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12 pages, 457 KB  
Article
Impaired Kidney Function, Subclinical Myocardial Injury, and Their Joint Associations with Cardiovascular Mortality in the General Population
by Ahmed E. Shatta, Mohamed A. Mostafa, Mohamed A. Attia, Tarek Ahmad Zaho, Richard Kazibwe and Elsayed Z. Soliman
J. Clin. Med. 2025, 14(19), 7123; https://doi.org/10.3390/jcm14197123 (registering DOI) - 9 Oct 2025
Abstract
Background: The combined impact of impaired kidney function and subclinical myocardial injury (SCMI) on cardiovascular (CV) mortality has not been well studied. We aimed to evaluate their individual and joint associations with cardiovascular mortality. Methods: We analyzed data from 6057 participants (mean age [...] Read more.
Background: The combined impact of impaired kidney function and subclinical myocardial injury (SCMI) on cardiovascular (CV) mortality has not been well studied. We aimed to evaluate their individual and joint associations with cardiovascular mortality. Methods: We analyzed data from 6057 participants (mean age 57.0 ± 13.0 years) in the U.S. Third National Health and Nutrition Examination Survey. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation. Electrocardiographic SCMI was defined as a cardiac infarction/injury score ≥ 10. CV mortality was determined from the National Death Index. Multivariable logistic regression assessed baseline cross-sectional associations between eGFR and SCMI. Cox proportional hazards models were used to examine the individual and combined associations of eGFR and SCMI with CV mortality. Results: At baseline, 1297 participants (21.4%) had SCMI. In multivariable logistic regression analysis, eGFR < 45 mL/min/1.73 m2 (vs. ≥45) was not associated with SCMI (OR [95% CI]: 1.10 [0.84–1.45]). Over a median follow-up of 18.4 years, 690 CV deaths occurred. In separate Cox models, both SCMI (vs. no SCMI) and eGFR < 45 (vs. ≥45) were associated with increased CV mortality risk (HR [95% CI]: 1.36 [1.16–1.60] and 1.56 [1.24–1.99], respectively). Compared with participants with eGFR ≥ 45 and no SCMI, those with both eGFR < 45 and SCMI had the highest CV mortality risk (HR [95% CI]: 2.36 [1.65–3.36]), followed by eGFR < 45 alone (1.47 [1.09–1.96]) and SCMI alone (1.33 [1.11–1.58]). Conclusions: Both reduced eGFR and SCMI were independently associated with CV mortality. Their coexistence showed the highest risk, but without statistical significance compared with each alone, possibly reflecting limited power and distinct mechanisms. Full article
(This article belongs to the Section Cardiovascular Medicine)
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17 pages, 1528 KB  
Article
Estimating the Contribution of Renal Function to Endothelial Dysfunction and Subclinical Inflammation with a Two-Cohort Study: Living Kidney Donors and Their Transplant Recipients
by Irina B. Torres, Carla Burballa, José M. González-Posada, Domingo Hernández, Esteban Porrini, Janire Perurena, Vicente Cortina, Manel Perelló, Dolores Redondo-Pachón, Ana González-Rine, Mercedes Cabello, Maria José Pérez-Sáez, Marta Crespo, Oriol Bestard, Daniel Serón and Francesc Moreso
Int. J. Mol. Sci. 2025, 26(19), 9535; https://doi.org/10.3390/ijms26199535 - 29 Sep 2025
Viewed by 237
Abstract
Living kidney transplantation offers the best results for end-stage renal disease patients, but concerns about cardiovascular risk after nephrectomy for kidney donors have been raised. We aimed to estimate the contribution of renal function to endothelial dysfunction (ED) and subclinical inflammation in a [...] Read more.
Living kidney transplantation offers the best results for end-stage renal disease patients, but concerns about cardiovascular risk after nephrectomy for kidney donors have been raised. We aimed to estimate the contribution of renal function to endothelial dysfunction (ED) and subclinical inflammation in a non-interventional, prospective, multicenter, longitudinal study with two cohorts: living kidney donors and their transplant recipients (registered clinical trial NCT02515643). The measured glomerular filtration rate (mGFR) by iohexol clearance, estimated GFR according to the CKD-EPI and MDRD-4 formulas, and levels of endothelial dysfunction (sVCAM-1, sICAM-1, E-selectin, von Willebrand Factor, pentraxin, and urinary albumin-to-creatinine ratio) and subclinical inflammation biomarkers (sIL-6, sTNF-R1, sTNF-R2, sTWEAK, and high-sensitivity C-reactive protein) were determined at baseline and 1-year follow-up. Fifty pairs of donors and recipients were recruited between 2015 and 2018. Among the endothelial dysfunction biomarkers, sVCAM-1 increased in donors and decreased in recipients (p < 0.01) while, among the inflammation biomarkers, sTNFR1 and sTNFR2 significantly increased in donors and decreased in recipients (p < 0.001). After transplantation, parallel increases and decreases in ED and subclinical inflammation biomarkers were observed in the donor and recipient cohorts, respectively. Long-term follow-up is needed to characterize the cardiovascular risk associated with these changes. Full article
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15 pages, 1109 KB  
Article
Assessing Fibrosis Progression and Endothelial Dysfunction in SSc-ILD and COPD: An Integrated Biomarker and CT Densitometry Approach
by Lyazat Ibrayeva, Irina Bacheva, Assel Alina and Olga Klassen
Medicina 2025, 61(9), 1572; https://doi.org/10.3390/medicina61091572 - 31 Aug 2025
Viewed by 482
Abstract
Background and Objectives: Chronic lung diseases act as multi-organ conditions in which systemic inflammation, vascular dysfunction, and fibrosis intersect. The pulmo-renal continuum—functional crosstalk between lungs and kidneys—remains poorly characterized. We compared year-long changes in endothelin-1 (ET-1), galectin-3 (Gal-3), renal indices (eGFR, ACR), and [...] Read more.
Background and Objectives: Chronic lung diseases act as multi-organ conditions in which systemic inflammation, vascular dysfunction, and fibrosis intersect. The pulmo-renal continuum—functional crosstalk between lungs and kidneys—remains poorly characterized. We compared year-long changes in endothelin-1 (ET-1), galectin-3 (Gal-3), renal indices (eGFR, ACR), and quantitative CT densitometry in COPD and systemic sclerosis-associated ILD (SSc-ILD). Materials and Methods: In this prospective observational study (January 2023–December 2024), 112 patients were consecutively enrolled (COPD, n = 58; SSc-ILD, n = 54). Assessments were performed at baseline and 12 months. ET-1 (ELISA) and Gal-3 (chemiluminescence) were measured in serum; eGFR was calculated by the creatinine-based CKD-EPI (2021) equation; ACR was photometric. High-resolution chest CT provided lung volume and parenchymal density (Hounsfield units) at six predefined axial levels per lung. Non-parametric statistics were applied: Wilcoxon signed-rank (within-group), Mann–Whitney U (between-group), and Spearman rank correlations for associations; results are reported with p-values (and 95% CIs). Results: Baseline eGFR was normal (COPD 90.37; SSc-ILD 92.4 mL/min/1.73 m2). eGFR declined by 6.76% in COPD (p = 0.001) and 3.16% in SSc-ILD (p = 0.029). ET-1 increased in both cohorts but more in COPD (+83.78%, p = 0.0002) than in SSc-ILD (+23.83%, p = 0.0001). Gal-3 rose significantly only in SSc-ILD (+10.2%, p = 0.043). FVC decreased in COPD (−4.01%, p = 0.01) and was unchanged in SSc-ILD. Total lung volume declined in SSc-ILD (−6.08%, p = 0.02) but not in COPD. CT density shifts were small: several slices in COPD and one slice (L6) in SSc-ILD reached statistical but not biological relevance. Conclusions: COPD exhibited larger vascular and renal biomarker shifts (ET-1 up, eGFR down, ACR up), suggesting systemic inflammation and early renal involvement. In SSc-ILD, biomarker and CT changes predominantly reflected pulmonary fibrosis progression with limited renal impact. Integrating biomarkers with quantitative CT may help delineate organ-specific trajectories along the pulmo-renal continuum; longer, larger studies are warranted. Limitations: This was a single-center cohort with a modest sample (58 COPD and 54 SSc-ILD) and a 12-month, two-time-point follow-up, which may not capture long-term trajectories and may limit it generalizability; larger multicenter studies with an extended follow-up are warranted. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Interstitial Lung Disease)
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15 pages, 1105 KB  
Article
NT-proBNP as an Independent Predictor of Long-Term All-Cause Mortality in Heart Failure Across the Spectrum of Glomerular Filtration Rate
by Anca Breha, Caterina Delcea, Andreea Cristina Ivanescu and Gheorghe-Andrei Dan
J. Clin. Med. 2025, 14(11), 3886; https://doi.org/10.3390/jcm14113886 - 31 May 2025
Viewed by 1644
Abstract
Background/Objectives: The coexistence of heart failure (HF) and chronic kidney disease (CKD) complicates management and worsens prognosis. NT-proBNP is a recognized biomarker for HF diagnosis and prognosis, yet its interpretation in CKD can be challenging due to confounding factors increasing its levels. This [...] Read more.
Background/Objectives: The coexistence of heart failure (HF) and chronic kidney disease (CKD) complicates management and worsens prognosis. NT-proBNP is a recognized biomarker for HF diagnosis and prognosis, yet its interpretation in CKD can be challenging due to confounding factors increasing its levels. This study aimed to evaluate the predictive value of NT-proBNP for all-cause long-term mortality in HF patients across various stages of renal dysfunction. Methods: Hospitalized HF patients were included in this observational, retrospective analysis. NT-proBNP levels and serum creatinine were measured on admission. The primary outcome was all-cause mortality. Patients were divided into three groups according to renal function estimated using the CKD-EPI formula: eGFR1 (>60 mL/min/1.73 m2), eGFR2 (30–60 mL/min/1.73 m2) and eGFR3 (<30 mL/min/1.73 m2). Results: The study included 716 HF patients with a mean age of 71 ± 10 years, 49% males. All-cause long-term mortality was 35% after a median follow-up of 59 months. The mortality rate increased from 29% in eGFR1 patients, to 43% in eGFR2, to 68% in eGFR3. Median NT-proBNP increased from 997 pg/mL in eGFR1 patients to 1586 pg/mL in eGFR2 to 4928 pg/mL in eGFR3. Cut-off values for predicting all-cause long-term mortality were NT-proBNP >1837 pg/mL in eGFR1 patients, >1413 pg/mL in eGFR2 and >6415 pg/mL in eGFR3. In multivariable Cox analysis, NT-proBNP was an independent predictor of all-cause long-term mortality in all eGFR groups. Conclusions: NT-proBNP on admission was an independent predictor of long-term all-cause mortality in hospitalized HF patients across all eGFR subgroups, with increasing cut-off levels in patients with renal dysfunction. Full article
(This article belongs to the Section Cardiology)
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16 pages, 1395 KB  
Article
Prediction of Glomerular Filtration Rate Following Partial Nephrectomy for Localized Renal Cell Carcinoma with Different Machine Learning Techniques
by Aleksander Ślusarczyk, Sumit Sharma, Karolina Garbas, Hanna Piekarczyk, Piotr Zapała, Jinhao Shi, Piotr Radziszewski, Le Qu and Łukasz Zapała
Cancers 2025, 17(10), 1647; https://doi.org/10.3390/cancers17101647 - 13 May 2025
Viewed by 891
Abstract
Background and Objectives: Partial nephrectomy (PN) is the preferred option for treating localized cT1 renal cell carcinoma (RCC), as it preserves renal function in most patients and offers non-inferior oncological outcomes compared to radical nephrectomy. In this study, we aimed to construct [...] Read more.
Background and Objectives: Partial nephrectomy (PN) is the preferred option for treating localized cT1 renal cell carcinoma (RCC), as it preserves renal function in most patients and offers non-inferior oncological outcomes compared to radical nephrectomy. In this study, we aimed to construct a predictive model for estimating the glomerular filtration rate (GFR) at one year after PN in patients with RCC, using various machine learning techniques. Methods: Retrospective data were collected from two academic centers, covering surgeries performed between 2010 and 2022. GFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration 2021 (CKD-EPI) formula. Univariable linear regression (LR) was used to identify significant clinical predictors of 1-year postoperative GFR, followed by multivariable LR. The dataset was split into training and testing cohorts in a 70:30 ratio. Internal validation was performed on the test cohort, and various machine learning methods, including artificial neural networks (ANNs), support vector machines (SVMs), random forests (RFs), and XGBoost, were compared. Results: Among 615 patients treated with PN, 415 had complete follow-up GFR data and were included in the analysis. Only 8.7% of patients experienced significant GFR loss (>30% decrease) at 1 year. Multivariable LR identified baseline GFR (Estimate: 0.76, p < 0.001), tumor diameter on imaging (Estimate: −1.65, p = 0.005), and Charlson Comorbidity Index (Estimate: −1.95, p < 0.001) as independent predictors of 1-year GFR (R2 = 0.67). A 10-fold cross-validation of the multivariable model yielded an R2 of 0.68. In the testing cohort, ANN, SVM, RF, and XGBoost did not outperform the LR model, with R2 values of 0.68, 0.66, 0.64, and 0.55, respectively. Conclusions: Preoperative factors, including baseline GFR, tumor size on imaging, and Charlson Comorbidity Index, are effective predictors of GFR at 1 year following PN. Our study demonstrates that a conventional LR model based on preoperative variables provides acceptable accuracy for predicting GFR after PN and is not inferior to more complex machine learning techniques. Full article
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13 pages, 655 KB  
Article
How to Evaluate Kidney Function in Elite Endurance Athletes: Pros and Cons of Different Creatinine-Based Formulas
by Giuseppe Di Gioia, Armando Ferrera, Andrea Serdoz, Alessandro Spinelli, Roberto Fiore, Lorenzo Buzzelli, Domenico Zampaglione and Maria Rosaria Squeo
J. Clin. Med. 2025, 14(9), 2955; https://doi.org/10.3390/jcm14092955 - 24 Apr 2025
Viewed by 2291
Abstract
Background: Various creatinine-based equations are used to estimate the glomerular filtration rate (eGFR) in athletes, but each has limitations. The aim of our study was to identify the most suitable formula for use in athletes. Methods: We evaluated 490 Olympic athletes (27 ± [...] Read more.
Background: Various creatinine-based equations are used to estimate the glomerular filtration rate (eGFR) in athletes, but each has limitations. The aim of our study was to identify the most suitable formula for use in athletes. Methods: We evaluated 490 Olympic athletes (27 ± 5.3 yo) with normal values of serum creatinine and no history of kidney diseases. Athletes were divided into those practicing skills and endurance disciplines. The EGFR was calculated with Cockcroft–Gault (CG), MDRD, MCQE and CKD-EPI, and classified as stages G1–G5 according to the Kidney Disease Improving Global Outcomes (KDIGO) GFR categories. Results: Endurance athletes showed higher serum creatinine (0.91 ± 0.14 mg/dL vs. 0.88 ± 0.13 mg/dL in skills, p = 0.014). The eGFR calculated with the CKD-EPI and MCQE formulas showed no differences between the groups. The CG formula produced a lower eGFR for endurance athletes (113.6 ± 27 mL/min/1.73 m2) compared to skills athletes (122.6 ± 30.8, p = 0.008), while MDRD produced higher values for endurance athletes (129.3 ± 25.8 vs. 122.6 ± 24 mL/min/1.73 m2, p = 0.004). According to CKD-EPI, all athletes were in G1, while with MCQE, 0.5% of skills athletes and 1% of endurance athletes were in G2. With the CG formula, a significant percentage of athletes were in G2 (13.2% of skills athletes and 18.5% of endurance athletes, p = 0.125). With the MDRD formula, 29 athletes (5.9%) were in G2 (6% for skills athletes and 5.8% for endurance athletes, p = 0.927). Conclusions: CKD-EPI and MCQE showed better stability and reliability, making them the most suitable for kidney function evaluation in athletes. Full article
(This article belongs to the Special Issue Advancements in Diagnostic Innovations in Sports Cardiology)
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11 pages, 667 KB  
Article
Performance of the 2021 Estimated Glomerular Filtration Rate CKD-EPI Refit and the European Kidney Function Consortium (EKFC) Formulas
by Evelyn O. Ilori, Casey R. Cai, Fatou Sahor, Brianna Wilson, Tanooha Veeramachaneni, Samir M. Parikh and Ibrahim A. Hashim
Diagnostics 2025, 15(8), 1047; https://doi.org/10.3390/diagnostics15081047 - 21 Apr 2025
Viewed by 1151
Abstract
Background: The glomerular filtration rate (GFR) is a universal clinical measure central to assessing kidney function and to the management of kidney disorders. Several formulas for the estimation of GFR are in use. The European Kidney Function Consortium (EKFC) formula has been [...] Read more.
Background: The glomerular filtration rate (GFR) is a universal clinical measure central to assessing kidney function and to the management of kidney disorders. Several formulas for the estimation of GFR are in use. The European Kidney Function Consortium (EKFC) formula has been reported to more accurately estimate the GFR as compared to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula and its recent version (REFIT equation) in European and African populations. However, validation of the EKFC equation in diverse U.S. populations, especially the Black subpopulation, is needed. Methods: Data from the electronic medical records of 75,442 individuals presenting to a large safety net county hospital with measurements of serum creatinine and/or iohexol clearance studies were used to calculate the estimated GFR (eGFR) and to determine CKD stage using the various reported eGFR formulas. The correlation between eGFR and measured GFR was determined for each equation. Results: The median eGFR for Black participants using the CKD-EPI, REFIT, and EKFC formulas was 130.6 mL/min/1.73 m2, 82.0 mL/min/1.73 m2, and 80.6 mL/min/1.73 m2 (p < 0.001), respectively. For White participants, the median eGFR using the CKD-EPI, REFIT, and EKFC formulas was 145.3 mL/min/1.73 m2, 105.6 mL/min/1.73 m2, and 99.2 mL/min/1.73 m2, respectively (p < 0.001). The REFIT equation underestimates the mGFR in Black individuals at eGFR < 80 mL/min per 1.73 m2 and in White individuals at eGFR > 20 mL/min per 1.73 m2. In comparison, the EKFC equation underestimates the mGFR at eGFR > 20 mL/min per 1.73 m2 in both Black and White individuals. The REFIT equation had the least absolute median bias as compared to EKFC and CKD-EPI in both Black and White participants (p < 0.0001). The P30 of the REFIT and EKFC equations was not statistically different for either Black or White participants (p = 0.16, p = 0.37). Conclusions: Although the accuracies (P30) of the EKFC and REFIT equations are not statistically significant (p = 0.16 and 0.37, Black and White individuals, respectively), adopting the EKFC formula in Americans requires the evaluation of each subpopulation. Both the EKFC and REFIT formulas underestimate the mGFR at a lower eGFR, which may have a direct impact on CKD classification for Black and White patients, with potentially significant implications for clinical management. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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11 pages, 1003 KB  
Article
Impact of Removing Race Coefficient from Glomerular Filtration Rate Estimation Equations on Antidiabetics Among Black Patients
by Dhakrit Rungkitwattanakul, Ebony Evans, Ewanna Brown, Kent Patterson Jr., Weerachai Chaijamorn, Taniya Charoensareerat, Sanaa Belrhiti, Uzoamaka Nwaogwugwu and Constance Mere
Pharmacy 2025, 13(2), 52; https://doi.org/10.3390/pharmacy13020052 - 2 Apr 2025
Viewed by 819
Abstract
Background: In 2021, the National Kidney Foundation–American Society of Nephrology (NKF-ASN) recommended the use of the 2021 refit equation without race; however, the effect of the removal is unclear. Our research aimed to examine the implications of antidiabetic dosing and eligibility on the [...] Read more.
Background: In 2021, the National Kidney Foundation–American Society of Nephrology (NKF-ASN) recommended the use of the 2021 refit equation without race; however, the effect of the removal is unclear. Our research aimed to examine the implications of antidiabetic dosing and eligibility on the new 2021 equation among Black patients. Methods: This is a retrospective analysis of patients receiving care at the diabetes treatment center (DTC) of an academic medical center. Estimated glomerular filtration rates (eGFRs) based on serum creatinine were calculated using the 2009 and 2021 CKD-EPI equations. A Monte Carlo simulation was performed to create 10,000 virtual patients. Dosing simulations based on each estimate of kidney function were performed for antidiabetics based on product labeling. The proportion and percentage of patients who were eligible based on the estimates were calculated. Results: The percentages of patients ineligible for metformin based on the estimates from the 2009 and 2021 CKD-EPI equations at the DTC were comparable (8.02% and 8.36%, respectively). In our 10,000 simulated virtual patients, the percentage of ineligibility increased only by 1%. For the GFR cut points of 20 mL/min and 25 mL/min, the rates of ineligibility were similar in our cohort and simulated patients. Conclusions: The exclusion of race from the 2021 CKD-EPI equation may slightly reduce medication eligibility among Black patients. Full article
(This article belongs to the Special Issue Medication Use and Patient Safety in Clinical Pharmacy)
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11 pages, 1032 KB  
Article
The Patient and Treatment Characteristics of Kidney Transplant Recipients with a Clinically Relevant Jaffe/Enzymatic Serum Creatinine Difference
by Kristina Boss, Susanne Stolpe, André Müller, Justa Friebus-Kardash, Bernd Wagner, Marc Wichert, Roland Assert, Lothar Volbracht, Andreas Stang, Bernd Kowall and Andreas Kribben
J. Clin. Med. 2025, 14(5), 1668; https://doi.org/10.3390/jcm14051668 - 28 Feb 2025
Cited by 1 | Viewed by 1198
Abstract
Background: Differences in serum creatinine (SCr) between the Jaffe and enzymatic methods affect the detection and staging of chronic kidney disease in kidney transplant recipients (KTRs). However, there are very limited data on the extent to which the detection of acute kidney injury [...] Read more.
Background: Differences in serum creatinine (SCr) between the Jaffe and enzymatic methods affect the detection and staging of chronic kidney disease in kidney transplant recipients (KTRs). However, there are very limited data on the extent to which the detection of acute kidney injury (AKI) is affected, what impact immunosuppression can have and whether a KTR-specific estimated glomerular filtration rate (eGFR) formula is beneficial. Methods: A total of 12,081 parallel Jaffe/enzymatic SCr (eSCr) measurements of adult outpatient KTRs (61% male, median age 53 years) in the same serum sample at the University Hospital Essen (Germany) between January 2020 and October 2023 were evaluated. AKI and CKD were defined according to current KDIGO guidelines. The GFR was estimated using CKD-EPI and KTR-specific formulas. Results: In about 1% of all measurements and 5% of the KTR patients, the SCr difference between the two methods was ≥ 0.3 mg/dl. A total of 81% of these patients were male; the median age was 52 years. High levels of immunosuppression, including when Belatacept was used, did not seem to have a clinically relevant impact on the difference between Jaffe and eSCr. The KTR-specific eGFR formula generally showed a greater agreement between Jaffe and eSCr than the CKD-EPI eGFR formula, but they showed differences in the classification of CKD stages, especially in less severe stages. Conclusions: Clinically relevant SCr differences between Jaffe and SCr are rare and depend on the type of immunosuppression. A KTR-specific eGFR formula could be beneficial in some cases, but there are limitations in less severe CKD stages. Full article
(This article belongs to the Section Nephrology & Urology)
19 pages, 2188 KB  
Article
Assessment of Vitamin D Metabolism Disorders in Hemodialysis Patients
by Maksymilian Hryciuk, Zbigniew Heleniak, Sylwia Małgorzewicz, Konrad Kowalski, Jędrzej Antosiewicz, Anna Koelmer, Michał Żmijewski and Alicja Dębska-Ślizień
Nutrients 2025, 17(5), 774; https://doi.org/10.3390/nu17050774 - 22 Feb 2025
Cited by 1 | Viewed by 1476
Abstract
Background: Patients with end-stage chronic diseases, especially those undergoing hemodialysis (HD), often experience mineral bone disease (MBD), leading to hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone (PTH). Vitamin D deficiency and metabolism disorders are also common, resulting from impaired conversion of 25(OH)D3 to its [...] Read more.
Background: Patients with end-stage chronic diseases, especially those undergoing hemodialysis (HD), often experience mineral bone disease (MBD), leading to hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone (PTH). Vitamin D deficiency and metabolism disorders are also common, resulting from impaired conversion of 25(OH)D3 to its active form, 1,25(OH)2D3, and reduced inactivation to 24,25(OH)2D3. This study aimed to assess the levels of 25(OH)D2, 25(OH)D3, 24,25(OH)2D3, 3-epi-25(OH)D3, and the vitamin D metabolism ratio (VMR) in patients with maintenance HD. Methods: A cross-sectional study was conducted on 66 HD patients (22–90 years, average 61.3 ± 16.4), with a control group of 206 adults without chronic kidney disease (CKD), both without cholecalciferol supplementation. Results: the HD patients had significantly lower 25(OH)D3 levels (15 ng/mL vs. 22 ng/mL) and higher deficiency rates (69% vs. 39%) compared to the controls. However, both groups showed similarly low levels of optimal vitamin D3. The HD patients had lower 24,25(OH)D3 levels (0.1 vs. 2.1 ng/mL) and a lower VMR (0.9% vs. 9%). 3-epi-25(OH)D3 levels and its ratio to 25(OH)D3 were significantly lower in the HD group. Alphacalcidol supplementation raised 1,25(OH)2D3 levels (30.4 vs. 16.2 pg/mL) without affecting other vitamin D metabolites. The HD patients had higher levels of 25(OH)D2 compared to the controls (0.61 vs. 0.31 ng/mL). Conclusions: Vitamin D3 reserves are lower, and both functional deficiency and impaired catabolism of vitamin D3 are present in HD patients compared to the general population. The VMR index is the most sensitive parameter for vitamin D3 deficiency assessment, highlighting the importance of measuring 24,25(OH)D3. Alphacalcidol supplementation increases 1,25(OH)2D3 levels without affecting other vitamin D metabolites. 25(OH)D2 is the only metabolite that was higher in HD patients than the controls. Full article
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10 pages, 506 KB  
Article
Efficacy and Safety of Phase 1 of Very Low Energy Ketogenic Therapy (VLEKT) in Subjects with Obesity and Mild Renal Impairment
by Ludovica Verde, Luigi Barrea, Martina Galasso, Stefania Lucà, Elisabetta Camajani, Antonio Pisani, Annamaria Colao, Massimiliano Caprio and Giovanna Muscogiuri
Nutrients 2025, 17(4), 721; https://doi.org/10.3390/nu17040721 - 18 Feb 2025
Cited by 2 | Viewed by 1938
Abstract
Background: Obesity impairs renal function through direct mechanisms, such as proinflammatory adipocytokine production, and indirect mechanisms, including obesity-related comorbidities. Despite the increasing prevalence of obesity and chronic kidney disease (CKD), clinical guidelines for their combined management remain lacking. Very Low Energy Ketogenic Therapy [...] Read more.
Background: Obesity impairs renal function through direct mechanisms, such as proinflammatory adipocytokine production, and indirect mechanisms, including obesity-related comorbidities. Despite the increasing prevalence of obesity and chronic kidney disease (CKD), clinical guidelines for their combined management remain lacking. Very Low Energy Ketogenic Therapy (VLEKT) has demonstrated efficacy in weight loss, but evidence on its safety and efficacy in individuals with obesity and mild renal impairment is limited. This study aimed to assess the efficacy and safety of Phase 1 of VLEKT in individuals with obesity and mild renal impairment. Methods: This cross-sectional study included 73 individuals with overweight or obesity (mean age 53.7 ± 8.8 years; BMI 35.3 ± 4.2 kg/m2) and an estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 m2 (evaluated using the CKD-EPI equation). Anthropometric (weight, BMI, and waist circumference) and biochemical parameters (fasting plasma glucose, insulin, cholesterol profile, triglycerides, AST, ALT, and urea) were collected at baseline and after 45 (±2) days of Phase 1 of VLEKT. Results: At baseline, 54.8% of participants had an eGFR <90 mL/min/1.73 m2, while 45.2% had an eGFR ≥ 90 mL/min/1.73 m2, with no significant differences in sex distribution. After 45 (±2) days of Phase 1 of VLEKT, both groups showed significant reductions in BMI (p < 0.001), waist circumference (p < 0.001), fasting plasma glucose (p ≤ 0.004), insulin (p < 0.001), HOMA-IR (p < 0.001), total cholesterol (p < 0.001), LDL cholesterol (p < 0.001), LDL/HDL ratio (p ≤ 0.002), triglycerides (p ≤ 0.009), AST (p ≤ 0.034), and ALT (p ≤ 0.009). Notably, the eGFR significantly increased in participants with an eGFR < 90 mL/min/1.73 m2 (p < 0.001), while no changes were observed in those with an eGFR ≥ 90 mL/min/1.73 m2. Conclusions: Phase 1 of VLEKT could effectively promote weight loss and metabolic improvements without compromising renal function, even in individuals with obesity and mild renal impairment. Further research is warranted to confirm the efficacy and safety of VLEKT and to assess outcomes across all protocol phases. Full article
(This article belongs to the Special Issue Clinical Impact of Ketogenic Diet)
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18 pages, 5865 KB  
Article
Distinct Urinary Proteome Changes Across Estimated Glomerular Filtration Rate Stages in a Cohort of Black South Africans
by Siyabonga Khoza, Jaya A. George, Previn Naicker, Stoyan H. Stoychev, Rethabile J. Mokoena, Ireshyn S. Govender and June Fabian
Int. J. Mol. Sci. 2025, 26(4), 1740; https://doi.org/10.3390/ijms26041740 - 18 Feb 2025
Viewed by 1094
Abstract
Kidney function parameters including estimated glomerular filtration rate (eGFR) and urine albumin excretion are commonly used to diagnose chronic kidney disease (CKD). However, these parameters are relatively insensitive, limiting their utility for screening and early detection of kidney disease. Studies have suggested that [...] Read more.
Kidney function parameters including estimated glomerular filtration rate (eGFR) and urine albumin excretion are commonly used to diagnose chronic kidney disease (CKD). However, these parameters are relatively insensitive, limiting their utility for screening and early detection of kidney disease. Studies have suggested that urinary proteomic profiles differ by eGFR stage, offering potential insights into kidney disease pathogenesis alongside opportunities to increase the sensitivity of current testing strategies. In this study, we characterized and compared the urinary proteome across different eGFR stages in a Black African cohort from rural Mpumalanga Province, South Africa. We stratified 81 urine samples by eGFR stage (mL/min/1.73 m2): Stage G1 (eGFR ≥ 90; n = 36), Stage G2 (eGFR 60–89; n = 35), and Stage G3–G5 (eGFR < 60; n = 10). Urine proteomic analysis was performed using an Evosep One liquid chromatography system coupled to a Sciex 5600 TripleTOF in data-independent acquisition mode. Nonparametric multivariate analysis and receiver operating characteristic (ROC) curves were used to assess the performance of differentially abundant proteins (DAPs). Pathway analysis was performed on DAPs. Creatinine-based eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. In this study, thirty-eight urinary proteins were differentially abundant for eGFR Stages 3–5 when compared to Stages G1 (AUC = 0.95; CI: 0.86–1) and G2 (AUC = 0.84; CI: 0.64–0.98). Notably, only six urinary proteins (Cystatin M (CST6), glutathione hydrolase 6 (GGT6), sushi domain containing 2 (SUSD2), insulin-like growth factor binding protein 6 (IGFBP6), heat shock protein 90 beta family member 1 (HSP90B1), and mannosidase alpha class 1A member 1 (MAN1A1)) were differentially abundant when comparing Stage G1 and Stage G2 with a modest AUC = 0.81 (CI: 0.67–0.92). Pathway analysis indicated that DAPs were associated with haemostasis and fibrin clot formation. In a rural cohort from South Africa, the urinary proteome differed by eGFR stage, and we identified six differentially abundant proteins which, in combination, could help to differentiate earlier eGFR stages with higher predictive accuracy than the currently available tests. Full article
(This article belongs to the Special Issue Molecular Research in Chronic Kidney Disease)
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15 pages, 1769 KB  
Article
Switching to the CKD-EPI but Not Modified FAS eGFR Formula Underdetects CKD Among Adolescents and Young Adults in México
by Alethia Paulina Monserrat Guzmán Núñez, Guido Filler, Olivier C. Barbier, Elodia Rojas Lima, Pablo Mendez-Hernández, Manolo Ortega-Romero, Maria Esther Díaz González de Ferris and Mara Medeiros
Children 2025, 12(2), 239; https://doi.org/10.3390/children12020239 - 17 Feb 2025
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Abstract
Background: Guidelines recommend switching the glomerular filtration rate (eGFR) estimation from the CKiD-U25 to the CKD-EPI formula at age 18. We investigated how this would affect chronic kidney disease (CKD) classification. Methods: Serum creatinine was enzymatically measured in 1061 samples from 914 community-based [...] Read more.
Background: Guidelines recommend switching the glomerular filtration rate (eGFR) estimation from the CKiD-U25 to the CKD-EPI formula at age 18. We investigated how this would affect chronic kidney disease (CKD) classification. Methods: Serum creatinine was enzymatically measured in 1061 samples from 914 community-based 10–23-year-olds from Tlaxcala, Mexico, a region where urinary biomarkers demonstrated early kidney damage associated with exposure to inorganic toxins in a pediatric population. We calculated their eGFR using CKiD-U25, modified Schwartz, the first and modified Pottel full-age spectrum (FAS), and CKD-EPI formulae. Correlation analysis characterized the CKD stage stratified by age and sex. Results: At baseline, the median age was 13 (IQR: 12, 15) years, and 55% were female. Median CKiD-U25 eGFR was 96.9 (IQR: 83.3, 113.3) mL/min/1.73 m2, significantly lower than the CKD-EPI eGFR, which was 140.8 (IQR: 129.9, 149.3) mL/min/1.73 m2 (p < 0.0001, Wilcoxon rank test). The mean bias was 36.99 ± 12.89 mL/min/1.73 m2. Pearson correlation was r = 0.8296 (95% confidence interval 0.0898–0.8474). There was a better correlation between the modified Schwartz (r = 0.9421 (0.9349, 0.9485)) and the Pottel FAS (r = 0.9299 (0.9212, 0.9376)) formulae. Agreement was deficient when the eGFR was >75 mL/min/1.73 m2 in younger age and female sex. Modified Schwartz identified 281 (26.4%) measurements as having CKD 2 and 3 (2+), U25 identified 401 (37.7%) measurements as having CKD 2+, FAS identified 267 (25.1%) and modified FAS identified 282 (30%) measurements as having CKD 2+, and CKD-EPI identified 51 (4.8%) measurements as having CKD 2+, respectively. Conclusions: In this population, there needed to be better agreement between the various eGFR formulae. CKD-EPI identifies substantially fewer at-risk participants as having CKD. Full article
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14 pages, 1570 KB  
Article
Effect of Combined Proteinuria and Increased Renal Resistive Index on Chronic Kidney Disease Progression: A Retrospective Longitudinal Study
by Giulio Romano, Nicholas Fiorini, Martina Bertoni, Stefania Rondinella, Laura Di Pietra, Marco F. Cola, Paolo De Martin, Maurizio Tonizzo, Lorenzo Desinan, Benedetta Boari, Roberto Manfredini and GianLuca Colussi
J. Clin. Med. 2025, 14(1), 228; https://doi.org/10.3390/jcm14010228 - 3 Jan 2025
Viewed by 1445
Abstract
Introduction: An increased renal resistive index (RRI) and proteinuria can predict an estimated glomerular filtration rate (eGFR) decline in patients with chronic kidney disease (CKD) of various causes. This study hypothesized that the RRI and proteinuria interact to determine disease progression in patients [...] Read more.
Introduction: An increased renal resistive index (RRI) and proteinuria can predict an estimated glomerular filtration rate (eGFR) decline in patients with chronic kidney disease (CKD) of various causes. This study hypothesized that the RRI and proteinuria interact to determine disease progression in patients with CKDs of unknown origin. Patients and Methods: One hundred and fifty six patients (age 76.0 ± 8.1 years, 63.5% males) were analyzed for anthropometric, kidney morphology, blood pressure, 24 h urinary protein excretion, and RRI. The CKD-EPI equation was used to calculate the eGFR at baseline and after a two-year follow-up. Patients with an elevated (≥0.80) or normal (<0.80) RRI and significant (≥150 mg/day) or physiological (<150 mg/day) proteinuria were evaluated for the likelihood of at least a 30% drop in the eGFR or the onset of end-stage kidney disease (endpoint). Results: Hypertension and diabetes were the predominant cardiovascular risk factors (90.4%). Fifty patients (32%) met the endpoint. Elevated RRIs (odds ratio, OR, 4.28; 95% confidence interval, CI, 1.82–10.6; p = 0.001) and significant proteinuria (OR 3.59, 95% CI 1.59–8.48, p = 0.003) were independent predictors of the endpoint in a multivariate logistic model. Patients with an elevated RRI and significant proteinuria were more likely to meet the endpoint (R1P1: 65.2%) compared to those with only proteinuria (R0P1: 39.5%, p = 0.043) or both normal factors (R0P0: 10.9%, p < 0.001) but not to those with only an elevated RRI (R1P0: 42.3%, p = 0.094). Continuous RRIs (partial correlation r = −0.245, p < 0.001) and 24 h urinary protein excretion (partial r = −0.226, p = 0.003) were inversely and independently correlated with eGFR% change. R1P1 showed a higher eGFR% reduction (−38.0% ± 20.4%) compared to R0P1 (−25.3% ± 19.0%, p = 0.043) and R0P0 (−8.8% ± 25.1%, p < 0.001) but not to R1P0 (−29.6% ± 21.0%, p = 0.192). Conclusions: An increased RRI and proteinuria were independent predictors of disease progression. When interaction was considered, the negative effect of an elevated RRI on CKD progression was evident in both proteinuric and non-proteinuric patients, whereas the negative effect of proteinuria on disease progression was only significant in patients with no elevated RRIs. Full article
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9 pages, 412 KB  
Article
Accuracy of Estimated Glomerular Filtration Rate Equations in Potential Vietnamese Living Kidney Donors
by Thang Diep, Tam Thai Thanh Tran, Chuan Khac Hoang and Sam Minh Thai
Transplantology 2024, 5(4), 312-320; https://doi.org/10.3390/transplantology5040031 - 21 Dec 2024
Viewed by 1589
Abstract
Background: The accurate assessment of the glomerular filtration rate (GFR) in potential living kidney donors (PLKDs) is essential for successful transplantation and safeguarding kidney donation practice. Scintigraphy-measured GFR (mGFR) is widely regarded as the clinical reference standard. Various estimated GFR (eGFR) equations, [...] Read more.
Background: The accurate assessment of the glomerular filtration rate (GFR) in potential living kidney donors (PLKDs) is essential for successful transplantation and safeguarding kidney donation practice. Scintigraphy-measured GFR (mGFR) is widely regarded as the clinical reference standard. Various estimated GFR (eGFR) equations, such as the Modification of Diet in Renal Disease (MDRD), Cockcroft–Gault (CG), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, have been developed; however, none have been specifically validated for Vietnamese PLKDs. This study aimed to evaluate the accuracy of eGFR formulas compared to mGFR in PLKDs. Methods: This convenience retrospective study analyzed 189 PLKDs at Cho Ray Hospital in Vietnam from January 2014 to December 2020. The eGFR was calculated using various formulas and compared to the mGFR assessed using 99mTechnetium-diethylenetriaminepentaacetic acid. Bias, accuracy, and Bland–Altman plots were used to assess the significance of the eGFR values. Results: The median mGFR was 94.20 mL/min/1.73 m2 (interquartile range [IQR]: 88.40–100.50). The eGFR values were as follows: 77.52 mL/min/1.73 m2 (IQR: 70.50–86.33) for CG; 76.14 mL/min/1.73 m2 (IQR: 68.05–83.37) for MDRD; 106.80 ± 15.24 mL/min/1.73 m2 for CKD-EPI cystatin C 2012; 96.44 ± 13.40 mL/min/1.73 m2 for CKD-EPI creatinine cystatin C 2012; 88.74 ± 13.27 mL/min/1.73 m2 for CKD-EPI creatinine 2021; and 101.32 ± 12.82 mL/min/1.73 m2 for CKD-EPI creatinine cystatin C 2021. Among these formulas, the CKD-EPI creatinine cystatin C 2012 (P30 = 98.96%) and 2021 (P30 = 97.92%) showed the best consistency with the mGFR, owing to their high accuracy, low bias, and narrow limits of agreement in the Bland–Altman plots. Conclusions: The CKD-EPI equations based on creatinine and cystatin C are reliable tools for donor screening. Full article
(This article belongs to the Section Solid Organ Transplantation)
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