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Resumo A elevada carga da doença renal, disparidades globais no cuidado renal e desfechos ruins da insuficiência renal impõem uma sobrecarga crescente aos indivíduos afetados e suas famílias, cuidadores e a própria comunidade geral. Educação em saúde é o grau em que indivíduos e organizações têm, ou que igualmente permitem que indivíduos tenham, capacidade de encontrar, compreender e utilizar informações e serviços para tomar decisões e ações conscientes relacionadas à saúde para si e outros. Mais do que enxergar educação em saúde como um problema dos pacientes, a melhoria dessa educação depende principalmente da comunicação e educação efetiva dos profissionais em parceria com aqueles que apresentam doença renal. Para formuladores de políticas renais, educação em saúde é pré-requisito para que organizações migrem para uma cultura que coloque a pessoa no centro dos cuidados. A crescente capacidade e acesso à tecnologia oferecem novas oportunidades para melhorar educação e conscientização sobre doença renal para todas as partes interessadas. Avanços nas telecomunicações, incluindo redes sociais, podem ajudar a melhorar a educação de pessoas e provedores. O Dia Mundial do Rim declara 2022 como o ano da "Saúde dos Rins para Todos" promovendo trabalho em equipe global no avanço de estratégias para preencher a lacuna na educação e conhecimento em saúde renal. Organizações renais devem trabalhar para mudar a narrativa da educação em saúde como um problema de pacientes, para sendo responsabilidade dos profissionais e formuladores de políticas. Ao engajar-se e apoiar formulação de políticas centradas na saúde renal, planejamento de saúde comunitária e abordagens de educação em saúde para todos, comunidades renais esforçam-se para prevenir doenças renais e permitir viver bem com elas.

Introduction: Inequitable distribution of health workforce limits access to healthcare services and contributes to adverse health outcomes. WHO recommends tracking health professionals from their points of entry into university and over their careers for the purpose of workforce development and planning. Previous research has focused on medical students and graduates' choice of practice location. Few studies have targeted nursing and allied health graduates' practice intentions and destinations. The Nursing and Allied Health Graduate Outcomes Tracking (NAHGOT) study is investigating factors affecting Australian nursing and allied health students and graduates' choice of graduate practice location over the course of their studies and up to 10 years after graduation by linking multiple data sources, including routinely collected university administrative and professional placement data, surveys of students and graduates, and professional registration data. Methods: By using a prospective cohort study design, each year a new cohort of about 2000 students at each participating university (Deakin University, Monash University and the University of Newcastle) is tracked throughout their courses and for 10 years after graduation. Disciplines include medical radiation practice, nursing and midwifery, occupational therapy, optometry, paramedicine, pharmacy, physiotherapy, podiatry and psychology. University enrolment data are collected at admission and professional placement data are collected annually. Students' practice destination intentions are collected via questions added into the national Student Experience Survey (SES). Data pertaining to graduates' practice destination, intentions and factors influencing choice of practice location are collected in the first and third years after graduation via questions added to the Australian Graduate Outcomes Survey (GOS). Additionally, participants may volunteer to receive a NAHGOT survey in the second and fourth-to-tenth years after graduation. Principal place of practice data are accessed via the Australian Health Practitioner Regulation Agency (Ahpra) annually. Linked data are aggregated and analysed to test hypotheses comparing associations between multiple variables and graduate practice location. Results: This study seeks to add to the limited empirical evidence about factors that lead to rural practice in the nursing and allied health professions. This prospective large-scale, comprehensive study tracks participants from eight different health professions across three universities through their pre-registration education and into their postgraduate careers, an approach not previously reported in Australia. To achieve this, the NAHGOT study links data drawn from university enrolment and professional placement data, the SES, the GOS, online NAHGOT graduate surveys, and Ahpra data. The prospective cohort study design enables the use of both comparative analysis and hypothesis testing. The flexible and inclusive study design is intended to enable other universities, as well as those allied health professions not regulated by Ahpra, to join the study over time. Conclusion: The study demonstrates how the systematic, institutional tracking and research approach advocated by the WHO can be applied to the nursing and allied health workforce in Australia. It is expected that this large-scale, longitudinal, multifactorial, multicentre study will help inform future nursing and allied health university admission, graduate pathways and health workforce planning. Furthermore, the project could be expanded to explore health workforce attrition and thereby influence health workforce planning overall.

Objectives Primary cilia are sensory organelles which co-ordinate several developmental/repair pathways including hedgehog signalling. Studies of human renal allografts suffering acute tubular necrosis have shown that length of primary cilia borne by epithelial cells doubles throughout the nephron and collecting duct, and then normalises as renal function returns. Conversely the loss of primary cilia has been reported in chronic allograft rejection and linked to defective hedgehog signalling. We investigated the fate of primary cilia in renal allografts suffering acute rejection. Results Here we observed that in renal allografts undergoing acute rejection, primary cilia were retained, with their length increasing 1 week after transplantation and remaining elevated. We used a mouse model of acute renal injury to demonstrate that elongated renal primary cilia in the injured renal tubule show evidence of smoothened accumulation, a biomarker for activation of hedgehog signalling. We conclude that primary cilium-mediated activation of hedgehog signalling is still possible during the acute phase of renal allograft rejection.

Symptom and quality of life (QOL) measures in patients with advanced chronic kidney disease are recognized indicators of patient-centred care and represent important research, quality and clinical measures. This study examined relationships between symptom burden, QOL and functional status and associations of symptoms and mortality risk. A multisite longitudinal cohort analysis was undertaken in chronic kidney disease stage 4/5 (no dialysis) and dialysis patients. Patients completed symptom and QOL measures (Palliative Care Outcome Symptom Score renal), World Health Organisation QOL Brief Version) and Karnofsky Performance scale. Clinical and demographic data were recorded.

The focus of this article is to define goals and resulting action plans that can be collectively embraced by interested stakeholders to facilitate new therapeutic approaches to mitigate chronic kidney disease progression. The specific goals include identifying druggable targets, increasing the capacity for preclinical and early clinical development, broadening the availability of new therapeutic approaches, and increasing investment in the development of new therapies to limit chronic kidney disease. Key deliverables include the establishment of new regional, national, and global consortia; development of clinical trial networks; and creation of programs to support the temporary mutual movement of scientists between academia and the biotechnology and pharmaceutical sector. Other deliverables include cataloging and maintaining up-to-date records to collate progress in renal research and development, inventorying the capacity of research and clinical networks, and describing methods to ensure novel drug development.

To determine whether geographic variation exists in osteoporosis knowledge, management, and barriers to care in the setting of premature ovarian insufficiency (POI), among general practitioners (GPs) and women with POI. Australian GPs completed an online questionnaire regarding osteoporosis knowledge, barriers to care and educational preferences for managing osteoporosis in POI. Women with POI/early menopause (EM) completed an online questionnaire regarding osteoporosis knowledge, risk factors and health beliefs. Clinicians and consumers in metropolitan areas were compared to those in rural areas. Of 688 GP respondents, 62.2% practised in major capital cities, 13.1% in major regional cities, 7.8% in regional centres, 8.7% in rural areas and 8.1% in remote areas. Mean ± SD osteoporosis knowledge score was 9.1 ± 1.5/13, with no difference by location. Forty-one percent of GPs reported barriers to care which varied by location. Of 316 women with POI/EM, 61.1% lived in metropolitan, 22.5% in regional, 11.7% in rural and 4.4% in remote locations. The mean osteoporosis knowledge score was 8.2 ± 3.1/20, with lower scores in women living in rural and remote versus metropolitan locations (difference − 1.3; 95% CI − 2.3, − 0.25; p = 0.02). Women in rural areas were less likely to use vitamin D supplements and more likely to have a family history of osteoporosis (both p

The prevalence of diabetes around the world has reached epidemic proportions and is projected to increase to 642 million people by 2040. Diabetes is already the leading cause of end-stage kidney disease (ESKD) in most developed countries, and the growth in the number of people with ESKD around the world parallels the increase in diabetes. The presence of kidney disease is associated with a markedly elevated risk of cardiovascular disease and death in people with diabetes. Several new therapies and novel investigational agents targeting chronic kidney disease patients with diabetes are now under development. This conference was convened to assess our current state of knowledge regarding optimal glycemic control, current antidiabetic agents and their safety, and new therapies being developed to improve kidney function and cardiovascular outcomes for this vulnerable population.

Background The increasing burden of chronic kidney disease (CKD) underpins the importance for improved early detection and management programs in primary care to delay disease progression and reduce mortality rates. eMAP:CKD is a pilot program for primary care aimed at addressing the gap between current and best practice care for CKD. Methods Customized software programs were developed to integrate with primary care electronic health records (EHRs), allowing real-time prompting for CKD risk factor identification, testing, diagnosis and management according to Kidney Health Australia's (KHA) best practice recommendations. Primary care practices also received support from a visiting CKD nurse and education modules. Patient data were analyzed at baseline (150 910 patients) and at 15 months (175 917 patients) following the implementation of the program across 21 primary care practices. Results There was improvement in CKD risk factor recognition (29.40 versus 33.84%; P < 0.001) and more complete kidney health tests were performed (3.20 versus 4.30%; P < 0.001). There were more CKD diagnoses entered into the EHR (0.48 versus 1.55%; P < 0.001) and more patients achieved KHA's recommended management targets (P < 0.001). Conclusion The eMAP:CKD program has shown an improvement in identification of patients at risk of CKD, appropriate testing and management of these patients, as well as increased documentation of CKD diagnosis entered into the EHRs. We have demonstrated efficacy in overcoming the verified gap between current and best practice in primary care. The success of the pilot program has encouraging implications for use across the primary care community as a whole.

In order to change the current state of chronic kidney disease knowledge and therapeutics, a fundamental improvement in the understanding of genetic and environmental causes of chronic kidney disease is essential. This article first provides an overview of the existing knowledge gaps in our understanding of the genetic and environmental causes of chronic kidney disease, as well as their interactions. The second part of the article formulates goals that should be achieved in order to close these gaps, along with suggested timelines and stakeholders that are to be involved. A better understanding of genetic and environmental factors and their interactions that influence kidney function in healthy and diseased conditions can provide novel insights into renal physiology and pathophysiology and result in the identification of novel therapeutic or preventive targets to tackle the global public health care problem of chronic kidney disease.

Aims and Objectives: To assess a dialysis nurse practitioner ( NP ) model of care by examining satisfaction, quality of life ( QOL ) and clinical outcomes of haemodialysis patients and explore experiences of dialysis nurses. Design: Mixed methods. Methods: Database analyses of dialysis indices amongst a sample ( n = 45 ) of haemodialysis patients; a survey ( n = 27 ) examining patient experience, satisfaction and QOL; and in-depth interviews with a sample ( n = 10 ) of nurses. Results: Nurses commended the NP role, with five themes emerging: “managing and co-ordinating”, “streamlining and alleviating”, “developing capability”, “supporting innovation and quality” and “connecting rurally”. Patients’ average age was 66 years and 71% were male. Patients’ satisfaction with the care they received was rated 3.5/4 or higher across seven parameters and the average QOL score was 7.9/10. Conclusion: The NP model of care is effective in enhancing patient care within a collaborative framework. The challenge is to sustain, and enhance the model, through mentorship programs for potential candidates.

Primary focal segmental glomerulosclerosis is an important cause of end-stage kidney disease with a high rate of recurrent disease after kidney transplantation. Current therapy achieves remission in only half of patients. Recent interest has focused on the potential role of galactose in binding and inactivating the putative circulating permeability factor, supported by in vitro and clinical case report studies. Orally active and without major adverse effects, galactose has a favourable treatment profile compared with current immunosuppressive treatment options. We describe our experience using galactose therapy in two patients with recurrent focal segmental glomerulosclerosis after renal transplantation. Galactose was associated with symptomatic improvement and stabilization of graft function in one case; the other case was complicated by concurrent malignancy. In both cases, we observed a marked reduction in proteinuria with galactose treatment.

Context: Providing year-long rural immersion as part of the medical degree is commonly used to increase the number of doctors with an interest in rural practice. However, the optimal duration and setting of immersion has not been fully established. This paper explores associations between various durations and settings of rural immersion during the medical degree and whether doctors work in rural areas after graduation. Methods: Eligible participants were medical graduates of Monash University between 2008 and 2016 in postgraduate years 1-9, whose characteristics, rural immersion information and work location had been prospectively collected. Separate multiple logistic regression and multinomial logit regression models tested associations between the duration and setting of any rural immersion they did during the medical degree and (i) working in a rural area and (ii) working in large or smaller rural towns, in 2017. Results: The adjusted odds of working in a rural area were significantly increased if students were immersed for one full year (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.15–2.79), for between 1 and 2 years (OR, 2.26; 95% CI, 1.54–3.32) and for 2 or more years (OR, 4.43; 95% CI, 3.03–6.47) relative to no rural immersion. The strongest association was for immersion in a mix of both regional hospitals and rural general practice (OR, 3.26; 95% CI, 2.31–4.61), followed by immersion in regional hospitals only (OR, 1.94; 95% CI, 1.39–2.70) and rural general practice only (OR, 1.91; 95% CI, 1.06–3.45). More than 1 year's immersion in a mix of regional hospitals and rural general practices was associated with working in smaller regional or rural towns (

Nephrogenic adenoma (NA) is a benign adenomatous lesion of the urinary tract. Long considered to be a rare phenomenon, case series from the renal transplant population suggest that it may be much more common within this group. Although NA is considered to be a lesion with low premalignant potential, hematuria, lower urinary tract symptoms, and recurrent urinary tract infections (UTIs) are frequently observed in the context of NA. Furthermore, after resection of NA, lesion recurrence and persistent symptoms are frequently observed. Here we present the case of a 69-year-old male renal transplant recipient with NA and associated recurrent UTIs despite cystoscopic resection of the primary lesion. This case is illustrative of the clinical impact of NA and the need for ongoing work into the development of strategies to manage this problematic phenomenon.

BACKGROUND: The Modifications of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) are 2 equations commonly used to estimate glomerular filtration rate (eGFR). The predictive performance offered by these equations, particularly in relation to clinical outcomes in elderly hypertensive patients, is not clear. METHODS: The Second Australian National Blood Pressure Study cohort was used to investigate the predictive performance of these 2 equations for long-term outcomes (median 10.8 years) in elderly treated hypertensive patients. Both equations were used to calculate eGFR in 6,083 patients aged ≥65 years and classified as having chronic kidney disease (CKD) or no CKD (eGFR ≥60ml/min/1.73 m2). RESULTS: More patients were classified as having no CKD using the CKD-EPI equation compared with the MDRD equation (72.1% vs. 69.4%; P = 0.001). Both equations performed similarly in risk prediction of all-cause and cardiovascular mortality with decreased eGFR, except for patients with baseline eGFR of 45-59ml/min/1.73 m2, where the CKD-EPI equation predicted higher risk of all-cause mortality compared with those with no CKD. However, the magnitude of difference in risk prediction was too small to be clinically meaningful. Both equations showed similar predictive performance. However, we observed longer survival and no higher risk in those who were reclassified as having no CKD using the CKD-EPI equation, but these patients were classified earlier as having CKD using the MDRD equation. CONCLUSIONS: There was no clinically relevant difference in predictive performance for long-term survival by eGFR calculated using either of these equations in this elderly hypertensive population.

Mycobacterium haemophilum is a rare isolate of non-tuberculous Mycobacterium which has been reported to affect immunocompromised patients. We report a case of a 32-year-old renal transplant patient with M. haemophilum infection initially involving his left sinus which was treated with appropriate antimicrobial therapy for thirteen months. Two weeks after cessation of antibiotics the infection rapidly recurred in his skin and soft tissues of his hands and feet. This case highlights the difficult diagnostic and therapeutic implications of atypical infections in transplant patients. To our knowledge this is the first reported case of relapsed M. haemophilum infection in a renal transplant recipient.

In diabetic patients with acute kidney injury (AKI), kidney biopsy often reveals non-diabetic kidney pathology. This case describes a patient with known Type 1 diabetes who presented with AKI, nephrotic syndrome and haematuria. Combination pathology of seronegative anti-glomerular basement membrane antibody-mediated glomerulonephritis (anti-GBM GN), membranous nephropathy (MN) and diabetic nephropathy (DN) was demonstrated. Strong linear GBM IgG-staining on biopsy with crescentic GN and clinical AKI led to a diagnosis of anti-GBM GN, although serum antibodies were not detectable. Features of DN, Kimmelstiel–Wilson nodules and albumin staining were also present, along with features of MN, such as subepithelial deposits on electron microscopy. Despite treatment with immunosuppression and plasmapheresis, there was no recovery of kidney function. Coexisting anti-GBM GN and MN is well recognized, but the concurrent diagnosis with DN has not been described.

Background Chronic kidney disease (CKD) and end-stage kidney disease (ESKD) are serious and growing health problems with enormous impact on psychological and social functioning. Despite high rates of comorbid depression and anxiety in these patient populations, and the adverse impact these have upon treatment adherence, quality of life, social connectedness and healthcare costs there has been little attention focused on the prevention or management of these problems. Thus, our aim was to evaluate the Dialysis Optimal Health Program (DOHP) that adopts a person-centred approach and engages collaborative therapy to educate and support those diagnosed with ESKD who are commencing dialysis. Methods The study design is a randomised controlled trial. Ninety-six adult patients initiating haemodialysis or peritoneal dialysis will be randomly allocated to either the intervention (DOHP) or usual care group. Participants receiving the intervention will receive nine (8 + 1 booster session) sequential sessions based on a structured information/workbook, psychosocial and educational supports and skills building. The primary outcome measures are depression and anxiety (assessed by the Hospital Anxiety and Depression Scale; HADS). Secondary outcomes include health-related quality of life (assessed by the Kidney Disease Quality of Life instrument; KDQOL), self-efficacy (assessed by General Self-Efficacy Scale) and clinical indices (e.g. albumin and haemoglobin levels). Cost-effectiveness analysis and process evaluation will also be performed to assess the economic value and efficacy of the DOHP. Primary and secondary measures will be collected at baseline and at 3-, 6-, and 12-month follow-up time points. Discussion We believe that this innovative trial will enhance knowledge of interventions aimed at supporting patients in the process of starting dialysis, and will broaden the focus from physical symptoms to include psychosocial factors such as depression, anxiety, self-efficacy, wellbeing and community support. The outcomes associated with this study are significant in terms of enhancing an at-risk population’s psychosocial health and reducing treatment-related costs and associated pressures on the healthcare system. Trial registration ANZCTR no. 12615000810516. Registered on 5 August 2015. Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1558-z) contains supplementary material, which is available to authorized users.

Background The balANZ trial recently reported that neutral pH, low glucose degradation product (biocompatible) peritoneal dialysis (PD) solutions significantly delayed anuria and reduced peritonitis rates compared with conventional solutions. This article reports a secondary outcome analysis of the balANZ trial with respect to peritoneal membrane function. Methods Adult, incident PD patients with residual renal function were randomized to receive either biocompatible or conventional (control) PD solutions for 2 years. Peritoneal equilibration tests were performed at 1, 6, 12, 18 and 24 months. Peritoneal small solute clearances and ultra-filtration (UF) were measured at 3, 6, 9, 12, 18 and 24 months. Results Of the 185 patients recruited into the trial, 85 patients in the Balance group and 82 patients in the control group had peritoneal membrane function evaluated. Mean 4-h dialysate:plasma creatinine ratios (D:P Cr 4h) at 1 month were significantly higher in the Balance group compared with controls (0.67 ± 0.10 versus 0.62 ± 0.10, P = 0.002). Over the 2-year study period, mean D:P Cr 4 h measurements remained stable in the Balance group but increased significantly in controls [difference −0.004 per month, 95% confidence interval (95% CI) −0.005 to −0.002, P < 0.001]. Similar results were obtained for dialysate glucose ratios (D/D0 glucose). Peritoneal UF was significantly lower in the Balance group than in controls at 3 and 6 months. Over the 2-year study period, peritoneal UF increased significantly in the Balance group but remained stable in controls (difference 24 mL/day/month, 95% CI 9–39, P = 0.002). No differences in peritoneal small solute clearances, prescribed dialysate fill volumes or peritoneal glucose exposure were observed between the two groups. Conclusions Biocompatible and conventional PD solutions exert differential effects on peritoneal small solute transport rate and UF over time. Adequately powered trials assessing the impact of these differential membrane effects on PD technique and patient survival rates are warranted.

Chronic kidney disease (CKD) is now a global health problem. One important strategy to prevent and manage CKD is to offer a prevention program which could detect CKD early as well as raise awareness of the disease. In Shanghai, a community-based study demonstrated that the prevalence of CKD was high while awareness was low. The results from Shanghai urged the necessity of a screening and prevention program of CKD. In Japan, the urinalysis screening system was established to early diagnose and prevent CKD. Due to modification of lifestyle and prevalence of diabetes, urine dip-stick test for microalbuminuria might be necessary in adults while screening for proteinuria and haematuria are necessary for students and young adults. In Taiwan, two CKD programs - a CKD care program and diabetic share care program - were initiated. The cost-effectiveness study indicated that both programs could reduce end-stage renal disease (ESRD) burden in Taiwan because integrated pre-ESRD care was important for patients with CKD stage 4 and stage 5 while a diabetic shared care program was cost-effective to prevent nephropathy to patients with diabetic mellitus. In Australia, studies demonstrated that screening of high-risk individuals as well as promoting awareness were cost-effective to early detection of CKD. Furthermore, opportunistic screening with emphasis on early detection was effective in CKD prevention. The studies from those regions share experiences on early prevention and management of CKD.

Excessive reactive oxygen species play a key role in the pathogenesis of diabetic nephropathy, but to what extent these result from increased generation, impaired antioxidant systems, or both is incompletely understood. Here, we report the expression, localization, and activity of the antioxidant thioredoxin and its endogenous inhibitor thioredoxin interacting protein (TxnIP) in vivo and in vitro. In normal human and rat kidneys, expression of TxnIP mRNA and protein was most abundant in the glomeruli and distal nephron (distal convoluted tubule and collecting ducts). In contrast, thioredoxin mRNA and protein localized to the renal cortex, particularly within the proximal tubules and to a lesser extent in the distal nephron. Induction of diabetes in rats increased expression of TxnIP but not thioredoxin mRNA. Kidneys from patients with diabetic nephropathy had significantly higher levels of TxnIP than control kidneys, but thioredoxin expression did not differ. In vitro, high glucose increased TxnIP expression in mesangial, NRK (proximal tubule), and MDCK (distal tubule/collecting duct) cells, and decreased the expression of thioredoxin in mesangial and MDCK cells. Knockdown of TxnIP with small interference RNA suggested that TxnIP mediates the glucose-induced impairment of thioredoxin activity. Knockdown of TxnIP also abrogated both glucose-induced 3H-proline incorporation (a marker of collagen production) and oxidative stress. Taken together, these findings suggest that impaired thiol reductive capacity contributes to the generation of reactive oxygen species in diabetes in a site- and cell-specific manner.

GUIDELINES a. Serum anti-neutrophil cytoplasmic antibody (ANCA) measurement should not be used alone in the initial diagnosis of ANCA-associated vasculitis (AAV) but should be used in combination with the gold standard of tissue diagnosis. (Level 1 evidence) b. Measurement of ANCA by both ELISA and indirect immunofluorescence (IIF) in combination ensures optimal test sensitivity and specificity. (Level I evidence) c. The use of serial ANCA monitoring alone is insufficient to predict relapse or monitor disease activity. (Level I evidence)

Chronic renal disease is characterized by declining renal function, loss of intrinsic renal cells, and their replacement with fibrotic tissue. This study investigates apoptosis and its regulation in the context of chronic renal disease. RNA was extracted from renal biopsies from patients with various forms of chronic renal disease. Expression of genes of the Bcl-2 family, death receptor pathway, and growth factors were measured by reverse-transcription real-time polymerase chain reaction. Apoptosis was detected by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling technique. Tubulointerstitial apoptosis was positively associated with tubulointerstitial injury and renal dysfunction and increased 2.3-fold per unit (U) increase in transforming growth factor beta(1) (TGFbeta(1)) mRNA (P0.05). Conversely, a 1 U increase in epidermal growth factor (EGF) mRNA was associated with a 47% decrease in tubulointerstitial apoptosis (P0.05). Tubulointerstitial injury was correlated with increased TGFbeta(1) and tumour necrosis factor alpha (TNFalpha) mRNA (P0.005) and decreased EGF mRNA (P0.05). Additionally, for a 10 U decrease in the glomerular filtration rate there was an estimated increase of 5 and 10% in TGFbeta(1) and TNFalpha mRNA, respectively (P0.05), whereas EGF mRNA decreased by an estimated 15% (P0.005). Therefore dysregulation of cytokine/growth factor expression plays a central role in the progression of chronic renal disease through contribution to renal cell loss, tubulointerstitial injury, and renal dysfunction.

Evidence relating the rate of change in renal function, measured as eGFR, after antihypertensive treatment in elderly patients to clinical outcome is sparse. This study characterized the rate of change in eGFR after commencement of antihypertensive treatment in an elderly population, the factors associated with eGFR rate change, and the rate's association with all-cause and cardiovascular mortality.Data from the Second Australian National Blood Pressure study were used, where 6083 hypertensive participants aged ≥65 years were enrolled during 1995-1997 and followed for a median of 4.1 years (in-trial). Following the Second Australian National Blood Pressure study, participants were followed-up for a further median 6.9 years (post-trial). The annual rate of change in the eGFR was calculated in 4940 participants using creatinine measurements during the in-trial period and classified into quintiles (Q) on the basis of the following eGFR changes: rapid decline (Q1), decline (Q2), stable (Q3), increase (Q4), and rapid increase (Q5).A rapid decline in eGFR in comparison with those with stable eGFRs during the in-trial period was associated with older age, living in a rural area, wider pulse pressure at baseline, receiving diuretic-based therapy, taking multiple antihypertensive drugs, and having blood pressure140/90 mmHg during the study. However, a rapid increase in eGFR was observed in younger women and those with a higher cholesterol level. After adjustment for baseline and in-trial covariates, Cox-proportional hazard models showed a significantly greater risk for both all-cause (hazard ratio, 1.28; 95% confidence interval, 1.09 to 1.52; P=0.003) and cardiovascular (hazard ratio, 1.40; 95% confidence interval, 1.11 to 1.76; P=0.004) mortality in the rapid decline group compared with the stable group over a median of 7.2 years after the last eGFR measure. No significant association with mortality was observed for a rapid increase in eGFR.In elderly persons with treated hypertension, a rapid decline in eGFR is associated with a higher risk of mortality.

OBJECTIVE—Studies in rodent models have suggested that reduction in renal transforming growth factor (TGF)-β1 may underlie the renoprotective effects of the renin-angiotensin system (RAS) blockade. However, the role of the RAS blockade in abrogating TGF-β in human disease is unknown. Accordingly, we sought to examine TGF-β gene expression and biological activity in human renal biopsies, before and after ACE inhibition. RESEARCH DESIGN AND METHODS—RNA was extracted from renal biopsies taken from participants in the Diabiopsies study, a randomized controlled 2-year trial of 4 mg/day perindopril versus placebo that reported a reduction in proteinuria and cortical matrix expansion in type 2 diabetic nephropathy. Biopsies taken at study entry and at 2 years were obtained in 12 patients (6 placebo and 6 taking perindopril). TGF-β1 and its receptor mRNA were quantified by real-time PCR, and its biological activity was assessed by examining the activation of its intracellular signaling pathway (phosphorylated Smad2) and the expression TGF-β–inducible gene H3 (βig-H3). RESULTS—At baseline, TGF-β1 expression was similar in both placebo- and perindopril-treated groups and was unchanged over a 2-year period in biopsies of placebo-treated subjects. In contrast, perindopril treatment led to a substantial diminution in TGF-β1 mRNA (mean 83% reduction, P < 0.05). Phosphorylated Smad2 immunolabeling and βig-H3 mRNA were similarly reduced with ACE inhibition (P < 0.05) but unchanged in the placebo group. No differences were noted in the gene expression of TGF-β receptor II in biopsies of either placebo- or perindopril-treated subjects. CONCLUSIONS—This study demonstrates that over a 2-year period, treatment with perindopril in patients with type 2 diabetes and nephropathy leads to a reduction in both renal TGF-β1 gene expression and its downstream activation.

SUMMARY: Background: Peritonitis has a significant impact upon morbidity and mortality of peritoneal dialysis (PD) patients. Gram-positive organisms account for the majority of infections and vancomycin is a cost effective broad-spectrum antimicrobial treatment for PD peritonitis, but this may lead to the emergence of multiple antibiotic-resistant organisms. The purpose of the present paper was to evaluate the efficacy of a non-vancomycin-based protocol comprising cephazolin and gentamicin, which was introduced in the present PD population as empirical treatment for peritonitis. Methods: The study involved 82 peritonitis episodes over a 4-year period in 58 patients, excluding those with previous methicillin-resistant staphylococcal peritonitis. Results: With cephazolin and gentamicin there was no apparent difference in response or relapse rates in comparison to reported studies using vancomycin-based first-line therapy protocols. Conclusion: We advocate initial treatment of PD peritonitis with non-vancomycin-based therapy given similar efficacy and the potential for reduction of resistant organisms.

Ongoing investigation into the relationship between the renin-angiotensin system (RAS) and the progression of diabetic renal disease has persisted for the past two decades. Experimental and clinical evidence suggests that the RAS has a pathogenic role, induced by its haemodynamic and non-haemodynamic mechanisms. The discovery of a local intrarenal RAS provides a rationale for investigating the components of RAS, specifically Angiotensin II (AngII) in the diabetic setting. AngII has multiple effects, including activating intracellular second messengers, transcription factors, extracellular matrix protein and also growth factors and cytokines, which lead to many of the structural and functional changes in the diabetic kidney. The beneficial effects afforded by RAS blockade further implicate AngII in the progression of diabetic nephropathy. Although AngII is a common suspect in the pathogenesis of diabetic nephropathy RAS blockade does not prevent patients from progressing to end stage renal disease. Evaluating other vasoactive factors, which have similar and distinct functions to AngII, will assist in understanding their potential role in the pathogenesis of diabetic nephropathy. A large number of researchers are studying vasoactive factors, however, the case for their role in diabetic nephropathy is inconclusive. Further investigation into the effects of inhibiting vasoactive compounds, including endothelin, urotensin II and vasopeptidases, together with inhibiting RAS, may provide another therapeutic avenue for treating diabetic nephropathy.

Despite the widespread use of statins, ACE inhibitors and aspirin, cardiovascular disease in diabetes remains a major public health burden. In addition to coronary artery disease, diabetes has also been repeatedly implicated in the pathogenesis of chronic heart failure (CHF), in which 20–30% of patients report diabetes as a co-morbidity. New therapeutic strategies targeted to the diabetic patient are therefore needed. The present review focuses on two such strategies in which drug development has recently advanced from the pre-clinical to clinical studies: the modulation of advanced glycation end products and protein kinase C activation.

BACKGROUND Minimal change disease (MCD) is one of the major causes of nephrotic syndrome both in children and adults. The pathogenesis of this condition is not clear and it has been suggested that a plasma permeability factor may play a role. Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, has been thought to be one the factors involved. The aim of this study was thus to investigate the role of VEGF in the pathogenesis of MCD. METHODS The expression of the gene for VEGF and VEGF receptor-2 (VEGFR-2) was estimated using in situ hybridization in renal biopsy specimens taken from patients with nephrotic syndrome and diagnosed histologically as MCD. The results were compared with those obtained in normal renal tissue. Biopsy specimens from eight patients diagnosed as having MCD were randomly selected for the study. The patients were aged 4-60 years at the time of the biopsy. There were four females and four males. All patients had presented with a nephrotic syndrome, five with recent onset of the disease, two with repeated attacks of the syndrome and one had reduced renal function. RESULTS The gene expression for VEGF, measured as the proportional glomerular area occupied by autoradiographic grains, was significantly less in the patients with MCD than in controls (1.9 +/- 0.4 vs 4.8 +/- 0.6%, P < 0.0025), whereas the gene expression for VEGFR-2 was no different to controls (1.9 +/- 0.4 vs 2.0 +/- 0.2%). CONCLUSIONS MCD is associated with a reduction in the expression of the gene for VEGF. As VEGF may play an important role in renal repair and survival, it is postulated that the deficiency, which we have shown, may lead to the dysregulation of the repair process in MCD.

Background andobjectivesThecalcimimeticcinacalcet reduced therisk of death or cardiovascular (CV) events in older, but not younger, patients with moderate to severe secondary hyperparathyroidism (HPT) who were receiving hemodialysis. To determine whether the lower risk in younger patients might be due to lower baseline CV risk and more frequent use of cointerventions that reduce parathyroid hormone (kidney transplantation, parathyroidectomy, and commercial cinacalcet use), this study examined the effects of cinacalcet in older ($65 years, n=1005) and younger (,65 years, n=2878) patients. Design, setting, participants, & measurements Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) was a global, multicenter, randomized placebo-controlled trial in 3883 prevalent patients on hemodialysis, whose outcomes included death, major CV events, and development of severe unremitting HPT. The age subgroup analysis was prespecified. ResultsOlderpatients hadhigher baselineprevalenceof diabetesmellitusandCV comorbidity. Annualizedrates of kidney transplantation and parathyroidectomy were .3-fold higher in younger relative to older patients and were more frequent in patients randomized to placebo. In older patients, the adjusted relative hazard (95% confidence interval) for the primary composite (CV) end point (cinacalcet versus placebo) was 0.70 (0.60 to 0.81); in younger patients, the relative hazard was 0.97 (0.86 to 1.09). Corresponding adjusted relative hazards for mortality were 0.68 (0.51 to 0.81) and 0.99 (0.86 to 1.13). Reduction in the risk of severe unremitting HPT was similar in both groups. Conclusions In the EVOLVE trial, cinacalcet decreased the risk of death and of major CV events in older, but not younger, patients with moderate to severe HPT who were receiving hemodialysis. Effect modification by age may be partly explained by differences in underlying CV risk and differential application of cointerventions that reduce parathyroid hormone. Clin J Am Soc Nephrol 10: ccc–ccc, 2015. doi: 10.2215/CJN.07730814

Background. Mutations in the gene coding for the podocyte slit-pore membrane protein, nephrin, are responsible for the Finnish-type congenital nephrotic syndrome. The present study sought to examine whether nephrin expression may also be altered in experimental diabetes, and how such changes related to the development of proteinuria. In addition, the study also sought to examine nephrin expression in animals treated with different anti-proteinuric therapies. Methods. Nephrin gene expression and localization were examined in rats with streptozotocin-induced diabetes at 6 months duration (proteinuric phase) and at 7 days (pre-proteinuric phase). In addition, the effects of anti-proteinuric drug therapies were also assessed in long-term diabetic rats, treated with either the angiotensin-converting enzyme inhibitor perindopril, or the blocker of advanced glycation end-product formation, aminoguanidine. Nephrin expression was determined using quantitative real-time PCR and in situ hybridization. Results. When compared with control animals, nephrin expression was reduced in the late proteinuric phase (45% reductionvs controls,P-0.01) but not in the early, pre-proteinuric phase of experimental diabetic nephropathy. While ACE inhibition and aminoguanidine both reduced proteinuria, only the former attenuated the diabetes-associated reduction in nephrin expression. Conclusions. These findings suggests that reduction in nephrin may be a determinant of glomerular hyperpermeability in diabetic nephropathy. Attenuation of these changes with ACE inhibition suggest that this mechanism may contribute to the anti-proteinuric effects of this, but not all classes of drug which reduce urinary protein in diabetic nephropathy.

Cyclosporine nephropathy (CyAN) is a major limiting factor in the otherwise successful widespread use of cyclosporine in solid organ transplant. Transforming growth factor-beta1 (TGF-beta1) has been implicated as an important fibrogenic cytokine in the development of this disease. TGF-beta-inducible gene-H3 (beta(ig)-H3) is a TGF-beta1- induced gene product, which acts as a marker for biologically active TGF-beta1. This study reports TGF-beta1 gene expression and beta(ig)-H3 tissue distribution in non-renal allograft CyAN. Renal tissue from nine patients who had developed CyAN after successful heart or heart-lung transplantation and from four kidneys removed for tumour were analyzed for TGF-beta1 gene expression beta(ig)-H3 protein with reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively. TGF-beta1 gene expression was increased in CyAN compared to nephrectomy (P

SUMMARY Platelet-derived growth factor (PDGF) is a pleiotropic cytokine synthesized by various resident renal cells and infiltrating cells. Its best-studied role in the kidney is in the mediation of glomerular mesangial cell proliferation. The relationship between expression of PDGFA, PDGFB and the receptor β (PDGFRβ) in human renal biopsies of immunoglobulin A nephropathy (IgAN), a disease characterized by mesangial cell proliferation, and thin membrane nephropathy (TMN), a non-proliferative glomerulopathy, was studied. Using competitive reverse transcriptase-polymerase chain reaction (RT-PCR), the quantity of mRNA molecules of each growth factor and the receptor was determined in renal biopsies from 20 patients with IgAN and 16 with TMN. In addition, eight nephrectomy samples with paired cortical and medullary samples were studied. There was no significant difference between the disease groups for PDGFA (TMN, 1409 ± 475 copy number/microgram RNA; IgAN, 691 ± 133, P = 0.35), PDGFB (TMN, 2280 ± 467; IgAN, 1465 ± 197, P = 0.10) or PDGFRβ (TMN, 1387 ± 273; IgAN, 1402 ± 344, P = 0.68). Analysis of nephrectomy samples showed higher constitutive expression of PDGFA and PDFGB in the medulla as compared with the cortex. However, further analysis of cortical samples in the IgAN group again failed to show a significant difference compared with TMN. We conclude that whole tissue analysis may have masked upregulation at glomerular level although it should reflect mRNA expression in the tubulointerstitial compartment.

Sir,Human immunodeficiency virus (HIV) infection is associated with a specific renal lesion HIV-associated nephropathy (HIVAN), a collapsing form of focal glomerulosclerosis (FGS) that presents wit...

Thioredoxin-interacting protein (TXNIP) is an endogenous inhibitor of the antioxidant thioredoxin, and a critical agent in the in vivo regulation of glucose. The well-described induction of TXNIP by high glucose may represent an important pathogenic trigger of complications arising in the diabetic environment, with sustained overexpression of TXNIP triggering the increased production of reactive oxygen species and collagen, both major contributors to the development of diabetic nephropathy (DN). To examine a possible therapeutic role for targeted TXNIP inhibition in DN, transgenic (mRen-2)27 rats were rendered diabetic with streptozotocin and then treated with 20 μM TXNIP deoxyribozyme (DNAzyme) delivered continuously over 12 weeks by an implanted osmotic mini-pump. Renal injury was measured using biochemical parameters of kidney function along with histological markers of damage. Catalytic activity of TXNIP DNAzyme was determined by TXNIP gene and peptide expression in the rat kidneys. TXNIP DNAzyme localization was demonstrated with a fluorescent-labelled TXNIP DNAzyme. A panel of markers was used to assess the extent of oxidative stress and renal fibrosis including superoxide level, nitrotyrosine staining, TGF-β1, NLRP3 and collagen IV expression. Fluorescent-labelled TXNIP DNAzyme was localized to tubulo-epithelial cells, but was not identified in glomeruli or endothelial cells. Elevated renal cortical TXNIP gene and protein expression seen in kidneys of DN animals were significantly attenuated by TXNIP DNAzyme (p < 0.05). Downstream markers of TXNIP activity, particularly oxidative stress, inflammasome signalling, tubulo-interstitial fibrosis and collagen deposition, were also attenuated in the tubulo-interstitium of DN rats treated with TXNIP DNAzyme. Consistent with the identified site of action of the DNAzyme, the effects of the TXNIP inhibition were limited to the tubulo-interstitial compartment. This study supports the role of TXNIP as an important mediator of progressive tubulo-interstitial fibrosis in DN, and also supports the notion of TXNIP inhibition as a potential new therapeutic target for DN.

Mycobacterium haemophilum is a rare isolate of non-tuberculous Mycobacterium which has been reported to affect immunocompromised patients. We report a case of a 32-year-old renal transplant patient with M. haemophilum infection initially involving his left sinus which was treated with appropriate antimicrobial therapy for thirteen months. Two weeks after cessation of antibiotics the infection rapidly recurred in his skin and soft tissues of his hands and feet. This case highlights the difficult diagnostic and therapeutic implications of atypical infections in transplant patients. To our knowledge this is the first reported case of relapsed M. haemophilum infection in a renal transplant recipient.

Purpose of review Urotensin II (UTS2), the most potent vasoconstrictor identified thus far, is an undecapeptide hormone with a structure that is highly conserved through mammalian phylogeny. In spite of its broad expression across the invertebrate and vertebrate world, the precise role of UTS2 in physiology and disease is still unknown. The first description of human UTS2 and its receptor brought initial promise of a potential therapeutic target for progressive renal disease, with vasoconstrictive and profibrotic actions within an autocrine and paracrine system and local renal generation that was upregulated with renal pathology. Recent findings However, the last decade has not brought the successful development of new treatments first hoped for, with one small human clinical trial bearing negative results. What has become apparent is that the spectrum of actions of UTS2 is broad and often paradoxical. This ancient hormone has both vasoconstrictor and vasodilatory actions, has both profibrotic and antiapoptotic activity, as well as actions which are highly contextual on the particular vascular bed studied and on the presence or absence of superimposed disease state. Summary With current development of newer UTS2 antagonists attempting to more closely replicate the ligand-receptor kinetics of UTS2 and its receptor, the focus on potential clinical applications of UTS2 inhibition has moved away from the kidney to the treatment of chronic lung and cardiovascular diseases.

The publication of the Australasian Creatinine Consensus Working Group's position statements in 2005 and 2007 resulted in automatic reporting of estimated glomerular filtration rate (eGFR) with requests for serum creatinine concentration in adults, facilitated the unification of units of measurement for creatinine and eGFR, and promoted the standardisation of assays. New advancements and continuing debate led the Australasian Creatinine Consensus Working Group to reconvene in 2010. The working group recommends that the method of calculating eGFR should be changed to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, and that all laboratories should report eGFR values as a precise figure to at least 90 mL/min/1.73 m(2). Age-related decision points for eGFR in adults are not recommended, as although an eGFR60 mL/min/1.73 m(2) is very common in older people, it is nevertheless predictive of significantly increased risks of adverse clinical outcomes, and should not be considered a normal part of ageing.If using eGFR for drug dosing, body size should be considered, in addition to referring to the approved product information. For drugs with a narrow therapeutic index, therapeutic drug monitoring or a valid marker of drug effect should be used to individualise dosing. The CKD-EPI formula has been validated as a tool to estimate GFR in some populations of non-European ancestry living in Western countries. Pending publication of validation studies, the working group also recommends that Australasian laboratories continue to automatically report eGFR in Aboriginal and Torres Strait Islander peoples. The working group concluded that routine calculation of eGFR is not recommended in children and youth, or in pregnant women. Serum creatinine concentration (preferably using an enzymatic assay for paediatric patients) should remain as the standard test for kidney function in these populations.