Life | Special Issue : Research Progress in Kidney Diseases

Research

29 pages, 7884 KB

Open AccessArticle

Differences on the Natural Course of Chronic Kidney Disease Progression, Induced by 5/6 Renal Ablation Model in Three Different Rat Stains: Wistar, Lewis, and Fischer 344

by Samuel de Jesus, Jr., Paloma Souza Noda, Ana Laura Rubio Francini, Flavio Teles Filho, Mariana Matera Veras, Ane Claudia Fernandes Nunes, Irene de Lourdes Noronha and Camilla Fanelli

Life 2026, 16(3), 420; https://doi.org/10.3390/life16030420 - 4 Mar 2026

Cited by 1 | Viewed by 793

Abstract

Almost 10% of the global population suffers from chronic kidney disease (CKD). The inexistence of a therapeutic to restore renal function motivates the scientific community to search for new treatments. The 5/6 nephrectomy (Nx) rat model is widely used to mimic human CKD, [...] Read more.

Almost 10% of the global population suffers from chronic kidney disease (CKD). The inexistence of a therapeutic to restore renal function motivates the scientific community to search for new treatments. The 5/6 nephrectomy (Nx) rat model is widely used to mimic human CKD, but the impact of strain-specific responses on disease progression remains unclear. Here, we aimed to compare CKD development in Wistar, Lewis, and Fischer rats submitted to the Nx model. In summary, even submitted to the same surgical procedure, the three studied rat strains presented distinct patterns of CKD progression: Wistar rats exhibited faster and sustained renal function loss, with exuberant hypertension, proteinuria, and renal inflammation, being considered as excellent models to study rapidly progressive human nephropathy. Lewis animals, in turn, presented mild low-progressive CKD, which make this rat strain especially useful to simulate intermediate degrees of human CKD and to develop long-term tests. Finally, Fischer rats submitted to Nx did not even develop hypertension, proteinuria, or glomerular damage within 30 days. Moreover, compared to Wistar rats, both Lewis and Fischer animals have a relatively higher basal number of nephrons and a lower number of whole blood leukocytes, which may have contributed to the renoprotection exhibited by these rat strains. Full article

(This article belongs to the Special Issue Research Progress in Kidney Diseases)

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19 pages, 307 KB

Open AccessArticle

Biomarkers for Early Detection of Cisplatin-Induced Nephrotoxicity

by Nikolay Dimov, Antoniya Yaneva, Evelina Valcheva, Gabriela Raycheva, Veselin Popov, Raya Delipavlova, Dimitar Nikolov and Zhanet Grudeva-Popova

Life 2025, 15(9), 1432; https://doi.org/10.3390/life15091432 - 12 Sep 2025

Cited by 2 | Viewed by 2135

Abstract

Nephrotoxicity is a common complication during antineoplastic therapy, particularly when platinum-based medications are used. Early detection of this condition is crucial for improving risk stratification and management, thereby enhancing decision-making in kidney disease treatment. However, traditional biomarkers for renal assessment lack sensitivity in [...] Read more.

Nephrotoxicity is a common complication during antineoplastic therapy, particularly when platinum-based medications are used. Early detection of this condition is crucial for improving risk stratification and management, thereby enhancing decision-making in kidney disease treatment. However, traditional biomarkers for renal assessment lack sensitivity in identifying early or subclinical damage, underscoring the need for novel and more precise markers. This study aimed to investigate the effectiveness of urinary KIM-1, clusterin, nephrin, and serum cystatin C in detecting nephrotoxicity associated with platinum-based therapies. A total of 43 patients with different oncological diseases participated in the prospective study, divided into two groups based on the nephrotoxic potential of the administered drugs: patients treated with cisplatin (high-risk group for nephrotoxicity) and patients treated with oxaliplatin/carboplatin (low-to-moderate risk group for nephrotoxicity). The results showed that nephrotoxicity, determined as a decrease in eGFR of >10 mL/min/1.73 m² at the sixth month after initiation of platinum-based therapy, occurred in 54.3% of cases, with 80% of these attributable to cisplatin-based therapy. Conventional renal biomarkers, such as the serum creatinine and urine albumin-creatinine ratio, have shown controversial results in the course of the study. In contrast, the patients treated with cisplatin, as well as those who developed nephrotoxicity, showed significant increases in the mean values of cystatin C (p < 0.001, respectively, p < 0.001), urinary KIM-1 (p = 0.005, respectively, p = 0.002), and urinary clusterin (p = 0.001, respectively, p = 0.001). Among the group with a low to moderate risk of nephrotoxicity including those treated with oxaliplatin/carboplatin, no statistically significant changes over time were observed in any of the biomarkers. These findings suggest that the aforementioned biomarkers can be used for the early detection of cisplatin-induced eGFR decline. Full article

(This article belongs to the Special Issue Research Progress in Kidney Diseases)

Review

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23 pages, 1879 KB

Open AccessReview

Environmental Pollution and Its Impact on Kidney Diseases: A Comprehensive Review of Current Evidence

by Seung Eun Lee and Yong Seek Park

Life 2026, 16(2), 291; https://doi.org/10.3390/life16020291 - 8 Feb 2026

Cited by 1 | Viewed by 1367

Abstract

Kidney disease is a growing global public health challenge that accounts for substantial morbidity, premature mortality, and rising healthcare costs. Although diabetes mellitus and hypertension remain the principal clinical risk factors for renal injury, accumulating evidence indicates that environmental pollution represents an independent [...] Read more.

Kidney disease is a growing global public health challenge that accounts for substantial morbidity, premature mortality, and rising healthcare costs. Although diabetes mellitus and hypertension remain the principal clinical risk factors for renal injury, accumulating evidence indicates that environmental pollution represents an independent and globally pervasive contributor to kidney disease burden. Long-term exposure to environmental toxicants, including heavy metals, ambient air pollutants, persistent organic pollutants, and endocrine-disrupting chemicals, has been consistently associated with acute kidney injury, an accelerated decline in renal function, and progression to end-stage kidney disease. The kidney is characterized by a high perfusion rate, specialized tubular transport systems, and a central role in xenobiotic metabolism and excretion, which confer heightened vulnerability to environmental insults. Experimental and epidemiological studies have demonstrated that pollutant exposure across the life course converges on shared pathogenic mechanisms, including oxidative stress, inflammatory signaling, mitochondrial dysfunction, fibrogenesis, and persistent epigenetic alterations. Importantly, environmental toxicants not only initiate renal injury, but they also impair intrinsic repair processes, exacerbating susceptibility to chronic and progressive kidney disease. This Review integrates population-based epidemiological data with experimental mechanistic evidence to define environmental exposures, renal cellular targets, and convergent molecular pathways underlying pollutant-induced nephrotoxicity, and aims to translate this knowledge into actionable strategies for kidney disease prevention, clinical risk stratification, and evidence-informed environmental policy. Full article

(This article belongs to the Special Issue Research Progress in Kidney Diseases)

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24 pages, 715 KB

Open AccessReview

Kidney Organoids: Current Advances and Applications

by Hiroyuki Nakanoh, Kenji Tsuji, Kazuhiko Fukushima, Naruhiko Uchida, Soichiro Haraguchi, Shinji Kitamura and Jun Wada

Life 2025, 15(11), 1680; https://doi.org/10.3390/life15111680 - 29 Oct 2025

Cited by 4 | Viewed by 6321

Abstract

Kidney organoids, derived from stem cells, including pluripotent stem cells and adult progenitor cells, have been reported as three-dimensional in vitro models that reflect key aspects of kidney development, structure, and function. Advances in differentiation protocols and tissue engineering have enabled the generation [...] Read more.

Kidney organoids, derived from stem cells, including pluripotent stem cells and adult progenitor cells, have been reported as three-dimensional in vitro models that reflect key aspects of kidney development, structure, and function. Advances in differentiation protocols and tissue engineering have enabled the generation of organoids that exhibit nephron-like structures, including glomerular and tubular structures. Kidney organoids have been widely applied in several directions, including disease modeling and therapeutic screening, drug nephrotoxicity evaluation, and regenerative medicine. In particular, kidney organoids offer a promising platform for studying genetic kidney diseases, such as polycystic kidney disease and congenital anomalies of the kidney and urinary tract (CAKUT), by allowing patient-specific modeling for the analysis of pathophysiology and therapeutic screening. Despite several current limitations, such as incomplete maturation, lack of full nephron segmentation, and variability between protocols and cell conditions, further technological innovations such as microfluidics and bioengineering may refine kidney organoid systems. This review highlights recent advances in kidney organoid research, outlines major applications, and discusses future directions to enhance their physiological relevance, functional maturity, and translational integration into preclinical and clinical nephrology. Full article

(This article belongs to the Special Issue Research Progress in Kidney Diseases)

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Other

Jump to: Research, Review

22 pages, 610 KB

Open AccessSystematic Review

Long Non-Coding RNAs and Micro RNAs in Chronic Kidney Disease: Recent Advances and Future Directions—A 5-Year Systematic Review

by Kanellos Skourtsidis, Despoina Ioannou, Georgios Kiosis, Konstantinos Stergiou, Maria Nefeli Georgaki, Theodora Papamitsou and Sofia Karachrysafi

Life 2026, 16(4), 579; https://doi.org/10.3390/life16040579 - 1 Apr 2026

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Abstract

Introduction: Chronic Kidney Disease (CKD) is a leading public health problem worldwide, with limited therapeutic options to halt its progression. Recent evidence implicates non-coding RNAs (ncRNAs), specifically long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), as critical regulators in renal pathophysiology and the transition [...] Read more.

Introduction: Chronic Kidney Disease (CKD) is a leading public health problem worldwide, with limited therapeutic options to halt its progression. Recent evidence implicates non-coding RNAs (ncRNAs), specifically long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), as critical regulators in renal pathophysiology and the transition from Acute Kidney Injury (AKI) to CKD. This review aims to synthesize recent findings regarding the role of ncRNAs in CKD pathogenesis, emphasizing their potential as diagnostic biomarkers and therapeutic targets. Methods: A systematic search was conducted in the PubMed/MEDLINE and Scopus databases for original research articles published over the last five years. Studies were selected based on specific eligibility criteria focusing on the correlation of ncRNAs with the development, diagnosis, and therapy of CKD. A total of 14 studies were included in the final review. Results: This review identified a dual landscape of ncRNAs function. Several lncRNAs, including H19, MALAT1, NEAT1_2, and LINC00963, were found to act as pathogenic drivers, promoting inflammation, apoptosis, and fibrosis through pathways such as TGF-β/Smad and NF-κB. Specifically, MALAT1 and NEAT1_2 are pivotal in driving the AKI-to-CKD transition. Conversely, specific miRNAs, such as miR-204, miR-26a, miR-451, miR-101, and miR-486-5p, exhibited protective effects by attenuating oxidative stress, preserving endothelial function, and inhibiting epithelial–mesenchymal transition (EMT). Dysregulation of these molecules was also observed in systemic conditions affecting the kidney, such as congestive heart failure and β-thalassemia. Conclusions: ncRNAs are central players in the molecular mechanisms underlying renal injury and maladaptive repair. The identified lncRNAs and miRNAs offer promising avenues for non-invasive diagnosis and the development of novel targeted therapies to prevent fibrosis and slow the progression of CKD. Full article

(This article belongs to the Special Issue Research Progress in Kidney Diseases)

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10 pages, 463 KB

Open AccessEditor’s ChoiceSystematic Review

Obinutuzumab Versus Rituximab for the Treatment of Primary Membranous Nephropathy: A Systematic Review and Meta-Analysis

by Andrew Lurie, Padideh Daneii, Sana Khan, Zoya Khan, Heena Mansuri and Anas Bizanti

Life 2026, 16(3), 434; https://doi.org/10.3390/life16030434 - 8 Mar 2026

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Abstract

Background: The benefit of specific B cell-targeted therapy in primary membranous nephropathy has been consistently demonstrated and is part of guideline-directed therapy. Though effective, Rituximab displays a highly variable response rate possibly owing to incomplete peripheral B cell depletion. Obinutuzumab is a second-generation [...] Read more.

Background: The benefit of specific B cell-targeted therapy in primary membranous nephropathy has been consistently demonstrated and is part of guideline-directed therapy. Though effective, Rituximab displays a highly variable response rate possibly owing to incomplete peripheral B cell depletion. Obinutuzumab is a second-generation anti-CD20 antibody which offers greater sustained peripheral B cell depletion and thus may result in improved clinical effect. This meta-analysis compares clinical efficacy of Obinutuzumab with Rituximab for the treatment of primary membranous nephropathy. Methods: A comprehensive search of PubMed, EMBASE, and Google Scholar was conducted on 10 October 2025. The search identified all studies which directly compared results of Obinutuzumab with Rituximab in the treatment of primary membranous nephropathy. Risk of bias was assessed using the Cochrane ROBINS-I tool. Data extraction and statistical analysis were performed using RevMan 5.1 software, assessing heterogeneity with the I² statistic. Results: Ultimately, three retrospective studies including a total of 161 participants were analyzed. The pooled estimated odds ratio for total clinical remission at 6 months was 2.84 (95% CI [1.42–5.69], p = 0.003, I² = 0%), and at 12 months was 12.25 ([95% CI 2.67–56.28]), p = 0.001, I² = 0%). The pooled estimated odds ratio for complete clinical remission at 6 months was 1.78 (95% CI [0.25–12.63], p = 0.57, I² = 0%) at 12 months was 4.12 (95% CI [1.36–12.48], p = 0.01, I² = 0%). The pooled estimated odds ratio for immunologic remission at 6 months was 6.18 (95% CI [1.57–24.39], p = 0.009, I² = 58%), and at 12 months was 5.56 (95% CI [1.50–20.64], p = 0.01, I² = 0%). The pooled estimated odds ratio for peripheral B cell depletion at 6 months was 3.91 (95% CI [0.99–15.40], p = 0.05, I² = 25%). Discussion: Obinutuzumab signals improvement in clinically relevant end points when compared with Rituximab for the treatment of primary membranous nephropathy but will require confirmation with head-to-head prospective data. The main limitations of this study include small sample sizes, geographic restriction, and retrospective design of the studies resulting in reduced generalizability. Other: There was no funding for this study. This review has been registered with PROSPERO (ID 1218735). Full article

(This article belongs to the Special Issue Research Progress in Kidney Diseases)

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12 pages, 265 KB

Open AccessOpinion

Peritoneal Dialysis Versus Extracorporeal Ultrafiltration Modalities in the Management of Acute Cardiorenal Syndrome with Diuretic Resistance

by Laura Elena Zamora-Cervantes, Enzo Vásquez-Jiménez, José Manuel Rodríguez-Chagolla, Mayra Eugenia Avilés-Ramírez, Viridiana Galicia Galicia, Roberto Galindo-López, Alberto Ramírez-Gil, Diego Sánchez-Hernández, Octavio René García-Flores and Hiram José Serrano-García

Life 2026, 16(2), 249; https://doi.org/10.3390/life16020249 - 2 Feb 2026

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Abstract

In cardiorenal Syndrome (CRS), diuretic resistance is frequent and congestion predominates in acute forms. In refractory cases, non-pharmacological ultrafiltration therapies have shown effectiveness on fluid removal, improved diuresis, and reduced rehospitalizations. However, the choice of modality remains individualized and resource-dependent. Both continuous renal [...] Read more.

In cardiorenal Syndrome (CRS), diuretic resistance is frequent and congestion predominates in acute forms. In refractory cases, non-pharmacological ultrafiltration therapies have shown effectiveness on fluid removal, improved diuresis, and reduced rehospitalizations. However, the choice of modality remains individualized and resource-dependent. Both continuous renal replacement therapy (CRRT) and peritoneal dialysis (PD) offer hemodynamic advantages, but CRRT carries risks such as infection, bleeding, and high cost. PD has also demonstrated benefits in acute settings, providing effective sodium removal, and no need for anticoagulation, though it is not considered first-line therapy. There are few studies comparing different renal replacement therapies (RRT) in patients with acute CRS and there is no evidence on diuretic resistance. So, the question arises: could there be an advantage of a modality beyond fluid removal? The scarcity of comparative studies underscores the need for randomized trials that move beyond the cardiocentric perspective and include patients at risk of diuretic resistance. Full article

(This article belongs to the Special Issue Research Progress in Kidney Diseases)

18 pages, 1924 KB

Open AccessSystematic Review

Urinary KIM-1 for Early Detection of Acute Kidney Injury in Neonates: A Systematic Review and Meta-Analysis

by Manapat Praditaukrit, Moragot Chatatikun, Aman Tedasen, Suntornwit Praditaukrit, Sirihatai Konwai, Jason C. Huang, Wiyada Kwanhian Klangbud and Atthaphong Phongphithakchai

Life 2025, 15(12), 1842; https://doi.org/10.3390/life15121842 - 30 Nov 2025

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Abstract

Acute kidney injury (AKI) is a significant clinical concern in neonates, threatening optimal outcomes. Early and accurate diagnosis is crucial; however, current methods lack sufficient sensitivity. This meta-analysis aimed to evaluate urinary kidney injury molecule-1 (uKIM-1) for AKI in neonates by quantifying differences [...] Read more.

Acute kidney injury (AKI) is a significant clinical concern in neonates, threatening optimal outcomes. Early and accurate diagnosis is crucial; however, current methods lack sufficient sensitivity. This meta-analysis aimed to evaluate urinary kidney injury molecule-1 (uKIM-1) for AKI in neonates by quantifying differences in uKIM-1 levels between AKI and non-AKI neonates. We systematically searched major databases for comparative studies. Quality assessment was performed using the Newcastle-Ottawa Scale, and the certainty of the evidence was assessed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. A random-effects meta-analysis estimated the pooled Hedges’ g in uKIM-1 levels, accounting for heterogeneity. Subgroup analyses explored sources of heterogeneity (continent, study design, sampling time, AKI definition). Publication bias was assessed using Egger’s and Begg’s tests, as well as with a funnel plot. Data from 13 studies involving 552 neonates indicated a significant association between elevated uKIM-1 levels and AKI. High heterogeneity was observed (I² = 80.32%). The pooled Hedges’ g was 0.62 (95% CI: 0.16–1.07, p = 0.01). Subgroup analysis showed stronger associations in African studies (Hedges’ g = 2.12), those using KDIGO (Hedges’ g = 0.96), cohort studies, and sampling within 2–4 days (Hedges’ g = 0.76). No publication bias was detected. This meta-analysis synthesizes evidence on uKIM-1 as an AKI biomarker. While uKIM-1 shows promise, high heterogeneity and diagnostic performance warrant further research to improve AKI detection and management in neonates. Full article

(This article belongs to the Special Issue Research Progress in Kidney Diseases)

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13 pages, 2924 KB

Open AccessCase Report

Stereotactic Ablative Radiotherapy for Delayed Retrobulbar Metastasis of Renal Cell Carcinoma: Therapeutic Outcomes and Practical Insights

by Sang Jun Byun, Byung Hoon Kim, Seung Gyu Park and Euncheol Choi

Life 2025, 15(8), 1176; https://doi.org/10.3390/life15081176 - 24 Jul 2025

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Abstract

We present a rare case of delayed retrobulbar and adrenal metastases from renal cell carcinoma (RCC), diagnosed 5.5 years after radical nephrectomy. The patient exhibited symptomatic orbital involvement, with imaging revealing a hypervascular retrobulbar mass and an incidental right adrenal lesion, indicative of [...] Read more.

We present a rare case of delayed retrobulbar and adrenal metastases from renal cell carcinoma (RCC), diagnosed 5.5 years after radical nephrectomy. The patient exhibited symptomatic orbital involvement, with imaging revealing a hypervascular retrobulbar mass and an incidental right adrenal lesion, indicative of an oligometastatic state. Owing to the patient’s refusal of surgical resection, stereotactic ablative radiotherapy (SABR) was delivered to the retrobulbar lesion at a total dose of 40 Gy in five fractions, concurrently with immune checkpoint inhibitor therapy. Treatment planning prioritized sparing adjacent critical structures, including the optic chiasm and brainstem. Follow-up over 4 years demonstrated sustained radiologic stability and volume reduction in both metastatic lesions without evidence of progression. This case underscores the potential efficacy of SABR in achieving durable local control of RCC metastases, particularly in anatomically constrained regions where surgery is unfeasible. Moreover, it highlights the value of a multidisciplinary, multimodal treatment approach incorporating advanced radiotherapy techniques and systemic immunotherapy. Lastly, it reinforces the importance of prolonged surveillance in RCC survivors due to the potential for late metastatic recurrence at uncommon sites. Full article

(This article belongs to the Special Issue Research Progress in Kidney Diseases)

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19 pages, 764 KB

Open AccessSystematic Review

Outcomes of Acute Kidney Injury in Melioidosis: A Systematic Review and Meta-Analysis

by Wiyada Kwanhian Klangbud, Moragot Chatatikun, Sa-ngob Laklaeng, Jitabanjong Tangpong, Pakpoom Wongyikul, Phichayut Phinyo, Jongkonnee Thanasai, Supphachoke Khemla, Chaimongkhon Chanthot and Atthaphong Phongphithakchai

Life 2025, 15(7), 1108; https://doi.org/10.3390/life15071108 - 15 Jul 2025

Cited by 1 | Viewed by 1707

Abstract

Background: Melioidosis is a severe infectious disease caused by Burkholderia pseudomallei, with high mortality rates, particularly in severe cases complicated by acute kidney injury (AKI). Objective: The objective of this study was to systematically review and quantitatively synthesize the impact of AKI [...] Read more.

Background: Melioidosis is a severe infectious disease caused by Burkholderia pseudomallei, with high mortality rates, particularly in severe cases complicated by acute kidney injury (AKI). Objective: The objective of this study was to systematically review and quantitatively synthesize the impact of AKI on mortality and other clinical outcomes—including ICU admission and the need for renal replacement therapy (RRT)—in patients with melioidosis. Methods: A systematic search was conducted in PubMed, Scopus, and Embase up to 16 May 2025. Studies reporting mortality, ICU admission, or RRT use in patients with AKI were included. A random-effects meta-analysis was performed to estimate the odds ratio (OR) for mortality associated with AKI. Results: Twenty-nine studies (380 patients) were included. AKI occurred in 123 patients (32.4%). The pooled analysis revealed that AKI patients had a significantly higher mortality risk than non-AKI patients (OR = 23.37; 95% CI: 13.97–39.10; p = 0.0082), with no significant heterogeneity (I² = 0%). Sensitivity analysis confirmed the robustness of this association. ICU admission and RRT data were frequently reported but were not suitable for meta-analysis due to insufficient data. Conclusions: AKI is a serious complication in melioidosis, significantly increasing the risk of mortality. Early recognition and aggressive management of AKI in melioidosis may be critical to improving clinical outcomes. Full article

(This article belongs to the Special Issue Research Progress in Kidney Diseases)

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