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46 pages, 3406 KB  
Review
IgA Nephropathy: Mechanisms, Risk Stratification, and Precision Therapy
by Sami Alobaidi
Diagnostics 2026, 16(9), 1259; https://doi.org/10.3390/diagnostics16091259 (registering DOI) - 22 Apr 2026
Abstract
IgA nephropathy is the most common primary glomerulonephritis worldwide and a leading cause of chronic kidney disease and kidney failure, with geographic and ancestral variation and a course ranging from asymptomatic urinary abnormalities to progressive loss of kidney function. This narrative review links [...] Read more.
IgA nephropathy is the most common primary glomerulonephritis worldwide and a leading cause of chronic kidney disease and kidney failure, with geographic and ancestral variation and a course ranging from asymptomatic urinary abnormalities to progressive loss of kidney function. This narrative review links the multi-hit model to risk stratification, biomarkers, current management, and emerging therapies, and highlights implementation gaps. Risk assessment is longitudinal, prioritizing proteinuria and estimated glomerular filtration rate trajectories and integrating Oxford MEST-C, prediction tools, and biomarker and multi-omics approaches, while recognizing limitations in histologic reproducibility and model calibration. Current management is anchored in optimized supportive care aimed at sustained proteinuria reduction and kidney protection, including intensive blood pressure control with maximal tolerated renin–angiotensin system blockade, dietary sodium restriction and lifestyle measures, and sodium–glucose co-transporter 2 inhibitors for eligible patients. For selected higher-risk patients with persistent proteinuria despite optimized supportive care, immunomodulatory strategies are discussed, including systemic corticosteroids and targeted-release budesonide (Nefecon), emphasizing structured toxicity risk mitigation and cautioning against assuming interchangeability among alternative oral budesonide formulations. Emerging therapies are organized around mechanism-aligned targets across the BAFF/APRIL axis, complement pathways, and endothelin-based approaches, with growing interest in sequencing and combination regimens layered on supportive care. Key gaps include reliance on surrogate endpoints, limited long-term durability and safety data, and uneven evidence for special populations. Full article
(This article belongs to the Special Issue Advances in Diagnostics of Chronic Kidney Disease)
14 pages, 283 KB  
Review
Risk Factors and Outcome in Living Kidney Donors: A Narrative Review
by Lucas-Gabriel Discălicău, Cătălin Baston, Bogdan-Marian Sorohan, Oana Moldoveanu, Silviu Guler-Margaritis, Pavel-Mihai Vișinescu and Ioanel Sinescu
Kidney Dial. 2026, 6(2), 28; https://doi.org/10.3390/kidneydial6020028 - 22 Apr 2026
Abstract
Background/Objectives: Candidates with cardiometabolic risk are considered for living kidney donation more frequently because of the global organ shortage. The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines introduced individualized risk assessment based on composite donor profiles rather than categorical exclusion, but the [...] Read more.
Background/Objectives: Candidates with cardiometabolic risk are considered for living kidney donation more frequently because of the global organ shortage. The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines introduced individualized risk assessment based on composite donor profiles rather than categorical exclusion, but the long-term implications of accepting donors with potential risk factors require careful evaluation. This review synthesizes current evidence on outcomes of living kidney donors with obesity, prediabetes, hypertension, and smoking. Methods: A literature search was conducted in PubMed/MEDLINE for studies published between 1 January 2000 and 28 February 2026, including cohort studies, registry analyses, meta-analyses, and clinical guidelines evaluating living kidney donors with obesity, smoking, prediabetes, or hypertension. Priority was given to large cohorts with long-term follow-up. Over 70 publications were included in the final synthesis. Findings were synthesized narratively by risk factors and outcomes. Results: Obesity was associated with an 86% increased end-stage kidney disease (ESKD) risk and 32% increased 20-year mortality. Central adiposity measures outperformed body mass index (BMI) for predicting estimated glomerular filtration rate (eGFR) decline. Post-donation weight gain increased the risk for developing hypertension and diabetes. Smoking conferred a 7.5-fold chronic kidney disease (CKD) risk, with impaired compensatory renal adaptation after donation. Prediabetic donors showed comparable outcomes to normoglycemic donors, with 57.8% reverting to normoglycemia at 10 years. Pre-donation hypertension increased 15-year ESKD risk 3-fold, but absolute risk remained low. At 15 years post-donation, over 50% of the donors developed hypertension. Glucagon-like peptide-1 (GLP-1) receptor agonists reduce diabetes progression by 73–94% in at-risk populations, but prospective studies in donors are lacking. Conclusions: Each risk factor carries quantifiable risks for individualized stratification. These risk factors usually coexist and interact. Refinement of risk prediction models, strategies for metabolic optimization and prospective evaluation of emerging pharmacologic therapies are key priorities. Full article
13 pages, 564 KB  
Article
The Importance of Plasma Renin Concentrations in Intensive Care Patients with Circulatory Shock
by Yasemin Bozkurt Turan and Sait Karakurt
J. Clin. Med. 2026, 15(9), 3184; https://doi.org/10.3390/jcm15093184 - 22 Apr 2026
Abstract
Background: Renin is a hypoperfusion marker and a good index of renin–angiotensin–aldosterone system (RAAS) activity. The purpose of this study was to evaluate whether the plasma renin concentration (PRC) can represent a tissue perfusion marker for predicting mortality in patients with circulatory shock [...] Read more.
Background: Renin is a hypoperfusion marker and a good index of renin–angiotensin–aldosterone system (RAAS) activity. The purpose of this study was to evaluate whether the plasma renin concentration (PRC) can represent a tissue perfusion marker for predicting mortality in patients with circulatory shock in intensive care. Methods: This prospective study included patients aged 18 years or older who were hospitalized in the intensive care unit (ICU). A total of 69 patients were enrolled, of whom 37 had circulatory shock and were all diagnosed with septic shock according to Sepsis-3 criteria, while 32 patients did not have shock. Patient groups were compared, and survival analysis was carried out. Mortality predictions of PRC, lactate and combined tests (including PRC, mottling scores, central venous saturation of oxygen, C-reactive protein, procalcitonin, and lactate) were investigated with ROC analysis. Results: ICU 28-day mortality was 36.2% (n = 25) and was significantly higher in patients with circulatory shock than those without (CS:21, 56.8% vs. NS:4, 12.5%, respectively, p < 0.001). The survival was significantly higher in patients without circulatory shock than those with shock (17 vs. 16 days; p = 0.038). The increase in mottling score (HR: 1.64 [95%CI: 1.15–2.33]; p < 0.01) and PRC (HR = 1.01 [95%CI: 1.00–1.02]; p < 0.05) levels and the decrease in glomerular filtration rate (GFR) (HR = 0.98 [95%CI: 0.96–0.99]; p < 0.05) were associated with decreased survival times in the ICU patients (p < 0.001). Combined tests yielded better prediction of mortality than PRC level alone. Conclusions: PRC may reflect circulatory shock and predict survival in critically ill patients; however, larger prospective studies incorporating serial PRC measurements are needed before it can be recommended as an independent biomarker of mortality. Full article
(This article belongs to the Special Issue Sepsis and Septic Shock: Diagnosis, Treatment, and Prognosis)
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19 pages, 1544 KB  
Article
Short-Term Effects of Structured Physical Activity With or Without Dietary Counselling in Early-Stage Chronic Kidney Disease Managed in Primary Care: A Non-Randomised Controlled Study
by Lorena Bosnar Zelenika, Dragana Tišma, Tamara Ciko, Pero Hrabač, Ivana Vuković Brinar and Valerija Bralić Lang
J. Clin. Med. 2026, 15(8), 3169; https://doi.org/10.3390/jcm15083169 - 21 Apr 2026
Abstract
Background/Objectives: To evaluate the short-term effects of structured physical activity (PA), alone or combined with dietary counselling, in early-stage chronic kidney disease (CKD) patients managed in primary healthcare (PHC). Methods: This non-randomised controlled study was conducted in Croatia from 1 September to [...] Read more.
Background/Objectives: To evaluate the short-term effects of structured physical activity (PA), alone or combined with dietary counselling, in early-stage chronic kidney disease (CKD) patients managed in primary healthcare (PHC). Methods: This non-randomised controlled study was conducted in Croatia from 1 September to 30 November 2025. Ninety adults aged 40–75 years with early-stage CKD were allocated to three groups: structured PA, combined PA and dietary counselling, or control. Interventions included kinesiologist-led PA and, in the combined group, dietitian-led Mediterranean/plant-based counselling. Outcomes included estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (ACR), cardiometabolic risk factors, behavioural measures, quality of life, and sleep quality. Statistical significance was set at p < 0.01. Results: Seventy-eight participants completed follow-up. Changes in eGFR did not differ between groups (p = 0.310). Mean ± standard deviation changes in ACR were −1.10 ± 6.37, −0.86 ± 2.88, and +1.18 ± 3.13 in the PA, combined, and control groups, respectively (p = 0.017, not meeting the prespecified significance threshold). Significant between-group differences were observed for selected patient-reported and PA outcomes, including emotional well-being, energy/fatigue, role limitations due to emotional problems, sedentary time, and total PA (all p ≤ 0.006). Conclusions: Structured PA, with or without dietary counselling, improved PA behaviour and selected patient-reported outcomes in early-stage CKD managed in PHC but did not demonstrate significant short-term effects on kidney-related outcomes. These findings support the feasibility of integrating lifestyle-oriented interventions into PHC as part of integrated CKD care, while larger, longer-term studies are needed. Full article
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9 pages, 1157 KB  
Article
Metformin Use and Clinical Outcomes in Very Elderly Patients with Type 2 Diabetes and Chronic Kidney Disease
by Michele Marchini
Medicina 2026, 62(4), 776; https://doi.org/10.3390/medicina62040776 - 16 Apr 2026
Viewed by 211
Abstract
Background and Objactives: Metformin is the most widely prescribed glucose-lowering therapy worldwide and is generally considered safe in patients with chronic kidney disease (CKD) with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2. However, very elderly patients are underrepresented in pivotal [...] Read more.
Background and Objactives: Metformin is the most widely prescribed glucose-lowering therapy worldwide and is generally considered safe in patients with chronic kidney disease (CKD) with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2. However, very elderly patients are underrepresented in pivotal trials, and evidence on metformin safety in this vulnerable population remains limited. We evaluated the association between metformin use and adverse clinical outcomes in very elderly patients with CKD and type 2 diabetes. Materials and Methods: We conducted a single-center retrospective observational study including 624 very elderly patients (age > 78 years) with CKD, type 2 diabetes mellitus, and eGFR > 30 mL/min/1.73 m2. Patients were stratified according to metformin exposure (309 metformin-treated and 315 controls). The primary composite outcome was the first occurrence of intensive care unit (ICU) admission, initiation of renal replacement therapy (RRT), lactic acidosis, or all-cause mortality. A propensity score-matched sensitivity analysis and hierarchical win ratio analysis were also performed to further address potential baseline confounding. Results: Over a median follow-up of 33.7 months, the primary composite outcome occurred more frequently in the metformin group than in controls (18.7% vs. 9.5%; HR 1.75; 95% CI 1.12–2.73; p = 0.013). Metformin use was associated with a higher risk of ICU admission (HR 2.33; 95% CI 1.33–4.08), RRT initiation (HR 1.90; 95% CI 1.14–3.16), and lactic acidosis (HR 3.14; 95% CI 1.75–5.65). All-cause mortality was numerically higher but not statistically significant (HR 1.57; 95% CI 0.89–2.78). In a propensity score-matched analysis including 260 matched pairs, the association between metformin exposure and adverse outcomes remained consistent, and hierarchical win ratio analysis favored the control group (win ratio 2.00; 95% CI 1.24–3.47). Conclusions: In very elderly patients with CKD and type 2 diabetes, metformin use was associated with a higher observed risk of adverse clinical outcomes. These findings support a cautious, individualized risk–benefit assessment when prescribing metformin in this population. Full article
(This article belongs to the Section Urology & Nephrology)
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11 pages, 1147 KB  
Article
Body Surface Area Indexing Attenuates Apparent Early eGFR Decline After Sleeve Gastrectomy: A Retrospective Cohort Study
by Emre Cankaya, Hakan Babaoglu, Feyza Bayrakdar Çağlayan, Semahat Karahisar Sirali, Oktay Banli, Mehmet Emin Demir and Fatih Dede
J. Clin. Med. 2026, 15(8), 3001; https://doi.org/10.3390/jcm15083001 - 15 Apr 2026
Viewed by 230
Abstract
Background: Early postoperative changes in creatinine-based estimated glomerular filtration rate (eGFR) after bariatric surgery can be misread as a kidney injury. During rapid weight loss, indexing eGFR to a fixed body surface area (BSA) of 1.73 m2 may alter apparent trajectories. [...] Read more.
Background: Early postoperative changes in creatinine-based estimated glomerular filtration rate (eGFR) after bariatric surgery can be misread as a kidney injury. During rapid weight loss, indexing eGFR to a fixed body surface area (BSA) of 1.73 m2 may alter apparent trajectories. We compared absolute (mL/min) and BSA-indexed (mL/min/1.73 m2) eGFR changes after sleeve gastrectomy, stratified by baseline glomerular hyperfiltration (GH). Methods: In this retrospective cohort of 145 adults undergoing laparoscopic sleeve gastrectomy, serum creatinine was obtained at baseline (≤30 days pre-op) and 3 months (post-op days 75–105). Indexed eGFR was calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 creatinine equation; BSA with the Mosteller formula; and absolute eGFR as indexed eGFR × (BSA/1.73). GH was defined as indexed eGFR ≥ 120 mL/min/1.73 m2. A REML mixed-effects model (Group, Time, Group × Time) with patient-cluster bootstrap inference was used. An age-adjusted sensitivity model including Age and Age × Time was also fitted. Results: Fifty-four participants (37%) met the GH criteria. Absolute eGFR declined by −26.6 mL/min in GH versus −17.3 mL/min in non-GH (difference-in-differences [DiD] −9.3 mL/min; 95% CI −13.9 to −4.7; p < 0.001). The indexed eGFR changes were smaller (−4.2 vs. −0.5 mL/min/1.73 m2; DiD −3.7; 95% CI −7.3 to −0.03; p = 0.048; bootstrap p_sign = 0.052). In the age-adjusted sensitivity model, the Group × Time interaction for absolute eGFR attenuated but remained statistically significant (−6.57 mL/min; 95% CI, −13.09 to −0.06; p = 0.048), whereas the corresponding interaction for indexed eGFR was attenuated and no longer statistically significant (−3.99 mL/min/1.73 m2; 95% CI −9.15 to 1.16; p = 0.129). Conclusions: Within three months after sleeve gastrectomy, participants with higher baseline indexed filtration showed a larger decline in absolute eGFR but only a small change in indexed eGFR. These results show that early postoperative creatinine-based eGFR trajectories are scale dependent and should be interpreted cautiously during rapid weight loss. Because postoperative acute kidney injury (AKI) was not adjudicated and direct kidney function markers were unavailable, this study does not distinguish physiological hemodynamic change from structural kidney injury. Reporting both absolute and indexed eGFR may improve early postoperative interpretation and help align dosing decisions with rapid changes in body size. Full article
(This article belongs to the Section Nephrology & Urology)
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19 pages, 657 KB  
Article
Association Between the Early Postoperative Changes in Serum Brain Natriuretic Peptide and Allograft Survival After Kidney Transplantation: A Retrospective Cohort Study
by Shih-Yu Chen, Chih-Chien Sung, Chien-Chang Kao, Sheng-Tang Wu, Wei-Hung Chan, Chun-Chang Yeh and Wei-Cheng Tseng
J. Clin. Med. 2026, 15(8), 2982; https://doi.org/10.3390/jcm15082982 - 14 Apr 2026
Viewed by 250
Abstract
Background: Kidney transplantation (KT) improves survival and quality of life in patients with end-stage kidney disease; however, long-term allograft survival remains a major challenge. Brain natriuretic peptide (BNP), a biomarker of cardiorenal stress and volume status, may be associated with early postoperative [...] Read more.
Background: Kidney transplantation (KT) improves survival and quality of life in patients with end-stage kidney disease; however, long-term allograft survival remains a major challenge. Brain natriuretic peptide (BNP), a biomarker of cardiorenal stress and volume status, may be associated with early postoperative physiological changes after KT. This study evaluated the association between early postoperative BNP changes and long-term allograft survival, and explored the potential role of BNP-derived parameters in relation to graft outcomes. Methods: This retrospective cohort study included adult recipients of deceased-donor KT between 2009 and 2018. Patients were categorized according to early graft function. Serum BNP levels were measured preoperatively and within postoperative 24 h, and the percentage increase (dBNP ratio) was calculated. Cox regression and receiver operating characteristic analyses were used to identify risk factors for graft failure and evaluate the discriminatory performance of BNP-derived biomarkers, respectively. Results: Among the 179 recipients, postoperative BNP levels and dBNP ratios differed significantly across graft function groups, with higher values in delayed graft function. After multivariate adjustment, the dBNP ratio remained significantly associated with graft failure (hazard ratio, 1.16; 95% confidence interval, 1.10–1.21; p < 0.001). Additionally, the dBNP ratio demonstrated better discriminatory performance for graft failure compared with postoperative BNP alone (area under the curve, 0.815 vs. 0.596; p < 0.001), with an exploratory cutoff of approximately 18%. Recipients with a dBNP ratio ≥ 18% had poorer early graft function, lower longitudinal estimated glomerular filtration rates, and significantly reduced graft survival. Conclusions: An increased early postoperative dBNP ratio was significantly associated with adverse long-term kidney allograft outcomes. However, given the potential for residual confounding, these findings should be interpreted as associative and hypothesis-generating rather than predictive. Full article
(This article belongs to the Section Nephrology & Urology)
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22 pages, 616 KB  
Review
The Gut–Kidney–Metabolic Axis: Impact of Gut-Derived Uremic Toxins on Insulin Resistance in Diabetic Kidney Disease
by Charlotte Delrue, Margaux Vinckier, Reinhart Speeckaert, Stefania Marzocco and Marijn M. Speeckaert
Int. J. Mol. Sci. 2026, 27(8), 3472; https://doi.org/10.3390/ijms27083472 - 13 Apr 2026
Viewed by 243
Abstract
Chronic kidney disease (CKD), especially diabetic kidney disease (DKD), is characterized not only by progressive loss of renal function but also by profound metabolic disturbances, including insulin resistance (IR). Emerging evidence implicates gut-derived uremic toxins as mediators linking intestinal dysbiosis to metabolic and [...] Read more.
Chronic kidney disease (CKD), especially diabetic kidney disease (DKD), is characterized not only by progressive loss of renal function but also by profound metabolic disturbances, including insulin resistance (IR). Emerging evidence implicates gut-derived uremic toxins as mediators linking intestinal dysbiosis to metabolic and renal injury. Several microbial metabolites, for example, indoxyl sulfate, p-cresyl sulfate, and trimethylamine-N-oxide, are known to accumulate in CKD due to decreased renal excretion and altered tubular secretion. In vitro and in vivo experiments indicate that these gut-derived nephrotoxins impair insulin signaling pathways in cells. This results in increased production of reactive oxygen species, activation of stress kinases, higher levels of inflammatory cytokines, and inhibitory serine phosphorylation of insulin receptor substrates. Consequently, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling is impaired, reducing cellular glucose uptake. At the same time, these toxins induce endothelial dysfunction and mitochondrial damage, not only causing systemic IR but also contributing to the progression of kidney disease. Observational data link higher plasma toxin levels with components of IR, rapid loss of renal function as measured by estimated glomerular filtration rate, and a high risk of cardiovascular events in CKD patients. Although causality in humans remains unproven, interventions targeting the microbiota, toxin binding, and oxidative stress pathways show promise. We propose an integrated gut–kidney–metabolic framework in which dysbiosis-driven toxin production may amplify IR and DKD progression. Full article
(This article belongs to the Special Issue Molecular Insights into Diabetic Nephropathy)
13 pages, 498 KB  
Article
Inappropriate Antimicrobial Dosing in Regard to Renal Function in a Tertiary Hospital in Greece—A Single-Center Point Prevalence Study
by Petros Ioannou, Andria Papazachariou, Stamatis Karakonstantis and Diamantis Kofteridis
Medicina 2026, 62(4), 743; https://doi.org/10.3390/medicina62040743 - 13 Apr 2026
Viewed by 291
Abstract
Background and Objectives: Appropriate antimicrobial dosing according to kidney function is essential to ensure therapeutic efficacy while minimizing toxicity and antimicrobial resistance. Despite established dosing guidelines and electronic prescribing systems, errors in renal dose adjustment of antimicrobials, particularly in the setting of [...] Read more.
Background and Objectives: Appropriate antimicrobial dosing according to kidney function is essential to ensure therapeutic efficacy while minimizing toxicity and antimicrobial resistance. Despite established dosing guidelines and electronic prescribing systems, errors in renal dose adjustment of antimicrobials, particularly in the setting of acute kidney injury, remain common among hospitalized patients. Materials and Methods: A point-prevalence study was conducted on 31 October 2024 at a tertiary-care hospital in Greece to evaluate the appropriateness of antimicrobial dosing in relation to renal function. Patient characteristics, renal parameters, and antimicrobial prescriptions were extracted from electronic medical records. Glomerular filtration rate (GFR) was estimated using the MDRD formula. Comparative analyses were performed between correctly and incorrectly dosed cases, and between overdosing and underdosing episodes. Results: A total of 235 hospitalized patients were evaluated (mean age 64.8 ± 18.6 years; 43.4% female). Overall, 15.7% (37/235) received at least one antimicrobial dose inappropriate for their renal function. Among 37 patients where dosing errors were identified, overdosing was noted in 23 (62.2%), underdosing in 16 (43.2%), adding up to 39 prescriptions, while in 2 patients (5.4%), both mistakes were noted in different prescribed antimicrobials. Drug-specific error rates varied considerably: ceftazidime and cefuroxime showed the highest rates of inappropriate dosing (40% each), followed by colistin (33.3%) and acyclovir (33.3%). Piperacillin/tazobactam, the most frequently prescribed agent (n = 50), had a 14% error rate, mainly due to underdosing (10%). Patients with dosing errors were significantly older (71.5 vs. 64.1 years, p = 0.0220) and had worse renal function, including higher serum creatinine (1.68 vs. 1.19 mg/dL, p = 0.0174), lower GFR (58.5 vs. 75.9 mL/min/1.73 m2, p = 0.0009), and more frequent dialysis (13.5% vs. 4.3%, p = 0.0422). They also received a higher median number of antimicrobials (2 vs. 1, p = 0.0185). Conclusions: Inappropriate antimicrobial dosing based on kidney function remains common in hospitalized patients, particularly among older individuals and those with impaired renal function or polypharmacy. Targeted antimicrobial stewardship strategies focusing on renal dose adjustment and agents that are more frequently dosed inappropriately, such as colistin, acyclovir, cefuroxime, and ceftazidime, as well as agents that are frequently prescribed despite a relatively lower rate of inappropriate dose, such as piperacillin/tazobactam, are needed to enhance prescribing safety and optimize therapeutic outcomes. Full article
(This article belongs to the Special Issue Emerging Strategies in Infection Control and Antimicrobial Therapy)
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13 pages, 418 KB  
Systematic Review
Injectable Lipid-Lowering Therapies in Chronic Kidney Disease: Efficacy, Outcomes, Safety and Implementation—A Systematic Review
by Joshua Louis Davies, Yimeng Zhang, Inuri Patabendi, Sudarshan Ramachandran and Jyoti Baharani
BioMed 2026, 6(2), 11; https://doi.org/10.3390/biomed6020011 - 12 Apr 2026
Viewed by 346
Abstract
Background/Objectives: Cardiovasc{Citation}ular disease accounts for 50% of chronic kidney disease (CKD) mortality, yet fewer than 40% of patients achieve guideline LDL-cholesterol (LDL-C) targets on statins. Injectable lipid-lowering therapies (ILLTs)—PCSK9 inhibitors and inclisiran—offer 50–70% LDL-C reductions but lack comprehensive CKD-specific evidence synthesis. This [...] Read more.
Background/Objectives: Cardiovasc{Citation}ular disease accounts for 50% of chronic kidney disease (CKD) mortality, yet fewer than 40% of patients achieve guideline LDL-cholesterol (LDL-C) targets on statins. Injectable lipid-lowering therapies (ILLTs)—PCSK9 inhibitors and inclisiran—offer 50–70% LDL-C reductions but lack comprehensive CKD-specific evidence synthesis. This systematic review evaluated ILLT efficacy, safety, and implementation across kidney function stages including dialysis. Methods: Following PROSPERO registration (CRD42024612594), we searched MEDLINE, Embase, Cochrane Library, CINAHL, and Google Scholar (1995–August 2025). Two reviewers independently screened studies using PICOS criteria: adults with CKD stages G3-G5, dialysis, or transplant recipients receiving injectable lipid therapies. Primary outcomes were LDL-C percentage change and major adverse cardiovascular events. Quality was assessed using NIH tools. Given heterogeneity, we performed narrative synthesis following SWiM guidance. Results: Eight studies (n = 28,013) met the criteria. The FOURIER trial demonstrated that evolocumab achieved 58–59% LDL-C reductions across kidney function strata (interaction p = 0.77) with preserved cardiovascular benefit (HR 0.82–0.89). Absolute risk reduction was greater in advanced CKD (2.5% vs. 1.7%), reflecting higher baseline rates. Pharmacokinetic studies showed no eGFR-exposure correlation requiring dose adjustment; evolocumab was not removed by haemodialysis. Inclisiran achieved a 67–80% PCSK9 reduction and a 35–58% LDL-C reduction across renal groups, with twice-yearly maintenance dosing. Both classes reduced non-HDL-C (45–50%), apoB (40–45%), and lipoprotein(a) (20–25%). Safety was favourable, with mild injection-site reactions (< 5%); no renal decline signals emerged. Conclusions: Evidence for injectable lipid-lowering therapies in CKD are driven largely by a single large post hoc subgroup analysis (FOURIER) and small phase 1–2 PK/PD studies, with minimal dialysis representation and no transplant data. These agents appear to provide substantial LDL-C reductions across CKD stages G3–G5 without dose adjustment, but cardiovascular and renal outcome data in advanced CKD and dialysis remain limited and should be interpreted cautiously. Full article
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12 pages, 565 KB  
Article
Associations Between Composite Host Vulnerability Score and Transfusion Outcomes After Trauma
by Yun-Chul Park, Young-Goun Jo, Hyun-Seok Jang, Eui-Sung Jeong and Ji-Hyoun Kang
Medicina 2026, 62(4), 732; https://doi.org/10.3390/medicina62040732 - 12 Apr 2026
Viewed by 249
Abstract
Background and Objectives: Outcomes after trauma are traditionally attributed to injury severity and acute physiologic derangement. However, host vulnerability at presentation—reflecting underlying physiologic and nutritional status—may also be associated with bleeding severity and transfusion requirements following acute injury. Whether such vulnerability contributes [...] Read more.
Background and Objectives: Outcomes after trauma are traditionally attributed to injury severity and acute physiologic derangement. However, host vulnerability at presentation—reflecting underlying physiologic and nutritional status—may also be associated with bleeding severity and transfusion requirements following acute injury. Whether such vulnerability contributes additional risk information beyond established factors remains incompletely understood. Materials and Methods: We conducted a retrospective cohort study of adult trauma patients using a single-center trauma registry. Host vulnerability was assessed using a composite score (CE; range 0–3) based on admission hypoalbuminemia (<3.5 g/dL), anemia (hemoglobin < 11 g/dL), and reduced renal function (estimated glomerular filtration rate < 60 mL/min/1.73 m2). Primary outcomes were any blood transfusion and massive transfusion, defined as transfusion of ≥10 units of packed red blood cells within 24 h of admission. Associations between CE score and transfusion outcomes were evaluated using univariable and multivariable logistic regression models adjusted for age, Injury Severity Score (ISS), admission lactate level, and systolic blood pressure (SBP). Results: Among 4105 trauma patients, transfusion requirements increased progressively with higher CE scores. Rates of any transfusion rose from 21.7% in patients with CE 0 to 78.6% in those with CE 3, while massive transfusion increased from 1.9% to 23.1% across the same categories. In multivariable analyses, each 1-point increase in CE score was independently associated with higher odds of any transfusion (adjusted odds ratio [aOR] 3.21, 95% confidence interval [CI] 2.80–3.68) and massive transfusion (aOR 1.73, 95% CI 1.45–2.07). Conclusions: A composite score reflecting host vulnerability at presentation was associated with bleeding severity and transfusion requirements after trauma, beyond injury severity and acute physiologic factors. These findings suggest that simple laboratory-based markers may provide additional information for early risk stratification of hemorrhagic outcomes after trauma. Full article
(This article belongs to the Special Issue Autoimmune Diseases: Advances and Challenges)
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18 pages, 1243 KB  
Article
Cardiorenal Interactions in Acute Decompensated Heart Failure: Associations Between Renal Dysfunction, Albuminuria, and Echocardiographic Markers of Myocardial Function
by Claudia Andreea Palcău, Livia Florentina Păduraru and Ana Maria Alexandra Stănescu
Life 2026, 16(4), 645; https://doi.org/10.3390/life16040645 - 11 Apr 2026
Viewed by 325
Abstract
Background: Renal dysfunction is common in patients hospitalized with acute decompensated heart failure (ADHF) and represents a key component of cardiorenal syndrome. However, the relationships between renal impairment, cardiorenal biomarkers, and echocardiographic markers of myocardial function remain incompletely characterized in ADHF populations. Methods: [...] Read more.
Background: Renal dysfunction is common in patients hospitalized with acute decompensated heart failure (ADHF) and represents a key component of cardiorenal syndrome. However, the relationships between renal impairment, cardiorenal biomarkers, and echocardiographic markers of myocardial function remain incompletely characterized in ADHF populations. Methods: We conducted a cross-sectional analysis of 144 consecutive patients hospitalized with ADHF. Renal dysfunction was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. Clinical, laboratory, and echocardiographic parameters were compared according to renal function. Correlation analyses, multivariable logistic regression, and receiver operating characteristic (ROC) curve analyses were performed to evaluate associations between renal dysfunction, cardiorenal biomarkers, and myocardial functional indices. Results: Patients with renal dysfunction were older (p = 0.002) and more frequently had diabetes mellitus (p = 0.006). Echocardiographic evaluation demonstrated significantly lower systolic mitral annular velocity (S′) (p < 0.001) and higher E/e′ ratios (p < 0.001) in patients with renal dysfunction, whereas left ventricular ejection fraction (p = 0.133) and global longitudinal strain (GLS) (p = 0.121) were similar between groups. Log-transformed NT-proBNP and albuminuria were significantly correlated with S′, GLS, and E/e′ (all p < 0.001). In multivariable analysis adjusted for clinically relevant confounders, chronic kidney disease (OR 8.16, 95% CI 2.13–31.34; p = 0.002) and the E/e′ ratio (OR 2.01, 95% CI 1.52–2.66; p < 0.001) remained independently associated with renal dysfunction. ROC analysis showed that E/e′ had the strongest ability to distinguish between patients with and without renal dysfunction (AUC 0.887, 95% CI 0.834–0.941; p < 0.001). Conclusions: Renal dysfunction in ADHF is associated with echocardiographic markers reflecting impaired longitudinal myocardial function and elevated filling pressure, with E/e′ emerging as the strongest echocardiographic correlate. The integration of echocardiographic parameters with cardiorenal biomarkers may improve the characterization of the cardiorenal profile in patients hospitalized with ADHF. Full article
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10 pages, 242 KB  
Article
Beyond Blood Pressure: Cardiac Structural and Functional Abnormalities in Hypertensive Postmenopausal Women with Mild-to-Moderate Chronic Kidney Disease
by Pasquale Palmiero, Francesca Amati, Lucrezia Bombini, Marco Matteo Ciccone and Maria Maiello
J. Clin. Med. 2026, 15(8), 2895; https://doi.org/10.3390/jcm15082895 - 10 Apr 2026
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Abstract
Background: Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality, even at early stages. Postmenopausal women represent a particularly vulnerable population due to estrogen deficiency, which promotes adverse cardiovascular remodeling. However, data specifically characterizing the cardiac phenotype of hypertensive postmenopausal [...] Read more.
Background: Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality, even at early stages. Postmenopausal women represent a particularly vulnerable population due to estrogen deficiency, which promotes adverse cardiovascular remodeling. However, data specifically characterizing the cardiac phenotype of hypertensive postmenopausal women with mild-to-moderate CKD remain limited. Methods: We conducted a prospective observational cohort study including 413 hypertensive postmenopausal women consecutively referred to a tertiary center between 2019 and 2022. Participants were stratified into a CKD group with stage 3 CKD (estimated glomerular filtration rate of 30–59 mL/min/1.73 m2; n = 213) and a control group without CKD (n = 200). All subjects underwent comprehensive clinical evaluation, laboratory testing, and standardized transthoracic echocardiography. The prevalence of left ventricular hypertrophy (LVH), left ventricular diastolic dysfunction (LVDD), and chronic coronary syndromes (CCS) was assessed. Multivariable logistic regression analyses were performed to evaluate independent associations between CKD and cardiovascular abnormalities. Results: Compared with controls, women with CKD showed a significantly higher prevalence of LVH (46.7% vs. 21.5%), LVDD (55.8% vs. 36.0%), and CCS (15.5% vs. 7.5%) (all p < 0.01). The coexistence of LVH and LVDD identified a high-risk cardiac phenotype that was markedly more frequent in the CKD group (41.3% vs. 12.5%). After adjustment for age, body mass index, blood pressure, duration of hypertension, smoking status, and antihypertensive therapy, stage 3 CKD remained independently associated with LVH, LVDD, and CCS. Conclusions: In hypertensive postmenopausal women, mild-to-moderate CKD is associated with a substantial burden of cardiac structural and functional abnormalities exceeding that attributable to hypertension alone, supporting early cardiovascular screening and an integrated cardiorenal approach. Full article
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12 pages, 761 KB  
Article
Cardiovascular Diseases Among Kidney Transplant Recipients at National Guard Hospital—Jeddah
by Nadia O. Elamin, Hala E. Danish, Razan O. Bawazir, Renad F. Alharthy, Renad I. Katib, Joud M. Alharthy, Maryam N. Alotibi and Turki A. Banamah
Healthcare 2026, 14(8), 987; https://doi.org/10.3390/healthcare14080987 - 9 Apr 2026
Viewed by 214
Abstract
Background: Cardiovascular disease (CVD) represents the second leading cause of death among kidney transplant recipients (KTRs). CVD risks post-transplantation increase with aging, obesity, dyslipidemia, diabetes, hypertension, inactivity, sleep disturbances, immunosuppressant medications use, and graft dysfunction. This study assessed CVD prevalence and risk factors [...] Read more.
Background: Cardiovascular disease (CVD) represents the second leading cause of death among kidney transplant recipients (KTRs). CVD risks post-transplantation increase with aging, obesity, dyslipidemia, diabetes, hypertension, inactivity, sleep disturbances, immunosuppressant medications use, and graft dysfunction. This study assessed CVD prevalence and risk factors among KTRs. Methods: A cross-sectional study was conducted at National Guard Hospital, Jeddah between 2012–2022. Information was collected from the patients’ medical records. Physical activity, sleep, and adherence to immunosuppressant therapy were evaluated via interviews with adult KTRs using the International Physical Activity Scale, Jenkins Sleep Scale, and Immunosuppressant Therapy Barrier Adherence Scale, respectively. Results: Sixty-four KTRs were included: 67% were males, and the median age was 44.7 years. Eighteen patients (28.1%) had CVD, and 61.1% of them developed ischemic heart disease. KTRs with CVD were older, had lower estimated glomerular filtration rate (eGFR), and higher Hemoglobin A1c (HbA1c), but these differences were not statistically significant (p > 0.05). Patients with CVD had significantly lower LDL (p = 0.02) and more aspirin and statin use (p < 0.05). Forty-five patients (70.3%) completed the interview; most of them had few sleep disturbances and good adherence to immunosuppressant therapy. Low physical activity was reported by KTRs with CVD. Conclusions: CVD was present in over one-quarter of KTRs. Patients with CVD were older, less active, had lower GFR, higher HbA1c, and significantly lower LDL. More use of aspirin and statin improved the glycemic control, physical activity, and medication adherence, and may help in reducing CVD burden among KTRs. Full article
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12 pages, 873 KB  
Communication
Analysis of Circulating and Urinary Levels of hsa-miRNA-770-5p in Diabetic Nephropathy
by Dimitar Nikolov, Georgi Nikolov, Mariela Geneva-Popova, Stanislava Popova-Belova, Mladen Naydenov and Mari Georgieva Karusheva
Biomolecules 2026, 16(4), 545; https://doi.org/10.3390/biom16040545 - 8 Apr 2026
Viewed by 252
Abstract
Background: Diabetic nephropathy (DN), also referred to as diabetic kidney disease, represents one of the most common microvascular complications of type 2 diabetes mellitus (T2DM) and remains a leading cause of end-stage renal disease worldwide. Conventional clinical markers, including albuminuria and estimated glomerular [...] Read more.
Background: Diabetic nephropathy (DN), also referred to as diabetic kidney disease, represents one of the most common microvascular complications of type 2 diabetes mellitus (T2DM) and remains a leading cause of end-stage renal disease worldwide. Conventional clinical markers, including albuminuria and estimated glomerular filtration rate (eGFR), are widely used for diagnosis and staging but may have limited sensitivity for detecting early renal injury and predicting disease progression. In recent years, circulating microRNAs (miRNAs) have emerged as promising non-invasive biomarkers that reflect underlying molecular mechanisms of diabetic nephropathy and may complement traditional clinical indicators. Objective: The present study aimed to evaluate serum and urinary levels of hsa-miRNA-770-5p across different stages of diabetic nephropathy and to assess its potential diagnostic value in relation to established indicators of renal function. Methods: A total of 257 participants were included and divided into four groups: healthy controls, patients with T2DM without nephropathy, patients with T2DM and DN in CKD stages I–II, and patients with DN undergoing maintenance hemodialysis (MHD). Serum and urinary levels of miRNA-770-5p were measured using quantitative real-time polymerase chain reaction (qPCR) and analyzed using the 2−ΔΔCt method. Statistical analyses included comparisons between groups using ANOVA, correlation analyses with renal function parameters such as eGFR and proteinuria/albuminuria, and receiver operating characteristic (ROC) curve analysis to evaluate diagnostic performance. Results: Serum levels of miRNA-770-5p were significantly elevated in patients with DN and in patients undergoing maintenance hemodialysis compared with healthy controls and patients with T2DM without nephropathy. In contrast, urinary levels of miRNA-770-5p were markedly reduced in patients with DN. Serum levels in patients with T2DM without nephropathy were slightly lower than those observed in healthy controls. Significant correlations were identified between miRNA-770-5p levels and renal function parameters, including eGFR and proteinuria/albuminuria, supporting the biological relevance of this microRNA in renal injury. ROC curve analysis demonstrated good discriminatory ability for differentiating DN from T2DM without nephropathy (serum AUC = 0.82; urine AUC = 0.79). Conclusions: hsa-miRNA-770-5p demonstrates distinct and opposite patterns in serum and urine that correlate with the severity of diabetic nephropathy. The complementary changes observed in circulating and urinary levels support the potential of miRNA-770-5p as a non-invasive biomarker that may complement conventional clinical markers and provide additional insight into the molecular mechanisms involved in the development and progression of diabetic nephropathy. Full article
(This article belongs to the Special Issue The Biomarkers in Renal Diseases)
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