Search

La administración de busulfán es ampliamente utilizada como parte del régimen de acondicionamiento en pacientes que se van a someter a trasplante de células madre hematopoyéticas. Se recomienda monitorizar las concentraciones plasmáticas de busulfán con el fin de optimizar la dosis en cada paciente y minimizar su toxicidad. El objetivo del presente estudio es validar un método analítico sencillo, rápido y costo-efectivo para la cuantificación de busulfán en plasma por cromatografía líquida acoplada a espectrometría de masas en tándem de aplicabilidad en la práctica clínica.

Administration of busulfan is extending rapidly as a part of a conditioning regimen in patients undergoing hematopoietic stem cell transplantation (HSCT). Monitoring blood plasma levels of busulfan is recommended for identifying the optimal dose in patients and for minimizing toxicity. The aim of this research was to validate a simple, rapid, and cost-effective analytical tool for measuring busulfan in human plasma that would be suitable for routine clinical use. This novel tool was based on liquid chromatography coupled to mass spectrometry.

The aim of this study was to harmonize the criteria for the Bhattacharya indirect method Microsoft Excel Spreadsheet for reference intervals calculation to reduce between-user variability and use these criteria to calculate and evaluate reference intervals for eight analytes in two different years. Anonymized laboratory test results from outpatients were extracted from January 1st 2018 to December 31st 2019. To assure data quality, we examined the monthly results from an external quality control program. Reference intervals were determined by the Bhattacharya method with the St Vincent's hospital Spreadsheet firstly using original criteria and then using additional harmonized criteria defined in this study. Consensus reference intervals using the additional harmonized criteria were calculated as the mean of four users' lower and upper reference interval results. To further test the operation criteria and robustness of the obtained reference intervals, an external user validated the Spreadsheet procedure. The extracted test results for all selected laboratory tests fulfilled the quality criteria and were included in the present study. Differences between users in calculated reference intervals were frequent when using the Spreadsheet. Therefore, additional criteria for the Spreadsheet were proposed and applied by independent users, such as: to set central bin as the mean of all the data, bin size as small as possible, at least three consecutive bins and a high proportion of bins within the curve. The proposed criteria contributed to the harmonization of reference interval calculation between users of the Bhattacharya indirect method Spreadsheet. [ABSTRACT FROM AUTHOR]

Primary or idiopathic focal segmental glomerulosclerosis (FSGS) is a kidney entity that involves the podocytes, leading to heavy proteinuria and in many cases progresses to end-stage renal disease. Idiopathic FSGS has a bad prognosis, as it involves young individuals who, in a considerably high proportion (∼15%), are resistant to corticosteroids and other immunosuppressive treatments as well. Moreover, the disease recurs in 30–50% of patients after kidney transplantation, leading to graft function impairment. It is suspected that this relapsing disease is caused by a circulating factor(s) that would permeabilize the glomerular filtration barrier. However, the exact pathologic mechanism is an unsettled issue. Besides its poor outcome, a major concern of primary FSGS is the complexity to confirm the diagnosis, as it can be confused with other variants or secondary forms of FSGS and also with other glomerular diseases, such as minimal change disease. New efforts to optimize the diagnostic approach are arising to improve knowledge in well-defined primary FSGS cohorts of patients. Follow-up of properly classified primary FSGS patients will allow risk stratification for predicting the response to different treatments. In this review we will focus on the diagnostic algorithm used in idiopathic FSGS both in native kidneys and in disease recurrence after kidney transplantation. We will emphasize those potential confusing factors as well as their detection and prevention. In addition, we will also provide an overview of ongoing studies that recruit large cohorts of glomerulopathy patients (Nephrotic Syndrome Study Network and Cure Glomerulonephropathy, among others) and the experimental studies performed to find novel reliable biomarkers to detect primary FSGS. [ABSTRACT FROM AUTHOR]

Immunosuppression based on calcineurin inhibitors (CNIs) has greatly improved organ transplantation, although subsequent nephrotoxicity significantly hinders treatment success. There are no currently available specific soluble biomarkers for CNI-induced nephrotoxicity and diagnosis relies on renal biopsy, which is costly, invasive and may cause complications. Accordingly, identification of non-invasive biomarkers distinguishing CNI-induced kidney tubular damage from that of other etiologies would greatly improve diagnosis and enable more precise dosage adjustment. For this purpose, HK-2 cells, widely used to model human proximal tubule, were treated with CNIs cyclosporine-A and FK506, or staurosporine as a calcineurin-independent toxic compound, and secretomes of each treatment were analyzed by proteomic means. Among the differentially secreted proteins identified, only fascin-1 was specifically released by both CNIs but not by staurosporine. To validate fascin-1 as a biomarker of CNI-induced tubular toxicity, fascin-1 levels were analyzed in serum and urine from kidney-transplanted patients under CNIs treatment presenting or not isometric vacuolization (IV), which nowadays represents the main histological hallmark of CNI-induced tubular damage. Patients with chronic kidney disease (CKD) and healthy volunteers were used as controls. Our results show that urinary fascin-1 was only significantly elevated in the subset of CNI-treated patients presenting IV. Moreover, fascin-1 anticipated the rise of sCr levels in serially collected urine samples from CNI-treated pulmonary-transplanted patients, where a decline in kidney function and serum creatinine (sCr) elevation was mainly attributed to CNIs treatment. In conclusion, our results point towards fascin-1 as a putative soluble biomarker of CNI-induced damage in the kidney tubular compartment., Competing Interests: None.

Background & Aims: The metabolic response to surgery includes a net loss of proteins that influences negatively the clinical evolution of the patients. We investigated the effect of perioperative nutrition on protein metabolism alterations immediately after surgery., Methods: A control group of 21 surgery patients were submitted to conventional perioperative nutritional protocol (18 h of fasting plus low-dose glucose after surgery). An experimental group of eight similar patients was given complete parenteral nutrition during 24 h before and 24 h after surgery. Nitrogen balance, whole body protein synthesis, breakdown, and 3-methylhistidine were determined before surgery and 24 h after surgery., Results: The immediate response to surgery with conventional nutritional management was a net protein loss (-1.023 g prot. kg(-1) day(-1)), caused by an increase in the protein breakdown (137.9% of preoperative values), while the protein synthesis remained unchanged (98.4%). The 3-methylhistidine excretion was not increased in respect to perioperative values, suggesting that the degraded protein was not from muscular origin. The experimental group with perioperative nutrition showed neither protein loss (+0.075 g prot. kg(-1) day(-1)) nor changes in protein synthesis or breakdown vs. preoperative values (96.3% and 88.0%, respectively)., Conclusion: Perioperative nutrition prevents the early protein losses after gastrointestinal surgery.