AM1- receptor dependent protection by intermedin of human vascular and cardiac non-vascular cells from ischaemia-reperfusion injury

Intermedin (IMD) protects rodent heart and vasculature from oxidative stress and ischaemia. Less is known about distribution of IMD and its receptors and the potential for similar protection in man. Expression of IMD and receptor components were studied in human aortic endothelium cells (HAECs), smooth muscle cells (HASMCs), cardiac microvascular endothelium cells (HMVECs) and fibroblasts (v-HCFs). Receptor subtype involvement in protection by IMD against injury by hydrogen peroxide (H2O2, 1 mmol l?¹) and simulated ischaemia and reperfusion were investigated using receptor component-specific siRNAs. IMD and CRLR, RAMP1, RAMP2 and RAMP3 were expressed in all cell types.When cells were treated with 1 nmol l?¹ IMD during exposure to 1 mmol l?¹ H2O2 for 4 h, viability was greater vs. H2O2 alone (P<0.05 for all cell types). Viabilities under 6 h simulated ischaemia differed (P<0.05) in the absence and presence of 1 nmol l?¹ IMD: HAECs 63% and 85%; HMVECs 51% and 68%; v-HCFs 42% and 96%. IMD 1 nmol l?¹ present throughout ischaemia (3 h) and reperfusion (1 h) attenuated injury (P<0.05): viabilities were 95%, 74% and 82% for HAECs, HMVECs and v-HCFs, respectively, relative to those in the absence of IMD (62%, 35%, 32%, respectively). When IMD 1 nmol l?¹ was present during reperfusion only, protection was still evident (P<0.05, 79%, 55%, 48%, respectively). Cytoskeletal disruption and protein carbonyl formation followed similar patterns. Pre-treatment (4 days) of HAECs with CRLR or RAMP2, but not RAMP1 or RAMP3, siRNAs abolished protection by IMD (1 nmol l?¹) against ischaemia-reperfusion injury. IMD protects human vascular and cardiac non-vascular cells from oxidative stress and ischaemia-reperfusion,predominantly via AM1 receptors.

Experiences of carers supporting dying renal patients managed without dialysis

Aim: To explore the impact of being a family carer to patients with stage 5 chronic kidney disease managed without dialysis.
Background: Increasing numbers of patients with renal disease worldwide are making the decision not to embark on dialysis. This group has significant physical and psychological symptom burdens similar to or greater than those in advanced cancer patients. Little is known about the impact on family carers.
Design: Exploratory, qualitative design.
Methods: The study was undertaken with 19 carers caring for patients managed in a Renal Supportive Care Service in the UK between 2006–2008. Sixty-one semi-structured interviews and detailed field notes inform the analysis.
Findings: ‘Caring from diagnosis to death’ was the overarching theme illustrated by three sub-themes: (i) Caregiver's plight – making sense of the disease and potential deterioration; (ii) Having to care indefinitely; and (iii) Avoiding talk of death. ‘Caring from diagnosis to death’ coincides with an original concept analysis of renal supportive care, which is considered an adjunct to the management of patients with renal disease at all stages of their illness.
Conclusion: There is a clear need for further research internationally and theory-based nursing interventions to support carers of patients managed without dialysis. The development of a holistic, integrated care pathway based on carer perspectives, which includes identification of information needs related to original diagnosis, associated comorbidities, treatment options, prognosis, and assistance in developing strategies to manage communication with patients as the end of life approaches, is required.

IHG-1 amplifies TGF-beta1 signaling and is increased in renal fibrosis

Induced in high glucose-1 (IHG-1) is an evolutionarily conserved gene transcript upregulated by high extracellular glucose concentrations, but its function is unknown. Here, it is reported that the abundance of IHG-1 mRNA is nearly 10-fold higher in microdissected, tubule-rich renal biopsies from patients with diabetic nephropathy compared with control subjects. In the diabetic nephropathy specimens, in situ hybridization localized IHG-1 to tubular epithelial cells along with TGF-beta1 and activated Smad3, suggesting a possible role in the development of tubulointerstitial fibrosis. Supporting this possibility, IHG-1 mRNA and protein expression also increased with unilateral ureteral obstruction. In the HK-2 proximal tubule cell line, overexpression of IHG-1 increased TGF-beta1-stimulated expression of connective tissue growth factor and fibronectin. IHG-1 was found to amplify TGF-beta1-mediated transcriptional activity by increasing and prolonging phosphorylation of Smad3. Conversely, inhibition of endogenous IHG-1 with small interference RNA suppressed transcriptional responses to TGF-beta1. In summary, IHG-1, which increases in diabetic nephropathy, may enhance the actions of TGF-beta1 and contribute to the development of tubulointerstitial fibrosis.

Elevated soluble cellular adhesion molecules are associated with increased mortality in a prospective cohort of renal transplant recipients

Increased plasma levels of cellular adhesion molecules (CAMs) have been shown to be predictors of all cause mortality in individuals with chronic renal failure 12 and patients with end-stage renal disease receiving haemodialysis 3. In renal transplant recipients the predictive value of CAMs has not been well characterised. The aim of this study was to assess the relationship between CAMs and all-cause mortality during prospective follow-up of a renal transplant cohort.

Which patients with renal colic should be referred?

Around 1-2 people per thousand present with an acute episode of pain caused by renal stones each year. Renal colic is classically sudden in onset, unilateral, and radiates from loin to groin. Renal pelvic or upper ureteric stones usually cause more flank pain and tenderness while lower ureteric stones cause pain radiating towards the ipsilateral testicle or labia. Other common symptoms include nausea and vomiting, haematuria and irritative LUTS. A febrile patient with renal colic requires immediate hospital admission. Symptoms suggestive of renal colic along with a positive dipstick for haematuria have a reported sensitivity of 84% and specificity of 99% but it is important to consider other differential diagnoses. An NSAID is preferred over an opiate drug as an initial analgesic choice as the NSAID can help reduce ureteric spasm. Diclofenac has the best evidence base for this class of analgesic. About 90% of stones will pass spontaneously and thus it is often appropriate to manage renal colic at home. Patients with signs of peritonitis, systemic infection, septic shock as well as those whose diagnosis is unclear should be referred urgently to hospital. Patients who are systemically unwell with renal stones are more likely to have an infected and obstructed urinary tract system that needs urgent imaging and possible drainage. All patients who are managed at home should have renal tract imaging within a week by fast track referral to radiology or as an urgent urology outpatient referral as per local guidelines to rule out an obstructed urinary system. Patients with recurrent stones should be advised to maintain a copious fluid intake (>2 L/day) to reduce the concentration of the urine. A reduction in salt intake (ideally

Maintenance treatment of renal anaemia in haemodialysis patients with methoxy polyethylene glycol-epoetin beta versus darbepoetin alfa administered monthly:a randomized comparative trial

Several studies with erythropoiesis-stimulating agents claim that maintenance therapy of renal anaemia may be possible at extended dosing intervals; however, few studies were randomized, results varied, and comparisons between agents were absent. We report results of a multi-national, randomized, prospective trial comparing haemoglobin maintenance with methoxy polyethylene glycol-epoetin beta and darbepoetin alfa administered once monthly.