Complement-here, there and everywhere, but what about the transplanted organ?

The part of the innate immune system that communicates and effectively primes the adaptive immune system was termed "complement" by Ehrlich to reflect its complementarity to antibodies having previously been described as "alexine" (i.e protective component of serum) by Buchner and Bordet. It has been established that complement is not solely produced systemically but may have origin in different tissues where it can influence organ specific functions that may affect the outcome of transplanted organs. This review looks at the role of complement in particular to kidney transplantation. We look at current literature to determine whether blockade of the peripheral or central compartments of complement production may prevent ischaemic reperfusion injury or rejection in the transplanted organ. We also review new therapeutics that have been developed to inhibit components of the complement cascade with varying degrees of success leading to an increase in our understanding of the multiple triggers of this complex system. In addition, we consider whether biomarkers in this field are effective markers of disease or treatment.

Diabetic nephropathy: What does the future hold?

The consensus management of diabetic nephropathy (DN) in 2015 involves good control of glycaemia, dyslipidaemia and blood pressure (BP). Blockade of the renin-angiotensin-aldosterone system using angiotensin-converting enzyme inhibitors, angiotensin-2 receptor blockers or mineralocorticoid inhibitors are key therapeutic approaches, shown to be beneficial once overt nephropathy is manifest, as either, or both, of albuminuria and loss of glomerular filtration rate. Some significant additional clinical benefits in slowing the progression of DN was reported from the Remission clinic experience, where simultaneous intensive control of BP, tight glycaemic control, weight loss, exercise and smoking cessation were prioritised in the management of DN. This has not proved possible to translate to more conventional clinical settings. This review briefly looks over the history and limitations of current therapy from landmark papers and expert reviews, and following an extensive PubMed search identifies the most promising clinical biomarkers (both established and proposed). Many challenges need to be addressed urgently as in order to obtain novel therapies in the clinic; we also need to examine what we mean by remission, stability and progression of DN in the modern era.

Management of the dialysis patient in general intensive care.

The incidence of end-stage renal disease (ESRD) is rising and represents an important group of patients admitted to intensive care units (ICU). ESRD patients have significant co-morbidities and specific medical requirements. Renal replacement therapy (RRT), cardiovascular disease, disorders of electrolytes, drug metabolism, and sepsis are discussed. This review provides a practical approach to problems specific to the ESRD patient and common problems on ICU that require special consideration in ESRD patients. ESRD patients are at risk of hyperkalaemia. I.V. insulin and nebulized salbutamol lower serum potassium until definitive treatment with RRT is instituted. ESRD patients are prone to hypocalcaemia, which requires i.v. replacement if associated with complications. Midazolam has delayed metabolism and elimination in renal impairment and should be avoided. Morphine and its derivatives accumulate in renal failure and shorter-acting opiates are preferable. The use of diuretics is limited to patients with residual urine output. When required, therapeutic systemic anticoagulation should be achieved with unfractionated heparin as it is reversible and its metabolism and clearance are independent of renal function. The risk of sepsis is higher among ESRD patients when compared with patients with normal renal function. Empiric treatment should include both Gram-positive and Gram-negative cover, and methicillin-resistant Staphylococcus aureus cover if the patient has a dialysis catheter. Cardiovascular events account for the majority of deaths among ESRD patients. Troponin-I and CK-MB in combination should be used as markers of acute myocardial damage in the appropriate context, whereas B-type natriuretic peptide and troponin-T values are of less value.

P2X(7) receptor at the heart of disease.

Purinergic signaling is a crucial component of disease whose pathophysiological basis is now well established. This review focuses on P2X(7), a unique bifunctional purinoreceptor that either opens a non selective cation channel or forms a large, cytolytic pore depending on agonist application and leading to membrane blebbing and to cell death either by necrosis or apoptosis.Activation of P2X(7) receptor has been shown to stimulate the release of multiple proinflammatory cytokines by activated macrophages, with the IL-1b to be the most extensively studied among them. These findings were verified by the use of knockout P2X(7) ((-/-)) mice.Update information coming from all fields of research implicate this receptor at the very heart of diseases such as rheumatoid arthritis, multiple sclerosis, depression, Alzheimer disease, and to kidney damage, in renal fibrosis and experimental nephritis.Clinical studies are currently underway with the newly developed selective antagonists for P2X(7) receptor, the results of which are eagerly anticipated. These studies together with data from in-vivo experiments with the P2X(7) knockout mice and in-vitro experiments will shed light in this exciting area.