Acute Kidney Injury Biomarkers and Hydration Outcomes at the Boston Marathon

The purpose of our field study was to investigate the effects of running the Boston Marathon on acute kidney injury (AKI) biomarkers. We hypothesized that biomarker values would be elevated immediately post-marathon but would resolve in the 24-h post-marathon. Secondarily, we sought to identify sex differences related to renal stress. Participants were 65 runners who completed the Boston Marathon (46 ± 9 years, 65.4 ± 10.8 kg). Urine samples were collected at three different time points (pre-marathon, post-marathon, and 24-h post-marathon). Blood samples were collected post-marathon and 24-h post-marathon. Urine specific gravity (USG) and AKI biomarkers were evaluated. Pre-marathon USG (1.012 ± 0.007) was significantly less than post-marathon (1.018 ± 0.008) and 24-h post-marathon (1.020 ± 0.009; P < 0.001). Male USG (1.024 ± 0.009) was significantly greater 24-h post-marathon than females (1.017 ± 0.008; P = 0.019). Urinary neutrophil gelatinase-associated lipocalin values were significantly greater over time (P < 0.001), and there was a main effect of sex with female urinary creatinine (UCr) greater than males at all three time points (P = 0.040). Post-marathonUCr (366.24 ± 295.16 mg/dl) was significantly greater than pre-marathon (206.65 ± 145.28.56 mg/dl; p < 0.001) and 24-h post-marathon was significantly lower than other time-points (93.90 ± 125.07 mg/dl; P < 0.001). FemaleUCr values were significantly greater than males 24-h post-marathon (P < 0.001). There was no difference in serum cystatin C (SCys) values post- or 24-h post-marathon (P = 0.178). Serum creatinine (SCr) significantly decreased between post-marathon and 24-h post-marathon, (P < 0.001). We can infer that the characteristics unique to the Boston Marathon may have attributed to prolonged elevations in AKI biomarkers. Sex differences were observed during the Boston Marathon warranting further investigation.

Renal Impairment Detectors: IGFBP-7 and NGAL as Tubular Injury Markers in Multiple Myeloma Patients

Background and Objectives: Urine insulin-like growth factor-binding protein 7 (IGFBP-7), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), and neutrophil gelatinase-associated lipocalin (NGAL) monomer are novel tubular kidney injury biomarkers. In multiple myeloma (MM), immunoglobulin free light chains (FLCs) play an integral role in renal impairment. This study aimed to investigate the correlation between new biomarkers and acclaimed parameters of renal failure, MM stage, and prognosis. Materials and Methods: The examined parameters included: urinary and serum cystatin-C, IGFBP-7, and TIMP-2, and urinary NGAL monomer in 124 enrolled patients. Results: Urinary and serum IGFBP-7 and urinary NGAL were higher among patients with an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, and positively correlated with urine light chains. Serum and urine IGFBP-7 and urine NGAL were greater among patients with a higher disease stage. In the whole study group, urinary concentrations of the studied markers were positively correlated with each other. In multiple linear regression, urinary IGFBP-7 and NGAL were associated with lower eGFR, independently of other urinary markers. Conclusions: Urinary IGFBP-7 and NGAL monomer may be useful markers of tubular renal damage in patients with MM. Biomarker-based diagnostics may contribute to earlier treatment that may improve renal outcomes and life expectancy in MM.

Evaluation of renal biomarkers, including symmetric dimethylarginine, following gentamicin-induced proximal tubular injury in the rat

Symmetric dimethylarginine (SDMA) is an excretory renal function biomarker shown to correlate well with glomerular filtration rate in dogs, cats, humans, and rats. The objectives of this study were to determine utility of serum SDMA as a renal biomarker in a rat model of gentamicin-induced renal injury and provide validation of a commercially available SDMA immunoassay for rat serum. Rats were randomly assigned to one of three dose levels of gentamicin (20, 50, or 100 mg/kg) or a vehicle control group and dosed once daily by subcutaneous injection for either four or ten days. Serum and urine renal biomarker evaluation including serum SDMA, hematologic and serum biochemical analysis, urinalysis, and histologic examination of kidney were performed. Prior to biologic validation, analytic validation of the SDMA immunoassay for rat serum was performed including assessment of assay accuracy, precision, analytical sensitivity, linearity, analyte stability, and interference testing. Among markers of excretory renal function SDMA and serum creatinine increased earliest and at the lowest gentamicin concentrations and were significantly increased in both the 50 mg/kg and the 100 mg/kg dosage levels in the 4 and 10-dose treatment groups compared to controls. Time- and dose-dependent increases were noted for all urinary biomarkers investigated in this study, with µALB being most responsive and OPN least responsive for detection of gentamicin-induced injury across dose levels and schedules investigated. The SDMA immunoassay met all set quality requirements assessed in analytical validation. This study is the first to investigate performance of serum SDMA as compared to other excretory renal function markers in a rat gentamicin acute toxicity model. In this study serum SDMA was an earlier biomarker for detection of gentamicin-induced toxicity than serum cystatin C, BUN, and creatinine clearance. The SDMA immunoassay provides a reliable commercially available assay for future renal investigations in rat models.

Serum and urinary biomarkers for early detection of acute kidney injury following Hypnale spp. envenoming

Background Hump-nosed pit viper (HNV; Hypnale spp.) bites account for most venomous snakebites in Sri Lanka. Acute kidney injury (AKI) is the most serious systemic manifestation (1–10%) following HNV envenoming. We aimed to identify the value of functional and injury biomarkers in predicting the development of AKI early following HNV bites. Methods We conducted a prospective cohort study of patients with confirmed HNV envenoming presenting to two large tertiary care hospitals in Sri Lanka. Demographics, bite details, clinical effects, complications and treatment data were collected prospectively. Blood and urine samples were collected from patients for coagulation and renal biomarker assays on admission, at 0-4h, 4-8h, 8-16h and 16-24h post-bite and daily until discharge. Follow-up samples were obtained 1 and 3 months post-discharge. Creatinine (sCr) and Cystatin C (sCysC) were measured in serum and kidney injury molecule-1 (uKIM-1), clusterin (uClu), albumin (uAlb), β2-microglobulin (uβ2M), cystatin C (uCysC), neutrophil gelatinase associated lipocalin (uNGAL), osteopontin (uOPN) and trefoil factor-3 (uTFF-3) were measured in urine. Definite HNV bites were based on serum venom specific enzyme immunoassay. Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to stage AKI. Two patients had chronic kidney disease at 3 month follow-up, both with pre-existing abnormal sCr, and one developed AKI following HNV envenoming. Results There were 52 patients with confirmed HNV envenoming; median age 48y (Interquartile range [IQR]:40-59y) and 29 (56%) were male. Median time to admission was 1.87h (IQR:1–2.75h). Twelve patients (23%) developed AKI (AKI stage 1 = 7, AKI stage 2 = 1, AKI stage 3 = 4). Levels of five novel biomarkers, the functional marker serum Cystatin C and the damage markers urinary NGAL, cystatin C, β2-microglobulin and clusterin, were elevated in patients who developed moderate/severe acute kidney injury. sCysC performed the best at 0–4 h post-bite in predicting moderate to severe AKI (AUC-ROC 0.95;95%CI:0.85–1.0) and no biomarker performed better than sCr at later time points. Conclusions sCysC appears to be a better marker than sCr for early prediction of moderate to severe AKI following HNV envenoming.

Identifying drug-related attributes to personalise antihypertensive agents: the outcome report of patients receiving metoprolol therapy

Background Currently, numerous antihypertensive drugs from different pharmacological classes are available; however, blood pressure control is achieved in only less than a third of patients treated for hypertension. Moreover, providing optimal and personalised treatment for hypertension is challenging. Therefore, in this study, we propose a ‘drug-related attributes’ sensitive spectrum. This novel concept can assist clinicians in selecting an optimal antihypertensive drug and improve blood pressure control after examining the attributes of a patient. Methods We collected clinical data on attributes related to hypertension and its therapy of inpatients from West China Hospital who received metoprolol therapy and constructed the sensitive spectrum using data-visualisation tools. Results Our analysis revealed that haematocrit, haemoglobin, serum creatinine, serum cystatin C, serum urea, age, sex, systolic pressure, diastolic pressure, pulse pressure, and heart rate are metoprolol-related attributes. Conclusion Our study showed that all metoprolol-related attributes identified are reasonable and helpful in improving the personalisation of metoprolol therapy. The proposed drug-related attributes spectrum can help personalise antihypertensive medication. Moreover, data-visualisation tools can be effectively used to mine the drug-related attributes sensitive spectrum.

Early Vascular Aging in Children With Tuberous Sclerosis Complex

Objectives: Experimental data indicate that activating mutations in the mTOR (mammalian target of rapamycin) pathway may lead to abnormal arterial wall structure. Vascular anomalies like arterial stenoses are reported in pediatric patients with tuberous sclerosis complex (TSC). In addition, large renal lesions (angiomyolipoma—AML and cysts) are risk factors for arterial hypertension in adult patients with TSC. This study aimed to assess blood pressure, including central blood pressure and arterial damage (early vascular aging—EVA) in children with TSC.Materials and Methods: In a group of 33 pediatric patients with TSC (11.13 ± 4.03 years, 15 boys, 18 girls), we evaluated peripheral and central office blood pressure, 24-h ambulatory blood pressure, and arterial damage: aortic pulse wave velocity (aPWV) [m/s], [Z-score], augmentation index (AIx75HR [%]), common carotid artery intima-media thickness (cIMT) [mm], [Z-score], stiffness of common carotid artery (E-tracking), renal lesions in magnetic resonance and ultrasonography, and selected biochemical parameters. The control group consisted of 33 healthy children (11.23 ± 3.28 years, 15 boys, 18 girls).Results: In TSC group 7 (21.2%) children had arterial hypertension, 27 (81.8%) children had renal angiomyolipomas, 26 (78.8%)—renal cysts, and 4 (12.1%) patients were treated with mTOR inhibitors (2 patients with everolimus and 2 patients with sirolimus) at the moment of evaluation. Children with TSC had higher central systolic blood pressure (AoSBP) (98.63 ± 9.65 vs. 90.45 ± 6.87 [mm Hg], p &lt; 0.001), cIMT (0.42 ± 0.05 vs. 0.39 ± 0.03 [mm], p = 0.011), cIMT Z-score (0.81 ± 1.21 vs. 0.16 ± 0.57, p = 0.007), aPWV (4.78 ± 0.81 vs. 4.25 ± 0.56 [m/s], p = 0.003) and aPWV Z-score (−0.14 ± 1.15 vs. −0.96 ± 0.87, p = 0.002) compared to healthy children, without differences in AIx75HR (8.71 ± 15.90 vs. 5.24 ± 11.12 [%], p = 0.319) and stiffness of common carotid artery. In children with TSC AoSBP correlated positively with serum cystatin C concentration (r = 0.377, p = 0.030) and with maximum diameter of renal cyst (R = 0.419, p = 0.033); mean arterial pressure (MAP) 24 h Z-score correlated with serum cystatin C concentration (R = 0.433, p = 0.013); and aPWV Z-score with daily urinary albumin loss [mg/24 h] (R = 0.412, p = 0.029).Conclusions: Children with tuberous sclerosis complex are at risk of elevated central blood pressure and early vascular aging. In children with TSC, blood pressure and arterial stiffness are related to renal involvement.

Analysis Of Serum Cystatin C Levels In People With Type 2 Diabetes Mellitus As A Biomarker Of Early Detection Of Atherosclerosis

Type 2 diabetes mellitus (DMT2) is associated with atherosclerosis, which causes the disease. cardiovascular and increased mortality. It is still difficult to detect ateroskelerosis in the early stages. Arterial stenosis often develops without symptoms in patients. DMT2, then causes cardiovascular disease. Therefore, development diagnostics to easily detect early-stage atherosclerosis are needed. In this study, we focused on cystatin C serum, an inhibitor of cysteine proteinase. Some research results, it has reported a significant correlation between serum Cystatin C levels and Arterial stiffness in a group of normal individuals. Cystatin C serum has a correlation strong with a value of elasticity of the carotid artery walls that reflect the degree of atherosclerosis subclinical. This is a new sign that is quite potential as a biomarker of early detection atherosclerosis. The purpose of the study is to know the picture serum Cystatin C levels as an early marker to determine the presence of possible complications of atherosclerosis in DMT2 patients, as well as the usefulness of Cystatin-C in predicting atherosclerosis of the early stages. Research methods are analytical research with use cross-sectional design. The study was conducted by calculating the value of Cystatin C blood serum with DMT2. The study subjects were people with DMT2 in RSUD.Labuang Baji Makassarand its network. Sum the sample in this study was 20 people. Determination of the research subject is done by conducting a search on medical records of DMT2 patients who meet the criteria of inclusion and exclusion to achieve minimum number of samples. The study subjects were classified into two groups based on medical record data searches are subclinical atherosclerosis group and nonclinical group ateroskelorosis. The research sample is a serum sample. Serum sample examination is carried out in the Clinical Prodia Laboratory using PENIA method. The results of this study reported the results that Cystatin-C Serum is closely correlated with subclinical atherosclerosis (arterial stiffness. Increase in serum cystatin-C levels indicates the risk of atherosclerosis in Patients with DMT2. The results of this study reported that serum cystatin C levels in dmt2 patients in the nonclinical atherosclerosis group (n = 10) showed normal cystatin levels (0.50 - 0.96 mg/L), while serum Cystatin-C levels in dmt2 group patients showed normal cystatin levels (0.50 - 0.96 mg/L), while serum cystatin-C levels in DMT2 group patients Subclinical atherosclerosis (n = 10) has an increase in serum cystatin-C levels (> 0.90 mg/L). Level cystatin C serum is associated with SA in DMT2 patients. Cystatin C was identified as a predictor of atherosclerosis risk, after adjusting for a variety of factors associated with diabetes.

Association Between Serum Cystatin C and Thyroid Diseases: A Systematic Review and Meta-Analysis

BackgroundCystatin C (CysC) is often used to diagnose and monitor renal diseases. Although some studies have investigated the association between serum CysC levels and thyroid diseases, their reported results were inconsistent. Therefore, the relationship between CysC levels and thyroid diseases remains controversial.AimThis meta-analysis aimed to statistically evaluate serum CysC levels in patients with thyroid diseases.MethodsA literature search was conducted using the PubMed, Web of Science, Embase, EBSCO, and Wiley Online Library databases. The following search terms were used for the title or abstract: “Cystatin C” or “CysC” in combination with the terms “thyroid disease”, “thyroid function”, “hypothyroidism”, or “hyperthyroidism”. The results of the systematic analysis were presented as standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs).ResultsEleven articles (1,265 cases and 894 controls) were included in the meta-analysis. The results of the meta-analysis showed that the serum CysC levels of patients with hyperthyroidism were significantly higher than those of the controls (SMD: 1.79, 95% CI [1.34, 2.25]), and the serum CysC levels of patients with hypothyroidism were significantly lower than those of the controls (SMD −0.59, 95% CI [−0.82, −0.36]). Moreover, the treatment of thyroid diseases significantly affected serum CysC levels.ConclusionsTo the best of our knowledge, this meta-analysis is the first to evaluate serum CysC levels in patients with thyroid diseases. Our findings suggest that thyroid function affects serum CysC levels and that serum CysC may be an effective marker for monitoring thyroid diseases.Systematic Review RegistrationPROSPERO [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=258022], identifier CRD42021258022].