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Background: Over the years, it was noticed that patients with diabetes have reached an alarming number worldwide. Diabetes presents many complications, including diabetic kidney disease (DKD), which can be considered the leading cause of end-stage renal disease. Current biomarkers such as serum creatinine and albuminuria have limitations for early detection of DKD. Methods: In our study, we used UHPLC-QTOF-ESI+-MS techniques to quantify previously analyzed metabolites. Based on one-way ANOVA and Fisher's LSD, untargeted analysis allowed the discrimination of six metabolites between subgroups P1 versus P2 and P3: tryptophan, kynurenic acid, taurine, l-acetylcarnitine, glycine, and tiglylglycine. Results: Our results showed several metabolites that exhibited significant differences among the patient groups and can be considered putative biomarkers in early DKD, including glycine and kynurenic acid in serum (p < 0.001) and tryptophan and tiglylglycine (p < 0.001) in urine. Conclusions: Although we identified metabolites as potential biomarkers in the present study, additional studies are needed to validate these results. [ABSTRACT FROM AUTHOR]

Background: The importance of identifying mortality biomarkers in chronic kidney disease (CKD), and especially in patients treated with hemodialysis (HD), has become evident. In addition to being a marker of tubulointerstitial injury, plasma kidney injury molecule-1 (KIM-1) has been mentioned in regard to HD patients as a risk marker for cardiovascular (CV) mortality and coronary artery calcification. The aim of this study was to assess the level of plasma KIM-1 as a marker of cardiovascular disease (CVD) and mortality in CKD5-HD patients (patients with CKD stage G5D treated with hemodialysis). Methods: We conducted a prospective case–control study that included 63 CKD5-HD patients (HD for 1–5 years) followed up for 48 months and a control group consisting of 52 non-dialysis patients diagnosed with CKD stages G1-G5 (ND-CKD). All patients had a CVD baseline assessment including medical history, echocardiography, and electrocardiography (ECG). Circulating plasma KIM-1 levels were determined with single-molecule counting immunoassay technology using an enzyme-linked immunosorbent assay. We obtained the following parameters: serum creatinine and urea; the inflammation markers CRP (C-reactive protein) and IL-6 (interleukin-6); and the anemia markers complete blood count, serum ferritin, and transferrin saturation (TSAT). Results: The mean plasma KIM-1 level was 403.8 ± 546.8 pg/mL, showing a statistically significant correlation with inflammation (CRP, R = 0.28, p = 0.02; IL-6, R = 0.36, p = 0.005) and with anemia (hematocrit, R = −0.5, p = −0.0316; hemoglobin (Hb), R = −0.5, p = 0.02). We found that patients with left ventricular hypertrophy (LVH) on echocardiography (59.7%) had significantly lower mean levels of plasma KIM-1 than patients from the control group (155.51 vs. 432.12 pg/mL; p = 0.026). Regarding the patients' follow-up, we assessed all-cause mortality as an endpoint. After 24 months of follow-up, we found a mortality rate of 22.23%, while after 48 months, the mortality rate was 50.73%. A plasma KIM-1 level < 82.98 pg/mL was significantly associated with decreased survival in hemodialysis patients (p < 0.001). Conclusions: In patients treated with hemodialysis, low levels of plasma KIM-1 were associated with cardiovascular changes and an increased risk of mortality. Plasma KIM-1 levels were significantly higher in HD patients compared to ND-CKD patients. [ABSTRACT FROM AUTHOR]

The increase in bacterial resistance is currently a global burden for the health care system. In order to evaluate the resistance rates of several bacteria from the most encountered cultures in clinical practice, we performed a retrospective analysis of all of the positive cultures from the year 2021 in a tertiary care hospital in Romania. Our analysis captured 3299 positive cultures. The median age of the patients was 62 years (IQR: 41–71 years old) with a slight predominance among females (53.1%). Overall, the most common cultures were urocultures, wound secretion cultures and blood cultures, and the most common identified bacteria were Escherichia coli, Staphylococcus aureus and Klebsiella spp. Positive cultures with the highest resistance rates were found in the bronchial aspirate cultures, catheter tip cultures, urocultures and blood cultures. Escherichia coli (n = 996) had the highest resistance to ampicillin (19.8%) and trimetoprim-sulfametoxazole (16.4%), while Staphylococcus aureus (n = 698) presented the highest resistance rates to clindamycin (27.4%) and oxaciline (19.7%). Klebsiella (n = 481) presented the highest resistance rates to piperaciline-tazobactam (25.2%) and ampicillin (20.4%), whereas Acinetobacter baumanii (n = 123) presented a resistance rate of more than 50% to carbapenems, gentamicin, ciprofloxacin and ceftazidime. The aim of our study was to identify bacterial resistance rates in order to provide updated clinical data to guide physicians in choosing the best empirical antibiotic treatment, especially in the west part of Romania. [ABSTRACT FROM AUTHOR]

Cerebrovascular disease accounts for major neurologic disabilities in patients with type 2 diabetes mellitus (DM). A potential association of mitochondrial DNA (mtDNA) and inflammation with cerebral vessel remodeling in patients with type 2 DM was evaluated. A cohort of 150 patients and 30 healthy controls were assessed concerning urinary albumin/creatinine ratio (UACR), synaptopodin, podocalyxin, kidney injury molecule-1 (KIM-1), N-acetyl-β-(D)-glucosaminidase (NAG), interleukins IL-17A, IL-18, IL-10, tumor necrosis factor-alpha (TNFα), intercellular adhesion molecule-1 (ICAM-1). MtDNA-CN and nuclear DNA (nDNA) were quantified in peripheral blood and urine by qRT-PCR. Cytochrome b (CYTB) gene, subunit 2 of NADH dehydrogenase (ND2), and beta 2 microglobulin nuclear gene (B2M) were assessed by TaqMan assays. mtDNA-CN was defined as the ratio of the number of mtDNA/nDNA copies, through analysis of the CYTB/B2M and ND2/B2M ratio; cerebral Doppler ultrasound: intima-media thickness (IMT)—the common carotid arteries (CCAs), the pulsatility index (PI) and resistivity index (RI)- the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs), the breath-holding index (BHI). The results showed direct correlations of CCAs-IMT, PI-ICAs, PI-MCAs, RI-ICAs, RI-MCAs with urinary mtDNA, IL-17A, IL-18, TNFα, ICAM-1, UACR, synaptopodin, podocalyxin, KIM-1, NAG, and indirect correlations with serum mtDNA, IL-10. BHI correlated directly with serum IL-10, and serum mtDNA, and negatively with serum IL-17A, serum ICAM-1, and NAG. In neurologically asymptomatic patients with type 2 DM cerebrovascular remodeling and impaired cerebrovascular reactivity may be associated with mtDNA variations and inflammation from the early stages of diabetic kidney disease. [ABSTRACT FROM AUTHOR]

Chronic kidney disease patients treated by hemodialysis present a high cardiovascular morbidity and mortality. There is an imperative need for novel biomarkers for identifying these patients and to offer possible therapeutically interventions. We performed a prospective observational cohort study on 77 patients in the period of October 2021–October 2023. We measured serum plasma levels of interleukin 1-beta, galectin 3, human suppression of tumorigenicity factor 2, bone morphogenetic protein 2 and fibroblastic growth factor 23 at the inclusion site. We evaluated the correlations of these biomarkers with cardiac function and structure evaluated by echocardiography. The mean age was 61.02 (±11.81) years, with 45 (56.2%) males and with a dialysis vintage of 4.95 (2.4–7.8) years. Median ejection fraction was 51 (43–54%), and more than two-thirds of the patients presented valvular calcifications. Overall mortality was 22%. Interleukin 1-beta was correlated positively with ejection fraction and global longitudinal strain and negatively with left atrium diameter and left ventricle telesystolic diameter. Galectin 3 values were negatively correlated with aortic valve fibrosis and mitral valve calcifications, and human suppression tumorigenicity factor 2 was negatively correlated with mitral valve calcifications. Some of these novel biomarkers could be used to better assess cardiovascular disease in patients on maintenance hemodialysis. [ABSTRACT FROM AUTHOR]

East-European data on cancer in patients undergoing hemodialysis (HD) are scarce. This study aimed to assess the pattern of cancer and related mortality in patients with end-stage kidney disease (ESKD) undergoing HD. Retrospectively analyzing data from 7 HD centers, this study examined 1377 incident HD patients divided into three groups: no-cancers (NoC), cancers that occurred prior to HD initiation (CPI) and de novo cancer developed after HD initiation (DNC). Mortality risk and survival trends within groups were analyzed using Cox regression and Kaplan-Meier methods. In the cohort, 89.46% of the patients had no cancer (NoC group), 3.63% had cancer before (CPI group), and 6.89% had cancer after HD initiation (DNC group). The mean time from HD initiation to DNC diagnosis was 1 [2.75] years. Older age was associated with a higher risk of developing DNC (p < 0.001). Chronic tubulointerstitial nephritis (CTIN) is more prevalent in cancer patients. The most common cancer sites among DNC patients were the digestive (29.47%) and urinary tracts (18.95%), while those in CPI subjects were hematologic (22%) and digestive (20%). Cancer was an independent predictor of mortality risk (HR = 6.9, 95% [CI]:4.5–10.6, p < 0.001). East-European ESKD patients undergoing HD have a high incidence of de novo cancers whose primary cancer sites are the digestive and urinary tracts. Almost half of the HD patients with CPI have hematologic and digestive tract cancers. Age and CTIN were associated with cancer risk. Cancer is an independent risk factor for all-cause mortality in patients undergoing hemodialysis (HD). [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) is one of the most debilitating complications of type 2 diabetes mellitus (T2DM), as it progresses silently to end-stage renal disease (ESRD). The discovery of novel biomarkers of early DKD becomes acute, as its incidence is reaching catastrophic proportions. Our study aimed to quantify previously identified metabolites from serum and urine through untargeted ultra-high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UHPLC-QTOF-ESI+-MS) techniques, such as the following: arginine, dimethylarginine, hippuric acid, indoxyl sulfate, p-cresyl sulfate, L-acetylcarnitine, butenoylcarnitine and sorbitol. The study concept was based on the targeted analysis of selected metabolites, using the serum and urine of 20 healthy subjects and 90 T2DM patients with DKD in different stages (normoalbuminuria—uACR < 30 mg/g; microalbuminuria—uACR 30–300 mg/g; macroalbuminuria—uACR > 300 mg/g). The quantitative evaluation of metabolites was performed with pure standards, followed by the validation methods such as the limit of detection (LOD) and the limit of quantification (LOQ). The following metabolites from this study resulted as possible biomarkers of early DKD: in serum—arginine, dimethylarginine, hippuric acid, indoxyl sulfate, butenoylcarnitine and sorbitol and in urine—p-cresyl sulfate. [ABSTRACT FROM AUTHOR]