Renal outcome in patients with newly diagnosed multiple myeloma: results from the UK NCRI Myeloma XI trial.

Renal injury is a common complication of multiple myeloma (MM) and is associated with adverse outcome. Despite this, the natural history of renal injury in patients with MM remains uncertain especially in the context of intensive therapy and novel therapies. To address the lack of data, we evaluated the renal function of 2334 patients from the UK National Cancer Research Institute Myeloma XI trial at baseline and at 12 months to assess renal function over time and the factors associated with change. Patients who had severe acute kidney injury or a requirement for dialysis were excluded. At 12 months of the 1450 evaluable patients planned for autologous transplantation; 204 (14%) patients had a decline in estimated glomerular filtration rate (eGFR) ≥25% from baseline, 341 (23.5%) had an improvement and 905 (62%) had no significant change in eGFR. Renal outcome at 12 months for the 884 evaluable patients who were not planned for transplant was similar. Improved renal function was more likely if patients were <70 years old, male, had an average eGFR <60 mL per minute per 1.73 m2 and a higher baseline free light chain level >1000 mg/L, and/or a free light chain response of >90%. It did not correlate with monoclonal-protein response, transplantation, or use of a bortezomib-based regimen. We show that with current therapies the proportion of patients who have a significant decline in renal function in the first 12 months is small. The greatest relative improvement in eGFR is seen in patients with high free light chain at baseline and a high light chain response. This trial was registered at http://www.isrctn.com as #49407852.

Post-transplant Monoclonal Gammopathy of Renal Significance: A Case Series.

Monoclonal gammopathy of renal significance (MGRS) is a new concept with evolving evidence for treatment. MGRS in the transplant kidney is a rare cause of renal transplant dysfunction that can lead to graft loss. Most cases of post-transplant MGRS are due to recurrent disease. Clone-specific chemotherapy is required to target the underlying clone, and this may improve graft survival; however, this can be challenging, as most patients are elderly with age-related comorbidities and may have complications associated with increasing immunosuppression. Here, we report 3 cases of renal allograft MGRS, and each case highlights different challenges in the diagnosis and management of this condition.

Repurposing of Fluvastatin Against Candida albicans CYP450 Lanosterol 14 α-demethylase, a Target Enzyme for Antifungal Therapy: An In silico and In vitro Study.

BACKGROUND: The incidence of fungal infections has increased significantly. Specifically the cases of candida albicans infection are increasing day by day and their resistance to clinically approved drugs is a major concern for humans. Various classes of antifungal drugs are available in the market for the treatment of these infections but unfortunately, none of them is able to treat the infection. OBJECTIVES: Thus, in the present investigation, we have repurposed the well-known drug (Fluvastatin) in the treatment of Candida albicans infections by using in silico, in vitro and ex vivo techniques. MATERIAL AND METHODS: Computational and in vitro techniques. RESULTS: Firstly, we developed and validated a simple model of CYP45014α-lanosterol demethylase of Candida albicans by using crystal structure of Mycobacterium tuberculosis (1EA1). Further, fluvastatin was docked with a validated model of CYP45014α-lanosterol demethylase and revealed good binding affinity as that of fluconazole. In vitro results (Percentage growth retardation, Fungal growth kinetics, Biofilm test and Post antifungal test) have shown good antifungal activity of fluvastatin. Finally, the results of MTT assay have shown non-cytotoxic effect of fluvastatin in murine splenocytes and thymocytes. CONCLUSION: However, further in vivo studies are required to confirm the complete role of fluvastatin as an antifungal agent.

Repurposing of Existing Statin Drugs for Treatment of Microbial Infections: How Much Promising?

Today's microbial infections' resistance to approved drugs, the emergence of new infectious diseases and lack of vaccines, create a huge threat to human health. Thus, there is an urgent need to create novel antimicrobial agents, but the high cost and prolonged timeline of novel drug discovery and development is the major barrier to make new drugs. Therefore, there is a need for specific cost effective approaches in order to identify new drugs for the treatment of various microbial infections. Drug repurposition is an alternative technique to find existing clinically approved drugs for other indications. This approach may enhance the portfolio of Pharmaceutical companies by reducing the time and money required for the development of new chemical entity. In literature, various studies have reported some encouraging results regarding the antimicrobial use of existing statin drugs. Further, some clinical studies have also shown the protective effect of statin drugs in reduction of the morbidity and mortality due to many infectious diseases but complete understanding is still lacking. Thus, there is a need for better understanding of the use of statin drugs, especially in the context of antimicrobial effects. In this review, we try to summarize the use of statin drugs in various infectious diseases and their proposed antimicrobial mechanism of action. Further, current challenges and future perspectives of repurposition of statin drugs as antimicrobial agents have also been discussed.

Successful Renal Outcome in Membranoproliferative Glomerulonephritis Following Treatment of the Underlying Subtle Clone: A Case Report.

Membranoproliferative glomerulonephritis (MPGN) secondary to a monoclonal gammopathy is a rare glomerular disease and is defined as a monoclonal gammopathy of renal significance. The disease is characterized by glomerular monotypic immunoglobulin deposits and specific changes on light microscopy and electron microscopy. Immunochemistry is required to establish monoclonality, and electron microscopy helps to characterize the deposits ultrastructurally. Investigation for the underlying monoclonal protein should be done. We report a case of MPGN secondary to monoclonal gammopathy of renal significance that responded to treatment of the underlying clone with chemotherapy, resulting in improvement in renal function. Patients with MPGN and immunoglobulin deposition should be evaluated for a monoclonal protein to guide the management strategy.