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New Advances in Chronic Kidney Disease: Biology, Diagnosis and Therapy

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 31 July 2024 | Viewed by 14807

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Dr. Susana Coimbra

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1. UCIBIO—Applied Molecular Biosciences Unit, Department of Biological Sciences, Faculdade de Farmácia da Universidade do Porto, 4050-313 Porto, Portugal
2. Associate Laboratory i4HB—Institute for Health and Bioeconomy, Faculdade de Farmácia da Universidade do Porto, 4050-313 Porto, Portugal
3. TOXRUN—Toxicology Research Unit, University Institute of Health Sciences, Cooperativa de Ensino Superior Politécnico e Universitário (CESPU), CRL, 4585-116 Gandra, Portugal
Interests: biomarkers; chronic kidney disease; inflammation; cardiovascular disease risk factors

Dr. Alice Santos-Silva

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Guest Editor

Laboratory of Biochemistry, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
Interests: cardiovascular risk factors; anemia of chronic kidney disease; obesity; inflammation
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Dear Colleagues,

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

A better understanding of the uremic milieu of CKD pathophysiology and of its relationship with its comorbidities will be a great achievement. The identification of biomarkers, or panel of biomarkers, of cardiorenal syndrome and early kidney injury will help clinicians in their therapeutic decisions and choosing earlier and more adequate therapeutic strategies, avoiding or minimizing CKD progression. The investigation of novel therapeutic approaches should also be encouraged.

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

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Keywords

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

Published Papers (9 papers)

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Research

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13 pages, 474 KiB

Open AccessArticle

Improved Ultrasound-Guided Balloon-Assisted Maturation Angioplasty Using Drug-Eluting Balloons in the First Autogenous Arteriovenous Fistula Procedure: Early Experience

by Domenico Mirabella, Ettore Dinoto, Edoardo Rodriquenz, Michele Bellomo, Andrea Miccichè, Paolo Annicchiarico and Felice Pecoraro

Biomedicines 2024, 12(5), 1005; https://doi.org/10.3390/biomedicines12051005 - 02 May 2024

Viewed by 161

Abstract

In patients with end-stage renal failure requiring hemodialysis, autogenous arteriovenous fistula (AVF) is preferred over tunneled dialysis catheters due to lower complications and costs. However, AVF maturation failure remains a common issue due to small vein size, multiple venipunctures, and other factors. Guidelines recommend using vessels of >2 mm for forearm AVFs and >3 mm for upper arm AVFs. This study investigates the use of intraoperative Doppler ultrasound (DUS)-guided Balloon-Assisted Maturation (BAM) with drug-eluting balloons (DEB) during initial AVF creation. Data from 114 AVF procedures, of which 27.2% underwent BAM, were analyzed. BAM was performed in 25 distal radio-cephalic and 6 proximal brachio-cephalic AVFs. With DUS guidance, vein stenosis was identified and treated using DEB. Technical success was achieved in all cases, with no early mortality. Early BAM-related complications were minimal, and no AVF thrombosis occurred. AVF maturation time was 15 days (SD: 3), and no further complications were reported during a mean follow-up of 10.38 months. Using BAM with DEB during AVF creation led to successful maturation and dialysis use without the need for secondary procedures. This study emphasizes the importance of identifying AVF failure risk early and utilizing DUS-guided procedures to enhance AVF outcomes. A more liberal use of intraoperative BAM could limit reinterventions in patients undergoing AVFs. Full article

(This article belongs to the Special Issue New Advances in Chronic Kidney Disease: Biology, Diagnosis and Therapy)

19 pages, 1796 KiB

Open AccessArticle

Circulating Lipoprotein Sphingolipids in Chronic Kidney Disease with and without Diabetes

by Maria F. Lopes-Virella, Samar M. Hammad, Nathaniel L. Baker, Richard L. Klein and Kelly J. Hunt

Biomedicines 2024, 12(1), 190; https://doi.org/10.3390/biomedicines12010190 - 15 Jan 2024

Viewed by 704

Abstract

Abnormalities of sphingolipid metabolism play an important role in diabetes. We compared sphingolipid levels in plasma and in isolated lipoproteins between healthy control subjects and two groups of patients, one with chronic kidney disease without diabetes (ND-CKD), and the other with type 2 diabetes and macroalbuminuria (D-MA). Ceramides, sphingomyelins, and sphingoid bases and their phosphates in LDL were higher in ND-CKD and in D-MA patients compared to controls. However, ceramides and sphingoid bases in HDL2 and HDL3 were lower in ND-CKD and in D-MA patients than in controls. Sphingomyelins in HDL2 and HDL3 were lower in D-MA patients than in controls but were normal in ND-CKD patients. Compared to controls, lactosylceramides in LDL and VLDL were higher in ND-CKD patients but not in D-MA patients. However, lactosylceramides in HDL2 and HDL3 were lower in both ND-CKD and D-MA patients than in controls. Plasma hexosylceramides in ND-CKD patients were increased and sphingoid bases decreased in both ND-CKD and D-MA patients. However, hexosylceramides in LDL, HDL2, and HDL3 were higher in ND-CKD patients than in controls. In D-MA patients, only C16:0 hexosylceramide in LDL was higher than in controls. The data suggest that sphingolipid measurement in lipoproteins, rather than in whole plasma, is crucial to decipher the role of sphingolipids in kidney disease. Full article

(This article belongs to the Special Issue New Advances in Chronic Kidney Disease: Biology, Diagnosis and Therapy)

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11 pages, 1295 KiB

Open AccessArticle

The Plasma Neurofilament Light Chain, Brain-Derived Neurotrophic Factor, and Risk of Depression in Chronic Hemodialysis Patients

by Martyna Stanisławska, Maja Roman and Michał Nowicki

Biomedicines 2024, 12(1), 103; https://doi.org/10.3390/biomedicines12010103 - 04 Jan 2024

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Abstract

Introduction: Depression is highly prevalent among hemodialysis patients. Understanding the relationship between the plasma neurofilament light chain (NfL) and brain-derived neurotrophic factor (BDNF) may help us to better understand the mechanisms of depression. This study determined their impact, alongside that of other factors, on the risk of depression in hemodialysis patients. Methods: The study enrolled 82 patients undergoing chronic hemodialysis. Serum NfL, BDNF, uric acid, urea, potassium, calcium, phosphorus, intact parathyroid hormone, and C-reactive protein (CRP) levels were measured. The patients completed the Beck Depression Inventory (BDI). Blood pressure values, body mass before and after hemodialysis, and weekly duration of hemodialysis in hours were assessed. For 19-month survival analysis, the patients were stratified according to baseline BDI scores. Results: Based on the BDI score, 18.3% of the patients had an increased risk of depression. Lower scores were associated with significantly longer duration of hemodialysis treatment (37.5 (25–57) 24 (14–37) months, p = 0.01). Within the 19-month survival analysis, 31.7% of patients died. The patients with BDI scores above the median had significantly lower survival than those below the median (log-rank test p = 0.02). No significant differences in serum BDNF levels (192.7 [125.2–278.2]; 207.7 [142.8–265.8] pg/mL, p = 0.40), or NfL concentrations (1431.5 [1182.6–1625.7]; 1494.6 [1335.7–1667] kDa, p = 0.52) were found between patients with lower and higher risk of depression. Patients with BDI scores above the median had significantly higher levels of CRP (9.6 [4.4–14]) than those with scores below the median (3.6 [2.2–7.5], p = 0.01). A significant positive correlation was found between the BDI score and serum CRP level (r = 0.38, p = 0.01). A significant negative correlation was observed between the BDI score and URR% value (r = −0.36, p = 0.02). Conclusions: Patients with lower BDI scores had a longer dialysis duration, indicating a potential negative association between depression risk and length of dialysis treatment. Neither serum NfL nor BDNF levels can serve as markers of depression risk in the dialysis population. Full article

(This article belongs to the Special Issue New Advances in Chronic Kidney Disease: Biology, Diagnosis and Therapy)

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18 pages, 4916 KiB

Open AccessArticle

Omega-3 Fatty Acids Attenuate Renal Fibrosis via AMPK-Mediated Autophagy Flux Activation

by Suyeon Han, Hyunsu Choi, Hyerim Park, Jwa-Jin Kim, Eu-Jin Lee, Young-Rok Ham, Ki-Rayng Na, Kang-Wook Lee, Yoon-Kyung Chang and Dae-Eun Choi

Biomedicines 2023, 11(9), 2553; https://doi.org/10.3390/biomedicines11092553 - 17 Sep 2023

Cited by 1 | Viewed by 1285

Abstract

The unilateral ureteral obstruction (UUO) injury model is well-known to mimic human chronic kidney disease, promoting the rapid onset and development of kidney injury. ω3-poly unsaturated fatty acids (PUFAs) have been observed to protect against tissue injury in many disease models. In this study, we assessed the efficacy of ω3-PUFAs in attenuating UUO injury and investigated their mechanism of action. The immortalized human proximal tubular cells human kidney-2 (HK2) were incubated for 72 h with docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) in various concentrations, in the presence or absence of transforming growth factor (TGF)-β. DHA/EPA reduced the epithelial–mesenchymal transition in the TGF-β-treated HK2 cells by enhancing autophagy flux and adenosine monophosphate-activated protein kinase (AMPK) phosphorylation. C57BL/6 mice were divided into four groups and treated as follows: sham (no treatment, n = 5), sham + ω3-PUFAs (n = 5), UUO (n = 10), and UUO + ω3-PUFAs (n = 10). Their kidneys and blood were harvested on the seventh day following UUO injury. The kidneys of the ω3-PUFAs-treated UUO mice showed less oxidative stress, inflammation, and fibrosis compared to those of the untreated UUO mice. Greater autophagic flux, higher amounts of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, Beclin-1, and Atg7, lower amounts of p62, and higher levels of cathepsin D and ATP6E were observed in the kidneys of the omega-3-treated UUO mice compared to those of the control UUO mice. In conclusion, ω3-PUFAs enhanced autophagic activation, leading to a renoprotective response against chronic kidney injury. Full article

(This article belongs to the Special Issue New Advances in Chronic Kidney Disease: Biology, Diagnosis and Therapy)

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16 pages, 1000 KiB

Open AccessArticle

Immunosenescence and Immune Exhaustion Are Associated with Levels of Protein-Bound Uremic Toxins in Patients on Hemodialysis

by Theodoros Tourountzis, Georgios Lioulios, Steven Van Laecke, Evdoxia Ginikopoulou, Vasiliki Nikolaidou, Eleni Moysidou, Stamatia Stai, Michalis Christodoulou, Asimina Fylaktou, Griet Glorieux and Maria Stangou

Biomedicines 2023, 11(9), 2504; https://doi.org/10.3390/biomedicines11092504 - 11 Sep 2023

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Abstract

Background: The accumulation of protein-bound uremic toxins (PBUTs) in chronic kidney disease may affect patients’ immune status. The aim of the study was to evaluate their potential impacts on lymphocyte alterations in patients on hemodialysis (HD). Methods: The plasma levels of PBUTs were assessed in 54 patients on HD and 31 healthy individuals, using ultra-performance liquid chromatography. The results correlated with the senescent and exhausted status of lymphocytes, based on certain surface molecules, analyzed by flow cytometry. Results: The plasma levels of PBUTs were significantly increased in the patients on HD compared with the healthy controls. The patients with residual kidney function had reduced hippuric acid (HA) levels, total (p = 0.03) and free (p = 0.04), and free IxS levels (p = 0.02). The total and free HA levels correlated negatively with less differentiated subpopulations, CD4+CD45RA+CD31+ (p = 0.037 and p = 0.027), CD8+CD28+CD57− (p = 0.01, p = 0.01), and naïve B cells (CD19+IgD+CD27−) (p = 0.04, p = 0.03). Both the total and the free pCS levels correlated positively with exhausted CD4 cells, p = 0.02 and p = 0.01, respectively. A multivariate analysis showed that IxS and age were the main independent parameters implicated in the reduction intotal CD4 and B lymphocytes and their naïve and early differentiated subsets. Conclusions: Increased PBUTs levels are associated with immune disturbances of patients on HD, HA, and IxS in the immunosenescent and pCS in the immunoexhaustion alterations. Full article

(This article belongs to the Special Issue New Advances in Chronic Kidney Disease: Biology, Diagnosis and Therapy)

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9 pages, 825 KiB

Open AccessArticle

Elevated Uric Acid Levels with Early Chronic Kidney Disease as an Indicator of New-Onset Ischemic Heart Disease: A Cohort of Koreans without Diabetes

by Sung-Bum Lee, Hui-Jeong Lee, Ha Eun Ryu, Byoungjin Park and Dong-Hyuk Jung

Biomedicines 2023, 11(8), 2212; https://doi.org/10.3390/biomedicines11082212 - 07 Aug 2023

Viewed by 1175

Abstract

Several studies have showed that hyperuricemia is related to the development of ischemic heart disease (IHD). There is also growing evidence indicating that hyperuricemia may contribute to the progression of IHD as a pathogenic factor. Ironically, uric acid can be an antioxidant agent, as shown in experimental studies. The aim of our study is to analyse the association between uric acid and IHD with early-stage chronic kidney disease (CKD). Data were assessed from 17,492 participants without cardiovascular disease from the Korean Genome and Epidemiology Study (KoGES) and Korea Health Insurance Review and Assessment (HIRA) data. The subjects were categorized as four groups according to CKD and uric acid levels. We retrospectively evaluated hazard ratios (HRs) with 95% confidence intervals (CIs) for IHD by using multivariate Cox regression analysis over a 4-year period from the baseline survey. During the follow-up, 335 individuals (3.4%; 236 men and 99 women) developed IHD. Compared to the participants without elevated uric acid and early CKD HRs for incident IHD according to uric acid levels and early CKD, the uric acid level was 1.13 (95% CI, 0.86–1.48) in participants with elevated uric acid and without early CKD, 0.99 (95% CI, 0.55–1.77) in participants without elevated uric acid and with early CKD, and 1.65 (95% CI, 1.03–2.66) in participants with elevated uric acid and early CKD after adjusting for confounding metabolic factors. Early CKD and high uric acid levels increased the risk of new-onset IHD (HR, 1.65; 95% CI, 1.03–2.66). Elevated uric acid levels were related to an increased risk of incident IHD in early-stage CKD patients. It is expected that uric acid can be a reliable predictor for IHD, even in early-stage CKD patients; thus, in those with CKD, proactively managing uric acid levels can play a significant role in reducing the risk of cardiovascular disease. Full article

(This article belongs to the Special Issue New Advances in Chronic Kidney Disease: Biology, Diagnosis and Therapy)

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16 pages, 3605 KiB

Open AccessArticle

Improved Survival Analyses Based on Characterized Time-Dependent Covariates to Predict Individual Chronic Kidney Disease Progression

by Chen-Mao Liao, Chuan-Tsung Su, Hao-Che Huang and Chih-Ming Lin

Biomedicines 2023, 11(6), 1664; https://doi.org/10.3390/biomedicines11061664 - 08 Jun 2023

Cited by 1 | Viewed by 1306

Abstract

Kidney diseases can cause severe morbidity, mortality, and health burden. Determining the risk factors associated with kidney damage and deterioration has become a priority for the prevention and treatment of kidney disease. This study followed 497 patients with stage 3–5 chronic kidney disease (CKD) who were treated at the ward of Taipei Veterans General Hospital from January 2006 to 2019 in Taiwan. The patients underwent 3-year-long follow-up sessions for clinical measurements, which occurred every 3 months. Three time-dependent survival models, namely the Cox proportional hazard model (Cox PHM), random survival forest (RSF), and an artificial neural network (ANN), were used to process patient demographics and laboratory data for predicting progression to renal failure, and important features for optimal prediction were evaluated. The individual prediction of CKD progression was validated using the Kaplan–Meier estimation method, based on patients’ true outcomes during and beyond the study period. The results showed that the average concordance indexes for the cross-validation of the Cox PHM, ANN, and RSF models were 0.71, 0.72, and 0.89, respectively. RSF had the best predictive performances for CKD patients within the 3 years of follow-up sessions, with a sensitivity of 0.79 and specificity of 0.88. Creatinine, age, estimated glomerular filtration rate, and urine protein to creatinine ratio were useful factors for predicting the progression of CKD patients in the RSF model. These results may be helpful for instantaneous risk prediction at each follow-up session for CKD patients. Full article

(This article belongs to the Special Issue New Advances in Chronic Kidney Disease: Biology, Diagnosis and Therapy)

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Review

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19 pages, 658 KiB

Open AccessReview

Novel Therapeutic Approaches in the Management of Chronic Kidney Disease

by Bartłomiej Dąbek, Jill Dybiec, Weronika Frąk, Piotr Fularski, Wiktoria Lisińska, Ewa Radzioch, Ewelina Młynarska, Jacek Rysz and Beata Franczyk

Biomedicines 2023, 11(10), 2746; https://doi.org/10.3390/biomedicines11102746 - 11 Oct 2023

Cited by 1 | Viewed by 3267

Abstract

Chronic kidney disease (CKD) is a progressive and incurable disease that impairs kidney function. Its prevalence is estimated to affect up to 800 million individuals within the general population, and patients with diabetes and hypertension are particularly at risk. This disorder disrupts the physiological mechanisms of the body, including water and electrolyte balance, blood pressure regulation, the excretion of toxins, and vitamin D metabolism. Consequently, patients are exposed to risks such as hyperkalemia, hyperphosphatemia, metabolic acidosis, and blood pressure abnormalities. These risks can be reduced by implementing appropriate diagnostic methods, followed by non-pharmacological (such as physical activity, dietary, and lifestyle adjustment) and pharmacological strategies after diagnosis. Selecting the appropriate diet and suitable pharmacological treatment is imperative in maintaining kidney function as long as possible. Drugs such as finerenone, canakinumab, and pentoxifylline hold promise for improved outcomes among CKD patients. When these interventions prove insufficient, renal replacement therapy becomes essential. This is particularly critical in preserving residual renal function while awaiting renal transplantation or for patients deemed ineligible for such a procedure. The aim of this study is to present the current state of knowledge and recent advances, providing novel insights into the treatment of chronic kidney disease. Full article

(This article belongs to the Special Issue New Advances in Chronic Kidney Disease: Biology, Diagnosis and Therapy)

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30 pages, 1471 KiB

Open AccessReview

Biomarkers for Kidney-Transplant Rejection: A Short Review Study

by Israa Sharaby, Ahmed Alksas, Mohamed Abou El-Ghar, Mona Eldeeb, Mohammed Ghazal, Dibson Gondim and Ayman El-Baz

Biomedicines 2023, 11(9), 2437; https://doi.org/10.3390/biomedicines11092437 - 31 Aug 2023

Viewed by 2454

Abstract

Kidney transplantation is the preferred treatment for end-stage renal failure, but the limited availability of donors and the risk of immune rejection pose significant challenges. Early detection of acute renal rejection is a critical step to increasing the lifespan of the transplanted kidney. Investigating the clinical, genetic, and histopathological markers correlated to acute renal rejection, as well as finding noninvasive markers for early detection, is urgently needed. It is also crucial to identify which markers are associated with different types of acute renal rejection to manage treatment effectively. This short review summarizes recent studies that investigated various markers, including genomics, histopathology, and clinical markers, to differentiate between different types of acute kidney rejection. Our review identifies the markers that can aid in the early detection of acute renal rejection, potentially leading to better treatment and prognosis for renal-transplant patients. Full article

(This article belongs to the Special Issue New Advances in Chronic Kidney Disease: Biology, Diagnosis and Therapy)

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