The epidemiology of early deep vein thrombosis in kidney transplant recipients
==============================================================================

* Wendi Qu
* Michelle Minkovich
* Ioana Clotea
* Olusegun Famure
* Yanhong Li
* Jason Y. Lee
* Markus Selzner
* S. Joseph Kim
* Anand Ghanekar

## Abstract

**Background:** Because kidney transplant recipients may be at increased risk for deep vein thrombosis (DVT) following transplantation, we investigated the incidence, risk factors, treatments and outcomes of early DVT among kidney transplant recipients.

**Methods:** An observational, single-centre cohort study was conducted among adult kidney transplant recipients from Jan. 1, 2005, to Dec. 31, 2016 with 1-year followup. Time to DVT was assessed using the Kaplan–Meier method. Cox proportional hazards and linear regression models were used to analyze risk factors for and outcomes of DVT.

**Results:** The cumulative incidence of DVT was 4.25% at 3 months after transplant. In multivariable analysis, the use of depleting induction agents (hazard ratio [HR] 2.13, 95% confidence interval [CI] 1.05–4.35]), white recipient race (HR 1.84. 95% CI 1.08–3.12), the use of kidneys from expanded criteria donors (HR 2.13, 95% CI 1.05–4.32) and lower recipient body mass index (HR 0.95, 95% CI 0.91–1.00) increased the risk for early DVT. Peritransplant DVT prophylaxis was not associated with early DVT. Early DVT was not associated with reduced graft function, death, graft failure or first hospital readmission.

**Conclusion:** Risk factors for early DVT in our cohort of kidney transplant recipients included white recipient race, use of depleting agents, lower recipient body mass index and use of expanded criteria donors. As practice patterns of donor and recipient selection in kidney transplantation evolve, the results of this study may aid in perioperative risk assessments and decision-making about the use of DVT prophylaxis.

Kidney transplantation is the treatment of choice for end-stage renal disease, offering recipients improved survival and quality of life compared with dialysis. However, kidney transplant recipients (KTRs) are 7 to 8 times more likely to develop venous thromboembolism (VTE) than the general population, with the highest risk in the early post-transplant period.1,2 Overall, the incidence of deep vein thrombosis (DVT) among KTRs ranges from 4.6% to 12.5%,3–5 with most DVT events occurring within 3 months of transplantation.2,4,5 VTE has been reported to have negative effects on graft function,6 graft survival2,7 and patient survival2,8 in KTRs.

Risk factors for developing VTE include major surgery lasting more than 45 minutes, prior VTE, restricted mobility, age older than 40 years9 and race.8,10–15 Other risk factors reported include autosomal dominant polycystic kidney disease (ADPKD),16 advanced chronic kidney disease8 and cytomegalovirus infection.17 To reduce the risk of VTE in KTRs, some have recommended routine perioperative mechanical prophylaxis such as compression stockings or prophylactic anticoagulation, or both.4,18

In recent years, practice patterns in kidney transplantation have changed, with the increasing use of higher risk kidney grafts from expanded criteria donors (ECDs).19 Furthermore, transplantation is increasingly being offered to recipients at higher risk in terms of age, comorbidities and body mass index (BMI).

In this context, we undertook this study to investigate the epidemiology of VTE in the modern era by studying a large and diverse cohort of KTRs at a high-volume North American centre.

## Methods

### Study population and design

An observational single-centre cohort study was conducted among adult KTRs from Jan. 1, 2005, to Dec. 31, 2016, with a minimum follow-up of 1 year. Exclusion criteria were a prior nonkidney transplant, simultaneous multiorgan transplant, transplants outside our centre and no immunosuppressive induction therapy after transplantation. This study received approval from the Research Ethics Board of the University Health Network.

### Data sources

DVT was defined as the partial or full occlusion of a vein in the deep venous system owing to a thrombus. Graft thromboses were excluded from this definition. Early DVT was defined as occurring within 3 months of transplant. Early DVT events were diagnosed by radiology, and data were collected through manual extraction from our centre’s Organ Transplant Tracking Record by examining ultrasound diagnostic reports and progress notes. Variables collected were the date and anatomic location of early DVT events, treatments after the event and outcomes. Baseline characteristics, confounders and graft outcome data were obtained from the Comprehensive Renal Transplant Research Information System.20 Data on DVT prophylaxis, defined as at least 1 dose of subcutaneous unfractionated heparin 5000 units administered between 24 hours before transplant and 48 hours after transplant, were collected from medication records in our centre’s electronic patient record. Uncertain cases were adjudicated by clinical experts.

### Risk factors and outcomes analysis

The risk factors for early DVT analyzed included recipient age at transplant, recipient race, recipient BMI, recipient history of cardiovascular disease (combined recipient history of coronary artery disease, peripheral vascular disease, congestive heart failure and stroke), years on dialysis before transplant, donor type, use of DVT prophylaxis, type of induction agent and transplant era.

DVT was also examined as an exposure variable in relation to clinical outcomes after transplant. Follow-up began 3 months after transplant and lasted for 1 year. Patients with primary graft nonfunction, graft failure, death or loss to follow-up within 3 months of transplant were excluded. Outcome variables were categorized into short-term and long-term outcomes. Short-term outcomes consisted of first hospital readmission after transplant, DVT and pulmonary embolus (PE). First hospital readmission was defined as the first overnight hospital stay after initial discharge after transplantation. DVT as an outcome had to present in a different anatomic location than the initial DVT event and had to be on or after the first DVT diagnosis date. PE was diagnosed by radiology and data were collected from patient medical records. The first early DVT diagnosis date was the origin for the analysis of short-term outcomes to ensure complete data capture. Short-term outcomes were evaluated up to 1 year after transplant.

Long-term outcomes included death-censored graft failure, death with graft function, total graft failure and graft function. Death-censored graft failure quantified graft failure events before death. Death with graft function quantified death events before graft failure. Total graft failure included both graft failure and death outcomes. Graft function was defined as the estimated glomerular filtration rate (eGFR) at 6 and 12 months after transplant. Three months after transplant was the origin for analysis of long-term outcomes. Patients with primary graft nonfunction after transplant, graft failure, death or loss to follow-up within 3 months of kidney transplant were excluded from the long-term outcome analysis. Long-term outcomes were evaluated up to Dec. 31, 2017.

### Statistical analysis

The incidence of early DVT was calculated using the Kaplan–Meier product limit method. Patients were censored if they had graft loss, death or loss to follow-up within the 3-month post-transplant period. Incidence was reported as the number of events per 100 person-months. Anatomic locations and treatments of DVT events were analyzed descriptively. Risk factors for early DVT were analyzed using univariable and multivariable Cox proportional hazards regression models to calculate the hazard ratio (HR) with 95% confidence interval (CI). Cox proportional hazards models were also used to investigate outcomes of death-censored graft failure, death with graft function, total graft failure and first hospital readmission after DVT event. Cox proportional hazards models were fitted to analyze associations between DVT and post-transplant outcomes. Violations of the proportionality assumptions were checked using log(−log[S(t)]) plots and the interactions between the risk factors with time and Schoenfeld residuals (no significant departures from proportionality were detected). Kaplan–Meier curves stratified by early DVT were produced for each outcome. Linear regression was used to analyze eGFR at 6 and 12 months after transplant. Second DVT and PE events were analyzed descriptively owing to low occurrence. Missing values in the Cox proportional hazards models were imputed using multiple imputation. All statistical analyses were conducted using STATA, version 12.0.

## Results

### Study population

The total number of patients in this study was 1667 after we applied the exclusion criteria (Figure 1). Four of the excluded patients had DVT. Among the included patients, the mean recipient age at transplant was 51.4 (standard deviation [SD] 13.4) years. Sixty-one percent of the recipients were male, 61.2% were white and 46.4% had a living donor. Among those who had a deceased donor, 34.5% (308) had an ECD, while 65.5% (585) had a non-ECD. The transplant era 2005–2009 had the most recipients (37.3%). Table 1 summarizes the patients’ baseline characteristics.

![Fig. 1](http://canjsurg.ca/https://www.canjsurg.ca/content/cjs/66/2/E162/F1.medium.gif)

[Fig. 1](http://canjsurg.ca/content/66/2/E162/F1)

Fig. 1 
Study population flow diagram.

View this table:
[Table 1](http://canjsurg.ca/content/66/2/E162/T1)

Table 1 
Baseline characteristics of recipients who experienced early deep vein thrombosis and their donors*

### Incidence of early DVT

During the 1-year follow-up, a total of 94 patients were diagnosed with DVT. Of those, 71 patients developed DVT within 3 months of kidney transplantation; the incidence was 4.2% and the incidence rate was 1.50 (95% CI 1.19–1.89) per 100 person-months (Figure 2). Most cases occurred in the lower limbs (28.4%), neck and chest (28.4%) and upper limbs (24.3%) (Table 2).

![Fig. 2](http://canjsurg.ca/https://www.canjsurg.ca/content/cjs/66/2/E162/F2.medium.gif)

[Fig. 2](http://canjsurg.ca/content/66/2/E162/F2)

Fig. 2 
Kaplan–Meier curve for early deep vein thrombosis (DVT) after kidney transplant.

View this table:
[Table 2](http://canjsurg.ca/content/66/2/E162/T2)

Table 2 
Location of first deep vein thrombotic events within 3 months after transplant

### Potential risk factors for early DVT

Univariable analysis showed that older recipient age at transplant (HR 1.02, 95% CI 1.00–1.04]), longer time on dialysis (HR 1.09, 95% CI 1.02–1.15]), deceased ECDs versus living donors (HR 2.70, 95% CI 1.46–4.97), deceased non-ECDs versus living donors (HR 2.00, 95% CI 1.13–3.52) and induction type (depleting agent v. non-depleting agent) (HR 2.33, 95% CI 1.15–4.76) were significant risk factors for DVT. Figure 3 shows the cumulative probabilities of early DVT according to select risk factors. In the multivariable Cox model, only deceased ECDs (HR 2.13, 95% CI 1.05–4.32) and induction type (depleting agent v. non-depleting agent) (HR 2.13, 95% CI 1.05–4.35) remained significant risk factors. In addition, some variables that were not significant in the univariable analysis were found to be significant in the multivariable analysis, including white recipient race (HR 1.84, 95% CI 1.08–3.12) and recipient BMI (HR 0.95, 95% CI 0.91–1.00). Recipient history of vascular disease and administration of DVT prophylaxis were not found to be significant in either univariable (Appendix 1, Supplementary Table 1, available at [www.canjsurg.ca/lookup/doi/10.1503/cjs.021821/tab-related-content](http://www.canjsurg.ca/lookup/doi/10.1503/cjs.021821/tab-related-content)) or multivariable analysis (Table 3).

![Fig. 3](http://canjsurg.ca/https://www.canjsurg.ca/content/cjs/66/2/E162/F3.medium.gif)

[Fig. 3](http://canjsurg.ca/content/66/2/E162/F3)

Fig. 3 
Cumulative probability of early deep vein thrombosis (DVT) by (A) recipient race (white v. non-white), (B) recipient body mass index (BMI), (C) induction type and (D) donor type. ECD = expanded criteria donor.

View this table:
[Table 3](http://canjsurg.ca/content/66/2/E162/T3)

Table 3 
Cox model for effect of risk factors on early deep vein thrombosis

### Outcome analysis

Clinical outcomes were assessed in 1621 KTRs after the exclusion criteria were applied (Appendix 1, Supplementary Figure 1). The baseline characteristics of patients are presented in Appendix 1, Supplementary Table 2. We determined how many patients developed a second DVT or a PE event following an early initial DVT (< 3 mo after transplant) or a later initial DVT (3–12 mo after transplant). A total of 16.9% (12/71) of patients with an early DVT experienced a second episode, 11 of which were PE; while 21.7% (5/23) patients with a later DVT experienced a second event, including 3 PE events (Appendix 1, Supplementary Table 3). Owing to the low event number, there was insufficient power for a statistical comparison of these groups.

The incidence rates of clinical outcomes after transplant are shown in Appendix 1, Supplementary Table 4. No short-term or long-term outcomes were found to be significantly associated with DVT (Appendix 1, Supplementary Figures 2 and 3), although death-censored graft failure approached significance in the multivariable Cox model (Appendix 1, Supplementary Table 5).

### DVT treatments

Among the 71 patients with early DVT events, 90.1% (64/71) were medically treated. One (1.4%) was treated with surgery alone. Four (5.6%) received both medical and procedural therapies, while 2 (2.8%) did not receive any treatment before the end of the study follow-up or their DVT resolution.

## Discussion

In this single-centre cohort study, we determined that the incidence of early DVT within 3 months after transplant in KTRs was 4.2%. Receipt of an organ from a deceased ECD, white recipient race and use of a depleting induction agent were found to significantly increase the risk of early DVT in the multivariable analysis. None of the studied outcomes, including first hospital readmission after transplant and graft-related outcomes, were significantly associated with early DVT in our cohort within the 1-year follow-up time frame.

The incidence of early DVT in our study was similar to values reported in the literature, which are between 4.6% and 6.6%.4,21 In addition, a comparison between the incidence of DVT within 3 months of transplant and more than 3 months after transplant confirmed findings from previous studies, where the incidence of DVT peaked in the first 3–5 months and plateaued thereafter.2,21 For example, during the 1-year follow-up, Kim and colleagues reported that 95% (57/60) of KTRs who developed DVT received the diagnosis within 3 months of transplant.21 This is probably associated with the hypercoagulable state after kidney transplantation, which elevates the risk of thromboembolic events (TEs), particularly within 6 months of transplant.22,23

Compared with the use of non-depleting agents, the use of depleting agents in induction therapy was a significant transplant-related risk factor for early DVT in KTRs. Very few studies have examined the effect of induction therapies on developing DVT. For instance, Verhave and colleagues did not find induction therapy to be relevant to DVT, but they failed to compare KTRs who received depleting and non-depleting agents.1 As depleting agents may be associated with thrombocytopenia24 that should be protective against DVT, our findings suggest that alternate mechanisms initiated by depleting agents such as pro-inflammatory cytokine release or a greater dependence on central venous catheters for administration of these agents may contribute to the higher risk of DVT observed.

Donor- and recipient-related risk factors included deceased ECD, recipient age and race; age was significant in univariable but not multivariable analysis. Older age and receipt of an organ from a deceased donor have been found to be risk factors in other studies.2,4 A possibility is that older recipient age and use of marginal kidneys result in a more complex postoperative course,25,26 potentially including TEs such as DVT. Lower incidences of TEs have also been reported in patients who receive kidneys from living as opposed to deceased donors.27 Additionally, our study found that white KTRs were more likely to develop early DVT than non-white KTRs. This result is in line with findings of many previous studies and may be related to white people having a higher chance of carrying subclinical factor V Leiden and prothrombin G20210A mutations that promote blood clotting; such mutations are rarely seen in Asian populations.28–30

The effect of DVT chemoprophylaxis using anticoagulants was assessed as a risk factor and was not significant in preventing DVT in our study. Inconsistent results were previously reported regarding DVT prophylaxis, with more studies reaching conclusions similar to those of our study that anticoagulants failed to reduce the number of DVT events.1,18,31,32 Verhave and colleagues did not observe a decrease in DVT cases after a heparin prophylaxis protocol was implemented,1 as was the case in our study, where no decrease in DVT was seen after the standard prophylaxis protocol came into effect in 2013. Conversely, Ubhi and colleagues reported 6 TEs in a group of patients without heparin treatment and none in the heparin-treated group.33 The authors concluded that chemoprophylaxis was effective, although the results did not reach statistical significance. Most guidelines regarding DVT prophylaxis suggest that patients at a lower risk for TE should use compression stockings, and only those at moderate to high risk should be given chemoprophylaxis such as heparin.1 Our results indicate that giving chemoprophylaxis to every KTR, regardless of their risk for TE, might not be effective in preventing early DVT.

Our study revealed a mild but significant association between lower BMI and increased risk of DVT. The small number of previous studies of DVT in KTRs have not revealed BMI as a risk factor.1–3 The relationship between obesity and VTE is highly controversial in the literature, though many have observed an “obesity paradox” in patients with a variety of conditions including renal disease in which obesity confers a protective effect with respect to cardiovascular outcomes.34 As the mean BMI of KTRs continues to increase over time commensurate with the trend in the general population, it is possible that our cohort of patients, with a wide BMI range in a relatively modern era, may be beginning to reveal similar protective effects of elevated BMI on some outcomes after kidney transplantation.

In our study, neither short- nor long-term outcomes were significantly related to early DVT. This was different from some studies that have reported a higher death rate and death-censored graft loss rate in patients with DVT.2 However, Lam and colleagues studied VTE, including both DVT and PE;2 because PE has been shown repeatedly to have a much higher mortality rate than DVT, it could contribute to the higher rate of adverse outcomes reported in their study. Furthermore, the short follow-up time of 1 year substantially limited the number of possible outcomes, especially long-term ones, that might truly be caused by DVT. Similar to our study, Ahn and colleagues had 1-year follow-up for the outcomes and did not find that DVT contributed to any outcomes.4

### Limitations

Our study has a few limitations. Owing to the retrospective nature of the study, risk factors specific to DVT such as factor V Leiden and prothrombin G20210A mutations, antiphospholipid antibody syndrome and a history of prior unprovoked DVT were not recorded in the database and could not be assessed. Our database also lacked information about factors that may have contributed to upper-extremity DVT such as a history of dialysis, site of dialysis access and known central venous stenosis. We tried to compensate for this lack of information by combining different variables to obtain data on a previously reported risk factor. For example, recipient history of cardiovascular disease consisted of 4 variables (recipient history of coronary artery disease, peripheral vascular disease, congestive heart failure and stroke) in the original data set. Additionally, we excluded some risk factors found to be significant in previous studies such as African race and autosomal dominant polycystic kidney disease to save degrees of freedom to maintain a higher statistical power. To ensure that our risk factor analysis still captured the most important information, we kept risk factors that were either widely reported in the literature (e.g., recipient age and donor type), related to kidney transplantation but had been rarely studied (e.g., induction agent type) or were expected to affect DVT incidence (e.g., DVT prophylaxis). Lastly, our study included only 1 year of post-transplant follow-up for the outcome of early DVT, so we were unable to fully capture and characterize the long-term outcomes such as death-censored graft failure that might be associated with early DVT in KTRs.

## Conclusion

This large single-centre study of a cohort of KTRs demonstrated that the incidence of early DVT in our cohort was comparable to values reported in the literature. Risk factors included white race, use of a depleting agent, lower BMI and donation from ECDs. Early DVT was not clearly associated with patient or graft survival. As practice patterns of donor and recipient selection in kidney transplantation evolve, these results may aid in perioperative risk assessments and decision-making with regard to use of DVT prophylaxis.

## Footnotes

*   * These authors contributed equally to this work.

*   **Competing interests:** J. Kim was a member of a data monitoring committee for a trial of a novel transplant medication sponsored by Eledon Pharmaceuticals. No other competing interests were declared.

*   **Contributors:** O. Famure, J. Kim and A. Ghanekar conceived the study. M. Minkovich and I. Clotea acquired the data, which W. Qu, Y. Li, J. Lee and M. Selzner analyzed. W. Qu, M. Minkovich, I. Clotea and A. Ghanekar wrote the article, which O. Famure, Y. Li, J. Lee, M. Selzner and J. Kim critically revised. All authors agreed to be accountable for all aspects of the work.

*   Accepted June 13, 2022.

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY-NC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is noncommercial (i.e., research or educational use), and no modifications or adaptations are made. See: [https://creativecommons.org/licenses/by-nc-nd/4.0/](https://creativecommons.org/licenses/by-nc-nd/4.0/)

## References

1.  Verhave JC, Tagalakis V, Suissa S, et al. The risk of thromboembolic events in kidney transplant patients. Kidney Int 2014;85:1454–60.
    
    

2.  Lam NN, Garg AX, Knoll GA, et al. Venous thromboembolism and the risk of death and graft loss in kidney transplant recipients. Am J Nephrol 2017;46:343–54.
    
    

3.  Andrassy J, Zeier M, Andrassy K. Do we need screening for thrombophilia prior to kidney transplantation? Nephrol Dial Transplant 2004;19(Suppl 4):iv64–8.
    
    [CrossRef](http://canjsurg.ca/lookup/external-ref?access_num=10.1093/ndt/gfh1045&link_type=DOI) 
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=15240853&link_type=MED&atom=%2Fcjs%2F66%2F2%2FE162.atom) 

4.  Ahn S, Kim M-H, Jun K-W, et al. The incidence and risk factors for deep vein thrombosis after kidney transplantation in Korea: single-center experience. Clin Transplant 2015;29:1181–6.
    
    

5.  Moscarelli L, Zanazzi M, Bertoni E, et al. Renin angiotensin system blockade and activated vitamin D as a means of preventing deep vein thrombosis in renal transplant recipients. Clin Nephrol 2011;75:440–50.
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=21543024&link_type=MED&atom=%2Fcjs%2F66%2F2%2FE162.atom) 

6.  Khalifeh A, Reif M, Tolayamat B, et al. Iliofemoral deep venous thrombosis in kidney transplant patients can cause graft dysfunction. J Vasc Surg Cases Innov Tech 2018;5:7–11.
    
    

7.  Abualhassan N, Aljiffry M, Thalib L, et al. Post-transplant venous thromboembolic events and their effect on graft survival. Saudi J Kidney Dis Transpl 2015;26:1–5.
    
    

8.  Abbott KC, Cruess DF, Agodoa LYC, et al. Early renal insufficiency and late venous thromboembolism after renal transplantation in the United States. Am J Kidney Dis 2004;43:120–30.
    
    [CrossRef](http://canjsurg.ca/lookup/external-ref?access_num=10.1053/j.ajkd.2003.08.047&link_type=DOI) 
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=14712435&link_type=MED&atom=%2Fcjs%2F66%2F2%2FE162.atom) 
    
    [Web of Science](http://canjsurg.ca/lookup/external-ref?access_num=000187907500015&link_type=ISI) 

9.  Caprini JA. Thrombosis risk assessment as a guide to quality patient care. Dis Mon 2005;51(2–3):70–8.
    
    [CrossRef](http://canjsurg.ca/lookup/external-ref?access_num=10.1016/j.disamonth.2005.02.003&link_type=DOI) 
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=15900257&link_type=MED&atom=%2Fcjs%2F66%2F2%2FE162.atom) 

10. Langer RM, Kahan BD. Sirolimus does not increase the risk for postoperative thromboembolic events among renal transplant recipients. Transplantation 2003;76:318–23.
    
    [CrossRef](http://canjsurg.ca/lookup/external-ref?access_num=10.1097/01.TP.0000071203.62964.DA&link_type=DOI) 
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=12883185&link_type=MED&atom=%2Fcjs%2F66%2F2%2FE162.atom) 
    
    [Web of Science](http://canjsurg.ca/lookup/external-ref?access_num=000184445400008&link_type=ISI) 

11. Martinovic Z, Basic-Jukic N, Pavlovic DB, et al. Importance of platelet aggregation in patients with end-stage renal disease. Acta Clin Croat 2013;52:472–7.
    
    

12. Guirguis NG, Eicher C, Hock L, et al. Thromboembolic risk factors in patients undergoing kidney transplant: implication of abnormally short activated partial thromboplastin time. Ann Clin Lab Sci 2003;33:396–400.
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=14584752&link_type=MED&atom=%2Fcjs%2F66%2F2%2FE162.atom) 

13. Wüthrich RP, Cicvara-Muzar S, Booy C, et al. Heterozygosity for the factor V Leiden (G1691A) mutation predisposes renal transplant recipients to thrombotic complications and graft loss. Transplantation 2001;72:549–50.
    
    [CrossRef](http://canjsurg.ca/lookup/external-ref?access_num=10.1097/00007890-200108150-00037&link_type=DOI) 
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=11502996&link_type=MED&atom=%2Fcjs%2F66%2F2%2FE162.atom) 

14. Ghisdal L, Broeders N, Wissing K-M, et al. Thrombophilic factors do not predict outcomes in renal transplant recipients under prophylactic acetylsalicylic acid. Am J Transplant 2010;10:99–105.
    
    [CrossRef](http://canjsurg.ca/lookup/external-ref?access_num=10.1111/j.1600-6143.2009.02855.x&link_type=DOI) 
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=19845577&link_type=MED&atom=%2Fcjs%2F66%2F2%2FE162.atom) 
    
    [Web of Science](http://canjsurg.ca/lookup/external-ref?access_num=000272882000016&link_type=ISI) 

15. Negrini S, Durrbach A, Becquemont L. Sirolimus-related systemic thrombotic microangiopathy after renal transplantation. Therapie 2014;69:175–7.
    
    

16. Jacquet A, Pallet N, Kessler M, et al. Outcomes of renal transplantation in patients with autosomal dominant polycystic kidney disease: a nationwide longitudinal study. Transpl Int 2011;24:582–7.
    
    [CrossRef](http://canjsurg.ca/lookup/external-ref?access_num=10.1111/j.1432-2277.2011.01237.x&link_type=DOI) 
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=21352383&link_type=MED&atom=%2Fcjs%2F66%2F2%2FE162.atom) 

17. Kazory A, Ducloux D, Coaquette A, et al. Cytomegalovirus-associated venous thromboembolism in renal transplant recipients: a report of 7 cases. Transplantation 2004;77:597–9.
    
    [CrossRef](http://canjsurg.ca/lookup/external-ref?access_num=10.1097/01.TP.0000109779.36669.0D&link_type=DOI) 
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=15084941&link_type=MED&atom=%2Fcjs%2F66%2F2%2FE162.atom) 
    
    [Web of Science](http://canjsurg.ca/lookup/external-ref?access_num=000189311600022&link_type=ISI) 

18. Bakkaloglu H, Salmaslioglu A, Tunca F, et al. Is heparinization necessary in the early postoperative period of renal transplantation from cadaveric donors? Transplant Proc 2012;44:1690–3.
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=22841244&link_type=MED&atom=%2Fcjs%2F66%2F2%2FE162.atom) 

19. Janjua HS, Hains DS, Mahan JD. Kidney transplantation in the United States: economic burden and recent trends analysis. Prog Transplant 2013;23:78–83.
    
    

20. Famure O, Phan N, Kim JS. Health information management for clinical monitoring, research and quality assurance: the Comprehensive Renal Transplant Research and Information System (CoReTRIS) database. Transplant 2012;94:326.
    
    

21. Kim JI, Kim M-H, Hwang JK, et al. The incidence and clinical significance of isolated distal deep vein thrombosis in kidney transplant recipient. Transplantation 2018;102:639.
    
    

22. Allen RD, Michie CA, Murie JA, et al. Deep venous thrombosis after renal transplantation. Surg Gynecol Obstet 1987;164:137–42.
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=3544275&link_type=MED&atom=%2Fcjs%2F66%2F2%2FE162.atom) 
    
    [Web of Science](http://canjsurg.ca/lookup/external-ref?access_num=A1987F884600009&link_type=ISI) 

23. Humar A, Johnson EM, Gillingham KJ, et al. Venous thromboembolic complications after kidney and kidney-pancreas transplantation: a multivariate analysis. Transplantation 1998;65:229–34.
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=9458020&link_type=MED&atom=%2Fcjs%2F66%2F2%2FE162.atom) 
    
    [Web of Science](http://canjsurg.ca/lookup/external-ref?access_num=000071688700015&link_type=ISI) 

24. Andress L, Gupta A, Siddiqi N, et al. Rabbit anti-thymocyte globulin induction in renal transplantation: review of the literature. Transpl Res Risk Manag 2014;6:9–21.
    
    

25. Lam NN, Kim SJ, Knoll GA, et al. The risk of cardiovascular disease is not increasing over time despite aging and higher comorbidity burden of kidney transplant recipients. Transplantation 2017;101:588–96.
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fcjs%2F66%2F2%2FE162.atom) 

26. Knoll GA. Kidney transplantation in the older adult. Am J Kidney Dis 2013;61:790–7.
    
    [CrossRef](http://canjsurg.ca/lookup/external-ref?access_num=10.1053/j.ajkd.2012.08.049&link_type=DOI) 
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=23261121&link_type=MED&atom=%2Fcjs%2F66%2F2%2FE162.atom) 
    
    [Web of Science](http://canjsurg.ca/lookup/external-ref?access_num=000317276600022&link_type=ISI) 

27. Osman Y, Shokeir A, Ali-el-Dein B, et al. Vascular complications after live donor renal transplantation: study of risk factors and effects on graft and patient survival. J Urol 2003;169:859–62.
    
    [CrossRef](http://canjsurg.ca/lookup/external-ref?access_num=10.1097/01.ju.0000050225.74647.5a&link_type=DOI) 
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=12576799&link_type=MED&atom=%2Fcjs%2F66%2F2%2FE162.atom) 
    
    [Web of Science](http://canjsurg.ca/lookup/external-ref?access_num=000180916500007&link_type=ISI) 

28. Hwang J-K, Kim J-M, Lim J-H, et al. Incidence of deep vein thrombosis in the first month after kidney transplantation in Korean versus Caucasian populations. Thromb Res 2013;131:e120–2.
    
    

29. Margaglione M, Grandone E. Population genetics of venous thromboembolism: a narrative review. Thromb Haemost 2011;105: 221–31.
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=20941456&link_type=MED&atom=%2Fcjs%2F66%2F2%2FE162.atom) 

30. Jang MJ, Bang S-M, Oh D. Incidence of venous thromboembolism in Korea: from the Health Insurance Review and Assessment Service database. J Thromb Haemost 2011;9:85–91.
    
    [CrossRef](http://canjsurg.ca/lookup/external-ref?access_num=10.1111/j.1538-7836.2010.04108.x&link_type=DOI) 
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=20942850&link_type=MED&atom=%2Fcjs%2F66%2F2%2FE162.atom) 

31. Poli D, Zanazzi M, Antonucci E, et al. Renal transplant recipients are at high risk for both symptomatic and asymptomatic deep vein thrombosis. J Thromb Haemost 2006;4:988–92.
    
    [CrossRef](http://canjsurg.ca/lookup/external-ref?access_num=10.1111/j.1538-7836.2006.01917.x&link_type=DOI) 
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=16689749&link_type=MED&atom=%2Fcjs%2F66%2F2%2FE162.atom) 

32. Osman Y, Kamal M, Soliman S, et al. Necessity of routine postoperative heparinization in non-risky live-donor renal transplantation: results of a prospective randomized trial. Urology 2007;69:647–51.
    
    [CrossRef](http://canjsurg.ca/lookup/external-ref?access_num=10.1016/j.urology.2006.12.017&link_type=DOI) 
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=17445644&link_type=MED&atom=%2Fcjs%2F66%2F2%2FE162.atom) 
    
    [Web of Science](http://canjsurg.ca/lookup/external-ref?access_num=000246474800013&link_type=ISI) 

33. Ubhi CS, Lam FT, Mavor AI, et al. Subcutaneous heparin therapy for cyclosporine-immunosuppressed renal allograft recipients. Transplantation 1989;48:886–7.
    
    [CrossRef](http://canjsurg.ca/lookup/external-ref?access_num=10.1097/00007890-198911000-00038&link_type=DOI) 
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=2815265&link_type=MED&atom=%2Fcjs%2F66%2F2%2FE162.atom) 

34. Ten Cate V, Koeck T, Prochaska J, et al. A targeted proteomics investigation of the obesity paradox in venous thromboembolism. Blood Adv 2021;5:2909–18.