Renal cell cancer:Nurses' role in prevention and management

In both the UK and throughout Europe, more patients are presenting with renal cell cancer (RCC), also known as renal cell carcinoma or kidney cancer. The overall survival rate varies depending on tumour grade, nodal involvement and metastasis. For those with metastasis survival drops to 10%. This article explores the risk factors associated with RCC diagnosis and staging, treatments including drugs and procedures and the role of the nurse in diagnosis and accurate assessment. Nurses are ideally suited to consider the physical, functional, social, and emotional status of their patients In addition, it is essential that the nurse has an understanding of new pharmaceutical therapies, which have been licensed to treat RCC, and a sound knowledge of the possible side effects and nursing management associated with these drugs.

A literature review of end-stage renal disease and cachexia:Understanding experience to inform evidence-based healthcare

Introduction: Cachexia is a major cause of morbidity and mortality in people who have end-stage renal disease (ESRD). The majority of research into cachexia in ESRD has focused on the biological aspects of the syndrome and potential treatment modalities. While this research is necessary, it predominately focuses on the physical impact of cachexia in ESRD. The multi-dimensional psychosocial ramifications of this syndrome have been highlighted in other end-stage illness trajectories, but have not been systematically explored in persons who have ESRD. Aim: This paper discusses why this research is necessary, alongside further studies to help define the pathophysiology of this syndrome. Conclusion: The rich insightful data gained from understanding the patients' illness experience will positively contribute to the limited knowledge base available and inform future holistic patient-centred care delivery which recognises and responds to not only the biological but also the psychosocial impact of cachexia. © 2013 European Dialysis and Transplant Nurses Association/European Renal Care Association.

Lipoxins attenuate renal fibrosis by inducing let-7c and suppressing TGFβR1

Lipoxins, which are endogenously produced lipid mediators, promote the resolution of inflammation, and may inhibit fibrosis, suggesting a possible role in modulating renal disease. Here, lipoxin A4 (LXA4) attenuated TGF-ß1-induced expression of fibronectin, N-cadherin, thrombospondin, and the notch ligand jagged-1 in cultured human proximal tubular epithelial (HK-2) cells through a mechanism involving upregulation of the microRNA let-7c. Conversely, TGF-ß1 suppressed expression of let-7c. In cells pretreated with LXA4, upregulation of let-7c persisted despite subsequent stimulation with TGF-ß1. In the unilateral ureteral obstruction model of renal fibrosis, let-7c upregulation was induced by administering an LXA4 analog. Bioinformatic analysis suggested that targets of let-7c include several members of the TGF-ß1 signaling pathway, including the TGF-ß receptor type 1. Consistent with this, LXA4-induced upregulation of let-7c inhibited both the expression of TGF-ß receptor type 1 and the response to TGF-ß1. Overexpression of let-7c mimicked the antifibrotic effects of LXA4 in renal epithelia; conversely, anti-miR directed against let-7c attenuated the effects of LXA4. Finally, we observed that several let-7c target genes were upregulated in fibrotic human renal biopsies compared with controls. In conclusion, these results suggest that LXA4-mediated upregulation of let-7c suppresses TGF-ß1-induced fibrosis and that expression of let-7c targets is dysregulated in human renal fibrosis.

Long-term renal outcomes of patients with type 1 diabetes mellitus and microalbuminuria:an analysis of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications cohort

Microalbuminuria is a common diagnosis in the clinical care of patients with type 1 diabetes mellitus. Long-term outcomes after the development of microalbuminuria are variable.

Lipoxidation products as biomarkers of oxidative damage to proteins during lipid peroxidation reactions

Oxidative stress is implicated in the pathogenesis of numerous disease processes including diabetes mellitus, atherosclerosis, ischaemia reperfusion injury and rheumatoid arthritis. Chemical modification of amino acids in protein during lipid peroxidation results in the formation of lipoxidation products which may serve as indicators of oxidative stress in vivo. The focus of the studies described here was initially to identify chemical modifications of protein derived exclusively from lipids in order to assess the role of lipid peroxidative damage in the pathogenesis of disease. Malondialdehye (MDA) and 4-hydroxynonenal (HNE) are well characterized oxidation products of polyunsaturated fatty acids on low-density lipoprotein (LDL) and adducts of these compounds have been detected by immunological means in atherosclerotic plaque. Thus, we first developed gas chromatography-mass spectrometry assays for the Schiff base adduct of MDA to lysine, the lysine-MDA-lysine diimine cross-link and the Michael addition product of HNE to lysine. Using these assays, we showed that the concentrations of all three compounds increased significantly in LDL during metal-catalysed oxidation in vitro. The concentration of the advanced glycation end-product N epsilon-(carboxymethyl)lysine (CML) also increased during LDL oxidation, while that of its putative carbohydrate precursor the Amadori compound N epsilon-(1-deoxyfructose-1-yl)lysine did not change, demonstrating that CML is a marker of both glycoxidation and lipoxidation reactions. These results suggest that MDA and HNE adducts to lysine residues should serve as biomarkers of lipid modification resulting from lipid peroxidation reactions, while CML may serve as a biomarker of general oxidative stress resulting from both carbohydrate and lipid oxidation reactions.

Advances in joint modelling: A review of recent developments with application to the survival of end stage renal disease patients

The use of joint modelling approaches is becoming increasingly popular when an association exists between survival and longitudinal processes. Widely recognized for their gain in efficiency, joint models also offer a reduction in bias compared with naïve methods. With the increasing popularity comes a constantly expanding literature on joint modelling approaches. The aim of this paper is to give an overview of recent literature relating to joint models, in particular those that focus on the time-to-event survival process. A discussion is provided on the range of survival submodels that have been implemented in a joint modelling framework. A particular focus is given to the recent advancements in software used to build these models. Illustrated through the use of two different real-life data examples that focus on the survival of end-stage renal disease patients, the use of the JM and joineR packages within R are demonstrated. The possible future direction for this field of research is also discussed. © 2013 International Statistical Institute.

Survival in dialysis patients is different between patients with diabetes as primary renal disease and patients with diabetes as a co-morbid condition.

AIMS/HYPOTHESIS:

A previous study in Dutch dialysis patients showed no survival difference between patients with diabetes as primary renal disease and those with diabetes as a co-morbid condition. As this was not in line with our hypothesis, we aimed to verify these results in a larger international cohort of dialysis patients.

METHODS:

For the present prospective study, we used data from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry. Incident dialysis patients with data on co-morbidities (n?=?15,419) were monitored until kidney transplantation, death or end of the study period (5 years). Cox regression was performed to compare survival for patients with diabetes as primary renal disease, patients with diabetes as a co-morbid condition and non-diabetic patients.

RESULTS:

Of the study population, 3,624 patients (24%) had diabetes as primary renal disease and 1,193 (11%) had diabetes as a co-morbid condition whereas the majority had no diabetes (n?=?10,602). During follow-up, 7,584 (49%) patients died. In both groups of diabetic patients mortality was higher compared with the non-diabetic patients. Mortality was higher in patients with diabetes as primary renal disease than in patients with diabetes as a co-morbid condition, adjusted for age, sex, country and malignancy (HR 1.20, 95% CI 1.10, 1.30). An analysis stratified by dialysis modality yielded similar results.

CONCLUSIONS/INTERPRETATION:

Overall mortality was significantly higher in patients with diabetes as primary renal disease compared with those with diabetes as a co-morbid condition. This suggests that survival in diabetic dialysis patients is affected by the extent to which diabetes has induced organ damage.

Retinal vascular geometry predicts incident renal dysfunction in young people with type 1 diabetes

OBJECTIVE - To examine the relationship between retinal vascular geometry parameters and development of incident renal dysfunction in young people with type 1 diabetes. RESEARCH DESIGN AND METHODS - This was a prospective cohort study of 511 adolescents with type 1 diabetes of at least 2 years duration, with normal albumin excretion rate (AER) and no retinopathy at baseline while attending an Australian tertiary-care hospital. AER was quantified using three overnight, timed urine specimen collections and early renal dysfunction was defined as AER >7.5 µg/min. Retinal vascular geometry (including length-to-diameter ratio [LDR] and simple tortuosity [ST]) was quantified from baseline retinal photographs. Generalized estimating equations were used to examine the relationship between incident renal dysfunction and baseline venular LDR and ST, adjusting for age, diabetes duration, glycated hemoglobin (A1C), blood pressure (BP), BMI, and cholesterol. RESULTS - Diabetes duration at baseline was 4.8 (IQR 3.3-7.5) years. After amedian 3.7 (2.3-5.7) years follow-up, 34% of participants developed incident renal dysfunction. In multivariate analysis, higher retinal venular LDR (odds ratio 1.7, 95% CI 1.2-2.4; quartile 4 vs. 1-3) and lower venular ST (1.6, 1.1-2.2; quartile 1 vs. 2-4) predicted incident renal dysfunction. CONCLUSIONS - Retinal venular geometry independently predicted incident renal dysfunction in young people with type 1 diabetes. These noninvasive retinal measures may help to elucidate early mechanistic pathways for microvascular complications. Retinal venular geometry may be a useful tool to identify individuals at high risk of renal disease early in the course of diabetes. © 2012 by the American Diabetes Association.

CD2AP is associated with end-stage renal disease in patients with type 1 diabetes

CD2-associated protein (CD2AP) is essential for podocyte function. CD2AP mutations have been found in patients with focal segmental glomerulosclerosis, a disease histologically resembling diabetic nephropathy and often progressing to end-stage renal disease (ESRD). We hypothesised that variations in the CD2AP gene may contribute to susceptibility to glomerular injury in diabetes and investigated if single-nucleotide polymorphisms (SNPs) in CD2AP are associated with diabetic nephropathy in patients with type 1 diabetes. The discovery cohort consisted of 2,251 Finnish patients with type 1 diabetes. SNPs were selected from the HapMap database to cover the CD2AP gene. The associations between genotyped SNPs and diabetic nephropathy or ESRD were analysed with the chi-squared test and logistic regression. Three SNPs were selected for replication in cohorts from Denmark, Italy, the United Kingdom and Ireland. None of the 15 successfully genotyped SNPs were associated with diabetic nephropathy when compared to patients with normal albumin excretion rate. However, when genotype frequencies in patients with ESRD were compared with all other patients, two CD2AP SNPs, rs9369717 and rs9349417, were found to be associated with ESRD. The meta-analysis of the original and two additional European cohorts resulted in significant p values