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A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Urology & Nephrology".

Deadline for manuscript submissions: 31 August 2026 | Viewed by 12306

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Special Issue Editors

Dr. Ruta Vaiciuniene

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Guest Editor

Nephrology Department, Lithuanian University of Health Sciences, Eiveniu 2, LT-50161 Kaunas, Lithuania
Interests: renal transplantation: biomarkers; survival; volemia; functional MRI

Prof. Dr. Inga Arune Bumblyte

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Guest Editor

Nephrology Department, Lithuanian University of Health Sciences, Eiveniu 2, LT-50161 Kaunas, Lithuania
Interests: cognitive disorders in CKD; prognostic factors and prevention of acute kidney injury; risk factors of CKD in primary care; biomarkers in kidney transplantation; diabetic nephropathy

Dr. Asta Stankuviene

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Guest Editor Assistant

Nephrology Department, Lithuanian University of Health Sciences, Eiveniu 2, LT-50161 Kaunas, Lithuania
Interests: glomerular diseases; aHUS; CKD; aging; survival

Special Issue Information

Dear Colleagues,

Kidney disease represents a growing global health burden, currently affecting an estimated 850 million individuals worldwide. Mortality from kidney-related disorders is projected to range between 5 million and 11 million deaths annually, positioning kidney dysfunction as the seventh leading cause of death. In 2010, approximately 2.6 million individuals underwent kidney replacement therapy, and this number is expected to more than double to 5.4 million by 2030. End-stage renal disease (ESRD) is associated with significant morbidity, premature mortality, and substantial healthcare costs while also profoundly impacting patients' quality of life.

Patients with ESRD frequently experience a wide spectrum of debilitating symptoms, including fatigue, reduced mobility, musculoskeletal pain, sleep disturbances, anxiety, sexual dysfunction, gastrointestinal distress, dyspnea, and pruritus. Beyond these physical manifestations, chronic kidney disease (CKD) imposes significant psychosocial challenges, leading to a diminished quality of life and restricted social participation.

The increasing prevalence of CKD is primarily driven by an aging population and the rising incidence of diabetes, cardiovascular disease, and hypertension—key risk factors for CKD onset and progression. Additional contributing factors include demographic shifts, the obesity epidemic, and the long-term health consequences of climate change. CKD is strongly linked to an elevated risk of cardiovascular disease, infections, mineral and bone disorders, anemia, malnutrition, cancer, and neurocognitive decline.

The management of ESRD necessitates complex treatment decisions, including dialysis (hemodialysis or peritoneal dialysis), kidney transplantation, or conservative care for patients with advanced age or severe comorbidities. While both hemodialysis (HD) and peritoneal dialysis (PD) improve survival, dialysis-related complications remain a significant concern. Studies indicate that 13.2% of patients receiving maintenance dialysis die per year, with a particularly poor prognosis in individuals over 70 years old, whose five-year survival rate remains below 40%. Kidney transplantation remains the optimal treatment for long-term survival; however, organ shortages pose a major challenge.

This Special Issue aims to highlight innovative research and advancements in the prevention and management of ESRD, dialysis and kidney transplantation, and strategies for improving both the quality of care and overall wellbeing of patients with ESRD. Authors are welcome to submit original articles, reports on novel treatment strategies and advances in decision making, clinical outcome studies, comparative studies, scoping reviews, systematic reviews, and meta-analyses.

We look forward to receiving your contributions to this Special Issue on end-stage renal disease.

Dr. Ruta Vaiciuniene
Prof. Dr. Inga Arune Bumblyte
Guest Editors

Dr. Asta Stankuviene
Guest Editor Assistant

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Keywords

kidney transplantation
hemodialysis
peritoneal dialysis
survival
management
quality of life

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10 pages, 5348 KB

Open AccessArticle

Preliminary Real-World Experience with Semaglutide in Obese Patients with Type 2 Diabetes on Chronic Hemodialysis: A Multicenter Pilot Study

by Alejandra Yugueros, Luis D’Marco, Alejandro Valero, Elena Vivó, Amparo Martínez-Mas, Manuel Calvé, Juan Carlos Alonso, Belén Vizcaíno, Mercedes González-Moya, Ana Checa-Ros, Asunción Sancho and Pablo Molina

Medicina 2026, 62(2), 386; https://doi.org/10.3390/medicina62020386 - 16 Feb 2026

Cited by 1 | Viewed by 916

Abstract

Background and Objectives: Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1RA) that has demonstrated metabolic and weight benefits in diabetic and obese patients with chronic kidney disease (CKD) who are not on dialysis; however, evidence in the hemodialysis (HD) population is scarce. Weight control and body composition optimization are particularly challenging in HD because of fluid shifts and the risk of protein-energy wasting. Materials and Methods: This prospective, multicenter, real-world, uncontrolled observational pilot study explored the short-term safety and changes in anthropometric and body-composition parameters after semaglutide initiation in obese adults with type 2 diabetes mellitus (T2DM) undergoing chronic HD. Patients were assessed at baseline and at 3 and 6 months. The primary endpoint was the change in body mass index (BMI), dry weight, and fat mass assessed by bioimpedance spectroscopy (BIS). Results: Thirteen patients were included (10 male, 77%), with a median age of 61.9 years (IQR 55–69). Semaglutide was started at 0.25 mg/week and titrated up to 1 mg/week according to tolerance. Three patients (23.1%) experienced transient nausea that was resolved over time or after dose adjustment, without discontinuation. From baseline to month +6, BMI decreased by a median of 1.5 kg/m² and dry weight by 5.0 kg, mainly driven by a median reduction in fat mass of 9 kg; lean tissue mass and serum albumin did not change significantly. Conclusions: In this small, uncontrolled exploratory study, semaglutide was generally well tolerated and was associated with short-term reductions in body weight and fat mass in obese patients with T2DM on HD. These findings are hypothesis-generating and require confirmation in larger controlled prospective studies to define safety and clinical benefit in this population. Full article

(This article belongs to the Special Issue End-Stage Kidney Disease (ESKD))

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12 pages, 946 KB

Open AccessArticle

Effect of Renin-Angiotensin System Inhibition on Residual Kidney Function in Peritoneal Dialysis

by Jing Xin Goh, Kamal Sud, Katrina Chau, Surjit Tarafdar, Elvira Dsouza, Nazim Bhimani and Ronald L. Castelino

Medicina 2026, 62(2), 282; https://doi.org/10.3390/medicina62020282 - 30 Jan 2026

Viewed by 657

Abstract

Background and Objectives: Renin-angiotensin system inhibitors (RASIs) are recommended to preserve residual kidney function (RKF) in patients on peritoneal dialysis (PD); however, evidence of benefit is inconsistent. This study evaluated the effect of RASI on RKF decline among patients undergoing PD. Materials and Methods: We conducted a retrospective cohort study among PD patients at a large metropolitan dialysis centre in Australia. RKF was assessed using residual Kt/V and urine volume from PD adequacy tests. Time zero was PD initiation. RASI exposure was modelled as a time-dependent variable to avoid immortal-time bias. Linear mixed-effects models were fitted for each outcome, including random intercepts and slopes for time (years since PD start) with unstructured covariance. Fixed effects included time, RASI(t), time × RASI(t), age, sex, baseline RKF, PD modality, PD infection episodes, loop diuretic use, and comorbidities. Results: Of 307 PD patients, 231 met the inclusion criteria; 111 (48.1%) received RASI. RASI users were younger than non-users [65 years (IQR 56–74) vs. 72 years (IQR 61–77); p = 0.014]. Residual Kt/V declined by 0.26 units/year; RASI exposure showed no significant effect on urine volume trajectory and a borderline slower Kt/V decline (interaction β = +0.038, p = 0.069). Hospitalisation and PD-related infection rates were similar between groups. Conclusions: RASI therapy was not associated with meaningful RKF preservation in PD patients in this cohort. While earlier studies suggested renoprotective effects of RASI while on PD, our findings align with recent evidence of mixed efficacy. Larger prospective trials are needed to clarify the role of RASI in maintaining RKF and improving long-term outcomes in PD. Full article

(This article belongs to the Special Issue End-Stage Kidney Disease (ESKD))

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12 pages, 670 KB

Open AccessArticle

Development of a Machine Learning-Based Predictive Model for Arteriovenous Fistula Occlusion After Surgery: A Retrospective Cohort Study from 2015 to 2025

by Jae Hoon Lee and Sang Gyu Kwak

Medicina 2025, 61(12), 2150; https://doi.org/10.3390/medicina61122150 - 2 Dec 2025

Viewed by 1258

Abstract

Background and Objectives: Arteriovenous fistula (AVF) occlusion remains a major cause of vascular access failure in hemodialysis patients. Early identification of high-risk patients may help prevent complications and improve outcomes. Materials and Methods: This retrospective cohort study included 1498 adult patients who underwent AVF creation between 2015 and 2025 at Daegu Catholic University Medical Center. Clinical, surgical, and laboratory variables were used to develop machine learning (ML) models for predicting AVF occlusion. Five algorithms—LightGBM, CatBoost, XGBoost, Random Forest, and Logistic Regression—were trained and evaluated using stratified five-fold cross-validation. Model performance was assessed using area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and calibration. SHAP (Shapley Additive Explanations) analysis was used to interpret variable importance. Results: Among the 1498 patients, 381 (25.4%) experienced AVF occlusion. LightGBM achieved the best performance (AUC = 0.887, accuracy = 0.858, specificity = 0.950), followed by CatBoost (AUC = 0.882) and XGBoost (AUC = 0.879). Calibration analysis demonstrated strong agreement between predicted and observed outcomes. SHAP analysis identified ferritin, hemoglobin, neutrophil percentage, and C-reactive protein as the most influential predictors, highlighting the role of inflammation and hematologic status in AVF failure. Conclusions: Gradient boosting-based ML models, particularly LightGBM and CatBoost, accurately predict AVF occlusion using routine clinical data. Explainable AI methods enhance interpretability, enabling early identification of high-risk patients and supporting precision vascular access management in hemodialysis care. Full article

(This article belongs to the Special Issue End-Stage Kidney Disease (ESKD))

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11 pages, 1462 KB

Open AccessArticle

Kinetics of Serum-Free Light Chain Removal by High-Cutoff Hemodialysis in Patients with Multiple Myeloma and Acute Renal Failure

by Wilma A. Veldman, Debora J. Weerman, Saskia Molog, Adry Diepenbroek, Wilfried W. H. Roeloffzen, Coen A. Stegeman and Casper F. M. Franssen

Medicina 2025, 61(11), 1977; https://doi.org/10.3390/medicina61111977 - 4 Nov 2025

Cited by 1 | Viewed by 788

Abstract

Background and objectives: Cast nephropathy is the main cause of acute renal failure in patients with multiple myeloma. There are conflicting data on whether removal of serum free light chains (sFLCs) with a high-cutoff (HCO) dialyzer has a favorable effect on the recovery of renal function. This may in part be explained by differences in the efficacy of sFLC removal by HCO dialysis and treatment responses to anti-plasma cell therapy between studies. We studied the removal of sFLCs during HCO treatment in detail in relation to treatment response. Materials and methods: Pre-dialysis serum and dialysate levels of sFLCs were simultaneously and repeatedly measured during the first two HCO treatments in 10 patients with kappa (κ)- and 5 patients with lambda (λ)-producing myeloma that presented with dialysis-dependent renal failure at our institution between 2009 and 2024. Results: The average change in sFLCs during 6 h treatments was −57 ± 13%, but it varied widely between −29% and −77%. Mean reductions in sFLCs were comparable for κ and λ (−61.4 ± 19.1% and −55 ± 16.7%, respectively; p = 0.78). The average clearance of sFLCs at 15 min after the start of HCO dialysis was 42.1 ± 8.5 and 27.4 ± 15.6 mL/min for κ and λ, respectively (p < 0.01). Clearances decreased to 27.2 ± 11.3 for κ and 13.8 ± 7.9 mL/min for λ after 6 h of HCO treatment (p = 0.042). Renal function recovered in 11 patients (73%). In three of the four patients whose renal function did not recover, sFLC levels were >5 g/L at any time beyond 2 weeks after the start of HCO treatment. Conclusions: Although the clearance of κ was higher compared to λ, reductions in sFLCs were similar for κ and λ. We speculate that this discrepancy is explained by greater adherence of λ to the HCO membrane. Patients whose renal function did not recover had less of a reduction in sFLC levels during HCO treatment, probably due to a suboptimal hematological response to anti-plasma cell therapy. Full article

(This article belongs to the Special Issue End-Stage Kidney Disease (ESKD))

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16 pages, 774 KB

Open AccessArticle

Nutritional Ultrasound in the Morphofunctional Assessment of Malnutrition in Patients Undergoing Incremental Versus Conventional Hemodialysis: A Comparative Study

by Elena Jiménez Mayor, José C. De La Flor, Avinash Chandu Nanwani, Celia Rodríguez Tudero, Estefanya García-Menéndez, Raul Elias, Hemily Chimoy, Marco Dominguez Davalos, Michael Cieza Terrones, Francisco Valga and Jesús Hernández Vaquero

Medicina 2025, 61(9), 1633; https://doi.org/10.3390/medicina61091633 - 9 Sep 2025

Cited by 2 | Viewed by 1253

Abstract

Background and Objectives: Nutritional status is essential for outcomes in hemodialysis (HD) patients. Incremental HD (iHD) may help preserve residual renal function, but its effect on nutrition and body composition is unclear. Nutritional ultrasound (NUS) offers a non-invasive way to assess muscle and fat, complementing methods like BIA. This study compared nutritional status using morphofunctional assessment in patients on iHD versus conventional HD (cHD). Material and Methods: This single-center observational cross-sectional study included 74 stable adult HD patients (>3 months). Patients were stratified into iHD (n = 13; 1–2 sessions/week) and cHD (n = 61; 3 sessions/week). Evaluations included clinical and biochemical parameters, BIA, handgrip strength, nutritional scores and NUS assessed mass muscle of anterior quadriceps rectus femoris (QRF), supramuscular fat (SMF), subcutaneous adipose tissue (SAT), and preperitoneal visceral fat (PPVF). Results: Patients on iHD exhibited a more favorable nutritional and inflammatory profile, with a lower risk of malnutrition and a reduced prevalence of protein-energy wasting (PEW) syndrome. Although BIA failed to clearly differentiate between groups, NUS identified better preservation of SMF in iHD patients (8.3 ± 2.5 vs. 6.6 ± 2 mm; p = 0.009), as well as higher preperitoneal visceral fat thickness (1.9 ± 4.9 vs. 0.6 ± 0.3 cm; p = 0.04). There was also a trend toward greater muscle thickness in the iHD group, such as the Y-axis (9.5 ± 2 vs. 8.5 ± 2.3 mm; p = 0.17) and cross-sectional area muscle of rectus femoris (CS-MARF in cm²) (2.9 ± 0.6 vs. 2.6 ± 0.8 mm; p = 0.1) of anterior QRF, although without reaching statistical significance. Conclusions: These results highlight the value of NUS as a sensitive method for assessing nutritional status in HD patients, particularly within individualized strategies such as iHD, where it may provide key complementary information not captured by conventional methods. Full article

(This article belongs to the Special Issue End-Stage Kidney Disease (ESKD))

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16 pages, 875 KB

Open AccessArticle

Association of Bioelectrical Impedance Analysis Parameters with Malnutrition in Patients Undergoing Maintenance Hemodialysis: A Cross-Sectional Study

by Minh D. Pham, Thang V. Dao, Anh T. X. Vu, Huong T. Q. Bui, Bon T. Nguyen, An T. T. Nguyen, Thuy T. T. Ta, Duc M. Cap, Toan D. Le, Phuc H. Phan, Ha N. Vu, Tuan D. Le, Toan Q. Pham, Thang V. Le, Thuc C. Luong, Thang B. Ta and Tuyen V. Duong

Medicina 2025, 61(8), 1396; https://doi.org/10.3390/medicina61081396 - 1 Aug 2025

Cited by 3 | Viewed by 1799

Abstract

Background and Objectives: Malnutrition is one of the most common complications in patients undergoing hemodialysis (HD) and is closely linked to increased morbidity and mortality. This study aimed to investigate the nutritional status of HD patients and the clinical relevance of bioelectrical impedance analysis (BIA) parameters such as the percent body fat (PBF), skeletal muscle mass index (SMI), extracellular water-to-total body water ratio (ECW/TBW), and phase angle (PhA) in assessing malnutrition in Vietnamese HD patients. Materials and Methods: This cross-sectional study was conducted among 184 patients undergoing hemodialysis in Hanoi, Vietnam. The BIA parameters were measured by the InBody S10 body composition analyzer, while malnutrition was assessed by the geriatric nutritional risk index (GNRI), with a GNRI <92 classified as a high risk of malnutrition. The independent BIA variables for predicting malnutrition and its cut-off values were explored using logistic regression models and a receiver operating characteristic (ROC) curve analysis, respectively. Results: Among the study population, 42.9% (79/184) of patients were identified as being at a high risk of malnutrition. The multivariate logistic regression analysis revealed that a higher ECW/TBW was independently associated with an increased risk of malnutrition, while the PBF, SMI, and PhA expressed significant and inverse associations with the malnutrition risk after adjusting for multiple confounders. The cut-off values for predicting the high risk of malnutrition in overall HD patients were determined to be 20.45%, 7.75 kg/m², 5.45°, and 38.03% for the PBF, the SMI, the PhA, and the ECW/TBW ratio, respectively. Conclusions: BIA parameters, including the PBF, SMI, PhA, and ECW/TBW ratio, could serve as indicators of malnutrition in general Vietnamese patients with HD. Full article

(This article belongs to the Special Issue End-Stage Kidney Disease (ESKD))

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17 pages, 1657 KB

Open AccessArticle

The Possibilities of Multiparametric Magnetic Resonance Imaging to Reflect Functional and Structural Graft Changes 1 Year After Kidney Transplantation

by Andrejus Bura, Gintare Stonciute-Balniene, Laura Velickiene, Inga Arune Bumblyte, Ruta Vaiciuniene and Antanas Jankauskas

Medicina 2025, 61(7), 1268; https://doi.org/10.3390/medicina61071268 - 13 Jul 2025

Cited by 4 | Viewed by 1147

Abstract

Background and Objectives: Non-invasive imaging biomarkers for the early detection of chronic kidney allograft injury are needed to improve long-term transplant outcomes. T1 mapping by magnetic resonance imaging (MRI) has emerged as a promising method to assess renal structure and function. This study aimed to determine the potential of MRI as a diagnostic tool for evaluating graft function and structural changes in kidney grafts 1 year after transplantation. Materials and Methods: Thirty-four kidney transplant recipients were prospectively recruited, with 27 completing the follow-up at one year. Renal MRI at 3T was performed to acquire T1, T2, and apparent diffusion coefficient (ADC) maps. Clinical parameters, including estimated glomerular filtration rate (eGFR), albumin-to-creatinine ratio (ACR), protein-to-creatinine ratio (PCR), and histological IF/TA scores, were collected. MRI parameters were compared across the groups stratified by clinical and histological markers. Diagnostic accuracy was assessed using receiver operating characteristic (ROC) analysis. Results: At 1 year, T1 corticomedullary differentiation (CMD) values were significantly higher in patients with elevated ACR (≥3 mg/mmol), PCR (≥15 mg/mmol), and mild to moderate or severe IF/TA, reflecting a reduction in the corticomedullary gradient. T1 CMD demonstrated moderate-to-good diagnostic performance in detecting ACR (AUC 0.791), PCR (AUC 0.730), and IF/TA (AUC 0.839). No significant differences were observed in T2 or ADC values across these groups. T1 CMD also showed a significant positive correlation with ACR but not with eGFR, suggesting a closer association with structural rather than functional deterioration. Conclusions: T1 mapping, particularly T1 CMD, shows promise as a non-invasive imaging biomarker for detecting chronic allograft injury and monitoring renal function 1 year after kidney transplantation. Full article

(This article belongs to the Special Issue End-Stage Kidney Disease (ESKD))

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11 pages, 401 KB

Open AccessArticle

Chronic Kidney Disease-Associated Pruritus in Patients Undergoing Haemodialysis—A Cross-Sectional Study

by Teng Wang, Jing-Xin Goh, Wubshet Tesfaye, Kamal Sud, Connie Van, Linda Le Do, Surjit Tarafdar and Ronald L. Castelino

Medicina 2025, 61(6), 993; https://doi.org/10.3390/medicina61060993 - 27 May 2025

Cited by 2 | Viewed by 2035

Abstract

Background and Objectives: Chronic kidney disease-associated pruritus (CKD-aP) is a burdensome symptom associated with impaired patient-reported outcomes. There is a paucity of research in this area with unclear aetiology, under-reporting of this symptom, and limited treatment options and management strategies in clinical settings. The objective of this study was to investigate the prevalence of CKD-aP, patient and dialysis-related factors associated with the occurrence of CKD-aP, and the correlation between CKD-aP severity and quality of life, sleep, anxiety, and depression. Materials and Methods: This cross-sectional study was conducted in 88 adult (≥18 years) patients undergoing haemodialysis at the outpatient dialysis centre at a major Australian tertiary care university teaching hospital. Demographic- and dialysis-related factors were obtained from electronic medical records and/or patients, while patient outcomes were determined from the self-reported questionnaires; 5-D itch scale, EQ-5D-5L, Patient Health Questionnaire-9, and Beck Anxiety Inventory. We compared demographic, patient-, and dialysis-related factors associated with CKD-aP. Results: Out of 88 patients, 67 (76%) agreed to participate in the study. In total, 27 patients (40%) reported having CKD-aP. Most participants experienced moderate CKD-aP severity (n = 12), followed by severe or very severe (n = 9) and mild (n = 6) symptoms. Whilst there was no significant difference in the demographic characteristics, number of medications, dialysis vintage, and Kt/V, a higher number of pruritic participants experienced obstructive sleep apnoea. There was a statistically significant correlation between CKD-aP severity and depression scores (p = 0.009). However, there were no significant correlation between CKD-aP and HRQOL (p = 0.506). The correlations between CKD-aP severity and outcomes such as sleep and anxiety were also not statistically significant, although they were marginally close (p = 0.069 and p = 0.095, respectively). Conclusions: This study reports a substantial prevalence of CKD-aP reported among patients undergoing HD and the association of severe CKD-aP with depression. Despite the limitation of a small sample size from a single dialysis centre, our findings suggest that the severity of CKD-aP may have implications for patient-reported outcomes. This warrants further investigation in larger-scale studies to better understand the association and optimise outcomes. Full article

(This article belongs to the Special Issue End-Stage Kidney Disease (ESKD))

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Review

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24 pages, 707 KB

Open AccessReview

Obesity and Its Clinical Implications in End-Stage Kidney Disease

by Kristina Petruliene, Alanta Zilinskiene, Ruta Vaiciuniene, Kestutis Vaiciunas, Inga Arune Bumblyte and Egle Dalinkeviciene

Medicina 2026, 62(1), 211; https://doi.org/10.3390/medicina62010211 - 20 Jan 2026

Viewed by 1025

Abstract

Both obesity and chronic kidney disease (CKD) are increasingly recognized as global epidemics. Their escalating incidence and far-reaching health implications highlight the urgent need for comprehensive prevention and management strategies. This review aims to clarify how obesity interacts with end-stage kidney disease (ESKD) and how to improve the management of obese patients receiving kidney replacement therapy. It also explores underlying mechanisms, current treatments, future directions, and ongoing controversies. By highlighting this intricate relationship, the review seeks to enhance clinical practice and promote further research toward more personalized care for this vulnerable population. Obesity is frequent in dialysis patients and creates challenges related to body composition, metabolism, and treatment. While higher body mass index (BMI) may appear to improve survival, this paradox does not offset the cardiovascular and functional risks of visceral and sarcopenic obesity. Obesity also increases post-transplant complications and can limit access to transplantation. Lifestyle changes rarely achieve lasting weight loss, whereas bariatric surgery—especially sleeve gastrectomy—can improve transplant eligibility with fewer complications. Weight-loss medications may be used before transplantation but remain insufficiently studied in ESKD. After transplantation, weight-reduction efforts should continue, with pharmacotherapy preferred over bariatric surgery. Comprehensive assessment strategies and individualized management approaches in ESKD patients are essential to optimize outcomes in this growing patient population. Full article

(This article belongs to the Special Issue End-Stage Kidney Disease (ESKD))

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12 pages, 1195 KB

Open AccessSystematic Review

Nonlinear Microscopy of ECM Remodeling in Renal and Vascular Tissues: A Systematic Review Integrating Human AVF Imaging

by Viltė Gabrielė Samsonė, Danielius Samsonas, Laurynas Rimševičius, Mykolas Mačiulis, Elena Osteikaitė, Birutė Vaišnytė, Edvardas Žurauskas, Virginijus Barzda and Marius Miglinas

Medicina 2026, 62(2), 317; https://doi.org/10.3390/medicina62020317 - 3 Feb 2026

Viewed by 681

Abstract

Background and Objectives: Extracellular matrix (ECM) and collagen remodeling contribute to chronic kidney disease (CKD) progression and vascular access dysfunction. Conventional histological techniques rely on staining and provide limited sensitivity for detecting early or subtle ECM alterations. Nonlinear optical imaging modalities, including second-harmonic generation (SHG), third-harmonic generation (THG), and multiphoton fluorescence (MPF) microscopy, enable label-free, high-resolution visualization of fibrillar collagen and may offer additional structural information. This study aimed to evaluate the added value of nonlinear imaging beyond conventional histology for assessing ECM remodeling in renal and vascular tissues. Materials and Methods: A systematic literature review was conducted in accordance with the PRISMA 2020 guidelines. PubMed and Web of Science were searched for studies published between 1 January 2015, and 4 April 2025, investigating ECM or collagen remodeling in renal or vascular tissues using SHG, THG, or MPF microscopy. After screening 115 records, 10 studies were included in the qualitative synthesis. In addition, representative SHG, THG, and MPF images of excised human arteriovenous fistula (AVF) tissue were acquired as illustrative feasibility examples to demonstrate the application of these imaging modalities. The use of human tissue was approved by the Vilnius Regional Biomedical Research Ethics Committee (approval No. 2022/6-1443-917). Results: The included studies demonstrated that nonlinear microscopy enables label-free assessment of collagen density, organization, and fiber orientation. SHG imaging differentiated healthy from diseased tissues and has been reported to support fibrosis assessment and staging in preclinical and selected clinical studies and revealed microstructural remodeling patterns not readily detected by conventional histology. The illustrative AVF images demonstrated collagen disorganization consistent with patterns reported in the reviewed literature and are presented solely to demonstrate imaging feasibility, without implying disease phenotype or clinical outcome associations. Conclusions: Nonlinear optical microscopy provides complementary structural information on ECM organization that is not accessible with standard histological techniques. Further validation and methodological standardization are required to support its broader application in clinical nephrology and vascular medicine. Full article

(This article belongs to the Special Issue End-Stage Kidney Disease (ESKD))

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