Dimethylarginines in Children after Anti-Neoplastic Treatment

Background and Objectives: According to a recent Cochrane systematic review, renal impairment can develop in 0–84% of childhood cancer survivors in the future. The renal function impairment in this patient group can be related to nephrectomy, nephrotoxic agents therapy, abdominal radiotherapy, and combinations of these treatment methods. In this study, in a population of patients after anti-neoplastic therapy, with particular emphasis on patients after Wilms’ tumour treatment, we compared new substances which play role in the chronic kidney disease (CKD) pathogenesis (asymmetric dimethylarginine—ADMA, symmetric dimethylarginine—SDMA) with standard renal function markers (e.g., creatinine and cystatin C in serum, creatinine in urine, etc.) to assess the usefulness of the former. Materials and Methods: Eighty-four children, without CKD, bilateral kidney tumours, congenital kidney defects, or urinary tract infections, with a minimum time of 1 year after ending anti-neoplastic treatment, aged between 17 and 215 months, were divided into three groups: group 1—patients after nephroblastoma treatment (n = 21), group 2—after other solid tumours treatment (n = 44), and group 3—after lymphoproliferative neoplasms treatment (n = 19). The patients’ medical histories were taken and physical examinations were performed. Concentrations of blood urea nitrogen (BUN), creatinine, cystatin C, C-reactive protein (CRP), ADMA, and SDMA in blood and albumin in urine were measured, and a general urine analysis was performed. The SDMA/ADMA ratio, albumin–creatine ratio, and estimated glomerular filtration rate (eGFR) were calculated. eGFR was estimated by three equations recommended to the paediatric population by the KDIGO from 2012: the Schwartz equation (eGFR1), equation with creatinine and urea nitrogen (eGFR2), and equation with cystatin C (eGFR3). Results: Both the eGFR1 and eGFR2 values were significantly lower in group 1 than in group 3 (eGFR1: 93.3 (83.1–102.3) vs. 116.5 (96.8–126.9) mL/min/1.73 m2, p = 0.02; eGFR2: 82.7 (±14.4) vs. 94.4 (±11.9) mL/min/1.73 m2, p = 0.02). Additionally, there were weak positive correlations between SDMA and creatinine (p < 0.05, r = 0.24), and cystatin C (p < 0.05, r = 0.32) and weak negative correlations between SDMA and eGFR1 (p < 0.05, r = −0.25), eGFR2 (p < 0.05, r = −0.24), and eGFR3 (p < 0.05, r = −0.32). Conclusions: The usefulness of ADMA and SDMA in the diagnosis of renal functional impairment should be assessed in further studies. eGFR, calculated according to equations recommended for children, should be used in routine paediatric practice.

Renal and Inflammation Markers—Renalase, Cystatin C, and NGAL Levels in Asymptomatic and Symptomatic SARS-CoV-2 Infection in a One-Month Follow-Up Study

The aim of our study was to evaluate the influence of asymptomatic infection and the occurrence of symptomatic COVID-19 on specific biochemical, renal, and immune parameters—renalase, neutrophil gelatinase-associated lipocalin (NGAL) cystatin C (CysC), and creatinine—and their weekly fluctuations during a one-month observation period in COVID-19 patients admitted to hospital. The study involved 86 individuals: 30 patients with diagnosed COVID-19, 28 people with asymptomatic infection confirmed with IgG antibodies—the IG(+) group—and 28 individuals without any (IgG, IgE) anti-SARS-CoV-2 antibodies—the IG(−) group. In the COVID-19 group, blood was drawn four times: (1) on day 0/1 after admission to hospital (C1 group), (2) 7 days later (C7 group), (3) 14 days later (C14 group), and (4) 28 days later (C28 group). In the IG(−) and IG(+) groups, blood was drawn once. There were no significant differences in creatinine, Cys C, and uric acid between any of the analyzed groups. NGAL levels were significantly higher in IG(+) and at all time-points in the COVID-19 groups than in controls. A similar observation was made for renalase at the C7, C14, and C28 time-points. Plasma renalase, NGAL, and CysC are unrelated to kidney function in non-critically ill COVID-19 patients and those with asymptomatic infection. Renalase and NGAL are most likely related to the activation of the immune system rather than kidney function. Asymptomatic SARS-CoV-2 infection causes a rise in plasma NGAL levels similar to those observed in symptomatic COVID-19 patients. Therefore, more attention should be paid to tracking and monitoring the health of these people.

Predicting Diagnostic Potential of Cathepsin in Epithelial Ovarian Cancer: A Design Validated by Computational, Biophysical and Electrochemical Data

Background: Epithelial ovarian cancer remains one of the leading variants of gynecological cancer with a high mortality rate. Feasibility and technical competence for screening and detection of epithelial ovarian cancer remain a major obstacle and the development of point of care diagnostics (POCD) may offer a simple solution for monitoring its progression. Cathepsins have been implicated as biomarkers for cancer progression and metastasis; being a protease, it has an inherent tendency to interact with Cystatin C, a cysteine protease inhibitor. This interaction was assessed for designing a POCD module. Methods: A combinatorial approach encompassing computational, biophysical and electron-transfer kinetics has been used to assess this protease-inhibitor interaction. Results: Calculations predicted two cathepsin candidates, Cathepsin K and Cathepsin L based on their binding energies and structural alignment and both predictions were confirmed experimentally. Differential pulse voltammetry was used to verify the potency of Cathepsin K and Cathepsin L interaction with Cystatin C and assess the selectivity and sensitivity of their electrochemical interactions. Electrochemical measurements indicated selectivity for both the ligands, but with increasing concentrations, there was a marked difference in the sensitivity of the detection. Conclusions: This work validated the utility of dry-lab integration in the wet-lab technique to generate leads for the design of electrochemical diagnostics for epithelial ovarian cancer.

Monitoring of Kidney Functions, Electrolytes and Volemia Analyzed by Application Example of Artificial Intelligence in Patients with Heart Failure

Basal renal function is a predictor of response to diuretic therapy and marker of poor prognosis. Simultaneous changes in renal function, sodium, potassium values and their interdependence are key parameters in addition to volemia for the assessment of cardiorenal balance. In our paper, an analysis of volemia, electrolytes, and renal function in heart failure was performed using an algorithm based on the ANFIS (Adoptive Neural Fuzzy Inference System), an intelligent approach to renal and heart function monitoring. The study included 90 subjects who were divided into two groups: clinical (n-80) and control (n-10). The base is composed of parameters B-type natriuretic peptide (NT-proBNP), sodium (Na), potassium (K), ejection fraction (EF), EPI creatinine-cystatin C formula and ANFIS expert system combined in neural network and fuzzy logic network. The results showed that the overall trend of data verification in the network with NT-proBNP, Na and K that we formed is approximately 15%, with which subjects can be classified according to the severity of hypervolemia, electrolyte disturbance and renal function. NT-proBNP (pg/mL) had the most influence on the EPI creatinine-cystatin C formula. Serum sodium (Na) has the most influence on the ejection fraction (EF).