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Search Results (1,343)

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11 pages, 864 KiB  
Article
The Added Value of Controlling Nutritional Status (Conut) Score for Preoperative Counselling on Significant Early Loss of Renal Function after Radical Nephrectomy for Renal Cell Carcinoma
by Matteo Boltri, Fabio Traunero, Luca Ongaro, Francesca Migliozzi, Fabio Vianello, Oliviero Lenardon, Francesco Visalli, Lorenzo Buttazzi, Daniele Maruzzi, Carlo Trombetta, Alchiede Simonato, Nicola Pavan and Francesco Claps
Cancers 2024, 16(20), 3519; https://doi.org/10.3390/cancers16203519 - 17 Oct 2024
Viewed by 170
Abstract
Background and Objectives: We aimed at evaluating the impact of Controlling Nutritional Status (CONUT) score on clinically significant decline in estimated glomerular filtration rate (eGFR) in patients with non-metastatic Clear Cell Renal Cell Carcinoma (ccRCC) undergoing radical nephrectomy (RN). Materials and methods: We [...] Read more.
Background and Objectives: We aimed at evaluating the impact of Controlling Nutritional Status (CONUT) score on clinically significant decline in estimated glomerular filtration rate (eGFR) in patients with non-metastatic Clear Cell Renal Cell Carcinoma (ccRCC) undergoing radical nephrectomy (RN). Materials and methods: We retrospectively analyzed a multi-institutional cohort of 140 patients with ccRCC who underwent RN between 2016 and 2018 at three Urological Centers. The CONUT score was calculated with an algorithm including serum albumin, total lymphocyte count, and cholesterol. Clinical and pathologic features were analyzed using Fisher’s exact test for categorical variables and a Mann–Whitney U test for continuous variables. To define the independent predictors of clinically significant eGFR decline, univariable (UVA) and multivariable (MVA) binomial logistic regression analyses were performed in order to assess the Odds Ratio (OR) with 95% Confidence Intervals (CIs). Results: The optimal cut-off value to discriminate between a low and high CONUT score was assessed by calculating the ROC curve. The area under the curve (AUC) was 0.67 (95%CI 0.59–0.78) with the most appropriate cut-off value at 2 points. Overall, 46 patients (32.9%) had a high CONUT score (>2). Statistically significant variables associated with eGFR decline at 24 months were age ≥ 70 (OR 2.01; 95%CI 1.17–3.09; p 0.05), stage II–III chronic kidney disease (CKD) (OR 6.05; 95%CI 1.79–28.3; p 0.001), and a high CONUT score (OR 3.98; 95%CI 1.58–10.4; p 0.004). Conclusions: The CONUT score is a low-time-consuming, cost-effective, and promising tool able to preoperatively screen patients at risk of developing CKD after a RN. Full article
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<p>Receiver operating characteristic (ROC) curve for preoperative prediction of clinically significant eGFR decline defined as the development of a stage ≥ IIIb CKD (eGFR &lt; 45 mL/min) at 24 months after RN. Abbreviations are as follows: eGFR: estimated glomerular filtration rate; CKD: chronic kidney disease; RN: radical nephrectomy.</p>
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<p>Receiver operating characteristic (ROC) curves for preoperative prediction of clinically significant eGFR decline defined as the development of a stage ≥ IIIb CKD (eGFR &lt; 45 mL/min) at 24 months after RN: (<b>a</b>) age ≥ 70 years old, AUC 0.61 (95%CI, 0.51–0.70); (<b>b</b>) preoperative CKD stage (II–IIIa), AUC 0.53 (95%CI, 0.43–0.62). Abbreviations are as follows: eGFR: estimated glomerular filtration rate; CKD: chronic kidney disease; RN: radical nephrectomy; AUC: area under the curve; CIs: Confidence Intervals.</p>
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17 pages, 696 KiB  
Systematic Review
Safety and Efficacy of Sodium-Glucose Transport Protein 2 Inhibitors and Glucagon-like Peptide-1 Receptor Agonists in Diabetic Kidney Transplant Recipients: Synthesis of Evidence
by Ioannis Bellos, Pagona Lagiou, Vassiliki Benetou and Smaragdi Marinaki
J. Clin. Med. 2024, 13(20), 6181; https://doi.org/10.3390/jcm13206181 - 17 Oct 2024
Viewed by 184
Abstract
Background: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of novel antidiabetics, namely, sodium-glucose transport protein 2 inhibitors (SGLT2-i) and glucagon-like peptide-1 receptor agonists (GLP1-RA), in diabetic kidney transplant recipients. Methods: Medline, Scopus, Web of Science, CENTRAL, and Clinicaltrials.gov [...] Read more.
Background: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of novel antidiabetics, namely, sodium-glucose transport protein 2 inhibitors (SGLT2-i) and glucagon-like peptide-1 receptor agonists (GLP1-RA), in diabetic kidney transplant recipients. Methods: Medline, Scopus, Web of Science, CENTRAL, and Clinicaltrials.gov were systematically searched from inception until 25 August 2024. Pooled estimates were obtained by applying random-effects models. Results: Overall, 18 studies (17 observational studies and one randomized controlled trial) were included. GLP1-RA were administered to 270 and SGLT2-i to 1003 patients. After GLP1-RA therapy, patients presented significantly lower glycated hemoglobin [mean difference (MD): −0.61%; 95% confidence interval (CI): −0.99; −0.23] and body weight (MD: −3.32 kg; 95% CI: −5.04; −1.59) but a similar estimated glomerular filtration rate (eGFR) and systolic blood pressure. After SGLT2-i therapy, patients had significantly lower glycated hemoglobin (MD: −0.40%, 95% CI: −0.57; −0.23) and body weight (MD: −2.21 kg, 95% CI: −2.74; −1.67), while no difference was noted in eGFR or systolic blood pressure. Preliminary data have shown an association between SGLT2-i use and a reduced risk of cardiovascular events, graft loss, and mortality. Evidence regarding the association between GLP1-RA and SGLT2-i and proteinuria was mixed. No significant effects on calcineurin inhibitor levels were observed. The risk of urinary tract infections was similar among patients treated with SGLT2-i or placebo (odds ratio: 0.84, 95% CI: 0.43; 1.64). Conclusions: Observational data suggest that GLP1-RA and SGLT2-i administration in diabetic kidney transplant recipients may be associated with better glycemic control and reduced body weight, presenting an acceptable safety profile. Full article
(This article belongs to the Special Issue Recent Advances and Complications of Kidney Transplantation)
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<p>Search plot diagram.</p>
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12 pages, 682 KiB  
Article
Relationship Between Serum Uromodulin as a Marker of Kidney Damage and Metabolic Status in Patients with Chronic Kidney Disease of Non-Diabetic Etiology
by Radmila Žeravica, Branislava Ilinčić, Dragan Burić, Ana Jakovljević, Veljko Crnobrnja, Dalibor Ilić and Marija Vukmirović Papuga
Int. J. Mol. Sci. 2024, 25(20), 11159; https://doi.org/10.3390/ijms252011159 - 17 Oct 2024
Viewed by 219
Abstract
Chronic kidney disease (CKD) is often associated with dyslipidemia, marked by lipid abnormalities that can worsen kidney function and increase cardiovascular risk. A promising biomarker for evaluating kidney function and metabolic status in chronic kidney disease (CKD) is serum uromodulin (sUmod). This study [...] Read more.
Chronic kidney disease (CKD) is often associated with dyslipidemia, marked by lipid abnormalities that can worsen kidney function and increase cardiovascular risk. A promising biomarker for evaluating kidney function and metabolic status in chronic kidney disease (CKD) is serum uromodulin (sUmod). This study sought to further investigate the relationship between sUmod levels and metabolic status in non-diabetic CKD patients. A sensitive ELISA method was used to determine sUmod levels in 90 adults with obstructive nephropathy and 30 healthy controls. Kidney function was assessed using the measured glomerular filtration rate (mGFR) through renal clearance of 99mTc-diethylenetriamine penta-acetic acid, along with cystatin C levels. Additionally, glycemic and lipid statuses were evaluated. sUmod concentrations showed a significant association with High-density lipoprotein (HDL) levels. Furthermore, CKD patients with lower sUmod levels had significantly lower Apolipoprotein A-I (Apo A-I) values compared to the control group. Significant predictors of lower sUmod concentrations identified in this study were higher glycemia (B = −15.939; p = 0.003) and lower HDL cholesterol levels (B = 20.588; p = 0.019). We conclude that, in addition to being significantly reduced in CKD patients, sUmod is a potential predictor of metabolic syndrome (MS) in this population. Lower sUmod concentrations, independent of mGFR, predict lower HDL cholesterol levels and higher glycemia values. Full article
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<p>A two-way between-groups analysis of variance to explore the impact of sex and mGFR (measured glomerular filtration rate) (CKD status) on sUmod (serum uromodulin) level.</p>
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<p>Correlation between sUmod (serum uromodulin) concentration and mGFR (measured glomerular filtration rate).</p>
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13 pages, 679 KiB  
Article
Adverse Events of Radioligand Therapy in Patients with Progressive Neuroendocrine Neoplasms: The Biggest Eastern European Prospective Study
by Adam Daniel Durma, Marek Saracyn, Maciej Kołodziej, Katarzyna Jóźwik-Plebanek, Dorota Brodowska-Kania, Beata Dmochowska, Adrianna Mróz, Beata Kos-Kudła and Grzegorz Kamiński
Cancers 2024, 16(20), 3509; https://doi.org/10.3390/cancers16203509 - 17 Oct 2024
Viewed by 177
Abstract
Background: Neuroendocrine neoplasms (NENs) are neoplastic tumors developing in every part of the body, mainly in the gastrointestinal tract and pancreas. Their treatment involves the surgical removal of the tumor and its metastasis, long-acting somatostatin analogs, chemotherapy, targeted therapy, and radioligand therapy (RLT). [...] Read more.
Background: Neuroendocrine neoplasms (NENs) are neoplastic tumors developing in every part of the body, mainly in the gastrointestinal tract and pancreas. Their treatment involves the surgical removal of the tumor and its metastasis, long-acting somatostatin analogs, chemotherapy, targeted therapy, and radioligand therapy (RLT). Materials and Methods: A total of 127 patients with progressive neuroendocrine neoplasms underwent RLT—4 courses, administered every 10 weeks—with the use of 7.4 GBq [177Lu]Lu-DOTA-TATE or tandem therapy with 1.85 GBq [177Lu]Lu-DOTA-TATE and 1.85 GBq [90Y]Y-DOTA-TATE. Assessment of short- and long-term complications, as well as the calculation of progression-free survival (PFS) and overall survival (OS) were performed. Results: RLT caused a statistically but not clinically significant decrease in blood morphology parameters during both short- and long-term observations. Glomerular filtration rate (GFR) significantly decreased only in a long-term observation after RLT; however, it was clinically acceptable. Computed predictions of progression-free survival (PFS) and overall survival (OS) indicated that five years post-RLT, there is a 74% chance of patients surviving, with only a 58.5% likelihood of disease progression. Conclusions: Computed predictions of PFS and OS confirmed treatment efficiency and good patient survival. RLT should be considered a safe and reliable line of treatment for patients with progressive NENs as it causes only a low number of low-grade adverse events. Full article
(This article belongs to the Special Issue Radioligand Therapy (RLT) in Neuroendocrine Neoplasms)
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<p>Overall survival probability calculations.</p>
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<p>Progression-free survival probability calculations.</p>
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19 pages, 494 KiB  
Review
The Potential Use of Targeted Proteomics and Metabolomics for the Identification and Monitoring of Diabetic Kidney Disease
by Nele Van Roy and Marijn M. Speeckaert
J. Pers. Med. 2024, 14(10), 1054; https://doi.org/10.3390/jpm14101054 - 11 Oct 2024
Viewed by 395
Abstract
Diabetic kidney disease (DKD) is a prevalent microvascular complication of diabetes mellitus and is associated with a significantly worse prognosis compared to diabetic patients without kidney involvement, other microvascular complications, or non-diabetic chronic kidney disease, due to its higher risk of cardiovascular events, [...] Read more.
Diabetic kidney disease (DKD) is a prevalent microvascular complication of diabetes mellitus and is associated with a significantly worse prognosis compared to diabetic patients without kidney involvement, other microvascular complications, or non-diabetic chronic kidney disease, due to its higher risk of cardiovascular events, faster progression to end-stage kidney disease, and increased mortality. In clinical practice, diagnosis is based on estimated glomerular filtration rate (eGFR) and albuminuria. However, given the limitations of these diagnostic markers, novel biomarkers must be identified. Omics is a new field of study involving the comprehensive analysis of various types of biological data at the molecular level. In different fields, they have shown promising results in (early) detection of diseases, personalized medicine, therapeutic monitoring, and understanding pathogenesis. DKD is primarily utilized in scientific research and has not yet been implemented in routine clinical practice. The aim of this review is to provide an overview of currently available data on targeted omics. After an extensive literature search, 25 different (panels of) omics were withheld and analyzed. Both serum/plasma and urine proteomics and metabolomics have been described with varying degrees of evidence. For all omics, there is still a relative paucity of data from large, prospective, longitudinal cohorts, presumably because of the heterogeneity of DKD and the lack of patient selection in studies, the complexity of omics technologies, and various practical and ethical considerations (e.g., limited accessibility, cost, and privacy concerns). Full article
(This article belongs to the Section Omics/Informatics)
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<p>Summary of literature search.</p>
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9 pages, 1835 KiB  
Article
Acute Effect of Three Aerobic Exercise Intensities on Glomerular Filtration Rate in Healthy Older Adults
by Marina Trejo-Trejo, Luis M. Gómez-Miranda and Arnulfo Ramos-Jiménez
Diseases 2024, 12(10), 249; https://doi.org/10.3390/diseases12100249 - 11 Oct 2024
Viewed by 378
Abstract
No consensus exists on whether acute aerobic exercise alters the glomerular filtration rate in older adults. Objective: To assess the immediate effects of three aerobic exercise intensities on the estimated glomerular filtration rate (eGFR) in healthy, sedentary older adults. Methods: Eighteen healthy, sedentary [...] Read more.
No consensus exists on whether acute aerobic exercise alters the glomerular filtration rate in older adults. Objective: To assess the immediate effects of three aerobic exercise intensities on the estimated glomerular filtration rate (eGFR) in healthy, sedentary older adults. Methods: Eighteen healthy, sedentary older adults (ten men and eight women) voluntarily participated in this study. The participants underwent three standardized aerobic exercise tests (100%, 80%, and 60% of the maximal heart rate) on a bicycle ergometer. Blood samples were collected to determine cholesterol, triacylglycerols, glucose, serum creatinine (Cr), Cystatin C (CysC) concentrations, and eGFR. Results: eGFR and serum concentrations of Cr and CysC were not modified at any exercise intensity. There was a negative correlation between blood total cholesterol vs. eGFR (R = −0.512, R = −0.582, R = −0.531; p < 0.05) at rest, 60%, and 100% of the maximal heart rate, respectively. In addition, a negative correlation existed for age vs. eGFR at 60% of the maximal heart rate (R = −0.516; p < 0.05). Conclusions: Short-duration aerobic exercise of low, moderate, and vigorous intensity did not significantly affect eGFR and is considered safe for kidney function in healthy, sedentary older adults. However, regular monitoring of kidney function in older people engaged in moderate- and high-intensity exercise is advised. Full article
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<p>Screened participation.</p>
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<p>Research protocol.</p>
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<p>Effect of exercise tests on serum concentration of (<b>a</b>) Cystatin C, (<b>b</b>) creatinine, and estimated glomerular filtration rate (eGFR) calculated by serum concentration of (<b>c</b>) Cystatin C (CysC) and (<b>d</b>) creatinine (Cr).</p>
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10 pages, 764 KiB  
Article
Effect of Difference in Serum Creatinine between Jaffe and Enzymatic Methods in Outpatient Kidney Transplant Recipients
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. 2024, 13(20), 6066; https://doi.org/10.3390/jcm13206066 - 11 Oct 2024
Viewed by 326
Abstract
Background: Deviations in serum creatinine (SCr), due to its determination using a Jaffe or an enzymatic method, have an effect on kidney disease detection and staging. It is not yet clear how large this effect is in kidney transplant recipients (KTRs). SCr measurement [...] Read more.
Background: Deviations in serum creatinine (SCr), due to its determination using a Jaffe or an enzymatic method, have an effect on kidney disease detection and staging. It is not yet clear how large this effect is in kidney transplant recipients (KTRs). SCr measurement differences are of particular importance here to evaluate the graft function. Methods: The results of all parallel SCr measurements (Jaffe and enzymatic method) of adult outpatient KTRs in the same serum sample at the University Hospital Essen (Germany) between January 2020 and October 2023 were evaluated. A Bland–Altman plot with 95% limits of agreement (LoA) was used to assess the difference between the Jaffe and the enzymatic SCr (eSCr). For all patients, we used the CKD-EPI 2009 and EKFC formula, and for patients ≥ 70 years, we also used the BIS1 formula for the determination of eGFR. Results: A total of 12,081 parallel SCr measurements from 1243 KTRs were analyzed, where 61% were male and the median age was 53 years. On average, Jaffe SCr was 0.03 mg/dL higher than eSCr (LoA −0.16; 0.21 mg/dL). On average, the eGFR determined by Jaffe SCr was 1.9 mL/min/1.73 m2 lower than the eGFR determined by eSCr (LoA −9.5; 5.7 mL/min/1.73 m2). The comparison of eGFR between the two SCr methods revealed a different CKD stage in 1589 (13%) of all analyzed measurements, most frequently between G2/G3a (41%) and G3a/G3b (24%). When using the EKFC and BIS1 formulas, there were approximately the same number of measurements leading to a different CKD stage. Conclusions: In more than every tenth SCr determination in outpatient KTRs, the difference between the Jaffe and enzymatic methods had an influence on the assignment to a CKD stage. This effect was comparably pronounced for all eGFR formulas applied. Full article
(This article belongs to the Section Nephrology & Urology)
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<p>Serum creatinine difference between Jaffe and enzymatic measurement methods.</p>
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<p>eGFR difference between Jaffe and enzymatic serum creatinine measurement methods.</p>
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12 pages, 614 KiB  
Article
Surgical Experience and Functional Outcomes after Laparoscopic and Robot-Assisted Partial Nephrectomy: Results from a Multi-Institutional Collaboration
by Carlo Andrea Bravi, Paolo Dell’Oglio, Angela Pecoraro, Zine-Eddine Khene, Riccardo Campi, Pietro Diana, Chiara Re, Carlo Giulioni, Alp Tuna Beksac, Riccardo Bertolo, Tarek Ajami, Kennedy Okhawere, Margaret Meagher, Arman Alimohammadi, Marco Borghesi, Andrea Mari, Daniele Amparore, Marco Roscigno, Umberto Anceschi, Giuseppe Simone, Nazareno Suardi, Antonio Galfano, Riccardo Schiavina, Federico Dehò, Karim Bensalah, Abdullah Erdem Canda, Vincenzo Ferrara, Antonio Alcaraz, Xu Zhang, Carlo Terrone, Shahrokh Shariat, Francesco Porpiglia, Alessandro Antonelli, Jihad Kaouk, Ketan Badani, Andrea Minervini, Ithaar Derweesh, Alberto Breda, Alexandre Mottrie, Francesco Montorsi and Alessandro Larcheradd Show full author list remove Hide full author list
J. Clin. Med. 2024, 13(19), 6016; https://doi.org/10.3390/jcm13196016 - 9 Oct 2024
Viewed by 565
Abstract
Background: In patients treated with partial nephrectomy, prior evidence showed that peri-operative outcomes, such as complications and ischemia time, improved as a function of the surgical experience of the surgeon, but data on functional outcomes after surgery are still scarce. Methods: We retrospectively [...] Read more.
Background: In patients treated with partial nephrectomy, prior evidence showed that peri-operative outcomes, such as complications and ischemia time, improved as a function of the surgical experience of the surgeon, but data on functional outcomes after surgery are still scarce. Methods: We retrospectively analyzed data of 4011 patients with a single, unilateral cT1a-b renal mass treated with laparoscopic or robot-assisted partial nephrectomy. The operations were performed by 119 surgeons at 22 participating institutions between 1997 and 2022. Multivariable models investigated the association between surgical experience (number of prior operations) and acute kidney injury (AKI) and recovery of at least 90% of baseline estimated glomerular filtration rate (eGFR) 1 yr after partial nephrectomy. The adjustment for case mix included age, Body Mass Index, preoperative serum creatinine, clinical T stage, PADUA score, warm ischemia time, pathologic tumor size, and year of surgery. Results: A total of 753 (19%) and 3258 (81%) patients underwent laparoscopic and robot-assisted partial nephrectomy, respectively. Overall, 37 (31%) and 55 (46%) surgeons contributed only to laparoscopic and robotic learning curves, respectively, whereas 27 (23%) contributed to the learning curves of both approaches. In the laparoscopic group, 8% and 55% of patients developed AKI and recovered at least 90% of their baseline eGFR, respectively. After adjusting for confounders, we did not find evidence of an association between surgical experience and AKI after laparoscopic partial nephrectomy (odds ratio [OR]: 0.9992; 95% confidence interval [CI]: 0.9963, 1.0022; p = 0.6). Similar results were found when 1-year renal function was the outcome of interest (OR: 0.9996; 95% CI: 0.9988, 1.0005; p = 0.5). Among patients who underwent robot-assisted partial nephrectomy, AKI occurred in 11% of patients, whereas 54% recovered at least 90% of their baseline eGFR. On multivariable analyses, the relationship between surgical experience and AKI after surgery was not statistically significant (OR: 1.0015; 95% CI: 0.9992, 1.0037; p = 0.2), with similar results when the outcome of interest was renal function one year after surgery (OR: 1.0001; 95% CI: 0.9980, 1.0022; p = 0.9). Virtually the same findings were found on sensitivity analyses. Conclusions: In patients treated with laparoscopic or robot-assisted partial nephrectomy, our data suggest that the surgical experience of the operating surgeon might not be a key determinant of functional recovery after surgery. This raises questions about the use of serum markers to assess functional recovery in patients with two kidneys and opens the discussion on what are the key steps of the procedure that allowed surgeons to achieve optimal outcomes since their initial cases. Full article
(This article belongs to the Special Issue Robot-Assisted Surgery in Urology)
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<p>Probability of recovering at least 90% of baseline eGFR after laparoscopic partial nephrectomy in relation to surgical experience (number of prior operations). Dashed lines are 95% confidence interval.</p>
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<p>Probability of recovering at least 90% of baseline eGFR after robot-assisted partial nephrectomy over surgical experience (number of prior operations). Dashed lines are 95% confidence interval.</p>
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12 pages, 747 KiB  
Article
Elevated Circulating Levels of Gut Microbe-Derived Trimethylamine N-Oxide Are Associated with Systemic Sclerosis
by Karen J. Ho, Lutfiyya N. Muhammad, Linh Ngo Khanh, Xinmin S. Li, Mary Carns, Kathleen Aren, Seok-Jo Kim, Priyanka Verma, Stanley L. Hazen and John Varga
J. Clin. Med. 2024, 13(19), 5984; https://doi.org/10.3390/jcm13195984 - 8 Oct 2024
Viewed by 540
Abstract
Background/Objectives: Alterations in fecal microbial communities in patients with systemic sclerosis (SSc) are common, but the clinical significance of this observation is poorly understood. Gut microbial production of trimethylamine (TMA), and its conversion by the host to trimethylamine N-oxide (TMAO), has clinical [...] Read more.
Background/Objectives: Alterations in fecal microbial communities in patients with systemic sclerosis (SSc) are common, but the clinical significance of this observation is poorly understood. Gut microbial production of trimethylamine (TMA), and its conversion by the host to trimethylamine N-oxide (TMAO), has clinical and mechanistic links to cardiovascular and renal diseases. Direct provision of TMAO has been shown to promote fibrosis and vascular injury, hallmarks of SSc. We sought to determine levels of TMAO and related metabolites in SSc patients and investigate associations between the metabolite levels with disease features. Methods: This is an observational case:control study. Adults with SSc (n = 200) and non-SSc controls (n = 400) were matched for age, sex, indices of renal function, diabetes mellitus, and cardiovascular disease. Serum TMAO, choline, betaine, carnitine, γ-butyrobetaine, and crotonobetaine were measured using stable isotope dilution liquid chromatography tandem mass spectrometry. Results: Median TMAO concentration was higher (p = 0.020) in SSc patients (3.31 [interquartile range 2.18, 5.23] µM) relative to controls (2.85 [IQR 1.88, 4.54] µM). TMAO was highest among obese and male SSc participants compared to all other groups. Following adjustment for sex, BMI, age, race, and eGFR in a quantile regression model, elevated TMAO levels remained associated with SSc at each quantile of TMAO. Conclusions: Patients with SSc have increased circulating levels of TMAO independent of comorbidities including age, sex, renal function, diabetes mellitus, and cardiovascular disease. As a potentially modifiable factor, further studies examining the link between TMAO and SSc disease severity and course are warranted. Full article
(This article belongs to the Special Issue Advances in Clinical Rheumatology)
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<p>Comparative analysis of serum TMAO concentration. Each comparison is shown with and without outlier observations. For the comparison of control and SSc groups, box plots of TMAO in the control and SSc groups is shown with (<b>A</b>) and without (<b>D</b>) the outlier observations in both groups. For the comparison based on SSc group and obesity, box plots of TMAO in each group are shown with (<b>B</b>) and without (<b>E</b>) the outlier observations in the non-obese groups (2 in control group and 1 in SSc group). For the comparison based on SSc group and sex, box plots of TMAO in each group are shown with (<b>C</b>) and without (<b>F</b>) the outlier observations in the female groups (two in control group and one in SSc group). Data shown are median with interquartile range. (<b>G</b>) Quantile regression analysis of the differences in TMAO at each quantile between the SSc and control groups. After adjusting for sex, BMI, age, race, and eGFR, SSc participants had an elevated TMAO level in comparison to control participants at all quantile of TMAO. Quantile regression estimated coefficients at each TMAO quantile are shown in <a href="#jcm-13-05984-t001" class="html-table">Table 1</a>.</p>
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<p>Heat map of serum metabolite concentrations in the SSc cohort. Metabolites are represented in the columns and individual participants are represented in the rows. As described in the text, 7 hierarchical clusters were initially identified and then regrouped into 2 clusters based on sample sizes. The final 2 groups are indicated on the left side of the figure by dark brown (<span class="html-italic">n</span> = 92) or tan (<span class="html-italic">n</span> = 108).</p>
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10 pages, 1635 KiB  
Article
Associations between Kidney Disease Progression and Metabolomic Profiling in Stable Kidney Transplant Recipients—A 3 Year Follow-Up Prospective Study
by Titus Andrian, Lucian Siriteanu, Luminița Voroneanu, Alina Nicolescu, Calin Deleanu, Andreea Covic and Adrian Covic
J. Clin. Med. 2024, 13(19), 5983; https://doi.org/10.3390/jcm13195983 - 8 Oct 2024
Viewed by 474
Abstract
Background: kidney transplant recipients are exposed to multiple pathogenic pathways that may alter short and long-term allograft survival. Metabolomic profiling is useful for detecting potential biomarkers of kidney disease with a predictive capacity. This field is still under development in kidney transplantation and [...] Read more.
Background: kidney transplant recipients are exposed to multiple pathogenic pathways that may alter short and long-term allograft survival. Metabolomic profiling is useful for detecting potential biomarkers of kidney disease with a predictive capacity. This field is still under development in kidney transplantation and metabolome analysis is faced with analytical challenges. We performed a cross-sectional study including stable kidney transplant patients and aimed to search for relevant associations between baseline plasmatic and urinary metabolites and relevant outcomes over a follow-up period of 3 years. Methods: we performed a cross-sectional study including 72 stable kidney transplant patients with stored plasmatic and urinary samples at the baseline evaluation which were there analyzed by nuclear magnetic resonance in order to quantify and describe metabolites. We performed a 3-year follow-up and searched for relevant associations between renal failure outcomes and baseline metabolites. Between-group comparisons were made after classification by observed estimated glomerular filtration rate slope during the follow-up: positive slope and negative slope. Results: The mean estimated GFR (glomerular filtration rate) was higher at baseline in the patients who exhibited a negative slope during the follow-up (63.4 mL/min/1.73 m2 vs. 55.8 mL/min/1.73 m2, p = 0,019). After log transformation and division by urinary creatinine, urinary dimethylamine (3.63 vs. 3.16, p = 0.027), hippuric acid (7.33 vs. 6.29, p = 0.041), and acetone (1.88 vs. 1, p = 0.023) exhibited higher concentrations in patients with a negative GFR slope when compared to patients with a positive GFR slope. By computing a linear regression, a significant low-strength regression equation between the log 2 transformed plasmatic level of glycine and the estimated glomerular filtration rate was found (F (1,70) = 5.15, p = 0.026), with an R2 of 0.069. Several metabolites were correlated positively with hand grip strength (plasmatic tyrosine with r = 0.336 and p = 0.005 and plasmatic leucine with r = 0.371 and p = 0.002). Other urinary metabolites were found to be correlated negatively with hand grip strength (dimethylamine with r = −0.250 and p = 0.04, citric acid with r = −0.296 and p = 0.014, formic acid with r = −0.349 and p = 0.004, and glycine with r = −0.306 and p = 0.01). Conclusions: some metabolites had different concentrations compared to kidney transplant patients with negative and positive slopes, and significant correlations were found between hand grip strength and urinary and plasmatic metabolites. Full article
(This article belongs to the Special Issue Clinical Advancements in Kidney Transplantation)
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<p>Significant differences in urinary metabolites in kidney transplant recipients with different GFR slope trajectories.</p>
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<p>Significant differences in plasmatic metabolites in kidney transplant recipients with different GFR slope trajectories.</p>
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<p>Significant linear relationship between plasmatic Glycine and estimated GFR.</p>
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<p>Correlation plots of statistically significant Pearson’s correlation among quantified metabolites (all log 2 transformed) with each other and with hand grip strength.</p>
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9 pages, 731 KiB  
Article
Impact of SGLT2-Inhibitor Therapy on Survival in Patients with Transthyretin Amyloid Cardiomyopathy: Analysis of a Prospective Registry Study
by Nora Schwegel, Christina Toferer, David K. Zach, Viktoria Santner, Viktoria Höller, Jakob Lugitsch, Markus Wallner, Johannes Gollmer, Faisal Aziz, Dirk von Lewinski, Ewald Kolesnik, Klemens Ablasser, Andreas Zirlik, Harald Sourij and Nicolas Verheyen
J. Clin. Med. 2024, 13(19), 5966; https://doi.org/10.3390/jcm13195966 - 8 Oct 2024
Viewed by 697
Abstract
Background: Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) represent a high-risk heart failure population with continued unmet therapeutic needs. Sodium–glucose co-transporter 2 inhibitors (SGLT2i) improve cardiovascular outcomes in patients with heart failure across the whole spectrum of ejection fraction, and first evidence regarding their [...] Read more.
Background: Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) represent a high-risk heart failure population with continued unmet therapeutic needs. Sodium–glucose co-transporter 2 inhibitors (SGLT2i) improve cardiovascular outcomes in patients with heart failure across the whole spectrum of ejection fraction, and first evidence regarding their safety and effectiveness in patients with ATTR-CM is arising. This study investigates the association between SGLT2i therapy and clinical outcomes in these patients. Methods: This is an analysis of a prospective registry conducted at a referral centre for hypertrophic cardiomyopathies including 116 patients with confirmed ATTR-CM. Fifty-one patients (44%) were treated with SGLT2i while 65 patients (56%) remained SGLT2i-naïve. Results: During a median follow-up of 2.6 (1.7–3.7) years, 38 patients (33%) died, of whom 11 patients (9%) received SGLT2i treatment and 27 patients (23%) were treatment-naïve. SGLT2i therapy was significantly associated with lower mortality (HR 0.457, 95%CI 0.227–0.922, p = 0.029). This association persisted after adjusting for age and sex (HR 0.479, 95%CI 0.235–0.977, p = 0.043) and after additional adjustment for eGFR, NT-proBNP, LVEF, and concomitant therapy with tafamidis (HR 0.328, 95%CI 0.141–0.760, p = 0.009). However, when potential immortal time bias was considered, this association lost statistical significance (HR 1.075, 95%CI 0.524–2.206, p = 0.843). No significant associations between SGLT2i therapy and worsening heart-failure hospitalization or cardiovascular mortality were observed. Conclusions: In crude analysis, SGLT2i therapy associates with better survival in patients with ATTR-CM. However, after adjustment for immortal time, this association becomes statistically insignificant. Hence, to draw final conclusions on the effectiveness of SGLT2i therapy in these patients, a randomized controlled trial is warranted. Full article
(This article belongs to the Special Issue Advances in Diagnosis and Treatment of Amyloidosis)
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<p>Flow chart of patient disposition. Patient disposition and Sodium–glucose co-transporter 2 inhibitor (SGLT2i) treatment status of included patients.</p>
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<p>Associations between SGLT2i therapy and all-cause mortality. Kaplan Meier plot illustrating event probability for all-cause mortality with (blue) and without (red) sodium-glucose co-transporter 2 inhibitor (SGLT2i) therapy.</p>
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10 pages, 664 KiB  
Article
Relation between Urine Cytological Findings and Renal Function in Patients with Kidney Stones in Taif, Saudi Arabia
by Sahar Ali Qahtani, Khadiga A. Ismail, Howaida M. Hagag, Maram Jamel Hulbah, Maha M. Bakhuraysah, Nidaa Mahmoud Johari, Salman Mohammed Alotaibi, Seham Alajmani, Hani Diafallah Alseyali, Manal Ali Ayoub, Khalid Abdullah Althagafi, Ali Awad Alnofaie, Abdulbadea Dawod Abdulaziz, Abdulhadi Samman, Hussain Noorwali, Mohammed S. Abdelwahed and Abdulkarim Hasan
Medicina 2024, 60(10), 1630; https://doi.org/10.3390/medicina60101630 - 5 Oct 2024
Viewed by 458
Abstract
Background and Objectives: Urine serves as a vital diagnostic fluid, and urine cytology analysis plays a crucial role in identifying urinary system illnesses such as bladder cancer and kidney stones. The Paris System for Reporting Urinary Cytology establishes a uniform method for [...] Read more.
Background and Objectives: Urine serves as a vital diagnostic fluid, and urine cytology analysis plays a crucial role in identifying urinary system illnesses such as bladder cancer and kidney stones. The Paris System for Reporting Urinary Cytology establishes a uniform method for diagnosing urinary tract cancer. This study aimed to provide valuable insights that can inform diagnostic strategies related to kidney stones and ultimately improve patient outcomes via the early detection of the cellular changes associated with kidney stones and their relation to kidney function tests. Materials and Methods: A comparative study was conducted and comprised two groups: group 1, consisting of 50 patients diagnosed with kidney stones, and group 2, comprising 50 patients diagnosed with other kidney diseases. Renal function tests and urinalysis (via the PAP staining of urine cellular deposits to detect nuclear changes) were performed, and the results were analyzed. Results: There was a statistically significant increase in urinary red blood cells, white blood cells, and nuclear reactive atypical changes in urinary sediments of kidney stone patients compared to the patients without stones, while there was a decrease in the estimated glomerular filtration rate (eGFR). eGFR showed a 96.7% specificity in detecting cases with nuclear reactive atypia. Conclusions: eGFR emerges as a reliable diagnostic marker for the comprehensive assessment of kidney stones, particularly when associated with nuclear atypia. The significant correlation between the indicators of chronic kidney disease, such as decreased eGFR, and the presence of kidney stones emphasizes the urgent need for efficient diagnostic practices. Full article
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<p>Age groups’ distribution among the two groups (blue column = group 1 and red column = group 2).</p>
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<p>(<b>A</b>): PAP stain 20×—urine sample. The cells show squamous cells from urethral contamination and reactive urothelial cells with nuclear atypia, deep-stained cells, and high nuclear:cytoplasmic ratio. The background contains inflammation cells. (<b>B</b>): PAP stain 40×—urine sample. The cells show reactive urothelial cells with nuclear hyperchromasia (atypia), deep-stained cells, and high nuclear:cytoplasmic ratio. (<b>C</b>): PAP stain 40×—urine sample. The background contains inflammation cells. The cells show reactive urothelial cells with nuclear atypia, high nuclear:cytoplasmic ratio, and irregular nuclear membrane.</p>
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17 pages, 1613 KiB  
Article
The Relationship between Vascular Biomarkers (Serum Endocan and Endothelin-1), NT-proBNP, and Renal Function in Chronic Kidney Disease, IgA Nephropathy: A Cross-Sectional Study
by Balázs Sági, Tibor Vas, Csenge Gál, Zoltán Horváth-Szalai, Tamás Kőszegi, Judit Nagy, Botond Csiky and Tibor József Kovács
Int. J. Mol. Sci. 2024, 25(19), 10552; https://doi.org/10.3390/ijms251910552 - 30 Sep 2024
Viewed by 406
Abstract
IgA nephropathy (IgAN) is the most common primary glomerular disease. Endothelin-1 (ET-1) is one of the strongest vasoconstrictor materials in the blood. The N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is associated with renal function and poor outcomes in chronic kidney disease (CKD). [...] Read more.
IgA nephropathy (IgAN) is the most common primary glomerular disease. Endothelin-1 (ET-1) is one of the strongest vasoconstrictor materials in the blood. The N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is associated with renal function and poor outcomes in chronic kidney disease (CKD). Serum endocan is a biomarker associated with proinflammatory cytokines, and the increase in the serum level plays a critical role in inflammatory, proliferative, and neovascularization processes and is associated with poor cardiovascular outcomes in patients with CKD too. Identifying high-risk patients using biomarkers could help to optimize their treatment. Ninety patients with biopsy-confirmed IgAN were included in the study (50 males/40 females, mean age: 54.9 ± 14.4 years). Serum endocan, ET-1, and NT-proBNP were measured by enzyme-linked immunosorbent assay kits. Echocardiography was performed, and carotid-femoral pulse wave velocity (cfPWV) was measured by SphygmoCor in this cross-sectional study. Patients were divided into two groups based on serum endocan median level (cut-off: 44 ug/L). There was significantly higher aorta systolic blood pressure (SBPao) (p = 0.013), NT-proBNP (p = 0.028), albumin/creatinine ratio (p = 0.036), and uric acid (p = 0.045) in the case of the higher endocan group compared to the lower. There was also significantly higher SBPao (p = 0.037) and NT-proBNP (p = 0.038) in the case of higher endothelin-1 (ET-1) levels compared to the lower (cut-off: 231 pg/mL) group by the two-sample t-test. Then, we divided the patients into two groups based on the eGFR (CKD 1–2 vs. CKD 3–5). The levels of serum endocan, NT-proBNP, cfPWV, SBPao, left ventricular mass index (LVMI), uric acid, and albuminuria were significantly higher in the CKD 3–5 group compared to the CKD 1–2 group. The serum endocan and NT-proBNP levels were significantly higher in the diastolic dysfunction group (p = 0.047, p = 0.015). There was a significant increase in serum endocan levels (CKD 1 vs. CKD 5; p = 0.008) with decreasing renal function. In IgAN, vascular biomarkers (endocan, ET-1) may play a role in endothelial dysfunction through vascular damage and elevation of SBPao. Serum endocan, ET-1, and NT-proBNP biomarkers may help to identify IgAN patients at high risk. Full article
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<p>Differences in SBPao (<b>A</b>), NT-proBNP (<b>B</b>), albumin/creatinine ratio (<b>C</b>), and uric acid level (<b>D</b>) in the cases of low and high endocan level groups (cut-off: 44 ug/L) in IgAN patients. Statistical analysis was performed by Student’s <span class="html-italic">t</span>-test. (* <span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Differences in SBPao (<b>A</b>) and NT-proBNP (<b>B</b>) in the case of low and high endothelin-1 level groups (cut-off: 231 pg/mL) in IgAN patients. Statistical analysis was performed by Student’s <span class="html-italic">t</span>-test (* <span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Differences in endocan (<b>A</b>), endothelin-1 (<b>B</b>), and SBPao (<b>C</b>) in the case of low and high NT-proBNP level groups (cut-off: 300 pg/mL) in IgAN patients. Statistical analysis was performed by Student’s <span class="html-italic">t</span>-test (* <span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Differences in serum endocan level (<b>A</b>), SBPao (<b>B</b>), LVMI (<b>C</b>), and uric acid (<b>D</b>) between CKD 1–2 vs. CKD 3–5 groups of IgAN patients. Statistical analysis was performed by Student’s <span class="html-italic">t</span>-test (* <span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Differences in serum NT-proBNP (<b>A</b>) and endocan (<b>B</b>) levels between IgAN patient groups with and without diastolic dysfunction. Statistical analysis was performed by Student’s <span class="html-italic">t</span>-test (* <span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Tendencies in changes of serum endocan level (<b>A</b>), serum endothelin level (<b>B</b>), NT-proBNP (<b>C</b>), and LVMI (<b>D</b>) from CKD 1 to CKD 5. NT-proBNP: N-terminal prohormone of brain natriuretic peptide; CKD: chronic kidney disease; LVMI: left ventricular mass index. NS: not significant. Statistical analysis was performed by Student’s <span class="html-italic">t</span>-test and Jonckheeres trend test analysis.</p>
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9 pages, 544 KiB  
Article
Implantable Cardioverter Defibrillators in Prevention of Sudden Cardiac Death in Kidney Transplant Recipients: A Case Series and an Appraisal of Current Evidence
by Ivana Juric, Lea Katalinic, Vesna Furic-Cunko, Bojan Jelakovic and Nikolina Basic-Jukic
J. Clin. Med. 2024, 13(19), 5820; https://doi.org/10.3390/jcm13195820 - 29 Sep 2024
Viewed by 385
Abstract
Background: Cardiovascular diseases, including sudden cardiac death (SCD), are the leading cause of mortality among kidney transplant recipients (KTRs). While implantable cardioverter defibrillators (ICDs) are established for SCD prevention in the general population, data on the benefits in patients with CKD is scarce [...] Read more.
Background: Cardiovascular diseases, including sudden cardiac death (SCD), are the leading cause of mortality among kidney transplant recipients (KTRs). While implantable cardioverter defibrillators (ICDs) are established for SCD prevention in the general population, data on the benefits in patients with CKD is scarce and controversial, and there is no established general consensus on their use in this group of patients. Furthermore, data for KTRs are lacking. The aim of this study is to present our experience with ICDs in KTRs and evaluate the outcomes in this population. Methods: We retrospectively analyzed medical records of KTRs who received a kidney allograft between October 1973 and December 2023 and received ICDs for the prevention of SCD. Results: Of 2282 KTRs, 10 patients (0.44%) underwent an ICD implantation with an average age of 60.6 years at the time of implantation; 9 were male. Primary prevention of SCD was the most common indication, with only one patient receiving an ICD following sudden cardiac arrest. The female patient received an ICD while on dialysis, and the rest of the patients received ICDs in the posttransplant period with an average time of 9.1 years after KT. Kidney allograft function was reduced in all patients at the time of the ICD implantation with an average estimated glomerular filtration rate (eGFR) of 44 mL/min/1.73 m2. No ICD-related complications were recorded. Six patients are alive with an average follow-up of 5.2 years. Conclusions: ICD implantation in carefully selected KTRs may offer survival benefits and can be a valuable tool in preventing SCD. Larger studies are needed to confirm these findings and establish clear guidelines for ICD use in this specific population. Full article
(This article belongs to the Section Nephrology & Urology)
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<p>Kidney allograft function following ICD implantation. The bold line: mean eGFR through time (for patients available for analysis at certain follow-up time point).</p>
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16 pages, 304 KiB  
Review
Chronic Kidney Disease Progression—A Challenge
by Silvio Maringhini and Carmine Zoccali
Biomedicines 2024, 12(10), 2203; https://doi.org/10.3390/biomedicines12102203 - 27 Sep 2024
Viewed by 487
Abstract
Chronic kidney disease (CKD) is a progressive condition characterized by a continuous decline in renal function, independent of the initial cause of damage or external factors such as infection, inflammation, or toxins. The accurate measurement of renal function, typically assessed using the glomerular [...] Read more.
Chronic kidney disease (CKD) is a progressive condition characterized by a continuous decline in renal function, independent of the initial cause of damage or external factors such as infection, inflammation, or toxins. The accurate measurement of renal function, typically assessed using the glomerular filtration rate (GFR), is crucial for managing CKD. The most accepted hypothesis for CKD progression is glomerular damage caused by hyperfiltration. Various factors can accelerate CKD progression, and several biomarkers have been identified to monitor this progression. Numerous studies have explored the risk factors associated with CKD progression, and some of these factors can be modified. Additionally, several drugs are now available that can reduce CKD progression. This review summarizes recent publications and highlights potential future research directions in CKD progression. It discusses the evolution of GFR measurement methods, the mechanisms driving CKD progression, and the latest findings on biomarkers and risk factors. Furthermore, it explores therapeutic strategies, including dietary modifications and pharmacological interventions, to slow CKD progression. Understanding these mechanisms and interventions is crucial for developing effective therapeutic strategies to prevent or slow CKD progression. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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