Biomedicines

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13 pages, 1221 KiB

Open AccessArticle

Trajectory of Irisin as a Predictor of Kidney-Related Outcomes in Patients with Asymptomatic Heart Failure

by Tetiana A. Berezina, Oleksandr O. Berezin, Uta C. Hoppe, Michael Lichtenauer and Alexander E. Berezin

Biomedicines 2024, 12(8), 1827; https://doi.org/10.3390/biomedicines12081827 - 12 Aug 2024

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Abstract

The purpose of the study is to elucidate whether irisin is a promising predictive biomarker for kidney-related events in patients with T2DM and concomitant asymptomatic HF. We prospectively enrolled 146 T2DM patients who had either evidence of structural cardiac abnormality or elevated levels [...] Read more.

The purpose of the study is to elucidate whether irisin is a promising predictive biomarker for kidney-related events in patients with T2DM and concomitant asymptomatic HF. We prospectively enrolled 146 T2DM patients who had either evidence of structural cardiac abnormality or elevated levels of N-terminal brain natriuretic pro-peptide (NT-proBNP) > 125 pmol/mL and followed them for 52 weeks. Structural cardiac abnormalities were used as the minimum from the following criteria: abnormal left ventricular (LV) global longitudinal strain (GLS) < −16%, LV hypertrophy, left atrial volume index > 34 mL/m², abnormal ratio of early transmitral diastolic filling velocity/early mitral annular velocity ≥ 13 units. All the patients underwent echocardiographic and Doppler examinations by two blinded, highly experienced echocardiographers. NT-proBNP, irisin, TNF-alpha, and hs-CRP were quantified in the serum at baseline, at 26 weeks, and at the end of the study. The kidney-related outcomes consisted of an eGFR reduction by 40% from baseline, or end-stage kidney disease, or kidney replacement therapy. We found that levels of irisin at baseline < 4.15 ng/mL and/or its decrease > 20% from baseline in T2DM patients predicted kidney-related events better than baseline levels/dynamic NT-proBNP and the use of SGLT2 inhibitors. In conclusion, we established that a low baseline level of irisin and its 20% decrease correlated with newly kidney-related events in T2DM patients with asymptomatic HFpEF/HFmrEF. Full article

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

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12 pages, 1868 KiB

Open AccessArticle

Erythropoietin Effect on Complement Activation in Chronic Kidney Disease

by Virginia Athanasiadou, Kleio Ampelakiotou, Eirini Grigoriou, Katherina Psarra, Alexandra Tsirogianni, Serena Valsami, Theodoros Pittaras, Eirini Grapsa and Maria G. Detsika

Biomedicines 2024, 12(8), 1746; https://doi.org/10.3390/biomedicines12081746 - 2 Aug 2024

Viewed by 721

Abstract

The complement system is an important part of innate immunity. Despite its known protective role, the complement system may contribute to increased inflammation and tissue injury in cases where its balanced activation is disrupted. The kidneys have been shown to be largely affected [...] Read more.

The complement system is an important part of innate immunity. Despite its known protective role, the complement system may contribute to increased inflammation and tissue injury in cases where its balanced activation is disrupted. The kidneys have been shown to be largely affected by complement dysregulation. The aim of the present study was to investigate the effect of erythropoietin administration, on the complement system, in chronic kidney disease patients. The study involved 20 patients with CKD who received erythropoietin and measurements of levels of complement factors C3a and C5a and complement regulatory proteins (CregPs) CD55, CD46, and CD59. An increase in serum C3a and C5a levels was observed in response to EPO therapy. The increase in C3a was statistically significant (p < 0.05) and concurrent with a statistically significant decrease in CD55 in CD4⁺ T cells (p < 0.05) and B cells (p < 0.05) and CD59 levels in CD4⁺ and CD8⁺ T cells (p < 0.05) at completion of EPO therapy compared with healthy controls. The above observations demonstrate that EPO induces complement activation in patients undergoing EPO therapy with a simultaneous restriction of CRegPs expression, thus possibly allowing the uncontrolled complement activation, which may contribute to tissue injury and disease progression. Full article

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

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17 pages, 23398 KiB

Open AccessArticle

Extracellular Vesicles Derived from Human Liver Stem Cells Counteract Chronic Kidney Disease Development and Cardiac Dysfunction in Remnant Kidney Murine Model: The Possible Involvement of Proteases

by Elena Ceccotti, Giulia Chiabotto, Massimo Cedrino, Alessandro Gambella, Luisa Delsedime, Alessandra Ghigo, Chiara Salio, Cristina Grange, Maria Beatriz Herrera Sanchez, Saveria Femminò, Marco Sassoè-Pognetto, Maria Felice Brizzi, Giovanni Camussi and Stefania Bruno

Biomedicines 2024, 12(7), 1517; https://doi.org/10.3390/biomedicines12071517 - 8 Jul 2024

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Abstract

Fibrosis is a marker of chronic kidney disease (CKD) and consists of the accumulation of the extracellular matrix (ECM) components, causing the progressive deterioration of kidney function. Human liver stem cells (HLSCs) have anti-fibrotic activity, and HLSC-derived extracellular vesicles (EVs) mediate this effect. [...] Read more.

Fibrosis is a marker of chronic kidney disease (CKD) and consists of the accumulation of the extracellular matrix (ECM) components, causing the progressive deterioration of kidney function. Human liver stem cells (HLSCs) have anti-fibrotic activity, and HLSC-derived extracellular vesicles (EVs) mediate this effect. Herein, we evaluated the ability of HLSC-EVs to reverse renal and cardiac alterations in a murine model of partial nephrectomy (PNx) that mimics human CKD development. Furthermore, we investigated the contribution of extracellular matrix remodeling-related proteases to the anti-fibrotic effect of HLSC-EVs. PNx was performed by ligation of both poles of the left kidney, followed one week later by the removal of the right kidney. EV treatment started 4 weeks after the nephrectomy, when renal and cardiac alternations were already established, and mice were sacrificed at week eight. HLSC-EV treatment improved renal function and morphology, significantly decreasing interstitial fibrosis, glomerular sclerosis, and capillary rarefaction. This improvement was confirmed by the decreased expression of pro-fibrotic genes. Moreover, EV treatment improved cardiac function and reduced cardiac fibrosis. HLSC-EVs shuttled different proteases with ECM remodeling activity, and matrix metalloproteinase 1 (MMP-1) was involved in their anti-fibrotic effect on renal tissue. HLSC-EV treatment interferes with CKD development and ameliorates cardiomyopathy in PNx mice. Full article

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

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15 pages, 300 KiB

Open AccessArticle

Impact of TNFRSF1B (rs3397, rs1061624 and rs1061622) and IL6 (rs1800796, rs1800797 and rs1554606) Gene Polymorphisms on Inflammatory Response in Patients with End-Stage Kidney Disease Undergoing Dialysis

by Susana Coimbra, Susana Rocha, Cristina Catarino, Maria João Valente, Petronila Rocha-Pereira, Maria Sameiro-Faria, José Gerardo Oliveira, José Madureira, João Carlos Fernandes, Vasco Miranda, Luís Belo, Elsa Bronze-da-Rocha and Alice Santos-Silva

Biomedicines 2024, 12(6), 1228; https://doi.org/10.3390/biomedicines12061228 - 31 May 2024

Viewed by 1018

Abstract

We aimed to study the impact of polymorphisms in the genes encoding interleukin-6 (IL6) and tumor necrosis factor receptor-2 (TNFR2), reported to be mortality risk predictors, in patients with end-stage kidney disease (ESKD) undergoing dialysis. TNFRSF1B (rs3397, rs1061624, and rs1061622) and IL6 (rs1800796, [...] Read more.

We aimed to study the impact of polymorphisms in the genes encoding interleukin-6 (IL6) and tumor necrosis factor receptor-2 (TNFR2), reported to be mortality risk predictors, in patients with end-stage kidney disease (ESKD) undergoing dialysis. TNFRSF1B (rs3397, rs1061624, and rs1061622) and IL6 (rs1800796, rs1800797, and rs1554606) polymorphisms were studied in patients with ESKD and controls; the genotype and allele frequencies and the associations with inflammatory and erythropoiesis markers were determined; deaths were recorded throughout the following two years. The genotype and allele frequencies for the TNFRSF1B rs3397 polymorphism were different in these patients compared to those in the controls and the global and European populations, and patients with the C allele were less common. Patients with the CC genotype for TNFRSF1B rs3397 presented higher hemoglobin and erythrocyte counts and lower TNF-α levels, suggesting a more favorable inflammatory response that seems to be associated with erythropoiesis improvement. Patients with the GG genotype for TNFRSF1B rs1061622 showed lower serum ferritin levels. None of the TNFRSF1B (rs3397, rs1061624, and rs1061622) or IL6 (rs1800796, rs1800797, and rs1554606) polymorphisms had a significant impact on the all-cause mortality rate of Portuguese patients with ESKD. Full article

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

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13 pages, 1994 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 - 2 May 2024

Viewed by 1146

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 [...] Read more.

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)

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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 1195

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 [...] Read more.

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 - 4 Jan 2024

Cited by 1 | Viewed by 1443

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, [...] Read more.

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 3 | Viewed by 2010

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 [...] Read more.

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

Viewed by 1084

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 [...] Read more.

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 - 7 Aug 2023

Viewed by 1641

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, [...] Read more.

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 - 8 Jun 2023

Cited by 2 | Viewed by 1740

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 [...] Read more.

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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17 pages, 7030 KiB

Open AccessReview

The Clinical Significance and Application of Heart Rate Variability in Dialysis Patients: A Narrative Review

by Rong-Na Jhen, Ping-Chen Wang, Yu-Ming Chang, Jsun-Liang Kao, Eric Chien-Hwa Wu and Chih-Chung Shiao

Biomedicines 2024, 12(7), 1547; https://doi.org/10.3390/biomedicines12071547 - 11 Jul 2024

Viewed by 1295

Abstract

Autonomic nervous system (ANS) dysfunction is prevalent in end-stage kidney disease (ESKD) patients, carrying significant risks for morbidity and mortality. Heart rate variability (HRV) is a simple and non-invasive method to evaluate ANS functions and predict prognoses in specific patient populations. Since there [...] Read more.

Autonomic nervous system (ANS) dysfunction is prevalent in end-stage kidney disease (ESKD) patients, carrying significant risks for morbidity and mortality. Heart rate variability (HRV) is a simple and non-invasive method to evaluate ANS functions and predict prognoses in specific patient populations. Since there is a lack of a clear understanding of the clinical significance of HRV in predicting prognoses in ESKD patients, an updated review on this topic is urgently warranted. The clinical significance of HRV in dialysis patients includes its associations with metabolic syndrome, nutritional status, intradialytic hypotension, vascular access failure, major adverse cardiovascular events, and mortality. These findings underscore the essential role of the autonomic reserve, which might denote the elevation of ANS activity as a response to external stimulus. Patients with a higher level of sympathetic activity at the resting stage, but who are unable to adequately elevate their sympathetic activity under stress might be susceptible to a worse outcome in critical circumstances. Further applications of HRV include HRV biofeedback, risk classification, and real-time HRV monitoring. Overall, HRV is an optimal tool for predicting prognoses in dialysis patients. Further study is encouraged in order to gain a clearer understanding of the clinical significance and application of HRV, and thereby enhance the care of ESKD patients. Full article

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

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23 pages, 851 KiB

Open AccessReview

Anemia of Chronic Kidney Disease—A Narrative Review of Its Pathophysiology, Diagnosis, and Management

by Krzysztof Badura, Jędrzej Janc, Joanna Wąsik, Szymon Gnitecki, Sylwia Skwira, Ewelina Młynarska, Jacek Rysz and Beata Franczyk

Biomedicines 2024, 12(6), 1191; https://doi.org/10.3390/biomedicines12061191 - 27 May 2024

Cited by 3 | Viewed by 5149

Abstract

Anemia is one of the most common chronic kidney disease (CKD) complications. It negatively affects patients’ quality of life and clinical outcomes. The pathophysiology of anemia in CKD involves the interplay of various factors such as erythropoietin (EPO) deficiency, iron dysregulation, chronic inflammation, [...] Read more.

Anemia is one of the most common chronic kidney disease (CKD) complications. It negatively affects patients’ quality of life and clinical outcomes. The pathophysiology of anemia in CKD involves the interplay of various factors such as erythropoietin (EPO) deficiency, iron dysregulation, chronic inflammation, bone marrow dysfunction, and nutritional deficiencies. Despite recent advances in understanding this condition, anemia still remains a serious clinical challenge in population of patients with CKD. Several guidelines have been published with the aim to systematize the diagnostic approach and treatment of anemia; however, due to emerging data, many recommendations vary between publications. Recent studies indicate a potential of novel biomarkers to evaluate anemia and related conditions such as iron deficiency, which is often present in CKD patients. Our article aims to summarize the pathophysiology of anemia in CKD, as well as the diagnosis and management of this condition, including novel therapeutic approaches such as hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHI). Understanding these complex subjects is crucial for a targeted approach to diagnose and treat patients with anemia in CKD effectively. Full article

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

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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 5 | Viewed by 7021

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 [...] Read more.

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

Cited by 2 | Viewed by 4454

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. [...] Read more.

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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15 pages, 2941 KiB

Open AccessSystematic Review

A Systematic Review and Meta-Analysis of MicroRNA as Predictive Biomarkers of Acute Kidney Injury

by Naomi Brown, Marius Roman, Douglas Miller, Gavin Murphy and Marcin J. Woźniak

Biomedicines 2024, 12(8), 1695; https://doi.org/10.3390/biomedicines12081695 - 30 Jul 2024

Cited by 1 | Viewed by 1163

Abstract

Acute kidney injury (AKI) affects 10–15% of hospitalised patients and arises after severe infections, major surgeries, or exposure to nephrotoxic drugs. AKI diagnosis based on creatinine level changes lacks specificity and may be delayed. MicroRNAs are short non-coding RNA secreted by all cells. [...] Read more.

Acute kidney injury (AKI) affects 10–15% of hospitalised patients and arises after severe infections, major surgeries, or exposure to nephrotoxic drugs. AKI diagnosis based on creatinine level changes lacks specificity and may be delayed. MicroRNAs are short non-coding RNA secreted by all cells. This review of studies measuring miRNAs in AKI aimed to verify miRNAs as diagnostic markers. The study included data from patients diagnosed with AKI due to sepsis, ischaemia, nephrotoxins, radiocontrast, shock, trauma, and cardiopulmonary bypass. Out of 71 studies, the majority focused on AKI in sepsis patients, followed by cardiac surgery patients, ICU patients, and individuals receiving nephrotoxic agents or experiencing ischaemia. Studies that used untargeted assays found 856 differentially regulated miRNAs, although none of these were confirmed by more than one study. Moreover, 68 studies measured miRNAs by qRT-PCR, and 2 studies reported downregulation of miR-495-3p and miR-370-3p in AKI patients with sepsis after the AKI diagnosis. In three studies, upregulation of miR-21 was reported at the time of the AKI diagnosis with a significant pooled effect of 0.56. MiR-21 was also measured 19–24 h after cardiac surgery in three studies. However, the pooled effect was not significant. Despite the considerable research into miRNA in AKI, there is a knowledge gap in their applicability as diagnostic markers of AKI in humans. Full article

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

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