Impaired Renal Function Research Articles

Background: Growing evidence suggests that left atrial dysfunction, or atrial cardiopathy, significantly increases mortality risk. Similarly, impaired renal function is a well-established predictor of mortality. However, the relationship between impaired renal function and atrial cardiopathy —and how their combined presence affects mortality risk—remains unexplored. Methods: This analysis included 6,573 participants (mean age 57.0 ± 13.0 years; 50.5% women; 74.6% White) from NHANES-III who underwent electrocardiogram (ECG) recording. We excluded individuals with an estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m 2 or major ECG abnormalities. The CKD-EPI equation was used to calculate eGFR. Atrial cardiopathy was defined from ECG tracings automatically processed at a central core facility as abnormal P-wave axis outside 0–75°, deep terminal negativity in V1 <100 µV, or prolonged P-wave duration in lead II >120 ms. Multivariable logistic regression assessed the cross-sectional association between impaired renal function (eGFR <45 vs. ≥45 mL/min/1.73 m 2 ) and atrial cardiopathy. Cox proportional hazards models evaluated the individual and combined associations of eGFR and atrial cardiopathy with mortality. Results: About 47.9% (n=3151) of the participants had atrial cardiopathy at baseline. In multivariable logistic regression model adjusted for sociodemographic and cardiovascular risk factors, eGFR <45 (compared to ≥45) mL/min/1.73 m 2 was associated with increased risk of atrial cardiopathy (OR (95% CI): 1.44(1.16–1.78)). During a median follow-up of 18.1 years, 3076 deaths occurred. Separate multivariable Cox proportional hazards models demonstrated that both atrial cardiopathy and eGFR <45 mL/min/1.73 m 2 (compared to ≥45) were associated with an increased risk of mortality (HR (95% CI): 1.12(1.04-1.20) and 1.50(1.34-1.68), respectively). Compared to participants with eGFR ≥ 45 mL/min/1.73 m 2 without atrial cardiopathy CM (reference group), those with coexistent eGFR <45 mL/min/1.73 m 2 and atrial cardiopathy exhibited substantially higher risk of mortality, which was higher than either condition alone; interaction p-value = 0.011 (Table). Conclusions: Impaired renal function is associated with increased risk of atrial cardiopathy, and both conditions independently predict mortality, and their coexistence exhibits a synergistic effect, substantially amplifying mortality risk beyond their individual contributions.

Cardiac and renal dysfunction are tightly linked, with each accelerating the other and undermining cardiovascular–kidney–metabolic health. Renal impairment is now recognized as a pivotal intermediary between metabolic risk factors and cardiovascular disease, particularly heart failure (HF). Recent single-cell RNA sequencing data has revealed shared inflammatory and fibrotic programs in both organs, yet the cellular and molecular drivers of their combined pathology remain incompletely defined. In the present study we integrated clinical and preclinical data to uncover pathways involved in mediating cardiac and renal dysfunction. Using the ICELL8 cx platform, we generated snRNA-seq libraries from frozen left ventricular (LV) tissue of healthy donors, HF patients, and HF + chronic kidney disease (CKD) patients (n=10/group, males and females, 30–70 years). We profiled 25,122 nuclei in total and snRNA sequencing identified 10 distinct cell populations with endothelial cells forming the bulk of cell types detected followed by fibroblasts and myeloid cells. Differential gene expression analysis highlighted pronounced transcriptional changes in endothelial cells, fibroblasts, myeloid cells, and pericytes. Compared to healthy donors, both diseased groups showed marked depletion of endothelial cells and pericytes that was more pronounced in HF + CKD patient samples, suggesting vascular dysfunction. Next, to establish causal associations between cardiac and renal dysfunction, we characterized 2 mouse models to study the impact of HF on renal function and CKD on cardiac function. The transverse aortic constriction (TAC) mouse model of HF (n = 15/group) displayed severe systolic dysfunction (ejection fraction 27.9 % vs 63.9 %; cardiac output 16.3 vs 23.3 mL/min), and persistent LV hypertrophy (198.5 vs 108.8 mg) via echocardiography. Kidney function measurements showed a progressive decline in GFR at 12 weeks post-surgery and reaching significance at 16 weeks post-surgery (946.6 vs 1 263 µL/min/100 g). Conversely, in the adenine model of CKD (n = 10/group), a sharp fall in GFR (194.9 vs 975.5 µL/min/100 g) was accompanied by a modest reduction cardiac output (13.3 vs 18.7 mL/min), and a compensatory rise in ejection fraction (74.7 % vs 67.2 %). Together, these integrated human and mouse datasets provide a detailed picture of cardiorenal pathophysiology and reveal alterations to cardiac endothelial and stromal cells in response to impaired renal function.

Background: Calcification is a well-established prognostic marker for coronary artery disease. However, its implications for renal artery stenosis are not well understood, particularly in patients with renovascular hypertension and impaired renal function undergoing revascularization. Objective: To investigate the impact of CKD stage and renal artery calcification assessed by intravascular ultrasound (IVUS) on renal functional outcomes after the revascularization in patients with renovascular hypertension. Methods: We conducted a retrospective analysis of patients with renovascular hypertension due to unilateral renal artery stenosis. All procedures were performed stent implantation under the guidance of IVUS. Plaque burden, presence of calcification, calcium arc, and stent area were assessed by IVUS. Patients were stratified into two groups based on their pre-procedural estimated glomerular filtration rate (eGFR): high-stage CKD (HS-CKD; eGFR ≧45 mL/min/1.73 m 2 ) and low-stage CKD (LS-CKD; eGFR <45 mL/min/1.73 m 2 ). Renal functional outcome was measured using delta eGFR, calculated as the difference between baseline and 1-year post-procedural eGFR. Associations between IVUS findings and delta eGFR were assessed in both the HS-CKD and LS-CKD groups. Results: A total of 33 patients (63.6% male, mean age 74.6 ± 9.1 years) were included. The follow-up duration was similar between the HS-CKD (n=13) and LS-CKD (n=20) groups (366 [267 to 381] vs. 356 [255 to 384] days, p=0.61). There was no significant difference in IVUS-derived vessel area, percent plaque area, and minimum stent area between the two groups. Renal artery calcification on IVUS was detected in 46.1% of the HS-CKD group and 65.0% of the LS-CKD group (p=0.28). In the HS-CKD group, the delta eGFR did not differ significantly between patients with and without calcification (−2 [−13 to 4] vs. 8 [−4 to 11.5] mL/min/1.73 m 2 , p=0.25). However, in the LS-CKD group, patients without calcification had a significantly lower delta eGFR than those with calcification (−4 [−6 to 1.5] vs. −1 [−2 to 8] mL/min/1.73 m 2 , p=0.04). No significant association was observed between calcium arc and delta eGFR in either group. Conclusion: In patients with renovascular hypertension due to unilateral renal artery stenosis, the presence of renal artery calcification has a potential association with renal function after revascularization, regardless of the degree of calcification, especially in those with lower stage CKD.

The anatomical and physiological congruence of cynomolgus macaques ( Macaca fascicularis ) to humans make them valuable models for translational research into heart failure (HF), renal disease (RD), and cardio-renal syndrome (CRS). In this study, we characterized aged cynomolgus monkeys with atherogenic diet-induced heart failure with reduced ejection fraction (HFrEF), including those with albuminuric RD—with or without changes in glomerular filtration rate (GFR)—to determine CRS progression and to compare findings with age-matched healthy controls. Sixty cynomolgus monkeys with HFrEF (mean ejection fraction [EF] 55.3% ± 0.7%) were studied. Animals were stratified into two groups based on baseline albuminuria status: microalbuminuric (HFrEF+RD; n=30) and normoalbuminuric (HFrEF-only, n=30). Multimodal diagnostics included cardiac 2D echocardiography, renal ultrasound, and biochemical analyses of urine and blood samples. Parameters assessed were 24-hour urine albumin-creatinine ratio (UACR), blood urea nitrogen, serum creatinine, and estimated GFR. Renal hemodynamics were evaluated by renal artery volume flow, peak systolic velocity, resistive index (RI), and pulsatility index (PI). HFrEF+RD animals exhibited a significant 2.8-fold increase in UACR over 25 weeks from 47.9±16.6 mg/g to 134.6±50.6 mg/g (p<0.001) while the UACR of the HFrEF-only animals remained stable. Baseline renal ultrasound revealed significantly lower renal artery volume flow (p<0.01) and peak systolic velocity (p<0.0001) in both HFrEF+RD and HFrEF-only groups compared to controls. GFR was moderately reduced in both groups implying mild to moderate renal functional impairment. Notably, RI and PI values remained within normal limits, consistent with early or less severe renal vascular injury. These findings reflected evolving CRS primarily characterized by progressive proteinuria and declining renal hemodynamics essentially in the HFrEF+RD cohort. These findings demonstrate that aged cynomolgus macaques with HFrEF develop CRS phenotypes closely resembling human disease, with HF contributing to progressive renal impairment through hemodynamic and molecular mechanisms. This NHP model offers significant translational potential to elucidate bidirectional heart-kidney interactions, and to enable the preclinical evaluation of novel therapeutic strategies targeting CRS.

Acute kidney injury (AKI) is a critical condition that exhibits rapid deterioration in renal function, which is typically accompanied by oxidative stress and inflammation. L-carvone, a chiral monoterpenoid ketone with robust anti-oxidative and anti-inflammatory capacities. The current research tried to examine the beneficial effect of L-carvone on AKI induced by endotoxin in mice and its underlying mechanisms. 36 BALB/c male mice were allocated into six groups: control (received normal saline only), model (obtained lipopolysaccharide (LPS) 10mg/kg as a single dose), and vehicle (received corn oil for five days, then LPS 10mg/kg on day five). The treatment groups received oral L-carvone at 25, 50 or 100mg/kg for five days before LPS. Kidneys and blood samples were taken twenty-24h following LPS injection for assessment. L-carvone substantially reduced serum concentrations of kidney injury molecule-(KIM)-1, blood urea nitrogen-(BUN), and creatinine, as well as improved renal pathological manifestations. Meanwhile, L-carvone also strikingly suppressed the inflammatory response as evidenced by significant decreases in the gene expressions of Toll-like receptor (TLR)-4, transcription factors like NF-κB, activator protein(AP)-1, and Interferon Regulatory Factor (IRF)-3 in renal tissue, resulting in attenuation of inflammatory elements, notably TNF-α and IL-1β. L-carvone also reduced the magnitude of the tubular injury score due to LPS. L-carvone abrogates LPS-induced AKI, blocking the TLR4-MYD88-dependent and TRIF-dependent signaling cascade, hence attenuating structural renal injuries and enhancing kidney function. L-carvone may have beneficial effects on LPS-induced AKI.

Physiologically based pharmacokinetic modeling of hydroxyurea: Implications for dose adjustment in patients with renal insufficiency.

Benzotriazole UV-stabilizer exposure in ring-billed gulls from an urban, freshwater harbour in Lake Ontario, Canada: evaluating contaminant bioaccumulation and potential health impacts.

Background: Sarcopenia and metabolic deterioration are major health concerns in adults aged ≥ 75 years with type 2 diabetes (T2DM), a population characterized by anabolic resistance, reduced dietary intake, and limited renal reserve. Optimizing protein nutrition may support muscle maintenance in this high-risk group, but clinical evidence for individualized high-protein guidance in the oldest-old population remains limited. Objective: We investigated whether an 18-month dietary intervention improves muscle mass and strength in adults aged ≥ 75 years with T2DM and whether serum amino acid (AA) and hormonal profiles reflect these changes. Methods: In this 18-month, single-arm, prospective intervention study, 44 community-dwelling adults aged ≥ 75 years with T2DM received individualized, dietitian-led nutritional guidance targeting a protein intake of approximately 1.4 g/kg ideal body weight (IBW)/day. Assessments at baseline and every 6 months included body composition, muscle strength, renal function, and fasting serum amino acid and hormonal profiles. Longitudinal changes were analyzed using paired t-tests and linear mixed-effects models. This trial was registered in the UMIN Clinical Trials Registry (UMIN000044687). Results: Skeletal muscle index and grip strength showed significant improvements at specific time points during follow-up (both p < 0.05), while gait speed improved at 6 months. Renal function remained clinically stable (eGFRcreat slope: +0.18 mL/min/1.73 m2/year; eGFRcys slope: −2.97 mL/min/1.73 m2/year), with no significant increase in CKD stage. Changes in glucagon correlated positively and C-peptide negatively with changes in skeletal muscle index, whereas glucagon was inversely associated with grip strength. Serum fibroblast growth factor 21 (FGF21) levels decreased over time, suggesting metabolic adaptation to the intervention. Conclusions: Individualized high-protein nutritional guidance for 18 months improved sarcopenia-related parameters, including skeletal muscle index and grip strength, without clinically significant deterioration of renal function in adults aged ≥ 75 years with T2DM. These findings support the feasibility and safety of protein-focused dietary counseling as a strategy to preserve muscle health in advanced age.

Integrated multi-omics profiling identifies Cmpk1 as a monocyte-specific therapeutic target for renal ischemia-reperfusion injury.

Modified Zn-MOF multifunctional nanoparticles for combination therapy of DN and exploratory study of the nephroprotective effect.

Glomerular Complications in Primary Myelofibrosis and the Role of Renal Transplantation: Systematic Review of The Current Evidence.

Chronic kidney disease represents a significant global health burden. Exposure to environmental endocrine-disrupting chemicals, particularly heavy metals and phthalate metabolites, is increasingly associated with renal dysfunction. However, previous research has primarily focused on individual chemicals, leaving a gap in understanding the health effects of real-world co-exposure to complex mixtures of these contaminants. We applied several statistical analysis methods (including multivariable logistic regression, restricted cubic splines regression, quantile g-computation, and Bayesian kernel machine regression) to examine data from 6902 adults participating in the National Health and Nutrition Examination Survey between 2005 and 2018. Lead (Pb) and cadmium were consistently associated with an increased risk of impaired renal function across all models. Pb exhibited a U-shaped exposure–response relationship. Mercury was not significantly associated with renal impairment. Among phthalates metabolites, mono-(2-ethyl-5-oxohexyl) phthalate was associated with an increased risk, whereas mono-(2-ethyl)hexyl phthalate was linked to a reduce risk. In mixture analyses, metals predominated the overall nephrotoxic associations (Bayesian kernel machine regression group PIP = 0.997), with Pb identified as the primary contributor. Significant interactions were observed between Pb and other metals, as well as several phthalate metabolites. Pb and cadmium are associated with nephrotoxicity, and their combined effects may be amplified when present in mixtures. Phthalates exhibit metabolite-specific associations and primarily act as effect modifiers. Regulatory frameworks must transition from single-chemical assessments to cumulative risk assessment paradigms to effectively address real-world co-exposures.

Appropriate dosing of piperacillin/tazobactam is crucial for hospitalized children and might be a challenge in case of augmented renal clearance. This study assessed the appropriateness of piperacillin dosing regimens recommended to attain pharmacokinetic/pharmacodynamic targets by pediatric guidelines using a population pharmacokinetic approach. A population pharmacokinetic model for piperacillin was developed using therapeutic drug monitoring observations collected in hospitalized children between 2012 and 2021. Subsequently, simulations were performed to evaluate whether dosing regimens recommended by various pediatric guidelines achieved the pharmacodynamic target [i.e. maintaining free piperacillin plasma concentrations above the minimum inhibitory concentration for 100% of the dosing interval (100% fT > MIC)] in case of augmented, normal and moderately impaired renal functions. The model best describing our 386 concentration values in 104 patients was a two-compartment model with allometric scaling of pharmacokinetic parameters based on bodyweight. Renal function also influenced clearance. Simulations revealed a risk of underdosing in patients with a creatinine clearance above 50 mL/min/1.73 m2 when piperacillin was administered as intermittent infusions, according to most guidelines. In contrast, continuous infusions consistently achieved the pharmacodynamic target even for MIC close to the limit of susceptibility. This study highlights the critical impact of renal function on piperacillin pharmacokinetics in pediatric patients. Continuous infusion regimens are necessary to ensure optimal drug exposure and efficacy, particularly in patients with augmented creatinine clearance. These results emphasize the need to revise pediatric dosing strategies considering a broader range of renal function.

This study analysed the safety and effectiveness of a 20% dose reduction of 177Lutetium-labelled prostate-specific membrane antigen (PSMA) radioligand therapy in patients with metastatic castration-resistant prostate carcinoma (mCRPC) and preexisting impaired renal function. In this retrospective study, 16 mCRPC patients with impaired renal function - estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 who received 177Lu-PSMA-I&T were identified. Median number of cycles was 4 (range 1-8 cycles), and median interval between cycles was 6 weeks. Renal function was monitored throughout the treatment. Therapy response was assessed via prostate-specific antigen (PSA) measurements. Patients received a 20% dose reduction from the standard dose of 7.4 GBq. Mean follow-up time was 8.5 months (range 2-37 months). Kaplan-Meier analysis was performed to obtain progression-free survival (PFS) and overall survival (OS). Mean baseline eGFR was 48 ml/min/1.73 m2 (range 21-59 ml/min/1.73 m2). Mean end-of-treatment eGFR was 51 ml/min/1.73 m2 (range 19-83 ml/min/1.73 m2). At the end of follow-up, the mean eGFR was 48 ml/min/1.73 m2 (range 20-83 ml/min/1.73 m2). There was no evidence that eGFR was affected by the 177Lu-PSMA-I&T treatment either after the last cycle or at the end of follow-up (P > 0.05). No patients suffered grade 4 renal toxicity. After 1 cycle, 50% of patients had a partial PSA response, which increased to 73% after two cycles. Median PFS was 12 months [95% confidence interval (CI): 4-14 months], and OS was 17 months (95% CI: 13-40 months). Findings support the feasibility of 177Lu-PSMA-I&T treatment in mCRPC patients with preexisting renal impairment (eGFR 21-59 ml/min/1.73 m2) when a 20% dose reduction is applied.

BACKGROUND: Renogram using Technetium-99m Diethylene Triamine Pentaacetic Acid (Tc-99m DTPA) is applied to evaluate renal perfusion, glomerular filtration rate (GFR), and urinary excretion. In patients with impaired renal function, delayed tracer elimination may increase accumulation in non-target organs such as the heart and liver, resulting in greater radiation exposure and reduced image quality. Studies examining the relationship between renal function and Tc-99m DTPA dose distribution remain limited, particularly in clinical settings in Indonesia. Therefore, in this study, an organ-level quantitative analysis of Tc-99m DTPA radiopharmaceutical dose distribution and absorbed dose using the Medical Internal Radiation Dose (MIRD) approach based on Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) imaging was performed.METHODS: Thirty adult patients undergoing renogram were categorized into low-GFR (&lt;60 mL/min/1.73 m²) and high-GFR (≥60 mL/min/1.73 m²) groups. Each patient received 4–5 mCi of Tc-99m DTPA intravenously. Organ activities were obtained from regions of interest (ROIs) on SPECT/CT images, and organ-level absorbed doses (mGy) were calculated using the MIRD formalism.RESULTS: In the low-GFR group, tracer retention in non-target organs increased, with absorbed doses up to twofold higher in the heart (0.0002–0.0136 mGy) and liver (0.0010–0.0178 mGy) compared to the high-GFR group. Renal absorbed doses ranged from 0.0001–0.0694 mGy, showing no significant difference between the left and right kidneys, while significant differences were observed in the heart and liver.CONCLUSION: GFR significantly affects the radiopharmaceutical dose distribution and absorbed dose of Tc-99m DTPA. Reduced renal function increases radiation exposure in non-target organs, whereas normal function results in a more localized renal dose distribution.KEYWORDS: Tc-99m DTPA, renogram, MIRD, glomerular filtration rate, absorbed dose, SPECT/CT, nuclear medicine

Crisugabalin is a novel calcium channel α2δ subunit ligand and a highly selective oral gamma-aminobutyric acid (GABA) analogue developed for the treatment of diabetic peripheral neuropathic pain (DPNP) and postherpetic neuralgia (PHN). This study investigated pharmacokinetic properties and safety of crisugabalin in subjects with renal impairment. This multicenter, nonrandomized, open-label Phase I study investigated the pharmacokinetics and safety of a single oral 20-mg dose of crisugabalin capsule in Chinese subjects with various degrees of renal function, categorized according to the absolute glomerular filtration rate (GFR). A total of 32 subjects (eight subjects per renal function category [normal, mild, moderate, or severe impairment]) were enrolled and completed the study. Blood samples were collected up to 72 h post-dose, along with fractionated urine samples. Active moiety exposures were calculated as the sum of unbound exposures for crisugabalin and its active metabolites. The t1/2 was prolonged with increasing severity of renal impairment. Compared to subjects with normal renal function, patients with mild, moderate and severe renal impairment showed increases in plasma crisugabalin Cmax by 6.00%, 13.83% and 21.63%, respectively. The AUC0-inf of plasma crisugabalin in patients with mild, moderate and severe renal impairment increased by 14.63%, 119.57% and 272.61%, respectively, compared to subjects with normal renal function. For patients with GFR < 60 mL/min, dosage adjustments of crisugabalin should be considered. To maintain comparable plasma drug concentrations in patients with impaired renal function, it is recommended that crisugabalin doses be decreased by approximately 50% for every 50% decline in GFR.

Hypertension is the most common cardiovascular risk factor in older adults, significantly contributingto morbidity and mortality. Its prevalence rises with age and is strongly associated with vascular aging, isolated systolic hypertension, and comorbidities, such as cognitive impairment and chronic kidney disease. However, treatment in older adults-especially those with frailty-requires a careful balance between benefit and potential harm. This review aimed to provide an updated synthesis of pathophysiological mechanisms, epidemiological trends, diagnostic considerations, and evidence‑based therapeutic approaches to arterial hypertension in older adults. Emphasis was placed on tailoring treatment strategies according to frailty and functional status. We conducted a narrative review of major international guidelines (European Society of Cardiology, European Society of Hypertension), clinical trials, and real‑world studies addressing hypertension in aging populations. Special focus was given to randomized controlled trials and observational studies stratified by frailty. Evidence supports blood pressure lowering in fit older adults, as demonstrated in trials such as HYVET, SPRINT‑SENIOR, and STEP, which showed significant reductions in cardiovascular events and mortality. Conversely, some studies (eg, PARTAGE, OPTiMiSE, and DANTE) highlighted the risks of overtreatment in frail or institutionalized patients, including hypotension, falls, and increased mortality. The presence of orthostatic hypotension, impaired renal function, and polypharmacy further complicates management. In conclusion, hypertension management in the elderly should follow a personalized approach based on a comprehensive geriatric assessment and frailty evaluation; patient‑centered goals are essential to guide treatment intensity, aiming to protect cardiovascular health without compromising safety, cognition, or functional independence. Future studies must include frailer populations to better inform clinical decisions.

Patient: Male, 50-year-oldFinal Diagnosis: Ureteral calculiSymptoms: No any symptomsClinical Procedure: —Specialty: UrologyObjective: Unusual clinical courseBackgroundThis report describes a 50-year-old man with large bilateral ureteral stones and hydronephrosis. Bilateral impacted large ureteral stones present significant clinical challenges and can lead to serious complications, such as hydronephrosis, urinary tract infections, and renal function impairment. Due to their size and location, treatment often requires advanced techniques and specialized equipment to achieve optimal outcomes while minimizing complications. In the present case, use of the smallest 6.3-Fr flexible ureteroscopy with holmium laser lithotripsy effectively managed the condition, demonstrating its utility in treating complex ureteral stones.Case ReportA 50-year-old man received a diagnosis of bilateral impacted ureteral stones. The right ureteral stone measured 22×10×10 mm, and the left stone was 11×10×8 mm, accompanied by hydronephrosis. After antibiotic therapy, flexible ureteroscopic lithotripsy was performed using a 6.3-Fr disposable digital flexible ureteroscope. Holmium laser fragmentation was followed by stone fragment retrieval using a vacuum-assisted ureteral access sheath. Postoperative computed tomography confirmed complete stone clearance and significant improvement in hydronephrosis. The patient had an uneventful recovery without significant complications.ConclusionsThe 6.3-Fr disposable flexible ureteroscope is highly effective for large impacted ureteral stones. Its small diameter minimizes ureteral trauma, enhances irrigation, and provides superior visualization. The vacuum-assisted ureteral access sheath facilitates efficient stone retrieval, reducing operative time and complications. This case highlights the potential advantages of the 6.3-Fr ureteroscope in treating complex urolithiasis, especially in patients with challenging anatomical conditions. Further studies and clinical trials are needed to validate its broader application and long-term outcomes.

Background/Objectives: Systemic sclerosis-associated interstitial lung disease (SSc-ILD) and chronic obstructive pulmonary disease (COPD) are linked to multi-organ vulnerability involving the lungs, heart, and kidneys. This study aimed to compare the annual changes in pulmonary, cardiac, and renal parameters in patients with SSc-ILD and COPD across three consecutive years, using both individual biomarkers and integrated composite profiles. Methods: This observational longitudinal study included repeated assessments in 2023, 2024, and 2025. Functional, laboratory, and imaging parameters were collected: 6-min walk test (6MWT), SpO2 (pre-/post-exercise), spirometry/CT lung volumes, gas exchange (pO2/pCO2/lactate), echocardiography [left ventricular ejection fraction (LVEF), estimated systolic pulmonary artery pressure (sPAP)], cardiac biomarkers (NT-proBNP, MR-proANP, hsTnT), renal markers [eGFR, creatinine, albuminuria, albumin-to-creatinine ratio (ACR)], heart rate variability (HRV), and renal CT densitometry. All markers were standardized (z-scores, higher values = worse). Subprofiles were generated and aggregated into three integrated profiles (cardiac, renal, pulmonary). Within-group dynamics were analyzed using the Wilcoxon signed-rank test (year-to-year deltas), between-group comparisons with the Mann–Whitney U test, effect sizes via Cliff’s delta, and multiple testing correction with the Benjamini–Hochberg false discovery rate (FDR). Results: Exercise tolerance declined in both groups: by 2025, 6MWT distance decreased by −10 m in SSc-ILD (p = 0.006; q = 0.010) and −20 m in COPD (p = 0.002; q = 0.004); post-exercise SpO2 fell in both cohorts (both p &lt; 0.001; q &lt; 0.001). MR-proANP remained consistently higher in SSc-ILD across all years (p ≤ 0.005; q ≤ 0.028). sPAP increased in both groups, reaching higher values in COPD by 2025 (p = 0.007; q = 0.033). NT-proBNP and hsTnT increased over time, while eGFR declined, and ACR rose in both cohorts (both p &lt; 0.001; q &lt; 0.001). HRV (HF/total power) decreased by 2025. Composite profiles showed: in 2023, the cardiac profile was worse in SSc-ILD (δ ≈ 0.27; p = 0.011; q = 0.048), but differences diminished by 2025; the renal profile was initially worse in SSc-ILD but later shifted unfavorably in COPD; the pulmonary profile showed no consistent between-group differences. Conclusions: Over three years, patients with SSc-ILD and COPD exhibited concordant deterioration in pulmonary, cardiac, and renal function. Distinct leading markers emerged: desaturation during exercise and neurohormonal activation (MR-proANP) in SSc-ILD, versus reduced 6MWT and higher sPAP in COPD. These findings support the need for integrated monitoring of the cardio–pulmo–renal continuum. Limitations include the observational design, multiple comparisons, and absence of advanced repeated-measures modeling.

Sepsis-associated acute kidney injury (S-AKI) is a critical and life-threatening clinical syndrome characterized by intricate pathophysiological mechanisms and lack of effective therapeutic strategies. Our previous investigations in a diabetic nephropathy model indicated the potential protective effect of the Vitamin D Receptor (VDR) in regulating autophagy. Nevertheless, the precise association and involvement regarding VDR and autophagy in sepsis-associated AKI remains unknown. This research aims to investigate the protective role and underlying mechanisms of VDR in mitigating S-AKI. Through establishment of S-AKI models in VDR knockout mice and treatment with vitamin D receptor agonist paricalcitol, we reported that VDR deficiency exacerbated renal functional deterioration and histological alterations induced by lipopolysaccharide, whereas VDR activation markedly ameliorated these impairments. Mechanistic inquiries revealed that VDR could restore the expression of ATG16L1, a key regulator in autophagosome formation, by inhibition of miR-20a-5p, thereby fostering autophago­some maturation and facilitating autophagic flux impaired by LPS in renal tubular epithelial cells. Moreover, luciferase and ChIP experiments corroborated the direct transcriptional regulation role of VDR on miR-20a-5p. Collectively, this investigation illuminates a novel pathway through which VDR regulate autophagic dysfunction induced by lipopolysaccharide via the VDR-miR20a-5p-ATG16L1 axis, thereby introducing a promising therapeutic target against sS-AKI.