Article Text
Abstract
Introduction To assess time trends in incidence, clinical characteristics, complications, and hospital outcomes among patients with type 1 diabetes (T1D), with type 2 diabetes (T2D), and patients without diabetes who underwent kidney transplant (KT); to identify variables associated with in-hospital mortality (IHM); and to determine the impact of the COVID-19 pandemic.
Research design and methods We used a nationwide discharge database to select KT recipients admitted to Spanish hospitals from 2016 to 2020. We stratified patients according to diabetes status. We used multivariable logistic regression to identify the variables associated with IHM.
Results A total of 14 594 KTs were performed in Spain (T2D, 22.28%; T1D, 3.72%). The number of KTs rose between 2016 and 2019 and and decreased from 2019 to 2020 in all groups. In patients with T2D, the frequency of KT complications increased from 21.08% in 2016 to 34.17% in 2020 (p<0.001). Patients with T2D had significantly more comorbidity than patients with T1D and patients without diabetes (p<0.001). Patients with T1D experienced KT rejection significantly more frequently (8.09%) than patients with T2D (5.57%).
COVID-19 was recorded in 26 out of the 2444 KTs performed in 2020, being found in 6 of the 39 patients deceased that year (15.38%) and in 0.83% of the survivors.
The variables associated with IHM were comorbidity and complications of KT. The presence of T1D was associated with IHM (OR 2.6; 95% CI 1.36 to 5.16) when patients without diabetes were the reference category. However, T2D was not associated with a higher IHM (OR 0.86; 95% CI 0.61 to 1.2).
Conclusions The COVID-19 pandemic led to a decrease in the number of transplants. Patients with T1D have more rejection of the transplanted organ than patients with T2D. Fewer women with T2D undergo KT. The presence of T1D is a risk factor for IHM.
- Type 2 Diabetes
- Kidney Transplantation
- COVID-19
- Incidence
Data availability statement
Data may be obtained from a third party and are not publicly available.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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WHAT IS ALREADY KNOWN ON THIS TOPIC
Several studies have reported that the incidence of kidney transplant (KT) in patients with diabetes has decreased or stabilized in recent years in different regions of the world.
Data regarding survival after KT in patients with diabetes are inconsistent, with lower values reported in KT recipients with diabetes than without this condition.
WHAT THIS STUDY ADDS
We analyzed KT admitted to hospitals from 2016 to 2020.
14 594 KTs were performed, 22.28% with type 2 diabetes (T2D) and 3.72% with type 1 diabetes (T1D).
In all groups, the number of KTs rose between 2016 and 2019, decreasing to 2020.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
Patients with T1D had KT rejections more frequently than patients with T2D.
The presence of T1D is a risk factor for in-hospital mortality after KT.
Introduction
Diabetes is one of the leading causes of end-stage renal disease, which results in a high risk of cardiovascular morbidity and mortality, as well as reduced quality of life.1
Currently, kidney transplant (KT) is considered the optimal therapeutic option for patients with type 1 diabetes (T1D) and end-stage renal disease, as it has been shown to reduce mortality more than dialysis.2
The presence of type 2 diabetes (T2D) negatively affects KT rates and survival in waitlisted patients.3 Patients with T2D are elderly and are more affected by comorbidities than patients without diabetes (eg, coronary artery disease, peripheral vascular disease, and hypertension).4
Several studies have reported that the incidence of KT in patients with diabetes has decreased or stabilized in recent years in different regions of the world.5–7 However, in Spain, a population-based study found that, between 2002 and 2013, the rate of KT in patients with diabetes increased.8 Likewise, data regarding survival after KT in patients with diabetes are inconsistent, showing better or worse survival values for transplant recipients, when compared with non-diabetes groups.3 9
Even if diabetes is a major comorbid condition in patients hospitalized with COVID-19, the effect of the pandemic on the number and outcome of KT recipients with diabetes requires further investigations.10–12 A recent meta-analysis concluded that KT recipients are at higher risk of severe complications and death from COVID-19 than the general population.11 Furthermore, KT recipients with diabetes have been reported to have a higher risk of mortality from COVID-19 than those without diabetes (24% vs 13%, p=0.02).12
The objectives of our study were as follows: (1) to assess time trends in the number and hospital outcomes (in-hospital hospital mortality (IHM) and the length of hospital stay (LOHS)) of patients with T1D, T2D, and patients without diabetes who underwent KT in Spain from 2016 to 2020; (2) to compare patients with T1D, patients with T2D, and patients without diabetes according to the study variables; (3) to identify variables associated with IHM among patients with T1D, patients with T2D, and patients without diabetes and the effect of diabetes type on IHM; and (4) to compare changes in the number, characteristics, and outcomes of KT in these three study populations from 2019 to 2020 as a result of the COVID-19 pandemic.
Methods
Study design and data source
To achieve the proposed objectives, we carried out an observational, retrospective, population-based study. The study period ran from January 1, 2016 to December 31, 2020 and was based on the Spanish National Hospital Discharge Database (RAE-CMBD, Registro de Actividad de Atención Especializada-Conjunto Mínimo Básico de Datos). The RAE-CMBD collects individual patient information (eg, sex, age, admission and discharge dates), diagnosis (1–20), and procedures (0–20), as well as the discharge destination (home, voluntary discharge, social institution, deceased). Diagnosis includes those conditions present at admission or diagnosed during hospitalization. Procedures include therapeutic or diagnostic procedures conducted during admission. The RAE-CMBD uses the International Classification of Diseases, 10th Revision (ICD-10) for coding.13
Study population and study variables
The study population included patients aged ≥18 years with an ICD-10 KT code in any position of the RAE-CMBD procedure fields (see codes in online supplemental table 1).
Supplemental material
The study population was stratified according to diabetes status as T1D, T2D, or not suffering diabetes, using the corresponding ICD-10 codes in any diagnostic position (online supplemental table 1).
The Charlson Comorbidity Index (CCI) was used to assess the presence of comorbidity, excluding diabetes and chronic kidney disease, based on a methodology described elsewhere.14 15
The presence of obesity was evaluated regardless of the diagnostic position (online supplemental table 1).
The complications of KT taken into account if recorded in any diagnostic position of the RAE-CMBD were KT rejection, KT failure, KT infection, other complications, and unspecified complications of KT (online supplemental table 1). We considered patients to have experienced ‘any complication of KT’ if one or more of the previously mentioned complications appeared in the diagnostic fields. In addition, we assessed the presence of pneumonia, sepsis, COVID-19, acute myocardial infarction, congestive heart failure, peripheral vascular disease, and cerebrovascular disease (online supplemental table 1).
To identify possible infections caused by specific microorganisms, we searched the database for the following codes: Staphylococcus bacteremia, Streptococcus bacteremia, Gram-negative bacteremia, Pseudomonas aeruginosa infection, and cytomegalovirus infection (online supplemental table 1).
LOHS was defined as the number of days between admission and discharge. IHM was the proportion of deaths during the hospital admission for KT.
The RAE-CMBD does not specifically identify the cause of death. To attempt to identify possible causes of death, we described and compared the prevalence of diagnoses most likely responsible for IHM among deceased subjects versus those who survived hospitalization, across patients without diabetes and those with T1D and T2D.
Statistical analysis
We described and compared the total number and characteristics of patients who underwent KT (T1D, T2D, and without diabetes).
The results of the descriptive statistical analysis are expressed as total frequencies with percentages for categorical variables and mean with SD or median with IQR for continuous variables.
The time trend was analyzed using the Cochran-Mantel-Haenszel statistic or Cochran-Armitage test for categorical variables and a linear regression t-test or Jonckheere-Terpstra test for continuous variables.
Categorical variables were compared using the Fisher’s exact test. Continuous variables were compared using the t-test or the Mann-Whitney test, as required.
We used multivariable logistic regression to identify the variables associated with IHM among patients who underwent KT according to diabetes status. Models were constructed including sex, age, year, comorbidities, and obesity as covariates. The results for these models are shown with the OR and 95% CI.
We used Stata V.14 to perform the statistical analysis (Stata, College Station, Texas, USA). Statistical significance was set at p<0.05 (two tailed).
Results
A total of 14 594 KTs were performed in Spain between 2016 and 2020. Of these, 3252 (22.28%) had a T2D code and 544 (3.72%) had a T1D code.
Time trends in the number and characteristics of KT recipients according to diabetes status
As can be seen in table 1, the number of KTs in patients with T1D increased between 2016 (102) and 2019 (126), with a marked decrease in the year 2020 (98). Over time, the frequency of KT in these patients increased in the 45–64 years age group (p=0.013), although the mean age remained stable. The frequency of obesity also increased significantly over time (1.96% in 2016 vs 8.16% in 2020; p=0.033).
In patients with T2D, the number of KTs rose between 2016 (536) and 2019 (749) and fell in 2020 (600). The mean age increased significantly between 2016 (62.41 years) and 2020 (64.12 years) (table 1). In 2016, 23.51% of patients with T2D who received a KT were women, increasing to 28.04% by the year 2019 and decreasing to 21.67% in the year 2020. The proportion of patients with CCI=1 increased significantly from 2016 to 2020 (20.71% in 2016 vs 29.67% in 2020; p=0.004).
In patients without diabetes, the number of KTs rose between 2016 and 2019 (2154 vs 2366), before decreasing sharply in 2020 (1746). From 2016 to 2020, the mean age increased significantly (53.47 vs 54.45; p=0.010), as did the presence of obesity (5.52% vs 8.42%; p=0.002) (table 1).
Time trends in the prevalence of complications and hospital outcomes among KT recipients according to diabetes status
The proportion of patients with T1D who experienced any complication of the KT increased, although not significantly, from 13.73% in 2016 to 26.53% in 2020 (p=0.162). KT rejection and transplant failure were the most frequently recorded complications (table 2) and remained unchanged over time.
Gram-negative bacteremia was recorded in 10.48–17.35% of patients, and P. aeruginosa infection in 3.97–8.82%, although the time trend was not significant for either of the two or for any other pathogen isolated, except for Staphylococcus bacteremia, which increased significantly (1.96% in 2016 vs 11.22% in 2020; p=0.021).
No significant variations in LOHS or IHM were observed over time, even if the value of IHM in the year 2020 was the highest observed in the time series (5.1%).
Regarding patients with T2D, the percentage of those who had any complication recorded in the discharge report increased significantly, from 21.08% in 2016 to 34.17% in 2020 (p<0.001). Specifically, significant increases were recorded for rejection (3.73% in 2016 vs 7.5% in 2020; p=0.007), KT failure (4.29% in 2016 vs 12.67% in 2020; p<0.001), and other complications of KT (7.28% in 2016 vs 13.33% in 2020; p<0.001). Likewise, the presence of Gram-negative bacteremia (11.57% and 16.5%; p=0.012) and P. aeruginosa infection (3.17% vs 6.83%; p<0.001) increased significantly over time (table 2).
In patients with T2D, no significant changes in LOHS or IHM were observed over the study period (0.75% in 2016 and 2.17% in 2020; p=0.248).
Findings for kidney complications were similar in patients without diabetes and in those with T2D. However, in this subgroup, no changes over time were found for any of the pathogens analyzed. The IHM ranged from 0.85% to 1.40% (p=0.370), and the LOHS decreased from a median of 13 days in 2016 to 1 day less in 2020 (p<0.001).
The COVID-19 code was not recorded in any patient with T1D, 10 (1.67%) patients with T2D and 16 (0.92%) patients without diabetes who underwent a KT in year 2020; the prevalence did not differ significantly between groups (table 2).
Comparison of characteristics, clinical variables, and hospital outcomes between KT recipients according to diabetes status and type
Among patients who underwent KT, those with T1D were significantly younger (45.97 years) than those with T2D (63.19 years) and patients without diabetes (54.27 years), while those with T2D were significantly older than the other subgroups, as can been seen in table 3.
The proportion of women among patients with T2D (25.92%) was significantly lower than among those with T1D (38.42%) and among patients without diabetes (37.65%). Patients with T2D showed significantly more comorbidity, measured as the mean CCI, than patients with T1D and patients without diabetes (all p<0.001).
Regarding KT complications, when the presence of any complication was analyzed, we found significant differences only between patients with T2D (27.06%) and patients with T1D (22.43%). Intermediate values were recorded for patients without diabetes (25.36%).
Specifically, patients with T1D experienced significantly more KT rejection (8.09%) than patients with T2D (5.57%).
Obesity was recorded more frequently among patients with T2D (17.11%) than among patients without diabetes (6.66%) and patients with T1D (4.59%) (both p<0.001).
When infections caused by specific microorganisms were analyzed, we found that patients with T1D more frequently had Staphylococcus bacteremia than the other subgroups and that they also had significantly more frequent Streptococcus bacteremia (0.92%) than patients without diabetes (0.33%). Patients with T2D more frequently had Gram-negative bacteremia than patients without diabetes (14.39% vs 11.7%; p<0.001). However, the presence of P. aeruginosa was significantly less frequent in patients without diabetes than in the other study groups (table 3).
The median LOHS was significantly higher in patients with T1D (16 days) than in the other two study groups and in those with T2D (14 days) than in patients without diabetes (12 days) (all p<0.001).
Crude IHM was not statistically different between patients with T1D (2.02%), patients with T2D (1.69%), and patients without diabetes (1.24%), as can been seen in table 3.
Variables associated with in-hospital mortality among KT recipients according to diabetes status and type
Online supplemental table 2 displays the prevalence of diagnoses most likely responsible for IHM among deceased subjects versus those who survived hospitalization, across patients without diabetes and those with T1D and T2D. Sepsis was registered at least 20 times more frequently among subjects who died in hospital compared with survivors across the three patient groups studied (0.84% vs 36.57% in patients without diabetes; 0.94% vs 18.18% in T1D; and 1.22% vs 25.45% in T2D; all p<0.001). Similarly, pneumonia was diagnosed in 0.76% of survivors vs 16.42% of patients without diabetes who died in the hospital. For T1D, the percentages found were 1.13% vs 27.27%, and for T2D, 1.16% vs 5.45%.
Experiencing any KT complication was found in 48.51% of deceased patients without diabetes, 72.73% with T1D, and 49.09% with T2D, with prevalence among survivors of 25.07%, 21.39%, and 26.68%, respectively (all differences p<0.001). The prevalence of major adverse cardiovascular events (MACEs), including acute myocardial infarction, congestive heart failure, peripheral vascular disease, and cerebrovascular disease, was significantly lower among the survivors of the three groups studied, although the differences were of a smaller magnitude than the previously discussed pathologies.
Among the 16 patients without diabetes with a COVID-19 code, 14 survived and 2 deceased (0.13% vs 1.49%; p<0.001), and among 10 patients with T2D, 6 survived and 4 died (0.19% vs 7.27%; p<0.001). None of the patients with T1D had a code recorded for COVID-19.
As can be seen in table 4, after multivariable adjustment, for the three study groups, higher CCI and experiencing any complications of the KT were associated with IHM. The presence of pneumonia was found to be significant for those without diabetes and those with T1D. Older age and Gram-negative bacteremia were risk factors for IHM only in patients without diabetes.
In the model that included patients with either type of diabetes (T1D or T2D), the variables significantly associated with IHM were CCI, any complication of KT, and pneumonia, although the risk of dying was not associated with type of diabetes (OR for T1D 1.96; 95% CI 0.86 to 4.45, reference category T2D).
Finally, when not having diabetes was used as the reference category, analysis of the entire database revealed the presence of T1D to be associated with IHM (OR 2.6; 95% CI 1.36 to 5.16). However, T2D was not associated with higher IHM (OR 0.86; 95% CI 0.61 to 1.2).
Differences in the characteristics and outcomes of KT between pre-pandemic years and 2020
The number of transplants decreased by 26.20%, 22.22%, and 19.89% for patients without diabetes, patients with T1D, and patients with T2D, respectively.
Among patients with T1D, the only significant difference (p=0.036) between the years 2019 and 2020 was the higher frequency of Staphylococcus bacteremia in 2020 (11.22%) than in 2019 (3.97%). IHM was higher in 2020, although the difference was not significant (0.79% vs 5.1%; p=0.088).
In the population with T2D, the percentage of women decreased from 2019 to 2020 (28.04% vs 21.67%; p=0.007), and the incidence of any complications of KT increased from 28.7% to 34.17% (p=0.031), as did that of KT-associated infection (1.6% vs 3.33%; p=0.046) and the presence of P. aeruginosa (3.74% vs 6.83%; p=0.001). No differences were recorded for LOHS or IHM.
For patients without diabetes, the presence of any complication of KT rose from 27.05% in 2019 to 31.04% in 2020 (p=0.005), with no significant changes observed for the remaining variables.
Finally, if we compare the IHM for the period 2016–2019 with the year 2020, we observed that for T1D, 1.12% (5 of 446) died in the pre-pandemic years and 5.10% (5 of 98) in year 2020 (p=0.023). The corresponding figures for T2D were 1.58% (42 of 2652) vs 2.17% (13 of 600) (p=0.317) and for patients without diabetes, 1.25% (113 of 9057) vs 1.20% (21 of 1746) (p=0.87).
Discussion
The results of this nationwide retrospective study based on diabetes status of more than 14 500 KTs performed in Spain between 2016 and 2020 revealed several key findings. First, the number of transplants decreased significantly in all study groups (T2D, T1D, patients without diabetes) in 2020 compared with 2019. Second, the number of complications associated with KT increased from 2016 to 2020, mainly in patients with T2D and patients without diabetes. Third, fewer transplants were performed in women with T2D than in the group with T1D and patients without diabetes. Fourth, the presence of comorbidity and complications was associated with IHM in all three study groups. Lastly, T1D, but not T2D, was associated with significantly higher IHM than in patients without diabetes.
Several epidemiological studies report an increase in rates of hospitalization for KT in patients with diabetes over time,8 16 and our results confirm this trend up to 2019.8 16 However, since 2020, a marked decrease has been observed in patients with T1D, patients with T2D, and patients without diabetes. A 51% decrease in transplant activity has been reported in the USA and a 91% decrease in France, largely due to the reduction in KT during the COVID-19 pandemic.17 Among the main factors that could have influenced this decrease in the number of transplants during the first year of the pandemic, we can highlight the need to preserve healthcare resources for patients with COVID-19 and to avoid COVID-19-related morbidity and mortality in immunocompromised patients considered to be at increased risk of severe disease.18
Our data show that in patients with T2D and patients without diabetes, the mean age at KT increased over time. KT in the elderly is now becoming more frequent in patients older than 65 years, increasing from 7% to 22%,19–21 and there is evidence that KT is associated with better patient survival than dialysis.22 The explanations for this finding are modifications in immunosuppressive regimens and management of comorbidity, which have led to a clinical improvement in affected patients.22
As we expected, the prevalence of obesity in patients undergoing KT increased over time, mainly in patients with T1D and patients without diabetes.8 However, the presence of obesity does not correlate with IHM. In studies carried out in other countries, no association was reported between obesity prior to KT and mortality after KT.23–25 Pieloch et al26 concluded that morbid obesity was not an independent predictor of post-KT mortality. However, morbidly obese KT recipients generate greater costs and readmission rates than non-obese patients.27
After KT, transplant-derived complications such as acute rejection and delayed graft function increased significantly throughout the study period in patients with T2D and patients without diabetes. The incidence of delayed graft function after KT is higher in people with diabetes, and some authors report rates as high as 50%.28 The underlying mechanisms of delayed graft function in people with diabetes are multifactorial and include impaired microvascular perfusion, increased oxidative stress, and altered immune response.29 The trend in the incidence of acute rejection after KT in patients with T2D is unclear owing to the heterogeneity of available studies and the lack of updated data, although it is thought to be related to the chronic inflammation and immune dysregulation that commonly affect this population.30 In contrast, the prevalence of other complications of KT increased in patients with T2D and patients without diabetes, while the prevalence of unspecified complications of KT decreased, thus pointing to a change in coding practices that should be clarified in future investigations.
In patients with diabetes, a significant increase was observed in the frequency of infections, mainly Gram-negative bacteremia and P. aeruginosa infection in patients with T2D and Staphylococcus bacteremia in patients with T1D. The results can be explained by intraoperative factors, such as the use of ureteral stents and prolonged indwelling bladder catheterization, and postoperative factors, such as acute graft dysfunction and rejection, as well as excessive immunosuppression as a result of rejection episodes.31
Patients with T2D are older and are more affected by comorbid conditions than patients with T1D. However, we observed a lower presence of women with T2D who underwent KT. In a recent study based on data from the US Renal Data System, the authors found that women with kidney failure due to T2D had 27% less access to the KT waitlist (HR 0.73; 95% CI 0.72 to 0.74) and 11% lower access to deceased donor transplantation after waitlisting than men (HR 0.89; 95% CI 0.86 to 0.92).32 One possible explanation is that women tend to have a higher incidence of autoimmune diseases and complications of diabetes, thus potentially leading doctors to think they are not good candidates for KT. In addition, women may have a higher probability of rejection of the transplanted organ owing to immunological and hormonal factors.32 33
Few studies have compared complications affecting the transplant recipients according to diabetes status (T1D and T2D). We found that rejection was more likely, and hospital stay longer in patients with T1D than patients with T2D. This disparity may be due to a combination of factors, such as diabetes-related complications or more advanced kidney disease.34 Likewise, IHM is higher in patients with T1D, although not significantly so. In a study based on the 2018 US Renal Data System, Harding et al35 found that the relative risk (RR) for post-KT mortality was higher among people with T1D (HR 1.95; 95% CI 1.88 to 2.03) and people with T2D (HR 1.65; 95% CI 1.62 to 1.69) than among patients without diabetes, concluding that a greater excess risk between T1D than T2D reflects what we see in the general population with diabetes and can be explained, in part, by a longer duration of diabetes in T1D than in T2D.
We found the presence of comorbidity and any complication of KT to be risk factors for mortality in all groups of patients who underwent KT. In addition, infection markers such as Gram-negative bacteremia in patients without diabetes and pneumonia were risk factors for IHM in patients with T1D and patients without diabetes. These predictors of worse outcomes after KT have been reported elsewhere.6 36 37
Several studies have indicated that the mortality rates of patients with T1D remain higher after KT than those of patients without diabetes, constituting a considerable challenge for the healthcare system owing to the multiple comorbidities associated with this group.2 35 In a population-based study using regional administrative data, Giorda et al38 concluded that the risk of mortality increased with age, in men, in patients with cardiovascular diseases, and in patients with T1D (RR 1.84; 95% CI 1.53 to 2.20). In our study, after multivariable adjustment, we observed that the presence of T1D was significantly associated with mortality during admission for KT when compared with patients without diabetes.
Consistent with data reported elsewhere,8 we found that the presence of T2D was not a risk factor for IHM during admission for KT. However, Lim et al9 found that patients with T2D who received a transplant were at least twice as likely to die as people without diabetes, although they suggested that the magnitude of the excess risk associated with T2D depended on age: younger transplant recipients with diabetes had at least a fivefold greater risk of all-cause mortality and death with a functioning graft than age-matched patients without diabetes, while the magnitude of the increased risk was attenuated in recipients older than 55 years. A key explanation for our results is that they likely reflect improvement in pre-transplant and post-transplant management of both diabetes and vascular risk factors.39
As previously mentioned, the RAE-CMBD does not collect specific causes of death. Online supplemental table 2 reveals that sepsis and pneumonia are diagnoses coded much more frequently among deceased patients compared with survivors among patients without diabetes, as well as patients with T1D and T2D, suggesting these pathologies as possible causes of death. Other studies also indicate infections as causes of early death in KT recipients.40 41
MACE has been identified as a significant cause of perioperative mortality after KT in the USA. Goyal et al found that of the 147 431 patients undergoing KT in the USA between 2004 and 2013, 9592 (6.5%) experienced a MACE event during hospitalization, corroborating our findings that heart failure was the most common event.42 However, these results were limited because, similarly to the RAE-CMBD, the database used could not ascertain the time sequence of MACE complication development during KT hospitalization.42
The COVID-19 code was recorded in 26 out of the 2444 KTs performed in 2020, being found in 6 of the 39 patients deceased that year (15.38%) and in 0.83% of the survivors. These findings reflect the previously demonstrated association between IHM and COVID-19 in KT recipients.11 12 43 44
It is still early to assess the effect of COVID-19 or the pandemic on IHM after KT. In our investigation, no significant differences were found in the IHM between years 2019 and 2020 in any of the study groups. However, if the pre-pandemic period (2016–2019) is compared with the year 2020, a significant difference is found for T1D (1.12% vs 5.10%; p=0.023). Due to the small number of patients and the fact that only 1 pandemic year was analyzed is difficult to suggest possible explanations for this association, even more if this finding does not appear in the T2D or the population without diabetes. Future studies should confirm these results.
The strengths of our study are its use of a national population database (RAE-CMBD) over a 5-year period with a methodology that has been reported elsewhere.8 However, our study is also subject to a series of limitations.
First, even if the RAE-CMBD collects practically all hospital admissions in Spain (>95%), it is an administrative database and, as such, does not collect all the variables included in the clinical history. Therefore, we lack information about diabetes such as duration, treatments (insulin ACE inhibitors/angiotensin receptor blockers or others), laboratory results (HbA1C, diabetes mellitus proteinuria level, residual kidney functions, etc), the use of newer technologies to improve disease control, or diabetes-related events or complications prior to hospitalization for KT. Furthermore, we were unable to determine whether onset of diabetes was before or after transplant. Future research should include and analyze these clinical variables.
Second, the validity of diabetes and other clinical conditions using ICD codes in health administrative databases, compared with clinical records, has been evaluated previously in Spain and other countries, concluding that it is reliable and can be used to address important research questions.45–50 Two Spanish studies evaluated the validity of the diabetes diagnosis in the RAE-CMBD, reporting sensitivity of 55% and 63.7%, specificity of around 97% and a kappa concordance index of 0.6 and 0.7.49 50 The fact that sensitivity is not very high implies that the condition is not coded in some patients who really have diabetes (false negatives), whereas the very high specificity means that almost all patients with a diabetes code really had this disease (very few false positives).
Regarding the validity of the RAE-CMBD procedure codes to identify subjects who have received a KT, the number, clinical and sociodemographic characteristics of our sample are nearly identical to those described by the Spanish National Transplant Organization for the 2016–2020 period, confirming the reliability of our methodology.51
In Spain, as in most countries, trained health record coders enter administrative codes according to standardized protocols and quality controls are conducted periodically to warrant the reliability of data. However, due to differences with other countries, our results must be compared with caution.13
Third, previous studies have reported an association of race with outcome after KT.42 In Spain, unlike other countries, race is not included as a variable in hospital databases nor population health surveys, this is so because in our country, the percentage of white inhabitants is over 85%.13 52 53 Fourth, it was only possible to assess IHM since we did not have information on the patients once they were discharged.
In conclusion, between 2016 and 2019, the number of KTs in Spain increased in all three study groups, although the COVID-19 pandemic was responsible for a considerable decrease in the number of transplants. Organ rejection was more frequent, and hospital stay longer in patients with T1D than in patients with T2D. Fewer women with T2D underwent KT. The main risk factors for IHM after KT in the three groups of patients were comorbidity and complications. Finally, the presence of T1D, but not T2D, was more of a risk factor for IHM than for patients without diabetes.
We provide relevant information on the benefit of KT in patients with diabetes in Spain. Our data can help to improve the quality of care and the allocation of healthcare resources.
Data availability statement
Data may be obtained from a third party and are not publicly available.
Ethics statements
Patient consent for publication
Ethics approval
The RAE-CMBD is owned by the Spanish Ministry of Health (SMH) and can be accessed upon request atestMinisterio/SolicitudCMBDdocs/201CMBDdocs/201CMBDdocs/2018_Formulario_Peticion_Datos_RAE_CMBD.pdf
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Contributors Conceptualization—AL-d-A and RJ-G. Methodology—JdM-D, ML-H, JJZ-L and NC-C. Validation—DC-A and FC. Data curation—VH-B and BR-G. Formal analysis—VH-B. Funding—AL-d-A and RJ-G. Writing (original draft)—AL-d-A, ML-H and RJ-G. Writing (review and editing)—JdM-D, FC, JJZ-L, NC-C, DC-A and BR-G. All authors have read and agreed to the published version of the manuscript. The
guarantor is RJ-G.
Funding This work has been supported by Grupo de Investigación en Epidemiología de las Enfermedades Crónicas de Alta Prevalencia en España (grant/award number 970970) and FIS (Fondo de Investigaciones Sanitarias—Health Research Fund, Instituto de Salud Carlos III) and co-financed by the European Union through the Fondo Europeo de Desarrollo Regional (FEDER, 'Una manera de hacer Europa') (grant/award number PI20/00118) Madrid Government (Comunidad de Madrid-Spain) under the Multiannual Agreement with Universidad Complutense de Madrid in line with Excellence Programme for university teaching staff, in the context of the V PRICIT (Regional Programme of Research and Technological Innovation) (grant/award number N/A).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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