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New Advances in Chronic Kidney Disease: Biology, Diagnosis and Therapy...
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New Advances in Chronic Kidney Disease: Biology, Diagnosis and Therapy (2nd Edition)

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: 31 July 2025 | Viewed by 5636

Special Issue Editors

Dr. Susana Coimbra

E-Mail Website
Guest Editor
1. UCIBIO—Applied Molecular Biosciences Unit, Department of Biological Sciences, Faculdade de Farmácia da Universidade do Porto, 4050-313 Porto, Portugal
2. Associate Laboratory i4HB—Institute for Health and Bioeconomy, Faculdade de Farmácia da Universidade do Porto, Porto, Portugal
3. TOXRUN—Toxicology Research Unit, University Institute of Health Sciences, Cooperativa de Ensino Superior Politécnico e Universitário (CESPU), CRL, 4585-116 Gandra, Portugal
Interests: biomarkers; chronic kidney disease; inflammation; cardiovascular disease risk factors
Special Issues, Collections and Topics in MDPI journals
Dr. Alice Santos-Silva

E-Mail Website
Guest Editor
UCIBIO i4HB, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal
Interests: chronic kidney disease; CKD anemia; cardiovascular disease risk; anemia; inflammation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Chronic kidney disease (CKD) is characterized by a progressive and usually irreversible deterioration of renal function. The worsening of CKD is associated with a high burden of comorbidities, and in patients on dialysis treatment for end-stage kidney disease (ESKD), the mortality rate is 10- to 20-fold higher than in the general population. ESKD patients commonly present with chronic inflammation, protein–energy malnutrition, and progressive cardiovascular disease (CVD), which is the most common cause of mortality. Inflammation can be a trigger and/or consequence of CKD; it may result from the primary cause of CKD, such as in diabetes and hypertension, and be favored by renal dysfunction changes (e.g., uremia, oxidative stress, metabolic acidosis).

Ensuring a better understanding of the uremic milieu of CKD pathophysiology and its relationship with its comorbidities is the main focus of this Special Issue. The identification of biomarkers, or panels of biomarkers, of cardiorenal syndrome and early kidney injury will help clinicians when making therapeutic decisions and choosing earlier and more adequate therapeutic strategies, thus avoiding or minimizing CKD progression. The investigation of novel therapeutic approaches should also be encouraged.

Dr. Susana Coimbra
Dr. Alice Santos-Silva
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • inflammation
  • kidney biomarkers
  • kidney injury
  • chronic kidney disease
  • dialysis
  • cardiorenal syndrome risk
  • CKD anemia
  • kidney physiopathology
  • CKD treatment

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Related Special Issue

Published Papers (5 papers)

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Research

12 pages, 540 KiB  
Article
Evaluation of Individual Cardiovascular Risk in Pre-Dialysis CKD Patients by Using the Ratio of Calcium–Phosphorus Product to Estimated Glomerular Filtration Rate (Ca × P/eGFR)
by Krasimir Kostov, Tatyana Simeonova, Borislav Ignatov and Tsvetelina Eftimova
Biomedicines 2025, 13(1), 235; https://doi.org/10.3390/biomedicines13010235 - 19 Jan 2025
Viewed by 1046
Abstract
Background: Chronic kidney disease (CKD) patients have an increased risk of cardiovascular disease (CVD), necessitating effective risk assessment methods. This study evaluates the calcium–phosphorus product (Ca × P) to estimated glomerular filtration rate (Ca × P/eGFR) ratio as a potential biomarker for predicting [...] Read more.
Background: Chronic kidney disease (CKD) patients have an increased risk of cardiovascular disease (CVD), necessitating effective risk assessment methods. This study evaluates the calcium–phosphorus product (Ca × P) to estimated glomerular filtration rate (Ca × P/eGFR) ratio as a potential biomarker for predicting CV risk in pre-dialysis CKD patients. Methods: Eighty-four CKD patients in stages G1–G4, according to the KDIGO criteria, were classified into CVD (n = 43) and non-CVD (n = 41) groups. Biochemical parameters, including serum creatinine (SCr), blood urea nitrogen (BUN), calcium (Ca), inorganic phosphate (Pi), parathyroid hormone (PTH), alkaline phosphatase (ALP), Ca × P, eGFR, and the Ca × P/eGFR ratio, were measured and calculated. Statistical analyses were performed to identify predictors of CV risk and evaluate the diagnostic reliability of the Ca × P/eGFR ratio for predicting the risk. Results: Significant differences were observed in SCr, BUN, eGFR (p < 0.001), and the Ca × P/eGFR ratio (p = 0.007) between the groups. Regression analysis indicated the Ca × P/eGFR ratio as a significant CVD risk predictor (p = 0.012, OR = 1.206, 95% CI: 1.042–1.395). Receiver Operating Characteristic (ROC) curve analysis revealed an AUC of 0.751 (p < 0.001, 95% CI: 0.645–0.857), with a sensitivity and specificity of the method of 74.4% and 70.7%, respectively. Significant correlations were found between the Ca × P/eGFR ratio and SCr, BUN, UA, Ca, Pi, PTH, and ALP. Conclusions: The Ca × P/eGFR ratio may serve as a significant predictor of CVD risk in pre-dialysis CKD patients, suggesting that its integration into routine evaluations could enhance CV risk stratification and management. Full article
(This article belongs to the Special Issue New Advances in Chronic Kidney Disease: Biology, Diagnosis and Therapy (2nd Edition))
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Figure 1

Figure 1
<p>Comparison of the Ca × P/eGFR ratio between patients with and without CVD in the entire CKD cohort. Ca × P/eGFR is presented in (mmol/L)<sup>2</sup>/(mL/min/1.73 m<sup>2</sup>). No—non-CVD group, Yes—CVD group, <span class="html-italic">p</span> &lt; 0.05, statistically significant.</p> Full article ">Figure 2
<p>ROC curve plot illustrating the diagnostic capability of the Ca × P/eGFR ratio to evaluate CV risk in CKD patients before dialysis. Abbreviations: ROC, Receiver Operating Characteristic; AUC, area under the curve; <span class="html-italic">p</span>, probability value.</p> Full article ">
9 pages, 1046 KiB  
Article
Efficacy of Hypoxia-Inducible Factor Prolyl-Hydroxylase Inhibitors in Renal Anemia: Enhancing Erythropoiesis and Long-Term Outcomes in Patients with Chronic Kidney Disease
by Yukina Yoshida, Tomoaki Takata, Sosuke Taniguchi, Kana Kageyama, Yudai Fujino, Hinako Hanada, Yukari Mae, Takuji Iyama, Katsuya Hikita and Hajime Isomoto
Biomedicines 2024, 12(12), 2926; https://doi.org/10.3390/biomedicines12122926 - 23 Dec 2024
Viewed by 951
Abstract
Background/Objectives: Renal anemia is one of the major complications associated with chronic kidney disease (CKD). Erythropoietin-stimulating agents (ESAs) are commonly used; however, some patients exhibit resistance. Hypoxia-inducible factor prolyl-hydroxylase inhibitors (HIF-PHIs) have emerged as a novel treatment for renal anemia, enhancing erythropoiesis and [...] Read more.
Background/Objectives: Renal anemia is one of the major complications associated with chronic kidney disease (CKD). Erythropoietin-stimulating agents (ESAs) are commonly used; however, some patients exhibit resistance. Hypoxia-inducible factor prolyl-hydroxylase inhibitors (HIF-PHIs) have emerged as a novel treatment for renal anemia, enhancing erythropoiesis and iron metabolism. Methods: We retrospectively analyzed laboratory data related to erythropoiesis from 105 patients with CKD before and after treatment with HIF-PHI or ESA. The dialysis initiation and mortality rates were also assessed over a median follow-up of 614 days. Results: HIF-PHI and ESA significantly increased the hemoglobin levels within 6 months of treatment (9.5 ± 1.0 to 10.7 ± 1.1, p < 0.01, and 9.9 ± 1.5 to 10.7 ± 1.2 g/dL, p < 0.01, respectively). The HIF-PHI group demonstrated a significant decrease in red cell distribution width (14.5 ± 1.9% to 13.8 ± 1.4%, p < 0.01), suggesting improved erythropoiesis, and exhibited a lower cumulative incidence of outcomes. The aged-adjusted multivariate analysis confirmed the independent association between HIF-PHI treatment and reduced risk of cumulative outcome (p = 0.042). Conclusions: HIF-PHIs can serve as an alternative to ESA for managing renal anemia in CKD, improving both hematological parameters and long-term outcomes. Full article
(This article belongs to the Special Issue New Advances in Chronic Kidney Disease: Biology, Diagnosis and Therapy (2nd Edition))
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Figure 1

Figure 1
<p>Study design. Of the 150 patients treated with HIF-PHI or ESA, 105 were included in the analysis. HIF-PHI: hypoxia-inducible factor prolyl-hydroxylase inhibitor; ESA: erythropoietin-stimulating agent.</p> Full article ">Figure 2
<p>Changes in erythropoiesis after HIF-PHI and ESA treatment. Red blood cell count (<b>A</b>), hemoglobin (<b>B</b>), hematocrit (<b>C</b>), red cell distribution width (<b>D</b>), mean corpuscular volume (<b>E</b>), mean corpuscular hemoglobin (<b>F</b>), mean corpuscular hemoglobin concentration (<b>G</b>), transferrin saturation (<b>H</b>), and ferritin (<b>I</b>) were measured before and 1 month, 3 months, and 6 months after the initiation of HIF-PHI or ESA treatment. The black line represents the results from patients treated with ESA. The red line represents the results from patients treated with HIF-PHI. The bars indicate the average ± SEM. The results of Dunnett’s test compared with baseline values: * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01. Welch’s <span class="html-italic">t</span>-test between the HIF-PHI and ESA groups: † <span class="html-italic">p</span> &lt; 0.05; †† <span class="html-italic">p</span> &lt; 0.01. HIF-PHI: hypoxia-inducible factor prolyl-hydroxylase inhibitor; ESA: erythropoietin-stimulating agent.</p> Full article ">Figure 3
<p>Kaplan–Meier survival analysis of long-term outcomes. Kaplan–Meier survival analysis of patients treated with HIF-PHI or ESA during a median follow-up of 614 days. The outcome was defined as the initiation of dialysis or all-cause death. The overall survival rate was significantly higher in patients treated with HIF-PHI. HIF-PHI: hypoxia-inducible factor prolyl-hydroxylase inhibitor; ESA: erythropoietin-stimulating agent.</p> Full article ">
12 pages, 2392 KiB  
Article
Urinary GADD45G Protein Excretion Is Associated with IgA Nephropathy Progression
by Min-Jeong Lee, Hyunee Yim, Ji Eun Park, Inwhee Park, Heungsoo Kim and Gyu-Tae Shin
Biomedicines 2024, 12(12), 2846; https://doi.org/10.3390/biomedicines12122846 - 14 Dec 2024
Viewed by 703
Abstract
Background: Growth arrest and DNA damage 45G (GADD45G) is a family of proteins involved in DNA damage response and cell growth arrest. In this study, we show evidence that urinary GADD45G protein is associated with the progression of IgA nephropathy. Methods: [...] Read more.
Background: Growth arrest and DNA damage 45G (GADD45G) is a family of proteins involved in DNA damage response and cell growth arrest. In this study, we show evidence that urinary GADD45G protein is associated with the progression of IgA nephropathy. Methods: Patients diagnosed with IgA nephropathy without reversible acute kidney injury at study initiation and with at least one subsequent serum creatinine (SCr) measurement were included. A 50% or greater increase in SCr level was used as an endpoint for the deterioration of renal function. Enzyme-linked immunosorbent assay (ELISA) was performed using a Human GADD45G ELISA kit. Renal biopsy tissues were stained with a monoclonal mouse anti-GADD45G antibody. Results: Forty-five patients whose renal biopsy revealed IgA nephropathy were enrolled. Urinary GADD45G and urinary protein concentrations were 1.26 [0.69–2.20] μg/g creatinine and 0.65 [0.24–1.60] g/g creatinine, respectively. Urinary GADD45G showed significant positive correlations with SCr-slopes and urinary protein. The SCr-slope of the highest tertile group of urinary GADD45G (above 1.95 μg/g creatinine) was significantly higher than that of the lowest tertile group (below 0.90 μg/g). Univariate Cox regression analysis showed that urinary GADD45G was significantly associated with deterioration of renal function. A Kaplan–Meier test showed a significant difference in event-free survival for deterioration of renal function between the highest urinary GADD45G tertile group and other tertile groups. The area under the receiver operating characteristics (ROC) curve indicated urinary GADD45G had a good performance in predicting renal outcome (cut-off point 1.67 μg/g, positive predictive value 36.8%, negative predictive value 100%). Immunohistochemistry showed that GADD45G was expressed across all pathologic grades of IgA nephropathy and mainly detected in the cytoplasm of renal tubules, whereas no staining was noted in normal tissues. Conclusions: Urinary GADD45G excretion was significantly associated with kidney disease progression in patients with IgA nephropathy. Full article
(This article belongs to the Special Issue New Advances in Chronic Kidney Disease: Biology, Diagnosis and Therapy (2nd Edition))
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Figure 1

Figure 1
<p>Comparison of clinical parameters between urinary GADD45G tertiles: Tertile3 showed significant differences in urinary GADD45G (<b>A</b>), urinary protein (<b>C</b>), and serum albumin (<b>F</b>) in comparison with both Tertile1 and Tertile2. Tertile3 also showed significant differences in SCr slope (<b>B</b>), serum cholesterol (<b>D</b>), and age (<b>E</b>) in comparison with tertile1. There was no significant difference in BMI (<b>G</b>) and initial SCr (<b>H</b>) between groups. * <span class="html-italic">p</span> &lt; 0.05 versus Tertile1 and Tertile2; # <span class="html-italic">p</span> &lt; 0.05 versus tertile1. Total patients, N = 45. Tertiles of urinary GADD45G (N = 15 for each tertile): Tertile1, lowest; Tertile2, middle; Tertile3, highest. SCr, serum creatinine; BMI, body mass index.</p> Full article ">Figure 2
<p>Kaplan–Meier estimates of renal survival based on tertiles of urinary GADD45G levels. The endpoint was an increase of 50% or more in SCr concentrations above baseline. Comparisons between groups were made using the log-rank test with pairwise post hoc comparisons. Total patients, N = 45. Tertiles of urinary GADD45G (N = 15 for each tertile): Tertile1, lowest; Tertile2, middle; Tertile3, highest. SCr, serum creatinine.</p> Full article ">Figure 3
<p>The area under the receiver operating characteristics (ROC) curve of urinary GADD45G. The endpoint is an increase in SCr concentration of at least 50% above baseline. The blue and the green lines represent the ROC curve and the random classifier, respectively. The points above the green line indicate a better probability than the random one. Total patients, N = 45.</p> Full article ">Figure 4
<p>Immunohistochemistry expression of GADD45G: Biopsy sections from the same patient with IgA nephropathy were incubated with a primary antibody (<b>A</b>) or without a primary antibody (<b>B</b>), with the negative control (<b>B</b>) showing the lack of DAB staining. (<b>C</b>) There was little or no staining in the normal tissue taken from normal parts of removed kidneys for renal tumors. (<b>D</b>,<b>E</b>) Representative examples of GADD45G staining for specimens of IgA nephropathy. (<b>D</b>) There was an extensive expression of GADD45G in the cytoplasm of tubular cells. (<b>E</b>) Mild GADD45G staining was also noted in Bowman’s epithelial cells and some glomerular cells. Tissues were stained with DAB (brown) and counterstained with hematoxylin (blue). The scale bar was produced by the ZEN imaging software according to the magnification.</p> Full article ">Figure 5
<p>Relationships of pathologic grades with urinary and tissue GADD45G: (<b>A</b>) Urinary GADD45G levels according to the Oxford classification. (<b>B</b>) Measured OD of GADD45G staining according to the Oxford classification. (<b>C</b>) OD of GADD45G staining according to their respective tertiles of urinary GADD45G concentrations. Tertiles of urinary GADD45G (N = 15 for each tertile): Tertile1, lowest; Tertile2, middle; and Tertile3, highest.</p> Full article ">
11 pages, 1147 KiB  
Article
Arterio-Venous Fistula Calcifications—Risk Factors and Clinical Relevance
by Iulia Dana Grosu, Oana Stirbu, Adalbert Schiller and Flaviu Bob
Biomedicines 2024, 12(11), 2464; https://doi.org/10.3390/biomedicines12112464 - 27 Oct 2024
Viewed by 883
Abstract
(1) Background: Arterio-venous fistulas (AVFs) are considered the gold-standard vascular access (VA) in patients on maintenance hemodialysis (HD) therapy. AVF calcifications represent a less studied VA related complication, even though HD patients are at a higher risk for extraosseous calcifications. The aim of [...] Read more.
(1) Background: Arterio-venous fistulas (AVFs) are considered the gold-standard vascular access (VA) in patients on maintenance hemodialysis (HD) therapy. AVF calcifications represent a less studied VA related complication, even though HD patients are at a higher risk for extraosseous calcifications. The aim of this study is to assess the prevalence and risk factors of AVF calcifications, as well as the 5-year impact on AVF functionality and on overall mortality. (2) Methods: We conducted a 5-year prospective study including 161 patients on maintenance HD therapy. At baseline, we collected data related to VA history, comorbidities, demographics, subjective global assessment scale (SGA), and biochemical parameters. All patients underwent a complete AVF ultrasound and we recorded AVF blood flow and the presence of AVF calcifications, stenoses, and aneurysms. (3) Results: In our study, we found an AVF calcification prevalence of 39%. In a univariate analysis, we found that patients with AVF calcifications were associated with other AVF complications as well (stenoses, aneurysms), had longer AVF and HD vintage, as well as higher serum calcium and PTH values. In a multivariate analysis, we found that patients with a longer HD vintage and higher calcium values were independently associated with AVF calcifications. AVF calcifications did not affect 5-year fistula patency, nor were they associated with a higher mortality risk in our group of patients. (4) Conclusions: AVF calcifications were a frequent finding in our analysis, but their presence does not seem to affect the 5-year AVF patency. Full article
(This article belongs to the Special Issue New Advances in Chronic Kidney Disease: Biology, Diagnosis and Therapy (2nd Edition))
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Figure 1

Figure 1
<p>Cox proportional hazards model of patients with AVF calcifications versus patients without AVF calcifications.</p> Full article ">Figure 2
<p>Cox proportional hazards model—5-year survival analysis of patients with versus without AVF calcifications.</p> Full article ">
10 pages, 236 KiB  
Article
Serum Hepatocyte Growth Factor Concentration Correlates with Albuminuria in Individuals with Optimal Blood Pressure and Untreated Arterial Hypertension
by Margareta Fistrek Prlic, Ivana Vukovic Brinar, Jelena Kos, Zivka Dika, Ema Ivandic, Mirjana Fucek and Bojan Jelakovic
Biomedicines 2024, 12(10), 2233; https://doi.org/10.3390/biomedicines12102233 - 30 Sep 2024
Viewed by 946
Abstract
Background/Objectives: Hepatocyte growth factor (HGF) is a protective factor against acute renal injury and chronic renal fibrosis. A positive correlation between HGF and blood pressure (BP) has been established. This study aimed to determine the association between serum HGF concentration and albuminuria in [...] Read more.
Background/Objectives: Hepatocyte growth factor (HGF) is a protective factor against acute renal injury and chronic renal fibrosis. A positive correlation between HGF and blood pressure (BP) has been established. This study aimed to determine the association between serum HGF concentration and albuminuria in subjects with optimal blood pressure (OBP) and untreated arterial hypertension (UAH), as well as its association with BP levels, serum glucose levels, and inflammatory markers. Methods: Data from 563 subjects were analyzed. Albuminuria was normalized to urine creatinine and expressed as the albumin/creatinine ratio (ACR). HGF, serum glucose, C-reactive protein, and blood leucocyte counts were measured. BP was measured and subjects were divided into optimal blood pressure (BP < 120/80 mmHg, N = 295) and untreated arterial hypertension (BP > 140/90 mmHg, N = 268) groups. Results: The subjects with UAH were significantly older and had higher values of body mass index, waist circumference, serum total and LDL cholesterol levels, triglyceride levels, fasting glucose levels, and ACR (all p < 0.001). A significant positive correlation was found between serum HGF concentration and ACR in both groups. There was no difference or correlation between HGF and BP or inflammatory markers in either group. The multivariate regression analysis identified serum HGF concentration as a strong predictor of ACR increase (Beta = 0.376, p < 0.001). Conclusion: This study found that serum HGF concentration is associated with albuminuria not only in individuals with untreated arterial hypertension, but also in those with optimal blood pressure. The results suggest that serum HGF is an independent predictor of ACR increase in both groups. Full article
(This article belongs to the Special Issue New Advances in Chronic Kidney Disease: Biology, Diagnosis and Therapy (2nd Edition))
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