Drug-induced acute interstitial nephritis: Prospective randomized trial comparing oral steroids and high-dose intravenous pulse steroid therapy in guiding the treatment of this condition

The most important aspect of treating drug-induced acute interstitial nephritis (AIN) is timely discontinuation of the offending drug. Steroids, oral as well as intravenous (IV), are used in the treatment of drug-induced AIN. The present study was undertaken to compare the efficacy of oral prednisolone versus IV suprapharmacological doses of corticosteroids in the treatment of drug-induced AIN. This prospective randomized controlled study included drug-induced AIN diagnosed on histopathology over a period of two years. Patients were randomized to oral prednisolone (Group A) 1 mg/kg for two weeks or pulse methylprednisolone (Group B) 30 mg/kg for three days (maximum 1 g) followed by oral prednisolone 1 mg/kg for two weeks, tapered over two weeks. Response was reported as complete remission (CR) [improvement in estimated glomerular filtration rate (eGFR) to ≥60 mL/min/1.73 m2], partial remission (PR) (improvement but eGFR <60 mL/min/1.73 m2), or nonresponders to steroids (no CR/PR). Steroid therapy was instituted to 31 biopsy-proven AIN cases (Group A - 16 and Group B - 15). Drugs implicated in the causation of AIN included pantoprazole, diclofenac, rifampicin, naproxen, aspirin, imipenem, piroxicam, cefixime, lornoxicam, Chinese herbs, etoricoxib, ciprofloxacin, and phenytoin. There was no difference in the baseline parameters between the two groups. At the end of follow-up, 58.06% achieved CR and 41.93% achieved PR. In Group A, nine (56.2%) achieved CR and seven (43.7%) achieved PR. In Group B, nine (60%) achieved CR and six (40%) achieved PR. There was no significant difference between the two groups. Pulses of high doses of corticosteroids have a significant but transient anti-inflammatory effect. Both oral and IV suprapharmacological doses of corticosteroids are equally effective in the treatment of drug-induced AIN, if used early

Chronic Kidney Disease in Children: A Review

Chronic kidney disease (CKD) in children is a life-consuming ailment with a variable but progressive course. CKD, in particular, the end stage kidney disease (ESKD) affects multiple body systems complexed with secondary complications that significantly and adversely affect the growth, development and quality of life. Although uncommon in children, CKD poses unique challenges to the health care delivery system to manage the primary renal disorders and extrarenal manifestations of CKD along with a heavy socioeconomic burden. Despite the availability of better management tools, there is a rise in incidence and prevalence of pediatric CKD for which wide range short- and long-term planning is inevitable that will lure the medicos to acquire the advanced nephrological training and skills, besides providing quality infrastructure and sustained socio-economic support. Our review is aimed to provide recent advances regarding the evaluation and management of pediatric CKD and its complications

The tumor microenvironment as driver of stemness and therapeutic resistance in breast cancer: New challenges and therapeutic opportunities

Background: Breast cancer (BC), the second most common cause of cancer-related deaths, remains a significant threat to the health and wellness of women worldwide. The tumor microenvironment (TME), comprising cellular components, such as cancer-associated fibroblasts (CAFs), immune cells, endothelial cells and adipocytes, and noncellular components such as extracellular matrix (ECM), has been recognized as a critical contributor to the development and progression of BC. The interplay between TME components and cancer cells promotes phenotypic heterogeneity, cell plasticity and cancer cell stemness that impart tumor dormancy, enhanced invasion and metastasis, and the development of therapeutic resistance. While most previous studies have focused on targeting cancer cells with a dismal prognosis, novel therapies targeting stromal components are currently being evaluated in preclinical and clinical studies, and are already showing improved efficacies. As such, they may offer better means to eliminate the disease effectively. Conclusions: In this review, we focus on the evolving concept of the TME as a key player regulating tumor growth, metastasis, stemness, and the development of therapeutic resistance. Despite significant advances over the last decade, several clinical trials focusing on the TME have failed to demonstrate promising effectiveness in cancer patients. To expedite clinical efficacy of TME-directed therapies, a deeper understanding of the TME is of utmost importance. Secondly, the efficacy of TME-directed therapies when used alone or in combination with chemo- or radiotherapy, and the tumor stage needs to be studied. Likewise, identifying molecular signatures and biomarkers indicating the type of TME will help in determining precise TME-directed therapies