Search Results (45)

Cardiorenal syndrome (CRS) reflects the intricate and bidirectional interplay between cardiac and renal dysfunction, commonly resulting in diagnostic uncertainty, therapeutic dilemmas and poor outcomes. While traditional biomarkers like serum creatinine (Cr) and natriuretic peptides remain widely used, their limitations in specificity, timing and contextual interpretation often hinder optimal management. This narrative review synthesizes the current evidence on established and emerging biomarkers in CRS, with emphasis on their clinical relevance, integration into real-world practice, and potential to inform precision therapy. Markers of glomerular filtration rate beyond creatinine—such as cystatin C—offer more accurate assessment in frail or sarcopenic patients, while tubular injury markers such as NGAL, KIM-1, and urinary L-FABP (uL-FABP) provide early signals of structural renal damage. The FDA-approved NephroCheck^® test—based on TIMP-2 and IGFBP7— enables risk stratification for imminent AKI up to 24 h before functional decline. Congestion-related markers such as CA125 and bio-adrenomedullin outperform natriuretic peptides in certain CRS phenotypes, particularly in right-sided heart failure or renally impaired patients. Fibrosis and inflammation markers (galectin-3, sST2, GDF-15) add prognostic insights, especially when combined with NT-proBNP or troponin. Rather than presenting biomarkers in isolation, this review proposes a framework that links them to specific clinical contexts—such as suspected decongestion-related renal worsening or persistent congestion despite therapy—to support actionable interpretation. A tailored, scenario-based, multi-marker strategy may enhance diagnostic precision and treatment safety in CRS. Future research should prioritize prospective biomarker-guided trials and standardized pathways for clinical integration. Full article

Acute kidney injury (AKI) is a frequent and severe complication in trauma patients, affecting up to 28% of intensive care unit (ICU) admissions and contributing significantly to morbidity, mortality, and long-term renal impairment. Trauma-related AKI (TRAKI) arises from diverse mechanisms, including hemorrhagic shock, ischemia–reperfusion injury, systemic inflammation, rhabdomyolysis, nephrotoxicity, and complex organ crosstalk involving the brain, lungs, and abdomen. Pathophysiologically, TRAKI involves early disruption of the glomerular filtration barrier, tubular epithelial injury, and renal microvascular dysfunction. Inflammatory cascades, oxidative stress, immune thrombosis, and maladaptive repair mechanisms mediate these injuries. Trauma-related rhabdomyolysis and exposure to contrast agents or nephrotoxic drugs further exacerbate renal stress, particularly in patients with pre-existing comorbidities. Traditional markers such as serum creatinine (sCr) are late indicators of kidney damage and lack specificity. Emerging structural and stress response biomarkers—such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), interleukin-18 (IL-18), C-C motif chemokine ligand 14 (CCL14), Dickkopf-3 (DKK3), and the U.S. Food and Drug Administration (FDA)-approved tissue inhibitor of metalloproteinases-2 × insulin-like growth factor-binding protein 7 (TIMP-2 × IGFBP-7)—allow earlier detection of subclinical AKI and better predict progression and the need for renal replacement therapy. Together, functional indices like urinary sodium and fractional potassium excretion reflect early microcirculatory stress and add clinical value. In parallel, risk stratification tools, including the Renal Angina Index (RAI), the McMahon score, and the Haines model, enable the early identification of high-risk patients and help tailor nephroprotective strategies. Together, these biomarkers and risk models shift from passive AKI recognition to proactive, personalized management. A new paradigm that integrates biomarker-guided diagnostics and dynamic clinical scoring into trauma care promises to reduce AKI burden and improve renal outcomes in this critically ill population. Full article

Systemic sclerosis (SSc) is an autoimmune disease associated with a high burden of morbidity and mortality due to organ complications. Pulmonary arterial hypertension (PAH) and cardiac involvement, characterized by chronic right ventricular (RV) pressure overload with consequent RV dysfunction and ultimately right heart failure (HF), are among these. A common comorbidity in SSc is chronic kidney disease (CKD). CKD is often present at the time of PAH diagnosis or a decline in renal function may occur during the course of the disease. CKD is strongly and independently associated with mortality in patients with PAH and HF. The cardiovascular and renal systems are closely interconnected, and disruption of this balance may result in cardiorenal syndrome (CRS). Type 2 CRS refers to CKD as a consequence of chronic HF. In clinical practice, non-specific markers such as troponin, B-type natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP), and serum creatinine aid in CRS diagnosis. More specific biomarkers, including cystatin C (CysC), neutrophil gelatinase-associated lipocalin (NGAL), galectin-3, and soluble urokinase plasminogen activator receptor (suPAR), have shown value for diagnosis and prognosis in CRS. This study aimed to evaluate comprehensively heart/kidney damage markers related to CRS in SSc patients compared with healthy controls (HC) and to examine their association with renal and cardiac ultrasound parameters. SSc patients showed significantly higher CRS markers than HC (p < 0.001). SSc patients with clinically diagnosed CRS had significantly elevated galectin-3, suPAR, sNGAL, and uNGAL levels (p < 0.05) than SSc patients without CRS. Positive correlations were found between renal resistive index (RRI) and NT-proBNP (r = 0.335, p < 0.05), and between RRI and suPAR (r = 0.331, p < 0.05). NT-proBNP, suPAR, galectin-3, sNGAL, and uNGAL emerge as promising biomarkers for the early detection of cardiac and renal involvement in SSc patients. Full article

Background/Objectives: COVID-19 is a systemic viral infection that may lead to serious complications including acute kidney injury that requires kidney replacement therapy. The primary aim of this study was to evaluate urinary SerpinA3 (uSerpinA3) excretion as a biomarker of kidney recovery at 90 days, and the mortality in patients with critical COVID-19 and AKI requiring kidney replacement therapy (KRT). Methods: The study included patients with critical COVID-19 on invasive mechanical ventilation (IMV) requiring KRT. Blood and urine samples were obtained when KRT was initiated (day zero), and thereafter on days 1, 3, 7, and 14 post-replacement. uSerpinA3, kidney injury molecule-1 (uKIM-1), and neutrophil gelatinase-associated lipocalin (uNGAL) were measured in urine, and interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor alpha (TNF-α) in peripheral blood. In addition, metabolomics in sample days zero and 3, and in the survivors on sample day 90 was performed by employing gas chromatography coupled with mass spectrometry. Results: A total of 60 patients were recruited, of whom 29 (48%) survived hospitalization and recovered kidney function by day 90. In the survivors, 79% presented complete recovery (CRR) and the remaining (21%) recovered partially (PRR). In terms of uSerpinA3, levels on days 7 and 14 predicted CRR, with AUC values of 0.68 (p = 0.041) and 0.71 (p = 0.030), respectively, as well as mortality, with AUC values of 0.75 (p = 0.007) and 0.76 (p = 0.015), respectively. Among the other biomarkers, the excretion of uKIM-1 on day zero of KRT had a superior performance as a CRR predictor [(AUC, 0.71 (p = 0.017)], and as a mortality predictor [AUC, 0.68 (p = 0.028)]. In the metabolomics analysis, we identified four distinct profiles; the metabolite that maintained statistical significance in predicting mortality was p-cresol glucuronide. Conclusions: This study strongly suggests that uSerpinA3 and uKIM-1 can predict CRR and mortality in patients with critical COVID-19 and AKI requiring KRT. Metabolic analysis appears promising for identifying affected pathways and their clinical impact in this population. Full article

Heartworm disease, caused by Dirofilaria immitis, often leads to pulmonary hypertension (PH), a serious cardiovascular complication in infected dogs. PH may impair renal function through hemodynamic and inflammatory mechanisms, even when traditional biomarkers such as serum creatinine and blood urea nitrogen (BUN) remain within normal ranges. This study aimed to assess urinary neutrophil gelatinase-associated lipocalin (uNGAL) levels in dogs naturally infected with D. immitis, with and without PH, to evaluate its potential as an early biomarker of renal dysfunction. Forty-two infected dogs were included and divided into two groups based on the presence (n = 14) or absence (n = 28) of PH, diagnosed via echocardiography. uNGAL concentrations were significantly higher in dogs with PH (mean 66.49 ± 6.67 ng/mL) compared to those without PH (mean 49.01 ± 14.48 ng/mL; p < 0.0001), despite normal creatinine and BUN values. No significant associations were found between uNGAL and sex, age, breed, or clinical signs. These findings suggest that uNGAL may serve as a sensitive biomarker of early renal impairment in dogs with heartworm disease and PH, even in the absence of overt azotemia, supporting its use in clinical evaluation and the monitoring of disease progression. Full article

Exercise training in extreme temperatures concurrent with hypohydration status may potentiate the development of acute kidney injury (AKI) in young, healthy persons. Background/Objectives: It is unknown how repeated training bouts in ambient higher temperatures and humidity may influence measures of AKI. The purpose of this study was to investigate hydration status and renal biomarkers related to AKI in NCAA Division I female soccer athletes during preseason conditioning. Methods: A convenience sample of n = 21 athletes were recruited (mean ± SEM; age: 19.3 ± 0.25 y; height: 169.6 ± 1.36 cm; mass: 68.43 ± 2.46 kg; lean body mass: 45.91 ± 1.13 kg; fat mass: 22.51 ± 1.69 kg; body fat %: 32.22 ± 1.32%). The average temperature was 27.43 ± 0.19 °C, and the humidity was 71.69 ± 1.82%. Body composition, anthropometric, workload, and 14 urine samples were collected throughout the preseason training period for urine specific gravity (USG), creatinine (uCr), cystatin C (uCyst-C), and neutrophil gelatinase-associated lipocalin (uNGAL) analyses. Results: Our investigation showed that, when compared to baseline (D0), the athletes maintained a USG-average euhydrated status (1.019 ± 0.001) and were euhydrated prior to each exhibition game (D5-Pre: p = 0.03; 1.011 ± 0.001; D10-Pre: p = 0.0009; 1.009 ± 0.001); uCr was elevated on D8 (p = 0.001; 6.29 ± 0.44 mg·dL⁻¹·LBM⁻¹) and D10-Post (p = 0.02; 6.61 ± 0.44 mg·dL⁻¹·LBM⁻¹); uCyst-C was elevated on D6 through D10 (p = 0.001; ~0.42 ± 0.01 mg·dL⁻¹); no differences were found in uNGAL concentration. The highest distance (m) displaced was found during exhibition games (D5: p = <0.0001; ~8.6 km and D10: p = <0.0001; ~9.6 km). During the preseason conditioning, the athletes maintained a euhydrated status (~1.019) via USG, an increase in uCr that averaged within a normal range (208 mg·dL⁻¹), and an increase in uCyst-C to near AKI threshold levels (0.42 mg·L⁻¹) for several practice sessions, followed by an adaptive decline. No differences were found in uNGAL, which may be explained by athlete variation, chosen time sample collection, and variation in training and hydration status. Conclusions: The athletes maintained a euhydrated status, and this may help explain why urinary markers did not change or meet the reference threshold for AKI. Full article

Dogs with acute congestive heart failure (CHF) can develop acute kidney injury (AKI); the prevalence of this condition has not been defined. This study aimed to assess the occurrence of AKI (increase in serum creatinine (sCr) ≥ 0.3 mg/dL) within 48 h from admission in dogs with myxomatous mitral valve disease (MMVD) with acute CHF, and the role of urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a predictive marker of AKI. This was a multicentric, prospective observational study. Thirty dogs were included. The types and dosages of the diuretics administered, as well as the serum and urinary chemistry, including uNGAL and uNGAL, to the urinary creatinine ratio (uNGALC), were determined at admission (T0) and after 24 (T24) and 48 (T48) hours of hospitalization. Nineteen dogs developed AKI. We found no statistically significant differences in sCr, uNGAL, uNGALC, diuretic dosage, or hours of hospitalization between dogs that developed AKI and those that did not. The urinary NGAL and uNGALC values were not statistically significantly different at any time point, while the sCr was higher at T24 and T48 than T0. Our findings suggest that AKI in MMVD dogs with CHF is primarily functional, driven by effective decongestion rather than severe tubular damage, with the benefits of decongestion outweighing transient increases in sCr. Full article

Background: Major adverse kidney events (MAKEs), including death, persistent AKI (pAKI), and renal replacement therapy, are more common in SARS-CoV-2-related ARDS. Invasive mechanical ventilation (IMV), systemic inflammation, and hemodynamic changes drive this risk. This study examines early IMV settings and urinary kidney biomarkers (UKBs) to better understand the development of MAKEs at 30 days. Methods: This prospective, cross-sectional cohort study was conducted in a single center between September and October 2021. This study included adults (≥18 years) diagnosed with ARDS due to SARS-CoV-2, requiring IMV within the first 6 h of admission. Exclusion criteria included a history of chronic kidney disease (CKD) and pregnant women. Initial mechanical ventilator settings were recorded after compliance-guided PEEP titration, and urine samples were collected for the analysis of UKBs at the same time. Our primary and secondary endpoints were to assess risk factors associated with MAKEs at 30 days and pAKI, respectively. Results: The cohort included 45 patients, with a median age of 57.75 (±18.64) years. In total, 32 (71%) developed MAKEs and 22 (48.8%) developed pAKI. MAKEs were associated with older age (adjusted odds ratio (aORs) = 1.23 95% CI: 1.00–1.22; p = 0.038) and higher driving pressure (ΔP) (aORs = 1.62, 95% CI:1.01–2.60, p = 0.043). Only urinary neutrophil gelatinase-associated lipocalin (uNGal) > 40 ng/mL was associated with pAKI (aORs = 8.54, 95% CI:1.75–41.65, p = 0.008). Conclusions: Early ventilator settings, particularly higher ΔP, play a critical role in the development of MAKEs. uN-Gal could enhance the early detection of pAKI, providing opportunities for timely interventions. Full article

Glomerulonephritis, caused by the deposition of immune complexes, can lead to kidney damage in dogs with canine monocytic ehrlichiosis (CME). The early diagnosis of renal insult is important to prevent severe kidney disease in infected dogs by Ehrlichia canis. This study aimed to investigate urinary biomarkers of renal function, neutrophil gelatinase (uNGAL), and kidney injury molecule-1 (uKIM-1) using the Luminex^® xMAP^® platform, and the proportion of mixed or high molecular weight proteinuria in dogs with CME. This study included blood samples of thirty dogs with clinical signs of CME and amplified DNA for E. canis (CME group) and six dogs of different breeds and both sexes, aged 3 to 7 years, that showed no clinical-laboratory alterations or tick parasitism and were tested negative for E. canis via PCR (control group). The total calcium, phosphorus (p < 0.05), urea (p < 0.001), creatinine (p < 0.05), urinary density (p < 0.05), urinary protein creatinine ratio (p < 0.001), uNGAL (p < 0.05), and uKIM-1 (p > 0.05), as well as the proportion of high molecular weight proteinuria and mixed proteinuria (p < 0.01), were measured. Elevated serum concentrations of creatinine, urea, and phosphorus combined with reduced urinary density, increased urinary creatinine–protein ratio, urinary NGAL, and mixed proteinuria detected renal damage in dogs with CME, while KIM -1 remained unchanged. uNGAL can detect early renal lesions, reflecting renal damage before a significant increase in serum creatinine occurs, and appears to be an early diagnostic biomarker in renal disease in dogs with CME. Full article

Background: The current gold standards for diagnosing acute kidney injury (AKI) are an increase in serum creatinine and a decrease in urine output, which are inadequate for rapid diagnosis. Neutrophil gelatinase-associated lipocalin (NGAL) is a 25-kDa protein produced and secreted by injured kidney tubule epithelial cells, and can serve as an early urinary biomarker for AKI. ProNephro AKI (NGAL) is an immunoassay for the quantitative determination of NGAL in urine (uNGAL) that recently received FDA clearance. A multisite, cross-sectional study was conducted to establish reference intervals for uNGAL in apparently healthy individuals. Methods: Urine samples were collected from apparently healthy individuals aged ≥3 months who met all inclusion criteria and no exclusion criteria. Specimens were temporarily stored at room temperature or 2–8 °C, then transferred into urinalysis tubes before being frozen and shipped for testing. uNGAL testing was performed using the ProNephro AKI (NGAL) immunoassay on a Roche cobas c501 analyzer. Results: Of the 688 individuals screened, 677 were eligible, and 629 (91.4%) of those were deemed evaluable. The 95th and 97.5th percentile uNGAL values for all pediatric participants were below the clinical cutoff of 125 ng/mL. uNGAL values were statistically significantly higher for female vs. male participants in both adult (p = 0.003) and pediatric groups (p < 0.001), while differences were not statistically significant for age, site location, race, or ethnicity. Conclusions: This study provides normal reference intervals for uNGAL with the ProNephro AKI (NGAL) clinical chemistry immunoassay that may be useful for interpreting patient results. Full article

Neutrophil gelatinase-associated lipocalin (NGAL) is a protein secreted by activated neutrophils and certain tissues. The aim of this study was to investigate the prognostic role of urinary neutrophil gelatinase-associated lipocalin (uNGAL) in hospitalized COVID-19 patients with regard to mortality. The prospective observational cohort study involved 86 hospitalized adult COVID-19 patients. Patients’ urine samples were collected upon admission and 48–72 h after admission. General anamnesis and clinical status information were obtained from medical records. Within 24 h of sample collection, urine aliquots were centrifuged, the supernatant was separated, and samples were frozen at −80 °C until uNGAL concentration measurement, which was performed within two years of sample collection. The patients were categorized into groups based on disease outcome (survived/deceased). Data analysis was performed to identify predictive factors and diagnostic indicators for the unfavorable outcome group using logistic regression and ROC curve methods. Logistic regression associated age, cardiomyopathy, invasive mechanical ventilation, and uNGAL concentration (follow-up sampling) with mortality. ROC analysis identified uNGAL concentration (follow-up sampling) as an indicator of mortality, with a cut-off value of >23.8 ng/mL. This study concludes that there is an association between disease outcome and uNGAL concentration in COVID-19 patients. However, understanding the dynamics of uNGAL concentration during COVID-19 remains limited, which is crucial for its effective clinical application. Full article

Background/Objectives: The incidence of acute kidney injury (AKI) has been steadily increasing. Despite its high prevalence, there is no pathogenetically rational therapy for AKI. This deficiency stems from the poor understanding of the pathogenesis of AKI. Renal ischemia/hypoxia is one of the leading causes of clinical AKI. This study investigates whether αMUPA mice, overexpressing the urokinase plasminogen activator (uPA) gene are protected against ischemic AKI, thus unraveling a potential renal damage treatment target. Methods: We utilized an in vivo model of I/R-induced AKI in αMUPA mice and in vitro experiments of uPA-treated HEK-293 cells. We evaluated renal injury markers, histological changes, mRNA expression of inflammatory, apoptotic, and autophagy markers, as compared with wild-type animals. Results: the αMUPA mice exhibited less renal injury post-AKI, as was evident by lower SCr, BUN, and renal NGAL and KIM-1 along attenuated adverse histological alterations. Notably, the αMUPA mice exhibited decreased levels pro-inflammatory, fibrotic, apoptotic, and autophagy markers like TGF-β, IL-6, STAT3, IKB, MAPK, Caspase-3, and LC3. By contrast, ACE-2, p-eNOS, and PGC1α were higher in the kidneys of the αMUPA mice. In vitro results of the uPA-treated HEK-293 cells mirrored the in vivo findings. Conclusions: These results indicate that uPA modulates key pathways involved in AKI, offering potential therapeutic targets for mitigating renal damage. Full article

Objective: To determine whether the urinary excretion of podocyte degradation products varies according to PCOS phenotype and metabolic syndrome (MetS). Methods: The concentrations of podocalyxin (PDX) and nephrin, chronic markers of podocyte damage, and neutrophil gelatinase-associated lipocalin (NGAL), a marker of acute glomerular damage, were analyzed in the morning urine samples of 50 PCOS patients and 50 healthy controls matched by age and BMI. Albuminuria was assessed by calculating the urine albumin–creatinine ratio (uACR). Results: The PDX, nephrin and NGAL concentrations of PCOS participants were significantly higher than those of the control group. While PDX, nephrin and NGAL levels of classic phenotypes were similar, they were higher than ovulatory and non-hyperandrogenic phenotypes. Significant increases in urinary levels of each podocyte protein were detected in PCOS patients with MetS compared to patients without MetS. A positive significant correlation between podocyte proteins and BMI, systolic blood pressure, testosterone, glucose, HOMA-IR and uACR. After adjusting for age and BMI, podocyte proteins were an independent risk factor for microalbuminuria. The incidence of microalbuminuria in PCOS increased 6-fold compared to controls. The frequency of microalbuminuria was higher in classical phenotypes than in ovulatory phenotype. The frequency of microalbuminuria in PCOS patients with MetS was 6.5 times higher than in PCOS patients without MetS. Conclusions: In PCOS accompanied by hyperandrogenemia or metabolic syndrome, leakage of acute and chronic podocyte breakdown products into the urine becomes more pronounced. Full article

Background: Urinary tract infections (UTIs) are very common bacterial infections in children. Early detection of renal parenchymal involvement in this setting can help clinicians make more effective treatment choices. The aim of this pilot study was to assess the ability of plasma and urinary neutrophil gelatinase-associated lipocalin (pNGAL and uNGAL) levels, measured using an automated system, to accurately predict renal parenchymal involvement in children with febrile UTIs. Methods: This prospective single-center study included 28 children aged ≥ 4 years with a first episode of febrile UTIs. All patients underwent magnetic resonance imaging. pNGAL, uNGAL, procalcitonin, C-reactive protein (CRP), and white blood cells were measured before antibiotic therapy. Results: The receiver operating characteristic (ROC) area under the curve for predicting acute pyelonephritis was 0.6 for pNGAL, 0.8 for CRP, 0.4 for PCT, and 0.4 for uNGAL. The ROC analyses showed an optimal cutoff of 141.0 ng/mL for pNGAL (sensitivity, 54.2%; specificity, 75.0%; positive predictive value, 92.9%; and negative predictive value, 21.4%). Conclusion: pNGAL and uNGAL did not effectively aid the early prediction of renal parenchymal involvement in children ≥ 4 years with febrile UTIs. The novelties of this study were the use of MRI as the gold standard and an automated biochemical method to measure NGAL. Full article

Chronic kidney disease (CKD) is one of the most important causes of chronic pediatric morbidity and mortality and places an important burden on the medical system. Current diagnosis and progression monitoring techniques have numerous sensitivity and specificity limitations. New biomarkers for monitoring CKD progression have been assessed. Neutrophil gelatinase-associated lipocalin (NGAL) has had some promising results in adults, but in pediatric patients, due to the small number of patients included in the studies, cutoff values are not agreed upon. The small sample size also makes the statistical approach limited. The aim of our study was to develop a fuzzy logic approach to assess the probability of pediatric CKD progression using both NGAL (urinary and plasmatic) and routine blood test parameters (creatinine and erythrocyte sedimentation rate) as input data. In our study, we describe in detail how to configure a fuzzy model that can simulate the correlations between the input variables ESR, NGAL-P, NGAL-U, creatinine, and the output variable Prob regarding the prognosis of the patient’s evolution. The results of the simulations on the model, i.e., the correlations between the input and output variables (3D graphic presentations) are explained in detail. We propose this model as a tool for physicians which will allow them to improve diagnosis, follow-up, and interventional decisions relative to the CKD stage. We believe this innovative approach can be a great tool for the clinician and validates the feasibility of using a fuzzy logic approach in interpreting NGAL biomarker results for CKD progression. Full article