1,721,111 research outputs found
Biomarkers and Precision Medicine in IgA Nephropathy
No full textThe field of biomarker research in IgA nephropathy has experienced a major boost in recent years with the publication of a large number of scientific reports. Candidate biomarkers from blood, urine, and renal tissue obtained through the use of clinical chemistry, molecular biology, and omics have been proposed for translation in clinical practice. Nevertheless, individual biomarkers often lack sensitivity and specificity with the consequent impairment of disease specificity. This review, moving on from the analysis of the four-hit hypothesis, illustrates the biomarkers linked to the abnormal glycosylation process of IgA1 and the immune complex formation. It also describes other serum and urinary biomarkers. Given the profound insights into the pleiotropic function of a single biomarker that is specific for a pathophysiological mechanism, this review suggests a novel approach based on a panel of biomarkers that covers the entire pathogenic process of the disease. Clinical bioinformatics that integrate genetic, clinical, and bioinformatics data sets could optimize the specific value of each biomarker in a multimarker panel. This is a promising approach for precision medicine and personalized therapy in IgA nephropathy. (C) 2018 Elsevier Inc. All rights reserved
MicroRNAs in glomerular diseases from pathophysiology to potential treatment target
No full textMiRNAs are regulators of gene expression in diverse biological and pathological courses in life. Their discovery may be considered one of the most important steps in the story of modern biology. miRNAs are packed within exosomes and released by cells for cellular communications; they are present in bodily fluids. Their study opens the way for understanding the pathogenetic mechanisms of many diseases; furthermore, as potential candidate biomarkers, they can be measured in bodily fluids for non-invasive monitoring of disease outcomes. The present review highlights recent advances in the role of miRNAs in the pathogenesis of primary and secondary glomerulonephritides such as IgA nephropathy, focal segmental glomerular sclerosis, lupus nephritis and diabetic nephropathy. The identification of reciprocal expression of miRNAs and their target genes provides the molecular basis for additional information on the pathogenetic mechanisms of kidney diseases. Finally, recent findings demonstrate that miRNAs can be considered as potential targets for novel drugs. © The Authors Journal compilatio
Is it time for personalized therapy in IgA nephropathy patients?
Full text linkRoccatello et al. [1] investigated the effectiveness and safety of mycophenolate mofetil (MMF) in combination with corticosteroids, compared to a 6-month course of glucocorticoids alone, in a group of 30 patients with proteinuric immunoglobulin A nephropathy (IgAN) who had active renal lesions (including proliferative endocapillary and extracapillary lesions and fibrinoid necrosis) identified through kidney biopsy. All patients received renin-angiotensin system blockers (RASBs) at the maximum tolerated dose as supportive therapy. The retrospective study demonstrated a significant reduction in proteinuria in both patient groups, with the mean follow-up period being 18.7 months for the first group receiving MMF in combination with corticosteroids, and 21.5 months for the group treated with corticosteroids alone. At the end of the follow-up period, the authors obtained a cumulative sparing dose of 6 g of corticosteroids in the group of patients who received the combined therapy (MMF and corticosteroids).
The study is limited by its retrospective design and the small number of patients included. However, it highlights two important points: first, the central importance of kidney biopsy in determining therapy for IgAN patients, and second, the potential for MMF to reduce the overall dose of corticosteroids required for treatment.
An international group of nephrologists dedicated 6 years (2004–2009) to developing the Oxford classification of the renal lesions in kidney biopsy from IgAN patients. Briefly, the classification is based on the grade of histological lesions as mesangial proliferation (M0,1), endocapillary proliferation (E0,1), glomerular sclerosis (S0,1) and tubulointerstitial lesions (T0,1,2). Eight years later, in 2017, the classification was revised and extracapillary proliferative lesions (C0,1,2) were included [2]. Thus, active renal lesions (E1 and C1,2) were differentiated from chronic renal lesions (T1,2). Unfortunately, the renal lesions were not considered in the first and second release of the KDIGO guidelines [3]. It is recommended that all patients receive intensive supportive therapy (renin-angiotensin system blockers) for at least 3–6 months following kidney biopsy. If the patient remains proteinuric (excreting more than 1 g per day) after this period, corticosteroids may be added to the treatment regimen. This means that active renal lesions become chronic in IgAN patients after 3 months of supportive therapy without immediate immunosuppressive therapy. This non-appropriate procedure has been adopted in all randomized clinical trials (RCTs) in the last 10 years, as shown in Table 1. The time lapse between the kidney biopsy and the randomization procedure fluctuated between 3 and 6 months of supportive therapy. All biopsy-proven IgAN patients (with active or chronic renal lesions) who were enrolled in those studies had chronic renal lesions because active renal lesions were not immediately treated with immunosuppressive therapy. There are several points to consider with this therapeutic approach. Firstly, corticosteroids may not be necessary for treating proteinuric IgAN patients with chronic renal lesions after supportive therapy. Newer drugs such as gliflozins and endothelin angiotensin receptor antagonists, when combined with RASBs, may effectively reduce proteinuria [4, 5]. Secondly, these drugs do not have to be limited to IgAN patients alone, but may also be used to treat other biopsy-proven chronic glomerular diseases. For example, sparsentan was initially shown to be effective and safe in patients with focal and segmental glomerular sclerosis [6] before being tested in IgAN patients [5]. Additionally, it is worth mentioning the targeted-release formulation, budesonide (Nefecon), a corticosteroid that has been shown to reduce proteinuria in IgAN patients. However, it is uncertain whether this drug can also reduce active renal lesions. It would be valuable to investigate the potential of Nefecon when combined with an antiproteinuric drug in treating IgAN patients with active renal lesions following kidney biopsy. Unfortunately, this hypothesis cannot be proved by the NEFIGAN and NEFIgArD studies because all patients received RASBs alone for at least 3 months before Nefecon therapy
Potential Reparative Role of Resident Adult Renal Stem/Progenitor Cells in Acute Kidney Injury
Full text linkHuman kidney is particularly susceptible to ischemia and toxins with consequential tubular necrosis and activation of inflammatory processes. This process can lead to the acute renal injury, and even if the kidney has a great capacity for regeneration after tubular damage, in several circumstances, the normal renal repair program may not be sufficient to achieve a successful regeneration. Resident adult renal stem/progenitor cells could participate in this repair process and have the potentiality to enhance the renal regenerative mechanism. This could be achieved both directly, by means of their capacity to differentiate and integrate into the renal tissues, and by means of paracrine factors able to induce or improve the renal repair or regeneration. Recent genetic fate-tracing studies indicated that tubular damage is instead repaired by proliferative duplication of epithelial cells, acquiring a transient progenitor phenotype and by fate-restricted clonal cell progeny emerging from different nephron segments. In this review, we discuss about the properties and the reparative characteristics of high regenerative CD133(+)/CD24(+) cells, with a view to a future application of these cells for the treatment of acute renal injury
DRG's and cost/efficacy indicators in nephrology and dialysis. Results at a hospital division
No full textThe Diagnosis Related Groups (DRGs) classification system correlates hospital performance with their relative costs and encourages more efficient productive processes. We report the following parameters: a) the distribution of hospital discharges according to the Major Diagnostic Categories (MDCs) and DRGs; b) the relationship between mean length of stay and threshold values; c) economic analysis of the cost-reimbursement pay-off. The results showed that 71.3% of DRGs belonged to nephro-urological MDC 11 and 28.7% in other internal MDCs (mainly involving cardiac and respiratory system). Of the latter, 67.7% were utilized for dialysis and transplant patients and kidney donors. In MDC 11 the most common DRGs were: the surgical DRG 315, produced by the vascular accesses for hemodialysis and by insertion of Tenckoff catheter for peritoneal dialysis, DRG 316 by cases of acute and chronic renal failure, DRG 332 by biopsy-proven glomerulonephritides. The length of stay was most commonly within range of one-third of threshold value for specific DRG; there was a low percentage of one-day stays and outlier cases. The economic analysis demonstrated that mean daily reimbursement sum was 590,714 ITL. Analysis of the overall costs yielded a mean daily cost of 455,838 ITL. In conclusion, quality indicators show that, appropriately, our specialist activity is largely devoted to the diagnosis and treatment of acute and chronic nephropathies and complications following dialysis and renal transplant
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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