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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 7925

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

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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 (9 papers)

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Research

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10 pages, 867 KiB  
Article
Role of Educational Level in Kidney Transplant Outcomes
by Francesco Leonforte, Pierfrancesco Veroux, Antonio Mistretta, Alessia Giaquinta, Martina Maria Giambra, Domenico Zerbo, Giuseppe Roscitano, Concetta De Pasquale, Maria Luisa Pistorio, Antonio D’Anna, Carmelo Cusmano, Roberta Granata, Giordana Riccioli, Marianna Scribano and Massimiliano Veroux
Biomedicines 2025, 13(4), 916; https://doi.org/10.3390/biomedicines13040916 - 9 Apr 2025
Viewed by 195
Abstract
Background: Kidney transplantation outcomes are correlated to many factors, including the socioeconomics conditions and the educational level. Methods: We evaluated the role of educational level on patient and graft survival in a population of 456 kidney transplant recipients. Patients were divided [...] Read more.
Background: Kidney transplantation outcomes are correlated to many factors, including the socioeconomics conditions and the educational level. Methods: We evaluated the role of educational level on patient and graft survival in a population of 456 kidney transplant recipients. Patients were divided into two groups on the basis of their pre-transplant educational status: patients with primary education (elementary or middle school, as low education) were compared with patients with a secondary school education (high school or a university degree, as high education). Results: Among the 456 patients considered for this analysis, 161 patients had a low educational status, and 295 had a high educational status. Patients with a low educational status were more rarely employed (66.1% vs. 32.5%, p < 0.001), with a high rate of retired patients compared to high-educational status patients (35.6% vs. 10.6%, p < 0.001). Although the educational status did not influence the graft function, the 1-year (88.1% vs. 96.2%, p = 0.0008), 5-year (77.6% vs. 88.8%, p = 0.001), and 10-year (62.1% vs. 75%, p = 0.003) graft survival rates were significantly lower in patients with low educational status compared with high-educational status patients, respectively. Patient survival at 1-year (94.4% vs. 97.6%, p = 0.073), 5-year (85% vs. 92.5%, p = 0.011), and 10-year (75.7% vs. 83.4%, p = 0.042) follow-up was significantly lower in patients with low educational status. Conclusions: Low socioeconomic conditions and educational level had a negative impact on kidney transplant outcomes. Improving access to education and providing targeted educational support and health literacy could enhance treatment adherence and reduce disparities in transplant 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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14 pages, 1353 KiB  
Article
Prognostic Significance of Visit-to-Visit Ultrafiltration Volume Variability in Hemodialysis Patients
by Balázs Sági, Tibor Vas, Éva Fejes and Botond Csiky
Biomedicines 2025, 13(3), 717; https://doi.org/10.3390/biomedicines13030717 - 14 Mar 2025
Viewed by 538
Abstract
Introduction: Patients on chronic hemodialysis (HD) have significantly higher mortality compared with the general population. Cardiovascular (CV) disease is the primary reason for death in these patients. Suboptimal extracellular fluid management increases the CV risk of HD patients. We aimed to study the [...] Read more.
Introduction: Patients on chronic hemodialysis (HD) have significantly higher mortality compared with the general population. Cardiovascular (CV) disease is the primary reason for death in these patients. Suboptimal extracellular fluid management increases the CV risk of HD patients. We aimed to study the effect of visit-to-visit ultrafiltration volume (UV) variability on CV events and mortality in chronic HD patients. Patients and Methods: In our study, 173 chronic HD patients were included (median age: 63 ± 13 years; 53% men). Ultrafiltration volume (UV) variability was analyzed retrospectively for 24 months. The standard deviation (SD) and coefficient of variation (CV) were calculated using the indices of UV variability. CV is the SD divided by the mean. The obtained parameters were SD and CV of the UV: UVSD and UVCV. UV data during the observation period were recorded and used to calculate UV variability. Routine transthoracal echocardiography was performed. Results: Patients were divided into groups based on the median of UVSD, low-UVSD (<568 mL) and high-UVSD (≥568 mL) group; and also based on the median of UVCV, low- (<0.29) and high-UVCV (≥0.29) group. All-cause mortality was significantly higher in the high compared to the low-UVSD (21/84 vs. 9/89; p < 0.001) group. Similarly, mortality was higher in the high-UVCV group compared to the low-UVCV group (18/78 vs. 12/95; p = 0.005) after 24 months. Major adverse CV event (MACE) rates were also significantly higher in the high- compared to the low-UVSD group (20/84 vs. 8/89; p < 0.001). Similarly, the MACE rate was significantly higher in the high-UVCV group compared to the low-UVCV group (15/78 vs. 13/95; p = 0.029) after 24 months. There was no significant difference between the groups in CV mortality. UVSD correlated with parathormone (PTH) level (r = 0.416; p = 0.015), and UVCV with total cholesterol (r = 0.419; p = 0.015). Left ventricular end-diastolic diameter (LVEDD) and end-systolic diameter (LVESD) were higher in the high-UVCV group compared to the low-UVCV group (49.95 vs. 52.08; p = 0.013 and 32.19 vs. 34.13; p = 0.034). Conclusions: According to our results, high UVSD and UVCD are associated with increased all-cause mortality and MACE rates but not CV mortality in chronic HD patients. Cardiovascular changes caused by increased UF volume variability during HD may contribute to higher CV morbidity and mortality in these patients. 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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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
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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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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
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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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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 798
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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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 1036
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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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 1021
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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19 pages, 1232 KiB  
Review
Chronic Allograft Nephropathy—A Narrative Review of Its Pathogenesis, Diagnosis, and Evolving Management Strategies
by Matthew Pittappilly, Mohammed Sharshir and Anil Paramesh
Biomedicines 2025, 13(4), 929; https://doi.org/10.3390/biomedicines13040929 - 9 Apr 2025
Viewed by 181
Abstract
Chronic allograft nephropathy is the leading cause of kidney allograft failure. Clinically, it is characterized by a progressive decline in kidney function, often in combination with proteinuria and hypertension. Histologically, interstitial fibrosis and tubular atrophy, along with features of glomerulosclerosis with occasional double [...] Read more.
Chronic allograft nephropathy is the leading cause of kidney allograft failure. Clinically, it is characterized by a progressive decline in kidney function, often in combination with proteinuria and hypertension. Histologically, interstitial fibrosis and tubular atrophy, along with features of glomerulosclerosis with occasional double contour appearance, arteriolar hyalinosis, and arteriosclerosis, are characteristic findings. The pathophysiology, though complex and incompletely understood, is thought to involve a sequence of immunologic and non-immunologic injuries eventually leading to tissue remodeling and scarring within the graft. The optimal strategy to prevent chronic allograft nephropathy is to minimize both immune- and non-immune-mediated graft injury. 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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13 pages, 2101 KiB  
Review
Calciphylaxis Following Parathyroidectomy in Chronic Kidney Disease Patients—Case Report and Literature Review
by Nada Akad, Stefana Catalina Bilha, Mugurel Apetrii, Fawzy Akad, Madalina Bilha, Mihai Hogas, Simona Hogas, Maria-Christina Ungureanu, Cristina Preda and Adrian Covic
Biomedicines 2025, 13(3), 715; https://doi.org/10.3390/biomedicines13030715 - 14 Mar 2025
Viewed by 529
Abstract
Calcific uremic arteriolopathy, also known as calciphylaxis, is a rare and often fatal condition most commonly occurring in patients with end-stage renal disease (ESRD). It is marked by extensive vascular calcification, resulting in tissue ischemia and the development of distinctive skin lesions. We [...] Read more.
Calcific uremic arteriolopathy, also known as calciphylaxis, is a rare and often fatal condition most commonly occurring in patients with end-stage renal disease (ESRD). It is marked by extensive vascular calcification, resulting in tissue ischemia and the development of distinctive skin lesions. We report the case of a 38-year-old male with ESRD due to polycystic kidney disease, who developed calciphylaxis lesions following total parathyroidectomy (PTx). We also performed an electronic search of PubMed and Google Scholar from inception until December 2024, using the following keywords: ‘chronic kidney disease’, ‘dialysis’, ‘calciphylaxis’, ‘calcific uremic arteriolopathy’, ‘secondary hyperparathyroidism’, and ‘parathyroidectomy’. A literature review of calciphylaxis cases following PTx in chronic kidney disease (CKD) patients identified 14 cases reported up to the manuscript’s writing. Although PTx can be a treatment option for calciphylaxis related to severe secondary hyperparathyroidism (SHPT), leading to clinical improvement in some patients, there are atypical calciphylaxis cases occurring after PTx. While the mechanism is not fully understood, the sudden reduction in parathormone (PTH) levels leading to hypocalcemia and decreased bone turnover, together with an increased calcium loading in a patient at risk for abnormal mineralization, may promote vascular and soft tissue calcification. However, the long-term impact of severe SHPT with a delayed post-PTx manifestation cannot be ruled out. Clinicians should consider calciphylaxis in CKD patients with new painful skin lesions. Skin biopsy remains controversial, but a thorough clinical examination, and, in some cases, imaging are essential for a correct diagnosis. A multidisciplinary, personalized approach is crucial, with careful management of post-PTx hypocalcemia and calcium supplementation. Further research is needed to enhance understanding and treatment strategies. 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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