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Review

Diabetes, Chronic Kidney Disease, and Vascular Ulcers: Prevention Strategies and Clinical Implications

by
Stefano Mancin
1,2,†,
Alfonso Zarrella
2,†,
Fabio Petrelli
3,
Simone Cosmai
2,
Daniela Cattani
1,2,
Diego Lopane
1,2,
Sarah Scollo
2,
Sara Morales Palomares
4,*,
Marco Sguanci
5,*,
Antonella Amendola
6,
Giovanni Cangelosi
7,‡ and
Beatrice Mazzoleni
2,‡
1
IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Milan, Italy
2
Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Milan, Italy
3
School of Pharmacy, Polo Medicina Sperimentale e Sanità Pubblica “Stefania Scuri”, Via Madonna Delle Carceri 9, 62032 Camerino, Italy
4
Department of Pharmacy, Health and Nutritional Sciences (DFSSN), University of Calabria, 87036 Rende, Italy
5
A.O. Polyclinic San Martino Hospital, Largo R. Benzi 10, 16132 Genova, Italy
6
Department of Health Sciences, Università Degli Studi di Milano, 20146 Milan, Italy
7
Unit of Diabetology, Asur Marche—Area Vasta 4 Fermo, 63900 Fermo, Italy
*
Authors to whom correspondence should be addressed.
†
Stefano Mancin and Alfonso Zarrella contributed equally as first authors to the manuscript.
‡
Giovanni Cangelosi and Beatrice Mazzoleni contributed equally as last authors to the manuscript.
Diabetology 2025, 6(2), 10; https://doi.org/10.3390/diabetology6020010
Submission received: 26 November 2024 / Revised: 25 January 2025 / Accepted: 1 February 2025 / Published: 5 February 2025
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Abstract

:
Background/Aim: Chronic kidney disease (CKD), primarily caused by diabetes, predisposes patients to a high risk of systemic complications, including vascular ulcers. This study aimed to evaluate the impact of arterial vascular ulcers in patients with CKD, with particular attention to predisposing factors including diabetes and prevention strategies. Methods: A narrative literature review was conducted, adopting the Scale for the Assessment of Narrative Review Articles (SANRA), using databases such as PubMed, CINAHL, Embase, and Cochrane Library, along with grey literature sources. Results: The literature review revealed a significant association between peripheral arterial disease (PAD) and CKD, highlighting the prevalence (41.5%) and associated risk factors, such as type 1 diabetes (OR, 2.993; 95% CI: 1.477–6.065, p = 0.002), type 2 diabetes (OR, 2.498; 95% CI: 1.466–4.256, p = 0.001), and hypertension (OR, 1.781; 95% CI: 1.293–2.450, p < 0.001) in hemodialysis patients. Preventive strategies were discussed, emphasizing the automation of ankle–brachial index (ABI) measurement. Conclusions: This review identifies risk factors and preventive strategies for PAD in CKD patients, emphasizing diabetes as a key contributor. Evidence supports current diagnostic approaches and guidelines but highlights the need for larger studies. Standardized protocols and targeted training are crucial for improved management.

1. Introduction

Diabetes represents one of the most significant global health challenges, with a steadily increasing prevalence. According to the latest data, over 537 million people worldwide are estimated to be living with diabetes, a number expected to rise to 783 million by 2045 [1]. This chronic non-communicable disease is not only a leading cause of premature mortality but also a primary risk factor for numerous complications, including chronic kidney disease (CKD) [2,3]. Indeed, diabetes is the leading cause of CKD in industrialized countries, accounting for approximately 40% of new cases requiring renal replacement therapy [4].
CKD is characterized by a progressive decline in renal function, significantly impacting the quality of life and posing a high risk of mortality [5]. Globally, around 850 million people are estimated to suffer from CKD, a number that continues to grow due to aging populations and the increasing prevalence of chronic conditions such as diabetes and hypertension [6,7]. CKD complications are numerous and include mineral and bone disorders, metabolic acidosis, dyslipidemia, chronic inflammation, and a markedly elevated cardiovascular risk [8,9,10]. In this context, the nutritional status of patients with CKD is frequently compromised, with a high prevalence of malnutrition [11,12]. This condition is closely linked to the metabolic and inflammatory complications of the disease, which exacerbate vascular damage, among other issues [13,14].
One of the most severe complications arising from the triad of diabetes, CKD, and vascular damage is the development of arterial vascular ulcers [15]. These lesions, which result from critical ischemia and an insufficient oxygen supply to tissues, are a significant cause of morbidity and mortality [16,17]. Arterial vascular ulcers are associated not only with chronic pain and recurrent infections but also with complications that dramatically increase the risk of major amputations and premature death [18,19]. The concurrent presence of diabetes, CKD, and vascular ulcers forms an extremely complex clinical scenario, which is characterized by progressive health deterioration and limited responsiveness to conventional treatments [20]. In this context, a further significant problem is represented by skin tears, defined as injuries resulting from the separation of the epidermis from the dermis, which are often caused by minor trauma, friction, or shearing forces [21]. These lesions are particularly common in elderly individuals or patients with fragile skin due to conditions such as diabetes, CKD, or vascular disorders [22,23]. While skin tears may initially appear as superficial wounds with a potential for uncomplicated healing, they are highly susceptible to becoming chronic and complex wounds in the presence of vascular complications [24]. Factors such as poor circulation, ischemia, and systemic inflammation can lead to delayed healing, infection, and the development of irregular granulation tissue [25]. The progression of skin tears into more severe lesions underscores the importance of early recognition and tailored management strategies to prevent further complications and improve outcomes in affected patients (Figure 1).
The triad of diabetes, CKD, and arterial vascular ulcers represents a particularly relevant clinical challenge [26]. The prevention and early identification of these complications are essential to reducing the disease burden and improving clinical outcomes. Identifying risk factors, implementing personalized preventive strategies, and initiating timely targeted treatments can play a crucial role in mitigating health deterioration in these patients [27].
The aim of this study is to examine the magnitude of the problem posed by the development of arterial vascular ulcers in patients with diabetes and CKD, with a specific focus on predisposing factors and preventive strategies. This study seeks to provide valuable insights for defining integrated management protocols aimed at improving clinical outcomes and reducing the incidence of severe complications, including major amputations.

2. Materials and Methods

2.1. Aims and Research Questions

2.1.1. Primary Objective

To explore the problem related to the development of arterial vascular ulcers in patients with diabetes and CKD. Research Question: What is the prevalence and incidence of arterial vascular ulcers in patients with diabetes and CKD, and how do these conditions interact to contribute to the onset of vascular complications?

2.1.2. Secondary Objectives

-
To identify the predisposing factors for the development of arterial vascular ulcers in this population.
Research Question:
What are the clinical, biological, and behavioral factors that most significantly contribute to the risk of developing arterial vascular ulcers in patients with diabetes and CKD?
-
To explore preventive strategies to reduce the incidence of arterial vascular ulcers and related complications.
Research Question:
Which preventive interventions (pharmacological, behavioral, or surgical) are most effective in reducing the incidence of arterial vascular ulcers and improving clinical outcomes in patients with diabetes and CKD?
-
To evaluate the effectiveness of an integrated management protocol in improving clinical outcomes and reducing major amputations.
Research Question:
Can the adoption of an integrated management protocol for patients with diabetes and CKD reduce the incidence of major amputations and improve patients’ quality of life?

2.2. Study Design

A narrative review of the literature was conducted to provide a comprehensive and systematic overview of the current state of knowledge in the field. This approach aims to synthesize the existing research on a specific topic, focusing on key developments and shifts in understanding, while identifying emerging trends and research gaps over time. To ensure methodological rigor and clarity in the presentation of the evidence, the review follows the principles of the Scale for the Assessment of Narrative Review Articles (SANRA) (Table S1) [28].

2.3. PICO Framework

This question was formulated using the PICO framework [29], a structured and rigorous approach that ensures that the research inquiry is specific, methodical, and comprehensive. By focusing on clearly defined population, intervention, comparator, and outcomes, the PICO framework provides a robust foundation for examining the effectiveness and relevance of interventions in clinical practice. This method is particularly valuable in reviews and studies aiming to synthesize evidence to address complex clinical challenges. The PICO components for this review are outlined in Table 1.

2.4. Search Strategy

The search was conducted in electronic databases such as PubMed, CINAHL, Embase, and the Cochrane Library, as well as gray literature sources: Google Scholar, the National Institute for Health and Care Excellence (NICE), and the Agency for Healthcare Research and Quality (AHRQ). The search was conducted using EndNote 20 software [30,31] and keywords such as “prevention”, “chronic kidney disease”, and “vascular ulcers”, appropriately combined with Boolean operators such as “AND” and “OR” in search strings tailored to the specificities of the various databases (Table S2).

2.5. Inclusion and Exclusion Criteria

Following the establishment of the research question for this study, inclusion and exclusion criteria were defined to ensure the selection of relevant, high-quality sources.

2.5.1. Inclusion Criteria

Primary and secondary studies, clinical guidelines from databases, and gray literature sources were included if they were available in Italian or English and focused on the prevention of vascular ulcers in patients with CKD, published within the last 10 years. Studies were selected based on their relevance to the review’s objectives and their alignment with pre-established research standards.

2.5.2. Exclusion Criteria

Articles that did not directly align with the review’s objectives or failed to meet the predetermined research standards were excluded. Publications with incomplete data were also excluded. Additionally, pilot or preliminary studies, articles not subjected to a rigorous peer-review process, and those relying solely on unverifiable self-reported data were excluded.

2.6. Data Extraction and Synthesis

The selected studies underwent a rigorous analysis process structured in two phases. In the first phase, studies were categorized according to various criteria: author, year of publication, type of study, analyzed sample, objective, intervention, and obtained outcomes. This categorization ensured a methodical approach for synthesizing the identified literature. In the second phase, an in-depth narrative synthesis was performed. This synthesis integrated the findings, providing a comprehensive overview of the topic while capturing the nuances and complexities inherent in each individual study.

3. Results

3.1. Screening

A total of 1797 records were identified through searches conducted in electronic databases such us PubMed, CINAHL, Cochrane Library, and Embase and by utilizing grey literature databases, such as Google Scholar, the National Institute for Health and Care Excellence (NICE), and the Agency for Healthcare Research and Quality (AHRQ). Subsequently, 90 duplicates were identified and removed. Through title screening, 1352 articles were deemed irrelevant; further screening of abstracts resulted in the exclusion of an additional 304 articles, leading to a selection of 51 records for full-text evaluation. Of these, 42 articles were excluded for not meeting the predefined inclusion criteria, ultimately resulting in 9 articles included in this narrative review (Figure 2).

3.2. Characteristics of the Included Studies

The nine studies included in this review [32,33,34,35,36,37,38,39,40] span from 2012 to 2024 and cover diverse geographical locations across Europe, Asia, Australia, and the United States, reflecting the global interest in investigating PAD and its relationship with CKD. They employ a range of study designs, including observational studies, case studies, cohort studies, reviews, meta-analyses, and clinical protocols and guidelines, each addressing specific aspects of PAD research. Most studies focus on the prevalence, risk factors, and management of PAD in CKD and dialysis patients, with others emphasizing prevention strategies and the development of clinical guidelines (Table 2).

3.3. Prevalence and Risk Factors

An observational study [32] identified multiple risk factors contributing to the onset of PAD in a cohort of hemodialysis patients. Among the factors highlighted, the presence of comorbidities such as diabetes mellitus and hypertension emerged as critical variables. These clinical conditions were associated with significant vascular alterations that promote the progression of peripheral vascular disease, revealing a high prevalence of PAD within this vulnerable population. In this study, PAD prevalence was determined by observing the absence of peripheral pulses. Out of 51 patients included, 23 exhibited absent pulses, leading to an estimated PAD prevalence of 41.5% in the analyzed sample. Notably, diabetes mellitus not only heightened the risk of developing vascular disease but also increased the likelihood of lower-limb complications, such as diabetic foot, a condition associated with severe clinical outcomes, including amputation and mortality. The findings of Azucena [32] indicated that hemodialysis patients with diabetes mellitus exhibited significantly higher PAD rates compared to those without this condition, underscoring the importance of careful clinical monitoring and targeted prevention strategies. Similarly, Sinjari et al. [33] further confirmed the relationship between CKD and PAD, reporting that 28% of CKD patients displayed signs of PAD. This study employed the Ankle–Brachial Index (ABI) as a diagnostic tool to assess peripheral perfusion impairment, finding a strong correlation between advanced CKD stages and the presence of coronary artery disease. Specifically, patients in advanced CKD stages had a significantly increased risk of developing cardiovascular complications, without statistically significant differences between PAD and non-PAD group outcomes. This suggests that the pathophysiological mechanisms underlying PAD might be intrinsically linked to the severity of CKD itself. In the same study [33], CKD patients exhibited higher rates of both incident and prevalent PAD, attributed not only to traditional cardiovascular risk factors but also to renal-specific risks such as a reduced Estimated Glomerular Filtration Rate (eGFR), albuminuria, chronic inflammation, oxidative stress, endothelial dysfunction, and pro-calcific, pro-fibrotic, and pro-thrombotic states. These findings emphasized the need for a multidisciplinary approach in managing this population, including implementing PAD screening programs for hemodialysis and CKD patients to identify high-risk individuals early and initiate preventive interventions. In particular, the comprehensive cardiovascular risk assessment and proper management of modifiable risk factors, such as glycemic control and blood pressure regulation, could significantly reduce the incidence of vascular complications in this clinically fragile population. The sum of this evidence outlines a complex but essential framework to guide future clinical interventions and research aimed at improving the quality of life for patients with PAD and CKD.
Another study [34] evaluated potential PAD risk factors among participants with CKD. The study employed various laboratory measurements and statistical analyses to examine the relationship between both traditional and novel risk factors and PAD incidence. Serum myeloperoxidase was measured using a chemiluminescent microparticle immunoassay, and urinary albumin was quantified through radioimmunoassay. Diabetes was defined based on fasting glucose levels or the use of antidiabetic medications, and eGFR was calculated using serum creatinine and cystatin C levels. During a median follow-up of 6.3 years, 589 of the 3169 participants developed PAD, a significant finding highlighting an increased risk in CKD patients compared to the general population. Participants with PAD had a mean age of 59.3 years and displayed a high prevalence of traditional risk factors such as diabetes (60.4%), hypertension (75.7%), and smoking. Alongside confirming the importance of traditional factors like advanced age, smoking, and physical inactivity, the study identified biomarkers of inflammation and insulin resistance as associated with an increased PAD risk, indicating a significant contribution of non-traditional factors. The ABI was used to diagnose PAD, with 516 cases defined by an ABI below 0.9 during the follow-up. Sensitivity analyses ensured the result robustness, confirming consistent findings across varying PAD definitions. This study emphasized the importance of monitoring both traditional and non-traditional risk factors in CKD patients to prevent PAD and improve the overall clinical management of this high-risk population.
Finally, a meta-analysis [35] investigated risk factors associated with foot ulcers in patients with CKD undergoing dialysis, offering evidence-based insights for prevention and therapeutic management. This study examined a sample of 1620 patients. The results revealed that male gender (OR 1.464; 95% CI: 1.082–1.980, p = 0.013), hypertension (OR 1.781; 95% CI: 1.293–2.450, p < 0.001), PAD (OR 5.014; 95% CI: 2.514–9.998, p < 0.001), type 1 diabetes (OR 2.993; 95% CI: 1.477–6.065, p = 0.002), and type 2 diabetes (OR 2.498; 95% CI: 1.466–4.256, p = 0.001) were identified as significant risk factors for the development of foot ulcers in this population. By contrast, female sex (OR 0.683; 95% CI: 0.505–0.924, p = 0.013) emerged as a protective factor against the occurrence of ulcers. No significant association was found between age and the risk of foot ulcers, nor was smoking identified as a major risk factor. Furthermore, the duration of diabetes did not significantly influence the development of ulcers. Sensitivity analyses and evaluations of publication bias demonstrated a high level of robustness and reliability in the findings.

3.4. Prevention Strategies

Several studies have analyzed prevention strategies for vascular ulcers in patients with CKD [36,37,38,39,40,41].

3.5. Multidisciplinary Interventions

Manewell et al. [36] emphasized the significance of multidisciplinary approaches for preventing and managing PAD and related ulcers. These strategies involve the coordinated efforts of physicians, nurses, dietitians, and physical therapists to address both clinical manifestations of PAD and its underlying risk factors. Key recommendations include the active management of cardiovascular risk factors, such as diabetes, hypertension, and dyslipidemia using pharmacological interventions and lifestyle modifications like balanced diets, regular physical activity, and smoking cessation. The study also highlighted the role of advanced technologies and patient education programs in improving adherence to treatment plans. Integrating digital tools, such as apps for monitoring physical activity and diet, was deemed especially effective in engaging patients actively in their care. These measures collectively aim to reduce PAD-related complications and mortality, promoting a holistic and proactive approach to managing chronic conditions and enhancing patient quality of life.
Another study [37] highlighted the need for integrated care in managing CKD and PAD, conditions often coexisting and leading to systemic and localized complications. The clinical complexity of these patients necessitates collaboration among nephrologists, cardiologists, vascular surgeons, and wound care specialists. This synergy allows for the development of personalized, multidimensional treatment plans that address physical, psychological, and social aspects of the disease. The integration of advanced diagnostic tools like automated ABI devices with multidisciplinary management represents a promising strategy for improving outcomes in lower-limb ulcer treatments.

3.6. Advanced Diagnostic Technologies

The importance of advanced diagnostic technologies was underscored by the NICE guideline [38], which reported that automated devices for ABI measurements significantly improved the management and healing of lower-limb ulcers. ABI, a key indicator of vascular health and tissue perfusion, is calculated by comparing the blood pressure at the ankles with that at the arms. Automated devices outperform traditional manual methods, offering higher accuracy, repeatability, and ease of use. These tools enable the regular and standardized monitoring of peripheral circulation, facilitating the early detection of complications and tailoring treatment plans to individual patient needs. The accurate and timely identification of arterial insufficiency allows clinicians to intervene effectively, using structured therapies to support tissue regeneration and healing.

3.7. Integrated Protocols for Wound Care

A recent retrospective study [39] designed and implemented a three-phase protocol for preventing and treating skin ulcers in CKD patients undergoing hemodialysis. The protocol included: (1) identifying challenges specific to wound care in dialysis patients and establishing a dedicated wound care nurse role; (2) optimizing dressing materials to enhance treatment effectiveness; (3) emphasizing patient-centered care, including tools for wound monitoring and feedback on patient satisfaction. The study involved 110 dialysis patients, focusing on high-risk individuals, mostly elderly and dependent, and also including patients with diabetes mellitus. Intensive training courses were conducted for healthcare professionals, and a structured database was created to track patient conditions, wound incidence, and healing times. The protocol led to a 46% reduction in ulcer incidence and improved the care quality. Significant improvements were observed in healing times within 90 days for diabetic ulcers, vasculopathic lesions, and skin lacerations. The use of educational materials and guidelines increased patient awareness and adherence to treatments.

3.8. Public Health Measures

Vaccination against influenza has shown benefits beyond preventing respiratory infections. Hu et al. [40] revealed that influenza vaccination significantly reduced the risk of incident PAD in early-stage CKD patients. This protective effect is attributed to the vaccine’s ability to lower systemic inflammation, a common exacerbator in chronic conditions like CKD, thereby reducing vascular complications and enhancing the overall cardiovascular health. Elderly patients with diabetes and CKD who received flu vaccines exhibited a notable reduction in PAD risk within four months post-vaccination. The potential effect could be difficult to replicate in larger heterogeneous populations and with a more rigorous study model.
A graphical summary of the results is shown in Figure 3.

4. Discussion

The findings of this review highlight that the combination of diabetes, CKD, and vascular ulcers presents a complex clinical challenge with a high risk of major complications. Evidence shows a high prevalence of PAD among CKD patients, reaching up to 41.5% [32]. The coexistence of CKD and diabetes greatly increases the risk of arterial vascular ulcers, which are linked to a high incidence of vascular complications such as ischemic ulcers and major amputations. These conditions share similar pathophysiological mechanisms with diabetic arterial vascular ulcers [32]. Diabetes plays a crucial role in this clinical scenario by intensifying the effects of CKD and arterial vascular ulcers. Previous studies [41,42] indicate that diabetes significantly raises the risk of PAD due to the interaction between chronic hyperglycemia, endothelial dysfunction, and systemic inflammation. In CKD patients, diabetes accelerates PAD onset, leading to severe complications and higher mortality rates [43]. The connection between PAD and CKD is complex and multifaceted, involving shared risk factors such as hypertension, dyslipidemia, and chronic inflammation. CKD contributes to the progression of PAD through mechanisms including endothelial dysfunction, arterial calcification, and oxidative stress, which impair vascular integrity and function [44,45,46]. Additionally, uremia-related toxins in CKD patients further exacerbate vascular damage and increase the susceptibility to atherosclerotic plaque formation [47,48,49]. Reduced kidney function also leads to an imbalance in the calcium–phosphorus metabolism, promoting vascular calcification and stiffness, which are key contributors to PAD progression [50,51,52,53]. The combined effect of these factors not only accelerates the development of PAD but also complicates its management, necessitating a multidisciplinary approach for effective prevention and treatment [39,54].
Diabetic patients progress to advanced PAD stages faster than those with other chronic conditions, such as hypertension and obesity, which also carry high cardiovascular risk [55]. CKD-specific factors, such as reduced eGFR and albuminuria, further worsen the vascular damage in diabetic patients [56]. Recent studies have identified biomarkers like myeloperoxidase and insulin resistance-related markers as potential tools for identifying patients at a higher risk of cardiovascular complications. These findings open new possibilities for therapeutic development [57,58].
A significant finding from this review is the critical role of multidisciplinary preventive strategies. These approaches address not only local lesions but also underlying risk factors, such as uncontrolled glycemia, dyslipidemia, and hypertension [36,37]. The effectiveness of these strategies is supported by robust evidence demonstrating that integrated management improves clinical outcomes and reduces the risk of severe complications [39]. The involvement of specialists from various disciplines, such as nephrologists, podiatrists, and vascular and wound care specialists, is essential for optimal management, improving therapeutic adherence and reducing the risk of major complications [37,59].
Advanced diagnostic technologies, such as automated devices for ABI measurement, play a pivotal role in improving diagnostic precision and enabling timely interventions [38]. For example, adopting automated ABI technologies has been shown to reduce the time required to diagnose peripheral ischemia in diabetic patients, leading to better clinical outcomes and fewer hospitalizations [60]. In addition, integrated management protocols and advanced wound dressings have shown significant benefits in ulcer healing and in reducing the risk of complications. These interventions are particularly relevant for diabetic patients with CKD, who are highly vulnerable to severe complications [39]. Similarly, prevention programs focusing on patient and caregiver education represent another cornerstone of effective management [61]. Targeted educational programs promoting the self-monitoring of blood glucose, the adoption of healthy lifestyles, and the early recognition of lesions have been shown to significantly reduce ulcer incidence in patients with diabetes and CKD [53]. Supporting evidence from studies on complex wounds demonstrates a reduced risk of ulcer development and associated complications among patients who participated in educational initiatives [62].
Finally, this review highlights that an integrated approach combining multidisciplinary strategies, advanced technologies, standardized protocols, and educational programs represents a promising model for preventing or identifying arterial vascular ulcers early in CKD patients. These interventions not only have the potential to improve the quality of life but also reduce the incidence of major complications and cardiovascular mortality. The future of clinical management will require a balance between technological innovation and personalized interventions, with a particular focus on the prevention of cardiovascular risk factors to mitigate the public health impact of these conditions.

4.1. Limitations of the Review

This review presents several limitations that may affect the interpretation of the results, principally determined by the substantial differences in interventions proposed in the included studies that do not consent the meta-analysis resume. The limited availability of evidence, along with the lack of a long-term follow-up, diminish the capacity to assess the enduring efficacy of the proposed interventions and represent another relevant limitation. Furthermore, the heterogeneity of prevention and training strategies directed at patients and caregivers constitutes an additional obstacle that may compromise the replicability and comparability of the findings. Variables such as the inclusion or exclusion of diabetic patients and practices such as vaccination and their declared potential beneficial effect may represent potential sources of bias in the results, impacting the quality of the conclusions drawn from the analyzed studies. An additional limitation of the conducted study is the lack of clear pharmacological indications, particularly regarding the class of SGLT2 inhibitors, which could certainly represent a potential preventive alternative for these patients; specific systematic studies on this topic are recommended.

4.2. Future Perspectives for Clinical Practice

To address the highlighted limitations, future research should focus on clinical studies with a long-term follow-up to better assess the sustainable efficacy of interventions in real-world settings. It is crucial to establish more standardized protocols for patient prevention and management, particularly for those with chronic conditions like CKD, to reduce the variability in clinical approaches. Additionally, studies focusing on specific patient subgroups, such as individuals with diabetes or other chronic care, will be essential to avoid bias and ensure that the results are more applicable to diverse clinical populations. As already established in the management of diabetes and chronic diseases in general [63,64,65,66,67,68,69], incorporating advanced technologies, such as wearable devices for continuous monitoring and artificial intelligence-driven tools for early diagnosis, could offer innovative solutions to enhance the management of complications associated with CKD and lower-extremity ulcers, ultimately improving clinical outcomes and patient care.

5. Conclusions

Arterial vascular ulcers are significant complications in patients with CKD, and the identified risk factors, including cardiovascular risks and diabetes, highlight the need for careful preventive management. This emphasizes the importance of multi-disciplinary strategies that integrate educational interventions to promote healthier lifestyles, such as increasing physical activity, and leveraging technological advancements for early diagnosis, such as the measurement of ABI or other vascular imaging techniques. The study also underscores the value of a multimodal approach in managing vascular complications and the need for training specialized personnel in the care of vascular ulcers. Moving forward, future research should focus on exploring the long-term efficacy of these preventive strategies and interventions, as well as the integration of emerging technologies in clinical practice. Finally, the continuous education of healthcare professionals remains critical to ensuring up-to-date knowledge and enhancing the competencies necessary for the effective management of these patients.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/diabetology6020010/s1. Table S1: Scale for the Assessment of Narrative Review Articles (SANRA) checklist; Table S2: Search strategy.

Author Contributions

Conceptualization, S.M. and A.Z.; methodology, S.M., D.L. and B.M.; software, S.M., M.S. and G.C.; validation, S.C., S.S. and D.C.; formal analysis, S.M.; investigation, A.Z.; resources, S.M.; data curation, S.M.P.; writing—original draft preparation, A.Z. and S.M.; writing—review and editing, S.M.P., S.C., D.C., D.L., S.S., M.S., A.A., F.P. and G.C.; visualization, S.M.P., S.C., D.C., D.L., S.S., M.S. and G.C.; supervision, S.M. and G.C.; project administration, B.M., S.M. and A.Z. contributed as first author to the manuscript; G.C. and B.M. contributed as last author to the manuscript. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Conflicts of Interest

The authors declare no conflicts of interest.

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Figure 1. Risk factor correlations between diabetes and CKD.
Figure 1. Risk factor correlations between diabetes and CKD.
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Figure 2. Flow diagram of the article inclusion process.
Figure 2. Flow diagram of the article inclusion process.
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Figure 3. Graphical representation for the study conclusion.
Figure 3. Graphical representation for the study conclusion.
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Table 1. PICO framework.
Table 1. PICO framework.
PICO ElementDetails
P (Population)Patients with CKD
I (Intervention)Explore preventive strategies for arterial vascular ulcers and related complications, such as vascular ulcers.
C (Comparator)Standard care or no targeted preventive intervention for vascular complications.
O (Outcome)Prevalence of arterial vascular ulcers, identification of risk factors, reduction in incidence/severity, and improvement in patient outcomes.
Table 2. Characteristics of the included studies.
Table 2. Characteristics of the included studies.
AuthorYearCountryStudy TypeSampleObjectiveInterventionResults
Yan
et al. [35]		2024ChinaMeta-analysis1620 (CKD)Investigate risk factors for ulcers in dialysis patientsAnalysis of 1554 patients for PAD–ulcer correlationPAD is a strong risk factor for ulcers in dialysis patients (OR 5.014)
Manewell et al. [36]2023AustraliaSystematic
review		150 (CKD)Synthesize prevention and management strategies for PADReview of PAD prevention and management strategiesIdentification of most effective strategies to prevent lower-limb complications
Sinjari et al. [33]2023IraqCross-sectional study175 (CKD)Examine PAD prevalence and risk factors in CKDPhysical exams, lab tests, and ABI testsA total of 28% of advanced CKD patients had PAD; no significant differences between PAD and non-PAD groups
NICE [38]2023UKGuidelineNA (PAD)Screening for PAD in patients with leg ulcersScreening using automated ABI devicesUse of automated ABI devices improves ulcer treatment and healing
Mancin et al. [39]2023ItalyClinical protocol110 (CKD patients on dialysis)Develop a detailed protocol for managing skin ulcers in a hospital dialysis settingImplementation of a clinical protocol for skin ulcer care in dialysis patientsA 46% reduction in the incidence of skin wounds
Hu et al. [40]2021TaiwanCase-crossover
study		46782 (CKD and PAOD)Assess the effect of flu vaccination on PADAnalysis of PAD incidence post-vaccinationFlu vaccination reduces PAOD risk in early CKD patients
Chen et al. [34]2016USACohort study3169 (PAD)Examine new risk factors for PAD in patients with CKDAnalysis of cardiovascular risk factorsAssociation between new risk factors and PAD incidence in CKD patients
Garimella et al. [37]2014USANarrative reviewNA (CKD)Provide an overview of PAD epidemiology, risk factors, and treatment in CKD patientsDevelopment of a collaborative healthcare system approachDevelopment of treatment guidelines for PAD in CKD patients
Azucena G [32]2012SpainObservational study51 (Patients on hemodialysis)Determine the prevalence of PAD in dialysis patientsAnalysis of risk factors for PADVascular status evaluation across four different risk levels
Legend. PAD: Peripheral Arterial Disease; CKD: Chronic Kidney Disease; ABI: Ankle–Brachial Index; IC: Intermittent Claudication; CLI: Critical Limb Ischemia; OR: Odds Ratio; DAPT: Dual Antiplatelet Therapy; NA: Not Applicable.
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Mancin, S.; Zarrella, A.; Petrelli, F.; Cosmai, S.; Cattani, D.; Lopane, D.; Scollo, S.; Morales Palomares, S.; Sguanci, M.; Amendola, A.; et al. Diabetes, Chronic Kidney Disease, and Vascular Ulcers: Prevention Strategies and Clinical Implications. Diabetology 2025, 6, 10. https://doi.org/10.3390/diabetology6020010

AMA Style

Mancin S, Zarrella A, Petrelli F, Cosmai S, Cattani D, Lopane D, Scollo S, Morales Palomares S, Sguanci M, Amendola A, et al. Diabetes, Chronic Kidney Disease, and Vascular Ulcers: Prevention Strategies and Clinical Implications. Diabetology. 2025; 6(2):10. https://doi.org/10.3390/diabetology6020010

Chicago/Turabian Style

Mancin, Stefano, Alfonso Zarrella, Fabio Petrelli, Simone Cosmai, Daniela Cattani, Diego Lopane, Sarah Scollo, Sara Morales Palomares, Marco Sguanci, Antonella Amendola, and et al. 2025. "Diabetes, Chronic Kidney Disease, and Vascular Ulcers: Prevention Strategies and Clinical Implications" Diabetology 6, no. 2: 10. https://doi.org/10.3390/diabetology6020010

APA Style

Mancin, S., Zarrella, A., Petrelli, F., Cosmai, S., Cattani, D., Lopane, D., Scollo, S., Morales Palomares, S., Sguanci, M., Amendola, A., Cangelosi, G., & Mazzoleni, B. (2025). Diabetes, Chronic Kidney Disease, and Vascular Ulcers: Prevention Strategies and Clinical Implications. Diabetology, 6(2), 10. https://doi.org/10.3390/diabetology6020010

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