Short-term patient and graft outcomes continue to improve after kidney and liver transplantation, with 1-year survival rates over 80%; however, improving longer-term outcomes remains a challenge. Improving the function of grafts and health of recipients would not only enhance quality and length of life, but would also reduce the need for retransplantation, and thus increase the number of organs available for transplant. The clinical transplant community needs to identify and manage those patient modifiable factors, to decrease the risk of graft failure, and improve longer-term outcomes.COMMIT was formed in 2015 and is composed of 20 leading kidney and liver transplant specialists from 9 countries across Europe. The group's remit is to provide expert guidance for the long-term management of kidney and liver transplant patients, with the aim of improving outcomes by minimizing modifiable risks associated with poor graft and patient survival posttransplant.The objective of this supplement is to provide specific, practical recommendations, through the discussion of current evidence and best practice, for the management of modifiable risks in those kidney and liver transplant patients who have survived the first postoperative year. In addition, the provision of a checklist increases the clinical utility and accessibility of these recommendations, by offering a systematic and efficient way to implement screening and monitoring of modifiable risks in the clinical setting.

/pdf/practical-recommendations-for-long-term-management-of-41r0cgop8b.pdf

Practical Recommendations for Long-term Management of Modifiable Risks in Kidney and Liver Transplant Recipients: A Guidance Report and Clinical Checklist by the Consensus on Managing Modifiable Risk in Transplantation (COMMIT) Group.

The cornerstone of nanoscience and nanotechnology are nanoparticles which have immense power and functional ability in diverse fields. Nanoparticles are synthesized by physical, chemical methos but limitations are due to its toxicity. We have discussed few green synthesis routes which are eco friendly and less toxic methods, including alage, microorganisms, plants etc.. Expoiting the potential of medicinal plants, is one of the green synthesis routes and is significant because the current therapeutic approaches have toxicity problems and microbial multidrug resistance issues. As the metal nanoparticles have received great attention across the globe, so in this study we have discussed and focused many different metallic nanoparticles obtained by green synthesis using medicinal plants. We have also discussed the types, size and medicinal properties like antibacterial, antifungal, anticancer, antiviral activities of nanoparticles. The biomolecules, secondary metabolites and coenzymes present in the plants help in easy reduction of metal ions to nanoparticles. Such nanoparticles are considered as potential antioxidants and promising candidates in cancer treatment. The simplified model summarises the green synthesis, its characterization using physicochemical means and their biomedical applications. Succinctly, we have discussed the recent advances in green synthesis of metallic nanoparticles, milestones, therapeutic applications and future perspectives of biosynthesized nanoparticles from some important medicinal plants.

Medicinal plants: Treasure trove for green synthesis of metallic nanoparticles and their biomedical applications

Diacerein is a symptomatic slow-acting drug in osteoarthritis (SYSADOA) with anti-inflammatory, anti-catabolic and pro-anabolic properties on cartilage and synovial membrane. It has also recently been shown to have protective effects against subchondral bone remodelling. Following the end of the revision procedure by the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency, the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) constituted a panel of 11 experts to better define the real place of diacerein in the armamentarium for treating OA. Based on a literature review of clinical trials and meta-analyses, the ESCEO confirms that the efficacy of diacerein is similar to that of non-steroidal anti-inflammatory drugs (NSAIDs) after the first month of treatment, and superior to that of paracetamol. Additionally, diacerein has shown a prolonged effect on symptoms of several months once treatment was stopped. The use of diacerein is associated with common gastrointestinal disorders such as soft stools and diarrhoea, common mild skin reactions, and, uncommonly, hepatobiliary disorders. However, NSAIDs and paracetamol are known to cause potentially severe hepatic, gastrointestinal, renal, cutaneous and cardiovascular reactions. Therefore, the ESCEO concludes that the benefit–risk balance of diacerein remains positive in the symptomatic treatment of hip and knee osteoarthritis. Furthermore, similarly to other SYSADOAs, the ESCEO positions diacerein as a first-line pharmacological background treatment of osteoarthritis, particularly for patients in whom NSAIDs or paracetamol are contraindicated.

/pdf/diacerein-benefits-risks-and-place-in-the-management-of-168qsl14z7.pdf

Diacerein: Benefits, Risks and Place in the Management of Osteoarthritis. An Opinion-Based Report from the ESCEO.

Drug-induced nephrotoxicity contributes to acute kidney injury (AKI) and represents a major problem in the clinical setting. We investigated the possible involvement of NLRP3 inflammasome activation in methotrexate (MTX)-induced nephrotoxicity and the protective potential of ferulic acid (FA), pointing out the role of PPARγ and Nrf2/HO-1 signaling. Rats that received MTX showed a significant increase in circulating creatinine and urea, and kidney Kim-1 levels along with multiple histological alterations. Reactive oxygen species (ROS), malondialdehyde and nitric oxide levels showed a significant increase in the kidney of rats that received MTX, while antioxidant defenses were diminished. FA ameliorated kidney function markers, prevented histological alterations, suppressed ROS production and enhanced antioxidant defenses. FA inhibited MTX-induced inflammasome activation as showed by the decreased phosphorylation of NF-κB, and expression of NLRP3, caspase-1 and IL-1β. MTX caused apoptosis marked by increased expression of BAX, cytochrome c and caspase-3, and suppressed Bcl-2, effects that were significantly reversed in FA-treated groups. In addition, FA up-regulated Nrf2/ARE/HO-1 signaling and PPARγ expression in the kidney of MTX-induced rats. In conclusion, activation of NLRP3 inflammasome may represent a new mechanism for MTX nephrotoxicity. FA up-regulated PPARγ and Nrf2 signaling, prevented overproduction of ROS, and suppressed NF-κB/NLRP3 inflammasome axis and apoptosis in the kidney of MTX-induced rats.

Ferulic acid protects against methotrexate nephrotoxicity via activation of Nrf2/ARE/HO-1 signaling and PPARγ, and suppression of NF-κB/NLRP3 inflammasome axis.

Neonates, infants, and children differ from adults in many aspects, not just in age, weight, and body composition. Growth, maturation and environmental factors affect drug kinetics, response and dosing in pediatric patients. Almost 80 % of drugs have not been studied in children, and dosing of these drugs is derived from adult doses by adjusting for body weight/size. As developmental and maturational changes are complex processes, such simplified methods may result in subtherapeutic effects or adverse events. Kidney function is impaired during the first 2 years of life as a result of normal growth and development. Reduced kidney function during childhood has an impact not only on renal clearance but also on absorption, distribution, metabolism and nonrenal clearance of drugs. ‘Omics’-based technologies, such as proteomics and metabolomics, can be leveraged to uncover novel markers for kidney function during normal development, acute kidney injury, and chronic diseases. Pharmacometric modeling and simulation can be applied to simplify the design of pediatric investigations, characterize the effects of kidney function on drug exposure and response, and fine-tune dosing in pediatric patients, especially in those with impaired kidney function. One case study of amikacin dosing in neonates with reduced kidney function is presented. Collaborative efforts between clinicians and scientists in academia, industry, and regulatory agencies are required to evaluate new renal biomarkers, collect and share prospective pharmacokinetic, genetic and clinical data, build integrated pharmacometric models for key drugs, optimize and standardize dosing strategies, develop bedside decision tools, and enhance labels of drugs utilized in neonates, infants, and children.

https://hsrc.himmelfarb.gwu.edu/cgi/viewcontent.cgi?article=2697&context=smhs_peds_facpubs

Effect of Kidney Function on Drug Kinetics and Dosing in Neonates, Infants, and Children

Pharmaceutical agents provide diagnostic and therapeutic utility that are central to patient care. However, all agents also carry adverse drug effect profiles. While most of these are clinically insignificant, some drugs may cause unacceptable toxicity that impacts negatively on patient morbidity and mortality. Recognizing adverse effects is important for administering appropriate drug doses, instituting preventive strategies, and withdrawing the offending agent due to toxicity. In the present article, we will review those drugs that are associated with impaired renal function. By focusing on pharmaceutical agents that are currently in clinical practice, we will provide an overview of nephrotoxic drugs that a treating physician is most likely to encounter. In doing so, we will summarize risk factors for nephrotoxicity, describe clinical manifestations, and address preventive and treatment strategies.

/pdf/drug-induced-impairment-of-renal-function-5d8inaaynn.pdf

Drug-induced impairment of renal function

Approach to the Diagnosis and Treatment of Hyponatremia in Pregnancy

https://www.kidney-international.org/article/S0085-2538(15)30135-6/pdf

A case of crystalline nephropathy

Blood pressure (BP) management is essential in patients with end-stage kidney disease (ESKD) on maintenance dialysis as hypertension is the most common cardiovascular risk factor in this population Even though this is true across all age groups, the aging process adds challenges to the evaluation and management of BP in dialysis patients In this chapter, we will review aspects related to the management of BP and the treatment of hypertension in patients on chronic maintenance dialysis, with a focus on issues that are modified by the aging process, being mindful of the caveat that data restricted to elderly patients are scanty

Managing Blood Pressure in the Elderly: What Is Different?

The kidneys are designed to perform several essential physiologic functions. Renal dysfunction in any form results in significant systemic manifestations in the human body. Patient with kidney dysfunction undergoing any surgical procedure presents unique challenges. Proper understanding of basic pathophysiology of renal disease, appropriate clinical evaluation prior to the surgery, and proper monitoring and care during the intraoperative and postoperative period are integral to achieving good surgical outcomes. This chapter addresses the basic concepts that should guide a surgeon when dealing with a patient with abnormal kidney function. A multidisciplinary approach to care is recommended when managing a patient with any form of kidney dysfunction during the perioperative phase. This involves appropriate consultation with patient’s primary care provider, nephrologist, and pharmacist as indicated.

George Sunny Pazhayattil

Papers

Drug-induced impairment of renal function

Approach to the Diagnosis and Treatment of Hyponatremia in Pregnancy

A case of crystalline nephropathy

Managing Blood Pressure in the Elderly: What Is Different?

Renal Disorders and Maxillofacial Surgery