References of "Jouret, François"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailDiscovery and pharmacological characterization of succinate receptor (SUCNR1/GPR91) agonists
Geubelle, Pierre ULg; Gilissen, Julie; Dilly, Sebastien et al

in British Journal of Pharmacology (in press)

Background and Purpose The succinate receptor (SUCNR1 or GPR91) has been described as a metabolic sensor that may be involved in homeostasis. Notwithstanding its implication in important (patho ... [more ▼]

Background and Purpose The succinate receptor (SUCNR1 or GPR91) has been described as a metabolic sensor that may be involved in homeostasis. Notwithstanding its implication in important (patho)physiological processes, the function of SUCNR1 has remained elusive because no pharmacological tools were available. We report on the discovery of the first family of synthetic potent agonists. Experimental Approach We screened a library of succinate analogues and analysed their activity on SUCNR1. In addition, we modelled a pharmacophore and a binding site for the receptor. New agonists were identified based on the information provided by these two approaches. Their activity was studied in various bioassays, including measurement of cAMP levels, [Ca2+]i mobilisation, TGF-α shedding and recruitment of arrestin 3. The in vivo impact of SUCNR1 activation by these new agonists was evaluated on rat blood pressure. Key Results We identified cis-epoxysuccinic acid and cis-1,2-cyclopropanedicarboxylic acid as agonists with an efficacy similar to the one of succinic acid. Interestingly, cis-epoxysuccinic acid was characterized by a 10 to 20 fold higher potency than succinate on the receptor. For example, cis-epoxysuccinic acid reduced cAMP levels with a pEC50 = 5.57 ± 0.02 (EC50 = 2.7 μM) as compared to succinate pEC50 = 4.54 ± 0.08 (EC50 = 29 μM). The rank order of potency of the three agonists was the same in all bioassays tested. In vivo, cis-epoxysuccinic and cis-1,2-cyclopropanedicarboxylic acid increased rat blood pressure to the same extent as succinate did. Conclusions and Implications We provide new agonist tools for SUCNR1 that should facilitate further research on this understudied receptor. [less ▲]

Detailed reference viewed: 28 (2 ULg)
Full Text
See detailThe use of mesenchymal stromal cells in solid organ transplantation
GREGOIRE, Céline ULg; DETRY, Olivier ULg; Jouret, François ULg et al

in The Biology and Therapeutic Applications of Mesenchymal Cells (in press)

Detailed reference viewed: 104 (65 ULg)
Full Text
Peer Reviewed
See detailThe lipid 5-phoshatase SHIP2 controls renal brush border ultrastructure and function by regulating ERM proteins activation
Sayyed, Sufyan Ali ULg; JOURET, François ULg; Vermeersch, Marjorie et al

in Kidney International (2017)

The microvillus brush border on the renal proximal tubule epithelium allows the controlled reabsorption of solutes that are filtered through the glomerulus and thus participates in general body ... [more ▼]

The microvillus brush border on the renal proximal tubule epithelium allows the controlled reabsorption of solutes that are filtered through the glomerulus and thus participates in general body homeostasis. Here, using the lipid 5-phosphatase Ship2 global knock-out mice, proximal tubule-specific Ship2 knock-out mice and a proximal tubule cell model where SHIP2 is inactivated, we show that SHIP2 is a negative regulator of microvilli formation, thereby controlling solute reabsorption by the proximal tubule. We found increased PtdIns(4,5)P2 substrate and decreased PtdIns4P product when SHIP2 was inactivated, associated with hyperactivated Ezrin/Radixin/Moesin proteins and increased Rho-GTP. Thus, inactivation of SHIP2 leads to increased microvilli formation and solute reabsorption by the renal proximal tubule. This may represent an innovative therapeutic target for renal Fanconi syndromes characterized by decreased reabsorption of solutes by this nephron segment. [less ▲]

Detailed reference viewed: 36 (7 ULg)
See detailThe closure of arteriovenous fistula is associated with a significant acceleration of eGFR decline in kidney transplant recipients
Jouret, François ULg; DELANAYE, Pierre ULg; VANDERWECKENE, Pauline ULg et al

Poster (2016, November)

Background The creation of arteriovenous fistula (AVF) may retard chronic kidney disease progression in the general population. Conversely, there is limited literature regarding the impact of AVF closure ... [more ▼]

Background The creation of arteriovenous fistula (AVF) may retard chronic kidney disease progression in the general population. Conversely, there is limited literature regarding the impact of AVF closure on renal function in kidney transplant recipients (KTR). Methods All KTR were retrospectively identified from 01/01/2007 to 31/12/2013, and grouped into: (0) no AVF; (1) closed AVF; and (2) left open AVF. Glomerular filtration rate was estimated (eGFR) upon MDRD and FAS equations. Linear mixed models calculated the slope and intercept of eGFR decline versus time, starting at 3 months post transplantation (Tx). Comparative analyses of eGFR slopes were performed among groups, as well as before vs after AVF closure in group 1. For the latter, time was balanced before vs after AVF closure, with at least 10 observations per patient. Results The cohort included 285 KTR (Table 1), with a median follow-up of 1750 days [1665; 2028]. Focusing on group 1, AVF closure occurred after a mean time of 653 ± 441 days post Tx, with a thrombosis/ligation ratio of 19/95. Balanced study periods before vs after AVF closure lasted 15.7 and 14.9 months, respectively. No difference was found between corresponding intercepts (p, 0.11). By contrast, eGFR slopes were significantly different before (0.043 ml/min/year) versus after (-0.176 ml/min/year) AVF closure (p, 0.0115). Similar observations were obtained using FAS equation Conclusion A significant acceleration of eGFR decline is observed over the 15 months following the closure of functioning AVF in KTR. [less ▲]

Detailed reference viewed: 33 (4 ULg)
Full Text
Peer Reviewed
See detailMyoferlin regulates cellular lipid metabolism and promotes metastases in triple-negative breast cancer
Blomme, Arnaud; Costanza, Brunella ULg; De Tullio, Pascal ULg et al

in Oncogene (2016)

Myoferlin is a multiple C2-domain-containing protein that regulates membrane repair, tyrosine kinase receptor function and endocytosis in myoblasts and endothelial cells. Recently it has been reported as ... [more ▼]

Myoferlin is a multiple C2-domain-containing protein that regulates membrane repair, tyrosine kinase receptor function and endocytosis in myoblasts and endothelial cells. Recently it has been reported as overexpressed in several cancers and shown to contribute to proliferation, migration and invasion of cancer cells. We have previously demonstrated that myoferlin regulates epidermal growth factor receptor activity in breast cancer. In the current study, we report a consistent overexpression of myoferlin in triple-negative breast cancer cells (TNBC) over cells originating from other breast cancer subtypes. Using a combination of proteomics, metabolomics and electron microscopy, we demonstrate that myoferlin depletion results in marked alteration of endosomal system and metabolism. Mechanistically, myoferlin depletion caused impaired vesicle traffic that led to a misbalance of saturated/unsaturated fatty acids. This provoked mitochondrial dysfunction in TNBC cells. As a consequence of the major metabolic stress, TNBC cells rapidly triggered AMP activated protein kinase-mediated metabolic reprogramming to glycolysis. This reduced their ability to balance between oxidative phosphorylation and glycolysis, rendering TNBC cells metabolically inflexible, and more sensitive to metabolic drug targeting in vitro. In line with this, our in vivo findings demonstrated a significantly reduced capacity of myoferlin-deficient TNBC cells to metastasise to lungs. The significance of this observation was further supported by clinical data, showing that TNBC patients whose tumors overexpress myoferlin have worst distant metastasis-free and overall survivals. This novel insight into myoferlin function establishes an important link between vesicle traffic, cancer metabolism and progression, offering new diagnostic and therapeutic concepts to develop treatments for TNBC patients. [less ▲]

Detailed reference viewed: 36 (8 ULg)
Full Text
Peer Reviewed
See detailThe closure of arteriovenous fistula in kidney transplant recipients is associated with an acceleration of kidney function decline
WEEKERS, Laurent ULg; VANDERWECKENE, Pauline ULg; pottel, hans et al

in Nephrology Dialysis Transplantation (2016)

ABSTRACT Background. The creation of arteriovenous fistula (AVF) may retard chronic kidney disease progression in the general population. Conversely, the impact of AVF closure on renal function in kidney ... [more ▼]

ABSTRACT Background. The creation of arteriovenous fistula (AVF) may retard chronic kidney disease progression in the general population. Conversely, the impact of AVF closure on renal function in kidney transplant recipients (KTRs) remains unknown. Methods. From 2007 to 2013, we retrospectively categorized 285 KTRs into three groups: no AVF (Group 0, n = 90), closed AVF (Group 1, n = 114) and left-open AVF (Group 2, n = 81). AVF closure occurred at 653 ± 441 days after kidney transplantation (KTx), with a thrombosis:ligation ratio of 19:95. Estimated glomerular filtration rate (eGFR) was determined using the Modification of Diet in Renal Disease equation. Linear mixed models calculated the slope and intercept of eGFR decline versus time, starting at 3 months post-KTx, with a median follow-up of 1807 days (95% confidence interval 1665–2028). Results. The eGFR slope was less in Group 1 (−0.081 mL/min/ month) compared with Group 0 (−0.183 mL/min/month; P = 0.03) or Group 2 (−0.164 mL/min/month; P = 0.09). Still, the eGFR slope significantly deteriorated after (−0.159 mL/min/month) versus before (0.038 mL/min/month) AVF closure (P= 0.03). Study periods before versus after AVF closure were balanced to a mean of 13.5 and 12.5 months, respectively, with at least 10 observations per patient (n = 99). Conclusions. In conclusion, a significant acceleration of eGFR decline is observed over the 12 months following the closure of a functioning AVF in KTRs. [less ▲]

Detailed reference viewed: 36 (11 ULg)
Full Text
Peer Reviewed
See detailNuclear Magnetic Resonance Metabolomic Profiling of Mouse Kidney, Urine and Serum Following Renal Ischemia/Reperfusion Injury.
Jouret, François ULg; Leenders, Justine ULg; Defraigne, Jean-Olivier ULg et al

in PLoS ONE (2016), 11(9), 1-14

Abstract BACKGROUND: Ischemia/reperfusion (I/R) is the most common cause of acute kidney injury (AKI). Its pathophysiology remains unclear. Metabolomics is dedicated to identify metabolites involved in ... [more ▼]

Abstract BACKGROUND: Ischemia/reperfusion (I/R) is the most common cause of acute kidney injury (AKI). Its pathophysiology remains unclear. Metabolomics is dedicated to identify metabolites involved in (patho)physiological changes of integrated living systems. Here, we performed 1H-Nuclear Magnetic Resonance metabolomics using urine, serum and kidney samples from a mouse model of renal I/R. METHODS: Renal 30-min ischemia was induced in 12-week-old C57BL/6J male mice by bilaterally clamping vascular pedicles, and was followed by 6, 24 or 48-hour reperfusion (n = 12/group). Sham-operated mice were used as controls. Statistical discriminant analyses, i.e. principal component analysis and orthogonal projections to latent structures (OPLS-DA), were performed on urine, serum and kidney lysates at each time-point. Multivariate receiver operating characteristic (ROC) curves were drawn, and sensitivity and specificity were calculated from ROC confusion matrix (with averaged class probabilities across 100 cross-validations). RESULTS: Urine OPLS-DA analysis showed a net separation between I/R and sham groups, with significant variations in levels of taurine, di- and tri-methylamine, creatine and lactate. Such changes were observed as early as 6 hours post reperfusion. Major metabolome modifications occurred at 24h post reperfusion. At this time-point, correlation coefficients between urine spectra and conventional AKI biomarkers, i.e. serum creatinine and urea levels, reached 0.94 and 0.95, respectively. The area under ROC curve at 6h, 24h and 48h post surgery were 0.73, 0.98 and 0.97, respectively. Similar discriminations were found in kidney samples, with changes in levels of lactate, fatty acids, choline and taurine. By contrast, serum OPLS-DA analysis could not discriminate sham-operated from I/R-exposed animals. CONCLUSIONS: Our study demonstrates that renal I/R in mouse causes early and sustained metabolomic changes in urine and kidney composition. The most implicated pathways at 6h and 24h post reperfusion include gluconeogenesis, taurine and hypotaurine metabolism, whereas protein biosynthesis, glycolysis, and galactose and arginine metabolism are key at 48h post reperfusion. [less ▲]

Detailed reference viewed: 44 (16 ULg)
Full Text
Peer Reviewed
See detailNon-invasive approaches in the diagnosis of acute rejection in kidney transplant recipients, part II: omics analyses of urine and blood samples
Erpicum, Pauline ULg; HANSSEN, Oriane ULg; WEEKERS, Laurent ULg et al

in Clinical Kidney Journal (2016)

Kidney transplantation (KTx) represents the best available treatment for patients with end-stage renal disease. Still, the full benefits of KTx are undermined by acute rejection (AR). The diagnosis of AR ... [more ▼]

Kidney transplantation (KTx) represents the best available treatment for patients with end-stage renal disease. Still, the full benefits of KTx are undermined by acute rejection (AR). The diagnosis of AR ultimately relies on transplant needle biopsy. However, such an invasive procedure is associated with a significant risk of complications and is limited by sampling error and interobserver variability. In the present review, we summarize the current literature about non-invasive approaches for the diagnosis of AR in kidney transplant recipients (KTRs), including in vivo imaging, gene-expression profiling and omics analyses of blood and urine samples. Most imaging techniques, such as contrast-enhanced ultrasound and magnetic resonance, exploit the fact that blood flow is significantly lowered in case of AR-induced inflammation. In addition, AR-associated recruitment of activated leucocytes may be detectable by 18F-fluorodeoxyglucose positron emission tomography. In parallel, urine biomarkers, including CXCL9/CXCL10 or a three-gene signature of CD3ε, CXCL10 and 18S RNA levels, have been identified. None of these approaches has yet been adopted in the clinical follow-up of KTRs, but standardization of analysis procedures may help assess reproducibility and comparative diagnostic yield in large, prospective, multicentre trials. [less ▲]

Detailed reference viewed: 52 (9 ULg)
Full Text
See detailAdministration of Third-Party Mesenchymal Stromal Cells at the Time of Kidney Transplantation: Interim Safety Analysis at One-Year Follow-Up
Erpicum, Pauline ULg; WEEKERS, Laurent ULg; DETRY, Olivier ULg et al

Conference (2016, April 28)

Objective. Mesenchymal stromal cells (MSC) therapy has been suggested in kidney transplantation (KTx). We report on the 1-year follow-up of an open-label phase I trial using MSC at the time of KTx ... [more ▼]

Objective. Mesenchymal stromal cells (MSC) therapy has been suggested in kidney transplantation (KTx). We report on the 1-year follow-up of an open-label phase I trial using MSC at the time of KTx. Methods. On postoperative day 3 (D3), third-party MSC (~2.0x106/kg) were administered to 7 non-immunized first-transplant recipients from deceased donors, under standard immunosuppression (Basiliximab, Tacrolimus, MMF and steroids). No HLA matching was required for MSC donors. In parallel, 7 comparable KTx recipients were included as controls. Written informed consent was obtained from all participants. Results. No hemodynamic or immune-allergic side-effect was noted at the time of MSC injection. Still, 1 patient with a history of ischemic heart disease had a NSTEMI ~3h after MSC infusion. Four MSC patients presented with CMV reactivation within 165 ± 96 days post KTx, whereas 3 controls had positive polyoma-BK viremia within 92 ± 4d post KTx. Three MSC patients were affected by pneumonia within 269 ± 98d post KTx, whereas 3 controls had urinary infection within 48 ± 43d post KTx. No MSC engraftment syndrome was observed. At D14, eGFR in MSC and control groups was 47.1 ± 6.8 and 39.7 ± 5.9 ml/min, respectively (p, 0.05). At 1 year, eGFR in MSC and control groups was 43.1 ± 17.8 and 53.9 ± 13.4 ml/min, respectively (p, 0.25). At 3-month protocol biopsy, no rejection was evidenced in MSC or control patients. Later on, 1 acute rejection was diagnosed at D330 in 1 MSC patient. No biopsy-proven AR was noted in controls. Three patients developed anti-HLA antibodies against MSC (n=1) or shared kidney/MSC (n=2) mismatches. Conclusions. MSC infusion was safe in all patients except one. Incidence of opportunist and non-opportunist infections was similar in both MSC and control groups. No MSC engraftment syndrome was documented. No difference in eGFR was found at 1 year post KTx. Putative immunization against MSC was observed in 3 patients. [less ▲]

Detailed reference viewed: 43 (7 ULg)
Full Text
Peer Reviewed
See detailLa polykystose rénale autosomique dominante : comment et pourquoi identifier les patients "rapidement progresseurs" vers l'insuffisance rénale terminale?
bodson, aurélie; MEUNIER, Paul ULg; Krzesinski, Jean-Marie ULg et al

in Revue Médicale de Liège (2016), 71(4), 184-192

Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disease characterised by the progressive development of multiple and bilateral cysts in kidneys and other organs. Most patients ... [more ▼]

Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disease characterised by the progressive development of multiple and bilateral cysts in kidneys and other organs. Most patients with ADPKD will develop, sooner or later, end-stage renal disease (ESRD). The morbidity and mortality associated with ESRD prompt physicians to identify early ADPKD patients considered as «rapid progressors», who have the greatest risk to rapidly develop ESRD. The rate of progression can be assessed by clinical - especially with the «predicting renal outcome in polycystic kidney disease score» (PROPKD-Score) -, biological (a decline of the glomerular filtration rate (GFR) of 4,4 - 5,9 ml/min/year and/or the doubling of serum creatinine within a 36-month period), or radiological criteria (total kidney volume (TKV) adjusted for the size > 600 cc/m and/or TKV annual growth rate > 5 %). Nowadays, there is no curative treatment for ADPKD. However, vasopressin-2 receptor antagonists, such as tolvaptan, appear to slow down the growth of renal cysts and the slope of GFR decline. The current management of ADPKD patients is mostly based on correcting the risk factors for progression, i.e. encouraging (over)-hydration, normalizing blood pressure, stimulating smoking cessation. [less ▲]

Detailed reference viewed: 67 (20 ULg)
Full Text
Peer Reviewed
See detailConcordance between Iothalamate and Iohexol Plasma Clearance
DELANAYE, Pierre ULg; LE GOFF, Caroline ULg; JOURET, François ULg et al

in American Journal of Kidney Diseases (2016), 68(2), 329-330

Detailed reference viewed: 19 (6 ULg)
Full Text
Peer Reviewed
See detailThe Uptake of 18F-FDG by Renal Allograft in Kidney Transplant Recipients Is Not Influenced by Renal Function.
Jadoul, Alexandre; LOVINFOSSE, Pierre ULg; Weekers, Laurent et al

in Clinical Nuclear Medicine (2016), 41(9), 683-7

PURPOSE OF THE REPORT: F-FDG PET/CT has been recently proposed as a noninvasive tool for the diagnosis of renal allograft acute rejection (AR) in kidney transplant recipients (KTRs). Still, the influence ... [more ▼]

PURPOSE OF THE REPORT: F-FDG PET/CT has been recently proposed as a noninvasive tool for the diagnosis of renal allograft acute rejection (AR) in kidney transplant recipients (KTRs). Still, the influence of kidney function on F-FDG uptake by renal grafts remains unknown. PATIENTS AND METHODS: We retrospectively identified all KTRs who underwent at least one F-FDG PET/CT. Kidney transplant recipients with documented pyelonephritis or AR were excluded. Estimated glomerular filtration rate (eGFR) was assessed using chronic kidney disease (CKD)-EPI equation. Mean standardized uptake values (SUVmean) of renal graft cortex and aorta were measured in 4 and 1 volumes of interest, respectively. Spearman rank correlation coefficient (rho) and analysis of variance (ANOVA) were performed. RESULTS: Eighty-two KTRs underwent F-FDG PET/CT for tumor staging (n = 46), suspected infection (n = 11), or fever of unknown origin (n = 25). Mean eGFR was 50 +/- 19 mL/min per 1.73 m, including CKD stage 1 (n = 3), stage 2 (n = 21), stage 3a (n = 20), stage 3b (n = 29), and stage 4 (n = 9). Mean kidney and aorta SUVmean were 1.8 +/- 0.2 and 1.7 +/- 0.3, respectively. No significant correlation was observed between eGFR and kidney SUVmean (rho, 0.119; P, 0.28) or aorta SUVmean (rho, -0.144; P, 0.20). ANOVA showed no difference of kidney (P, 0.62) and aorta (P, 0.85) SUVmean between CKD groups. Mean coefficient of variation (on the basis of kidney SUVmean of >3 consecutive F-FDG PET/CT in 15 patients with no significant change of eGFR) reached 13.1%. CONCLUSIONS: The uptake of F-FDG by renal allografts within an hour postinjection is not significantly impacted by CKD. [less ▲]

Detailed reference viewed: 33 (13 ULg)
Full Text
Peer Reviewed
See detailFluorodeoxyglucose F Positron Emission Tomography Coupled With Computed Tomography in Suspected Acute Renal Allograft Rejection.
LOVINFOSSE, Pierre ULg; Weekers, L.; Bonvoisin, C. et al

in American Journal of Transplantation (2016)

Management of kidney transplant recipients (KTRs) with suspected acute rejection (AR) ultimately relies on kidney biopsy; however, noninvasive tests predicting nonrejection would help avoid unnecessary ... [more ▼]

Management of kidney transplant recipients (KTRs) with suspected acute rejection (AR) ultimately relies on kidney biopsy; however, noninvasive tests predicting nonrejection would help avoid unnecessary biopsy. AR involves recruitment of leukocytes avid for fluorodeoxyglucose F18 (18 F-FDG), thus 18 F-FDG positron emission tomography (PET) coupled with computed tomography (CT) may noninvasively distinguish nonrejection from AR. From January 2013 to February 2015, we prospectively performed 32 18 F-FDG PET/CT scans in 31 adult KTRs with suspected AR who underwent transplant biopsy. Biopsies were categorized into four groups: normal (n = 8), borderline (n = 10), AR (n = 8), or other (n = 6, including 3 with polyoma BK nephropathy). Estimated GFR was comparable in all groups. PET/CT was performed 201 +/- 18 minutes after administration of 3.2 +/- 0.2 MBq/kg of 18 F-FDG, before any immunosuppression change. Mean standard uptake values (SUVs) of both upper and lower renal poles were measured. Mean SUVs reached 1.5 +/- 0.2, 1.6 +/- 0.3, 2.9 +/- 0.8, and 2.2 +/- 1.2 for the normal, borderline, AR, and other groups, respectively. One-way analysis of variance demonstrated a significant difference of mean SUVs among groups. A positive correlation between mean SUV and acute composite Banff score was found, with r2 = 0.49. The area under the receiver operating characteristic curve was 0.93, with 100% sensitivity and 50% specificity using a mean SUV threshold of 1.6. In conclusion, 18 F-FDG PET/CT may help noninvasively prevent avoidable transplant biopsies in KTRs with suspected AR. [less ▲]

Detailed reference viewed: 80 (26 ULg)
Full Text
Peer Reviewed
See detailInternational Multi-Specialty Delphi Survey: Identification of Diagnostic Criteria for Hepatic and Renal Cyst Infection.
Lantinga, Marten A.; Darding, Alexander J. M.; de Sevaux, Ruud G. L. et al

in Nephron (2016), 134(4),

BACKGROUND: Cyst infection is one of the complications of autosomal dominant polycystic kidney disease and polycystic liver disease. The diagnosis is typically made on a mix of clinical, laboratory and ... [more ▼]

BACKGROUND: Cyst infection is one of the complications of autosomal dominant polycystic kidney disease and polycystic liver disease. The diagnosis is typically made on a mix of clinical, laboratory and imaging abnormalities but the importance of individual items is uncertain. We aimed to perform a Delphi survey amongst physicians to achieve consensus on diagnostic criteria. METHODS: We retrieved diagnostic items from the literature and conducted physician and patient interviews. All items were combined to create the online questionnaire. Participants rated each item during 3 consecutive rounds. Items were rated for diagnostic helpfulness for hepatic and renal cyst infection on a 9-point scale with anchors, from extremely unimportant (n = 1) to extremely important (n = 9). We determined consensus with the disagreement index. The median rating of each item was calculated and categorized into inappropriate (</=3.4), uncertain (3.5-6.4) or appropriate (>/=6.5). By combining all items that reached an appropriate consensus rating, we developed a diagnostic algorithm based on expert consensus. RESULTS: We invited 58 physicians to participate in the survey. In total, 35 (60%) responded to round 1 of which 91% (n = 32) and 86% (n = 30) responded to round 2 and 3, respectively. The final panel included 23 nephrologists, 5 hepatologists, a nuclear medicine specialist and an infectious disease physician from 11 countries (male 67%, mean age 47 +/- 11 years, median clinical experience 21 years). The panel rated the diagnostic helpfulness of 59 potential items. Ultimately, 22 hepatic and 26 renal items were rated appropriate, including positive blood cultures and fluorodeoxyglucose positron-emission CT imaging. Ultrasonography and absence of intracystic bleeding were amongst those deemed uncertain or inappropriate. Subsequently, by combining items rated appropriate, we developed a clinical tool to diagnose hepatic and renal cyst infection. CONCLUSIONS: We identified diagnostic items for hepatic and renal cyst infection and developed an expert-based diagnostic algorithm, which may aid physicians in the diagnostic work-up. A prospective study is necessary to validate this algorithm. [less ▲]

Detailed reference viewed: 13 (0 ULg)
Full Text
Peer Reviewed
See detailmTOR Regulates Endocytosis and Nutrient Transport in Proximal Tubular Cells.
Grahammer, Florian; Ramakrishnan, Suresh K.; Rinschen, Markus M. et al

in Journal of the American Society of Nephrology : JASN (2016)

Renal proximal tubular cells constantly recycle nutrients to ensure minimal loss of vital substrates into the urine. Although most of the transport mechanisms have been discovered at the molecular level ... [more ▼]

Renal proximal tubular cells constantly recycle nutrients to ensure minimal loss of vital substrates into the urine. Although most of the transport mechanisms have been discovered at the molecular level, little is known about the factors regulating these processes. Here, we show that mTORC1 and mTORC2 specifically and synergistically regulate PTC endocytosis and transport processes. Using a conditional mouse genetic approach to disable nonredundant subunits of mTORC1, mTORC2, or both, we showed that mice lacking mTORC1 or mTORC1/mTORC2 but not mTORC2 alone develop a Fanconi-like syndrome of glucosuria, phosphaturia, aminoaciduria, low molecular weight proteinuria, and albuminuria. Interestingly, proteomics and phosphoproteomics of freshly isolated kidney cortex identified either reduced expression or loss of phosphorylation at critical residues of different classes of specific transport proteins. Functionally, this resulted in reduced nutrient transport and a profound perturbation of the endocytic machinery, despite preserved absolute expression of the main scavenger receptors, MEGALIN and CUBILIN. Our findings highlight a novel mTOR-dependent regulatory network for nutrient transport in renal proximal tubular cells. [less ▲]

Detailed reference viewed: 14 (0 ULg)