8, SAS Institute Inc.). Those variables were: recipient age (years), recipient race (Caucasian or Indo-Asian), donor source (living or deceased donor), BMI (> or ≤30 kg/m2), recipient gender (female or male) and hepatitis C viral status (infected or not).
The probability of graft failure and patient death over time was analyzed by Kaplan-Meier survival plots using Prism 3.0 software. Survival differences between groups were analyzed using the log rank test. Graft survival curves were censored for graft loss due to patient death. A p-value <0.05 was considered to indicate statistical significance.
Baseline pre-transplant clinical characteristics of the Hammersmith Hospital cohort of patients were similar for Caucasians and Indo-Asians (Table 1). The mean age of the two groups was similar (p = 0.88). There was a larger proportion of men undergoing transplantation and live donation within the Caucasian group, although neither parameter was significantly different. Mean follow-up was not significantly different for the two groups. The burden of co-morbid disease pre-transplantation was largely similar, although there was a higher prevalence of pre-transplant diabetes mellitus in the Indo-Asian population (p = 0.04). There was no significant difference between the two groups in the degree of HLA mismatch.
Table 1. Baseline pre-transplant clinical characteristics of patients transplanted at the Hammersmith Hospital 1996–2000
Caucasian N = 90
Indo-Asian N = 46
Mean age in years (± SD)
Mean follow-up in years (± SD)
Deceased donor (N)
Live related donor (N)
Pre-emptive transplantation (N)
Ischemic heart disease (N)
Peripheral vascular disease (N)
Diabetes mellitus (N)
Average HLA-A mismatch (± SD)
Average HLA-B mismatch (± SD)
Average HLA-DR mismatch (± SD)
Mean total prednisolone exposure (± SD) (arbitrary units)
Mean total ciclosporin exposure (± SD) (arbitrary units)
The cohort drawn from the LOTESS registry data (Table 2) also showed this difference in pre-transplant diabetes mellitus (p = 0.001). However, as with the Hammersmith cohort, this group showed no other differences between the two groups in pre-transplant co-morbidity, age or HLA mismatch.
Table 2. Baseline pre-transplant clinical characteristics for the LOTESS database cohort 1995–1998
Caucasian (N = 4262)
Indo-Asian (N = 254)
Mean age in years (±SD)
42.6 (± 13.9)
42.3 (± 13.2)
Myocardial infarction (N)
Ischemic heart disease (N)
Peripheral vascular disease (N)
Diabetes mellitus (N)
Average HLA-A mismatch (± SD)
Average HLA-B mismatch (± SD)
Average HLA-DR mismatch (± SD)
Outcomes following transplantation
In the Hammersmith Hospital cohort, there was no significant difference between the two ethnic groups in the incidence of delayed graft function (p = 0.47), overall incidence of acute rejection in the first year (p = 0.11) or rate of steroid-resistant rejection (p = 0.09), although there was a trend toward less total and steroid-resistant rejection in the Indo-Asian group (Table 3). The median time to first rejection was significantly later in the Indo-Asian group (Indo-Asian 27 days vs. Caucasians 12 days, p = 0.001—Figure 1).
Table 3. The incidence of post-transplantation complications within the Hammersmith Hospital cohort
Caucasian N = 90
Indo-Asian N = 46
Delayed graft function (N)
Acute rejection in 1st year (N)
>1 acute rejection episodes in 1st year (N)
Mean time to 1st rejection (days) (±SD)
Steroid-resistant rejection (N)
At 5 years, there was no significant difference in patient survival or graft survival in the Hammersmith (p = 0.87 and 0.86, respectively), or LOTESS (p = 0.67 for both) cohorts or, at 3 years, in the National Transplant Database (p = 0.85 and p = 0.81, respectively) (Figure 2).
There were no significant differences between the Caucasian and Indo-Asian groups in serum creatinine at 1 and 3 years (Figure 3) (mean values ± standard deviations 1 year: Caucasian = 135 ±72.2 μmol/L vs. Indo-Asian = 121 ± 35.3 μmol/L (p = 0.16); 3 years: Caucasian = 136 ± 48.2 μmol/L vs. Indo-Asian = 136 ± 31.9 μmol/L (p = 0.83)). Similarly, there was no significant difference between the ethnic groups in the incidence of post-transplant hyperlipidemia, as reported by 3-year triglyceride and cholesterol levels (3-year mean values ± standard deviations—triglyceride: Caucasian = 1.9 ± 0.9 μmol/L vs. Indo-Asian = 2.0 ± 0.9 μmol/L (p = 0.41); cholesterol: Caucasian = 4.9 ± 0.9 μmol/L vs. Indo-Asian = 4.8 ± 1.2 μmol/L (p = 0.74)) (Figure 4), as well as by proportion of patients on lipid-lowering medication (7.1% Caucasians vs. 9.5% Indo-Asians (p = 0.67)). There was no significant difference in 1-year systolic and diastolic pressure (Figure 5) or proportion of patients off anti-hypertensive medication (15.6% Caucasians vs. 21.7% Indo-Asians (p = 0.19)).
The most striking difference between the two ethnic groups is in the incidence of new post-transplantation diabetes mellitus (PTDM). We found that PTDM was between two and three times more frequent in the Indo-Asian population. This is seen in both the Hammersmith (Indo-Asians 10.9% vs. Caucasians 3.3%, p = 0.02) and LOTESS (Indo-Asians 5.5% vs. Caucasians 1.6%, p < 0.0001) cohorts (Figure 6A and B). In the LOTESS dataset, there was no significant difference in the proportion of patients in each group who had a body mass index (BMI) ≥30 kg/m2 (p = 0.18). Data on BMI were not available for the Hammersmith cohort.
In binary logistic regression analysis of the Hammersmith cohort, only Indo-Asian ethnicity was identified as an independent risk factor for the development of new PTDM (Table 4). For the LOTESS cohort, Indo-Asian ethnicity, greater recipient age and recipient positivity for hepatitis C were all independent predictors of new PTDM, while BMI, donor source and recipient gender showed no significant relationship (Table 4). All these relationships remained true whether or not Hammersmith patients were included or excluded from the LOTESS cohort prior to analysis.
Table 4. Multivariate analysis of factors associated with development of new post-transplantation diabetes mellitus
Male (compared to female)
Living donation (compared to deceased donor source)
Indo-Asian recipient (compared to Caucasian)
Hepatitis C positivity (compared to negativity)
BMI >30 (compared to ≤30)
Not only was there more PTDM in the Indo-Asian population, but it also occurred at a significantly earlier time point (Figure 6C and D). In the Hammersmith cohort, the median onset of PTDM was 10.9 months in the Caucasian population, compared to a median of 5.5 months in the Indo-Asian population (p < 0.001).
The data presented in this paper indicate very good patient and graft survival in Indo-Asian renal transplant recipients, with results comparable to those achieved in Caucasians. The numbers of patients studied allow us to have a much higher level of confidence than before about graft outcome in this population. Our data contrast with those in the study of Jeffrey et al. (6) which probably reflects the fact that the patients described in that report were transplanted several years before those reported in the current paper and clinical practice has improved over that period. Our data confirm the findings of Loucaidou et al. (7) and Higgins et al. (8) and, because of the greater numbers involved in the current study, allow us to allay some of the anxieties raised by the late (but non-significant) trend toward deteriorating outcomes among Indo-Asians in the former study. It is important to remember that there is significant heterogeneity within the Indo-Asian population (10,11), which may explain different results in studies performed in different localities. However, by incorporating data from the LOTESS and National Transplant Databases, the current study suggests that the heterogeneity in UK Indo-Asians might not be an important factor in this matter.
This study extends previous work by considering the differential impact of transplantation on other factors that commonly complicate renal transplantation (12,13). It was gratifying to see no difference in hypertension, hypercholesterolemia or hypertriglyceridemia between the two ethnic groups and not surprising to see a major difference in the incidence of post-transplant diabetes mellitus. The magnitude of this difference is, however, very striking and clearly represents a significant challenge.
One of the possible explanations for the differences between the studies of Jeffrey et al. and Loucaidou et al. is that the former recruited in the cyclosporin era whereas the latter treated all patients with tacrolimus. However, we believe that this is not likely to be the explanation since, in our study, all patients were treated with cyclosporin. Given the increased diabetogenic potential of tacrolimus (14), one could argue that cyclosporin should be the preferred calcineurin-inhibitor in the Indo-Asian transplant population. However, even on cyclosporin, the incidence of PTDM is high and an alternative argument would be that tacrolimus might facilitate steroid withdrawal, which could potentially reduce the risk of glucose intolerance. We do not yet know which of these two approaches would have quantitatively the greater effect on decreasing glucose intolerance in this population.
These detailed observations on the Hammersmith cohort of patients are retrospective and benefit from being presented alongside parallel information from the much larger LOTESS cohort and National Transplant Database. Although the LOTESS data were collected prospectively, there is significantly less detail available and there is much more heterogeneity, for example in the way these patients were treated when compared to the Hammersmith cohort. The same could be said of the National Transplant Database, which undoubtedly represents the most comprehensive review of UK renal transplant experience available, again collected prospectively. The National Transplant Database has the additional benefit over the LOTESS data that it is not restricted to patients receiving cyclosporin, although it should be noted that cyclosporin was the dominant immunosuppressive agent in use in the UK at the time. Unfortunately, in the era reported in this paper, no reliable data on co-morbidities were available for the National Transplant Database. Both the LOTESS data and National Transplant Database are descriptive and were not trials with extensive inclusion and exclusion criteria. However, the multicenter nature of data acquisition in both the LOTESS and National Transplant Databases will decrease the impact of variation in uncontrolled variables and has the great strength of allowing us to assert that our local Hammersmith observations are in line with these broad surveys of UK experience.
So, while there are clearly concerns when presenting different datasets collected in different fashions with different limitations, their strengths were complementary and analysis of all three data sets came to the same conclusions on the similarity of patient and graft survival in Caucasian and Indo-Asian renal transplant recipients. Similarly, the Hammersmith and LOTESS cohorts show the same increased incidence of PTDM in the Indo-Asian community. Accordingly, we believe the reliability of the message is increased by virtue of the fact that these somewhat different data sets produce a common message.
In conclusion, it is clear that Indo-Asian patients, who suffer from such a high prevalence of end-stage renal disease, do as well as Caucasians following renal transplantation, with respect to patient and graft survival and graft function. Post-transplantation lipid levels and blood pressures are comparable, but the Indo-Asian group has a particularly high incidence of post-transplantation diabetes mellitus. This should be a consideration in tailoring immunosuppression in this group.