Urinary Transforming Growth Factor-beta 1 as a marker of response to immunosuppressive treatment, in patients with crescentic nephritis

BACKGROUND: Crescentic nephritis is characterized by formation of cellular crescents that soon become fibrotic and result in irreversible damage, unless an effective immunosuppressive therapy is rapidly commenced. TGF-β(1 )is involved in the development of crescents through various pathways. The aim of this study was to identify whether the determination of urinary TGF-β(1 )levels in patients with crescentic nephritis could be used as a marker of response to treatment. METHODS: Fifteen patients with crescentic nephritis were included in the study. The renal expression of TGF-β(1 )was estimated in biopsy sections by immunohistochemistry and urinary TGF-β(1 )levels were determined by quantitative sandwich enzyme immunoassay (EIA). TGF-β(1 )levels were determined at the time of renal biopsy, before the initiation of immunosuppressive treatment (corticosteroids, cyclophosphamide and plasma exchange). Twelve patients with other types of proliferative glomerulonephritis and ten healthy subjects were used as controls. RESULTS: Improvement of renal function with immunosuppressive therapy was observed in 6 and stabilization in 4 patients (serum creatinine from 3.2 ± 1.5 to 1.4 ± 0.1 mg/dl and from 4.4 ± 1.2 to 4.1 ± 0.6 mg/dl, respectively). In 5 patients, with severe impairment of renal function who started on dialysis, no improvement was noted. The main histological feature differentiating these 5 patients from others with improved or stabilized renal function was the percentage patients with poor response to treatment were the percentage of glomeruli with crescents and the presence of ruptured Bowman's capsule and glomerular necrosis. Urinary TGF-β(1 )levels were significantly higher in patients who showed no improvement of renal function with immunosuppressive therapy (930 ± 126 ng/24 h vs. 376 ± 84 ng/24 h, p < 0.01). TGF-β(1 )was identified in crescents and tubular epithelial cells, whereas a significant correlation of TGF-β(1 )immunostaining with the presence of fibrocellular cresents was observed (r = 0.531, p < 0,05). CONCLUSION: Increased TGF-β(1 )renal expression and urinary excretion that is related to the response to immunosuppressive therapy was observed in patients with crescentic nephritis. Evaluation of urinary TGF-β(1 )levels may be proved a useful marker of clinical outcome in patients with crescentic nephritis

Prevalence, microbiological features, and risk factors for periprosthetic joint infections in oncologic patients following tumor resection and megaprosthetic reconstruction

Periprosthetic joint infection (PJI) after tumor resection and megaprosthetic reconstruction of bone defects is a common complication. The purpose of this study was to evaluate the prevalence of these infections, assess their microbiological profile, and identify perioperative risk factors for these complications. A single-center retrospective cohort study was conducted including 273 patients, who had undergone musculoskeletal tumor resection and megaprosthetic reconstruction. The medical records of these patients were screened for several parameters, including development of postoperative PJI. All reviewed parameters were compared between patients who developed infections and those who did not. Infection developed in 36 patients, indicating an incidence of 13.2 % (95 % confidence interval (CI): 9.4 %–17.8 %). The most common isolated pathogens in patients with PJI included coagulase-negative staphylococci (n=20; 56 %), followed by Staphylococcus aureus (n=9; 25 %). Multivariable logistic regression analysis indicated that development of PJI was associated with diabetes (odds ratio (OR): 7.64; 95 % confidence interval (CI): 1.36–42.7; p=0.020), a lower albumin level (OR: 0.10; 95 % CI: 0.02–0.49; p=0.005), and a prolonged duration of surgery (OR: 4.30; 95 % CI: 1.08–17.1; p=0.038). Our results indicate that certain parameters such as diabetes, low albumin levels, and prolonged duration of surgery are associated with a higher risk of infection.</p

Brain dysfunction in tubular and tubulointerstitial kidney diseases

Kidney function has two important elements: glomerular filtration and tubular function (secretion and reabsorption). A persistent decrease in glomerular filtration rate (GFR), with or without proteinuria, is diagnostic of chronic kidney disease (CKD). While glomerular injury or disease is a major cause of CKD and usually associated with proteinuria, predominant tubular injury, with or without tubulointerstitial disease, is typically non-proteinuric. CKD has been linked with cognitive impairment, but it is unclear how much this depends on a decreased GFR, altered tubular function or the presence of proteinuria. Since CKD is often accompanied by tubular and interstitial dysfunction, we explore here for the first time the potential role of the tubular and tubulointerstitial compartments in cognitive dysfunction. To help address this issue we selected a group of primary tubular diseases with preserved GFR in which to review the evidence for any association with brain dysfunction. Cognition, mood, neurosensory and motor disturbances are not well characterized in tubular diseases, possibly because they are subclinical and less prominent than other clinical manifestations. The available literature suggests that brain dysfunction in tubular and tubulointerstitial diseases is usually mild and is more often seen in disorders of water handling. Brain dysfunction may occur when severe electrolyte and water disorders in young children persist over a long period of time before the diagnosis is made. We have chosen Bartter and Gitelman syndromes and nephrogenic diabetes insipidus as examples to highlight this topic. We discuss current published findings, some unanswered questions and propose topics for future research

Cognitive disorders in patients with chronic kidney disease: Approaches to prevention and treatment

Background: Cognitive impairment is common in patients with chronic kidney disease (CKD), and early intervention may prevent the progression of this condition. Methods: Here, we review interventions for the complications of CKD (anemia, secondary hyperparathyroidism, metabolic acidosis, harmful effects of dialysis, the accumulation of uremic toxins) and for prevention of vascular events, interventions that may potentially be protective against cognitive impairment. Furthermore, we discuss nonpharmacological and pharmacological methods to prevent cognitive impairment and/or minimize the latter's impact on CKD patients' daily lives. Results: A particular attention on kidney function assessment is suggested during work-up for cognitive impairment. Different approaches are promising to reduce cognitive burden in patients with CKD but the availabe dedicated data are scarce. Conclusions: There is a need for studies assessing the effect of interventions on the cognitive function of patients with CKD

Nephrectomy in autosomal dominant polycystic kidney disease: A consensus statement of the ERA Genes &amp; Kidney Working Group

\ua9 2025 The Author(s). A substantial number of patients with autosomal dominant polycystic kidney disease (ADPKD) undergo a nephrectomy, especially in workup for a kidney transplantation. Currently, there is no evidence-based algorithm to guide clinicians about which patients should undergo nephrectomy, the optimal timing of this procedure, or the preferred surgical technique. This systematic review-based consensus statement aimed to answer important questions regarding nephrectomy in ADPKD. A literature review was performed and extended to a meta-analysis when possible. For this purpose, PubMed and EMBASE were searched up to May 2024. Fifty-four publications, describing a total of 2391 procedures, were included. In addition, an exploratory questionnaire was sent to urologists, nephrologists, and transplant surgeons. These sources were used to develop practice points about indications, complications, mortality, and timing and technique of nephrectomy. In addition, data on renal embolization as a potential alternative to nephrectomy were explored and summarized. To reach consensus, practice points were defined and improved in three Delphi survey rounds by experts of the European Renal Association Working Group Genes &amp; Kidney and the European Association of Urology Section of Transplantation Urology. A total of 23 practice points/statements were developed, all of which reached consensus. Among others, it was deemed that nephrectomy can be performed successfully for various indications and is an intermediate risk procedure with acceptable mortality and minimal impact on kidney graft function when performed before, in the same session or after transplantation. The complication rate seems to increase when the procedure is performed as an emergency. During the workup for transplantation, patient complaints should be assessed routinely by questionnaires to indicate symptom burden. Deciding on the need for nephrectomy and exploring potential alternatives such as kidney embolization should be a process of shared decision-making, preferably after multidisciplinary consultation

Glucocorticoid signaling and osteoarthritis

Glucocorticoids are steroid hormones synthesized and released by the adrenal cortex. Their main function is to maintain cell homeostasis through a variety of signaling pathways, responding to changes in an organism&apos;s environment or developmental status. Mimicking the actions of natural glucocorticoids, synthetic glucocorticoids have been recruited to treat many diseases that implicate glucocorticoid receptor signaling such as osteoarthritis. In osteoarthritis, synthetic glucocorticoids aim to alleviate inflammation and pain. The variation of patients’ response and the possibility of complications associated with their long-term use have led to a need for a better understanding of glucocorticoid receptor signaling in osteoarthritis. In this review, we performed a literature search in the molecular pathways that link the osteoarthritic joint to the glucocorticoid receptor signaling. We hope that this information will advance research in the field and propose new molecular targets for the development of more optimized therapies for osteoarthritis. © 2018 Elsevier B.V

T helper (Th)-cytokines in the urine of patients with primary glomerulonephritis treated with immunosuppressive drugs: Can they predict outcome?

Background: Glomerulonephritides (GNs) represent common causes of chronic kidney disease associated with a wide spectrum of clinical and histological features. Various factors that activate the inflammatory cascade are involved in the development of kidney injury. The aim of this study was to estimate the urinary excretion of pro-inflammatory (IL-2, INF-γ, TNF-α, IL-6, IL-17) and anti-inflammatory (IL-4, IL-10, TGF-β1) cytokines, as well as the chemokine MCP-1 in patients with various types of GN treated by immunosuppressive drugs and to identify any prognostic value of excreted cytokines for future renal function. Patients and methods: Ninety-seven patients (62. M/35. F, age 53.1. ±. 15.6. years) with primary glomerulonephritis and 32 healthy controls were studied. The original diagnoses were membranous nephropathy (MN, n = 36), IgA nephropathy (IgAN, n = 31) and minimal changes disease or focal segmental glomerulosclerosis (MCD/FSGS, n = 30). All patients had been treated with immunosuppressive drugs and, at the time of measurement of urinary cytokine excretion, were either in clinical remission or still had active disease with persistent proteinuria. Results: GN patients had significantly higher levels of all cytokines and MCP-1 compared to healthy controls. A strong positive correlation between TGF-β1 and MCP-1 concentrations was observed in all GN patients. Increased urinary excretion of all tested cytokines apart from TNF-α and TGF-β1 was observed even in patients with clinical remission. The main difference between patients with proteinuria and those in clinical remission was the level of MCP-1 urinary excretion. The urinary excretion of MCP-1 and TGF-β1 was significantly higher in patients with MN who showed deterioration of renal function over a follow-up period of five years. Conclusions: Increased levels of cytokines are observed in the urine of patients with different types of glomerulonephritis, even after the achievement of clinical remission with the administration of immunosuppressive drugs. Urinary excretion of MCP-1 and TGF-β1 indicates the ongoing inflammatory and fibrotic processes in the kidney and is probably related to unfavourable outcomes. © 2015 Elsevier Ltd

Efficacy of antimicrobial coated orthopaedic implants on the prevention of periprosthetic infections: A systematic review and meta-analysis

Introduction: Implant-associated infections are a major problem in orthopaedic surgery. Local delivery systems of antimicrobial agents on the implant surface have attracted great interest recently. The purpose of this study was to identify antimicrobial coatings currently used in clinical practice, examining their safety and effectiveness in reducing post-operative infection rates. Materials and Methods: A systematic review was conducted in four databases (Medline, Embase, Cochrane, Cinahl) according to the Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) guidelines up to December 2019, using the key words &quot;orthopaedic implant coated&quot;, &quot;coated implant infection&quot;, &quot;silver coating &quot;and &quot;antibiotic coating&quot;. Results: Seven articles involving 1307 patients (561 with coated implants and 746 controls who were not) comparing the incidence of periprosthetic infections after the application of internal fracture fixation, total arthroplasties and endoprostheses were evaluated. Three different coating technologies were identified: gentamicin coating for tibia nail and total arthroplasties; silver technology and povidone-iodine coating for tumour endoprostheses and titanium implants. Meta-analysis demonstrated that patients who were treated with antimicrobial coated implants presented lower infection rates compared to controls over the seven studies (Q = 6.1232, I2 = 0.00, 95% CI: 1.717 to 4.986, OR: 2.926, Z= 3.949, p&lt;0.001). Subgroup statistical analysis revealed that each coating technique was effective in the prevention of periprosthetic infections (Q = 9.2606, I2 = 78.40%, 95% CI: 1.401 to 4.070, OR: 2.388, Z= 3.200, p&lt;0.001). Conclusion: All technologies were reported to have good biocompatibility and were effective in the reduction of post-operative peri-prosthetic infection rates. Copyright: © 2020 Olga D. Savvidou et al