8,9 Wakai et al.8 reported a scoring system to predict renal outcome in patients with IgA nephropathy using a nationwide prospective study from 1995 to 2002. Although the quality of some data collected by the postal survey is limited and the influence of therapy could not be considered, the scoring system will serve as a useful prognostic RXDX-106 research buy tool for this disease in clinical practice.8 Goto et al.9 reported that the risk of deterioration in renal

function can be quickly estimated using clinical information obtained in routine examinations for IgA nephropathy. In 2005, the reply rate from the renal units was 82.7% and 2285 cases were analyzed. Median follow-up periods were 87 months (inter-quartile 42–122). In the results, 252 cases (11.2%) were on dialysis and 21 cases (0.9%) were deceased. Renal survival after 10 years was 0.843 (95% confidence interval = 0.830–0.867). Predictive factors after 10 years were as follows: (i) male sex: (ii) under learn more 30 years old; (iii) diastolic hypertension; (iv)

heavy proteinuria; (v) mild haematuria; (vi) low serum albumin; and (vii) elevated serum creatinine and impaired renal pathology.10 It appears that substantial renal deterioration can be validly estimated using these predictive factors in patients with IgA nephropathy. Immunoglobulin A nephropathy is one of the major causes of CKD in the world. Early diagnosis, treatment and improvement of predictive factors for a long duration may lead to better renal prognosis in patients with IgA nephropathy. I sincerely thank my colleagues in the Division of Nephrology

at Juntendo University, Tokyo and Professor Masayuki Endoh, Division of Nephrology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Kanagawa, Japan. The Authors state that there is no conflict of interest regarding the material discussed in the manuscript. “
“Aim:  Glucocorticoid therapy has been used in childhood nephrotic syndrome since the 1950s, where see more the characteristic change is effacement of the actin-rich foot process of glomerular podocytes. Recent studies have shown that glucocorticoids, in addition to their general immunosuppressive and anti-inflammatory effects, have a direct effect on podocytes, regulate some apoptotic factors, and increase the stability of actin filaments. However, the precise mechanism(s) underlying the protective effects of glucocorticoids on podocytes remain unclear. It is known that adriamycin (ADR) can induce podocyte foot process effacement and trigger massive proteinuria in rodent models. However, few reports have examined the direct role of ADR in podocyte actin rearrangement in vitro.

Replication and transcription activator (RTA) from Kaposi’s sarcoma-associated herpesvirus Gefitinib mw (KSHV) also reduces TRIF levels, likely through a proteasome-mediated pathway.[8] Other TLR adaptor proteins are also affected – the hepatitis B virus HBeAg protein uses its precore specific sequence, which shows homology to the TIR motif, to compete with TIR-containing proteins Mal and TRAM to impede their interactions with downstream signalling molecules.[9] A second class of PRRs is the retinoic acid inducible gene I (RIG-I)-like

receptor (RLR) family, including RIG-I and melanoma differentiation-associated gene 5 (MDA5).[10] The RLRs detect cytoplasmic dsRNA, interact with the adaptor mitochondrial antiviral signalling protein (MAVS) and activate NF-κB

and IRF3. Like TLRs, RLRs are hindered by viruses. For instance, the N protein from human respiratory syncytial virus (RSV) inhibits MDA5 and MAVS,[11] whereas the HIV protease decreases cytoplasmic RIG-I levels by targeting the sensor to the lysosome.[12] In contrast, the V proteins of several paramyxoviruses promote an interaction between RIG-I and LGP2,[13] an RLR that lacks signalling capacity.[14] Several viruses target RIG-I via viral de-ubiquitinating enzymes (DUBs), such as Arterivirus non-structural protein LY2157299 2, Nairovirus L protein,[15] KSHV ORF64,[16] severe acute respiratory syndrome coronavirus (SARS-CoV) papain-like proteases,[17] and foot-and-mouth disease virus (FMDV) Lbpro.[18] These DUBs remove K63-linked ubiquitin on RIG-I, preventing its interaction with MAVS.[19] MAVS is also a popular focus of viral antagonists. The influenza A protein PB1-F2 binds the transmembrane domain of MAVS, causing a drop in the mitochondrial membrane potential,[20] which is required for MAVS function.[21] Coxsackievirus B3 encodes the cysteine

protease 3Cpro, which directly cleaves both TRIF and MAVS, impeding both the TLR3 and RLR pathways, respectively.[22] Finally, the hepatitis B virus protein HBx associates with and cAMP blocks the action of MAVS.[23] The adaptor protein STING, which interacts with RIG-I and MAVS and is involved in the detection of cytosolic DNA,[24] is also affected by viral proteins, such as the protease complex NS2B3 of Dengue virus, which cleaves STING into inactive fragments.[25] Interestingly, the papain-like proteases from human coronavirus NL63 and SARS-CoV, which possess protease and DUB enzyme activities, disrupt the dimerization of STING by decreasing its level of ubiquitination.[17] Several viral proteins target both TLRs and RLRs at the expression level.

Total resection of lesions was performed in all cases, and at an average follow-up of 15 months, all patients are alive and well with no evidence of recurrence. Preoperative diagnosis of CNS RDD is challenging. Surgical removal of lesions is an effective treatment. More research is needed to clarify the effectiveness of other treatment options such as RO4929097 concentration radiosurgery and corticosteroid therapy. “
“Limited information exists about the impact of cytogenetic alterations on the protein expression profiles of individual meningioma cells and their association with the clinico-histopathological characteristics of the disease. The aim of this study

is to investigate the potential association this website between the immunophenotypic profile of single meningioma cells and the most relevant features of the tumour. Multiparameter flow cytometry (MFC) was used to evaluate the immunophenotypic profile of tumour cells (n=51 patients) and the Affymetrix U133A chip was applied for the analysis of the gene expression profile (n=40) of meningioma samples, cytogenetically characterized by interphase fluorescence in situ hybridization. Overall, a close association between the pattern of protein expression and the cytogenetic profile of tumour cells was found. Thus, diploid tumours displayed higher levels of expression of the CD55 complement regulatory protein, tumours

carrying isolated monosomy 22/del(22q) showed greater levels of bcl2 and PDGFRβ and meningiomas carrying complex karyotypes displayed a greater proliferation index and decreased expression of the CD13 ectoenzyme, Atorvastatin the CD9 and CD81 tetraspanins, and the Her2/neu growth factor receptor.

From the clinical point of view, higher expression of CD53 and CD44 was associated with a poorer outcome. Here we show that the protein expression profile of individual meningioma cells is closely associated with tumour cytogenetics, which may reflect the involvement of different signalling pathways in the distinct cytogenetic subgroups of meningiomas, with specific immunophenotypic profiles also translating into a different tumour clinical behaviour. “
“Naturally occurring transmissible spongiform encephalopathies (TSEs) accumulate disease-specific forms of prion protein on cell membranes in association with pathognomonic lesions. We wished to determine whether synthetic prion protein disorders recapitulated these and other subcellular TSE-specific changes. SSLOW is a TSE initiated with refolded synthetic prion protein. Five terminally sick hamsters previously intracerebrally inoculated with third passage SSLOW were examined using light and immunogold electron microscopy. SSLOW-affected hamsters showed widespread abnormal prion protein (PrPSSLOW) and amyloid plaques. PrPSSLOW accumulated on plasma lemmas of neurites and glia without pathological changes.

The enhanced cross-presentation was independent of TLR-signaling and inducible at low concentrations of antigen. Furthermore, the addition of 3-sulfo-LeA or tri-GlcNAc

to OVA protein enhanced the frequency of IFN-γ-producing CD4+ T cells, illustrating Th1 skewing. Previous studies showed that the MR specifically binds high mannose, fucose and GlcNAc residues via the carbohydrate recognition domains (CRD) 7, 24. Of the eight CRDs, CRD4-5 are sufficient to generate the affinity of the whole receptor for natural ligands. Moreover, the MR contains an N-terminal CR domain, demonstrated to bind novel sulfated saccharides 9, 25. In this study, we show that murine DC-expressed MR strongly binds to sulfated blood antigens such as 3-sulfo-LeA and GlcNAc. When these glycans were

conjugated to OVA, increased binding and uptake of the neo-glycoconjugates was https://www.selleckchem.com/products/GDC-0980-RG7422.html detected compared to native OVA, which itself is mannosylated. Interestingly, 3-sulfo-LeA and tri-GlcNAc bind to different sites of the MR. Whereas tri-GlcNAc binds to the CRD, 3-sulfo-LeA binds the MR via the CR domain 8–10. Nevertheless these sulfated glycans exert similar potentiating Vismodegib datasheet effects. When chemically conjugated to OVA, these novel MR-specific ligands direct antigen more potently to the MR and enhance cross-presentation of antigens to CD8 T cells when compared to native OVA. This enhancement in cross-presentation is predominantly mediated by the MR as cross-presentation was greatly reduced in MR−/− splenic DCs. The fact that cross-presentation of the neo-glycoconjugates by MR−/− BMDCs was not completely abolished may be explained by binding MAPK inhibitor of these glycans to other receptors, such as SIGNR1 and SIGNR3 26, although their presence on myeloid DCs has not been formally shown. Although we could exclude the involvement of SIGNR1 since

SIGNR1−/− DCs did not show any reduced antigen binding and uptake (data not shown), we cannot completely exclude the involvement of other lectin receptors or processes such as pinocytosis in the uptake of these neo-glycosylated proteins. Thus, we concluded that the MR is predominantly involved in the enhanced induction of antigen presentation, due to this glycan modification. The potentiating effect of tri-GlcNAc may lie in its higher affinity for the MR than mannose resulting in increased responses 7. Since 3-sulfo-LeA binds the CR region instead of the CRD, it cannot compete with mannose. However, binding to the CR region might be with stronger affinity than of mannose to the CRD, although to our knowledge a direct comparison between these ligands and regions has not been described. CR-ligand binding may elicit stronger responses than CRD-ligand binding. This is underlined by the fact that the response to OVA-3-sulfo-LeA is stronger than to native OVA.

© 2014 Wiley Periodicals, Inc. Microsurgery 34:562–567, 2014. “
“Reconstruction of soft-tissue defects of the knee has always been a challenging task to the plastic surgeon. In some cases, local or regional flaps are too small or have limited arc of rotation

for adequate coverage. Free flaps can be technically demanding and time consuming. We report for the first time an antegrade anterolateral thigh perforator flap advancement, used to reconstruct the knee soft tissue defect in a 54-year-old man. The operative procedure required Cell Cycle inhibitor skeletonizing the perforators of anterolateral thigh flap and advancing the flap in the defect. The postoperative course was uneventful with the patient returned to normal daily buy Enzalutamide activity and full range of motion 3-months postoperatively. The shorter operating time with decreased donor-site morbidity make this flap as a valuable alternative for soft-tissue reconstruction of the knee. © 2010 Wiley-Liss, Inc. Microsurgery, 2010. “
“Two work-horse approaches to postmastectomy breast reconstruction are the deep inferior epigastric perforator flap and the superior gluteal artery perforator (SGAP) flap [and its variation, the lateral septocutaneous superior gluteal artery perforator flap]. Our purpose was fourfold: 1) to analyze our experience with the SGAP flaps for simultaneous bilateral breast reconstruction; 2) to analyze our experience with lateral septocutaneous

superior gluteal artery perforator flaps for that procedure; 3) to compare our results with those in the literature; and 4) to highlight the importance of preoperative three-dimensional computed tomographic angiography. A

retrospective chart review was completed for 23 patients who underwent breast reconstruction between December 2005 and January 2010 via an SGAP flap (46 flaps). We reviewed flap weight, ischemia time, length of stay, overall flap survival, fat necrosis development, and emergency re-exploration. Mean weights were 571.2 ± 222.0 g (range 186–1,117 g) and 568.0 ± 237.5 g (range 209–1,115 g) for the left and right buttock flap, respectively. Mean ischemia time was 129.1 ± 15.7 and 177.7 ± 24.7 minutes for the first and second flap, respectively. Mean hospital stay was 5.3 ± 2.5 days. All flaps survived. Fat necrosis developed in five flaps (10.8%), and emergency re-exploration was required in three Phospholipase D1 patients (three flaps). When harvesting abdominal tissue is a poor option, the SGAP flap is an efficacious procedure for patients desiring autologous breast reconstruction, and bilateral procedures can be performed simultaneously. © 2012 Wiley Periodicals, Inc. Microsurgery, 2012. “
“Background: Hidradenitis suppurativa is a debilitating disease with a tendency to form abscesses, sinus tracts, and scar formation. In this report, our experience with reconstruction of hidradenitis lesions of the gluteal and perianal/perineal area using superior and inferior gluteal artery perforator flaps (SGAP and IGAP) are discussed.

[12] Strains of R. arrhizus have received much attention in connection PD0325901 with the decomposition of biodegradable plastics.[13] Since the description of Rhizopus arrhizus by Fischer [14] in 1892 numerous species have been described in Rhizopus differing slightly in morphology, intensity of sporulation, temperature tolerance, or substrate choice.[15] After a comprehensive study of morphological features, temperature tolerance and mating, Schipper [15] synonymized 29 species with Rhizopus arrhizus (as R. oryzae). Nearly at the same time Ellis [16] concluded conspecifity of R. arrhizus, Amylomyces rouxii

and R. delemar based on DNA renaturation experiments and proposed to accommodate them in three varieties. In their monograph on the genus Rhizopus Zheng et al. [17] Ibrutinib supplier maintained the varieties arrhizus and delemar

and introduced the new variety tonkinensis. In a molecular phylogenetic study linked to this monograph, Liu et al. [18] used internal transcribed spacer (ITS) and the pyrG gene encoding the orotidine 5′-monophosphate decarboxylase. Their data supported only the var. arrhizus and var. delemar, while strains of the var. tonkinensis were not included in the trees. In the same year Abe et al. [19] showed by multi-locus studies of four different markers that the varieties arrhizus and delemar represent two phylogenetic species differing in their production selleck inhibitor of organic acids. As consequence the authors treated

the fumaric-malic acid producing R. delemar as a separate species from the lactic acid producing R. arrhizus (as R. oryzae). Var. tonkinensis was individualized in the molecular phylogenetic analyses of Abe et al. [19] and as a consequence it was synonymized with R. arrhizus (as R. oryzae). Gryganskyi et al. [20] analyzed the two species distinguished by Abe et al. [19] by molecular phylogeny based on additional markers including mating type genes. It was noted that ITS distances between R. arrhizus and R. delemar were very small compared to the remaining Rhizopus species, and there were no compensatory base changes (CBC) in the ITS region as indication of separate species.[20] In addition, zygospore formation between strains of R. arrhizus and R. delemar as observed by Schipper [15] was confirmed. There are no significant morphological, ecological, clinical and epidemiological differences known between the two species. Therefore the aim of the present study was to evaluate phylogenetic and biological species boundaries in R. arrhizus and close relatives, based on an extended set of strains. For that purpose mating tests, multi-locus studies, amplified fragment length polymorphism (AFLP) profiling and analyses of physiological parameters such as cardinal growth temperatures and enzyme spectra were performed. The results of Abe et al. [19] and Gryganskyi et al. [20] show clearly that R.

The aims of the WG were to form

a European registry, collecting cases of mucormycosis from various European countries. During the period 2005–2007, 230 cases were submitted from 13 countries.[6] While this study and others studies have characterised risk factors BGJ398 mouse for mortality in mucormycosis, there is no reported contemporary, international, case–controlled study of the epidemiological, metabolic and immunological risk factors for mucormycosis that would facilitate early clinical diagnosis. The newly configured ZWG2 markedly expands the number of participating centres and countries and is now known as the ECMM/ISHAM WG. The database will be migrated to the auspices of the Infection Control Program at ELPIDA in Athens, Greece. The portal for remote data entry will remain http://www.zygomyco.net/. For the first time, infected patients and two contemporaneous case–controls will be included prospectively. Prognostic variables will also be built into the new database for infected patients and non-infected controls. The database will now include multiple expanded and risk variables with high levels of quantitative refinements summarised in Table 1. The new database will establish for the first time an international profile for the epidemiology,

clinical manifestations, risk factors and outcome of mucormycosis. Denominators will be established for select groups of underlying conditions, particularly leukaemia and allogeneic HSCT Glutamate dehydrogenase in order to provide a marker for incidence. selleck kinase inhibitor These two populations are most readily tracked in institutions. All participating investigators will enrol infected patients and two contemporaneous controls who will be followed through the duration of treatment and for 6 month follow-up for a total duration of 1 year, whichever

is shorter. All cases of mucormycosis entered through Fungiscope (http://www.fungiquest.net/) will be shared with the ZWG2 study. Concurrent untreated controls will be identified for these cases by the investigator enrolling the patient with mucormycosis. Early identification of host factors is an important strategy for assessment of the Bayesian prior probability of a patient’s risk for invasive mucormycosis. The classic host factors for mucormycosis are diabetic ketoacidosis and profound and persistent neutropenia. However, not all patients with diabetic ketoacidosis or profound and persistent neutropenia develop mucormycosis. Additional data are required to understand risk factors in these populations. Moreover, other host groups, including those with allogeneic HSCT, type 2 diabetes, low birth weight infants, burns and trauma, solid organ transplantation, autoimmune disorders and illicit intravenous drug use are also at risk (Table 2). Identification of certain clinical manifestations in association with risk factors may further refine early diagnostic accuracy and predictive power.

4, P < 0·05). Triptolide and dexamethasone were equally effective in reducing levels of BALF TGF-β1 (512 ± 54 MK-8669 versus 524 ± 67 pg/ml, Fig. 4, P > 0·05). There was no significant difference between the TRP and DEX groups. We demonstrated that triptolide inhibited airway remodelling and reduced TGF-β1 expression. Recent reports have demonstrated an improved method for investigating the expression of active TGF-β1 signalling in situ,25 which involves examination of the expression of the intracellular effectors, Smads. Therefore, we investigated the expression patterns of phosphor-Smad2/3 (pSmad2/3) and Smad7 in the lung specimens following administration

of dexamethasone to investigate any effect on active TGF-β signalling in airway lesions. Data were normalized to the levels of GAPDH. An increase AZD3965 datasheet in expression of pSmad2/3 was observed during prolonged allergen challenge, whereas administration of triptolide and dexamethasone both considerably decreased pSmad2/3 expression (0·73 ± 0·07 versus 0·55 ± 0·04 and 0·51 ± 0·07, Fig. 5, Table 2, P < 0·01). In contrast with pSmad2/3, Smad7 was markedly up-regulated in mice treated with triptolide or dexamethasone compared with the OVA-sensitized/challenged group (0·44 ± 0·03 and 0·44 ± 0·04 versus 0·29 ± 0·06, Fig. 5, Table 2, P < 0·01). There was no significant difference of pSmad2/3 and Smad7 in mice treated with triptolide

and dexamethasone (Fig. 5, Table 2, P > 0·05).

In this study, we NADPH-cytochrome-c2 reductase established a mouse model of airway remodelling by repetitive OVA-challenge which replicated many of the features of the human disease asthma with a high degree of fidelity. Therefore, we investigated whether administration of triptolide could inhibit the progress of airway remodelling in mice exposed to repetitive allergen challenge, as well as determining whether triptolide could modulate the expression of signalling molecules of the TGF-β1/Smad pathway, which may in turn modulate airway remodelling. Recent morphological examination of airway tissues with bronchial asthma has revealed that abnormalities in airways, including goblet cell hyperplasia, mucous gland hypertrophy, subepithelial fibrosis and smooth muscle cell hyperplasia or hypertrophy, are in part irreversible.2,3 It is generally accepted that tissue remodelling is a process of wound healing for the maintenance of homeostasis after various injuries. Normally the process means the repair of injured tissues both morphologically and functionally; however, prolonged inflammation may induce remodelling of airways which could differ from wound healing. True to the observed clinical and symptomatic variability, remodelling can be elevated by as much as 50–300% in asthma patients who have died, and from 10 to 100% in subjects who have milder cases.26 Triptolide may offer a much needed therapeutic strategy for asthma airway remodelling.

1). Responder PBMC were incubated with sotrastaurin 0, 25, 50, 100 or 250 ng/ml 60 min before the stimulator cells were added. A dose-dependent effect of the study drug on alloresponsiveness was observed: the mean proliferative response decreased HKI-272 clinical trial in the presence of 25, 50 100 and 250 ng/ml sotrastaurin from 37250

to 21617, 18487, 9500 and 3191 cpm, respectively (all P < 0·0001; mean percentage of inhibition 40, 49, 74 and 92, respectively, Fig. 1). For each experiment the IC50 was calculated. The median IC50 for sotrastaurin was 90 nM (45 ng/ml) (molecular mass 499 acetate). To study the effect of sotrastaurin on the IL-2-driven STAT-5 activation by Tregs, whole blood samples of three healthy volunteers were incubated with and without 100 ng/ml sotrastaurin in the presence of IL-2. In the absence of this cytokine STAT-5 was not phosphorylated in Tregs (all <4% pSTAT-5). After stimulation ITF2357 concentration with IL-2, 47·5% (median) of Tregs phosphorylated STAT-5, which was similar in the presence of sotrastaurin (median

50·5%, Fig. 2). To study the effect of sotrastaurin on the function of CD4+CD25high Treg, PBMC and CD25low populations, co-culture experiments were performed in blood bank donor samples (n = 11). Alloreactive response in MLR to irradiated stimulator cells was compared between PBMC and CD4+CD25low responder populations after depletion of CD4+CD25high T cells. Depletion of the Treg fraction from the PBMC resulted in a 91·3% increase in the proliferative response (P < 0·05). Subsequently, the suppressive capacity of these isolated Tregs was determined in co-culture experiments with CD25low responder cells in a 1 : 5 ratio. We set the Teff proliferation as Aspartate 100%, and compared this to the proliferation after addition of sotrastaurin and after co-culture with Tregs. Tregs significantly inhibited alloproliferation in the absence (median inhibition 47%, P = 0·002) and presence of 50 ng/ml sotrastaurin (median inhibition 35%, P = 0·002). This difference in inhibition was not statistically significant (P = 0·33) (Fig. 3). Fourteen patients were treated with sotrastaurin

and seven patients were treated with neoral. Blood samples were collected pre-, 3 and 6 months after transplantation. At 6 months, 17 patients still used their study drug regimen (10 sotrastaurin versus seven neoral patients). The reasons for discontinuing the study drug were various, among them adverse events related to the use of sotrastaurin, neoral and everolimus. The absolute numbers of different lymphocyte subsets were measured using flow cytometry. The numbers of CD3+ T cells, CD4+ helper T cells, CD8+ cytotoxic T cells, CD16+56+ NK cells, CD19+ B cells and the ratio of CD4+/CD8+ T cells did not change significantly over this 6-month period (Table 2). The Treg population was defined as cells with high CD25 expression in combination with slightly less CD4 expression in combination with high FoxP3 and no or low expression of CD127 (IL-7R-α) expression (Fig.

Background: The Renal Health Clinical Network (RHCN) in Victoria established a Renal Key Performance Indicator (KPI) working group in 2011. The group developed four KPIs related to CKD and dialysis. The transplant working group of the RHCN developed two additional KPIs. Methods: A data collection and bench-marking program was established with permission to participate from the CEO of each health service. Data is collected monthly by the

Department of Health using a specific website portal. The KPI working group are responsible for analysing data each quarter and ensuring indicators remain accurate and relevant. Each indicator has clear definitions and targets. We report a summary of KPI trends over AZD2014 purchase 2013. Results: Each health service providing end-stage kidney disease management was able to submit data regularly with no additional funding, using “craft groups” already present in each of the services. The KPIs encompassed (1) patient education, (2) timely creation of vascular access, (3) the proportion of patients dialysing at home, (4)

the incidence of peritonitis in PD, (5) incidence of pre-emptive renal transplantation, and (6) timely listing of patients for deceased donor transplantation. Most of the KPIs have been associated with improved performance over time. The most difficult KPIs for units to achieve have been the number of patients dialysing at home (KPI 3) and timely listing of patients for transplantation Leukocyte receptor tyrosine kinase (KPI 6). Conclusions: KPI implementation SAR245409 in vivo has been established in Victoria with no additional funding required. There is some early evidence that use of KPIs has improved the performance of individual units. 208 WEB-BASED CHRONIC KIDNEY DISEASE OUTREACH AND CONNECTING CARE PROGRAM IJ KATZ, S PIRABHAHAR, J KELLY, A O’SULLIVAN,

G YOUSSEF, C LANE, S ONG, F BRENNAN, E JOSLAND, G MANGOS, P SHANMUNGASUNDARAM, S TRANTER, M BROWN St George Hospital and University of New South Wales, Sydney, Australia Aim: To assess a) efficacy and safety of web based management for CKD patients in primary care (PC) versus a nephrology practice b) at a later stage, cost effectiveness and CKD progression in high risk (HR) patients. Background: PC management of early CKD has been shown to be equivalent to nephrologist care. Opportunistic screening of HR individuals and follow up by general practitioners (GPs) is the most sustainable form of care for CKD. A web ‘cloud’ based referral and review system was established in order to deal with the high burden of CKD and chronic diseases (CD). Methods: This program allows GPs and hospital-based doctors to manage patients with or at risk of CKD and receive specialist opinions online. Patient referrals are stratified and HR patients (eGFR < 30 mL/min/1.73 m2) and/or albuminuria (>30 mg/mmol/L) are randomised to nephrologist face to face vs. online consultation. HR patients are followed four monthly. Those referred for other reasons (e.g.