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•Recent evidence reports microplastics’ presence in human tissues and fluids.•MicroRaman spectroscopy is employed to detect microplastics in biological samples.•66 microparticles ...fragments were found in 10 kidney tissues and 10 urine samples and 26 out 66 were characterized.•SpeComp open-access software was developed to ease microRaman spectra comparison.•The most often detected pieces and pigments are polyethylene, polystyrene, hematite.
There is a growing concern within the medical community about the potential burden of microplastics on human organs and tissues. In this study, we investigated by microRaman spectroscopy the presence of microplastics in human kidneys and urine. Moreover, an open-access software was developed and validated for the project, which enabled the comparison between the investigated spectra and a self-created spectral database, thus enhancing the ability to characterize polymers and pigments in biological matrices. Healthy portions of ten kidneys obtained from nephrectomies, as well as ten urine samples from healthy donors were analyzed: 26 particles in both kidney and urine samples were identified, with sizes ranging from 3 to 13 μm in urine and from 1 to 29 μm in kidneys. The most frequently determined polymers are polyethylene and polystyrene, while the most common pigments are hematite and Cu-phthalocyanine. This preclinical study proves the presence of microplastics in renal tissues and confirms their presence in urine, providing the first evidence of kidney microplastics deposition in humans.
Plastic pollution became a main challenge for human beings as demonstrated by the increasing dispersion of plastic waste into the environment. Microplastics (MPs) have become ubiquitous and humans ...are exposed daily to inhalation or ingestion of plastic microparticles. Recent studies performed using mainly spectroscopy or spectrometry-based techniques have shown astounding evidence for the presence of MPs in human tissues, organs and fluids. The placenta, meconium, breast milk, lung, intestine, liver, heart and cardiovascular system, blood, urine and cerebrovascular liquid are afflicted by MPs’ presence and deposition. On the whole, obtained data underline a great heterogeneity among different tissue and organs of the polymers characterized and the microparticles’ dimension, even if most of them seem to be below 50–100 µm. Evidence for the possible contribution of MPs in human diseases is still limited and this field of study in medicine is in an initial state. However, increasing studies on their toxicity in vitro and in vivo suggest worrying effects on human cells mainly mediated by oxidative stress, inflammation and fibrosis. Nephrological studies are insufficient and evidence for the presence of MPs in human kidneys is still lacking, but the little evidence present in the literature has demonstrated histological and functional alteration of kidneys in animal models and cytotoxicity through apoptosis, autophagy, oxidative stress and inflammation in kidney cells. Overall, the manuscript we report in this review recommends urgent further study to analyze potential correlations between kidney disease and MPs’ exposure in human.
While blue LED (b-LED) light is increasingly being studied for its cytotoxic activity towards bacteria in therapy of skin-related infections, its effects on eukaryotic cells plasticity are less well ...characterized. Moreover, since different protocols are often used, comparing the effect of b-LED towards both microorganisms and epithelial surfaces may be difficult. The aim of this study was to analyze, in the same experimental setting, both the bactericidal activity and the effects on human keratinocytes. Exposure to b-LED induced an intense cytocidal activity against Gram-positive (i.e,
) and Gram-negative (i.e.,
) bacteria associated with catheter-related infections. Treatment with b-LED of a human keratinocyte cell line induced a transient cell cycle arrest. At the molecular level, exposure to b-LED induced a transient downregulation of Cyclin D1 and an upregulation of p21, but not signs of apoptosis. Interestingly, a transient induction of phosphor-histone γ-H2Ax, which is associated with genotoxic damages, was observed. At the same time, keratinocytes underwent a transient epithelial to mesenchymal transition (EMT)-like phenotype, characterized by E-cadherin downregulation and SNAIL/SLUG induction. As a functional readout of EMT induction, a scratch assay was performed. Surprisingly, b-LED treatment provoked a delay in the scratch closure. In conclusion, we demonstrated that b-LED microbicidal activity is associated with complex responses in keratinocytes that certainly deserve further analysis.
: The combination therapy of platinum and pembrolizumab looks like a promising treatment in advanced non-small-cell lung cancer. However, both platinum-based chemotherapy and pembrolizumab can lead ...to AKI. AKI can occur due to acute tubular necrosis or interstitial nephritis. It is essential to identify the drug responsible for renal damage. For this purpose, we used new immunohistochemistry markers (p53 and anti-PD1 analysis).
: A 77-year-old female patient with advanced non-small-cell lung cancer received the PD-1 inhibitor pembrolizumab and platinum-based chemotherapy carboplatin. The patient, after 60 days, experienced AKI. A kidney biopsy was performed, and two new immunohistochemical techniques for p53 (experimental markers of ATN from platinum) and anti-PDL1 (experimental markers of PD-1 inhibitors nephritis) were employed. Renal biopsies revealed severe tubular damage. No infiltration was detected, and the immunohistochemical assessment of PDL-1 was negative. The expression of p53 was positive. The renal biopsy suggested platinum-induced acute tubular necrosis. After discontinuing steroids and reducing carboplatin, the patient continued with pembrolizumab, and their renal function returned to normal within two months.
: Combining checkpoint inhibitors and platinum-based therapies may result in AKI. The standard method of examining kidney tissue may not provide sufficient information about the effects of these drugs on the kidneys. To address this issue, we recommend incorporating an assessment of the analysis of the expression of PDL1 and p53. This personalized approach will help identify the best treatment option for the patient while ensuring the best possible cancer treatment plan.
The standard method for assessing chronic renal damage is renal biopsy, which has limitations due to its invasiveness. Ultrasound elastography is a non-invasive technique that quantifies tissue ...elasticity and can be used to determine Young's modulus (YM). Although this breakthrough technology has been successfully employed to evaluate liver stiffness and the extent of fibrosis, its application in kidney-related conditions still needs improvement.
Our study aimed to verify the correlation between renal elastography and the chronic histological score determined via renal biopsy, evaluate the correlation between elastography and response to treatment in the short-term follow-up (6 months), and compare elastography data between renal disease patients (AKD-P) and healthy controls (HP).
The analyzed population consisted of 82 patients (41 HP and 41 AKD-P). The AKD-P were divided into responders (R) or non-responders (NR) based on the criteria established by the guidelines. No association was found between renal stiffness and chronic histological score. Elastography data revealed median YM values of 6.15 kPa for AKD-P and 12.2 kPa for HP, with a statistically significant difference. The median YM values of the R and NR groups were 7.4 KPa and 5.6 KPa, respectively (
= 0.037).
Patient responsiveness was associated with YM, with lower values observed in the NR group. We also found that the healthy controls exhibited significantly higher YM values than the renal disease population.
Abstract
Background and Aims
The RFR (renal functional reserve) is the difference between the stimulated glomerular filtration rate (GFR) and the baseline GFR. This difference can be expressed in ...absolute terms (mL/min) or relative terms (percentage of increment relative to the baseline GFR). This index makes it possible to highlight a subclinical renal functional deterioration when the laboratory values of creatinine are still within the normal range. Measurement of RFR by protein load (1 g/kg of oral protein) (RFR-T) is now considered the gold standard for RFR assessment. RFR measured with protein load (RFR-T) predicts the risk of acute kidney injury (AKI) or chronic kidney disease (CKD) in both healthy and diseased patients and is particularly useful in patients with apparently normal renal function before stress candidate for interventions at real risk of renal failure (kidney donors, cardiac surgery, bone marrow transplants). However, the protein load test has a long duration (about 5 hours), requires numerous blood and urine samples, and is challenging to use on a large scale. Recent studies have proposed another method based on the variation of the renal intraparenchymal resistance index (IRRIV-T). In this case, the stress to which the kidney is mechanical. That is a weight (saline bag, representing 10% of the body weight) placed on the abdomen of the supine patient, which induces maximal renal vasodilation. The sampling of the intraparenchymal resistance doppler indices before and after the weight application would correlate, in preliminary studies, with the RFR tested with the protein load. Thus, offering a fast and non-invasive method. Eventually, comparing these divergent diagnostic procedures can guide us in choosing the most cost-effective approach to gain deeper insight into renal health. (Fig. 1)
Method
Our cross-sectional study aimed to compare the classic protein loaded RFR test (RFR-T) with the new IRRIV ultrasound test (IRRIV-T). This real-life study includes a normal-renal function population of 42 patients. Anthropometric parameters and cardiovascular risk factors were evaluated, and blood and urinary tests were performed. The inclusion criteria were: (i) age greater than 18 years; (ii) eGFR CKD-EPI > 60 mL/min/1.73 m2. Exclusion criteria were: (i) non-steroidal inflammatory drugs (NSAIDs), (ii) ultrasound evidence of renal morphological changes or artery stenosis. Each patient underwent oral protein load testing (RFR-T) and an ultrasound test (IRRIV-T). Pearson's correlation index analyzed the comparison between the 2 tests.
Results
There was no statistically significant correlation between RFR-T and IRRIV-T in terms of the RFR either in absolute numbers (R = 0.14, p = 0.37) or in percentage values (R = 0.15, p = 0.33). (Fig. 2) Based on our experience, the IRRIV test proved unreliable in evaluating RFR compared with the gold standard (RFR-T). Therefore, not suitable to be used as a possible alternative to the oral protein load test.
Conclusion
Unlike previous studies, our survey is a real-life study. Many of our patients have pathologies or take drugs that could alter the hemodynamic and the renal vascular response, consequently changing the outcome of the IRRIV test. However, it is a real-life experience that aims to offer a practical point of view, bringing to light the possible limitations of the ultrasound test when applied to a standard evaluation population and not to a healthy or highly selected population as in the only three previous works published in the literature up to now. Our work is the first original real-life study in this field.
Abstract
BACKGROUND AND AIMS
Haematopoietic stem cell transplantation (HSCT) is an effective treatment for myelo-lymphoproliferative disorders. Acute kidney injury (AKI) is a major complication of ...HSCT (incidence ≈15%–60%), usually occurs in the first 100 days post-transplant, and is associated with a significant increase in mortality and morbidity. In addition, it can lead to chronic renal failure (CKD). There are no scores to predict which patients will develop AKI or CKD post-HSCT. Routine pre-HSCT evaluation only considers the estimated glomerular filtrate value (eGFR) without examining the renal functional reserve (RFR). RFR is defined as the ability of the kidney to increase its glomerular filtration rate in response to higher functional demand (as in the case of HSCT).
METHOD
This prospective study aimed to evaluate the ability of RFR in HSCT candidate patients to stratify the risk of AKI incidence within 100 days of transplantation and predict eventual functional recovery. The secondary purpose was to identify the risk factors for the onset of AKI.
A total of 41 HSCT candidate patients with normal baseline GFR (bGFR) were included in the study. A total of 15 days before the HSCT, a multiparametric nephrological evaluation and RFR test (RFR-T) were performed using an oral protein load (1–1.2 g/kg) with freeze-dried products (Prother®) and 10 mL/kg of oral hydration. GFR after protein loading (glomerular stress filtration rate, sGFR) and bGFR were measured with body surface corrected endogenous creatinine clearance (CrCl). Blood samples were taken at predefined time intervals concerning oral protein load (120–180–240 min). RFR was defined as the difference between the maximum value of sGFR and bGFR expressed as a percentage (normal RFR > 25%).
RESULTS
No correlation was found between bGFR and RFR values. Consistent with the literature, 25 of 41 patients (61%) developed AKI. Comparing the group that developed AKI with those that did not, no statistically significant differences emerged related to demographic, clinical, or multiparameter screening characteristics. RFR was lower in AKI + patients than in AKI- patients, with a value at the borderline of statistical significance (P = 0.06). Among the 25 patients who developed AKI, 7 patients (30%) recovered normal renal function in the follow-up, while 18 patients (70%) developed CKD. 71% of patients who recovered renal function demonstrated an RFR value>25%; no demographic and multiparameter screening variables correlated with the development of post-HSCT CKD.
CONCLUSION
RFR is a dynamic parameter with respect to the bGFR. It allows the identification of conditions of subclinical functional deterioration, capable of affecting both the onset of AKI and CKD post-HSCT. No other multiparameter screening variable has shown potential utility in this type of predictive assessment. The stratification of the risk of kidney injury through RFR represents the most promising marker in this sense. A reliable prediction of the risk of renal complication in these patients could lead to accurate multidisciplinary management able to improve the prognosis quoad vitam (severe in the case of AKI post-HSCT) and quoad valetudinem (severe in case of CKD post-HSCT).
Cardiovascular events (CVE) remain the leading cause of mortality in hemodialysis (HD) patients. The ability to assess the risk of short-term CVE is of great importance. Soluble suppression of ...tumorogenicity-2 (sST2) is a novel biomarker that better stratifies risk of CVE than troponins in patients with heart failure. Few studies have investigated the role of sST2 in the HD population. The aim of this single-center study was to assess the predictive ability of sST2 on CVE in comparison to high-sensitive cardiac troponin I (hs-cTnI) and B-type natriuretic peptide (BNP) in HD patients.
This study used a prospective, observational cohort design. We enrolled 40 chronic HD patients asymptomatic for chest pain and without recent history of acute coronary syndrome. We tested sST2 pre-/post-HD, hs-cTnI, and BNP. Demographic/dialytic/echocardiographic data were evaluated. We recorded the number of CVE for 12 months. The patients were classified into 2 groups: those who developed CVE and those who did not.
Ten of the 40 patients (25%) developed CVE during a 12-month follow-up. Increased sST2 levels (p < 0.0001) as well as hs-cTnI and BNP are predictive of CVE. When analyzing biomarkers as binary variables for values above or below the normal range, the correlation remained significant only for sST2 (p = 0.001). A small variation in sST2 levels before and after HD sessions was found (-2.1 ng/mL). sST2 was correlated with left ventricular (LV) echocardiographic data: LV mass index (p = 0.0001), LV ejection fraction (p = 0.01), and diastolic bulging of septum (p = 0.015). BNP and sST2 combination increased the prediction of CVE in a statistical model.
Our study confirms that sST2 is useful for stratifying CV risk in the HD population. sST2 can be evaluated simply as a dichotomous value higher or lower than the normal range, making it easily interpretable. Dialysis and residual diuresis did not affect significantly sST2. A multimarker approach that incorporates sST2 and BNP may improve the prediction of CVE.
Autogenous radial-cephalic direct wrist arteriovenous fistula (RC-AVF) in the non-dominant arm is the gold standard for dialysis vascular access. However, the RC-AVF non-maturation rate is ...significant (≃ 40%) due to an increasingly elderly and comorbid population incidence. A detailed identification of the biological cascade underlying arteriovenous fistula (AVF) maturation could be the key to clinical research aimed at identify the group of patients at risk of primary AVF failure. Currently, careful post-operative monitoring remains the most crucial aspect to overcome the problem of impaired maturation. Up to 80% of patients with immature RC-AVF have problems potentially solvable with early endovascular or surgical correction. Physical examination by experienced practitioners in conjunction with duplex ultrasound examination (DUS) can identify physical signs of non-maturation, understand the underlying cause, and drive for a tailored early planning to treat the complication. New approaches for the early assessment of AVF maturation are under study. Techniques to promote RC-AVF maturation performed through the administration of pre-or peri-operative drugs have missed up to now to prove an efficacy in improving fistula success. The new techniques tested after surgery appear to hold future promise for improving fistula maturation.
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