Key words : Implantable Doppler probe, Kidney graft loss, Kidney transplant surgery, Risk factors

Introduction

Chronic kidney disease is a progressive disorder that affects 1 in 10 individuals worldwide.¹ Around 30?000 people in the United Kingdom rely on dialysis to stay alive.2 Apart from lung and pancreas cancers, most cancers have a better prognosis than hemodialysis.³ A systematic review of 9 studies across Europe concluded that 50% of patients with end-stage renal disease die within 5 years from worsening of symptoms and complications from hemodialysis.⁴

A successful kidney transplant significantly improves long-term survival for patients with end-stage renal disease.5 Kidney transplant can enhance generalized health, mental well-being, and quality of life by enabling recipients to resume physical and social activities.5

There are insufficient numbers of transplant kidneys available for donation, while the demand has increased over the years.6 The main reason is a globally increasing prevalence of chronic kidney disease because of the rising population experiencing diabetes mellitus and hypertension.1 The COVID-19 pandemic also took a significant toll on the economic and functional capacity of health care systems across the world.7 Consequently, the past 2 years have witnessed an unprecedented reduction in transplant activity.⁷

Early graft loss (EGL) is defined as kidney graft loss within the first 3 months postoperatively.⁸ Early graft loss due to vascular complications constitutes 3.5% to 5.7% of total kidney transplants.⁹ Individually, the incidence of arterial complications is reported as 0.2% to 7.5%, whereas the incidence of venous complications is reported as 0.1% to 8.2%.⁹

To ensure better utilization of the limited pool of donated organs, it is paramount to reduce EGL.¹⁰ Two strategies to improve kidney graft outcomes have been advocated. First, the risk factors leading to EGL should be identified early in kidney transplant recipients.¹¹ Higher optimization, precautionary measures, and extensive monitoring should be undertaken in patients at high risk to reduce complications.¹¹ Second, monitoring technologies that assist in the early detection of vascular complications should be explored, as only prompt intervention can rescue a compromised graft.¹²

An implantable Doppler (ID) probe is a blood flow monitoring device.13 The ID probe is applied to the vessels intraoperatively (Figure 1). A connecting wire links the probe to an external monitor (Figure 2). The probe uses flow-sensing technology and converts the kinetic energy of the blood flow into audible Doppler signals. The continuous signals indicate patency of the vascular anastomosis, whereas cessation of signals imply occlusion.14 Implantable Doppler probes have been used successfully for surveillance of microvascular anastomoses in cardiovascular, liver transplant, plastic, and breast reconstructive surgeries.15 Likewise, an ID probe may assist in the early identification of vascular complications critical to reducing kidney graft loss.

This study aimed to assess risk factors and preventable measures for EGL in kidney transplant recipients from the Southwest of UK. The objective was to identify whether the recipients’ demographic characteristics and comorbidities or the use of an implantable blood flow monitoring device had a statistically significant association with EGL.

Materials and Methods

In this retrospective observational study, we extracted data of 472 recipients of kidney transplants performed between January 2015 to March 2023 from the prospectively maintained patient database at the Southwest Transplant Centre (Plymouth, UK). The demographic characteristics, comorbidities, and use of a postoperative implantable blood flow monitoring device were analyzed individually against EGL in all kidney transplant recipients (Table 1).

We conducted bivariate analysis using chi-square tests with a contingency table to identify the recipient risk factors that had a statistically significant association with EGL. Similarly, the use of a blood flow monitoring device in kidney transplant recipients was analyzed against EGL to assess whether there was a statistically significant association.

We performed data analyses using descriptive and inferential statistics using IBM SPSS version 25.0.16 Continuous data (eg, age, body mass index [BMI]) were expressed as means and SD. Categorical variables (eg, sex, type of graft, dialysis modality) were expressed as frequency (percentages). Inferential statistics comprised the chi-square test with a contingency table. We used chi-square tests to compare the variables in the research question as all variables were categorical. Using a resultant significance level (alpha) of 0.05, we concluded that an association between the categorical variables was statistically significant if the resultant significance level (alpha) was ?.05.

We obtained ethical approval (No. 21/SUR/626) from the Research and Development Department of the University Hospitals Plymouth NHS Trust, where data compilation and analyses were undertaken.

Results

Descriptive statistics
Our cohort included 472 patients who underwent kidney transplant in the Southwest region of the UK from 2015 to 2023 (307 male patients [65%] and 165 female patients [35%]). The mean age of the patients was 52.62 ± 15.37 years, and mean BMI (in kilograms divided by height in meters squared) was 27.53 ± 4.99. The average wait time for a patient to have a suitable kidney transplant was 626 days. There were 12 cases (2.5%) of EGL due to vascular complications.

The most common causes of primary renal disease recorded were immunoglobulin A nephropathy (9.2%), autosomal dominant polycystic kidney disease (7.9%), diabetic nephropathy (6.8%), and focal segmental glomerulosclerosis (5.8%). Among the cohort, 57% of patients were on hemodialysis, 18% were on peritoneal dialysis, and 25% had preemptive transplant procedures (2% with a failing transplant). Of total transplants, 43% of kidneys were from donors after brain death, 28% were from donors after circulatory death, and 29% were from living donors.

Inferential statistics
A recipient’s smoking habit, the number of prior kidney transplants, and a history of thromboem-bolism showed a significant association with EGL (Table 2).

Other variables showed no significant association with EGL, including recipient age >60 years, type of allograft, number of graft arteries, recipient BMI >30, dialysis modality, cardiovascular disease in recipient, peripheral vascular disease in recipient, hypertension in recipient, diabetes mellitus in recipient, recipient’s bladder outflow obstructive pathology, donor age >60 years, donor BMI >30, diabetes mellitus in donor, hypertension in donor, donor smoking, peripheral vascular disease in donor, and cardiovascular disease in donor (Table 3).

Likewise, the use of an implantable blood flow monitoring device in kidney transplant recipients was not significantly associated with EGL.

Discussion

There is a growing disparity between the kidney graft supply and demand. The criteria for organ donation have expanded, and recipients considered high risk are accepted for transplantation. Consequently, efforts aimed at optimizing graft utilization have also increased. A vital strategy to improve graft outcomes is to identify and safeguard against risk factors for graft loss. In our study, risk factor analysis identified recipient smoking, the number of prior kidney transplants, and history of thromboembolism as factors that influenced the risk of EGL in our population of kidney transplant recipients in the Southwest of UK.

Studies in the literature support these findings. In a systemic review from Foroutan and colleagues of 35 primary studies, the authors identified recipient smoking and history of thromboembolism as risk factors associated with 1-year death-censored kidney graft loss.17 Matas and colleagues conducted a single-center risk factor analysis involving 1467 primary kidney transplants and identified history of thromboembolism and technical surgical compli-cations as risk factors for thrombosis-related graft loss.¹¹

Although no other independent risk factor for thrombosis-related graft loss was identified in our study, other studies have implied a risk of graft loss from other factors. In a literature review, Keller and colleagues suggested that recipient factors like age <5 or >50 years, peritoneal dialysis, diabetes mellitus, atherosclerosis, hemodynamic instability, nonuse of aspirin, and delayed graft function increased the risk of graft loss.⁹ Moreover, the cumulative effects of individual unrelated factors increased the overall risk of complications in a kidney transplant recipient.¹⁸

With the findings mentioned above, strategies to mitigate risk factors like cessation of smoking, aggressive medical control of the comorbidities, intraoperative well-monitored fluid management, low-molecular-weight heparin, and postoperative use of aspirin are warranted.¹⁹ Thorough attention should also be placed on technical details during kidney implantation to prevent complications like intimal dissection and vessel kinking.¹⁹

A thrombosed kidney graft can only be salvaged if diagnosed in time.²⁰ Presently, kidney transplant recipients are monitored postoperatively by clinical assessment and color duplex ultrasonography.²¹ There is a potential requirement for a postoperative blood flow monitoring device in clinical practice.²² Implantable Doppler probes have been used intermittently as blood flow monitoring devices in the postoperative graft surveillance of kidney transplant recipients at our center.²³ The bivariate analysis conducted in this study allowed us to investigate a possible association between the use of the monitoring device and EGL. The results suggested that the use of ID probe monitoring in our cohort of kidney transplant recipients was not significantly associated with EGL. This finding is not in line with earlier studies that describe ID probes as useful monitoring adjuncts in liver, plastic, and breast reconstructive surgeries.^24-26 This reflects clinical equipoise, warranting further controlled studies to investigate the potential role for a monitoring device.²⁷

A retrospective, observational study design was selected to recruit all patients who had kidney transplants during the past 6 years at our center. This reduced confounding factors like selection bias and effects of attrition, which have been observed in prospective studies.²⁸ The chi-square test was used to investigate any significant association between the variables and EGL. A study limitation is the inability to account for the effects of potential confounders (ie, other covariables) or provide strength of association.²⁹ Another drawback of the chi-square test was that the expected counts in each category must not be small to ensure the accuracy of the P value and validity of results.³⁰ A substantial effect size (ie, EGL) to study may be acquired by performing an analysis in a large sample size of kidney transplant recipients.

This preliminary study allowed an opportunity to explore the risk factors in a kidney transplant population from the Southwest of UK. The findings in this sample population are potentially transferable to the general population in the NHS. A prospective larger sample size study with a multivariate logistic regression model is planned to further elaborate on the results and account for the limitations encountered in our present study.

Conclusions

Meticulous attention given to controlling risk factors before kidney transplant reduces graft loss. Surveillance by clinical assessment and serial radiological monitoring can be offered to patients at high risk and with nonmodifiable risk factors. Further controlled studies are warranted to evaluate an implantable blood flow monitoring device in clinical practice.

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