1.
Design and optimization strategies for the development of new drugs that treat chronic kidney disease.
Ramos, AM, Fernández-Fernández, B, Pérez-Gómez, MV, Carriazo Julio, SM, Sanchez-Niño, MD, Sanz, A, Ruiz-Ortega, M, Ortiz, A
Expert opinion on drug discovery. 2020;(1):101-115
Abstract
Introduction: Chronic kidney disease (CKD) is characterized by increased risks of progression to end-stage kidney disease requiring dialysis and cardiovascular mortality, predicted to be among the five top causes of death by 2040. Only the design and optimization of novel strategies to develop new drugs to treat CKD will contain this trend. Current therapy for CKD includes nonspecific therapy targeting proteinuria and/or hypertension and cause-specific therapies for diabetic kidney disease, autosomal dominant polycystic kidney disease, glomerulonephritides, Fabry nephropathy, hemolytic uremic syndrome and others.Areas covered: Herein, the authors review the literature on new drugs under development for CKD as well as novel design and development strategies.Expert opinion: New therapies for CKD have become a healthcare priority. Emerging therapies undergoing clinical trials are testing expanded renin-angiotensin system blockade with double angiotensin receptor/endothelin receptor blockers, SGLT2 inhibition, and targeting inflammation, the immune response, fibrosis and the Nrf2 transcription factor. Emerging therapeutic targets include cell senescence, complement activation, Klotho expression preservation and microbiota. Novel approaches include novel model systems that can be personalized (e.g. organoids), unbiased systems biology-based identification of new therapeutic targets, drug databases that speed up drug identification and repurposing, nanomedicines that improve drug delivery and RNA targeting to expand the number of targetable proteins.
2.
Anemia of Inflammation with An Emphasis on Chronic Kidney Disease.
Begum, S, Latunde-Dada, GO
Nutrients. 2019;(10)
Abstract
Iron is vital for a vast variety of cellular processes and its homeostasis is strictly controlled and regulated. Nevertheless, disorders of iron metabolism are diverse and can be caused by insufficiency, overload or iron mal-distribution in tissues. Iron deficiency (ID) progresses to iron-deficiency anemia (IDA) after iron stores are depleted. Inflammation is of diverse etiology in anemia of chronic disease (ACD). It results in serum hypoferremia and tissue hyperferritinemia, which are caused by elevated serum hepcidin levels, and this underlies the onset of functional iron-deficiency anemia. Inflammation is also inhibitory to erythropoietin function and may directly increase hepcidin level, which influences iron metabolism. Consequently, immune responses orchestrate iron metabolism, aggravate iron sequestration and, ultimately, impair the processes of erythropoiesis. Hence, functional iron-deficiency anemia is a risk factor for several ailments, disorders and diseases. Therefore, therapeutic strategies depend on the symptoms, severity, comorbidities and the associated risk factors of anemia. Oral iron supplements can be employed to treat ID and mild anemia particularly, when gastrointestinal intolerance is minimal. Intravenous (IV) iron is the option in moderate and severe anemic conditions, for patients with compromised intestinal integrity, or when oral iron is refractory. Erythropoietin (EPO) is used to treat functional iron deficiency, and blood transfusion is restricted to refractory patients or in life-threatening emergency situations. Despite these interventions, many patients remain anemic and do not respond to conventional treatment approaches. However, various novel therapies are being developed to treat persistent anemia in patients.
3.
Clostridium Difficile Infection in the Nephrology Ward.
Dudzicz, S, Adamczak, M, Więcek, A
Kidney & blood pressure research. 2017;(5):844-852
Abstract
Clostridium difficile is currently the most frequently identified pathogen causing antibiotic-associated diarrhea and the main cause of nosocomial diarrhea. In recent years, increases incidence of infection, severe infection, recurrent infection and mortality from Clostridium difficile infection (CDI) have been observed. This may be a consequence of excessive antibiotic use and spread of the hypervirulent epidemic BI/NAP1/027 strain of Clostridium difficile. The main risk factors for CDI are: antibiotic therapy, previous hospitalizations and number of comorbid conditions. Prevention of CDI mainly is focused in two directions: reducing the exposure of patients to the disease pathogen by intensifying hygiene measures, and reducing the impact of risk factors. A meta-analyses of clinical studies (observational, cohort and case control) showed significantly higher risk of CDI and CDI recurrence in patients with chronic kidney disease and increased mortality risk in chronic kidney disease patients with CDI comparing those without CDI. Increased risk of CDI in patients with chronic kidney disease can be caused by: frequent antibiotic therapy associated with numerous infections resulting in intestinal microflora dysfunction, frequent hospitalizations, older age of the patients and an impaired immune system. Among preventative measures against CDI, the use of probiotics were also studied. In patients hospitalized in nephrology ward highly significant reduction of the CDI incidence was observed after the introduction of Lactobacillus plantarum 299v as CDI prophylaxis. Therefore, the use of Lactobacillus plantarum 299v seems to be a promising method of CDI prevention in chronic kidney disease patients hospitalized in nephrology ward.