Editorial

4 pages, 186 KiB

Open AccessEditorial

Chronic Kidney Disease: Early Detection, Mechanisms, and Therapeutic Implications

by Charlotte Delrue and Marijn M. Speeckaert

J. Pers. Med. 2023, 13(10), 1447; https://doi.org/10.3390/jpm13101447 - 28 Sep 2023

Cited by 1 | Viewed by 556

Chronic Kidney Disease (CKD) constitutes a global health crisis, silently affecting millions worldwide [...] Full article

(This article belongs to the Special Issue Chronic Kidney Disease: Early Detection, Mechanisms, and Therapeutic Implications)

Research

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15 pages, 2134 KiB

Open AccessArticle

Nomogram-Based Chronic Kidney Disease Prediction Model for Type 1 Diabetes Mellitus Patients Using Routine Pathological Data

by Nakib Hayat Chowdhury, Mamun Bin Ibne Reaz, Sawal Hamid Md Ali, Shamim Ahmad, María Liz Crespo, Andrés Cicuttin, Fahmida Haque, Ahmad Ashrif A. Bakar and Mohammad Arif Sobhan Bhuiyan

J. Pers. Med. 2022, 12(9), 1507; https://doi.org/10.3390/jpm12091507 - 14 Sep 2022

Cited by 3 | Viewed by 1882

Abstract

Type 1 diabetes mellitus (T1DM) patients are a significant threat to chronic kidney disease (CKD) development during their life. However, there is always a high chance of delay in CKD detection because CKD can be asymptomatic, and T1DM patients bypass traditional CKD tests [...] Read more.

Type 1 diabetes mellitus (T1DM) patients are a significant threat to chronic kidney disease (CKD) development during their life. However, there is always a high chance of delay in CKD detection because CKD can be asymptomatic, and T1DM patients bypass traditional CKD tests during their routine checkups. This study aims to develop and validate a prediction model and nomogram of CKD in T1DM patients using readily available routine checkup data for early CKD detection. This research utilized 1375 T1DM patients’ sixteen years of longitudinal data from multi-center Epidemiology of Diabetes Interventions and Complications (EDIC) clinical trials conducted at 28 sites in the USA and Canada and considered 17 routinely available features. Three feature ranking algorithms, extreme gradient boosting (XGB), random forest (RF), and extremely randomized trees classifier (ERT), were applied to create three feature ranking lists, and logistic regression analyses were performed to develop CKD prediction models using these ranked feature lists to identify the best performing top-ranked features combination. Finally, the most significant features were selected to develop a multivariate logistic regression-based CKD prediction model for T1DM patients. This model was evaluated using sensitivity, specificity, accuracy, precision, and F1 score on train and test data. A nomogram of the final model was further generated for easy application in clinical practices. Hypertension, duration of diabetes, drinking habit, triglycerides, ACE inhibitors, low-density lipoprotein (LDL) cholesterol, age, and smoking habit were the top-8 features ranked by the XGB model and identified as the most important features for predicting CKD in T1DM patients. These eight features were selected to develop the final prediction model using multivariate logistic regression, which showed 90.04% and 88.59% accuracy in internal and test data validation. The proposed model showed excellent performance and can be used for CKD identification in T1DM patients during routine checkups. Full article

(This article belongs to the Special Issue Chronic Kidney Disease: Early Detection, Mechanisms, and Therapeutic Implications)

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10 pages, 1520 KiB

Open AccessArticle

Hydrogen Sulfide-to-Thiosulfate Ratio Associated with Blood Pressure Abnormalities in Pediatric CKD

by Chien-Ning Hsu, Wei-Ling Chen, Wei-Ting Liao, Guo-Ping Chang-Chien, Sufan Lin and You-Lin Tain

J. Pers. Med. 2022, 12(8), 1241; https://doi.org/10.3390/jpm12081241 - 29 Jul 2022

Cited by 1 | Viewed by 1518

Abstract

Identifying children with chronic kidney disease (CKD) at high risk of cardiovascular disease (CVD) and ensuring they receive appropriate treatment can prevent CVD events and mortality later in life. Hydrogen sulfide (H₂S) is a gaseous signaling molecule participating in CVD and [...] Read more.

Identifying children with chronic kidney disease (CKD) at high risk of cardiovascular disease (CVD) and ensuring they receive appropriate treatment can prevent CVD events and mortality later in life. Hydrogen sulfide (H₂S) is a gaseous signaling molecule participating in CVD and CKD. Thiosulfate is not only an oxidation product of H₂S but is also a H₂S donor. We examined whether H₂S, thiosulfate, and their combined ratio have differential associations with CVD risk markers in 56 children and adolescents aged 6–18 years with CKD stages G1–G4. Up to two-thirds of CKD children showed higher BP load on 24 h ambulatory blood pressure monitoring (ABPM), even in the early stage. CKD children with ABPM abnormalities had a higher H₂S-to-thiosulfate ratio, while H₂S-related parameters were not affected by the severity of CKD. The H₂S-to-thiosulfate ratio was positively correlated with 24 h systolic BP (SBP), nighttime SBP, and carotid artery intima-media thickness (cIMT). After adjusting for confounders, H₂S was negatively associated with LV mass, thiosulfate was positively associated with 24-DBP, and the H₂S-to-thiosulfate ratio was positively correlated with nighttime SBP and cIMT. Our data demonstrate differential associations in circulating H₂S, thiosulfate, and their combined ratio with CVD risk in childhood CKD. Further studies are required to determine whether targeting the H₂S signaling pathway can develop novel therapeutic strategies against CVD in this high-risk population. Full article

(This article belongs to the Special Issue Chronic Kidney Disease: Early Detection, Mechanisms, and Therapeutic Implications)

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7 pages, 443 KiB

Open AccessArticle

Contribution of Hypoalbuminemia and Anemia to the Prognostic Value of Plasma p-Cresyl Sulfate and p-Cresyl Glucuronide for Cardiovascular Outcome in Chronic Kidney Disease

by Francis Verbeke, Raymond Vanholder, Wim Van Biesen and Griet Glorieux

J. Pers. Med. 2022, 12(8), 1239; https://doi.org/10.3390/jpm12081239 - 28 Jul 2022

Cited by 2 | Viewed by 1446

Abstract

Free plasma concentrations of protein-bound uremic toxins (PBUTs) may be influenced by serum albumin and hemoglobin. The potential association of serum albumin and hemoglobin with free levels of p-cresyl sulfate (pCS) and p-cresyl glucuronide (pCG) and their predictive value for cardiovascular morbidity and [...] Read more.

Free plasma concentrations of protein-bound uremic toxins (PBUTs) may be influenced by serum albumin and hemoglobin. The potential association of serum albumin and hemoglobin with free levels of p-cresyl sulfate (pCS) and p-cresyl glucuronide (pCG) and their predictive value for cardiovascular morbidity and mortality were explored. A total of 523 non-dialysis chronic kidney disease (CKD) stages G1–G5 patients were prospectively followed for the occurrence of fatal or non-fatal cardiovascular events over a 5.5-year period. A negative correlation was found between albumin and between hemoglobin, and both total and free pCS and pCG. In multiple linear regression, PBUTs were negatively associated with eGFR (estimated glomerular filtration rate) and hemoglobin but not albumin. In multivariate Cox regression analysis, albumin was a predictor of outcome, independent of pCS and pCG, without interactions between albumin and pCS or pCG. The relation of low hemoglobin with adverse outcome was lost when albumin was entered into the model. Lower concentrations of pCS and pCG are associated with higher serum albumin and hemoglobin. This may indicate that there are two pathways in the blood that potentially contribute to attenuating the vasculotoxic effects of these PBUTs. The association of PBUTs with cardiovascular risk is not explained by albumin levels, which remains a strong and independent predictor for adverse outcome. Full article

(This article belongs to the Special Issue Chronic Kidney Disease: Early Detection, Mechanisms, and Therapeutic Implications)

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15 pages, 1259 KiB

Open AccessArticle

Early Diagnosis of Kidney Damage Associated with Tobacco Use: Preventive Application

by Javier Tascón, Marta Prieto, Alfredo G. Casanova, Francisco J. Sanz, Miguel A. Hernández Mezquita, Miguel Barrueco Ferrero, Manuel A. Gomez-Marcos, Luis Garcia-Ortiz, Laura Vicente-Vicente, Ana I. Morales and on behalf of BIOTAB Team

J. Pers. Med. 2022, 12(7), 1032; https://doi.org/10.3390/jpm12071032 - 24 Jun 2022

Cited by 3 | Viewed by 1963

Abstract

Although long-term smoking has been associated with chronic kidney disease, its effect on kidney function in early stages has not been clarified. Therefore, the proposed objectives were: (1) to identify subclinical kidney damage in smokers, through a panel of biomarkers; (2) to evaluate [...] Read more.

Although long-term smoking has been associated with chronic kidney disease, its effect on kidney function in early stages has not been clarified. Therefore, the proposed objectives were: (1) to identify subclinical kidney damage in smokers, through a panel of biomarkers; (2) to evaluate the progression of subclinical kidney damage after two years of consumption in these patients; and (3) study whether quitting smoking reduces kidney damage. A prospective study was carried out (patients recruited from a primary care centre and a clinical smoking unit). Kidney function was assessed using a panel of biomarkers and compared between smokers and non-smokers, taking into account potential risk factors for kidney damage. These results show, for the first time in the literature, the relationship between smoking and early (subclinical) kidney damage and provide a panel of biomarkers capable of detecting this condition (Neutrophil gelatinase-associated lipocalin, Kidney injury molecule-1, N-acetyl-beta-D-glucosaminidase, transferrin, and ganglioside-activating protein GM2). This study also indicates that subclinical damage is maintained when use continues, but can be reversed if patients stop smoking. The use of these biomarkers as diagnostic tools can be a preventive measure in the development of chronic kidney disease associated with smoking and in the prevention of acute events associated with potentially nephrotoxic pharmacological treatment in smokers. Trial registration number: NCT03850756. Full article

(This article belongs to the Special Issue Chronic Kidney Disease: Early Detection, Mechanisms, and Therapeutic Implications)

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10 pages, 1309 KiB

Open AccessArticle

Comparison of Human Urinary Exosomes Isolated via Ultracentrifugation Alone versus Ultracentrifugation Followed by SEC Column-Purification

by Kun Huang, Sudha Garimella, Alyssa Clay-Gilmour, Lucia Vojtech, Bridget Armstrong, Madison Bessonny and Alexis Stamatikos

J. Pers. Med. 2022, 12(3), 340; https://doi.org/10.3390/jpm12030340 - 24 Feb 2022

Cited by 15 | Viewed by 2429

Abstract

Chronic kidney disease is a progressive, incurable condition that involves a gradual loss of kidney function. While there are no non-invasive biomarkers available to determine whether individuals are susceptible to developing chronic kidney disease, small RNAs within urinary exosomes have recently emerged as [...] Read more.

Chronic kidney disease is a progressive, incurable condition that involves a gradual loss of kidney function. While there are no non-invasive biomarkers available to determine whether individuals are susceptible to developing chronic kidney disease, small RNAs within urinary exosomes have recently emerged as a potential candidate to use for assessing renal function. Ultracentrifugation is the gold standard for urinary exosome isolation. However, extravesicular small RNA contamination can occur when isolating exosomes from biological fluids using ultracentrifugation, which may lead to misidentifying the presence of certain small RNA species in human urinary exosomes. Therefore, we characterized human urinary exosomal preparations isolated by ultracentrifugation alone, or via ultracentrifugation followed by size exclusion chromatography (SEC) column-purification. Using nanoparticle tracking analysis, we identified SEC fractions containing robust amounts of exosome-sized particles, that we further characterized using immunoblotting. When compared to exosomal preparations isolated by ultracentrifugation only, SEC fractionated exosomal preparations showed higher levels of the exosome-positive marker CD81. Moreover, while the exosome-negative marker calnexin was undetectable in SEC fractionated exosomal preparations, we did observe calnexin detection in the exosomal preparations isolated by ultracentrifugation alone, which implies contamination in these preparations. Lastly, we imaged SEC fractionated exosomal preparations using transmission electron microscopy to confirm these preparations contained human urinary exosomes. Our results indicate that combining ultracentrifugation and SEC column-purification exosome isolation strategies is a powerful approach for collecting contaminant-free human urinary exosomes and should be considered when exosomes devoid of contamination are needed for downstream applications. Full article

(This article belongs to the Special Issue Chronic Kidney Disease: Early Detection, Mechanisms, and Therapeutic Implications)

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9 pages, 1229 KiB

Open AccessArticle

Gut Microbiome Profiling Uncovers a Lower Abundance of Butyricicoccus in Advanced Stages of Chronic Kidney Disease

by Tessa Gryp, Karoline Faust, Wim Van Biesen, Geert R. B. Huys, Francis Verbeke, Marijn Speeckaert, Jeroen Raes, Mario Vaneechoutte, Marie Joossens and Griet Glorieux

J. Pers. Med. 2021, 11(11), 1118; https://doi.org/10.3390/jpm11111118 - 29 Oct 2021

Cited by 12 | Viewed by 2679

Abstract

Chronic kidney disease (CKD) is characterized by the accumulation of uremic toxins which exert deleterious effects on various organ systems. Several of these uremic toxins originate from the bacterial metabolization of aromatic amino acids in the colon. This study assessed whether the gut [...] Read more.

Chronic kidney disease (CKD) is characterized by the accumulation of uremic toxins which exert deleterious effects on various organ systems. Several of these uremic toxins originate from the bacterial metabolization of aromatic amino acids in the colon. This study assessed whether the gut microbial composition varies among patients in different stages of CKD. Uremic metabolites were quantified by UPLC/fluorescence detection and microbial profiling by 16S rRNA amplicon sequencing. Gut microbial profiles of CKD patients were compared among stages 1–2, stage 3 and stages 4–5. Although a substantial inter-individual difference in abundance of the top 15 genera was observed, no significant difference was observed between groups. Bristol stool scale (BSS) correlated negatively with p-cresyl sulfate and hippuric acid levels, irrespective of the intake of laxatives. Butyricicoccus, a genus with butyrate-generating properties, was decreased in abundance in advanced stages of CKD compared to the earlier stages (p = 0.043). In conclusion, in this cross-sectional study no gradual differences in the gut microbial profile over the different stages of CKD were observed. However, the decrease in the abundance of Butyricicoccus genus with loss of kidney function stresses the need for more in-depth functional exploration of the gut microbiome in CKD patients not on dialysis. Full article

(This article belongs to the Special Issue Chronic Kidney Disease: Early Detection, Mechanisms, and Therapeutic Implications)

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Review

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20 pages, 942 KiB

Open AccessReview

The Potential Applications of Raman Spectroscopy in Kidney Diseases

by Charlotte Delrue and Marijn M. Speeckaert

J. Pers. Med. 2022, 12(10), 1644; https://doi.org/10.3390/jpm12101644 - 03 Oct 2022

Cited by 4 | Viewed by 1855

Abstract

Raman spectroscopy (RS) is a spectroscopic technique based on the inelastic interaction of incident electromagnetic radiation (from a laser beam) with a polarizable molecule, which, when scattered, carries information from molecular vibrational energy (the Raman effect). RS detects biochemical changes in biological samples [...] Read more.

Raman spectroscopy (RS) is a spectroscopic technique based on the inelastic interaction of incident electromagnetic radiation (from a laser beam) with a polarizable molecule, which, when scattered, carries information from molecular vibrational energy (the Raman effect). RS detects biochemical changes in biological samples at the molecular level, making it an effective analytical technique for disease diagnosis and prognosis. It outperforms conventional sample preservation techniques by requiring no chemical reagents, reducing analysis time even at low concentrations, and working in the presence of interfering agents or solvents. Because routinely utilized biomarkers for kidney disease have limitations, there is considerable interest in the potential use of RS. RS may identify and quantify urinary and blood biochemical components, with results comparable to reference methods in nephrology. Full article

(This article belongs to the Special Issue Chronic Kidney Disease: Early Detection, Mechanisms, and Therapeutic Implications)

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17 pages, 708 KiB

Open AccessEditor’s ChoiceReview

Emerging Biomarkers for Early Detection of Chronic Kidney Disease

by Maja Mizdrak, Marko Kumrić, Tina Tičinović Kurir and Joško Božić

J. Pers. Med. 2022, 12(4), 548; https://doi.org/10.3390/jpm12040548 - 31 Mar 2022

Cited by 34 | Viewed by 7289

Abstract

Chronic kidney disease (CKD) is a major and serious global health problem that leads to kidney damage as well as multiple systemic diseases. Early diagnosis and treatment are two major measures to prevent further deterioration of kidney function and to delay adverse outcomes. [...] Read more.

Chronic kidney disease (CKD) is a major and serious global health problem that leads to kidney damage as well as multiple systemic diseases. Early diagnosis and treatment are two major measures to prevent further deterioration of kidney function and to delay adverse outcomes. However, the paucity of early, predictive and noninvasive biomarkers has undermined our ability to promptly detect and treat this common clinical condition which affects more than 10% of the population worldwide. Despite all limitations, kidney function is still measured by serum creatinine, cystatin C, and albuminuria, as well as estimating glomerular filtration rate using different equations. This review aims to provide comprehensive insight into diagnostic methods available for early detection of CKD. In the review, we discuss the following topics: (i) markers of glomerular injury; (ii) markers of tubulointerstitial injury; (iii) the role of omics; (iv) the role of microbiota; (v) and finally, the role of microRNA in the early detection of CKD. Despite all novel findings, none of these biomarkers have met the criteria of an ideal early marker. Since the central role in CKD progression is the proximal tubule (PT), most data from the literature have analyzed biomarkers of PT injury, such as KIM-1 (kidney injury molecule-1), NGAL (neutrophil gelatinase-associated lipocalin), and L-FABP (liver fatty acid-binding protein). Full article

(This article belongs to the Special Issue Chronic Kidney Disease: Early Detection, Mechanisms, and Therapeutic Implications)

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